FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Mulligan, JK Lathers, DMR Young, RI AF Mulligan, Jennifer Konopa Lathers, Deanne M. R. Young, Rita I. TI TUMOR-SECRETED VEGF-A DISRUPTS ENDOTHELIAL CELL STIMULATION OF T-CELL, MACROPHAGE AND NK CELL FUNCTIONS SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Mulligan, Jennifer Konopa] Med Univ South Carolina, Med, Charleston, SC 29485 USA. [Lathers, Deanne M. R.; Young, Rita I.] Ralph Johnson VA Med Ctr, Res Serv, Charleston, SC 29485 USA. [Lathers, Deanne M. R.] MUSC, Otolaryngol, Charleston, SC 29485 USA. [Young, Rita I.] MUSC, Hematol Oncol, Charleston, SC 29485 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 49.5 PG 1 WC Immunology SC Immunology GA V44OL UT WOS:000209758203242 ER PT J AU Myers, RC You, YY Wang, Y Carter, RH AF Myers, Riley C. You, Yuying Wang, Yue Carter, Robert H. TI Diminished FDC activation within germinal centers of CD19-deficient mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Myers, Riley C.; You, Yuying] Univ Alabama Birmingham, Microbiol, Birmingham, AL 35294 USA. [Carter, Robert H.] Univ Alabama Birmingham, Med & Microbiol, Birmingham, AL 35294 USA. [Wang, Yue] Medlmmune, Gaithersburg, MD 20878 USA. [Carter, Robert H.] Birmingham VAMC, Birmingham, AL 35223 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 92.8 PG 2 WC Immunology SC Immunology GA V44OL UT WOS:000209758200154 ER PT J AU Pascal, V Yamada, E Martin, MP Alter, G Alffeld, M Carrington, M Anderson, SK McVicar, DW AF Pascal, Veronique Yamada, Eriko Martin, Maureen P. Alter, Galit Alffeld, Marcus Carrington, Mary Anderson, Stephen K. McVicar, Daniel W. TI Functional evidence supporting the predicted role of KIR3DS1 in the host response to HIV: KIR3DS1 is an activating receptor expressed by human Natural Killer cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Pascal, Veronique; Yamada, Eriko; McVicar, Daniel W.] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA. [Martin, Maureen P.; Carrington, Mary] NCI, Lab Genom Divers, SAIC Frederick Inc, Frederick, MD 21702 USA. [Alter, Galit; Alffeld, Marcus] Harvard Med Sch, Partners AIDS Res Ctr, Infect Dis Unit, Massachusetts Gen Hosp,Div AIDS, Boston, MA 02129 USA. [Anderson, Stephen K.] NCI, Canc & Inflammat Program, SAIC Frederick Inc, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 52.5 PG 2 WC Immunology SC Immunology GA V44OL UT WOS:000209758200313 ER PT J AU Pipkin, ME Cruz-Guilloty, F Lichtenheld, MG Rao, A AF Pipkin, Matthew Eugene Cruz-Guilloty, Fernando Lichtenheld, Mathias Georg Rao, Anjana TI Regulation of the Perforin Locus by IL-2 During CD8+T-cell Differentiation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Pipkin, Matthew Eugene; Cruz-Guilloty, Fernando; Rao, Anjana] Harvard Med Sch, CBR Inst Biomed Res, Dept Pathol, Boston, MA 02115 USA. [Lichtenheld, Mathias Georg] Univ Miami, Dept Microbiol & Immunol, Miller Sch Med, Miami, FL 33136 USA. [Lichtenheld, Mathias Georg] Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 35.49 PG 1 WC Immunology SC Immunology GA V44OL UT WOS:000209758201061 ER PT J AU Romero, VA Zuniga, J Azocar, J Clavijo, OP Chung, RT Amos, CI Yunis, EJ AF Romero, Viviano A. Zuniga, Joaquin Azocar, Jose Clavijo, Olga P. Chung, Raymond T. Amos, Christopher I. Yunis, Edmond J. TI NK cell inhibition receptor genes and HLA-DRB1*1201 in Spontaneous Clearance of Hepatitis Virus Infection. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Romero, Viviano A.; Zuniga, Joaquin; Clavijo, Olga P.; Yunis, Edmond J.] Dana Farber Canc Inst, Canc Immunol & AIDS, Boston, MA 02115 USA. [Zuniga, Joaquin] Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico. [Azocar, Jose] Northgate Med Ctr, Springfield, MA 01103 USA. [Chung, Raymond T.] Massachusetts Gen Hopsital, Gastroenterol, Boston, MA 02114 USA. [Amos, Christopher I.] Univ Texas MD Anderson Canc Ctr, Epidemiol & Biomath, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 35.16 PG 1 WC Immunology SC Immunology GA V44OL UT WOS:000209758201043 ER PT J AU Sarkar, S Kalia, V Haining, WN Konieczny, BT Subramaniam, S Ahmed, R AF Sarkar, Surojit Kalia, Vandana Haining, W. Nicholas Konieczny, Bogumila T. Subramaniam, Shruti Ahmed, Rafi TI Length of Antigenic Stimulation During Expansion Dictates Commitment to CD8 T Cell Memory Subsets SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Sarkar, Surojit; Kalia, Vandana; Konieczny, Bogumila T.; Subramaniam, Shruti; Ahmed, Rafi] Emory Univ, Atlanta, GA 30322 USA. [Haining, W. Nicholas] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 43.6 PG 2 WC Immunology SC Immunology GA V44OL UT WOS:000209758200213 ER PT J AU Walsh, JE Young, MRI AF Walsh, Jarrett Elbert Young, M. Rita I. TI TGF-beta Induces Microvascular Endothelial Cell Migration and PP-2A Inactivation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Walsh, Jarrett Elbert] Med Univ South Carolina, Microbiol & Immunol, Charleston, SC 29425 USA. [Young, M. Rita I.] Med Univ South Carolina, Otolaryngol & Med, Charleston, SC 29425 USA. [Young, M. Rita I.] Ralph H Johnson VAMC, Res Serv, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA B65 PG 2 WC Immunology SC Immunology GA V44OL UT WOS:000209758200167 ER PT J AU Wang, JH Hsu, HC Yang, P Wu, Q Job, G Chen, J Timares, L Mountz, JD AF Wang, John Hsien Hsu, Hui-Chen Yang, PingAr Wu, Qi Job, Godwin Chen, Jian Timares, Laura Mountz, John D. TI INCREASED EXPRESSION OF IFN-ALPHA AND IL-6 BY HYPERACTIVE PLASMACYTOID DENDRITIC CELLS IN BXD2 AUTOIMMUNE MICE SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Hoover, AL 35226 USA. Birmingham VA Med Ctr, Hoover, AL 35226 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 130.25 PG 2 WC Immunology SC Immunology GA V44OL UT WOS:000209758200052 ER PT J AU Wuest, T Luster, A Campbell, I Farber, J Carr, D AF Wuest, Todd Luster, Andrew Campbell, Iain Farber, Joshua Carr, Daniel TI CXCL10 is required for the recruitment of leukocytes responsible for controlling herpes simplex virus-1 infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Wuest, Todd] OUHSC, Dept Ophthalmol, Microbiol & Immunol, Oklahoma City, OK 73104 USA. [Luster, Andrew] Harvard Med Sch, Massachusettts Gen Hosp, Rheum Allergy & Immunol, Boston, MA USA. [Campbell, Iain] Univ Sydney, Mol Biol, Sydney, NSW 2006, Australia. [Farber, Joshua] NIAID, NIH, Bethesda, MD 20892 USA. [Carr, Daniel] OUSHC, Ophthalmol, Oklahoma City, OK 73104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 43.19 PG 2 WC Immunology SC Immunology GA V44OL UT WOS:000209758200217 ER PT J AU Blackard, JT Kang, MH St Clair, JB Lin, WY Kamegaya, Y Sherman, KE Koziel, MJ Peters, MG Andersen, J Chung, RT AF Blackard, Jason T. Kang, Minhee St. Clair, J. Benjamin Lin, Wenyu Kamegaya, Yoshitaka Sherman, Kenneth E. Koziel, Margaret James Peters, Marion G. Andersen, Janet Chung, Raymond T. CA Aids Clinical Trials Grp A5071 S TI Viral factors associated with cytokine expression during HCV/HIV co-infection SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID CHRONIC HEPATITIS-C; HUMAN-IMMUNODEFICIENCY-VIRUS; NECROSIS-FACTOR-ALPHA; HEPATOCELLULAR-CARCINOMA; INTRAHEPATIC EXPRESSION; INTERFERON THERAPY; SUSTAINED RESPONSE; ELEVATED LEVELS; MESSENGER-RNA; INTERLEUKIN-8 AB Co-infection with human immunodeficiency virus ( HIV) is associated with reduced hepatitis C virus ( HCV) treatment response and accelerated HCV disease. Cytokines, as mediators of immune responses, inflammation, and fibrogenesis, may underlie important differences in HCV pathogenesis during HIV co-infection. We previously found that serum interleukin-8 ( IL-8) and tumor necrosis factor-alpha ( TNF-alpha) increased after HCV therapy with interferon ( IFN) in HCV/HIV co-infected patients; however, cytokine levels were not predictive of HCV therapeutic response. Here, we examined viral factors associated with expression of IL-8, TNF-alpha, and transforming growth factor-beta 1 ( TGF-beta 1) in uninfected, HCV mono-infected, HIV mono-infected, and HCV/HIV co-infected persons. HIV co-infection was associated with decreased IL-8 detection but not TNF-alpha detection. A significant interaction effect demonstrated that HIV infection was associated with elevated TGF-beta 1 in HCV-positive individuals but not in HCV-negative individuals. The induction of a sustained profibrotic signal, such as TGF-beta 1, by HIV may cause accelerated liver fibrosis during HCV/HIV co-infection and may hinder the host's ability to mount an effective HCV-specific immune response. Further studies are warranted to identify noninvasive markers of liver disease for the clinical management of HCV disease, particularly when liver biopsies have not been performed or are contraindicated. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Univ Cincinnati, Coll Med, Div Digest Dis, Cincinnati, OH 45267 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Univ Calif San Francisco, Div Gastroenterol, San Francisco, CA 94143 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825, Boston, MA 02114 USA. EM rtchung@partners.org FU NIAID NIH HHS [AI38855, P30 AI042851, U01 AI069502, P30-AI42851, AI38858, U01 AI038855, U01 AI038858] NR 21 TC 8 Z9 8 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD APR PY 2007 VL 27 IS 4 BP 263 EP 269 DI 10.1089/jir.2006.0147 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 164CO UT WOS:000246210500002 PM 17477814 ER PT J AU Sato, N Moore, BW Keevey, S Drazba, JA Hasan, T Maytin, EV AF Sato, Nobuyuki Moore, Brian W. Keevey, Samantha Drazba, Judy A. Hasan, Tayyaba Maytin, Edward V. TI Vitamin D enhances ALA-induced protoporphyrin IX production and photodynamic cell death in 3-D organotypic cultures of keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID NONMELANOMA SKIN-CANCER; AMINOLEVULINIC-ACID; RAT KERATINOCYTES; EPIDERMAL DIFFERENTIATION; THERAPY; HYALURONAN; TRANSCRIPTION; PRINCIPLES; APOPTOSIS; CALCIUM AB Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is based upon the intracellular synthesis of protoporphyrin IX (PpIX), which absorbs light and targets metabolically active cells. We tested the hypothesis that levels of PpIX within keratinocytes might be increased by vitamin D (Vit D), a differentiation-promoting hormone. Vit D promoted terminal differentiation in monolayer cultures of rat epidermal keratinocytes (REKs), but high PpIX signals were found only in stratifying islands. To simulate a normal epidermis, REKs were grown in organotypic cultures. The presence of Vit D (10(-10) (M) for 4 days) led to heightened expression of terminal differentiation markers (stratum corneum, K10, and loricrin). PpIX levels, at 4 hours after addition of ALA (1 mm), were significantly increased in the Vit D-preconditioned cultures by confocal fluorescence microscopy and semiquantitative image analysis. Maximal PpIX induction was seen at (Vit D) 10(-12) -10(-10) (M). Phototoxic cell killing after exposure to 635 nm light was significantly higher in Vit D-preconditioned cultures. No differences in apoptotic markers between Vit D and control cultures were seen, suggesting that Vit D augments photodynamic cell death via alternative pathways (e.g., necrosis). In summary, Vit D may be useful as a biological enhancer of ALA-based PDT. C1 Cleveland Clin Fdn, Lerner Res Inst, Dept Biomed Engn, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Lerner Res Inst, Digital Imaging Core, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Wellmab Ctr Photomed, Boston, MA 02114 USA. Cleveland Clin Fdn, Dept Dermatol, Cleveland, OH 44195 USA. RP Maytin, EV (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Dept Biomed Engn, 9500 Euclid Ave,ND-20, Cleveland, OH 44195 USA. EM maytine@ccf.org FU NCI NIH HHS [P01-CA84203] NR 34 TC 32 Z9 32 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2007 VL 127 IS 4 BP 925 EP 934 DI 10.1038/sj.jid.5700595 PG 10 WC Dermatology SC Dermatology GA 151TV UT WOS:000245314600027 PM 17068479 ER PT J AU Asgari, M Bertenthal, D Sen, S Sahay, A Chren, M AF Asgari, M. Bertenthal, D. Sen, S. Sahay, A. Chren, M. TI Patient satisfaction with treatments of nonmelanoma skin cancer SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 68th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2007 CL Los Angeles, CA SP Soc Investigat Dermatol C1 Kaiser Permanente No CA, Oakland, CA USA. San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RI Asgari, Maryam/O-4947-2016 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2007 VL 127 SU 1 MA 378 BP S63 EP S63 PG 1 WC Dermatology SC Dermatology GA 152UP UT WOS:000245387800375 ER PT J AU Bergman, H Watson, A Williams, C Kvedar, J AF Bergman, H. Watson, A. Williams, C. Kvedar, J. TI The development and evaluation of an electronic visit (e-visit) program for the management of acne SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 68th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2007 CL Los Angeles, CA SP Soc Investigat Dermatol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Connected Hlth, Boston, MA 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2007 VL 127 SU 1 MA 316 BP S53 EP S53 PG 1 WC Dermatology SC Dermatology GA 152UP UT WOS:000245387800314 ER PT J AU De Guzman Strong, C Patel, S Wertz, PW Wang, C Yang, F Meltzer, PS Andl, T Millar, SE Ho, I Pai, S Segre, JA AF De Guzman Strong, C. Patel, S. Wertz, P. W. Wang, C. Yang, F. Meltzer, P. S. Andl, T. Millar, S. E. Ho, I. Pai, S. Segre, J. A. TI Epidermal-specific deletion of GATA-3 results in selective barrier deficiency SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 68th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2007 CL Los Angeles, CA SP Soc Investigat Dermatol C1 NHGRI, Bethesda, MD 20892 USA. Natl Canc Inst, Bethesda, MD USA. Univ Iowa, Iowa City, IA USA. Univ Penn, Philadelphia, PA 19104 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2007 VL 127 SU 1 MA 573 BP S96 EP S96 PG 1 WC Dermatology SC Dermatology GA 152UP UT WOS:000245387800568 ER PT J AU Friedman, AJ Phan, J Tang, D Oren, A Modlin, R Kim, J AF Friedman, A. J. Phan, J. Tang, D. Oren, A. Modlin, R. Kim, J. TI Chitosan nanoparticles: Agent for topical treatment of cutaneous inflammatory and infectious diseases SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 68th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2007 CL Los Angeles, CA SP Soc Investigat Dermatol C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Dermatol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. W Los Angeles Vet Adm, Ctr Med, Los Angeles, CA USA. New York Hosp Queens, Queens, NY USA. RI Liu, Philip/C-9638-2011 NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2007 VL 127 SU 1 MA 776 BP S130 EP S130 PG 1 WC Dermatology SC Dermatology GA 152UP UT WOS:000245387800773 ER PT J AU Goerge, T Bergmeier, W Cifuni, SM Ho-Tin-Noe, BH Wagner, DD AF Goerge, T. Bergmeier, W. Cifuni, S. M. Ho-Tin-Noe, B. H. Wagner, D. D. TI Defective inside-out activation of beta 2 integrins inhibits cutaneous reverse passive Arthus reaction in CalDAG-GEFI -/- mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 68th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2007 CL Los Angeles, CA SP Soc Investigat Dermatol C1 Harvard Med Sch, CBR Inst, Dept Pathol, Boston, MA 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2007 VL 127 SU 1 MA 75 BP S13 EP S13 PG 1 WC Dermatology SC Dermatology GA 152UP UT WOS:000245387800075 ER PT J AU Hocker, TH Singh, MK Tsao, H AF Hocker, T. H. Singh, M. K. Tsao, H. TI Molecular evidence reveals complex link between ultraviolet radiation and melanoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 68th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2007 CL Los Angeles, CA SP Soc Investigat Dermatol C1 Harvard Med Sch, Boston, MA USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2007 VL 127 SU 1 MA 107 BP S18 EP S18 PG 1 WC Dermatology SC Dermatology GA 152UP UT WOS:000245387800106 ER PT J AU Hu, J Chiu, MW Cotliar, J Kim, J Peng, D AF Hu, J. Chiu, M. W. Cotliar, J. Kim, J. Peng, D. TI The effectiveness of teledermatology in pigmented skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 68th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2007 CL Los Angeles, CA SP Soc Investigat Dermatol C1 Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Dept Dermatol, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Ctr, Div Dermatol, Los Angeles, CA 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2007 VL 127 SU 1 MA 366 BP S61 EP S61 PG 1 WC Dermatology SC Dermatology GA 152UP UT WOS:000245387800363 ER PT J AU Idriss, SZ Kvedar, JC Watson, AJ AF Idriss, S. Z. Kvedar, J. C. Watson, A. J. TI Psoriasis e-communities: exploring the benefits of online support SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 68th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2007 CL Los Angeles, CA SP Soc Investigat Dermatol C1 Ctr Connected Hlth, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2007 VL 127 SU 1 MA 375 BP S63 EP S63 PG 1 WC Dermatology SC Dermatology GA 152UP UT WOS:000245387800371 ER PT J AU Jin, K Nishimura, EK Akasaka, E Nakano, H Hanada, K Sawamura, D Fisher, DE Imokawa, G AF Jin, K. Nishimura, E. K. Akasaka, E. Nakano, H. Hanada, K. Sawamura, D. Fisher, D. E. Imokawa, G. TI Biphasic signalings leading to mitf protein expression in endothelin-1 stimulated human melanocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 68th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2007 CL Los Angeles, CA SP Soc Investigat Dermatol C1 Hirosaki Univ, Sch Med, Hirosaki, Aomori 036, Japan. Kanazawa Univ, Canc Res Inst, Kanazawa, Ishikawa 920, Japan. Harvard Univ, Childrens Hosp, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. Tokyo Univ Technol, Sch Bion, Tokyo, Japan. 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2007 VL 127 SU 1 MA 888 BP S148 EP S148 PG 1 WC Dermatology SC Dermatology GA 152UP UT WOS:000245387800883 ER PT J AU Kajiya, K Hirakawa, S Detmar, M AF Kajiya, K. Hirakawa, S. Detmar, M. TI Vascular endothelial growth factor-A mediates ultraviolet B-induced impairment of lymphatic vessel function SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 68th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2007 CL Los Angeles, CA SP Soc Investigat Dermatol C1 Shiseido Life Sci Res Ctr, Yokohama, Kanagawa, Japan. Swiss Fed Inst Technol, Inst Pharmaceut Sci, Zurich, Switzerland. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Boston, MA 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2007 VL 127 SU 1 MA 2 BP S1 EP S1 PG 1 WC Dermatology SC Dermatology GA 152UP UT WOS:000245387800005 ER PT J AU Katiyar, SK Katiyar, S Elmets, CA Meeren, SM AF Katiyar, S. K. Katiyar, S. Elmets, C. A. Meeren, S. M. TI Interleukin-12-deficiency promotes angiogenesis in UV-induced skin tumors SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 68th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2007 CL Los Angeles, CA SP Soc Investigat Dermatol C1 Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2007 VL 127 SU 1 MA 9 BP S2 EP S2 PG 1 WC Dermatology SC Dermatology GA 152UP UT WOS:000245387800009 ER PT J AU Kawasumi, M Lemos, B Nghiem, P AF Kawasumi, M. Lemos, B. Nghiem, P. TI Chemical and ultraviolet induced carcinogenesis in mice expressing dominant negative ATR in skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 68th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2007 CL Los Angeles, CA SP Soc Investigat Dermatol C1 Univ Washington, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Harvard Med Sch, Charlestown, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2007 VL 127 SU 1 MA 133 BP S23 EP S23 PG 1 WC Dermatology SC Dermatology GA 152UP UT WOS:000245387800134 ER PT J AU Lemos, B Garneski, K Feng, B Chin, L Nghiem, P AF Lemos, B. Garneski, K. Feng, B. Chin, L. Nghiem, P. TI Recurrent genetic alterations in Merkel cell carcinoma revealed by array-comparative genomic hybridization SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 68th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2007 CL Los Angeles, CA SP Soc Investigat Dermatol C1 Univ Washington, Seattle, WA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2007 VL 127 SU 1 MA 131 BP S22 EP S22 PG 1 WC Dermatology SC Dermatology GA 152UP UT WOS:000245387800130 ER PT J AU Li, W Li, Y Guan, S Fan, J Cheng, C Bright, A Chin, C Chen, M Woodley, D AF Li, W. Li, Y. Guan, S. Fan, J. Cheng, C. Bright, A. Chin, C. Chen, M. Woodley, D. TI Extracellular heat shock protein-90alpha: linking hypoxia to skin cell motility and wound healing SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 68th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2007 CL Los Angeles, CA SP Soc Investigat Dermatol C1 Univ So Calif, Los Angeles, CA USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2007 VL 127 SU 1 MA 213 BP S36 EP S36 PG 1 WC Dermatology SC Dermatology GA 152UP UT WOS:000245387800211 ER PT J AU Tierney, EP Kimball, AB AF Tierney, E. P. Kimball, A. B. TI Employment migration patterns of dermatology residents SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 68th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2007 CL Los Angeles, CA SP Soc Investigat Dermatol C1 Henry Ford Hlth Syst, Detroit, MI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2007 VL 127 SU 1 MA 342 BP S57 EP S57 PG 1 WC Dermatology SC Dermatology GA 152UP UT WOS:000245387800339 ER PT J AU Yang, G Bosenberg, M Tsao, H AF Yang, G. Bosenberg, M. Tsao, H. TI Loss of the Xeroderma Pigmentosum C (xpc) gene enhances melanoma photocarcinogenesis in Ink4a-Arf-deficient mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 68th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2007 CL Los Angeles, CA SP Soc Investigat Dermatol C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Univ Vermont, Burlington, VT 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2007 VL 127 SU 1 MA 179 BP S30 EP S30 PG 1 WC Dermatology SC Dermatology GA 152UP UT WOS:000245387800176 ER PT J AU Yao, M Bujold, KE Redmond, RW Kochevar, IE AF Yao, M. Bujold, K. E. Redmond, R. W. Kochevar, I. E. TI Closure of skin excisions and incisions using a rapid, light-activated technique SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 68th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 09-12, 2007 CL Los Angeles, CA SP Soc Investigat Dermatol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2007 VL 127 SU 1 MA 848 BP S142 EP S142 PG 1 WC Dermatology SC Dermatology GA 152UP UT WOS:000245387800845 ER PT J AU Sakata, S Lebeche, D Sakata, N Sakata, Y Chemaly, ER Liang, LF Tsuji, T Takewa, Y del Monte, F Peluso, R Zsebo, K Jeong, D Park, WJ Kawase, Y Hajjar, RJ AF Sakata, Susumu Lebeche, Djamel Sakata, Naoya Sakata, Yuri Chemaly, Elie R. Liang, Li Fan Tsuji, Tsuyoshi Takewa, Yoshiaki del Monte, Federica Peluso, Richard Zsebo, Krisztina Jeong, Dongtak Park, Woo Jin Kawase, Yoshiaki Hajjar, Roger J. TI Restoration of mechanical and energetic function in failing aortic-banded rat hearts by gene transfer of calcium cycling proteins SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE gene therapy; heart failure; energetic function; SERCA2a; parvalbumin ID SARCOPLASMIC-RETICULUM CA2+-ATPASE; VENTRICULAR-FUNCTION; DIASTOLIC FUNCTION; HUMAN MYOCARDIUM; IN-VIVO; DILATED CARDIOMYOPATHY; OVERLOAD HYPERTROPHY; FAILURE; DYSFUNCTION; MODEL AB The aim of this study was to examine whether short- and long-term gene transfer of Ca2+ handling proteins restore left ventricular (LV) mechanoenergetics in aortic banding-induced failing hearts. Aortic-banded rats received recombinant adenoviruses carrying sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) (Banding + SERCA), parvalbumin (Banding + Parv) or beta-galactosidase (Banding + beta gal), or an adeno-associated virus carrying SERCA2a (Banding + AAV.SERCA) by a catheter-based technique. LV mechanoenergetic function was measured in cross-circulated hearts. "Banding", "Banding + beta gal" and "Banding + saline" groups showed lower end-systolic pressure at 0.1 ml intraballoon water (ESP0.1), higher end-diastolic pressure at 0.1 ml intraballoon water (EDP0.1) and slower LV relaxation rate, compared with "Normal" and "Sham". However, "Banding + SERCA" and "Banding + Parv" showed high ESP0.1, low EDP0.1, and fast LV relaxation rate. In "Banding", "Banding + beta gal" and "Banding + saline", slope of relation between cardiac oxygen consumption and systolic pressure-volume area, O-2 Cost of total mechanical energy, was twice higher than normal value, whereas slope in "Baning + SERCA" and "Banding + Parv" was similar to normal value. Furthermore, O-2 cost of LV contractility in the 3 control banding groups was similar to 3 times higher than normal value, whereas O-2 Cost of contractility in "Banding + SERCA", "Banding + AAV.SERCA" and "Banding + Parv" was as low as normal value. Thus, high O-2 costs of total mechanical energy and of LV contractility in failing hearts indicate energy wasting both in chemomechanical energy transduction and in calcium handling. Improved calcium handling by both short- and long-term overexpression of SERCA2a and parvalbumin transforms the inefficient energy utilization into a more efficient state. Therefore enhancement of calcium handling either by resequestration into the SR or by intracellular buffering improves not only mechanical but energetic function in failing hearts. (c) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Nara Med Univ, Sch Med, Dept Physiol 2, Kashihara, Nara 634, Japan. Nara Med Univ, Sch Med, Dept Thorac & Cardiovasc Surg, Kashihara, Nara 634, Japan. Targeted Genet, Seattle, WA USA. Celladon Inc, La Jolla, CA USA. RP Hajjar, RJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM rhajjar@partners.org FU NHLBI NIH HHS [R01 HL078691, R01 HL080498, R01 HL083156, HL057263, HL080498, HL083156, K08 HL069842, R01 HL057263, K01 HL076659, R01 HL088434, HL071763, R01 HL071763] NR 38 TC 74 Z9 74 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD APR PY 2007 VL 42 IS 4 BP 852 EP 861 DI 10.1016/j.ujmcc.2007.01.003 PG 10 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 165EU UT WOS:000246287600018 PM 17300800 ER PT J AU Liao, JC Mastali, M Li, Y Gau, V Suchard, MA Babbitt, J Gornbein, J Landaw, EM McCabe, ERB Churchill, BM Haake, DA AF Liao, Joseph C. Mastali, Mitra Li, Yang Gau, Vincent Suchard, Marc A. Babbitt, Jane Gornbein, Jeffrey Landaw, Elliot M. McCabe, Edward R. B. Churchill, Bernard M. Haake, David A. TI Development of an advanced electrochemical DNA biosensor for bacterial pathogen detection SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID URINARY-TRACT-INFECTIONS; 16S RIBOSOMAL-RNA; UROLOGIC DISEASES; ESCHERICHIA-COLI; AMERICA PROJECT; NUCLEIC-ACIDS; RESOURCE USE; ELECTRODE; SENSORS; TRENDS AB Electrochemical sensors have the capacity for rapid and accurate detection of a wide variety of target molecules in biological fluids. We have developed an electrochemical sensor assay involving hybridization of bacterial 16S rRNA to fluorescein-modified detector probes and to biotin-modified capture probes anchored to the sensor surface. Signal is generated by an oxidation-reduction current produced by the action of horseradish peroxidase conjugated to an anti-fluorescein monoclonal Fab. A previous study found that this electrochemical sensor strategy could identify uropathogens in clinical urine specimens. To improve assay sensitivity, we examined the key steps that affect the current amplitude of the electrochemical signal. Efficient lysis and release of 16S rRNA from both gram-negative and -positive bacteria was achieved with an initial treatment with Triton X-100 and lysozyme followed by alkaline lysis, resulting in a 12-fold increase in electrochemical signal compared with alkaline lysis alone. The distance in nucleotides between the target hybridization sites of the detector and capture probes and the location of fluorescein modification on the detector probe contributed to a 23-fold change in signal intensity. These results demonstrate the importance of target-probe and probe-probe interactions in the detection of bacterial 16S rRNA using an electrochemical DNA sensor approach. C1 VA Greater LA Healthcare, Div Infect Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90024 USA. GeneFluidics Inc, Monterey, CA USA. RP Haake, DA (reprint author), VA Greater LA Healthcare, Div Infect Dis, 111F, Los Angeles, CA 90073 USA. EM dhaake@ucla.edu RI Liao, Joseph/J-5874-2015 FU NIBIB NIH HHS [R01 EB000127] NR 24 TC 69 Z9 70 U1 2 U2 21 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD APR PY 2007 VL 9 IS 2 BP 158 EP 168 DI 10.2353/jmoldx.2007.060052 PG 11 WC Pathology SC Pathology GA 153JB UT WOS:000245427600005 PM 17384207 ER PT J AU Niv, N Lopez, SR Glynn, SM Mueser, K AF Niv, Noosha Lopez, Steven R. Glynn, Shirley M. Mueser, Kim TI The role of substance use in families' attributions and affective reactions to their relative with severe mental illness SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE dual diagnosis; drug abuse; schizophrenia; bipolar disorder; caregivers ID EXPRESSED EMOTION; SYMPTOM DIMENSIONS; SCHIZOPHRENIA; ALCOHOLISM; ABUSE; ADDICTION; DISORDER; MEXICAN; RELAPSE AB This study compared relatives' attributions and affective reactions toward patients with severe mental illness (SMI) only (N = 32) and patients with dual SMI and a substance use disorder (N = 36). Family members of patients with dual disorders perceived their ill relatives to have greater control over the causes of their psychiatric symptoms and to be more responsible for their symptoms than did family members of patients with SMI only. Key relatives of dual-diagnosed patients also reported more negative affect toward the patient than did key relatives of patients with SMI only, but the two groups did not differ in their level of positive affect. Consistent with attribution theory, severity of patients' substance abuse was positively associated with relatives' attributions of controllability, which, in turn, were positively associated with judgments of responsibility. Furthermore, judgments of responsibility were positively related to negative affect and inversely related to positive affect. C1 Calif State Univ Los Angeles, Integrated Subst Abuse Program, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90025 USA. Calif State Univ Los Angeles, Dept Psychol, Los Angeles, CA 90025 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Dartmouth Coll Sch Med, Concord, NH USA. RP Niv, N (reprint author), Calif State Univ Los Angeles, Integrated Subst Abuse Program, Dept Psychiat & Biobehav Sci, 1640 S Sepulveda Blvd,Suite 200, Los Angeles, CA 90025 USA. EM noosha23@yahoo.com FU NIMH NIH HHS [MH62629, MH14584] NR 43 TC 6 Z9 7 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD APR PY 2007 VL 195 IS 4 BP 307 EP 314 DI 10.1097/01.nmd.0000243793.64279.48 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 158KM UT WOS:000245790400005 PM 17435480 ER PT J AU Ott, CH Lueger, RJ Kelber, ST Prigerson, HG AF Ott, Carol H. Lueger, Robert J. Kelber, Sheryl T. Prigerson, Holly G. TI Spousal bereavement in older adults - Common, resilient, and chronic grief with defining characteristics SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE bereavement; common grief; resilience in grief; chronic grief; complicated grief; grief clusters ID COMPLICATED GRIEF; SOCIAL SUPPORT; TRAUMATIC GRIEF; DEPRESSIVE SYMPTOMS; PHYSICAL HEALTH; PATTERNS; LIFE; WIDOWHOOD; QUALITY; HELP AB The purpose of this study was to identify empirically patterns of grief among 141 older bereaved spouses. A longitudinal hierarchical cluster procedure with the Ward agglomeration method was used to identify distinct clusters based on grief scores. Three clusters were identified: common (49%), resilient (34%), and chronic (17%) grief Members of the common grief cluster experienced elevated levels of grief and depressive symptoms that decreased over time. Members of the resilient cluster experienced the lowest levels of grief and depression and the highest quality of life. The chronic grief cluster experienced the highest levels of grief and depression, more sudden deaths, the lowest self-esteem, and the highest marital dependency. The majority in this chronic cluster also met proposed criteria for a diagnosis of complicated grief. Five out of every six bereaved spouses adjusted well over time, and about a third of these showed considerable resilience without negative consequences. One out of six experienced a chronic grief syndrome. Early identification of this syndrome can lead to referral to newly emergent treatments specific for grief. C1 Univ Wisconsin, Coll Nursing, Milwaukee, WI 53201 USA. St Edwards Univ, Austin, TX 78704 USA. Harvard Univ, Sch Med, Ctr Psychooncol & Palliat Care Res,Brigham & Wome, Dana Farber Canc Inst,Dept Psychiat, Cambridge, MA 02138 USA. RP Ott, CH (reprint author), Univ Wisconsin, Coll Nursing, POB 413, Milwaukee, WI 53201 USA. EM carolott@uwm.edu FU NCI NIH HHS [R01 CA106370, CA106370]; NIMH NIH HHS [MH56529, MH63892] NR 59 TC 50 Z9 51 U1 4 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD APR PY 2007 VL 195 IS 4 BP 332 EP 341 DI 10.1097/01.nmd.0000243890.93992.1e PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 158KM UT WOS:000245790400009 PM 17435484 ER PT J AU Doyle, R Mick, E Biederman, J AF Doyle, Robert Mick, Eric Biederman, Joseph TI Convergence between the Achenbach youth self-report and structured diagnostic interview diagnoses in ADHD and non-ADHD youth SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE ADHD; youth self-report; CBCL ID CHILD-BEHAVIOR CHECKLIST; PSYCHIATRIC DIAGNOSES; COMORBIDITY AB We evaluated the convergence of Achenbach youth self-report (YSR) scales with attention-deficit hyperactivity disorder (ADHD) and psychiatric comorbidity derived from self-report structured interviews. Subjects were 251 youths older than 12 years assessed with YSR scales and directly obtained structured diagnostic interview. We evaluated the strength of association between each YSR scale and structured-interview derived diagnoses using total predictive value (TPV) and odds ratios (OR). Excellent convergence was found between the YSR attention problems with the structured interview derived diagnosis of ADHD, between the YSR delinquent behavior scale and the diagnosis of conduct disorder, and between the YSR anxiety/depression and withdrawn scales and the diagnosis of major depression, and between the YSR social problems and somatic scales and the diagnosis of anxiety. These findings indicate that the YSR could serve as a rapid and cost-effective diagnostic tool to identify major psychopathology in high-risk adolescents. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Pediat Psychopharmacol Unit, Boston, MA 02114 USA. RP Doyle, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Pediat Psychopharmacol Unit, WACC 725,15 Parkman St, Boston, MA 02114 USA. EM rdoyle@partners.org OI Mick, Eric/0000-0001-8505-8145 NR 7 TC 10 Z9 11 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD APR PY 2007 VL 195 IS 4 BP 350 EP 352 DI 10.1097/01.nmd.0000253732.79172.43 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 158KM UT WOS:000245790400011 PM 17435486 ER PT J AU Pannu, R Christie, DK Barbosa, E Singh, I Singh, AK AF Pannu, Ravinder Christie, Douglas K. Barbosa, Ernest Singh, Inderjit Singh, Avtar K. TI Post-trauma Lipitor treatment prevents endothelial dysfunction, facilitates neuroprotection, and promotes locomotor recovery following spinal cord injury SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE endothelium; gliosis; MMP9; RhoA; spinal cord injury; statins ID NITRIC-OXIDE SYNTHASE; TUMOR-NECROSIS-FACTOR; BLOOD-BRAIN-BARRIER; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; AMYLOID PRECURSOR PROTEIN; COA REDUCTASE INHIBITORS; RAT PRIMARY ASTROCYTES; GROWTH CONE COLLAPSE; FUNCTIONAL RECOVERY; MULTIPLE-SCLEROSIS AB We have previously reported neuroprotection in spinal cord injury (SCI) by Lipitor [atorvastatin (AT)]-pre-treatment. Though informative, pre-treatment studies find only limited clinical application as trauma occurrence is unpredictable. Therefore, this study investigates the efficacy of AT treatment post-SCI. In a rat model of contusion-SCI resulting in complete hindlimb paralysis, AT treatment (5 mg/kg; gavage) was begun 2, 4, or 6 h post-SCI followed by a once daily dose thereafter for 6 weeks. While the placebo vehicle (VHC)-SCI rats showed substantial functional deficit, AT-SCI animals exhibited significant functional recovery. AT diminished injury-induced blood-spinal cord barrier (BSCB) dysfunction with significantly reduced infiltration and tumor necrosis factor-alpha/interleukin-1 beta/inducible nitric oxide synthase expression at site of injury. BSCB protection in AT-SCI was attributable to attenuated matrix metalloproteinase-9 (MMP9) expression - a central player in BSCB disruption. Furthermore, endothelial MMP9 expression was found to be RhoA/ROCK pathway-mediated and regulated by AT through an isoprenoid-dependent mechanism. Attenuation of these early inflammatory events reduced secondary damage. Significant reduction in axonal degeneration, myelin degradation, gliosis, and neuronal apoptosis with resultant enhancement in tissue sparing was observed in AT-SCI compared with VHC-SCI. In summary, this novel report presenting the efficacy of post-injury AT treatment might be of critical therapeutic value as effective treatments are currently unavailable for SCI. C1 Med Univ S Carolina, Charles Darby Childrens Res Inst, Dept Pediat, Ctr Dev Neurol Disorders, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Dept Pathol & Lab Med, Charleston, SC USA. RP Singh, AK (reprint author), Med Univ S Carolina, Charles Darby Childrens Res Inst, Dept Pediat, Ctr Dev Neurol Disorders, Room 509,173 Ashley Ave, Charleston, SC 29425 USA. EM singhi@musc.edu FU NCRR NIH HHS [C06RR018823]; NINDS NIH HHS [NS-22576, NS-34741, NS-37766, NS-40810] NR 77 TC 51 Z9 57 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 2007 VL 101 IS 1 BP 182 EP 200 DI 10.1111/j.1471-4159.2006.04354.x PG 19 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 145SU UT WOS:000244885600017 PM 17217414 ER PT J AU Price, DA Owens, WA Gould, GG Frazer, A Roberts, JL Daws, LC Giuffrida, A AF Price, David A. Owens, William A. Gould, Georgianna G. Frazer, Alan Roberts, James L. Daws, Lynette C. Giuffrida, Andrea TI CB1-independent inhibition of dopamine transporter activity by cannabinoids in mouse dorsal striatum SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE anandamide; basal ganglia; cannabinoid; chronoamperometry; dopamine transporter; striatum ID NIGRA PARS RETICULATA; NUCLEUS-ACCUMBENS; SUBSTANTIA-NIGRA; GABAERGIC NEUROTRANSMISSION; ENDOGENOUS CANNABINOIDS; NEURONAL SUBPOPULATIONS; GLOBUS-PALLIDUS; AWAKE RATS; RECEPTOR; RELEASE AB Cannabinoid drugs are known to affect dopaminergic neurotransmission in the basal ganglia circuitry. In this study, we used in vitro and in vivo techniques to investigate whether cannabinoid agonists and antagonist could affect dopaminergic transmission in the striatum by acting at the dopamine transporter. Incubation of striatal synaptosomes with the cannabinoid agonists WIN55,212-2 or methanandamide decreased dopamine uptake (IC50 = 2.0 mu mol/L and 3.1 mu mol/L, respectively). A similar inhibitory effect was observed after application of the inactive WIN55,212-2 isomer, S(-)WIN55,212-3. The CB1 antagonist AM251 did not reverse WIN55,212-2 effect but rather mimicked it. WIN55,212-2 and AM251 partially displaced the binding of the cocaine analog [H-3]WIN35,428, thus acting as dopamine transporter pseudo-substrates in the high micromolar range. High-speed chronoamperometry measurements showed that WIN55,212-2 (4 mg/kg, i.p.) caused significant release of endogenous dopamine via activation of CB1 receptors, followed by a reduction of dopamine clearance. This reduction was CB1-independent, as it was mimicked by S(-)WIN55,212-3. Administration of AM251 (1 and 4 mg/kg, i.p.) increased the signal amplitude and reduced the clearance of dopamine pressure ejected into the striatum. These results indicate that both cannabinoid agonists and antagonists inhibit dopamine transporter activity via molecular targets other than CB1 receptors. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. Audie L Murphy Vet Affairs Med Ctr, San Antonio, TX USA. RP Giuffrida, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, 7703 Floyd Curl Dr,MC 6205, San Antonio, TX 78229 USA. EM giuffrida@uthscsa.edu OI Gould, Georgianna/0000-0002-5470-8763 FU NIA NIH HHS [T32 AG021890]; NIDA NIH HHS [DA 018922]; NINDS NIH HHS [NS 050401] NR 52 TC 24 Z9 27 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 2007 VL 101 IS 2 BP 389 EP 396 DI 10.1111/j.1471-4159.2006.04383.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 151TD UT WOS:000245312800009 PM 17250681 ER PT J AU Freeman, SH Raju, S Hyman, BT Frosch, MP Irizarry, MC AF Freeman, Stefanie H. Raju, Susan Hyman, Bradley T. Frosch, Matthew P. Irizarry, Michael C. TI Plasma A beta levels do not reflect brain A beta levels SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer disease; beta-amyloid; biomarkers; neurodegneration ID PROGRESSIVE SUPRANUCLEAR PALSY; RICHARDSON-OLSZEWSKI-SYNDROME; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; CONSENSUS RECOMMENDATIONS; NEUROPATHOLOGIC CRITERIA; POSTMORTEM DIAGNOSIS; PROTEIN; DEMENTIA AB Cerebral accumulation of amyloid P protein (AP) is characteristic of Alzheimer disease (AD). AP can be detected in cerebrospinal fluid and in plasma. Although plasma Ap has been proposed as a marker of risk of AD, it is unknown how plasma levels relate to neuropathologic levels. We compared plasma levels of A beta 40 and A beta 42 obtained during life with biochemical and pathologic levels in frontal and temporal neocortex in 25 individuals (17 AD, 3 control, and 5 non-AD dementia) who (lied a median of I year after blood collection. Plasma levels of A beta 40 and A beta 42 were not associated with any of the brain measures, even after adjusting for age and interval between plasma collection and death. The APOE epsilon 4 allele may modify the relationship between plasma A beta 42 and formic acid-extractable A beta 42, with an inverse correlation in APOE epsilon 4 carriers and a positive correlation in those lacking APOE '-4. We conclude that plasma levels of A beta 40 and A beta 42 are not robust correlates of histologic or biochemically assessed amyloid burdens in brain, although the influence of the APOE genotype should be further explored. C1 Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Alzheimer Res Unit, MassGen Inst Neurodegenerat Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Freeman, SH (reprint author), Massachusetts Gen Hosp East, Alzheimers Dis Res Unit, B114,114 16th St, Charlestown, MA 02129 USA. EM sfreeman1@partners.org FU NIA NIH HHS [P01AG004953, AG05134]; NINDS NIH HHS [T32NS048005] NR 29 TC 48 Z9 48 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD APR PY 2007 VL 66 IS 4 BP 264 EP 271 DI 10.1097/NEN.0b013e31803d3ae4 PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 173DD UT WOS:000246852800003 PM 17413317 ER PT J AU Maison, SF Parker, LL Young, L Adelman, JP Zuo, J Liberman, MC AF Maison, Stephane F. Parker, Lisan L. Young, Lucy Adelman, John P. Zuo, Jian Liberman, M. Charles TI Overexpression of SK2 channels enhances efferent suppression of cochlear responses without enhancing noise resistance SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID OUTER HAIR-CELLS; NICOTINIC ACETYLCHOLINE-RECEPTORS; CROSSED OLIVOCOCHLEAR BUNDLE; ACOUSTIC INJURY; GUINEA-PIG; ELECTROMOTILITY; STIMULATION; PROTECTION; MICE; INHIBITION AB Cochlear hair cells express SK2, a small-conductance Ca(2+)-activated K(+) channel thought to act in concert with Ca(2+)-permeable nicotinic acetylcholine receptors (nAChRs) alpha 9 and alpha 10 in mediating suppressive effects of the olivocochlear efferent innervation. To probe the in vivo role of SK2 channels in hearing, we examined gene expression, cochlear function, efferent suppression, and noise vulnerability in mice overexpressing SK2 channels. Cochlear thresholds, as measured by auditory brain stem responses and otoacoustic emissions, were normal in overexpressers as was overall cochlear morphology and the size, number, and distribution of efferent terminals on outer hair cells. Cochlear expression levels of SK2 channels were elevated eightfold without striking changes in other SK channels or in the alpha 9/alpha 10 nAChRs. Shock-evoked efferent suppression of cochlear responses was significantly enhanced in overexpresser mice as seen previously in alpha 9 overexpresser mice; however, in contrast to alpha 9 overexpressers, SK2 overexpressers were not protected from acoustic injury. Results suggest that efferent-mediated cochlear protection is mediated by other downstream effects of ACh-mediated Ca(2+) entry different from those involving SK2-mediated hyperpolarization and the associated reduction in outer hair cell electromotility. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02115 USA. St Jude Childrens Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA. Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97201 USA. RP Maison, SF (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM sfm@epl.meei.harvard.edu FU NCI NIH HHS [CA-21765, P30 CA021765]; NIDCD NIH HHS [R01DC-06471, P30 DC-05029, R01 DC000188, P30 DC005209, R01 DC006471, R01DC-0188] NR 38 TC 16 Z9 16 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD APR PY 2007 VL 97 IS 4 BP 2930 EP 2936 DI 10.1152/jn.01183.2006 PG 7 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 188OT UT WOS:000247929900032 PM 17267753 ER PT J AU Adelson, DW Kosoyan, HP Wang, YH Steinberg, JZ Tache, Y AF Adelson, David W. Kosoyan, Hovsep P. Wang, Yuhua Steinberg, Justin Z. Tache, Yvette TI Gastric vagal efferent inhibition evoked by intravenous CRF is unrelated to simultaneously recorded vagal afferent activity in urethane-anesthetized rats SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; DORSAL MOTOR NUCLEUS; IMMERSION-RESTRAINT STRESS; ACUTE LIVER-INJURY; IN-VITRO; SUBDIAPHRAGMATIC VAGUS; ABDOMINAL-SURGERY; MESSENGER-RNAS; RECEPTORS; NEURONS AB Corticotropin-releasing factor (CRF) injected peripherally or released in response to stressful challenges to the organism reduces gastric tone and contractility, in part by vagal pathways. However, information on the changes in gastric vagal impulse activity evoked by peripheral CRF administration is entirely lacking. Using a novel "dual recording" method in urethane-anesthetized rats, vagal efferent (VE) and afferent (VA) impulse activities were recorded simultaneously from separate, fine bundles dissected from the ventral gastric vagus nerve branch innervating the glandular stomach. Activity records for 38 VA single units (SUs) and 33 VE SUs were sorted from multiunit records obtained from 13 preparations. Intravenous (iv) administration of saline had no effect on multiunit VE activity, whereas CRF (1 mu g/kg, iv) immediately inhibited VE activity, reaching a nadir of 54 +/- 8.0% of preinjection levels at 3.0 min postinjection. CRF (1 mu g/kg, iv) inhibited 25/33 (75.8%) VE SUs and excited three of 33 (9.1%) VE SUs. In contrast to potent effects on VE activity, iv CRF did not alter multiunit VA activity. Single-unit analysis, however, revealed five of 38 (13.1%) VA SUs excited by iv CRF at widely varying latencies (suggesting an indirect mode of action) and one inhibited VA SU. VA SUs excited after iv CRF did not respond during gastric distention and vice versa. These experiments are the first to use simultaneous recording of gastric VA and VE units. The data demonstrate a predominantly inhibitory influence of iv CRF on VE outflow to the hindstomach, not driven by gastric vagovagal reflex activity. C1 Univ Calif Los Angeles, W Los Angeles VAMC, VAGLAHS, Digest Dis Res Ctr,CURE, Los Angeles, CA 90073 USA. RP Adelson, DW (reprint author), Univ Calif Los Angeles, W Los Angeles VAMC, VAGLAHS, Digest Dis Res Ctr,CURE, Bldg 115,Rm 325,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM dadelson@ucla.edu OI Adelson, David/0000-0002-4623-6030 FU NIDDK NIH HHS [R01 DK-33061, R21 DK-074736, DK-41301] NR 65 TC 7 Z9 7 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD APR PY 2007 VL 97 IS 4 BP 3004 EP 3014 DI 10.1152/jn.01143.2006 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 188OT UT WOS:000247929900039 PM 17314242 ER PT J AU Stella, SL Hu, WD Vila, A Brecha, NC AF Stella, Salvatore L., Jr. Hu, Wanda D. Vila, Alejandro Brecha, Nicholas C. TI Adenosine inhibits voltage-dependent Ca2+ influx in cone photorecevtor terminals of the tiger salamander retina SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE FM 4-64; synaptored-C2; fluo-4; VAMP; piccolo ID ENDOGENOUS ADENOSINE; SYNAPTIC-TRANSMISSION; ROD PHOTORECEPTORS; MAMMALIAN RETINA; CALCIUM INFLUX; GANGLION-CELLS; RAT RETINA; RECEPTORS; RELEASE; NEURONS AB Endogenous adenosine has already been shown to inhibit transmitter release from the rod synapse by suppressing Ca2+, influx through voltage-gated Ca2+, channels. However, it is not clear how adenosine modulates the cone synapse. Cone photoreceptors, like rod photoreceptors, also possess L-type Ca2+, channels that regulate the release of L-glutamate. To assess the impact of adenosine on Ca2+, influx though voltage-gated Ca2+ channels in cone terminals, whole-cell perforated-patch clamp recording and Ca2+ imaging with fluo-4 were used on isolated cones and salamander retinal slices. Synaptic markers (VAMP and piccolo) and activity-clependent dye labeling revealed that tiger salamander cone terminals contain a broad, vesicle-filled cytoplasmic extension at the base of the somatic compartment, which is unlike rod terminals that contain one or more thin axons, each terminating in a large bulbous synaptic terminal. The spatiotemporal Ca2+ responses of the cone terminals do not differ significantly from the Ca2+ responses of the soma or inner segment like that observed in rods. Whole-cell recording of cone Ica and Ca2+ imaging of synaptic terminals in cones demonstrate that adenosine inhibited both Ica and the depolarization-evoked Ca2+ increase in cone terminals in a dose-dependent manner from 1 to 50 mu M, with an EC50 of 15.6 mu M. These results indicate that, as in rods, adenosine's ability to suppress voltage-dependent Ca2+ channels at the cone synapse will limit the amount of L-glutamate released. Therefore, adenosine has an inhibitory effect on L-glutamate release at the first synapse, which likely favors elevated adenosine levels in the dark or during dark-adapted conditions. (c) 2007 Wiley-Liss, Inc. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Stella, SL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, 10833 Le Conte Ave,Box 951763,CHS 73-323, Los Angeles, CA 90095 USA. EM sstella@mednet.ucla.edu OI Stella Jr., Salvatore/0000-0003-1971-2537 FU NEI NIH HHS [R01 EY015573, R01 EY004067, R56 EY004067, EY 04067, EY 15573]; NIDDK NIH HHS [DK 41301, P30 DK041301] NR 52 TC 12 Z9 12 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD APR PY 2007 VL 85 IS 5 BP 1126 EP 1137 DI 10.1002/jnr.21210 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 157NK UT WOS:000245726700021 PM 17304584 ER PT J AU Morrison, LJ Scott, JO Block, SD AF Morrison, Laura J. Scott, Judy Opatik Block, Susan D. CA Amer Board Hospice Palliative Med TI Developing initial competency-based outcomes for the hospice and palliative medicine subspecialist: Phase I of the hospice and palliative medicine competencies project SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID EDUCATION AB As a newly recognized subspecialty, the field of hospice and palliative medicine (HPM) must transition existing pathways for board certification, fellowship standards, and fellowship accreditation to one based on the Accreditation Council for Graduate Medical Education and American Board of Medical Specialties competency framework. The Competencies Work Group of the American Board of Hospice and Palliative Medicine, using an iterative process informed by the field, has developed a set of Initial Competency-based Outcomes for the HPM Subspecialist. These competencies will set the standard for the "competent hospice and palliative medicine subspecialist physician," guiding future HPM fellowship training and potential midcareer HPM training opportunities. Lessons learned are highlighted. C1 Baylor Coll Med, Inst Palliat Med, Sect Geriatr, Methodist Hosp, Houston, TX 77030 USA. Amer Board Hospice & Palliat Med, Silver Spring, MD USA. Harvard Univ, Sch Med,Ctr Palliat Care, Brigham & Womens Hosp, Dana Farber Canc Inst,Div Psychol Oncol & Palliat, Boston, MA USA. RP Morrison, LJ (reprint author), Baylor Coll Med, Inst Palliat Med, Sect Geriatr, Methodist Hosp, 1709 Dryden,Suite 850, Houston, TX 77030 USA. EM lmorriso@bcm.tmc.edu OI Morrison, Laura/0000-0002-9610-9435 FU PHS HHS [1-K01-HP-00117] NR 7 TC 21 Z9 21 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD APR PY 2007 VL 10 IS 2 BP 313 EP 330 DI 10.1089/jpm.2006.9980 PG 18 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 165AJ UT WOS:000246275900014 PM 17472502 ER PT J AU Weissman, DE Ambuel, B Von Gunten, CF Block, S Warm, E Hallenbeck, J Milch, R Brasel, K Mullan, PB AF Weissman, David E. Ambuel, Bruce Von Gunten, Charles F. Block, Susan Warm, Eric Hallenbeck, James Milch, Robert Brasel, Karen Mullan, Patricia B. TI Outcomes from a national multispecialty palliative care curriculum development project SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID OF-LIFE CARE; MEDICAL-EDUCATION; RESIDENTS; KNOWLEDGE; PROGRAMS; TRAINEES; SKILLS AB Background: In 1998 we completed a successful regional pilot project in palliative care curriculum development among 32 internal medicine residency programs recruited from the mid-western United States. Between 1999 and 2004 this project was expanded to include 358 U. S. programs, from four specialties, based on new training requirements in internal medicine, family medicine, neurology, and general surgery. Objective: To assess the 1-year outcomes from residency programs participating in a national multispecialty palliative care curriculum development project. Measurement: Outcome data obtained from residency programs' responses to a structured progress report 12 months after enrolling in the project and from published residency project reports. Results: Three hundred fifty-eight residency programs, representing 27% of all eligible training programs in the four specialties, participated in the project. Outcome data was available from 224 residencies (63%). Most programs started new teaching in pain, non-pain symptom management, and communication skills. More than 50% of programs integrated palliative care topics within established institutional grand rounds, morbidity/mortality conferences or morning report. More than 70% of internal medicine and family practice programs began new direct patient care training opportunities utilizing hospital-based palliative care or hospice programs. New faculty development initiatives and use of quality improvement projects to drive curriculum change were reported in less than 50% of programs. Conclusions: Focused short-term instruction in palliative care curriculum development, in a diverse group of residency programs, is feasible and associated with significant curriculum change. C1 Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Calif San Diego, San Diego Hospice & Palliat Care, San Diego, CA 92103 USA. Dana Farber Canc Ctr, Boston, MA USA. Univ Cincinnati, Cincinnati, OH USA. Stanford Univ, Palo Alto Vet Hosp, Stanford, CA 94305 USA. SUNY Buffalo, Ctr Hospice & Palliat Care, Buffalo, NY 14260 USA. Univ Michigan, Sch Med, Ann Arbor, MI USA. RP Weissman, DE (reprint author), Froedtert Hosp, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. EM dweissma@mcw.edu OI Ambuel, Bruce/0000-0002-9837-5729 NR 30 TC 22 Z9 22 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD APR PY 2007 VL 10 IS 2 BP 408 EP 419 DI 10.1089/jpm.2006.0183 PG 12 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 165AJ UT WOS:000246275900025 PM 17472513 ER PT J AU Goldstein, NE Fischberg, D AF Goldstein, Nathan E. Fischberg, Daniel TI Update in hospice and palliative care 2005 SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Review ID TRIAL C1 CUNY Mt Sinai Sch Med, Dept Geriatr, New York, NY 10029 USA. James J Peters VA Med Ctr, Bronx, NY USA. Queens Med Ctr, Pain & Palliat Care Dept, Honolulu, HI USA. RP Goldstein, NE (reprint author), CUNY Mt Sinai Sch Med, Dept Geriatr, 1 Gustave Levy Pl,Box 1070, New York, NY 10029 USA. EM Nathan.Goldstein@mssm.edu NR 6 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD APR PY 2007 VL 10 IS 2 BP 476 EP 482 DI 10.1089/jpm.2006.0167 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 165AJ UT WOS:000246275900031 ER PT J AU Mota, RMV Mankin, H AF Mota, Ronald M. V. Mankin, Henry TI Use of plain radiography to optimize skeletal outcomes in children with type 1 Gaucher disease in Brazil SO JOURNAL OF PEDIATRIC ORTHOPAEDICS LA English DT Article DE Gaucher disease; lysosomal storage; pediatric; bone changes ID ENZYME REPLACEMENT THERAPY; RECOMMENDATIONS; REGISTRY AB Background: Gaucher disease is the most common lysosomal storage disease and is caused by deficient production and activity of the lysosomal enzyme beta-glucosidase (glucocerebrosidase), resulting in progressive accumulation of glucosylceramide (glucocerebroside) in lysosomes of cells of the reticuloendothelial system in the spleen, liver, and marrow. Clinical manifestations include anemia, thrombocytopenia, hepatosplenomegaly, and bone complications, including bone pain, bone marrow infiltration, lytic lesions, osteopenia, pathological fractures, and avascular necrosis. Early, adequate, and sustained treatment with enzyme replacement therapy (ERT) available since 1991 can change the natural history of the disease, particularly in children. Skeletal complications are usually the major source of disease morbidity and disability and although magnetic resonance imaging and dual-energy x-ray absorptiometry densitometry are recommended for monitoring, these are not readily available in all countries. Methods: We describe 18 Brazilian children with type I Gaucher disease with bone involvement who were followed with plain radiography for at least 8 months after beginning imiglucerase ERT (initial dose, 15-60 U/kg body weight/15 days). Bone involvement noted by plain radiograph included marrow infiltration, osteopenia, pathological fractures, osteonecrosis, lytic lesions, and Erlenmeyer flask deformity. Patients were questioned about bone crises. Results: Patients were followed for up to 10 years (mean follow-up, 4 years and 4 months 3 years and 3 months). Bone changes were visible by plain radiographs in all patients. Clinical and radiological improvement was noted in 13 (72%) of 18 patients; bone lesions worsened in 5 (28%) of 18 patients. The final ERT dose for the 13 patients who improved was 55 +/- 10 U/kg (range, 30-60 U/kg), and the final ERT dose for the 5 who Worsened was 29 2 U/kg (range, 26-30 U/kg); this difference was statistically significant (P < 0.03). Conclusions: When other imaging technologies are not available, skeletal response to ERT in children with type 1 Gaucher disease can be monitored effectively by plain radiography. Higher doses of ERT (50-60 U/kg / 15 days) may be required for improvement of skeletal manifestations. Clinical Evidence: Case series; level 4. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Socor Hosp, Dept Pediat Orthoped, Belo Horizonte, MG, Brazil. RP Mankin, H (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 1122A Jackson Bldg, Boston, MA 02114 USA. EM hmankin@partners.org NR 14 TC 3 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-6798 J9 J PEDIATR ORTHOPED JI J. Pediatr. Orthop. PD APR-MAY PY 2007 VL 27 IS 3 BP 347 EP 350 PG 4 WC Orthopedics; Pediatrics SC Orthopedics; Pediatrics GA 154XE UT WOS:000245540500019 PM 17414023 ER PT J AU El-Hallak, M Binstadt, BA Leichtner, AM Bennett, CM Neufeld, EJ Fuhlbrigge, RC Zurakowski, D Sundel, RP AF El-Hallak, Moussa Binstadt, Bryce A. Leichtner, Alan M. Bennett, Carolyn M. Neufeld, Ellis J. Fuhlbrigge, Robert C. Zurakowski, David Sundel, Robert P. TI Clinical effects and safety of rituximab for treatment of refractory pediatric autoimmune diseases SO JOURNAL OF PEDIATRICS LA English DT Article ID JUVENILE RHEUMATOID-ARTHRITIS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; B-LYMPHOCYTE DEPLETION; DOSE METHOTREXATE; HEMOLYTIC-ANEMIA; THERAPY; CELLS; CHILDREN; TRIAL; ANTIBODIES AB Objective: To evaluate the safety, tolerability, and clinical effects of rituximab, an anti-CD20 monoclonal antibody, in the treatment of severe pediatric autoimmune diseases. Study design: We reviewed the records of 10 patients treated with rituximab for severe, refractory autoimmune diseases at a single tertiary care children's hospital. Adverse events as well as treatment effects were recorded. Results: All patients received 4 weekly doses of rituximab at 375 mg/m(2) per dose. One patient died as the result of complications of her underlying systemic lupus erythernatosus 7 weeks after rituximab therapy. Three patients had serious infections, all of which resolved with standard therapy. Rituximab led to transient or sustained improvement in clinical and laboratory parameters in nine subjects. At a median follow-up of 9 months, the median prednisone dose was reduced in the responders by 0.75 mg/kg per day (mean decrease of 63%), and four patients were able to discontinue corticosteroids entirely. With longer follow-up (median, 22 months), we found that 5 of 9 patients remained clinically stable after rituximab, therapy, whereas 4 patients had recurrent or new features of their underlying autoimmune disorders requiring additional corticosteroids or other immunosuppressive medications. Conclusions: Rituximab had an acceptable toxicity profile in this group of patients with severe, refractory autoimmune diseases, although there were three serious infections and one patient death. Rituximab appears to be beneficial for patients with refractory autoimmune diseases and may reduce corticosteroid exposure. Although rituximab therapy provided a durable clinical benefit for some patients in. this population, other patients bad reemergence of their underlying autoimmune disease. C1 Childrens Hosp Boston, Rheumatol Program, Dept Med, Boston, MA 02115 USA. Childrens Hosp Boston, Program Gastroenterol, Dept Med, Boston, MA 02115 USA. Childrens Hosp Boston, Program Hematol, Dept Med, Boston, MA 02115 USA. Childrens Hosp Boston, Dept Orthopaed Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02115 USA. RP Sundel, RP (reprint author), Childrens Hosp Boston, Rheumatol Program, Dept Med, 300 Longwood Ave, Boston, MA 02115 USA. EM robert.sundel@childrens.harvard.edu RI Neufeld, Ellis/F-9331-2011; Binstadt, Bryce/N-1305-2013; OI Binstadt, Bryce/0000-0003-3127-3856; Sundel, Robert/0000-0002-0083-5695 NR 37 TC 40 Z9 45 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD APR PY 2007 VL 150 IS 4 BP 376 EP 382 DI 10.1016/j.jpeds.2006.10.067 PG 7 WC Pediatrics SC Pediatrics GA 154VJ UT WOS:000245535600013 PM 17382113 ER PT J AU Zemnick, C Woodhouse, SA Gewanter, RM Raphael, M Piro, JD AF Zemnick, Candice Woodhouse, Shermian A. Gewanter, Richard M. Raphael, Michael Piro, John D. TI Rapid prototyping technique for creating a radiation shield SO JOURNAL OF PROSTHETIC DENTISTRY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Prosthodontic-Society CY FEB, 2006 CL Chicago, IL SP Amer Prosthodont Soc ID DEVELOPING FACIAL PROSTHESES; MOHS MICROGRAPHIC SURGERY; COMPUTED-TOMOGRAPHY; CAD/CAM TECHNIQUES; FABRICATION; STEREOLITHOGRAPHY; SURFACE; DESIGN; INTEGRATION; TECHNOLOGY AB Radiation therapy for the treatment of head and neck skin cancer poses challenges because of the inherently uneven tissue topography of the face and the need to protect surrounding unaffected tissues. The use of a customized radiation shield that combines tissue-equivalent bolus material with protective material addresses these issues. This article describes a technique using rapid prototyping to design and fabricate an extraoral radiation shield. This innovative application provides an expedient, standardized approach for delivering radiotherapy to the face, which is not only more comfortable for the patient, but allows more precise treatment delivery. C1 Bronx Vet Adm Med Ctr, Bronx, NY 10468 USA. Columbia Univ, Div Prosthodont, Coll Dent Med, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Radiat Oncol, New York, NY USA. Direct Dimens Inc, Owings Mills, MD USA. RP Zemnick, C (reprint author), Bronx Vet Adm Med Ctr, Bronx, NY 10468 USA. EM cbz2001@columbia.edu NR 26 TC 9 Z9 9 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3913 J9 J PROSTHET DENT JI J. Prosthet. Dent. PD APR PY 2007 VL 97 IS 4 BP 236 EP 241 DI 10.1016/j.prosdent.2007.02.005 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 169KU UT WOS:000246591900009 PM 17499094 ER PT J AU Nierenberg, AA Trivedi, MH Fava, M Biggs, MM Shores-Wilson, K Wisniewski, SR Balasubrainani, GK Rush, AJ AF Nierenberg, Andrew A. Trivedi, Madhukar H. Fava, Maurizio Biggs, Melanie M. Shores-Wilson, Kathy Wisniewski, Stephen R. Balasubrainani, G. K. Rush, A. John TI Family history of mood disorder and characteristics of major depressive disorder: A STAR*D (sequenced treatment alternatives to relieve depression) study SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE family; history; major depressive disorder ID UNIPOLAR DEPRESSION; ANXIOUS DEPRESSION; SYMPTOMATOLOGY IDS; SPECTRUM DISEASE; RATING SCALE; SUBTYPES; RELATIVES; DIAGNOSIS; VALIDITY; ONSET AB Introduction: Clinicians routinely ask patients with major depressive disorder (MDD) about their family history. It is unknown, however, if patients who report a positive family history differ from those who do not. This study compared the demographic and clinical features of a large cohort of treatment-seeking outpatients with non-psychotic MDD who reported that they did or did not have at least one first-degree relative who had either MDD or bipolar disorder. Methods: Subjects were recruited for the STAR*D multicenter trial. Differences in demographic and clinical features for patients with and without a family history of mood disorders were assessed after correcting for age, sex, race, and ethnicity. Results: Patients with a family history of mood disorder (n = 2265; 56.5%) were more frequently women and had an earlier age of onset of depression, as compared to those without such a history (n = 1740; 43.5%). No meaningful differences were found in depressive symptoms, severity, recurrence, depressive subtype, or daily function. Conclusions: Women were twice as likely as men to report a positive family history of mood disorder, and a positive family history was associated with younger age of onset of MDD in the proband. Consistent with prior research, early age of onset appears to define a familial and, by extension, genetic subtype of major depressive disorder. (c) 2006 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75230 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA 15260 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, ACC 812,15 Parkman St, Boston, MA 02114 USA. EM anierenberg@partners.org RI Biggs, Dr. Melanie/C-1468-2010; OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01MH90003] NR 47 TC 31 Z9 33 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD APR-JUN PY 2007 VL 41 IS 3-4 BP 214 EP 221 DI 10.1016/j.jpsychires.2006.02.005 PG 8 WC Psychiatry SC Psychiatry GA 122GP UT WOS:000243214000003 PM 16690084 ER PT J AU Simon, NM Zalta, AK Otto, MW Ostacher, MJ Fischmann, D Chow, CW Thompson, EH Stevens, JC Demopulos, CM Nierenberg, AA Pollack, MH AF Simon, Naomi M. Zalta, Alyson K. Otto, Michael W. Ostacher, Michael J. Fischmann, Diana Chow, Candice W. Thompson, Elizabeth H. Stevens, Julie C. Demopulos, Christina M. Nierenberg, Andrew A. Pollack, Mark H. TI The association of comorbid anxiety disorders with suicide attempts and suicidal ideation in outpatients with bipolar disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the Association-for-Behavioral-and-Cognitive-Therapies CY NOV, 2005 CL Washington, DC SP Assoc Behav & Cognit Therapies DE bipolar disorder; anxiety disorder; comorbid; suicide; suicidal ideation; social anxiety disorder ID TREATMENT ENHANCEMENT PROGRAM; PANIC DISORDER; I-DISORDER; STEP-BD; GENERAL-POPULATION; RISK-FACTORS; BEHAVIOR; PREDICTORS; TIME; CARE AB Individuals with bipolar disorder are at increased risk for suicide attempts and completion. Although anxiety may be a modifiable suicide risk factor among bipolar patients, anxiety disorder comorbidity has not been highlighted as critical in identification of high-risk individuals nor has its treatment been integrated into suicide prevention strategies. In this study, ancillary to the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), 120 outpatients with bipolar disorder completed detailed assessment of suicidal ideation and behaviors. We examined the association of current and lifetime comorbid anxiety disorders with suicidal ideation and behaviors univariately and with adjustment for potential confounders in regression models. Lifetime anxiety disorders were associated with a more than doubling of the odds of a past suicide attempt, and current anxiety comorbidity was associated with a more than doubling of the odds of current suicidal ideation. Individuals with current anxiety disorders had more severe suicidal ideation, a greater belief suicide would provide relief, and a higher expectancy of future suicidal behaviors. However, some of these associations appeared to be better accounted for by measures of bipolar severity including an earlier age at bipolar onset and a lack of current bipolar recovery. Comorbid anxiety disorders may play a role in characteristics of bipolar disorder that then elevate risk for suicidal ideation and attempts. While further research is needed to establish the precise nature of these associations, our data support that the presence of comorbid anxiety disorders in individuals with bipolar disorder should trigger careful clinical assessment of suicide risk. (c) 2006 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Dept Psychiat, 185 Cambridge St,Suite 2200,Simches Res Bldg, Boston, MA 02114 USA. EM NSIMON@Partners.org OI Ostacher, Michael/0000-0003-0353-7535; Zalta, Alyson/0000-0002-5159-8431 FU NIMH NIH HHS [MH01831-01] NR 48 TC 81 Z9 84 U1 2 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD APR-JUN PY 2007 VL 41 IS 3-4 BP 255 EP 264 DI 10.1016/j.jpsychires.2006.08.004 PG 10 WC Psychiatry SC Psychiatry GA 122GP UT WOS:000243214000008 PM 17052730 ER PT J AU Goldstein, EA Heaton, JT Stepp, CE Hillman, RE AF Goldstein, Ehab A. Heaton, James T. Stepp, Cara E. Hillman, Robert E. TI Training effects on speech production using a hands-free electromyographically controlled electrolarynx SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE alaryngeal speech treatment; artificial larynx; electromyography; laryngectomy; speech ID TOTAL LARYNGECTOMY; MUSCLES; COMMUNICATION; PROSTHESIS; STRAP; ARM; REHABILITATION; PHONATION; SPEAKERS; SIGNALS AB Purpose: The electrolarynx (EL) is a widely used device for alaryngeal speech, but it requires manual operation and produces voice that typically has a constant fundamental frequency. An electromyographically controlled EL (EMG-EL).was designed and implemented to provide hands-free control with dynamic pitch modulation. Method: Three participants who underwent total laryngectomy surgery and 4 participants with normal voice were trained to produce EMG-EL speech through a multiple-baseline, successive-stage protocol. Baseline performance was established through 3 testing probes, followed by multiple hour-long training sessions. Results: At the end of the training, all participants learned to initiate, sustain, and terminate EMG-EL activation in correspondence with articulation, and most were able to modulate the pitch to produce intonational contrasts. After completing the testing/training protocol, 1 of the 3 participants, who underwent total laryngectomy was encouraged to independently use the EMG-ELat his residence. This participant sustained his performance for an additional 6 weeks and also used the EMG-EL successfully to communicate over the phone. Conclusions: Our findings suggest that some participants with laryngectomies and vocally normal individuals can learn to produce hands-free speech using the EMG-EL device within a few hours and that significant additional gains in device control (particularly pitch modulation) are attainable through subsequent training sessions. C1 Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, England. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, England. RP Heaton, JT (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM jheaton@partners.org FU NIDCD NIH HHS [R01-DC006449] NR 42 TC 10 Z9 10 U1 0 U2 3 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD APR PY 2007 VL 50 IS 2 BP 335 EP 351 DI 10.1044/1092-4388(2007/024) PG 17 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 168XR UT WOS:000246557800006 PM 17463233 ER PT J AU Silver, J Mayer, RS AF Silver, Julie Mayer, R. Samuel TI Barriers to pain management in the rehabilitation of the surgical oncology patient SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE cancer pain; surgical oncology; rehabilitation; opioid ID QUALITY-OF-LIFE; CANCER PAIN; PHYSICAL-ACTIVITY; HEALTH-STATUS; OPIOIDS; PREVALENCE; THERAPIES; FENTANYL; TRIAL; COMPLICATIONS AB Virtually every surgical oncology patient faces pain, and it can become a major barrier to rehabilitation and quality of life. Pain must be assessed as to its severity, etiology (somatic, visceral, or neuropathic), causation (directly from malignancy or from treatment side effects), and its impact on daily function. Treatments can include physical modalities, exercise, opioids, adjuvant medications, and interventional techniques. Barriers to treatment may include side effects, finances, and attitudes. New technologies in medication delivery systems, intrathecal pumps, injections, and surgery have greatly strengthened the armamentarium available to manage pain. J. Surg. Oncol. 2007;95:427-435. (C) 2007 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA 02115 USA. Spaulding Rehabil Hosp, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Dept PM&R, Baltimore, MD USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. RP Silver, J (reprint author), 570 Worcester Rd, Boston, MA USA. EM jksilver@bics.bwh.harvard.edu NR 75 TC 8 Z9 10 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD APR 1 PY 2007 VL 95 IS 5 BP 427 EP 435 DI 10.1002/jso.20780 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 165EY UT WOS:000246288000009 PM 17377956 ER PT J AU Kalluri, R Shera, CA AF Kalluri, Radha Shera, Christopher A. TI Near equivalence of human click-evoked and stimulus-frequency otoacoustic emissions SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID OTO-ACOUSTIC EMISSIONS; DISTORTION-PRODUCT; HUMAN EAR; BASILAR-MEMBRANE; FINE-STRUCTURE; GUINEA-PIG; PURE-TONE; DPOAE; WAVE; COCHLEA AB Otoacoustic emissions (OAEs) evoked by broadband clicks and by single tones are widely regarded as originating via different mechanisms within the cochlea. Whereas the properties of stimulus-frequency OAEs (SFOAEs) evoked by tones are consistent with an origin via linear mechanisms involving coherent wave scattering by preexisting perturbations in the mechanics, OAEs evoked by broadband clicks (CEOAEs) have been suggested to originate via nonlinear interactions among the different frequency components of the stimulus (e.g., intermodulation distortion). The experiments reported here test for bandwidth-dependent differences in mechanisms of OAE generation. Click-evoked and stimulus-frequency OAE input/output transfer functions were obtained and compared as a function of stimulus frequency and intensity. At low and moderate intensities human CEOAE and SFOAE transfer functions are nearly identical. When stimulus intensity is measured in "bandwidth-compensated" sound-pressure level (cSPL), CEOAE and SFOAE transfer functions have equivalent growth functions at fixed frequency and equivalent spectral characteristics at fixed intensity. This equivalence suggests that CEOAEs and SFOAEs are generated by the same mechanism. Although CEOAEs and SFOAEs are known by different names because of the different stimuli used to evoke them, the two OAE "types" are evidently best understood as members of the same emission family. (c) 2007 Acoustical Society of America. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Speech & Hearing Figure Biosci & Technol Program, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Shera, CA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. EM shera@epl.meei.harvard.edu FU NIDCD NIH HHS [R01 DC03687, R01 DC003687] NR 47 TC 72 Z9 74 U1 0 U2 2 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD APR PY 2007 VL 121 IS 4 BP 2097 EP 2110 DI 10.1121/1.2435981 PG 14 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 156ZE UT WOS:000245687600027 PM 17471725 ER PT J AU Tufts, JB Molis, MR AF Tufts, Jennifer B. Molis, Michelle R. TI Perception of roughness by listeners with sensorineural hearing loss SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID MUSICAL TENSION; DISSONANCE; NOISES; PITCH AB The perception of auditory roughness presumably results from imperfect spectral or temporal resolution. Sensorineural hearing loss, by affecting spectral resolution, may therefore alter roughness perception. In this study, normal-hearing and hearing-impaired listeners estimated the roughness of amplitude-modulated tones varying in carrier frequency, modulation rate, and modulation depth. Their judgments were expected to reflect effects of impaired spectral resolution. Instead, their judgments were similar, in most respects, to those of normally-hearing listeners, except at very slow modulation rates. Results suggest that mild-to-moderate sensorineural hearing loss increases the roughness of slowly fluctuating signals. (c) 2007 Acoustical Society of America. C1 Univ Connecticut, Dept Commun Sci, Storrs, CT 06269 USA. Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, Portland, OR 97207 USA. RP Tufts, JB (reprint author), Univ Connecticut, Dept Commun Sci, 850 Balton Ave,Unit 1085, Storrs, CT 06269 USA. EM jennifer.tufts@uconn.edu; michelle.molis@va.gov FU NIDCD NIH HHS [DC 00626] NR 13 TC 4 Z9 4 U1 0 U2 3 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD APR PY 2007 VL 121 IS 4 BP EL161 EP EL167 DI 10.1121/1.2710744 PG 7 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 156ZE UT WOS:000245687600066 PM 17471762 ER PT J AU Greenberg, CC Regenbogen, SE Studdert, DM Lipsitz, SR Rogers, SO Zinner, MJ Gawande, AA AF Greenberg, Caprice C. Regenbogen, Scott E. Studdert, David M. Lipsitz, Stuart R. Rogers, Selwyn O. Zinner, Michael J. Gawande, Atul A. TI Patterns of communication breakdowns resulting in injury to surgical patients SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID SIGN-OUT SYSTEM; ADVERSE EVENTS; OPERATING-ROOM; MANAGEMENT; CARE; ERRORS; AVIATION; LESSONS; CLAIMS AB BACKGROUND: Communication breakdowns are a common threat to surgical safety, but there are little data to guide initiatives to improve communication. STUDY DESIGN: In surgeon-review of 444 surgical malpractice claims from 4 liability insurers, we identified 60 cases involving communication breakdowns resulting in harm to patients. Two surgeon-reviewers analyzed these cases to identify common characteristics and associated factors. Based on identified patterns, potential interventions to prevent communication breakdowns were developed and their potential impact was assessed. RESULTS: The 60 cases involved 81 communication breakdowns, occurring in the preoperative (38%), intraoperative (30%), and postoperative periods (32%). Seventy-two percent of cases involved one communication breakdown. The majority of breakdowns were verbal communications (92%) involving 1 transmitter and 1 receiver (64%). Attending surgeons were the most common team member involved. Status asymmetry (74%) and ambiguity about responsibilities (73%) were commonly associated factors. Forty-three percent of communication breakdowns occurred with handoffs and 39% with transfers in the patient's location. The most common Communication breakdowns involved residents failing to notify the attending surgeon of critical events and a failure of attending-to-attending handoffs. Proposed interventions could prevent 45% to 73% of communication breakdowns in this cases series. CONCLUSIONS: Serious communication breakdowns occur across the continuum of care, typically result from a failure in verbal communication between a surgical attending and another caregiver, and often involve ambiguity about responsibilities. Interventions to prevent these breakdowns should involve: defined triggers that mandate communication with an attending surgeon; structured handoffs and transfer protocols; and standard use of read-backs. (J Am Coll Surg 2007;204: 533-540. (C) 2007 by the American College of Surgeons). C1 Brigham & Womens Hosp, Div Surg Oncol, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Greenberg, CC (reprint author), Brigham & Womens Hosp, Div Surg Oncol, Ctr Surg & Publ Hlth, 75 Francis St, Boston, MA 02115 USA. EM ccgreenberg@partners.org OI Gawande, Atul/0000-0002-1824-9176 NR 25 TC 281 Z9 285 U1 3 U2 27 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD APR PY 2007 VL 204 IS 4 BP 533 EP 540 DI 10.1016/j.jamcollsurg.2007.01.010 PG 8 WC Surgery SC Surgery GA 152NR UT WOS:000245369200002 PM 17382211 ER PT J AU Sailhamer, EA Chen, Z Ahuja, N Velmahos, GC de Moya, M Rhee, P Shults, C Alam, HB AF Sailhamer, Elizabeth A. Chen, Zheng Ahuja, Naresh Velmahos, George C. de Moya, Marc Rhee, Peter Shults, Christian Alam, Hasan B. TI Profound hypothermic cardiopulmonary bypass facilitates survival without a high complication rate in a swine model of complex vascular, splenic, and colon injuries SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 92nd Annual Clinical Congress of the American-College-of-Surgeons CY OCT, 2006 CL Chicago, IL SP Amer Coll Surg ID UNCONTROLLED HEMORRHAGIC-SHOCK; MILD PERIOPERATIVE HYPOTHERMIA; CIRCULATORY ARREST; CARDIAC-ARREST; LETHAL HEMORRHAGE; MODERATE HYPOTHERMIA; PROLONGS SURVIVAL; WOUND-INFECTION; BRAIN-DAMAGE; TRAUMATIC EXSANGUINATION AB BACKGROUND: Induction of a profound hypothermia for emergency preservation and resuscitation in severe hemorrhagic shock can improve survival from lethal injuries, but the impact of hypothermia on bleeding and infectious complications has not been completely determined. STUDY DESIGN: Uncontrolled hemorrhage was induced in 26 swine (95 to 135 lbs) by creating an iliac artery and vein injury, and 30 minutes later, by lacerating the descending thoracic aorta. Through a left thoracotomy approach, profound total body hypothermia (10 degrees C) was induced (2 degrees C/min) by infusing cold organ preservation solution into the aorta. The experimental groups were: vascular injuries alone (group 1, n = 10), vascular and colon injuries (group 2, n = 8), and vascular, colon, and splenic injuries (group 3, n = 8). All injuries were repaired during 60 minutes of low-flow cardiopulmonary bypass (CPB) with hemodilution and profound hypothermia; then the animals were slowly rewarmed (0.5 degrees C/min) back to normothermia. Survivors were monitored for 6 weeks for postoperative bleeding, neurologic deficits, cognitive function (learning new skills), organ dysfunction, and septic complications. RESULTS: Six-week survival rates were 90% in group 1,87.5% in group 2, and 75% in group 3 (p > 0.05). One animal in each group died from acute cardiac failure during the early postoperative phase. Splenic salvage was possible in all animals, and none required complete splenectomy for hemorrhage control. All surviving animals were neurologically intact, displayed normal learning capacity, and had no longterm organ dysfunction. None of the animals had postoperative hemorrhage or experienced septic complications. One animal in group 3 died on the ninth postoperative day because of bowel obstruction (volvulus). CONCLUSIONS: Induction of profound hypothermia can preserve the viability of key organs during repair of lethal injuries. This strategy can be used even in the presence of solid organ and bowel injuries to improve survival, without any considerable increase in postoperative complication rates. (J Am Coll Surg 2007;204:642-653. (C) 2007 by the American College of Surgeons). C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. Washington Hosp Ctr, Dept Surg, Washington, DC 20010 USA. RP Alam, HB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. FU NHLBI NIH HHS [R01 HL71698] NR 57 TC 23 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD APR PY 2007 VL 204 IS 4 BP 642 EP 653 DI 10.1016/j.jamcollsurg.2007.01.017 PG 12 WC Surgery SC Surgery GA 152NR UT WOS:000245369200015 PM 17382224 ER PT J AU Friedlander, AH Yagiela, JA Mahler, ME Rubin, R AF Friedlander, Arthur H. Yagiela, John A. Mahler, Michael E. Rubin, Robert TI The pathophysiology, medical management and dental implications of adult attention-deficit/hyperactivity disorder SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE attention-deficit/hyperactivity disorder; drug interactions; attention; dental care for disabled ID DEFICIT HYPERACTIVITY DISORDER; ADVERSE DRUG-INTERACTIONS; PSYCHIATRIC COMORBIDITY; PSYCHOSOCIAL TREATMENTS; CHILDHOOD-ONSET; SUBSTANCE-ABUSE; BRAIN ACTIVITY; UNITED-STATES; PRIMARY-CARE; DOUBLE-BLIND AB Background. Few published reports in the dental literature have focused on adult attention-deficit/hypersctivity disorder (ADHD) and its dental implications. Types of Studies Reviewed. The authors conducted a MEDLINE search for the period 2000 through 2005 using the terms "adult" and "attention-deficit" to define ADHD's pathology, medical treatment and dental implications. Results. ADHD is a development condition that affects slightly more than 4% of the adult U.S. population. Its symptoms include inattention, hyperactivity and impulsivity that can cause personal, social, occupational and leisure-time dysfunction. Medications used to treat the disorder include stimulants, selective noradrenergic uptake inhibitors and tricyclic antidepressants. Clinical Implications. The oral health of people with ADHD may be compromised by inattention and impulsivity that impair home care regimens and can lead to cigarette addiction, which may cause oral cancer and damage to periodontium, and excessive ingestion of caffeinated sugar-laden soft drinks that promote dental caries. To safely care for this patient population, dentists must be familiar with the stimulant and nonstimulant medications used to treat adult ADHD, because these drugs can cause adverse orofacial and systemic reactions and interact adversely with dental therapeutic agents. C1 VA Greater Los Angeles Healthcare Syst, Neurobehav Clin, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Dept Psychiat & Mental Hlth, Los Angeles, CA 90073 USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, Neurobehav Clin, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthur.friedlander@med.va.gov RI Reis, Aline/G-9573-2012 NR 74 TC 9 Z9 11 U1 2 U2 10 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD APR PY 2007 VL 138 IS 4 BP 475 EP 482 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 158AM UT WOS:000245763100020 PM 17403737 ER PT J AU Braun, U McCullough, L Kunik, M AF Braun, U. McCullough, L. Kunik, M. TI Racial/ethnic differences in the use of mental health services in seriously ill veterans. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriat Soc C1 DeBakey VA Med Ctr, HSRD CoE, Houston, TX USA. BCM, Houston, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S199 EP S199 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500585 ER PT J AU Burnett, J Coverdale, J Kelly, PA Pickens, S Dyer, C AF Burnett, J. Coverdale, J. Kelly, P. A. Pickens, S. Dyer, C. TI Variables that predict depression in a sample of self-neglecting geriatric outpatients. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriat Soc C1 Consortium Res Elder Self Neglect, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Harris Cty Hosp Dist, Houston, TX USA. Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S189 EP S189 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500556 ER PT J AU Day, H AF Day, H. TI Identifying barriers and solutions to effective nursing physician communication: A qualitative study. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriat Soc C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S38 EP S38 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500109 ER PT J AU Devadoss, R Green, GL Carter, DN Latini, DM Kaniu-Mwaniki, P Barker, JC Sands, LP Chren, M Walter, LC Knight, SJ AF Devadoss, R. Green, G. L. Carter, D. N. Latini, D. M. Kaniu-Mwaniki, P. Barker, J. C. Sands, L. P. Chren, M. Walter, L. C. Knight, S. J. TI Understanding treatment related symptom outcomes among prostate cancer patients. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriat Soc C1 SUNY Syracuse, Upstate Med Univ, Syracuse, NY USA. San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Baylor Coll Med, Houston Ctr Quality Care & Utilizat Studies, Houston, TX 77030 USA. Michael E De Bakey Vet Affairs Med Ctr, Houston, TX USA. Purdue Univ, W Lafayette, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S59 EP S59 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500171 ER PT J AU Dyer, CB Burnett, J Pickens, S Vogel, M Regev, T Kim, L Kelly, PA AF Dyer, C. B. Burnett, J. Pickens, S. Vogel, M. Regev, T. Kim, L. Kelly, P. A. TI The self-neglect severity Scale: A sensitive screening tool. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriat Soc C1 Consortium Res Elder Self Neglect, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Haris Cty Hosp Dist, Houston, TX USA. ME Debakey Vet Affairs Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S201 EP S201 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500590 ER PT J AU Edes, T Tompkins, H AF Edes, T. Tompkins, H. TI Quality measure of reduction of inpatient days during home based primary care (HBPC). SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriat Soc C1 US Dept Vet Affairs, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S6 EP S7 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500019 ER PT J AU Fermin, E Sanchez-Reilly, S Wittenberg-Lyles, E AF Fermin, E. Sanchez-Reilly, S. Wittenberg-Lyles, E. TI Evaluating the impact of interdisciplinary family meetings among caregivers of older adults. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriatr Soc C1 Univ Texas Hlth Sci Ctr San Antonio, GRECC, San Antonio, TX 78285 USA. So Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas San Antonio, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S59 EP S60 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500172 ER PT J AU Jamshed, N Martin, J Josephson, K Khan-Hudson, A Vandenberg, T Martinez, S Alessi, C AF Jamshed, N. Martin, J. Josephson, K. Khan-Hudson, A. Vandenberg, T. Martinez, S. Alessi, C. TI Functional recovery and cognitive impairment among older people receiving rehabilitation in a nursing home. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriat Soc C1 VA Greater Los Angeles, GRECC, North Hills, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S215 EP S215 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500630 ER PT J AU Kinard, TN Sanchez-Reilly, S Lee, S AF Kinard, T. N. Sanchez-Reilly, S. Lee, S. TI Functional assessment among geriatric cancer patients. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriat Soc C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S208 EP S209 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500611 ER PT J AU LoConte, N Gleason, C Gunter-Hunt, G Carlsson, C Siebers, M AF LoConte, N. Gleason, C. Gunter-Hunt, G. Carlsson, C. Siebers, M. TI Screening for and prevalence of firearm access and driving among veterans with dementia. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriat Soc C1 Univ Wisconsin, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Med Ctr, Ctr Gerontol & Hlth Care Res, Madison, WI USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S104 EP S104 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500305 ER PT J AU McGory, ML Jain, S Sekeris, E Leonardi, MJ Shekelle, PG Ko, CY AF McGory, M. L. Jain, S. Sekeris, E. Leonardi, M. J. Shekelle, P. G. Ko, C. Y. TI Does physician specialty influence quality measure development for elderly surgical patients? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriat Soc C1 Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S217 EP S217 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500635 ER PT J AU Millan, J Rudolph, JL Salow, MJ AF Millan, J. Rudolph, J. L. Salow, M. J. TI Pharmacologic Intervention in Late Life (PILL) Clinic: a geriatric model of care to optimize medication management. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriat Soc C1 GRECC, VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S100 EP S100 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500294 ER PT J AU Pickens, S Burnett, J Naik, A Dyer, CB AF Pickens, S. Burnett, J. Naik, A. Dyer, C. B. TI Characterizing elders who self-neglect based on the Kohlman evaluation of living skills. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriat Soc C1 Baylor Coll Med, Houston, TX 77030 USA. DeBakey Vet Affairs Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S160 EP S160 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500471 ER PT J AU Prilata, AA Bancroft, J Jones, R Costa, M Gensure, R Kiel, D Lipsitz, LA AF Prilata, A. A. Bancroft, J. Jones, R. Costa, M. Gensure, R. Kiel, D. Lipsitz, L. A. TI Fallers have loss of postural complexity during a cognitive task. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriat Soc C1 HSL, Boston, MA USA. HMS, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S5 EP S5 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500015 ER PT J AU Rudolph, JL Salow, M Millan, J Angelini, M McGlinchey, R AF Rudolph, J. L. Salow, M. Millan, J. Angelini, M. McGlinchey, R. TI The anticholinergic risk scale is associated with anticholinergic side effects. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriat Soc C1 VA Boston Healthcare Syst, GRECC, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Coll Pharm, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S195 EP S195 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500574 ER PT J AU Ruzicka, SA Sanchez-Reilly, S AF Ruzicka, S. A. Sanchez-Reilly, S. TI The impact of a geriatric palliative consultation service in a tertiary setting: A pilot study. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriat Soc C1 Univ Texas, Hlth Sci Ctr, Sch Nursing, San Antonio, TX 78285 USA. South Texas Vet Hlth Care Syst, GRECC, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S151 EP S151 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500445 ER PT J AU Sanchez-Reilly, S Zeber, J Copeland, L Pugh, M Wolff, P Karnad, A AF Sanchez-Reilly, S. Zeber, J. Copeland, L. Pugh, M. Wolff, P. Karnad, A. TI Cancer among "oldest of the old": Prevalence rates, medical comorbidities, and treatment modalities. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriat Soc C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S205 EP S205 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500601 ER PT J AU Sanchez-Reilly, S Wittenberg-Lyles, E AF Sanchez-Reilly, S. Wittenberg-Lyles, E. TI Evaluating ACP communication. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriatr Soc C1 Univ Texas Hlth Sci Ctr San Antonio, GRECC, San Antonio, TX 78285 USA. Univ Texas San Antonio, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S129 EP S130 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500381 ER PT J AU Seitan, L Sanchez-Reilly, S Wittenberg-Lyles, E Lee, S AF Seitan, L. Sanchez-Reilly, S. Wittenberg-Lyles, E. Lee, S. TI The impact of a geriatric consult service on caregiver's perception of inpatient care. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriatr Soc C1 Univ Cent Del Caribe, Sch Med, Bayamon, PR 78285 USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX USA. Univ Texas San Antonio, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S161 EP S161 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500473 ER PT J AU Shah, FA Boockvar, K AF Shah, F. A. Boockvar, K. TI Drug prescribing practices during patient transfer. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriat Soc C1 Mt Sinai Sch Med, Dept Geriatr, New York, NY USA. James J Peters VA Med Ctr, Dept Geriatr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S147 EP S147 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500432 ER PT J AU Shanley, E Tio-Matos, I Merriam, GR AF Shanley, E. Tio-Matos, I. Merriam, G. R. TI Half a century of estrogen use in a nonagenarian: 54 years of cardioprotection? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriat Soc C1 VA Puget Sound, Tacoma, WA USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S117 EP S117 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500342 ER PT J AU Shanley, E Falzgraf, S AF Shanley, E. Falzgraf, S. TI Bochdalek hernia: An uncommon cause for a common symptom in elders. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriat Soc C1 VA Puget Sound, Tacoma, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S116 EP S116 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500341 ER PT J AU Silverman, GK Temel, J Podgurski, LM Paulk, ME Jackson, VA Block, SD Buss, MK Prigerson, HG AF Silverman, G. K. Temel, J. Podgurski, L. M. Paulk, M. E. Jackson, V. A. Block, S. D. Buss, M. K. Prigerson, H. G. TI Do aggressive treatments in the last week of life harm quality of death? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriat Soc C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Dana Farber Canc Inst, Ctr Psychooncol & Palliative Care Res, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas So western, Sch Med, Dallas, TX USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S2 EP S2 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500006 ER PT J AU Smiechowska, JK Asnicar, MA Taffet, GE Smith, RG Garcia, JM AF Smiechowska, J. K. Asnicar, M. A. Taffet, G. E. Smith, R. G. Garcia, J. M. TI Ghrelin effects on body weight and body composition in cisplatin induced cachexia. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriat Soc C1 Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA. DeBakey Vet Affairs Med Ctr, Houston, TX USA. Hartford Fdn, Ctr Excellence Geriatricse, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S166 EP S166 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500488 ER PT J AU Steinman, MA Rosenthal, GE Landefeld, CS AF Steinman, M. A. Rosenthal, G. E. Landefeld, C. S. TI Are drugs-to-avoid criteria an accurate diagnostic tool for problem prescribing? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriat Soc C1 San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Iowa City VA Healthcare Syst, Iowa City, IA USA. Univ Iowa, Iowa City, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S7 EP S7 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500021 ER PT J AU Sun, B Hoffman, JR Mangione, CM Mower, WR AF Sun, B. Hoffman, J. R. Mangione, C. M. Mower, W. R. TI Older age predicts short-term, serious events after syncope. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriat Soc C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S122 EP S122 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500359 ER PT J AU Villarreal, D Ross, J Sanchez-Reilly, S Wittenberg-Lyles, E Lee, S AF Villarreal, D. Ross, J. Sanchez-Reilly, S. Wittenberg-Lyles, E. Lee, S. TI Breaking barriers: An interdisciplinary educational intervention to improve pain among older adults. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriatr Soc C1 Univ Texas Hlth Sci Ctr San Antonio, GRECC, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas San Antonio, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2007 VL 55 IS 4 SU S BP S187 EP S188 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 157WQ UT WOS:000245752500551 ER PT J AU Daimon, M Gillinov, AM Liddicoat, JR Saracino, G Fukuda, S Koyama, Y Hayase, M Cohn, WE Ellis, SG Thomas, JD Shiota, T AF Daimon, Masao Gillinov, A. Marc Liddicoat, John R. Saracino, Giuseppe Fukuda, Shota Koyama, Yasushi Hayase, Motoya Cohn, William E. Ellis, Stephen G. Thomas, James D. Shiota, Takahiro TI Dynamic change in mitral annular area and motion during percutaneous mitral annuloplasty for ischemic mitral regurgitation: Preliminary animal study with real-time 3-dimensional echocardiography SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID VENTRICULAR SYSTOLIC DYSFUNCTION; OVINE MODEL; DILATED CARDIOMYOPATHY; HEART-FAILURE; VALVE REPAIR; SHAPE; REDUCTION; RECONSTRUCTION; FEASIBILITY; DILATATION AB We used a novel 3-dimensional (3D) echocardiographic technique to evaluate the impact of a coronary sinus-based percutaneous transvenous mitral annuloplasty (PTMA) on dynamic changes in mitral annular geometry and motion during the cardiac cycle in 8 sheep with ischemic mitral regurgitation. Using real-time 3D echocardiographic data before and after PTMA, 10 points along the saddle-shaped annulus were identified. For every 3D volume/frame during a cardiac cycle, we assessed mitral annular area and excursion defined as the traveling distance of the annular center. The PTMA device reduced both minimum and maximal mitral annular area (9.5 +/- 0.9-7.0 +/- 0.6 and 12.8 +/- 1.3-9.8 +/- 1.5 cm(2), P < .001 for both, respectively) with reduction of mitral regurgitation jet area (5.1 +/- 2.3-1.2 +/- 0.8 cm(2), P < .001), whereas it did not significantly impair mitral annular excursion amplitude (8-3 +/- 1.1-7.0 +/- 1.9 mm, P = .13). This 3D echocardiographic method noninvasively enabled dynamic study of mitral annular geometry and motion with quantitative analysis of the impact of PTMA. C1 Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Texas Heart Inst, Houston, TX 77025 USA. RP Shiota, T (reprint author), Cleveland Clin Fdn, Dept Cardiovasc Med, Desk F15,9500 Euclid Ave, Cleveland, OH 44195 USA. EM shiorar@ccf.org OI Daimon, Masao/0000-0002-7616-3477 NR 34 TC 20 Z9 20 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD APR PY 2007 VL 20 IS 4 BP 381 EP 388 DI 10.1016/j.echo.2006.08.029 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 159QL UT WOS:000245881100008 PM 17400117 ER PT J AU Yosefy, C Levine, RA Solis, J Vaturi, M Handschumachcr, MD Hung, J AF Yosefy, Chaim Levine, Robert A. Solis, Jorge Vaturi, Mordehay Handschumachcr, Mark D. Hung, Judy TI Proximal flow convergence region as assessed by real-time 3-dimensional echocardiography: Challenging the hemispheric assumption SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID ISOVELOCITY SURFACE-AREA; COLOR DOPPLER FLOW; ISCHEMIC MITRAL REGURGITATION; IN-VITRO; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; VALVULAR REGURGITATION; QUANTITATIVE ASSESSMENT; CLINICAL-SIGNIFICANCE; VELOCITY PROFILE; ORIFICE SHAPE AB Objective: Traditionally, a hemispheric assumption for the proximal flow convergence region (PFCR) is used when calculatitig mitral regurgitant (MR) effective orifice area (EROA). However, 2-dimensional (2D) echocardiography limits evaluation of the complete PFCR contour. Real-time 3-dimensional (3D) echocardiography (RT3D) allows direct assessment of the true PFCR contour. We hypothesized that the PFCR contour is not necessarily hemispheric, but rather hemielliptic, and aimed to apply a hemielliptic calculation, based on the 3D contour of the PFCR for more accurate MR quantification. Methods: In all, 50 patients with MR underwent RT3D to characterize PFCR contour as hemispheric or hemielliptic. MR. EROA by RT3D-derived PFCR was calculated using a hemielliptic formula using 3D data. The 2D EROA was computed using standard hemispheric assumption. EROAs calculated from 2D and RT3D data were compared with quantitative Doppler EROA (mitiral inflow - aortic outflow/MR time-velocity integral), used as an independent comparison. Results: Only 1 of 50 patients (2%) had a hemispheric PFCR contour by RT3D. The remaining had hemielliptic PFCR contours. Compared with Doppler method, 2D echocardiography significantly underestimated EROA (0.34 +/- 0.14 vs 0.48 +/- 0.25 cm(2), P < .001). RT3D EROA was not significantly different from Doppler EROA (0.52 +/- 0.17 vs 0.48 +/- 0.25, P = not significant). Of 33 patients with Doppler EROA greater than 0.3 cm(2) (>= moderate-severe MR), 45% (15 of 33) were underestimated as having mild to moderate MR by 2D EROA. Conclusions: The true PFCR contour as shown by RT3D is generally not hemispheric but hemielliptic, tracking the orifice contour. Based on this 3D shape, a hemielliptic approach can be used for practical clinical application with improved MR quantification. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Hung, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, VBK 508,55 Fruit St, Boston, MA 02114 USA. EM jhung@partners.org FU NHLBI NIH HHS [K23 HL04504, K24 HL67434, R01 HL38176] NR 47 TC 61 Z9 62 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD APR PY 2007 VL 20 IS 4 BP 389 EP 396 DI 10.1016/j.echo.2006.09.006 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 159QL UT WOS:000245881100009 PM 17400118 ER PT J AU Colvin, RB AF Colvin, Robert B. TI Antibody-mediated renal allograft rejection: Diagnosis and pathogenesis SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID CAPILLARY C4D DEPOSITION; DONOR KIDNEY-TRANSPLANTATION; ACUTE HUMORAL REJECTION; PERITUBULAR CAPILLARIES; HISTOLOGIC-FINDINGS; ENDOTHELIAL-CELLS; HLA ANTIBODIES; ACTIVATING ANTIBODIES; ORGAN-TRANSPLANTATION; COMPLEMENT ACTIVATION AB Alloantibodies to HLA class I or II and other antigens expressed by endothelium cause a variety of effects on renal transplants, ranging from acute to chronic rejection, and even apparent graft acceptance (accommodation). Recognition of these conditions and appropriate therapy requires demonstration of C4d in biopsies, commonly confirmed by tests for circulating alloantibody. Substantial practical experience by pathologists in the interpretation and pitfalls of C4d stains are reviewed along with considerations of the clinical significance and pathologic mechanisms of the different effects of antibody on the endothelium of the renal allograft. Clinical trials will be needed to ascertain the optimal treatment for the newly appreciated conditions chronic humoral rejection and accommodation. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Colvin, RB (reprint author), Massachusetts Gen Hosp, Dept Pathol, Thier 831, Boston, MA 02114 USA. EM colvin@helix.mgh.harvard.edu NR 61 TC 305 Z9 333 U1 2 U2 11 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD APR PY 2007 VL 18 IS 4 BP 1046 EP 1056 DI 10.1681/ASN.2007010073 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 154RE UT WOS:000245524300006 PM 17360947 ER PT J AU Perkins, BA Ficociello, LH Ostrander, BE Silva, KH Weinberg, J Warram, JH Krolewski, AS AF Perkins, Bruce A. Ficociello, Linda H. Ostrander, Betsy E. Silva, Kristen H. Weinberg, Janice Warram, James H. Krolewski, Andrzej S. TI Microalbuminuria and the risk for early progressive renal function decline in type 1 diabetes SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; URINARY ALBUMIN EXCRETION; SERUM CYSTATIN-C; EARLY NATURAL-HISTORY; STRUCTURAL-CHANGES; KIDNEY-FUNCTION; NEPHROPATHY; MELLITUS; MARKER; PROTEINURIA AB This study aimed to establish the time of initiation and the determinants of renal function decline in type 1 diabetes. Until now, such decline has been assumed to be a late-occurring event associated with proteinuria. A total of 267 patients with normoalbuminuria and 301 patients with microalbuminuria were followed for 8 to 12 yr. Linear trends (slopes) in GFR were estimated by serial measurement of serum cystatin C. Cases of early renal function decline were defined by loss in cystatin C GFR that exceeded -3.3%/yr, a threshold that corresponds to the 2.5th percentile of the distribution of GFR slopes in an independent nondiabetic normotensive population. Cases of early renal function decline occurred in 9% (mean slope -4.4; range -5.9 to -3.3%/yr) of the normoalbuminuria group and 31% (mean slope -7.1; range -23.8 to -3.3%/yr) of the microalburninuria group (P < 0.001). Risk for early renal function decline depended on whether microalbuminuria regressed, remained stable, or progressed, rising from 16 to 32 and 68%, respectively (P < 0.001). In multivariate analysis, risk for decline was higher after age 35 yr or when glycosylated hemoglobin exceeded 9% but did not vary with diabetes duration, smoking, BP, or angiotensin-converting enzyme inhibitor treatment. Contrary to the existing paradigm of diabetic nephropathy, progressive renal function decline in type 1 diabetes is an early event that occurs in a large proportion of patients with microalburninuria. Together with testing for microalburninuria, clinical protocols using cystatin C to diagnose early renal function decline and track response to therapeutic interventions should be developed. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Harvard Sch Publ Hlth, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Univ Toronto, Div Endocrinol, Toronto, ON, Canada. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM andrzej.krolewski@joslin.harvard.edu FU NIDDK NIH HHS [DK067638, DK41526] NR 54 TC 173 Z9 183 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD APR PY 2007 VL 18 IS 4 BP 1353 EP 1361 DI 10.1681/ASN.2006080872 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 154RE UT WOS:000245524300038 PM 17329575 ER PT J AU Ikonomidis, JS Jones, JA Barbour, JR Stroud, RE Clark, LL Kaplan, BS Zeeshan, A Bavaria, JE Gorman, JH Spinale, FG Gorman, RC AF Ikonomidis, John S. Jones, Jeffery A. Barbour, John R. Stroud, Robert E. Clark, Leslie L. Kaplan, Brooke S. Zeeshan, Ahmed Bavaria, Joseph E. Gorman, Joseph H., III Spinale, Francis G. Gorman, Robert C. TI Expression of matrix metalloproteinases and endogenous inhibitors within ascending aortic aneurysms of patients with bicuspid or tricuspid aortic valves SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 86th Annual Meeting of the American-Association-for-Thoracic-Surgery CY APR 29-MAY 03, 2006 CL Philadelphia, PA SP Amer Assoc Thorac Surg ID ACTIVATION; THROMBUS; CANCER; VIVO; WALL AB Objective: The mechanisms contributing to ascending thoracic aortic aneurysms associated with bicuspid aortic valves may differ from ascending thoracic aortic aneurysms with tricuspid aortic valves. Matrix metalloproteinases and their endogenous inhibitors have been causally linked to ascending thoracic aortic aneurysm formation. This study tested the hypothesis that specific and different matrix metalloproteinase and tissue inhibitors of metalloproteinase profiles would be observed in ascending thoracic aortic aneurysm samples from patients with bicuspid aortic valves versus tricuspid aortic valves. Methods: Ascending thoracic aortic aneurysm samples taken from patients with bicuspid aortic valve ( n = 53) and patients with tricuspid aortic valve ( n = 46) were assessed for representative subtypes of all matrix metalloproteinase classes and all 4 known tissue inhibitors of metalloproteinases. Levels were compared [ optical density units, median ( interquartile range)] both to reference control ascending aortic samples ( n = 26) and within each valve group by aneurysm diameter ( <= 3.9 cm, 4.0-5.9 cm and >= 6.0 cm). Results: Different and specific matrix metalloproteinase and tissue inhibitors of metalloproteinase profiles were observed in the ascending thoracic aortic aneurysm groups. In bicuspid aortic valves, matrix metalloproteinase-2 increased by 34% when compared with either tricuspid aortic valves or control (P <.05), and matrix metalloproteinase-14 decreased by 59% compared with tricuspid aortic valves ( P <.05). In tricuspid aortic valve samples, tissue inhibitors of metalloproteinase-2 decreased by 35% when compared with either tricuspid aortic valves or control (P <.05), and matrix metalloproteinase-13 increased by 140% in the 4.0- to 5.9- cm diameter range ( P <.05). Conclusions: A unique matrix metalloproteinase and tissue inhibitor of metalloproteinase portfolio was observed in ascending thoracic aortic aneurysms from patients with bicuspid aortic valve compared with patients with tricuspid aortic valve. These differences, suggesting disparate mechanisms of extracellular matrix remodeling, may provide unique biochemical targets for ascending thoracic aortic aneurysm prognostication and treatment in these 2 groups of patients. C1 Med Univ S Carolina, Div Cardiothorac Surg, Dept Cardiothorac Surg, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. Univ Penn, Div Cardiothorac Surg, Philadelphia, PA 19104 USA. RP Ikonomidis, JS (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Dept Cardiothorac Surg, Ralph H Johnson Vet Affairs Med Ctr, Suite 409 CSB,96 Jonathan Lucas St, Charleston, SC 29425 USA. EM ikonomij@musc.edu FU NHLBI NIH HHS [HL 059165-07, R01 HL075488-01] NR 26 TC 92 Z9 93 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD APR PY 2007 VL 133 IS 4 BP 1028 EP 1036 DI 10.1016/j.jtcvs.2006.10.083 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 149AI UT WOS:000245118100027 PM 17382648 ER PT J AU Rich, JD Maraganore, JM Young, E Lidon, RM Adelman, B Bourdon, P Charenkavanich, S Hirsh, J Theroux, P Cannon, CP AF Rich, Jonathan D. Maraganore, John M. Young, Edward Lidon, Rosa-Maria Adelman, Burt Bourdon, Paul Charenkavanich, Supoat Hirsh, Jack Theroux, Pierre Cannon, Christopher P. TI Heparin resistance in acute coronary syndromes SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE anticoagulation; heparin; resistance ID ACUTE MYOCARDIAL-INFARCTION; MOLECULAR-WEIGHT HEPARIN; UNFRACTIONATED HEPARIN; INDUCED THROMBOCYTOPENIA; ANTICOAGULANT RESPONSE; THROMBIN INHIBITOR; ANTITHROMBIN-III; RANDOMIZED-TRIAL; PLASMA-PROTEINS; BINDING AB Background Maintaining a therapeutic level of anticoagulation with unfractionated heparin remains a major challenge for clinicians because of the wide variability of patient responses, which may be explained by variable binding of heparin to plasma proteins. Direct thrombin inhibitors may offer an advantage in more predictable anticoagulation. Methods Plasma samples from normal volunteers, stable coronary artery disease (CAD) patients, unstable angina patients, and acute myocardial infarction patients were obtained. A fixed concentration of heparin (.13 U/ml) or bivalirudin (1.6 mu g/ml) was added to plasma from each of the four study groups and measurement of the APTT was performed. In addition, a pool of plasma from patients with acute MI was diluted in pooled normal plasma, and heparin or bivalirudin was added to the plasma preparation and APTT measurements performed. Results In heparin-treated plasma samples, mean APTT values were 443 +/- 137% baseline for normal volunteers, 347 +/- 1.16% for patients with stable CAD, 290 +/- 124% for patients with unstable angina (p < 0.05), and 230 +/- 120% for patients with acute MI (p < 0.05). APTT did not differ across the four groups treated with bivalirudin. There was a much higher degree of variability in APTT values in heparin treated controls (272%-671%, SD similar to 30%) compared to bivalirudin treated controls (284-499%, SD similar to 12%). When the "acute MI pool" was diluted in pooled normal plasma at fixed concentrations of either bivalirudin (1.6 mu g/ml) or heparin (0.13 U/ml), there was a sharp decrease in heparin activity from 407% baseline (at 0% acute MI pool) to values as low as 126% baseline (at 100% acute MI pool). A markedly different pattern was seen in the bivalirudin treated samples, where a trend towards decreased APTT values was seen only at the 100% acute MI pool. Conclusion Both heparin variability and resistance may limit optimal antithrombotic therapy with heparin in patients with ACS and constitutes a potential advantage of direct antithrombin blockade with bivalirudin. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Biogen Idec Inc, Med Res, Cambridge, MA 02142 USA. McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada. Montreal Heart Inst, Div Cardiol, Montreal, PQ H1T 1C8, Canada. McMaster Univ, Dept Med, Hamilton, ON, Canada. RP Cannon, CP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM cpcannon@partners.org NR 34 TC 10 Z9 11 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD APR PY 2007 VL 23 IS 2 BP 93 EP 100 DI 10.1007/s11239-006-9049-9 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 150UB UT WOS:000245244000002 PM 17221324 ER PT J AU Taft, CT Vogt, DS Marshall, AD Panuzio, J Niles, BL AF Taft, Casey T. Vogt, Dawne S. Marshall, Amy D. Panuzio, Jillian Niles, Barbara L. TI Aggression among combat veterans: Relationships with combat exposure and symptoms of posttraumatic stress disorder, dysphoria, and anxiety SO JOURNAL OF TRAUMATIC STRESS LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the International-Society-for-Traumatic-Stress-Studies (ISTSS) CY NOV 02-05, 2005 CL Toronto, CANADA SP Int Soc Traumat Stress Studies, Natl Inst Ment Hlth ID ADMINISTERED PTSD SCALE; VIETNAM VETERANS; PSYCHOMETRIC PROPERTIES; NEGATIVE AFFECT; FIT INDEXES; DEPRESSION; VIOLENCE; INVENTORY; BEHAVIOR; ANGER AB Prior research has revealed heightened aggressive behavior among veterans with PTSD. This study tested a model examining the interrelationships among combat exposure, posttraumatic stress disorder (PTSD) symptoms, dysphoric symptoms, and anxiety symptoms in predicting aggressive behavior in a sample of 265 male combat veterans seeking diagnostic assessment of PTSD. Combat exposure was indirectly associated with aggression primarily through its relationship with PTSD symptoms. Symptoms of PTSD were directly related to aggression, and indirectly related to aggression through dysphoric symptoms. Results highlight the role of PTSD symptoms and dysphoric symptoms with respect to aggressive behavior among this population, and suggest the relevance of aggression theory to the study of combat veterans. C1 VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. Boston Univ, Dept Psychiat, Sch Med, Boston, MA 02215 USA. RP Taft, CT (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 116B-2,150 S Huntington Ave, Boston, MA 02130 USA. EM casey.taft@va.gov NR 56 TC 71 Z9 72 U1 3 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD APR PY 2007 VL 20 IS 2 BP 135 EP 145 DI 10.1002/jts.20197 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 159BV UT WOS:000245841300003 PM 17427912 ER PT J AU Graff, JN Mori, M Li, H Garzotto, M Penson, D Potosky, AL Beer, TM AF Graff, Julie N. Mori, Motomi Li, Hong Garzotto, Mark Penson, David Potosky, Arnold L. Beer, Tomasz M. TI Predictors of overall and cancer-free survival of patients with localized prostate cancer treated with primary androgen suppression therapy: Results from the prostate cancer outcomes study SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; androgen antagonists; mortality; nomograms ID QUALITY-OF-LIFE; RADICAL PROSTATECTOMY; DEPRIVATION THERAPY; HORMONAL-THERAPY; RADIATION-THERAPY; PRACTICE PATTERNS; CARCINOMA; TRIAL; MEN AB Purpose: Primary androgen suppression therapy for clinically localized prostate cancer is increasingly common in the United States despite a lack of supportive evidence for its use. We determined which demographic and clinical factors predict overall and cancer specific survival with this treatment strategy in patients enrolled in the Prostate Cancer Outcomes Study. Materials and Methods: In 1994 to 1995 the Prostate Cancer Outcomes Study recruited 3,533 men diagnosed with prostate cancer. Clinical and treatment information was abstracted from medical records and demographic characteristics were obtained from patient surveys 6, 12, 24 and 60 months after diagnosis. Overall and cancer specific mortality was analyzed through December 2002 using the Kaplan-Meier method and Cox regression. Results: A total of 276 patients had organ confined (cTl-2) prostatic adenocarcinoma and received primary androgen suppression therapy within 1 year of diagnosis. Median followup for censored patients was 7.6 years (range 1.1 to 8.1). Five-year overall and cancer specific survival was 66% (95% CI 59-72) and 91% (95% CI 86-94), respectively. Independent predictors of shorter overall survival were patient age 75 years or older, prostate specific antigen 20 ng/ml or greater, Gleason score 7 or greater and abnormal digital rectal examination. Gleason score 7 or greater, prostate specific antigen 20 ng/ml or greater and a low comorbidity index were independent predictors of shorter cancer specific survival. Conclusions: The use of primary androgen suppression therapy in the Prostate Cancer Outcomes Study data set resulted in 91% 5-year cancer specific survival. Advanced age, and factors that reflect tumor burden and biology were predictive of overall survival, while cancer specific survival was predicted by tumor factors and the burden of comorbid conditions. A nomogram for predicting overall survival at 5 years was constructed. C1 Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Div Urol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Biostat Shared Resource, Inst Canc, Portland, OR 97239 USA. Portland VA Med Ctr, Urol Sect, Portland, OR USA. Univ So Calif, Dept Urol, Norris Canc Ctr, Los Angeles, CA 90089 USA. Univ So Calif, Dept Prevent Med, Norris Canc Ctr, Los Angeles, CA 90089 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Beer, TM (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, Mail Code CR-145,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM beert@ohsu.edu FU NCI NIH HHS [N01PC67010, N01PC67009, N01PC67005, N01PC67006, N01PC67000, N01PC67007] NR 20 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 2007 VL 177 IS 4 BP 1307 EP 1312 DI 10.1016/j.juro.2006.11.054 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 148QV UT WOS:000245090600030 PM 17382720 ER PT J AU McDougal, WS AF McDougal, W. Scott TI Detection of sentinel node micrometastasis by step section and immunohistochemistry in patients with prostate cancer - Editorial comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP McDougal, WS (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 2007 VL 177 IS 4 BP 1317 EP 1317 DI 10.1016/j.juro.2006.11.137 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 148QV UT WOS:000245090600032 ER PT J AU Lima, MA Marzocchetti, A Autissier, P Tompkins, T Chen, YP Gordon, J Clifford, DB Gandhi, RT Venna, N Berger, JR Koralnik, IJ AF Lima, Marco A. Marzocchetti, Angela Autissier, Patrick Tompkins, Troy Chen, Yiping Gordon, Jennifer Clifford, David B. Gandhi, Rajesh T. Venna, Nagagopal Berger, Joseph R. Koralnik, Igor J. TI Frequency and phenotype of JC virus-specific CD8(+) T lymphocytes in the peripheral blood of patients with progressive multifocal leukoencephalopathy SO JOURNAL OF VIROLOGY LA English DT Article ID MULTIPLE-SCLEROSIS; CELL DIFFERENTIATION; VP1 POLYPEPTIDES; IMMUNE-RESPONSE; BK VIRUS; NATALIZUMAB; MEMORY; THERAPY; POLYOMAVIRUS; INDIVIDUALS AB JC virus (JCV)-specific CD8(+) cytotoxic T lymphocytes (CTL) are associated with a favorable outcome in patients with progressive multifocal leukoencephallopathy (PML) and cross-recognize the polyomavirus BK virus (BKV). We sought to determine the frequency and phenotype in fresh blood of CD8(+) T cells specific for two A*0201-restricted JCV epitopes, VP1(p36) and VP1(p100), and assess their impact on JC and BK viremia and viruria in 15 healthy subjects, eight human immunodeficiency virus-positive (HIV+) individuals, and nine HIV+ patients with PML (HIV+ PML patients) classified as survivors. After magnetic preenrichment of CD8(+) T cells, epitope-specific cells ranged from 0.001% to 0.22% by tetramer staining, with no significant difference among the three study groups. By use of seven-color How cytometry, there was no predominant differentiation phenotype subset among JCV-specific CD8(+) T cells in healthy individuals, HIV+ subjects, or HIV+ PML patients. However, in one HIV+ PML patient studied in the acute phase, there was a majority of activated effector memory cells. BKV DNA was undetectable in all blood samples by quantitative PCR, while a low JC viral load was found in the blood of only one HIV+ and two HIV+ PML patients. JCV and BKV DNA were detected in 33.3% and 13.3% of all urine samples, respectively, independent of the presence of JCV-specific CTL. The detection of JCV DNA in the urine was associated with the presence of a JCV VP1(p100) CTL response. Immunotherapies aiming at increasing the cellular immune response against JCV may be valuable in the treatment of HIV+ individuals with PML. C1 Harvard Univ, Dept Neurol, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Harvard Univ, Div Viral Pathogenesis, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Univ Fed Rio de Janeiro, Sch Med, Rio De Janeiro, Brazil. Temple Univ, Ctr Neurovirol & Canc Biol, Philadelphia, PA 19122 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO USA. Washington Univ, Sch Med, Dept Med, St Louis, MO USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. Univ Kentucky, Coll Med, Dept Neurol, Lexington, KY USA. RP Koralnik, IJ (reprint author), Harvard Univ, Dept Neurol, Beth Israel Deaconess Med Ctr, Sch Med, Res E,Room 213C, Boston, MA 02215 USA. EM ikoralni@bidmc.harvard.edu FU NIAID NIH HHS [P30 AI060354, P30 AI 60354, R01 NS/AI 041198]; NINDS NIH HHS [NS 047029, R01 NS041198, R01 NS047029] NR 37 TC 39 Z9 41 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2007 VL 81 IS 7 BP 3361 EP 3368 DI 10.1128/JVI.01809-06 PG 8 WC Virology SC Virology GA 147FF UT WOS:000244988100032 PM 17229701 ER PT J AU Tami, C Silberstein, E Manangeeswaran, M Freeman, GJ Umetsu, SE DeKruyff, RH Umetsu, DT Kaplan, GG AF Tami, Cecilia Silberstein, Erica Manangeeswaran, Mohanraj Freeman, Gordon J. Umetsu, Sarah E. DeKruyff, Rosemarie H. Umetsu, Dale T. Kaplan, Gerardo G. TI Immunoglobulin A (IgA) is a natural ligand of hepatitis A virus cellular receptor 1 (HAVCR1), and the association of IgA with HAVCR1 enhances virus-receptor interactions SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL-ACTIVATION; TIM GENE FAMILY; MONOCLONAL-ANTIBODY 190/4; KIDNEY INJURY MOLECULE-1; NECROSIS-FACTOR-ALPHA; HEPATITIS-A; PERIPHERAL TOLERANCE; HUMAN MONOCYTES; MUCIN-DOMAIN; RICH REGION AB The hepatitis A virus cellular receptor 1 (HAVCR1/TIM1), a member of the T-cell immunoglobulin mucin (TIM) family, is an important atopy susceptibility gene in humans. The exact natural function of HAVCR1/ TIM1 and the inverse association between HAV infection and prevention of atopy are not well understood. To identify natural ligands of human HAVCR1/TIM1, we used an expression cloning strategy based on the binding of dog cells transfected with a human lymph node cDNA library to a RAVCR1/TIM1 Fc fusion protein. The transfected cells that bound to the human HAVCR1/TIM1 Fc contained cDNA of human immunoglobulin alpha 1 heavy (Ig alpha 1) and lambda light (Ig lambda) chain and secreted human IgA1 lambda antibody that bound to the cell surface. Cotransfection of the isolated Ig alpha 1 and Ig lambda cDNAs to naive dog cells resulted in the secretion of IgA1 lambda that bound to HAVCR1/TIM1 Fc but not to a poliovirus receptor Fc fusion protein in a capture enzyme-linked immunosorbent assay. The interaction of HAVCR1/TIM1 with IgA was inhibited by monoclonal antibodies (MAbs) against Ig alpha 1 and Ig lambda, excess IgA1 lambda, or anti-HAVCR1/TIM1 MAN IgA did not inhibit HAV infection of African green monkey cells, suggesting that the IgA and the virus binding sites are in different epitopes on HAVCR1/TIM1. IgA enhanced significantly the neutralization of HAV by HAVCR1/TIM1 Fc. Our results indicate that IgA1 lambda is a specific ligand of HAVCR1/TIM1 and that their association has a synergistic effect in virus-receptor interactions. C1 US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis & Related Emerging Agents, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Northwestern Univ, Feinberg Sch Med, Dept Immunol Microbiol, Chicago, IL 60611 USA. Harvard Univ, Childrens Hosp, Sch Med, Karp Labs,Div Immunol, Boston, MA 02115 USA. RP Kaplan, GG (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis & Related Emerging Agents, Bethesda, MD 20892 USA. EM GK@helix.nih.gov FU NIAID NIH HHS [P01 AI 54456, P01 AI054456] NR 53 TC 25 Z9 28 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2007 VL 81 IS 7 BP 3437 EP 3446 DI 10.1128/JVI.01585-06 PG 10 WC Virology SC Virology GA 147FF UT WOS:000244988100039 PM 17229699 ER PT J AU Jayasekera, JP Moseman, EA Carroll, MC AF Jayasekera, Jerome P. Moseman, E. Ashley Carroll, Michael C. TI Natural antibody and complement mediate neutralization of influenza virus in the absence of prior immunity SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNOGLOBULIN-M; STREPTOCOCCUS-PNEUMONIAE; BINDING LECTIN; COMPONENT C3; SECRETED IGM; HOST-DEFENSE; HUMAN-SERUM; INFECTION; MICE; AUTOANTIBODIES AB Early control of virus replication by the innate immune response is essential to allow time for the generation of a more effective adaptive immune response. As an important component of innate immunity, complement has been shown to be necessary for protection against numerous microbial infections. This study was undertaken to investigate the role of complement in neutralizing influenza virus. Results demonstrated that the classical pathway of complement mediated serum neutralization of influenza virus. Although nonimmune serum neutralized influenza virus, the mechanism of virus neutralization (VN) required antibody, as sera from RAG1-deficient mice lacked VN activity; moreover, purified natural immunoglobulin M (IgM) restored VN activity to antibody-deficient sera. The mechanism of VN by natural IgM and complement was associated with virion aggregation and coating of the viral hemagglutinin receptor; however, viral lysis did not significantly contribute to VN. Additionally, reconstitution of RAG1-deficient mice with natural IgM resulted in delayed morbidity during influenza virus infection. Collectively, these results provide evidence that natural IgM and the early components of the classical pathway of complement work in concert to neutralize influenza virus and that this interaction may have a significant impact on the course of influenza viral pneumonia. C1 CBR, Biomed Res Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Carroll, MC (reprint author), CBR, Biomed Res Inst, 800 Huntington Ave, Boston, MA 02115 USA. EM carroll@cbr.med.harvard.edu NR 37 TC 112 Z9 115 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2007 VL 81 IS 7 BP 3487 EP 3494 DI 10.1128/JVI.02128-06 PG 8 WC Virology SC Virology GA 147FF UT WOS:000244988100044 PM 17202212 ER PT J AU Honeyborne, I Prendergast, A Pereyra, F Leslie, A Crawford, H Payne, R Reddy, S Bishop, K Moodley, E Nair, K van der Stok, M McCarthy, N Rousseau, CM Addo, M Mullins, JI Brander, C Kiepiela, P Walker, BD Goulder, PJR AF Honeyborne, Isobella Prendergast, Andrew Pereyra, Florencia Leslie, Alasdair Crawford, Hayley Payne, Rebecca Reddy, Shabashini Bishop, Karen Moodley, Eshia Nair, Kriebashnie van der Stok, Mary McCarthy, Noel Rousseau, Christine M. Addo, Marylyn Mullins, James I. Brander, Christian Kiepiela, Photini Walker, Bruce D. Goulder, Philip J. R. TI Control of human immunodeficiency virus type 1 is associated with HLA-B*13 and targeting of multiple gag-specific CD8(+) T-cell epitopes SO JOURNAL OF VIROLOGY LA English DT Article ID CLASS-I ALLELES; VIRAL LOAD; LYMPHOCYTE RESPONSES; HIV-1 INFECTION; ESCAPE MUTATION; HLA-B; AIDS; TRANSMISSION; PROGRESSION; REVERSION AB To better understand relationships between CD8(+) T-cell specificity and the immune control of human immunodeficiency virus type 1 (HIV-1), we analyzed the role of HLA-B*13, an allele associated with low viremia, in a cohort of 578 C clade-infected individuals in Durban, South Africa. Six novel B*13-restricted cytotoxic T lymphocyte epitopes were defined from analyses of 37 B*13-positive subjects, including three Gag epitopes. These B*13-restricted epitopes contribute to a broad Gag-specific CD8(+) response that is associated with the control of viremia. These data are consistent with data from studies of other HIA-class I alleles associated with HIV control that have shown that the targeting of multiple Gag epitopes is associated with relative suppression of viremia. C1 Dept Paediat, Oxford OX1 3SY, England. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4013 Durban, South Africa. Dept Zool, Oxford OX1 3SY, England. Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA. RP Goulder, PJR (reprint author), Peter Medawar Bldg Pathogen Res,S Pks Rd, Oxford OX1 3SY, England. EM philip.goulder@ndm.ox.ac.uk RI McCarthy, Noel/K-3314-2012; OI Brander, Christian/0000-0002-0548-5778; Bishop, Karen/0000-0003-4935-7708 FU Medical Research Council [G0500384]; NIAID NIH HHS [2R01 AI 46995-06, N01 AI 15422, P30 AI027757, R01 AI 067073, R01 AI046995, R01 AI067073]; Wellcome Trust NR 40 TC 107 Z9 112 U1 2 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2007 VL 81 IS 7 BP 3667 EP 3672 DI 10.1128/JVI.02689-06 PG 6 WC Virology SC Virology GA 147FF UT WOS:000244988100066 PM 17251285 ER PT J AU Streblow, DN van Cleef, KWR Kreklywich, CN Meyer, C Smith, P Defilippis, V Grey, F Fruh, K Searles, R Bruggeman, C Vink, C Nelson, JA Orloff, SL AF Streblow, Daniel N. van Cleef, Koen W. R. Kreklywich, Craig N. Meyer, Christine Smith, Patricia Defilippis, Victor Grey, Finn Fruh, Klaus Searles, Robert Bruggeman, Cathrien Vink, Cornelis Nelson, Jay A. Orloff, Susan L. TI Rat cytomegalovirus gene expression in cardiac allograft recipients is tissue specific and does not parallel the profiles detected in vitro SO JOURNAL OF VIROLOGY LA English DT Article ID COUPLED RECEPTOR GENE; MURINE CYTOMEGALOVIRUS; HEART-TRANSPLANTS; CHRONIC REJECTION; INFECTIOUS VIRUS; SALIVARY-GLANDS; PROTEIN; TRANSCRIPTION; CELLS; VIVO AB Rat cytomegalovirus (RCMV) is a beta-herpesvirus with a 230-kbp genome containing over 167 open reading frames (ORFs). RCMV gene expression is tightly regulated in cultured cells, occurring in three distinct kinetic classes (immediate early, early, and late). However, the extent of viral-gene expression in vivo and its relationship to the in vitro expression are unknown. In this study, we used RCW-specific DNA microarrays to investigate the viral transcriptional profiles in cultured, RCMV-infected endothelial cells, fibroblasts, and aortic smooth muscle cells and to compare these profiles to those found in tissues from RCMV-infected rat heart transplant recipients. In cultured cells, RCMV expresses approximately 95% of the known viral ORFs with few differences between cell types. By contrast, in vivo viral-gene expression in tissues from rat heart allograft recipients is highly restricted. In the tissues studied, a total of 80 viral genes expressing levels twice above background (5,000 to 10,000 copies per mu g total RNA) were detected. In each tissue type, there were a number of genes expressed exclusively in that tissue. Although viral mRNA and genomic DNA levels were lower in the spleen than in submandibular glands, the number of individual viral genes expressed was higher in the spleen (60 versus 41). This finding suggests that the number of viral genes expressed is specific to a given tissue and is not dependent upon the viral load or viral mRNA levels. Our results demonstrate that the profiles, as well as the amplitude, of viral-gene expression are tissue specific and are dramatically different from those in infected cultured cells, indicating that RCMV gene expression in vitro does not reflect viral-gene expression in vivo. C1 Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA. Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Beaverton, OR 97006 USA. Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. Univ Maastricht, Dept Med Microbiol, Maastricht, Netherlands. RP Streblow, DN (reprint author), Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, 505 SW 185th St, Beaverton, OR 97006 USA. EM streblow@ohsu.edu FU NHLBI NIH HHS [HL083194, R01 HL065754, HL71695, R01 HL071695, HL65754, R01 HL083194, R01 HL066238, HL 66238-01]; NIAID NIH HHS [AI21640, R01 AI021640] NR 30 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2007 VL 81 IS 8 BP 3816 EP 3826 DI 10.1128/JVI.02425-06 PG 11 WC Virology SC Virology GA 157BF UT WOS:000245692900016 PM 17251289 ER PT J AU Lichterfeld, M Yu, XG Mui, SK Williams, KL Trocha, A Brockman, MA Allgaier, RL Waring, MT Koibuchi, T Johnston, MN Cohen, D Allen, TM Rosenberg, ES Walker, BD Altfeld, M AF Lichterfeld, Mathias Yu, Xu G. Mui, Stanley K. Williams, Katie L. Trocha, Alicja Brockman, Mark A. Allgaier, Rachel L. Waring, Michael T. Koibuchi, Tomohiko Johnston, Mary N. Cohen, Daniel Allen, Todd M. Rosenberg, Eric S. Walker, Bruce D. Altfeld, Marcus TI Selective depletion of high-avidity human immunodeficiency virus type 1 (HIV-1)-specific CD8(+) T cells after early HIV-1 infection SO JOURNAL OF VIROLOGY LA English DT Article ID CELLULAR IMMUNE-RESPONSES; ANTIRETROVIRAL THERAPY; INTERLEUKIN-7 RECEPTOR; LYMPHOCYTE RESPONSE; PROTECTIVE IMMUNITY; AFFINITY MATURATION; EFFECTOR ACTIVITY; VIRAL ESCAPE; IN-VIVO; ANTIGEN AB Human immunodeficiency virus type I (HIV-1)-specific CD8(+) T cells in early infection are associated with the dramatic decline of peak viremia, whereas their antiviral activity in chronic infection is less apparent. The functional properties accounting for the antiviral activity of HIV-1-specific CD8(+) T cells during early infection are unclear. Using cytokine secretion and tetramer decay assays, we demonstrated in intraindividual comparisons that the functional avidity of HIV-1-specific CD8(+) T cells was consistently higher in early infection than in chronic infection in the presence of high-level viral replication. This change of HIV-1-specific CD8(+) T-cell avidity between early and chronic infections was linked to a substantial switch in the clonotypic composition of epitope-specific CD8(+) T cells, resulting from the preferential loss of high-avidity CD8(+) T-cell clones. In contrast, the maintenance of the initially recruited clonotypic pattern of HIV-1-specific CD8(+) T cells was associated with low-level set point HIV-1 viremia. These data suggest that high-avidity HIV-1-specific CD8(+) T-cell clones are recruited during early infection but are subsequently lost in the presence of persistent high-level viral replication. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA USA. Howard Hughes Med Inst, Chevy Chase, MD USA. Fenway Community Hlth, Boston, MA USA. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St, Boston, MA 02129 USA. EM maltfeld@partners.org RI Allen, Todd/F-5473-2011; OI Brockman, Mark/0000-0001-6432-1426 NR 60 TC 77 Z9 78 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2007 VL 81 IS 8 BP 4199 EP 4214 DI 10.1128/JVI.01388-06 PG 16 WC Virology SC Virology GA 157BF UT WOS:000245692900051 PM 17287271 ER PT J AU Daelemans, D Lu, R De Clercq, E Engelman, A AF Daelemans, Dirk Lu, Richard De Clercq, Erik Engelman, Alan TI Characterization of a replication-competent, integrase-defective human immunodeficiency virus (HIV)/simian virus 40 chimera as a powerful tool for the discovery and validation of HIV integrase inhibitors SO JOURNAL OF VIROLOGY LA English DT Article ID SELECTIVE-INHIBITION; ANTIVIRAL ACTIVITY; POTENT INHIBITOR; DEXTRAN SULFATE; TREATMENT-NAIVE; PRIMARY TARGET; CHICORIC ACID; TYPE-1; CELLS; MECHANISM AB Integrase is actively studied as an antiviral target, but many inhibitors selected from biochemical screens fail to inhibit human immunodeficiency virus (HIV) replication or primarily affect off-site targets. Here we develop and validate a replication-competent, simian virus 40-HIV integrase mutant chimera as a novel tool to classify the mechanism of action of potential integrase inhibitors. Whereas the mutant was more susceptible than the wild type to entry, reverse transcriptase, and protease inhibitors, it specifically resisted the action of integrase inhibitor L-870,810. We furthermore demonstrate inhibition of integration by GS-9137 and GS-9160 and off-site targeting by the 6-aminoquinolone antibiotic WM-5. C1 Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA 02115 USA. RP Daelemans, D (reprint author), Katholieke Univ Leuven, Rega Inst Med Res, Minderbroedersstr 10, B-3000 Louvain, Belgium. EM dirk.daelemans@rega.kuleuven.be FU NIAID NIH HHS [R01 AI052014, AI39394, AI52014, R01 AI039394, R37 AI039394] NR 32 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2007 VL 81 IS 8 BP 4381 EP 4385 DI 10.1128/JVI.02637-06 PG 5 WC Virology SC Virology GA 157BF UT WOS:000245692900074 PM 17287285 ER PT J AU Carnes, M Bigby, J AF Carnes, Molly Bigby, Judyann TI Jennifer fever in academic medicine SO JOURNAL OF WOMENS HEALTH LA English DT Editorial Material C1 Univ Wisconsin, Dept Med, Madison, WI 53715 USA. William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI USA. Women Vet Hlth Program, Madison, WI USA. Brigham & Womens Hosp, Dept Med, Harvard Med Sch Ctr Excellence Womens Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Carnes, M (reprint author), Univ Wisconsin, Dept Med Psychiat & Ind & Syst Engn, Ctr Womens Hlth Res, WISELI, 700 Regent St,Suite 301, Madison, WI 53715 USA. EM mlcarnes@wisc.edu FU NIGMS NIH HHS [R01 GM088477] NR 5 TC 1 Z9 1 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD APR PY 2007 VL 16 IS 3 BP 299 EP 301 DI 10.1089/jwh.2007.E072 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 158GB UT WOS:000245778600002 PM 17439375 ER PT J AU Ochala, J Frontera, WR Dorer, DJ Van Hoecke, J Krivickas, LS AF Ochala, Julien Frontera, Walter R. Dorer, David J. Van Hoecke, Jacques Krivickas, Lisa S. TI Single skeletal muscle fiber elastic and contractile characteristics in young and older men SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID MECHANICAL-PROPERTIES; FILAMENT OVERLAP; MYOSIN-FILAMENTS; SARCOMERE LENGTH; FORCE GENERATION; FLEXOR MUSCLES; IN-VITRO; STIFFNESS; ACTIN; AGE AB The current investigation was designed to: (a) assess the impact of aging on elastic characteristics of single skeletal muscle fibers from young (N = 6) and older men (N = 6); and (b) correlate the potential changes, with the fiber contractile properties. Chemically skinned single muscle fibers (n = 235) from vastus lateralis muscle were maximally activated. Maximal force and cross-sectional area were measured, and specific force calculated. The slack test was used to measure maximal unloaded shortening velocity. A quick release of 0.15% of fiber length was applied to determine instantaneous stiffness. The myosin heavy chain isoform composition of each single fiber was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Aging induces changes in both fiber elasticity (i.e., increased instantaneous stiffness) and contractility (i.e., reduced specific force and unloaded shortening velocity) in type I and IIa fibers. However, the changes in fiber stiffness may not directly influence contractile characteristics alterations. C1 Harvard Univ, Sch Med, Boston, MA USA. Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Muscle Cell Physiol Lab, Boston, MA USA. Univ Bourgogne, Fac Sci Sport, Equipe INSERM ERM Motr Plast, Dijon, France. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Ochala, J (reprint author), Univ Uppsala Hosp, Dept Neurosci Clin Neurophysiol, Entrance 85,3rd Floor, SE-75185 Uppsala, Sweden. OI Ochala, Julien/0000-0002-6358-2920 FU NIA NIH HHS [AG18844-01] NR 45 TC 48 Z9 50 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD APR PY 2007 VL 62 IS 4 BP 375 EP 381 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 228WN UT WOS:000250763400006 PM 17452730 ER PT J AU Delmonico, FL Dew, MA AF Delmonico, F. L. Dew, M. A. TI Living donor kidney transplantation in a global environment SO KIDNEY INTERNATIONAL LA English DT Review DE kidney transplant donor care ID LIVE-ORGAN DONOR; UNITED-NETWORK; EXCHANGE; DONATION; PROCUREMENT; GUIDELINES; ATTITUDES; PROGRAM; ETHICS; WORLD AB Live donor kidney transplantation has become a widely sought treatment by patients with end-stage renal failure. As the outcome for the genetically and emotionally related live donor transplants is the same, this review considers live kidney transplantation from the broad scope of current international practice. Unrelated live donor transplantation can now be performed for incompatible donor recipient pairs via a simultaneous paired kidney donation. However, acceptance of the scientific data that an unrelated live donor transplant can now be performed successfully should not be misconstrued as an acceptance that an unrelated kidney may be purchased via a vendor sale. At a recent World Health Organization ( WHO) conference of Middle East transplant professionals a statement of unequivocal opposition to commercialism was drafted. In the United States, the Institute of Medicine has recently published a significant report that affirms the legal prohibition of organ sales. These documents are in accord with the guiding principles of the WHO and the membership policy of The Transplantation Society. The person who gives consent to be a donor should be competent, willing to donate, free of coercion, medically and psychosocially suitable, and fully informed of the risks and benefits as a donor. With these principles established, the Amsterdam Forum has set forth a comprehensive list of medical criteria that is now used internationally in the evaluation of potential kidney donors. Guidelines of a psychosocial evaluation are also presented in this report for individuals who come forward through internet solicitation and other public appeals. It is now evident that the annual number of available deceased donors will not resolve the ongoing shortage of organs. Nevertheless, live donor kidney transplantation may not be the realistic final solution to an international public health epidemic of renal failure that is the result of an aging population of patients that have had inadequate preventive medical care. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Soc, Boston, MA 02114 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. RP Delmonico, FL (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM DMA@transplantation-soc.org NR 30 TC 39 Z9 43 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD APR PY 2007 VL 71 IS 7 BP 608 EP 614 DI 10.1038/sj.ki.5002125 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 154JB UT WOS:000245501900005 PM 17290291 ER PT J AU Huang, YQ White, DP Malhotra, A AF Huang, Yaqi White, David P. Malhotra, Atul TI Use of computational modeling to predict responses to upper airway surgery in obstructive sleep apnea SO LARYNGOSCOPE LA English DT Article DE apnea; model; finite element; breathing; lung; sleep; upper airway ID PHARYNGEAL COLLAPSE AB Objectives. Despite the well-recognized consequences of obstructive sleep apnea (OSA), its treatment remains unsatisfactory. Therapeutic strategies are complicated by often poor adherence in the case of continuous positive airway pressure or the highly variable efficacy in the case of many upper airway surgeries. Computational models of the upper airway using finite element analysis to simulate the effects of various anatomic and physiologic manipulations on pharyngeal mechanics could be helpful in predicting surgical success. Study Design. Computational and physiologic study. Methods: Using representative OSA magnetic resonance images and experimentally measured upper airway dilator muscle activities, we developed a working two-dimensional and a partial three-dimensional model of the upper airway. Results: As predicted from experimental measurements, the OSA model airway has a closing pressure of -2 cm H2O. Manipulations such as palatal stiffening, palatal resection, and tongue stiffening all have demonstrable effects on pharyngeal mechanics. We have also developed a partial three-dimensional OSA model in which we simulate the mechanics of the pharyngeal airway in the midsagittal and parasagittal. slices, spanning more than 1 inch in thickness. Using this model, we have observed important effects of tongue and palatal stiffening on anteroposterior collapse of the pharyngeal airway. Conclusions: Our data suggest that computational modeling is feasible and can be used to generate hypotheses for subsequent clinical trials regarding anatomic manipulations in OSA. We further believe that the goal of individualizing OSA therapy on the basis of underlying mechanisms could be facilitated by computational modeling. C1 Brigham & Womens Hosp, BIDMC, Sleep Disorders Res Program, Sleep Med Div,Pulm & Crit Care Div, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Malhotra, A (reprint author), Brigham & Womens Hosp, BIDMC, Sleep Disorders Res Program, Sleep Med Div,Pulm & Crit Care Div, 75 Francis St, Boston, MA 02115 USA. EM amalhotra1@partners.org FU NHLBI NIH HHS [R01 HL073146-03, R01-HL73146, R01 HL073146]; NIA NIH HHS [K23 AG024837, K23 AG024837-04, AG024837] NR 15 TC 37 Z9 41 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD APR PY 2007 VL 117 IS 4 BP 648 EP 653 DI 10.1097/MLG.0b013e318030ca55 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 152QR UT WOS:000245377400017 PM 17415135 ER PT J AU Bredy, TW Wu, H Crego, C Zellhoefer, J Sun, YE Barad, M AF Bredy, Timothy W. Wu, Hao Crego, Cortney Zellhoefer, Jessica Sun, Yi E. Barad, Mark TI Histone modifications around individual BDNF gene promoters in prefrontal cortex are associated with extinction of conditioned fear SO LEARNING & MEMORY LA English DT Article ID PROTEIN-SYNTHESIS; NEUROTROPHIC FACTOR; VALPROIC ACID; MEMORY EXTINCTION; RAT HIPPOCAMPUS; MOUSE MODEL; AMYGDALA; REQUIRES; CONSOLIDATION; MICE AB Extinction of conditioned fear is an important model both of inhibitory learning and of behavior therapy for human anxiety disorders. Like other forms of learning, extinction learning is long-lasting and depends on regulated gene expression. Epigenetic mechanisms make an important contribution to persistent changes in gene expression; therefore, in these studies, we have investigated whether epigenetic regulation of gene expression contributes to fear extinction. Since brain-derived neurotrophic factor ( BDNF) is crucial for synaptic plasticity and for the maintenance of long-term memory, we examined histone modifications around two BDNF gene promoters after extinction of cued fear, as potential targets of learning-induced epigenetic regulation of gene expression. Valproic acid ( VPA), used for some time as an anticonvulsant and a mood stabilizer, modulates the expression of BDNF, and is a histone deacetylase ( HDAC) inhibitor. Here, we report that extinction of conditioned fear is accompanied by a significant increase in histone H4 acetylation around the BDNF P4 gene promoter and increases in BDNF exon I and IV mRNA expression in prefrontal cortex, that VPA enhances long-term memory for extinction because of its HDAC inhibitor effects, and that VPA potentiates the effect of weak extinction training on histone H4 acetylation around both the BDNF P1 and P4 gene promoters and on BDNF exon IV mRNA expression. These results suggest a relationship between histone H4 modification, epigenetic regulation of BDNF gene expression, and long-term memory for extinction of conditioned fear. In addition, they suggest that HDAC inhibitors may become a useful pharmacological adjunct to psychotherapy for human anxiety disorders. C1 Semel Inst Neurosci & Human Behav, Brain Res Inst, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Barad, M (reprint author), Semel Inst Neurosci & Human Behav, Brain Res Inst, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. EM mbarad@mednet.ucla.edu RI Wu, Hao/G-4145-2013 OI Wu, Hao/0000-0002-1256-6891 NR 45 TC 277 Z9 290 U1 2 U2 34 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD APR PY 2007 VL 14 IS 4 BP 268 EP 276 DI 10.1101/lm.500907 PG 9 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 162BI UT WOS:000246060900006 PM 17522015 ER PT J AU Friedman, LS AF Friedman, Lawrence S. TI Liver transplantation for sickle cell hepatopathy SO LIVER TRANSPLANTATION LA English DT Editorial Material ID INTRAHEPATIC CHOLESTASIS; HEPATITIS-C; ANEMIA; DISEASE; PATIENT; TRANSFUSION; EXCHANGE; FAILURE; CHILDREN C1 Newton Wellesley Hosp, Dept Med, Newton, MA 02462 USA. Harvard Univ, Sch Med, Boston, MA USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Friedman, LS (reprint author), Newton Wellesley Hosp, Dept Med, 2014 Washington St, Newton, MA 02462 USA. EM lfriedman@partners.org NR 31 TC 4 Z9 4 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD APR PY 2007 VL 13 IS 4 BP 483 EP 485 DI 10.1002/lt.21031 PG 3 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 155RT UT WOS:000245596400003 PM 17394145 ER PT J AU He, J Zhou, F Shao, K Hang, J Wang, H Rayburn, E Xiao, ZX Lee, SW Xue, Q Feng, XL Shi, SS Zhang, CY Zhang, S AF He, Jie Zhou, Fang Shao, Kang Hang, Jie Wang, Hui Rayburn, Elizabeth Xiao, Zhi-xiong Lee, Sam W. Xue, Qi Feng, Xiao-li Shi, Su-sheng Zhang, Cui-yan Zhang, Sen TI Overexpression of Pin1 in non-small cell lung cancer (NSCLC) and its correlation with lymph node metastases SO LUNG CANCER LA English DT Article DE Pin1; overexpression; non-small cell lung cancer; lymph node metastases ID PROLYL ISOMERASE PIN1; BETA-CATENIN; BREAST-CANCER; CYCLIN D1; EXPRESSION; CARCINOMA; MDM2; PHOSPHORYLATION; ISOMERIZATION; MITOSIS AB Background: Pin1 isomerizes the bonds of molecules important for numerous oncogenic and cell-signaling pathways, including Bcl-2, p53, c-Jun, beta-catenin, NF-kappa B, cyclin D1, c-Myc and Raf-1. This can cause a change in conformation leading to alterations in catalytic activity, protein-protein interactions, subcellular localization and protein stability. These alterations have been shown to be associated with cell transformation and cancer progression. Pin1 is overexpressed in several different human cancers. This is the first report of Pin1 overexpression in clinical samples of non-small cell lung cancer (NSCLC). Methods: Protein expression levels of Pin1 in tumor and normal lung specimens were analyzed for expression of Pin1, cyclin D1, p53 and MDM2 using immunohistochemistry and compared to several clinicopathological characteristics. The mRNA expression of Pin1 was also analyzed using quantitative real-time RT-PCR and compared to clinicopathological characteristics. Results: Pin1 protein was shown to be overexpressed in NSCLC tumor samples, and correlated with lymph node positive disease and tumor stage. High expression of MDM2 also correlated with lymph node positive disease and with poorly differentiated tumors. High expression of MDM2 also correlated with lymph node positive disease and with poorly differentiated tumors. High expression levels of Pin1 correlated with high levels of p53 or MDM2 protein, but did not show a correlation with cyclin D1. However, high levels of MDM2 correlated with cyclin D1 overexpression. Pin1 mRNA was expressed significantly more often in the tumors of smokers than of non-smokers. The relationship between the expression of protein and mRNA of Pin1 has obviously showed that protein expression isn't significantly associated with mRNA expression. Conclusions: Pin1 is overexpressed in many different cancers, including NSCLC, and may possibly be used as a tumor marker or as a target for cancer therapy. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Peking Union Med Coll, Canc Hosp & Inst, Beijing 100021, Peoples R China. Chinese Acad Med Sci, Beijing 100021, Peoples R China. Univ Alabama, Dept Pharmacol & Toxicol, Birmingham, AL 35294 USA. Univ Alabama, Div Clin Pharmacol, Birmingham, AL 35294 USA. Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pharmacol, Boston, MA 02118 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02129 USA. RP He, J (reprint author), Chinese Acad Med Sci, Canc Hosp & Inst, Dept Thorac Surg, POB 2258, Beijing 100021, Peoples R China. EM prof.hejie@263.net NR 31 TC 25 Z9 30 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD APR PY 2007 VL 56 IS 1 BP 51 EP 58 DI 10.1016/j.lungcan.2006.11.024 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 158HF UT WOS:000245781700007 PM 17275947 ER PT J AU Mori, S Endo, M Komatsu, S Yashiro, T Kandatsu, S Baba, M AF Mori, Shinichiro Endo, Masahiro Komatsu, Shuhei Yashiro, Tomoyasu Kandatsu, Susumu Baba, Masayuki TI Four-dimensional measurement of lung tumor displacement using 256-multi-slice CT-scanner SO LUNG CANCER LA English DT Article DE computed tomography; lung cancer; internal margin; target volume; respiratory ID REAL-TIME; PERFORMANCE EVALUATION; COMPUTED-TOMOGRAPHY; RADIATION-THERAPY; TARGET VOLUMES; MOTION; RADIOTHERAPY; RECONSTRUCTION; TRACKING; PRECISE AB The concept of internal target volume is of marked importance for radiotherapy to lung tumors as respiration-induced motion is important. Individualized assessment of motion is required as tumor site may not predict the extent or pattern of tumor motion. We performed volumetric cine scanning using the 256-multi-slice CT (256MSCT) to study tumor motion during free breathing in 14 inpatients who were treated with carbon-ion radiotherapy. Motion assessment in 16 respiratory phases of the cine CT revealed most tumors to show hysteresis-like behavior. Isocenter displacement between peak exhalation and inhalation for the average of the right and left lungs were 7 mm, 7 mm and 15 mm for the upper, middle and tower lobes, respectively. Cine CT with the 256MSCT improved the evaluation of tumor displacement and overcomes some of the limitations associated with current CT methods. Volumetric cine CT data provides useful data on motion for planning in all radiation approaches for Lung tumors. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Natl Inst Radiol Sci, Res Ctr Charged Particle Therapy, Chiba 260, Japan. Natl Inst Radiol Sci, Dept Planning & Management, Chiba 260, Japan. Natl Inst Radiol Sci, Hosp, Chiba 260, Japan. RP Mori, S (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM smori1@partners.org OI Mori, Shinichiro/0000-0002-0412-4399 NR 37 TC 26 Z9 28 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD APR PY 2007 VL 56 IS 1 BP 59 EP 67 DI 10.1016/j.lungcan.2006.11.011 PG 9 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 158HF UT WOS:000245781700008 PM 17157951 ER PT J AU Costa, DB Li, SG Kocher, O Feins, RH Keller, SM Schiller, JH Johnson, DH Tenen, DG Halmos, B AF Costa, Daniel B. Li, Sigui Kocher, Olivier Feins, Richard H. Keller, Steven M. Schiller, Joan H. Johnson, David H. Tenen, Daniel G. Halmos, Balazs TI Immunohistochemical analysis of C/EBP alpha in non-small cell lung cancer reveals frequent down-regulation in stage II and IIIA tumors: A correlative study of E3590 SO LUNG CANCER LA English DT Article DE lung cancer; C/EBP alpha; transcription factor; immunohistochemistry; non-small cell lung cancer; squamous cell carcinoma; survival ID BINDING-PROTEIN-ALPHA; ACUTE MYELOID-LEUKEMIA; POSTOPERATIVE ADJUVANT THERAPY; PROGNOSTIC-SIGNIFICANCE; TRANSCRIPTION FACTORS; RANDOMIZED-TRIAL; CEBPA MUTATIONS; EXPRESSION; MICE; RAS AB Purpose: We sought to determine the association of C/EBP alpha expression status with clinical, pathologic and molecular characteristics, as well as outcomes, in non-small-cell lung cancer (NSCLC). This is the first comprehensive study of this transcription factor in patients with NSCLC. Patients and methods: Our cohort originated from ECOG 3590 (randomized trial of postoperative adjuvant therapy with thoracic radiation or cisplatin and etoposide plus thoracic radiation in patients with completely resected stages II and IIIA NSCLC; and its laboratory correlate, ECOG 4592). One hundred and sixty four tumor samples contained sufficient material for immunohistochemical (IHC) analysis. C/EBPa tumor staining was compared to that of basal bronchial cells (3+). 0 or 1+ (weak) suggested tack of, white 2 or 3+ (strong) suggested C/EBP alpha expression. Results: Ninety tumors (55%) had 0 or 1+ C/EBP alpha staining, and the remaining 74 (45%) 2 or 3+. Patients with squamous cell carcinomas had a higher percentage of weak C/EBP alpha IHC staining compared to other histologies to = 0.048) and there was a trend for toss of C/EBP alpha in poorly differentiated compared to welt differentiated tumors (p = 0.07). There was no association between C/EBP alpha IHC and mutations in p53 or K-ras. The median disease-free survival for patients with weak and strong C/EBP alpha. IHC expression was 29.6 and 30.6 months, respectively (p = 0.94). The median overall survival between the weak and strong groups was 43.5 and 38.5 months, respectively (p = 0.83). Conclusions: Loss of expression of C/EBP alpha is seen in over half of stage II and IIIA NSCLC, specifically in squamous cell carcinomas and poorly differentiated tumors. Since down-regulation of C/EBP alpha. is a common event in NSCLC, further elucidation of the involvement of C/EBP alpha in the pathogenesis and progression of lung cancer may identify novel therapeutic targets. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Inst Med, Sch Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Univ N Carolina, Chapel Hill, NC USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Vanderbilt Univ, Nashville, TN USA. Case Western Reserve Univ, Div Hematol Oncol, Cleveland, OH 44106 USA. RP Tenen, DG (reprint author), Harvard Univ, Inst Med, Sch Med, HIM-954,77 Louis Pasteur Ave, Boston, MA 02215 USA. EM dtenen@bidmc.harvard.edu RI Johnson, David/A-7437-2009; OI Costa, Daniel/0000-0002-0689-395X; Tenen, Daniel/0000-0002-6423-3888 FU NCI NIH HHS [P20 CA090578, PA20-CA090578] NR 36 TC 16 Z9 17 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD APR PY 2007 VL 56 IS 1 BP 97 EP 103 DI 10.1016/j.lungcan.2006.11.023 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 158HF UT WOS:000245781700012 PM 17239984 ER PT J AU Ramel, MC Emery, CS Foulger, R Goberdhan, DCI van den Heuvel, M Wilson, C AF Ramel, M-C. Emery, C. S. Foulger, R. Goberdhan, D. C. I. van den Heuvel, M. Wilson, C. TI Drosophila SnoN modulates growth and patterning by antagonizing TGF-beta signalling SO MECHANISMS OF DEVELOPMENT LA English DT Article DE SnoN; Ski; Drosophila; growth; wing vein; TGF-beta; cancer; decapentaplegic ID SKI ONCOPROTEIN; FEEDBACK-REGULATION; CELL-PROLIFERATION; MORPHOGEN GRADIENT; PROGNOSTIC MARKER; TUMOR-SUPPRESSOR; WING DEVELOPMENT; OPTOMOTOR-BLIND; HUMAN-MELANOMA; SMAD PROTEINS AB Signalling by TGF-beta ligands through the Smad family of transcription factors is critical for developmental patterning and growth. Disruption of this pathway has been observed in various cancers. In vertebrates, members of the Ski/Sno protein family can act as negative regulators of TGF-beta signalling, interfering with the Smad machinery to inhibit the transcriptional output of this pathway. In some contexts ski/sno genes function as tumour suppressors, but they were originally identified as oncogenes, whose expression is up-regulated in many tumours. These growth regulatory effects and the normal physiological functions of Ski/Sno proteins have been proposed to result from changes in TGF-beta signalling. However, this model is controversial and may be over-simplified, because recent findings indicate that Ski/Sno proteins can affect other signalling pathways. To address this issue in an in vivo context, we have analyzed the function of the Drosophila Ski/Sno orthologue, SnoN. We found that SnoN inhibits growth when overexpressed, indicating a tumour suppressor role in flies. It can act in multiple tissues to selectively and cell autonomously antagonise signalling by TGF-beta ligands from both the BMP and Activin sub-families. By contrast, analysis of a snoN mutant indicates that the gene does not play a global role in TGF-beta-mediated functions, but specifically inhibits TGF-beta-induced wing vein formation. We propose that SnoN normally functions redundantly with other TGF-beta pathway antagonists to finely adjust signalling levels, but that it can behave as an extremely potent inhibitor of TGF-beta signalling when highly expressed, highlighting the significance of its deregulation in cancer cells. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Univ Oxford, Dept Physiol Anat & Genet, MRC, Funct Genet Unit, Oxford OX1 3QX, England. Univ Kent, Res Sch Biosci, Dept Biosci, Canterbury CT2 7NJ, Kent, England. RP Ramel, MC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, D1524,44 Binney St, Boston, MA 02115 USA. EM marie-christine.ramel@anat.ox.ac.uk OI Foulger, Rebecca/0000-0001-8682-8754 FU Medical Research Council [MC_U137761451] NR 75 TC 10 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD APR PY 2007 VL 124 IS 4 BP 304 EP 317 DI 10.1016/j.mod.2006.12.006 PG 14 WC Developmental Biology SC Developmental Biology GA 157YN UT WOS:000245757600004 PM 17289352 ER PT J AU Iezzoni, LI AF Iezzoni, Lisa I. TI Finally present on admission but needs attention SO MEDICAL CARE LA English DT Editorial Material C1 Harvard Univ, Inst Hlth Policy, Sch Med, Massachusetts Gen Hosp, Boston, MA 02214 USA. RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02214 USA. EM liezzoni@partners.org NR 9 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD APR PY 2007 VL 45 IS 4 BP 280 EP 282 DI 10.1097/01.mlr.0000259078.54902.fe PG 3 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 157EO UT WOS:000245701600002 PM 17496709 ER PT J AU Zhang, QW Safford, M Miller, D Crystal, S Rajan, M Tseng, CL Pogach, L AF Zhang, Quanwu Safford, Monika Miller, Donald Crystal, Stephen Rajan, Mangala Tseng, Chin-Lin Pogach, Leonard TI Short-term statin exposure is associated with reduced all-cause mortality in persons with diabetes SO MEDICAL CARE LA English DT Article; Proceedings Paper CT 63rd Annual Meeting of the American-Diabetes-Association CY JUN 13-17, 2003 CL NEW ORLEANS, LA SP Amer Diabet Assoc DE statins; mortality; diabetes ID CORONARY-HEART-DISEASE; PLACEBO-CONTROLLED TRIAL; OF-VETERANS-AFFAIRS; LOWERING TREATMENT; CHOLESTEROL LEVELS; RANDOMIZED-TRIALS; ELDERLY PATIENTS; PRAVASTATIN; METAANALYSIS; THERAPY AB Background: The survival benefit of statins in nontrial populations of persons with diabetes is unknown. Objective: We sought to determine all-cause mortality in fiscal year 2001 (FYOI) after statin initiation in FY 99 and/or FYOO in individuals with diabetes in the Veterans Healthcare Administration (VHA). Methods: Using a retrospective longitudinal cohort analysis, we analyzed 201,102 veterans with diabetes from 104 VHA facilities with medical, pharmacy, and laboratory information from VHA and Medicare databases. Patients with statin exposure, defined as ha, medication possession coverage > 50% of eligible days in FY99 and/or FY00, were characterized as initiators if no statin prescription was found in FY98. Otherwise, they were characterized as continuing users. We defined 4 statin exposure groups: FY99 only, FY00 only, both FY99 and 00, and neither year. All-cause mortality was determined in FY01 Propensity score matched comparisons were used to corroborate results from mixed effects logistic models. Results: FYOI mortality was no different between FY99-only initiators and the nonexposure group (odds ratio [OR] = 1.08, P = 0.429). In contrast, FY00-only and FY99-00 initiator groups showed odds ratio of 0.75 (P < 0.0001) and 0.71 (P < 0.0001), respectively. There was a similar benefit for continuing users. Propensity analysis demonstrated consistent findings. Increased statin adherence from > 50% to > 75% was associated with increased benefit (OR = 0.71, P < 0.0001 versus OR = 0.62, P = 0.0002). Conclusions: One to 2-year statin exposure is associated with a 25% to 29% risk reduction in all-cause mortality of the subsequent year in a high-risk diabetes cohort. C1 Ctr Healthcare Knowledge Management, Dept Vet Affairs New Jersey Healthcare Syst, E Orange, NJ 07018 USA. Birmingham VA Med Ctr, Deep S Ctr Effect, Birmingham, AL USA. Univ Alabama, Birmingham, AL USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Bedford Vet Affairs Med, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. Rutgers State Univ, New Brunswick, NJ USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. RP Pogach, L (reprint author), Ctr Healthcare Knowledge Management, Dept Vet Affairs New Jersey Healthcare Syst, 385 Tremont Ave, E Orange, NJ 07018 USA. EM Leonard.Pogach@med.va.gov NR 28 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD APR PY 2007 VL 45 IS 4 BP 308 EP 314 DI 10.1097/01.mlr.0000250227.94196.f0 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 157EO UT WOS:000245701600007 PM 17496714 ER PT J AU Xiang, HF Song, JS Chin, DWH Cormack, RA Tishler, RB Makrigiorgos, GM Court, LE Chin, LM AF Xiang, Hong F. Song, Jun S. Chin, David W. H. Cormack, Robert A. Tishler, Roy B. Makrigiorgos, G. Mike Court, Laurence E. Chin, Lee M. TI Build-up and surface dose measurements on phantoms using micro-MOSFET in 6 and 10 MV x-ray beams and comparisons with Monte Carlo calculations SO MEDICAL PHYSICS LA English DT Article DE micro-MOSFET; surface dose; skin dose; head and neck IMRT; breast cancer radiotherapy; Monte Carlo simulation ID IN-VIVO DOSIMETRY; RADIATION-THERAPY; RADIOTHERAPY; SKIN; DETECTOR AB This work is intended to investigate the application and accuracy of micro-MOSFET for superficial dose measurement under clinically used MV x-ray beams. Dose response of micro-MOSFET in the build-up region and on surface under MV x-ray beams were measured and compared to Monte Carlo calculations. First, percentage-depth-doses were measured with micro-MOSFET under 6 and 10 MV beams of normal incidence onto a flat solid water phantom. Micro-MOSFET data were compared with the measurements from a parallel plate ionization chamber and Monte Carlo dose calculation in the build-up region. Then, percentage-depth-doses were measured for oblique beams at 0 degrees-80 degrees onto the flat solid water phantom with micro-MOSFET placed at depths of 2 cm, 1 cm, and 2 mm below the surface. Measurements were compared to Monte Carlo calculations under these settings. Finally, measurements were performed with micro-MOSFET embedded in the first I mm layer of bolus placed on a flat phantom and a curved phantom of semi-cylindrical shape. Results were compared to superficial dose calculated from Monte Carlo for a 2 turn thin layer that extends from the surface to a depth of 2 mm. Results were (1) Comparison of measurements with MC calculation in the build-up region showed that micro-MOSFET has a water-equivalence thickness (WET) of 0.87 mm for 6 MV beam and 0.99 rum for 10 MV beam from the flat side, and a WET of 0.72 mm for 6 MV beam and 0.76 mm for 10 MV beam from the epoxy side. (2) For normal beam incidences, percentage depth dose agree within 3%-5% among micro-MOSFET measurements, parallel-plate ionization chamber measurements, and MC calculations. (3) For oblique incidence on the flat phantom with micro-MOSFET placed at depths of 2 cm, I cm, and 2 mm, measurements were consistent with MC calculations within a typical uncertainty of 3%-5%. (4) For oblique incidence on the flat phantom and a curved-surface phantom, measurements with micro-MOSFET placed at 1.0 mm agrees with the MC calculation within 6%, including uncertainties of micro-MOSFET measurements of 2%-3% (1 standard deviation), MOSFET angular dependence of 3.0%-3.5%, and 1%-2% systematical error due to phantom setup geometry asymmetry. Micro-MOSFET can be used for skin dose measurements in 6 and 10 MV beams with an estimated accuracy of 6%. (c) 2007 American Association of Physicists in Medicine. C1 Harvard Univ, Sch Med, Dana Farber & Brigham Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. RP Xiang, HF (reprint author), Harvard Univ, Sch Med, Dana Farber & Brigham Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. EM hxiang@lroc.havard.edu; lcourt@lroc.havard.edu; lchin@lroc.harvard.edu OI Cormack, Robert/0000-0001-5553-9984 NR 21 TC 25 Z9 25 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD APR PY 2007 VL 34 IS 4 BP 1266 EP 1273 DI 10.1118/1.2710951 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 159CH UT WOS:000245842500015 PM 17500458 ER PT J AU Turner, GM Soubret, A Ntziachristos, V AF Turner, Gordon M. Soubret, Antoine Ntziachristos, Vasilis TI Inversion with early photons SO MEDICAL PHYSICS LA English DT Article DE time-resolved imaging; tomography ID DIFFUSE OPTICAL TOMOGRAPHY; BOLTZMANN TRANSPORT-EQUATION; SPARSE LINEAR-EQUATIONS; INFINITE UNIFORM MEDIUM; DISCRETE RANDOM-MEDIA; PULSE-PROPAGATION; TURBID MEDIA; COMPUTED-TOMOGRAPHY; RADIATIVE-TRANSFER; ANALYTIC SOLUTION AB Optical tomography using early photons can improve resolution and reduce the ill-posed nature of the inversion problem. In this work we use 360' projection experimental data to investigate the inversion performance of three commonly used numerical inversion methods: the random algebraic reconstruction technique (rART), singular value decomposition (SVD), and the conjugate-gradient-type method LSQR. Results are contrasted to each other and the effects of different photon propagation models are also investigated. We find that all methods perform adequately given appropriate regularization parameters, and that an experimentally measured photon weight function yields superior results over two approximate weights that have been previously used. (c) 2007 American Association of Physicists in Medicine. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Lab Bioopt & Mol Imaging, Hillsborough, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Ntziachristos, V (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Lab Bioopt & Mol Imaging, CNY 149 13th St 5406, Hillsborough, MA 02129 USA. EM vasilis@helix.mgh.harvard.edu FU PHS HHS [R01000750] NR 63 TC 8 Z9 8 U1 0 U2 4 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD APR PY 2007 VL 34 IS 4 BP 1405 EP 1411 DI 10.1118/1.2437103 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 159CH UT WOS:000245842500029 PM 17500472 ER PT J AU Jiang, HY Seco, J Paganetti, H AF Jiang, Hongyu Seco, Joao Paganetti, Harald TI Effects of Hounsfield number conversion on CT based proton Monte Carlo dose calculations SO MEDICAL PHYSICS LA English DT Article DE Geant4; Monte Carlo; proton therapy; CT Hounsfield conversion ID ELECTRON-DENSITY; STOPPING-POWER; PHOTON BEAMS; THERAPY; DISTRIBUTIONS; SIMULATION; RADIOTHERAPY AB The Monte Carlo method provides the most accurate dose calculations on a patient computed tomography (CT) geometry. The increase in accuracy is, at least in part, due to the fact that instead of treating human tissues as water of various densities as in analytical algorithms, the Monte Carlo method allows human tissues to be characterized by elemental composition and mass density, and hence allows the accurate consideration of all relevant electromagnetic and nuclear interactions. On the other hand, the algorithm to convert CT Hounsfield numbers to tissue materials for Monte Carlo dose calculation introduces uncertainties. There is not a simple one to one correspondence between Hounsfield numbers and tissue materials. To investigate the effects of Hounsfield number conversion for proton Monte Carlo dose calculations, clinical proton treatment plans were simulated using the Geant4 Monte Carlo code. Three Hounsfield number to material conversion methods were studied. The results were compared in forms of dose volume histograms of gross tumor volume and clinical target volume. The differences found are generally small but can be dosimetrically significant. Further, different methods may cause deviations in the predicted proton beam range in particular for deep proton fields. Typically, slight discrepancies in mass density assignments play only a minor role in the target region, whereas more significant effects are caused by different assignments in elemental compositions. In the presence of large tissue inhomogeneities, for head and neck treatments, treatment planning decisions could be affected by these differences because of deviations in the predicted tumor coverage. Outside the target area, differences in elemental composition and mass density assignments both may play a role. This can lead to pronounced effects for organs at risk, in particular in the spread-out Bragg peak penumbra or distall regions. In addition, the significance of the elemental composition effect (dose to water vs. dose to tissue) is tissue-type dependent and is also affected by nuclear reactions. (c) 2007 American Association of Physicists in Medicine. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM hpaganetti@partners.org RI Seco, Joao/J-4451-2012 FU NCI NIH HHS [P01 CA021239-28, P01 CA021239, P01 CA21239] NR 24 TC 45 Z9 45 U1 0 U2 6 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD APR PY 2007 VL 34 IS 4 BP 1439 EP 1449 DI 10.1118/1.2715481 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 159CH UT WOS:000245842500032 PM 17500475 ER PT J AU Li, H Liang, HP Castrillon, DH DePinho, RA Olson, EN Liu, ZP AF Li, Hao Liang, Hanping Castrillon, Diego H. DePinho, Ronald A. Olson, Eric N. Liu, Zhi-Ping TI FoxO4 regulates tumor necrosis factor alpha-directed smooth muscle cell migration by activating matrix metalloproteinase 9 gene transcription SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NF-KAPPA-B; EXTENDS LIFE-SPAN; MATRIX METALLOPROTEINASES; NEOINTIMAL HYPERPLASIA; FORKHEAD; JNK; DIFFERENTIATION; RESPONSES; GROWTH; TRANSLOCATION AB Phenotypic modulation of vascular smooth muscle cells (SMCs) in the blood vessel wall from a differentiated to a proliferative state during vascular injury and inflammation plays an important role in restenosis and atherosclerosis. Matrix metalloproteinase 9 (MMP9) is a member of the NIMP family of proteases, which participate in extracellular matrix degradation and turnover. MMP9 is upregulated and required for SMC migration during the development of restenotic and atherosclerotic lesions. In this study, we show that FoxO4 activates transcription of the MMP9 gene in response to tumor necrosis factor alpha (TNF-alpha) signaling. Inhibition of FoxO4 expression by small interfering RNA or gene knockout reduces the abilities of SMCs to migrate in vitro and inhibit neointimal formation and MMP9 expression in vivo. We further show that both the N-terminal, Sp1-interactive domain and the C-terminal transactivation domain of FoxO4 are required for FoxO4-activated MMP9 transcription. TNF-alpha signaling upregulates nuclear FoxO4. Our studies place Fox04 in the center of a transcriptional regulatory network that links gene transcription required for SMC remodeling to upstream cytokine signals and implicate FoxO4 as a potential therapeutic target for combating proliferative arterial diseases. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75390 USA. Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Appl Canc Sci, Belfer Fdn Inst Innovat Canc Sci,Dana Farber Canc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Liu, ZP (reprint author), Univ Texas, SW Med Ctr, Dept Internal Med, 6000 Harry Hines Blvd, Dallas, TX 75390 USA. EM Zhi-Ping.Liu@utsouthwestern.edu FU NCI NIH HHS [P01 CA 095616, P01 CA095616]; NHLBI NIH HHS [R01 HL 085749-01, R01 HL085749] NR 33 TC 56 Z9 65 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2007 VL 27 IS 7 BP 2676 EP 2686 DI 10.1128/MCB.01748-06 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 153CY UT WOS:000245410500023 PM 17242183 ER PT J AU Taniguchi, CM Aleman, JO Ueki, K Luo, J Asano, T Kaneto, H Stephanopoulos, G Cantley, LC Kahn, CR AF Taniguchi, Cullen M. Aleman, Jose O. Ueki, Kohjiro Luo, Ji Asano, Tomoichiro Kaneto, Hideaki Stephanopoulos, Gregory Cantley, Lewis C. Kahn, C. Ronald TI The p85 alpha regulatory subunit of phosphoinositide 3-kinase potentiates c-Jun N-terminal kinase-mediated insulin resistance SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; RHO-FAMILY GTPASES; PHOSPHATIDYLINOSITOL 3-KINASE; MICE LACKING; SIGNALING PATHWAYS; P85; GLUCOSE; OBESITY; ALPHA; GENE AB Insulin resistance is a defining feature of type 2 diabetes and the metabolic syndrome. While the molecular mechanisms of insulin resistance are multiple, recent evidence suggests that attenuation of insulin signaling by c-Jun N-terminal kinase (JNK) may be a central part of the pathobiology of insulin resistance. Here we demonstrate that the p85 alpha regulatory subunit of phosphoinositide 3-kinase (PI3K), a key mediator of insulin's metabolic actions, is also required for the activation of JNK in states of insulin resistance, including high-fat diet-induced obesity and JNK1 overexpression. The requirement of the p85a regulatory subunit for JNK occurs independently of its role as a component of the PI3K heterodimer and occurs only in response to specific stimuli, namely, insulin and tunicamycin, a chemical that induces endoplasmic reticulum stress. We further show that insulin and p85 activate JNK by via cdc42 and MKK4. The activation of this cdc42/JNK pathway requires both an intact N terminus and functional SH2 domains within the C terminus of the p85 alpha regulatory subunit. Thus, p85 alpha plays a dual role in regulating insulin sensitivity and may mediate cross talk between the PI3K and stress kinase pathways. C1 Harvard Univ, Joslin Diabet Ctr, Sch Med, Boston, MA 02215 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Univ Tokyo, Grad Sch Med, Dept Metab Dis, Tokyo, Japan. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. Univ Tokyo, Fac Med, Dept Internal Med 3, Tokyo 113, Japan. Osaka Univ, Grad Sch Med, Dept Internal Med & Therapeut A8, Suita, Osaka, Japan. RP Kahn, CR (reprint author), Harvard Univ, Joslin Diabet Ctr, Sch Med, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [CA089021, P01 CA089021]; NIDDK NIH HHS [DK33201, DK34834, DK55545, R01 DK033201, R01 DK055545]; NIGMS NIH HHS [GM41890, R01 GM041890, R37 GM041890] NR 55 TC 47 Z9 48 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2007 VL 27 IS 8 BP 2830 EP 2840 DI 10.1128/MCB.00079-07 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 155DP UT WOS:000245558300005 PM 17283057 ER PT J AU Wang, XZ Kennedy, RD Ray, K Stuckert, P Ellenberger, T D'Andrea, AD AF Wang, XiaoZhe Kennedy, Richard D. Ray, Kallol Stuckert, Patricia Ellenberger, Tom D'Andrea, Alan D. TI Chk1-mediated phosphorylation of FANCE is required for the Fanconi anemia/BRCA pathway SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CYCLE CHECKPOINT KINASE; DNA-DAMAGE; S-PHASE; RECOMBINATION REPAIR; HUMAN CHK1; PROTEIN; BRCA1; ACTIVATION; IRRADIATION; ORTHOLOG AB The eleven Fanconi anemia (FA) proteins cooperate in a novel pathway required for the repair of DNA cross-links. Eight of the FA proteins (A, B, C, E, F, G, L, and M) form a core enzyme complex, required for the monoubiquitination of FANCD2 and the assembly of FANCD2 nuclear foci. Here, we show that, in response to DNA damage, Chk1 directly phosphorylates the FANCE subunit of the FA core complex on two conserved sites (threonine 346 and serine 374). Phosphorylated FANCE assembles in nuclear foci and colocalizes with FANCD2. A nonphosphorylated mutant form of FANCE (FANCE-T346A/S374A), when expressed in a FANCE-deficient cell line, allows FANCD2 monoubiquitination, FANCD2 foci assembly, and normal S-phase progression. However, the mutant FANCE protein fails to complement the mitomycin C hypersensitivity of the transfected cells. Taken together, these results elucidate a novel role of Chk1 in the regulation of the FA/BRCA pathway and in DNA cross-link repair. Chk1-mediated phosphorylation of FANCE is required for a function independent of FANCD2 monoubiquitination. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu RI Kennedy, Richard/J-3489-2012 OI Kennedy, Richard/0000-0003-4737-6163 FU NCI NIH HHS [F32 CA009361, T32 CA009361, T43CA09361]; NHLBI NIH HHS [P50 HL054785, R01 HL052725, P01-HL54785, R01-HL52725, R37 HL052725]; NIDDK NIH HHS [R01-DK43889, R01 DK043889] NR 32 TC 93 Z9 97 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2007 VL 27 IS 8 BP 3098 EP 3108 DI 10.1128/MCB.02357-06 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 155DP UT WOS:000245558300027 PM 17296736 ER PT J AU Wagner, JK Brun, YV AF Wagner, Jennifer K. Brun, Yves V. TI Out on a limb: how the Caulobacter stalk can boost the study of bacterial cell shape SO MOLECULAR MICROBIOLOGY LA English DT Review ID ASTICCACAULIS-BIPROSTHECUM; NUTRIENT-UPTAKE; SWARMER CELLS; CRESCENTUS; PROSTHECAE; MORPHOGENESIS; CROSSBANDS; PROTEIN; BIOGENESIS; TRANSPORT AB Understanding the mechanisms underlying the establishment of different bacterial cell shapes and the advantage that a particular shape imparts is one of the most fascinating and challenging areas of study in microbiology. One remarkable example of bacterial morphogenesis is the elaboration of long, tubular extensions of the cell envelope of certain aquatic bacteria. These appendages (also called prosthecae or stalks) possess features that make them particularly amenable models for experiments designed to uncover general principles of cell morphogenesis and of cell shape function. Recent evidence supports the hypothesis that stalk synthesis in Caulobacter crescentus is a specialized form of cell elongation that confers to the cell substantial advantages in nutrient uptake. Further insights into the mechanisms and function of stalk synthesis will require a multidisciplinary systems biology approach using principles and methodologies from ecology and evolutionary biology to biophysics and mathematical modelling. C1 Indiana Univ, Dept Biol, Bloomington, IN 47405 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Cambridge, MA 02139 USA. RP Brun, YV (reprint author), Indiana Univ, Dept Biol, Bloomington, IN 47405 USA. EM ybrun@indiana.edu OI Herman, Jennifer/0000-0003-4100-8167 FU NIAID NIH HHS [5T32AI007061]; NIGMS NIH HHS [GM61336, R01 GM051986, GM51986, GM07757] NR 41 TC 20 Z9 20 U1 2 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD APR PY 2007 VL 64 IS 1 BP 28 EP 33 DI 10.1111/j.1365-2958.2007.05633.x PG 6 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 159VB UT WOS:000245894600004 PM 17376069 ER PT J AU Monkul, ES Hatch, JP Nicoletti, MA Spence, S Brambilla, P Lacerda, ALT Sassi, R Mallinger, AG Keshavan, MS Soares, JC AF Monkul, E. S. Hatch, J. P. Nicoletti, M. A. Spence, S. Brambilla, P. Lacerda, A. L. T. Sassi, R. B. Mallinger, A. G. Keshavan, M. S. Soares, J. C. TI Fronto-limbic brain structures in suicidal and non-suicidal female patients with major depressive disorder SO MOLECULAR PSYCHIATRY LA English DT Article DE suicide; depression; mood disorders; affective disorders; magnetic resonance imaging; limbic system ID SUBGENUAL PREFRONTAL CORTEX; ORBITOFRONTAL CORTEX; BIPOLAR DISORDER; MOOD DISORDERS; ANATOMICAL MRI; AMYGDALA ENLARGEMENT; DECISION-MAKING; UNIPOLAR; VOLUMES; ABNORMALITIES AB Our knowledge about the neurobiology of suicide is limited. It has been proposed that suicidal behavior generally requires biological abnormalities concomitant with the personality trait of impulsivity/aggression, besides an acute psychiatric illness or psychosocial stressor. We investigated fronto-limbic anatomical brain abnormalities in suicidal and non-suicidal adult female patients with unipolar depression. Our sample consisted of seven suicidal unipolar patients, 10 non-suicidal unipolar patients and 17 healthy female comparison subjects. The criterion for suicidality was one or more documented lifetime suicide attempts. A 1.5T GE Signa Imaging System running version Signa 5.4.3 software was used to acquire the magnetic resonance imaging images. All anatomical structures were measured blindly, with the subjects' identities and group assignments masked. We used analysis of covariance with age and intracranial volume as covariates and the Tukey-Kramer procedure to compare suicidal patients, non-suicidal patients and healthy comparison subjects. Suicidal patients had smaller right and left orbitofrontal cortex gray matter volumes compared with healthy comparison subjects. Suicidal patients had larger right amygdala volumes than non-suicidal patients. Abnormalities in the orbitofrontal cortex and amygdala in suicidal patients may impair decision-making and predispose these patients to act more impulsively and to attempt suicide. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders,MOOD CNS Program, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Orthodont, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78229 USA. Audie L Murphy Div, S Texas Vet Hlth Care Syst, San Antonio, TX USA. Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. Univ Udine, Dept Pathol & Expt & Clin Med, Sect Psychiat, I-33100 Udine, Italy. Univ Fed Sao Paulo, Dept Psychiat, LiNC, Sao Paulo, Brazil. Sci Inst IRCCS E Medea, Udine, Italy. Univ Sao Paulo, Inst Psychiat, BR-05508 Sao Paulo, Brazil. Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15260 USA. Wayne State Univ, Sch Med, Dept Psychiat & Behav Sci, Detroit, MI 48202 USA. RP Soares, JC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders,MOOD CNS Program, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM soares@uthscsa.edu RI Lacerda, Acioly/A-7052-2010; brambilla, paolo/B-4184-2010 OI Lacerda, Acioly/0000-0002-9370-0449; brambilla, paolo/0000-0002-4021-8456 FU NCRR NIH HHS [RR020571]; NIMH NIH HHS [MH 01736, MH 30915] NR 43 TC 114 Z9 120 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD APR PY 2007 VL 12 IS 4 BP 360 EP 366 DI 10.1038/sj.mp.4001919 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 151TH UT WOS:000245313200006 PM 17389903 ER PT J AU McCarthy, JR Kelly, KA Sun, EY Weissleder, R AF McCarthy, Jason R. Kelly, Kimberly A. Sun, Eric Y. Weissleder, Ralph TI Targeted delivery of multifunctional magnetic nanoparticles SO NANOMEDICINE LA English DT Review DE atherosclerosis; cancer; data mining; fluorescence imaging; high-throughput screening; iron oxide; magnetic nanoparticle; magnetic resonance imaging; molecular imaging; peptide targeting; phage display ID SUPERPARAMAGNETIC IRON-OXIDE; ADHESION MOLECULE-1 EXPRESSION; DIVERSITY-ORIENTED SYNTHESIS; RISK-ASSESSMENT STRATEGIES; CONTRAST MR-ANGIOGRAPHY; LYMPH-NODE METASTASES; VIVO PHAGE DISPLAY; TAT PEPTIDE; BIOMEDICAL APPLICATIONS; VULNERABLE PATIENT AB Magnetic nanoparticles and their magnetofluorescent analogues have become important tools for in vivo imaging using magnetic resonance imaging and fluorescent optical methods. A number of monodisperse magnetic nanoparticle preparations have been developed over the last decade for angiogenesis imaging, cancer staging, tracking of immune cells (monocyte/macrophage, T cells) and for molecular and cellular targeting. Phage display and data mining have enabled the procurement of novel tissue- or receptor-specific peptides, while high-throughput screening of diversity-oriented synthesis libraries has identified small molecules that permit or prevent uptake by specific cell types. Next-generation magnetic nanoparticles are expected to be truly multifunctional, incorporating therapeutic functionalities and further enhancing an already diverse repertoire of capabilities. C1 Harvard Univ, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP McCarthy, JR (reprint author), Harvard Univ, Sch Med, Ctr Mol Imaging Res, 149 13th St,Rm 5406, Charlestown, MA 02129 USA. EM jason_mccarthy@hms.harvard.edu FU NCI NIH HHS [U54-CA119349, U54-CA126515]; NHLBI NIH HHS [UO1-HL080731] NR 95 TC 146 Z9 150 U1 8 U2 48 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 EI 1748-6963 J9 NANOMEDICINE-UK JI Nanomedicine PD APR PY 2007 VL 2 IS 2 BP 153 EP 167 DI 10.2217/17435889.2.2.153 PG 15 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA 159IR UT WOS:000245859500008 PM 17716118 ER PT J AU Blair, JA Rauh, D Kung, C Yun, CH Fan, QW Rode, H Zhang, C Eck, MJ Weiss, WA Shokat, KM AF Blair, Jimmy A. Rauh, Daniel Kung, Charles Yun, Cai-Hong Fan, Qi-Wen Rode, Haridas Zhang, Chao Eck, Michael J. Weiss, William A. Shokat, Kevan M. TI Structure-guided development of affinity probes for tyrosine kinases using chemical genetics SO NATURE CHEMICAL BIOLOGY LA English DT Article ID GROWTH-FACTOR-RECEPTOR; CELL LUNG-CANCER; IRREVERSIBLE INHIBITORS; C-SRC; ACQUIRED-RESISTANCE; PROTEIN-KINASE; EGF RECEPTOR; GEFITINIB; MUTATION; DOMAIN AB As key components in nearly every signal transduction pathway, protein kinases are attractive targets for the regulation of cellular signaling by small-molecule inhibitors. We report the structure-guided development of 6-acrylamido-4-anilinoquinazoline irreversible kinase inhibitors that potently and selectively target rationally designed kinases bearing two selectivity elements that are not found together in any wild-type kinase: an electrophile-targeted cysteine residue and a glycine gatekeeper residue. Cocrystal structures of two irreversible quinazoline inhibitors bound to either epidermal growth factor receptor (EGFR) or engineered c-Src show covalent inhibitor binding to the targeted cysteine (Cys797 in EGFR and Cys345 in engineered c-Src). To accommodate the new covalent bond, the quinazoline core adopts positions that are different from those seen in kinase structures with reversible quinazoline inhibitors. Based on these structures, we developed a fluorescent 6-acrylamido-4-anilinoquinazoline affinity probe to report the fraction of kinase necessary for cellular signaling, and we used these reagents to quantitate the relationship between EGFR stimulation by EGF and its downstream outputs-Akt, Erk1 and Erk2. C1 Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA. Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA. Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Brain Tumor Res Ctr, San Francisco, CA 94143 USA. Max Planck Soc, Chem Genom Ctr, D-44227 Dortmund, Germany. RP Shokat, KM (reprint author), Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA. EM shokat@cmp.ucsf.edu RI Rauh, Daniel/G-1595-2013 FU NCI NIH HHS [CA080942, CA116020]; NCRR NIH HHS [RR001614, RR015804]; NIAID NIH HHS [AI44009] NR 50 TC 122 Z9 123 U1 0 U2 24 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD APR PY 2007 VL 3 IS 4 BP 229 EP 238 DI 10.1038/nchembio856 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 148UW UT WOS:000245103000013 PM 17334377 ER PT J AU Shlipak, MG AF Shlipak, Michael G. TI Cystatin C as a marker of glomerular filtration rate in chronic kidney disease: influence of body composition SO NATURE CLINICAL PRACTICE NEPHROLOGY LA English DT Editorial Material DE chronic kidney disease; cystatin C; glomerular filtration rate; lean mass ID SERUM CREATININE; IMPACT C1 San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Shlipak, MG (reprint author), San Francisco VA Med Ctr, Gen Internal Med Sect, 111A1,4150 Clement St, San Francisco, CA 94121 USA. EM shlip@itsa.ucsf.edu NR 5 TC 10 Z9 10 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8323 J9 NAT CLIN PRACT NEPHR JI Nat. Clin. Pract. Nephrol. PD APR PY 2007 VL 3 IS 4 BP 188 EP 189 DI 10.1038/ncpneph0404 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 150KI UT WOS:000245215300004 PM 17290239 ER PT J AU Taplin, ME AF Taplin, Mary-Ellen TI Drug Insight: role of the androgen receptor in the development and progression of prostate cancer SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Review DE androgen; androgen receptor; antiandrogen; deprivation therapy; prostate cancer ID LIGAND-BINDING DOMAIN; N-TERMINAL DOMAIN; PHASE-I; GENE AMPLIFICATION; ADRENAL ANDROGENS; HORMONAL-THERAPY; TRANSACTIVATION FUNCTION; MOLECULAR-MECHANISM; DEPRIVATION THERAPY; INDEPENDENT GROWTH AB Functional androgen receptor (AR) signaling is necessary for the development of prostate cancer. The therapeutic effect of androgen deprivation therapy for prostate cancer was described over 60 years ago and this treatment remains the mainstay of systemic therapy despite its transient response duration. It has become clear that AR expression and signaling remains intact as the disease evolves from androgen-sensitive cancer to classically (but perhaps inaccurately) termed hormone refractory prostate cancer. Through several genetic and epigenetic adaptations, prostate tumors continue to rely on AR growth signaling and they thus remain targets of 'hormonal' therapy. The development of new strategies and drugs that can abrogate AR signaling will probably result in important clinical benefits. The biology of androgen independence and the development of new approaches targeting AR signaling are reviewed herein. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Taplin, ME (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. EM mtaplin@partners.org NR 84 TC 130 Z9 132 U1 3 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD APR PY 2007 VL 4 IS 4 BP 236 EP 244 DI 10.1038/ncponc0765 PG 9 WC Oncology SC Oncology GA 151HT UT WOS:000245281800010 PM 17392714 ER PT J AU Walker, JA Bernards, A AF Walker, James A. Bernards, Andre TI Drosophila melanogaster neurofibromatosis-1: ROS, not Ras? SO NATURE GENETICS LA English DT Editorial Material ID MITOCHONDRIA; NEURONS AB A new study suggests that manipulating the expression of a Drosophila melanogaster neurofibromatosis-1 ortholog affects organismal lifespan through protein kinase A-mediated regulation of mitochondrial respiration and reactive oxygen species production. These results provide a new and unexpected twist to the study of NF1 signaling. C1 Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02129 USA. RP Walker, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02129 USA. EM abernard@helix.mgh.harvard.edu NR 12 TC 2 Z9 2 U1 0 U2 1 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 APR PY 2007 VL 39 IS 4 BP 443 EP 445 DI 10.1038/ng0407-443 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 151EE UT WOS:000245271200011 PM 17392804 ER PT J AU Aschenbrenner, K D'Cruz, LM Vollmann, EH Hinterberger, M Emmerich, J Swee, LK Rolink, A Klein, L AF Aschenbrenner, Katharina D'Cruz, Louise M. Vollmann, Elisabeth H. Hinterberger, Maria Emmerich, Jan Swee, Lee Kim Rolink, Antonius Klein, Ludger TI Selection of Foxp3(+) regulatory T cells specific for self antigen expressed and presented by Aire(+) medullary thymic epithelial cells SO NATURE IMMUNOLOGY LA English DT Article ID PROMISCUOUS GENE-EXPRESSION; CLASS-II MOLECULES; CENTRAL TOLERANCE; IN-VIVO; NEGATIVE SELECTION; INTERCELLULAR TRANSFER; POSITIVE SELECTION; CLONAL DELETION; DENDRITIC CELLS; STROMAL CELLS AB The parameters specifying whether autoreactive CD4(+) thymocytes are deleted ( recessive tolerance) or differentiate into regulatory T cells ( dominant tolerance) remain unresolved. Dendritic cells directly delete thymocytes, partly through cross-presentation of peripheral antigens ` promiscuously' expressed in medullary thymic epithelial cells ( mTECs) positive for the autoimmune regulator Aire. It is unclear if and how mTECs themselves act as antigen-presenting cells during tolerance induction. Here we found that an absence of major histocompatibility class II molecules on mTECs resulted in fewer polyclonal regulatory T cells. Furthermore, targeting of a model antigen to Aire(+) mTECs led to the generation of specific regulatory T cells independently of antigen transfer to dendritic cells. Thus, 'routing' of mTEC-derived self antigens may determine whether specific thymocytes are deleted or enter the regulatory T cell lineage. C1 Res Inst Mol Pathol, A-1030 Vienna, Austria. Univ Basel, Dept Clin & Biol Sci, Ctr Biomed, CH-4051 Basel, Switzerland. Harvard Univ, CBR Inst Biomed Res, Dept Pathol, Brigham & Womens Hosp,Med Sch, Boston, MA 02115 USA. RP Klein, L (reprint author), Res Inst Mol Pathol, Dr Bohr Gasse 7, A-1030 Vienna, Austria. EM klein@imp.univie.ac.at RI Klein, Ludger/G-8785-2011 NR 52 TC 301 Z9 310 U1 3 U2 14 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 APR PY 2007 VL 8 IS 4 BP 351 EP 358 DI 10.1038/ni1444 PG 8 WC Immunology SC Immunology GA 148LK UT WOS:000245075900010 PM 17322887 ER PT J AU Mitoma, J Bao, XF Petryanik, B Schaerli, P Gauguet, JM Yu, SY Kawashima, H Saito, H Ohtsubo, K Marth, JD Khoo, KH von Andrian, UH Lowe, JB Fukuda, M AF Mitoma, Junya Bao, Xingfeng Petryanik, Bronislawa Schaerli, Patrick Gauguet, Jean-Marc Yu, Shin-Yi Kawashima, Hiroto Saito, Hideo Ohtsubo, Kazuaki Marth, Jamey D. Khoo, Kay-Hooi von Andrian, Ulrich H. Lowe, John B. Fukuda, Minoru TI Critical functions of N-glycans in L-selectin-mediated lymphocyte homing and recruitment SO NATURE IMMUNOLOGY LA English DT Article ID HIGH ENDOTHELIAL VENULES; CORE-2 BRANCHING BETA-1,6-N-ACETYLGLUCOSAMINYLTRANSFERASE; SIALYL-LEWIS-X; P-SELECTIN; GLYCOPROTEIN LIGAND-1; TYROSINE SULFATION; PROTEIN EPITOPES; O-GLYCANS; NODES; IDENTIFICATION AB Lymphocyte homing is mediated by specific interaction between L-selectin on lymphocytes and the carbohydrate ligand 6-sulfo sialyl Lewis X on high endothelial venules. Here we generated mice lacking both core 1 extension and core 2 branching enzymes to assess the functions of O-glycan-borne L-selectin ligands in vivo. Mutant mice maintained robust lymphocyte homing, yet they lacked O-glycan L-selectin ligands. Biochemical analyses identified a class of N-glycans bearing the 6-sulfo sialyl Lewis X L-selectin ligand in high endothelial venules. These N-glycans supported the binding of L-selectin to high endothelial venules in vitro and contributed in vivo to O-glycan-independent lymphocyte homing in wild-type and mutant mice. Our results demonstrate the critical function of N-glycan-linked 6-sulfo sialyl Lewis X in L-selectin-dependent lymphocyte homing and recruitment. C1 Burke Med Res Inst, Glycobiol Program, Canc Res Ctr, La Jolla, CA 92037 USA. Case Western Reserve Univ, Dept Pathol, Sch Med, Cleveland, OH 44106 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Acad Sinica, Inst Biol Chem, Taipei 11529, Taiwan. Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. RP Fukuda, M (reprint author), Burke Med Res Inst, Glycobiol Program, Canc Res Ctr, La Jolla, CA 92037 USA. EM minoru@burnham.org RI von Andrian, Ulrich/A-5775-2008 FU NCI NIH HHS [P01 CA71932, CA48737]; NIAID NIH HHS [AI061663, AI069259]; NIAMS NIH HHS [AR42689]; NIDDK NIH HHS [DK48247] NR 53 TC 101 Z9 104 U1 0 U2 1 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 APR PY 2007 VL 8 IS 4 BP 409 EP 418 DI 10.1038/ni1442 PG 10 WC Immunology SC Immunology GA 148LK UT WOS:000245075900016 PM 17334369 ER PT J AU Korn, T Reddy, J Gao, WD Bettelli, E Awasthi, A Petersen, TR Backstrom, BT Sobel, RA Wucherpfennig, KW Strom, TB Oukka, M Kuchroo, VK AF Korn, Thomas Reddy, Jayagopala Gao, Wenda Bettelli, Estelle Awasthi, Amit Petersen, Troels R. Backstrom, B. Thomas Sobel, Raymond A. Wucherpfennig, Kai W. Strom, Terry B. Oukka, Mohamed Kuchroo, Vijay K. TI Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation SO NATURE MEDICINE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; RECEPTOR TRANSGENIC MICE; IN-VIVO; MULTIPLE-SCLEROSIS; DENDRITIC CELLS; OLIGODENDROCYTE GLYCOPROTEIN; RHEUMATOID-ARTHRITIS; LUPUS-ERYTHEMATOSUS; ENCEPHALOMYELITIS; FOXP3 AB Treatment with ex vivo-generated regulatory T cells (T-reg) has been regarded as a potentially attractive therapeutic approach for autoimmune diseases. However, the dynamics and function of T-reg in autoimmunity are not well understood. Thus, we developed Foxp3gfp knock-in (Foxp3gfp.KI) mice and myelin oligodendrocyte glycoprotein (MOG)(35-55)/IA(b) (MHC class II) tetramers to track autoantigen-specific effector T cells (T-eff) and T-reg in vivo during experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. MOG tetramer-reactive, Foxp3(+) T-reg expanded in the peripheral lymphoid compartment and readily accumulated in the central nervous system (CNS), but did not prevent the onset of disease. Foxp3(+) T cells isolated from the CNS were effective in suppressing naive MOG-specific T cells, but failed to control CNS-derived encephalitogenic T-eff that secreted interleukin (IL)-6 and tumor necrosis factor (TNF). Our data suggest that in order for CD4(+)Foxp3(+) T-reg to effectively control autoimmune reactions in the target organ, it may also be necessary to control tissue inflammation. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Transplant Res Ctr, Boston, MA 02115 USA. Malaghan Inst Med Res, Wellington, New Zealand. Vet Affairs Hlth Care Syst, Lab Serv, Palo Alto, CA 94304 USA. Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Oukka, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. EM moukka@rics.bwh.harvard.edu; vkuchroo@rics.bwh.harvard.edu RI Reddy, Jay/K-7200-2014; OI Reddy, Jay/0000-0003-4082-9254; Korn, Thomas/0000-0002-3633-0955 FU NIAID NIH HHS [P01 AI039671, R01 AI044880]; NINDS NIH HHS [R01 NS045937, 1P01NS38037-04, 1R01NS045937-01, 1R01NS046414, 2R01NS35685-06, 2R37NS30843-11, P01 NS038037, R01 NS035685, R01 NS046414, R37 NS030843]; PHS HHS [1R01A144880-03, 2P01A139671-07] NR 47 TC 483 Z9 498 U1 2 U2 23 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 APR PY 2007 VL 13 IS 4 BP 423 EP 431 DI 10.1038/nm1564 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 154YG UT WOS:000245543900030 PM 17384649 ER PT J AU El Khoury, J Toft, M Hickman, SE Means, TK Terada, K Geula, C Luster, AD AF El Khoury, Joseph Toft, Michelle Hickman, Suzanne E. Means, Terry K. Terada, Kinya Geula, Changiz Luster, Andrew D. TI Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease SO NATURE MEDICINE LA English DT Article ID AMYLOID-BETA-PROTEIN; CENTRAL-NERVOUS-SYSTEM; MONOCYTE CHEMOATTRACTANT PROTEIN-1; TRANSGENIC MICE; PRECURSOR PROTEIN; SCAVENGER RECEPTOR; MOUSE MODEL; A-BETA; CHEMOKINE RECEPTORS; REACTIVE MICROGLIA AB Microglia are the principal immune cells of the brain. In Alzheimer disease, these brain mononuclear phagocytes are recruited from the blood and accumulate in senile plaques. However, the role of microglia in Alzheimer disease has not been resolved. Microglia may be neuroprotective by phagocytosing amyloid-beta (A beta), but their activation and the secretion of neurotoxins may also cause neurodegeneration. Ccr2 is a chemokine receptor expressed on microglia, which mediates the accumulation of mononuclear phagocytes at sites of inflammation. Here we show that Ccr2 deficiency accelerates early disease progression and markedly impairs microglial accumulation in a transgenic mouse model of Alzheimer disease (Tg2576). Alzheimer disease mice deficient in Ccr2 accumulated Ab earlier and died prematurely, in a manner that correlated with Ccr2 gene dosage, indicating that absence of early microglial accumulation leads to decreased A beta clearance and increased mortality. Thus, Ccr2-dependent microglial accumulation plays a protective role in the early stages of Alzheimer disease by promoting Ab clearance. C1 Ctr Immunol & Inflammat Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Charlestown, MA 02129 USA. Okayama Univ, Sch Med, Dept Neurol Surg, Okayama 7008558, Japan. Beth Israel Deaconess Med Ctr, Lab Neurodegenerat & Aging Res, Boston, MA 02215 USA. RP El Khoury, J (reprint author), Ctr Immunol & Inflammat Dis, Div Rheumatol Allergy & Immunol, 149 13th St, Charlestown, MA 02129 USA. EM jelkhoury@partners.org; luster.andrew@mgh.harvard.edu NR 50 TC 415 Z9 421 U1 1 U2 22 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 APR PY 2007 VL 13 IS 4 BP 432 EP 438 DI 10.1038/nm1555 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 154YG UT WOS:000245543900031 PM 17351623 ER PT J AU Litkouhi, B Kwong, J Lo, CM Smedley, JG McClane, BA Aponte, M Gao, ZJ Sarno, JL Hinners, J Welch, WR Berkowitz, RS Mok, SC Garner, EIO AF Litkouhi, Babak Kwong, Joseph Lo, Chun-Min Smedley, James G., III McClane, Bruce A. Aponte, Margarita Gao, Zhijian Sarno, Jennifer L. Hinners, Jennifer Welch, William R. Berkowitz, Ross S. Mok, Samuel C. Garner, Elizabeth I. O. TI Claudin-4 overexpression in epithelial ovarian cancer is associated with hypomethylation and is a potential target for modulation of tight junction barrier function using a C-terminal fragment of Clostridium perfringens enterotoxin SO NEOPLASIA LA English DT Article DE ovarian cancer; claudin-4; gene expression; therapy; methylation ID CARCINOMA IN-SITU; GENE-EXPRESSION; PROTEINS CLAUDIN-3; SURFACE EPITHELIUM; PANCREATIC-CANCER; CELLS; TUMORS; IDENTIFICATION; TUMORIGENESIS; METHYLATION AB BACKGROUND: Claudin-4, a tight junction (TJ) protein and receptor for the C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE), is overexpressed in epithelial ovarian cancer (EOC). Previous research suggests DNA methylation is a mechanism for claudin-4 overexpression in cancer and that C-CPE acts as an absorption-enhancing agent in claudin-4-expressing cells. We sought to correlate claudin-4 overexpression in EOC with clinical outcomes and TJ barrier function, investigate DNA methylation as a mechanism for overexpression, and evaluate the effect of C-CPE on the TJ. METHODS: Claudin-4 expression in EOC was quantified and correlated with clinical outcomes. Claudin-4 methylation status was determined, and claudin-4-negative cell lines were treated with a demethylating agent. Electric cell-substrate impedance sensing was used to calculate junctional (paracellular) resistance (Rb) in EOC cells after claudin-4 silencing and after C-CPE treatment. RESULTS: Claudin-4 overexpression in EOC does not correlate with survival or other clinical endpoints and is associated with hypomethylation. Claudin-4 overexpression correlates with Rb and C-CPE treatment of EOC cells significantly decreased Rb in a dose and claudin-4-dependent noncytotoxic manner. CONCLUSIONS: C-CPE treatment of EOC cells leads to altered TJ function. Further research is needed to determine the potential clinical applications of C-CPE in EOC drug delivery strategies. C1 Harvard Univ, Div Gynecol Oncol, Dept Obstet Gynecol & Reprod Biol, Brigham & Womens Hosp,Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. Univ S Florida, Dept Phys, Tampa, FL 33620 USA. Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Litkouhi, B (reprint author), Harvard Univ, Div Gynecol Oncol, Dept Obstet Gynecol & Reprod Biol, Brigham & Womens Hosp,Sch Med, 75 Francis St, Boston, MA 02115 USA. EM blitkouhi@partners.org RI Kwong, Joseph/H-2368-2013 FU NCI NIH HHS [P50 CA105009, R33CA103595, R33 CA103595, P50CA105009]; NIAID NIH HHS [R37 AI019844, R37AI19844] NR 46 TC 62 Z9 68 U1 1 U2 4 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 APR PY 2007 VL 9 IS 4 BP 304 EP 314 DI 10.1593/neo.07118 PG 11 WC Oncology SC Oncology GA 158OY UT WOS:000245802000005 PM 17460774 ER PT J AU Pollack, IF Jakacki, RI Blaney, SM Hancock, ML Kieran, MW Phillips, P Kun, LE Friedman, H Packer, R Banerjee, A Geyer, JR Goldman, S Poussaint, TY Krasin, MJ Wang, YF Hayes, M Murgo, A Weiner, S Boyett, JM AF Pollack, Ian F. Jakacki, Regina I. Blaney, Susan M. Hancock, Michael L. Kieran, Mark W. Phillips, Peter Kun, Larry E. Friedman, Henry Packer, Roger Banerjee, Anu Geyer, J. Russell Goldman, Stewart Poussaint, Tina Young Krasin, Matthew J. Wang, Yanfeng Hayes, Michael Murgo, Anthony Weiner, Susan Boyett, James M. TI Phase I trial of imatinib in children with newly diagnosed brainstem and recurrent malignant gliomas: A Pediatric Brain Tumor Consortium report SO NEURO-ONCOLOGY LA English DT Article DE brainstem; children; dose-limiting toxicity; enzyme-inducing anticonvulsant drugs; imatinib mesylate; intratumoral hemorrhage; malignant glioma; maximum tolerated dose; phase I trial ID CHRONIC MYELOID-LEUKEMIA; GROWTH-FACTOR RECEPTOR; ABL TYROSINE KINASE; CANCER GROUP; FACTOR PDGF; PHILADELPHIA-CHROMOSOME; MESYLATE STI571; CELL-LINES; INHIBITION; EXPRESSION AB This study estimated the maximum tolerated dose (MTD) of imatinib with irradiation in children with newly diagnosed brainstem gliomas, and those with recurrent malignant intracranial gliomas, stratified according to use of enzyme-inducing anticonvulsant drugs (EIACDs). In the brainstem glioma stratum, imatinib was initially administered twice daily during irradiation, but because of possible association with intratumoral hemorrhage (ITH) was subsequently started two weeks after irradiation. The protocol was also amended to exclude children with prior hemorrhage. Twenty-four evaluable patients received therapy before the amendment, and three of six with a brainstem tumor experienced dose-limiting toxicity (DLT): one had asymptomatic ITH, one had grade 4 neutropenia and, one had renal insufficiency. None of 18 patients with recurrent glioma experienced DLT. After protocol amendment, 3 of 16 patients with brainstem glioma and 2 of 11 patients with recurrent glioma who were not receiving EIACDs experienced ITH DLTs, with three patients being symptomatic. In addition to the six patients with hemorrhages during the DLT monitoring period, 10 experienced ITH (eight patients were symptomatic) thereafter. The recommended phase II dose for brainstem gliomas was 265 mg/m(2). Three of 27 patients with brainstem gliomas with imaging before and after irradiation, prior to receiving imatinib, had new hemorrhage, excluding their receiving imatinib. The MTD for recurrent high-grade gliomas without EIACDs was 465 mg/m(2), but the MTD was not established with EIACDs, with no DLTs at 800 mg/m(2). In summary, recommended phase II imatinib doses were determined for children with newly diagnosed brainstem glioma and recurrent high-grade glioma who were not receiving EIACDs. Imatinib may increase the risk of ITH, although the incidence of spontaneous hemorrhages in brainstem glioma is sufficiently high that this should be considered in studies of agents in which hemorrhage is a concern. C1 Childrens Hosp Pittsburgh, Dept Neurosurg, Pittsburgh, PA 15213 USA. Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. Pediat Brain Tumor Consortium, Operat & Biostat Ctr, Memphis, TN 38105 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. St Jude Childrens Hosp, Memphis, TN 38105 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Childrens Hosp & Med Ctr, Seattle, WA 98105 USA. Childrens Mem Hosp, Chicago, IL 60614 USA. Childrens Hosp, Boston, MA 02115 USA. Novartis Pharmaceut Corp, E Hanover, NJ 07936 USA. NCI, Bethesda, MD 20892 USA. Childrens Cause Canc Advocacy, Silver Spring, MD 20910 USA. RP Pollack, IF (reprint author), Childrens Hosp Pittsburgh, Dept Neurosurg, 3705 5th Ave, Pittsburgh, PA 15213 USA. EM ian.pollack@chp.edu OI Kieran, Mark/0000-0003-2184-7692 FU NCI NIH HHS [U01 CA081457, U01 CA81457]; NCRR NIH HHS [M01 RR000188, M01 RR00188-37] NR 51 TC 95 Z9 96 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2007 VL 9 IS 2 BP 145 EP 160 DI 10.1215/15228517-2006-031 PG 16 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 154EJ UT WOS:000245489300009 PM 17293590 ER PT J AU Ullrich, NJ Marcus, K Turner, CD Zimmerman, MA Lehmann, LE Gillan, E Kieran, M Chi, SN AF Ullrich, N. J. Marcus, K. Turner, C. D. Zimmerman, M. A. Lehmann, L. E. Gillan, E. Kieran, M. Chi, S. N. TI Transverse myelitis after high-dose chemotherapy and autologous stem cell transplant for primitive neuroectodermal tumors SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th International Symposium on Pediatric Neuro-Oncology CY JUL 06-09, 2006 CL Nara, JAPAN C1 Harvard Med Sch, Dana Farber Canc Inst, Pediat Brain Tumor Program, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2007 VL 9 IS 2 BP 175 EP 175 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 154EJ UT WOS:000245489300035 ER PT J AU Zimmerman, MA Turner, C Chi, S Chordas, C Scott, RM Goumnerova, L Proctor, M Marcus, K Pomeroy, S Ullrich, N Kieran, MW AF Zimmerman, M. A. Turner, C. Chi, S. Chordas, C. Scott, R. M. Goumnerova, L. Proctor, M. Marcus, K. Pomeroy, S. Ullrich, N. Kieran, M. W. TI Glomerular filtration rate in comparison to serum creatinine and audiologic results in predicting toxicity in pediatric patients receiving vincristine and carboplatin SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th International Symposium on Pediatric Neuro-Oncology CY JUL 06-09, 2006 CL Nara, JAPAN C1 Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2007 VL 9 IS 2 BP 175 EP 175 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 154EJ UT WOS:000245489300036 ER PT J AU Gilheeney, SW Williams, C DiGiorlani, U Chi, S Turner, C Ullrich, N Goumnerova, L Scott, RM Marcus, K Lehmann, L Kieran, M AF Gilheeney, S. W. Williams, C. DiGiorlani, U. Chi, S. Turner, C. Ullrich, N. Goumnerova, L. Scott, R. M. Marcus, K. Lehmann, L. Kieran, M. TI Pineoblastoma in the pediatric population: Review of a single institution's experience SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th International Symposium on Pediatric Neuro-Oncology CY JUL 06-09, 2006 CL Nara, JAPAN C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp Boston, Dept Neuropathol Neurol Neurosurg & Radiat Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2007 VL 9 IS 2 BP 201 EP 201 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 154EJ UT WOS:000245489300150 ER PT J AU Gilheeney, SW Scott, RM Chi, S Turner, C Ullrich, N Marcus, K Gillan, E Dunsmore, K Kieran, MW AF Gilheeney, S. W. Scott, R. M. Chi, S. Turner, C. Ullrich, N. Marcus, K. Gillan, E. Dunsmore, K. Kieran, M. W. TI Treatment of Von Hippel Lindau-associated hemangioblastoma in pediatric patients with bevacizumab (avastin) SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th International Symposium on Pediatric Neuro-Oncology CY JUL 06-09, 2006 CL Nara, JAPAN C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Childrens Hosp, Dept Radiat Oncol, Boston, MA USA. Connecticut Childrens Med Ctr, Dept Oncol, Hartford, CT USA. Univ Virginia, Childrens Med Ctr, Dept Oncol, Charlottesville, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2007 VL 9 IS 2 BP 204 EP 204 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 154EJ UT WOS:000245489300163 ER PT J AU Chi, SN Snuderl, M DeGirolami, U Goumnerova, L Gordon, A Thomas, A Turner, CD Zimmerman, M Chordas, C Ullrich, N Kieran, MW AF Chi, S. N. Snuderl, M. DeGirolami, U. Goumnerova, L. Gordon, A. Thomas, A. Turner, C. D. Zimmerman, M. Chordas, C. Ullrich, N. Kieran, M. W. TI Does histologic grade correlate with clinical outcome in pediatric intracranial ependymoma? SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th International Symposium on Pediatric Neuro-Oncology CY JUL 06-09, 2006 CL Nara, JAPAN C1 Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2007 VL 9 IS 2 BP 217 EP 218 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 154EJ UT WOS:000245489300225 ER PT J AU Snuderl, M Chi, SN Chan, JA Hladikova, M Rubin, MA Kieran, MW Ligon, KL AF Snuderl, M. Chi, S. N. Chan, J. A. Hladikova, M. Rubin, M. A. Kieran, M. W. Ligon, K. L. TI Oligodendroglial lineage marker expression in ependymal tumors SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th International Symposium on Pediatric Neuro-Oncology CY JUL 06-09, 2006 CL Nara, JAPAN C1 Childrens Hosp, Brigham & Womens Hosp, Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2007 VL 9 IS 2 BP 218 EP 218 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 154EJ UT WOS:000245489300228 ER PT J AU Katsel, P Li, C Haroutunian, V AF Katsel, Pavel Li, Celeste Haroutunian, Vahram TI Gene expression alterations in the sphingolipid metabolism pathways during progression of dementia and Alzheimer's disease: A shift toward ceramide accumulation at the earliest recognizable stages of Alzheimer's disease? SO NEUROCHEMICAL RESEARCH LA English DT Article DE Alzheimer's disease; dementia; ceramide; glycosphingolipid; sphingolipid metabolism; postmortem; gene expression; microarray; brain regions ID AMYLOID-BETA-PEPTIDE; CORONARY-ARTERY-DISEASE; LOW-DENSITY-LIPOPROTEIN; NEUTRAL SPHINGOMYELINASE; SIGNAL-TRANSDUCTION; APOLIPOPROTEIN-E; NEUROFIBRILLARY TANGLES; EXECUTIVE FUNCTION; CEREBRAL-ISCHEMIA; COGNITIVE DECLINE AB There is mounting evidence linking A beta(42) generation in Alzheimer's disease (AD) with sphingomyelin catabolism. Using microarray technology to study 17 brain regions from subjects with varying severity of AD and dementia we detected multiple gene expression abnormalities of the key enzymes that control sphingolipid metabolism. These changes were correlated with the progression of clinical dementia. The upregulation of gene expression of the enzymes controlling synthesis de novo of Cer and the downregulation of the enzymes involved in glycosphingolipid synthesis was evident as early in disease progression as in mild dementia. Together these changes suggest a shift in sphingolipid metabolism towards accumulation of Cer, depletion of glycosphingolipids and the reduction of synthesis of the anti-apoptosis signaling lipid-sphingosine 1-phosphate as a function of disease progression. This disrupted balance within the sphingolipid metabolism may trigger signaling events promoting neurodegeneration across cortical regions. This potential mechanism may provide a link between lipid metabolism disturbance and AD. C1 Vet Adm Med Ctr, Dept Psychiat, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. James J Peters VA Med Ctr, Dept Psychiat, Bronx, NY 10468 USA. RP Katsel, P (reprint author), Vet Adm Med Ctr, Dept Psychiat, Room 4F-20,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM pavel.katsel@mssm.edu FU NIA NIH HHS [AG 02219] NR 68 TC 107 Z9 108 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD APR PY 2007 VL 32 IS 4-5 BP 845 EP 856 DI 10.1007/s11064-007-9297-x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 149GG UT WOS:000245134500031 PM 17342407 ER PT J AU Dyk, K Sano, M AF Van Dyk, Kathleen Sano, Mary TI The impact of nutrition on cognition in the elderly SO NEUROCHEMICAL RESEARCH LA English DT Review DE Alzheimer's Disease; Dementia Cognitive Impairment; nutrition ID INCIDENT ALZHEIMER-DISEASE; RANDOMIZED CONTROLLED-TRIAL; DIETARY FATTY-ACIDS; VITAMIN-E; POSTMENOPAUSAL WOMEN; SERUM VITAMIN-B-12; FOLATE STATUS; DOUBLE-BLIND; OLD-AGE; RISK AB The possibility that nutritional manipulation may protect against cognitive decline and dementia is an inviting prospect. However data supporting a beneficial effect of a particular dietary pattern is limited. Although studies have demonstrated a health benefit to dietary plans that are high in fiber, whole grains, natural sugar and fish while maintaining lower intake in meat dairy and poultry, the ability to identify the most salient factors of these diets have been unsuccessful. Several aspects of diet have been studied in detail and provided support for potential mechanisms for improving cognition. Clinical trials have explored these mechanisms through supplementation studies with minimal benefits being observed. Continuing work to hone the mechanisms and refine our knowledge of dietary benefits is described. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. James J Peters VAMC, Bronx, NY 10468 USA. RP Sano, M (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM Mary.sano@mssm.edu OI Van Dyk, Kathleen/0000-0003-1500-930X NR 66 TC 0 Z9 0 U1 1 U2 8 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD APR PY 2007 VL 32 IS 4-5 BP 893 EP 904 DI 10.1007/s11064-006-9241-5 PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 149GG UT WOS:000245134500034 ER PT J AU Kochunov, P Thompson, PM Lancaster, JL Bartzokis, G Smith, S Coyle, T Royall, DR Laird, A Fox, PT AF Kochunov, P. Thompson, P. M. Lancaster, J. L. Bartzokis, G. Smith, S. Coyle, T. Royall, D. R. Laird, A. Fox, P. T. TI Relationship between white matter fractional anisotropy and other indices of cerebral health in normal aging: Tract-based spatial statistics study of aging SO NEUROIMAGE LA English DT Article ID MYELINATED NERVE-FIBERS; MAPPING CORTICAL CHANGE; DIFFUSION-TENSOR; GRAY-MATTER; ALZHEIMERS-DISEASE; HUMAN BRAIN; IN-VIVO; NEUROPSYCHIATRIC DISORDERS; STRUCTURAL INTEGRITY; PROBABILISTIC ATLAS AB White matter (WM) fractional anisotropy (FA) is thought to be related to WM integrity and decline in FA is often used as an index of decreasing WM health. However, the relationship of FA to other structural indices of cerebral health has not been well studied. We hypothesized that the decline in WM health will be associated with changes in several other indices of cerebral health. In this manuscript we studied the correlation between whole-brain/hemispheric/corpus callosum FA and gray matter (GM) thickness, sulcal span, and the volume of T2-hyperintense WM in a group of 31 healthy aging individuals (12 males/19 females) aged 57-82 years old. Individual subjects' FA measures were calculated from diffusion tracing imaging (DTI) data using tract-based spatial statistics-an approach specifically designed and validated for voxel-wise multi-subject FA analysis. Age-controlled correlation analysis showed that whole-brain average FA values were significantly and positively correlated with the subject's average GM thickness and negatively correlated with hyperintense WM volume. Intra-hemispheric correlations between FA and other measures of cerebral health had generally greater effect sizes than inter-hemispheric correction, with correlation between left FA and left GM thickness being the most significant (r=0.6, p < 0.01). Regional analysis of FA values showed that late-myelinating fiber tracts of the genu of corpus callosum had higher association with other cerebral health indices. These data are consistent with the hypothesis that late-myelinating regions of the brain bear the brunt of age-related degenerative changes. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Res Imaging Ctr, San Antonio, TX 78284 USA. Univ Calif Los Angeles, David Geffen Sch Med, Lab Neuroimaging, Dept Neurol,Div Brain Mapping, Los Angeles, CA 90095 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90073 USA. Univ Oxford, Ctr Funct MRI Brain, Oxford, England. Univ Texas, Dept Psychol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. RP Kochunov, P (reprint author), Univ Texas, Hlth Sci Ctr, Res Imaging Ctr, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM kochunov@uthscsa.edu RI Lancaster, Jack/F-2994-2010; Kochunov, Peter/E-4711-2010; Laird, Angela/B-5800-2010; Fox, Peter/B-4725-2010; OI Fox, Peter/0000-0002-0465-2028; Smith, Stephen/0000-0001-8166-069X FU NCRR NIH HHS [RR019771]; NIA NIH HHS [AG021431, P50 AG 16570]; NIBIB NIH HHS [EB01651]; NIDA NIH HHS [P20 MH/ DA52176]; NIMH NIH HHS [MH066029]; NLM NIH HHS [LM05639] NR 62 TC 130 Z9 131 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR 1 PY 2007 VL 35 IS 2 BP 478 EP 487 DI 10.1016/j.neuroimage.2006.12.021 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 151LY UT WOS:000245293100004 PM 17292629 ER PT J AU D'Arceuil, HE Westmoreland, S de Crespigny, AJ AF D'Arceuil, Helen E. Westmoreland, Susan de Crespigny, Alex J. TI An approach to high resolution diffusion tensor imaging in fixed primate brain SO NEUROIMAGE LA English DT Article ID CEREBRAL WHITE-MATTER; MR MICROSCOPY; RESONANCE; POSTMORTEM; MOUSE; ANISOTROPY; HISTOLOGY; PARAMETERS; SPECIMENS; PATHOLOGY AB High resolution ay vivo diffusion tensor imaging (DTI) studies of neural tissues can improve our understanding of brain structure. In these studies we can modiN the tissue relaxation properties of the fixed tissues to better suite the scanner hardware. We investigated the use of Gd-DTPA contrast agent to provide the optimum signal-to-noise (SNR) ratio in 3D DTI scans of formalin fixed nonhuman primate brains at 4.7 T. Relaxivity measurements in gray and white matter allowed us to optimize the Gd concentration for soaking the brains, resulting in a 2 fold improvement in SNR for the 3D scans. FA changed little with Gd concentrations up to 10 mM although ADC was reduced at 5 and 10 miNt. Comparison of in vivo, fresh ex vivo and fixed brains showed no significant FA changes but reductions in ADC of about 50% in fresh ex vivo, and 64% and 80% in fixed gray and white matter respectively. Studies of the temperature dependence of diffusion in these tissues suggested that a 30 degrees increase in sample temperature may yield an improvement of up to 55% in SNR-efficiency for a given diffusion weighting. Our Gd soaking regimen appeared to have no detrimental effect on standard histology of the fixed brain sections. Our methods yield both high SNR and spatial resolution DTI data in fixed primate brains, allowing us to perform high resolution tractography which will facilitate the process of 'validation' of DTI fiber tracts against traditional measures of brain fiber architecture. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, NMR Ctr, Neuroradiol Sect, Dept Radiol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr, Charlestown, MA 02129 USA. Harvard Univ, New England Reg Primate Res Ctr, Southborough, MA USA. RP de Crespigny, AJ (reprint author), Massachusetts Gen Hosp, NMR Ctr, Neuroradiol Sect, Dept Radiol, Rm 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM alexdec@nmr.mgh.harvard.edu FU NCRR NIH HHS [P41RR14075, S10RR016811]; NIBIB NIH HHS [EB00790]; NINDS NIH HHS [NS41285, R01 NS041285-04] NR 43 TC 84 Z9 84 U1 1 U2 1 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 APR 1 PY 2007 VL 35 IS 2 BP 553 EP 565 DI 10.1016/j.neuroimage.2006.12.028 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 151LY UT WOS:000245293100011 PM 17292630 ER PT J AU Ahveninen, J Lin, FH Kivisaari, R Autti, T Hamalainen, M Stufflebeam, S Belliveau, JW Kahkonen, S AF Ahveninen, Jyrki Lin, Fa-Hsuan Kivisaari, Reetta Autti, Taina Hamalainen, Matti Stufflebeam, Steven Belliveau, John W. Kahkonen, Seppo TI MRI-constrained spectral imaging of benzodiazepine modulation of spontaneous neuromagnetic activity in human cortex SO NEUROIMAGE LA English DT Article ID BRAIN METABOLIC-RESPONSES; CORTICAL SURFACE; MAGNETOENCEPHALOGRAPHIC DATA; COORDINATE SYSTEM; AUDITORY-CORTEX; CEREBRAL-CORTEX; EEG; LORAZEPAM; MEG; LOCALIZATION AB Spontaneous electromagnetic brain rhythms have been widely used in human neuropharmacology, but their applicability is complicated by the difficulties to localize their origins in the human cortex. Here, we used a novel multi-modal non-invasive imaging approach to localize lorazepam (30 mu g/kg i.v.) modulation of cortical generators of spontaneous brain rhythms. Eight healthy subjects were measured with 306-channel magnetoencephalography (MEG) in a double-blind, randomized, placebo-controlled (saline), crossover design. For anatomically realistic source modeling, wavelet-transformed MEG data were combined with high-resolution MRI to constrain the current locations to the cortical mantle, after which individual data were co-registered to surface-based coordinate system for the calculation of group statistical parametric maps of drug effects. The distributed MRI-constrained MEG source estimates demonstrated decreased alpha (10 Hz) activity in and around the parieto-occipital sulcus and in the calearine sulcus of the occipital lobe, following from increased GABA(A)-inhibition by lorazepam. Anatomically constrained spectral imaging displays the cortical loci of drug effects on oscillatory brain activity, providing a novel tool for human pharmacological neuroimaging. (c) 2007 Published by Elsevier Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, MIT,Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. Univ Helsinki, Cent Hosp, Dept Radiol, Helsinki, Finland. Univ Helsinki, Dept Psychol, Cognit Brain Res Unit, SF-00100 Helsinki, Finland. Univ Helsinki, Cent Hosp, BioMag Lab, Ctr Engn, SF-00100 Helsinki, Finland. Helsinki Brain Res Ctr, Helsinki, Finland. RP Ahveninen, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MIT,Athinoula A Martinos Ctr Biomed Imaging, CNY149 13th St, Charlestown, MA 02129 USA. EM jyrki@nmr.mgh.harvard.edu RI Hamalainen, Matti/C-8507-2013; Lin, Fa-Hsuan/G-6988-2012 OI Lin, Fa-Hsuan/0000-0002-9539-1731 FU NCRR NIH HHS [P41 RR14075]; NICHD NIH HHS [R01 HD040712]; NINDS NIH HHS [R01 NS037462] NR 39 TC 18 Z9 18 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR 1 PY 2007 VL 35 IS 2 BP 577 EP 582 DI 10.1016/j.neuroimage.2006.12.033 PG 6 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 151LY UT WOS:000245293100013 PM 17300962 ER PT J AU Nummemnaa, A Auranen, T Hamalainen, MS Jaaskelainen, IP Lampinen, J Sams, M Vehtari, A AF Nummemnaa, Aapo Auranen, Toni Hamalainen, Matti S. Jaaskelainen, Iiro P. Lampinen, Jouko Sams, Mikko Vehtari, Aki TI Hierarchical Bayesian estimates of distributed MEG sources: Theoretical aspects and comparison of variational and MCMC methods SO NEUROIMAGE LA English DT Article DE MEG source reconstruction; hierarchical modeling; variational Bayes; Markov chain Monte Carlo; sensitivity analysis ID INVERSE PROBLEM; CORTICAL ACTIVITY; LOCALIZATION; EEG; RECONSTRUCTION; CONSTRAINTS; FMRI AB Magnetoencephalography (MEG) provides millisecond-scale temporal resolution for noninvasive mapping of human brain functions, but the problem of reconstructing the underlying source currents from the extracranial data has no unique solution. Several distributed source estimation methods based on different prior assumptions have been suggested for the resolution of this inverse problem. Recently, a hierarchical Bayesian generalization of the traditional minimum norm estimate (NINE) was proposed, in which the variance of distributed current at each cortical location is considered as a random variable and estimated from the data using the variational Bayesian (VB) framework. Here, we introduce an alternative scheme for performing Bayesian inference in the context of this hierarchical model by using Markov chain Monte Carlo (MCMC) strategies. In principle, the MCMC method is capable of numerically representing the true posterior distribution of the currents whereas the VB approach is inherently approximative. We point out some potential problems related to hyperprior selection in the previous work and study some possible solutions. A hyperprior sensitivity analysis is then performed, and the structure of the posterior distribution as revealed by the MCMC method is investigated. We show that the structure of the true posterior is rather complex with multiple modes corresponding to different possible solutions to the source reconstruction problem. We compare the results from the VB algorithm to those obtained from the MCMC simulation under different hyperparameter settings. The difficulties in using a unimodal variational distribution as a proxy for a truly multimodal distribution are also discussed. Simulated MEG data with realistic sensor and source geometries are used in performing the analyses. (c) 2006 Elsevier Inc. All rights reserved. C1 Helsinki Univ Technol, Lab Computat Engn, Espoo 02015, Finland. Helsinki Univ Technol, Adv Magnet Imaging Ctr, FIN-02150 Espoo, Finland. Harvard Univ, MIT, Sch Med, Massachusetts Gen Hosp,Athinoula A Martinos Ctr B, Charlestown, MA 02139 USA. RP Nummemnaa, A (reprint author), Helsinki Univ Technol, Lab Computat Engn, POB 9203, Espoo 02015, Finland. EM Aapo.Nummenmaa@hut.fi RI Jaaskelainen, Iiro/C-7392-2012; Sams, Mikko/G-7060-2012; Vehtari, Aki/A-7584-2008; Hamalainen, Matti/C-8507-2013; Lampinen, Jouko/D-3927-2014; Auranen, Toni/J-7137-2012 OI Jaaskelainen, Iiro/0000-0001-6001-6950; Vehtari, Aki/0000-0003-2164-9469; NR 39 TC 39 Z9 41 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR 1 PY 2007 VL 35 IS 2 BP 669 EP 685 DI 10.1016/j.neuroimage.2006.05.001 PG 17 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 151LY UT WOS:000245293100021 PM 17300961 ER PT J AU Xu, GL Liu, XF Meyer, JS Yin, Q Zhang, RL AF Xu, Gelin Liu, Xinfeng Meyer, John Stirling Yin, Qin Zhang, Renliang TI Cognitive performance after carotid angioplasty and stenting with brain protection devices SO NEUROLOGICAL RESEARCH LA English DT Article DE angioplasty; carotid stenosis; cognition; psychometrics; stroke ID PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; TRANSCRANIAL DOPPLER; ENDARTERECTOMY; IMPAIRMENT; RECONSTRUCTION; PERFUSION; DEMENTIA; STENOSIS; DISEASE; SURGERY AB Objective: Neuropsychological outcomes after carotid endarterectomy (CEA) have been investigated extensively. However, cognitive impacts of carotid angioplasty and stenting (CAS), an emerging alternative to CEA, have not been studied. This study is aimed at investigating pattern and degree of cognitive changes after CAS among patients with high-grade carotid stenosis. Patients and methods: Fifty-four patients with high-grade carotid artery stenosis and received elective CAS were followed. Sixty-six patients with similar medical conditions requiring carotid angiography (CAG) were enrolled as controls. Cognitive functions among patients in both groups were evaluated at baseline and follow-ups utilizing a battery of neuropsychometric tests. Results were analysed by inter-group and within-group comparisons. Results: There were no statistically significant differences between CAS and CAG patients regarding demographic characteristics, risk factors for stroke and baseline cognitive performance (p > 0.05). CAS patients performed significantly better than CAG patients in Rey auditory verbal learning tests (RAVLT) at week 1 (41.2 +/- 5.2 versus 37.4 +/- 4.0, p < 0.001) and week 12 follow-ups (43.3 +/- 7.7 versus 37.3 +/- 4.5, p < 0.001). Comparison of z score also indicated CAS patients improved significantly more than CAG patients in RAVLT at both weeks 1 (1.08 +/- 1.29 versus 0.25 +/- 0.99, p < 0.001) and 12 follow-ups (1.62 +/- 1.95 versus 0.05 +/- 1.02, p < 0.001). Conclusion: CAS patients demonstrated improvement in verbal memory after procedures. Correction of cerebral hypoperfusion and reduction of artery-to-artery embolization after CAS are postulated responsible for the cognitive improvement. C1 Nanjing Univ, Sch Med, Jinling Hosp, Dept Neurol, Nanjing 210002, Jiangsu, Peoples R China. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Michael E DeBakey Vet Adm Med Ctr, Cerebrovasc Res Lab, Houston, TX USA. RP Xu, GL (reprint author), Nanjing Univ, Sch Med, Jinling Hosp, Dept Neurol, 305 E Zhongshan Rd, Nanjing 210002, Jiangsu, Peoples R China. EM gelinxu@gmail.com OI Xu, Gelin/0000-0002-6194-0341 NR 29 TC 27 Z9 34 U1 0 U2 2 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 0161-6412 J9 NEUROL RES JI Neurol. Res. PD APR PY 2007 VL 29 IS 3 BP 251 EP 255 DI 10.1179/016164107X159216 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 165JJ UT WOS:000246301100006 PM 17178010 ER PT J AU Belman, AL Chitnis, T Renoux, C Waubant, E AF Belman, Anita L. Chitnis, Tanuja Renoux, Christel Waubant, Emmanuelle CA Int Pediat MS Study Grp TI Challenges in the classification of pediatric multiple sclerosis and future directions SO NEUROLOGY LA English DT Article; Proceedings Paper CT Workshop on Consensus Definitions Proposed for Pediatric Multiple Sclerosis and Related Disorders CY FEB, 2004 CL CANADA SP Int Pediat MS Study Grp ID ACUTE DISSEMINATED ENCEPHALOMYELITIS; EARLY-ONSET; DIAGNOSTIC-CRITERIA; CHILDHOOD; FEATURES; GUIDELINES AB To improve care for children with multiple sclerosis ( MS) and to advance understanding of the underlying biologic mechanisms through collaborative research studies, criteria for case definitions of pediatric MS and related CNS demyelinating disorders were proposed by the International Pediatric MS Study Group. Issues raised during development of these definitions and rationale behind criteria proposed are summarized in this article, as are potential international multicenter research studies that would be facilitated by the application of a uniform set of definitions. C1 SUNY Stony Brook, Med Ctr, Sch Med HSC 12 020, Dept Neurol, Stony Brook, NY 11794 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Hop Neurol, Serv Neurol, Lyon, France. UCSF, Multiple Sclerosis Ctr, San Francisco, CA USA. RP Belman, AL (reprint author), SUNY Stony Brook, Med Ctr, Sch Med HSC 12 020, Dept Neurol, Stony Brook, NY 11794 USA. EM abelman@notes.cc.sunysb.edu NR 20 TC 16 Z9 18 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2007 VL 68 SU 2 BP S70 EP S74 DI 10.1212/01.wnl.0000259421.40556.76 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 158HJ UT WOS:000245782100010 PM 17438242 ER PT J AU Pohl, D Waubant, E Banwell, B Chabas, D Chitnis, T Weinstock-Guttman, B Tenembaum, S AF Pohl, D. Waubant, E. Banwell, B. Chabas, D. Chitnis, T. Weinstock-Guttman, B. Tenembaum, S. CA Int Pediat MS Study Grp TI Treatment of pediatric multiple sclerosis and variants SO NEUROLOGY LA English DT Article; Proceedings Paper CT Workshop on Consensus Definitions Proposed for Pediatric Multiple Sclerosis and Related Disorders CY FEB, 2004 CL CANADA SP Int Pediat MS Study Grp ID MYELINOCLASTIC DIFFUSE SCLEROSIS; BALOS CONCENTRIC SCLEROSIS; ACUTE DISSEMINATED ENCEPHALOMYELITIS; PLACEBO-CONTROLLED TRIAL; SECONDARY PROGRESSIVE MS; INTRAVENOUS IMMUNOGLOBULIN THERAPY; RANDOMIZED CONTROLLED TRIAL; SCHILDERS-DISEASE; DOUBLE-BLIND; INTERFERON BETA-1A AB Studies in adult patients with multiple sclerosis ( MS) suggest significant benefit of early treatment initiation. However, there are no approved therapies for children and adolescents with MS. For adult MS, tolerability and efficacy of several immunomodulatory and immunosuppressive drugs have been demonstrated. Guidelines for the use of these MS therapies in children do not exist. Several small cohort studies of the safety and tolerability of disease-modifying therapies ( DMT) in children and adolescents with MS have been recently reported. The side effects of interferon beta ( IFNB) and glatiramer acetate ( GA) appear to be similar to those reported by adults. The long-term tolerability and safety have yet to be established and efficacy data have yet to be studied. In view of the potential for significant long-term physical and cognitive disability in children with MS, and recent evidence that initiation of immunomodulatory therapy early in the course of MS improves long-term prognosis, an increasing number of children and adolescents with MS are being offered the DMT approved for adults. This review summarizes current knowledge of DMT in pediatric MS and experience in several centers treating pediatric MS and MS variants such as neuromyelitis optica or Devic disease, Balo concentric sclerosis, Marburg acute MS, and Schilder disease ( myelinoclastic diffuse sclerosis). Finally, an overview of symptomatic MS therapies and experiences with these treatments in pediatric patients is provided. C1 Univ Calif San Francisco, MS Ctr, San Francisco, CA 94117 USA. Univ Gottingen, Dept Pediat & Pediat Neurol, D-3400 Gottingen, Germany. Univ Toronto, Hosp Sick Children, Dept Pediat Neurol, Toronto, ON M5G 1X8, Canada. Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Boston, MA 02115 USA. Natl Pediat Hosp, Dept Pediat Neurol, Buenos Aires, DF, Argentina. RP Waubant, E (reprint author), Univ Calif San Francisco, MS Ctr, 350 Parnassus St,Suite 908, San Francisco, CA 94117 USA. EM Emmanuelle.Waubant@ucsf.edu NR 131 TC 53 Z9 59 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2007 VL 68 SU 2 BP S54 EP S65 DI 10.1212/01.wnl.0000259407.40023.ab PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 158HJ UT WOS:000245782100008 PM 17438239 ER PT J AU Tenembaum, S Chitnis, T Ness, J Hahn, JS AF Tenembaum, Silvia Chitnis, Tanuja Ness, Jayne Hahn, Jin S. CA Int Pediat MS Study Grp TI Acute disseminated encephalomyelitis SO NEUROLOGY LA English DT Article; Proceedings Paper CT Workshop on Consensus Definitions Proposed for Pediatric Multiple Sclerosis and Related Disorders CY FEB, 2004 CL CANADA SP Int Pediat MS Study Grp ID MYELIN BASIC-PROTEIN; ACUTE HEMORRHAGIC LEUKOENCEPHALITIS; MULTIPHASIC DISSEMINATED ENCEPHALOMYELITIS; ACUTE NECROTIZING ENCEPHALOPATHY; ONSET MULTIPLE-SCLEROSIS; INTRAVENOUS IMMUNOGLOBULIN THERAPY; ACUTE DISSEMINATED ENCEPHALITIS; BONE-MARROW-TRANSPLANTATION; BARR-VIRUS INFECTION; POSTINFECTIOUS ENCEPHALITIS AB Acute disseminated encephalomyelitis ( ADEM) is an immune-mediated inflammatory disorder of the CNS characterized by a widespread demyelination that predominantly involves the white matter of the brain and spinal cord. The condition is usually precipitated by a viral infection or vaccination. The presenting features include an acute encephalopathy with multifocal neurologic signs and deficits. Children are preferentially affected. In the absence of specific biologic markers, the diagnosis of ADEM is still based on the clinical and radiologic features. Although ADEM usually has a monophasic course, recurrent or multiphasic forms have been reported, raising diagnostic difficulties in distinguishing these cases from multiple sclerosis ( MS). The International Pediatric MS Study Group proposes uniform definitions for ADEM and its variants. We discuss some of the difficulties in the interpretation of available literature due to the different terms and definitions used. In addition, this review summarizes current knowledge of the main aspects of ADEM, including its clinical and radiologic diagnostic features, epidemiology, pathogenesis, and outcome. An overview of ADEM treatment in children is provided. Finally, the controversies surrounding pediatric MS and ADEM are addressed. C1 Natl Pediat Hosp Dr JP Garrahan, Dept Pediat Neurol, Buenos Aires, DF, Argentina. Harvard Univ, Brigham & Womens Hosp, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Alabama, Dept Pediat, Birmingham, AL USA. Stanford Univ, Med Ctr, Div Pediat Neurol, Stanford, CA 94305 USA. RP Tenembaum, S (reprint author), Natl Pediat Hosp Dr JP Garrahan, Dept Neurol, Pediat Multiple Sclerosis Clin, Buenos Aires, DF, Argentina. EM silviatenembaum@hotmail.com NR 157 TC 243 Z9 261 U1 1 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2007 VL 68 SU 2 BP S23 EP S36 DI 10.1212/01.wnl.0000259404.51352.7f PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA 158HJ UT WOS:000245782100005 PM 17438235 ER PT J AU Vestri, HS Maianu, L Moellering, DR Garvey, WT AF Vestri, Helliner S. Maianu, Lidia Moellering, Douglas R. Garvey, W. Timothy TI Atypical antipsychotic drugs directly impair insulin action in adipocytes: Effects on glucose transport, lipogenesis, and antilipolysis SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE second-generation antipsychotics; adipocyte; insulin resistance; lipolysis; glucose transport; obesity ID PRIMARY CULTURED ADIPOCYTES; CLOZAPINE; RAT; SCHIZOPHRENIA; RESISTANCE; RECEPTORS; BRAIN; METABOLITES; RISPERIDONE; MECHANISMS AB Treatment with second-generation antipsychotics (SGAs) has been associated with weight gain and the development of diabetes mellitus, although the mechanisms are unknown. We tested the hypothesis that SGAs exert direct cellular effects on insulin action and substrate metabolism in adipocytes. We utilized two cultured cell models including 3T3-L1 adipocytes and primary cultured rat adipocytes, and tested for effects of SGAs risperidone (RISP), clozapine (CLZ), olanzapine (OLZ), and quetiapine (QUE), together with conventional antipsychotic drugs butyrophenone (BUTY), and trifluoperazine (TFP), over a wide concentration range from 1 to 500 mu M. The effects of antipsychotic drugs on basal and insulin-stimulated rates of glucose transport were studied at 3 h, 15 h, and 3 days. Both CLZ and OLZ (but not RISP) at doses as low as 5 mu M were able to significantly decrease the maximal insulin-stimulated glucose transport rate by similar to 40% in 3T3-L1 cells, whereas CLZ and RISP reduced insulin-stimulated glucose transport rates in primary cultured rat adipocytes by similar to 50-70%. Conventional drugs (BUTY and TFP) did not affect glucose transport rates. Regarding intracellular glucose metabolism, both SGAs (OLZ, QUE, RISP) and conventional drugs (BUTY and TFP) increased basal and/or insulin-stimulated glucose oxidation rates, whereas rates of lipogenesis were increased by CLZ, OLZ, QUE, and BUTY. Finally, rates of lipolysis in response to isoproterenol were reduced by the SGAs (CLZ, OLZ, QUE, RISP), but not by BUTY or TFP. These experiments demonstrate that antipsychotic drugs can differentially affect insulin action and metabolism through direct cellular effects in adipocytes. However, only SGAs were able to impair the insulin-responsive glucose transport system and to impair lipolysis in adipocytes. Thus, SGAs directly induce insulin resistance and alter lipogenesis and lipolysis in favor of progressive lipid accumulation and adipocyte enlargement. These effects of SGAs on adipocytes could explain, in part, the association of SGAs with weight gain and diabetes. C1 Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL USA. RP Vestri, HS (reprint author), Univ Alabama, Dept Nutr Sci, Webb 244,1675 Univ Blvd, Birmingham, AL 35294 USA. EM helliner@uab.edu FU NIDDK NIH HHS [DK-38765] NR 38 TC 85 Z9 88 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD APR PY 2007 VL 32 IS 4 BP 765 EP 772 DI 10.1038/sj.npp.1301142 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 146SV UT WOS:000244955900003 PM 16823387 ER PT J AU McNeely, MJ Fujimoto, WY Leonetti, DL Tsai, EC Boyko, EJ AF McNeely, Marguerite J. Fujimoto, Wilfred Y. Leonetti, Donna L. Tsai, Elaine C. Boyko, Edward J. TI The association between birth weight and visceral fat in middle-age adults SO OBESITY LA English DT Article DE risk factors; type 2 diabetes; body composition; Asian Americans ID DIABETES-MELLITUS; BODY-COMPOSITION; YOUNG MEN; ADIPOSITY; OBESITY; GROWTH; RISK; CHILDHOOD; COHORT; FETAL AB Objective: Low birth weight, a proxy for fetal underdevelopment, is associated with increased risk of developing type 2 diabetes during adulthood. Low birth weight is also associated with central obesity, but little is known about the association between birth weight and visceral adiposity. The purpose of this study is to test the hypothesis that lower birth weight is associated with increased amounts of visceral fat in middle-age adults. Research Methods and Procedures: This is an observational study of 91 adults (58 men and 33 women) 40 +/- 6 years of age (mean standard deviation). Ethnicity was either Japanese American (79%) or non-Hispanic white (21%). Birth weight was obtained from State Departments of Health. Measurements included smoking status, BMI, and visceral (intra-abdominal) fat measured by computed tomography. Results: Visceral fat was not associated with birth weight after adjustment for age, sex, ethnicity, BMI, or smoking status (p = 0.76). There was no evidence that the association between birth weight and visceral fat varied by age, sex, or ethnicity. Discussion: We found no evidence that low birth weight is associated with increased visceral fat in middle-age adults. C1 Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98105 USA. Univ Washington, Dept Anthropol, Seattle, WA 98105 USA. Vet Affairs Puget Sound Hlth Care Syst, Vet Affairs Epidemiol Res & Informat Ctr, Seattle, WA USA. RP McNeely, MJ (reprint author), Univ Washington, Dept Med, Div Gen Internal Med, 4311 11th Ave NE,Suite 230, Seattle, WA 98105 USA. EM mcneely@u.washington.edu FU NCRR NIH HHS [RR-00037]; NHLBI NIH HHS [HL-49293]; NICHD NIH HHS [R24 HD042828, R24 HD042828-10]; NIDDK NIH HHS [DK-17047, DK-31170] NR 20 TC 11 Z9 11 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBESITY JI Obesity PD APR PY 2007 VL 15 IS 4 BP 816 EP 819 DI 10.1038/oby.2007.596 PG 4 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 157OI UT WOS:000245729300004 PM 17426314 ER PT J AU Barcenas, CH Wilkinson, AV Strom, SS Cao, Y Saunders, KC Mahabir, S Hernandez-Valero, MA Forman, MR Spitz, MR Bondy, ML AF Barcenas, Carlos H. Wilkinson, Anna V. Strom, Sara S. Cao, Yumei Saunders, Katherine C. Mahabir, Somdat Hernandez-Valero, Maria A. Forman, Michele R. Spitz, Margaret R. Bondy, Melissa L. TI Birthplace, years of residence in the United States, and obesity among Mexican-American adults SO OBESITY LA English DT Article DE weight gain; Hispanics; acculturation; public health ID BODY-MASS INDEX; SOCIOECONOMIC-STATUS; NATIONAL SAMPLE; ACCULTURATION; PREVALENCE; IMMIGRANTS; NATIVITY; SCALE; WOMEN AB Objective: To evaluate the association between birthplace (Mexico or U.S.) and obesity in men and women and to analyze the relationship between duration of U.S. residency and prevalence of obesity in Mexican immigrants. Research Methods and Procedures: We used cross-sectional data from 7503 adults of Mexican descent residing in Harris County, TX, to evaluate the relationships among BMI, birthplace, and years of residency in the U.S., controlling for demographic characteristics, physical activity level, and acculturation level. Results: U.S.-born adults had an increased risk (between 34% and 65%) of obesity compared with their Mexican-born counterparts. After controlling for recognized confounders and risk factors, this association was maintained in the highly acculturated only. Among highly acculturated obese U.S.-born men, 6% of the cases were attributable to the joint effect of birthplace and acculturation; in women, this proportion was 25%. Among Mexican-born women, there was an increasing trend in mean BMI with increasing duration of residency in the U.S.. Compared with immigrants who had lived in the U.S. for <5 years, Mexican-born women who had resided in the U.S. for >= 15 years had an adjusted BMI mean difference of 2.12 kg/m(2) (95% confidence interval, 1.53-2.72). Discussion: Mexican-born men and women have a lower risk of obesity than their U.S.-born counterparts, but length of U.S. residency among immigrants, especially in women, is directly associated with risk of obesity. Development of culturally specific interventions to prevent obesity in recent immigrants may have an important public health effect in this population. C1 Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Unit 1340, Houston, TX 77030 USA. Med Coll Georgia, Dept Internal Med, Augusta, GA 30912 USA. Boston VA Healthcare Syst, Boston, MA USA. Univ Texas, MD Anderson Canc Ctr, Ctr Res Minor Hlth, Houston, TX 77030 USA. NCI, Lab Biosyst & Canc, Canc Res Ctr, Bethesda, MD 20892 USA. RP Bondy, ML (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Unit 1340, 1155 Pressler Blvd, Houston, TX 77030 USA. EM mbondy@mdanderson.org RI Mahabir, Somdat/A-9788-2008 NR 32 TC 95 Z9 95 U1 2 U2 10 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBESITY JI Obesity PD APR PY 2007 VL 15 IS 4 BP 1043 EP 1052 DI 10.1038/oby.2007.537 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 157OI UT WOS:000245729300031 PM 17426341 ER PT J AU Grady, D Cohen, B Tice, J Krisof, M Olyaie, A Sawaya, GF AF Grady, Deborah Cohen, Beth Tice, Jeffrey Krisof, Margaret Olyaie, Azin Sawaya, George F. TI Ineffectiveness of sertraline for treatment of menopausal hot flushes - A Randomized controlled trial SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID POSTMENOPAUSAL WOMEN; BREAST-CANCER; DOUBLE-BLIND; FLASHES; VENLAFAXINE; PAROXETINE; ESTROGEN; METAANALYSIS; INSTRUMENT; FLUOXETINE AB OBJECTIVE: To estimate the effect of the selective serotonin reuptake inhibitor sertraline on hot flush frequency and severity in perimenopausal and postmenopausal women. METHODS: We performed a randomized, blinded, placebo-controlled trial in women aged 40 to 60 years with 14 or more hot flushes per week (N=99). Women were randomly assigned initially to daily oral sertraline (50 mg) or identical placebo for 2 weeks. if no substantial side effects were noted, the dose was increased to two tablets daily (100 mg sertraline or placebo) and continued for an additional 4 weeks. Hot flush frequency and severity were recorded on a daily diary. Hot flush score was calculated as frequency multiplied by severity. Participants also completed questionnaires addressing quality of life, menopausal symptoms, sleep quality, sexual function, mood, and side effects. RESULTS: After 6 weeks of treatment, hot flush frequency decreased similarly in both the placebo (38%) and sertraline (39%) groups (P=.94). Mean hot flush scores also decreased similarly in both groups (41% and 42%, respectively, P=.86). Compared with placebo, women in the sertraline group were more likely to report gastrointestinal complaints, dry mouth, and dizziness. Treatment with sertraline also resulted in greater worsening of scores on the Medical Outcomes Study (MOS) Short Form 36 standardized physical component and the global Female Sexual Function Index. Results were similar in women at least 80% adherent to study medication. CONCLUSION: Treatment with sertraline did not improve hot flush frequency or severity in generally healthy perimenopausal and postmenopausal women, but was associated with bothersome side effects. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00283192. C1 Univ Calif San Francisco, Womens Hlth Clin Res Ctr, San Francisco, CA 94115 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Grady, D (reprint author), Univ Calif San Francisco, Womens Hlth Clin Res Ctr, 1635 Divisadero St,Suite 600, San Francisco, CA 94115 USA. EM Deborah.Grady@ucsf.edu NR 24 TC 53 Z9 55 U1 0 U2 1 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 APR PY 2007 VL 109 IS 4 BP 823 EP 830 DI 10.1097/01.AOG.0000258278.73505.fa PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 195AI UT WOS:000248384500006 PM 17400842 ER PT J AU Park, Y Popescu, G Badizadegan, K Dasari, RR Feld, MS AF Park, YongKeun Popescu, Gabriel Badizadegan, Kamran Dasari, Ramachandra R. Feld, Michael S. TI Fresnel particle tracing in three dimensions using diffraction phase microscopy SO OPTICS LETTERS LA English DT Article ID COMPLEX FLUIDS; MICRORHEOLOGY; DYNAMICS; SCATTERING; TRACKING AB We have developed a novel experimental technique for tracking small particles in three dimensions with nanometer accuracy. The longitudinal positioning of a micrometer-sized particle is determined by using the Fresnel approximation to describe the transverse distribution of the wavefront that originated in the particle. The method utilizes the high-sensitivity quantitative phase imaging capability of diffraction phase microscopy recently developed in our laboratory. We demonstrate the principle of the technique with experiments on Brownian particles jittering in water both in bulk and in the vicinity of a boundary. The particles are localized in space within an error cube of 20 nm x 20 nm x 20 nm for a 33 Hz acquisition rate and 20 s recording time. (c) 2007 Optical Society of America. C1 MIT, GR Harrison Spect Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Park, Y (reprint author), MIT, GR Harrison Spect Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RI Park, YongKeun/B-9017-2009 FU NCRR NIH HHS [P41 RR 02594] NR 16 TC 50 Z9 50 U1 1 U2 7 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD APR 1 PY 2007 VL 32 IS 7 BP 811 EP 813 DI 10.1364/OL.32.000811 PG 3 WC Optics SC Optics GA 148XE UT WOS:000245109900028 PM 17339945 ER PT J AU Teles, F Haffajee, AD Socransky, SS AF Teles, F. Haffajee, A. D. Socransky, S. S. TI Multiple displacement amplification as an aid in checkerboard DNA-DNA hybridization SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE bacteria; DNA probes; multiple displacement amplification; oral biofilm ID ROLLING-CIRCLE AMPLIFICATION; WHOLE GENOME AMPLIFICATION; SUBGINGIVAL PLAQUE; POLYMERASE; FIDELITY; PCR AB Objective: The study aimed to determine if multiple displacement amplification could be used to provide abundant target DNA and DNA probes for checkerboard DNA-DNA hybridization. Methods: Multiple displacement amplification was used to amplify 1 and 10 ng DNA from 16 individual bacterial species, DNA from single colonies, from a mixture of 20 bacterial species and oral biofilm samples, such as supragingival plaque, subgingival plaque, buccal swab and root canal samples. Samples in reaction buffer were heat-denatured at 95 degrees C for 3 min and cooled to 4 degrees C. Phi 29 DNA polymerase was added and the mixture was incubated at 30 degrees C for 16-18 h. The quantity of the product was evaluated by the Picogreen assay. The amplified material was labeled with digoxigenin. The probes were compared with probes obtained from unamplified DNA using checkerboard DNA-DNA hybridization. Both amplified DNA and unamplified DNA were used as targets on the membrane. Amplified oral biofilm samples were compared to unamplified samples using checkerboard DNA-DNA hybridization. Results: The DNA yield ranged from 4 to 11 mu g. DNA-DNA hybridization showed that the amplified genome of each species used either as target or as probe provided signals equivalent to controls and that amplification of a mixture of species provided signals comparable to those provided by the unamplified source mixture. Amplified oral biofilm samples exhibited comparable proportions of bacterial DNA when compared to the original unamplified samples. Conclusions: The multiple displacement amplification technique is a simple and reliable method to uniformly amplify DNA for use in checkerboard DNA-DNA hybridization. It is also a useful tool in the amplification of clinical samples. C1 Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral Med, Boston, MA 02115 USA. RP Teles, F (reprint author), Forsyth Inst, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. EM fteles@forsyth.org FU NIDCR NIH HHS [T32-DE-07327, DE-12108, DE-14242] NR 21 TC 13 Z9 13 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD APR PY 2007 VL 22 IS 2 BP 118 EP 125 DI 10.1111/j.1399-302X.2007.00333.x PG 8 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA 137GA UT WOS:000244279800007 PM 17311635 ER PT J AU Ilyas, AM Jupiter, JB AF Ilyas, Asif M. Jupiter, Jesse B. TI Distal radius fractures - Classification of treatment and indications for surgery SO ORTHOPEDIC CLINICS OF NORTH AMERICA LA English DT Article ID COLLES FRACTURES; YOUNG-ADULTS; INTRAARTICULAR FRACTURES; INTERNAL-FIXATION; JOINT MECHANICS; OPEN REDUCTION; INSTABILITY; PREDICTION; DEFORMITY; END AB Distal radius fractures are common injuries. Multiple classification systems have highlighted the evolution of the understanding of distal radius fractures. Understanding the classifications of distal radius fractures is important in identifying the important aspects that affect their outcome. Surgical indications of distal radius fractures can be divided into the following categories: patient factors, fracture reduction, fracture stability, and the presence of associated injuries. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. RP Jupiter, JB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Hand Serv, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. EM jjupiter1@partners.org NR 41 TC 12 Z9 14 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 0030-5898 J9 ORTHOP CLIN N AM JI Orthop. Clin. North Am. PD APR PY 2007 VL 38 IS 2 BP 167 EP + DI 10.1016/j.ocl.2007.01.002 PG 8 WC Orthopedics SC Orthopedics GA 188UR UT WOS:000247945300004 PM 17560399 ER PT J AU Peterson, DD Morse, L Pham, L Stashenko, P Battaglino, R AF Peterson, Derek D. Morse, Leslie Pham, Lan Stashenko, Philip Battaglino, Ricardo TI Fluoxetine increases longitudinal growth of fetal metatarsals SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract CT 7th International Symposium on Osteoporosis CY APR 18-22, 2007 CL Washington, DC SP Natl Osteoporosis Fdn C1 Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI ARTINGTON PA ASHBOURNE HOUSE, THE GUILDWAY, OLD PORTSMOUTH ROAD, ARTINGTON GU3 1LP, GUILDFORD, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD APR PY 2007 VL 18 SU 2 BP S193 EP S193 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 160YR UT WOS:000245981100002 ER PT J AU Moore, MG Deschler, DG AF Moore, Michael G. Deschler, Daniel G. TI Clopidogrel (Plavix) reduces the rate of thrombosis in the rat tuck model for microvenous anastomosis SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID FREE FLAPS; HEAD; RECONSTRUCTION; EXPERIENCE; SURGERY; ASPIRIN AB OBJECTIVE: To evaluate the effect of clopidogrel on the rate of thrombosis in a rat model for venous microvascular failure. STUDY DESIGN AND SETTING: Forty rats were treated with clopidogrel or saline control via gastric gavage in a randomized, blinded fashion. After allowing for absorption and activation, each femoral vein was isolated and a venous "tuck" procedure was performed. The bleeding time and vessel patency were subsequently evaluated. RESULTS: The rate of vessel thrombosis was decreased in the clopidogrel-treated group compared to controls (7.9% vs 31.4%, P < 0.025). The bleeding time was longer in the clopidogrel-treated group compared to controls (250 +/- 100 seconds vs 173 +/- 59 seconds, P < 0.015). CONCLUSION: Clopidogrel decreased the rate of thrombosis in the rat model for venous microvascular failure. SIGNIFICANCE: The use of clopidogrel may reduce the rate of venous thrombosis after free tissue transfer and may be indicated in select patients. (C) 2007 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Moore, MG (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM michael_moore@meei.harvard.edu NR 15 TC 8 Z9 9 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD APR PY 2007 VL 136 IS 4 BP 573 EP 576 DI 10.1016/j.otohns.2006.06.1276 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 154PB UT WOS:000245518600012 PM 17418254 ER PT J AU Groeneveld, PW Matta, MA Suh, JJ Yang, FF Shea, JA AF Groeneveld, Peter W. Matta, Mary A. Suh, Janice J. Yang, Feifei Shea, Judy A. TI Quality of life among implantable cardioverter-defibrillator recipients in the primary prevention therapeutic era SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE defibrillators; implantable; quality of life ID HEART-FAILURE; TRIAL; ICD; MORBIDITY; MORTALITY; ATTITUDES; ANXIETY; SHOCKS AB Background: Although patients receiving implantable cardioverter-defibrillators (ICDs) for primary prevention of sudden cardiac death are the fastest growing segment of the ICD recipient population, the quality-of-life (QOL) effects of the ICD among primary prevention patients are not well understood. The purpose of this study was to measure and compare the health-related QOL among primary and secondary prevention ICD recipients, and to determine predictive factors for high or low QOL in each group. Methods: Forty-five primary prevention and 75 secondary prevention ICD recipients receiving routine care in electrophysiology clinics within the University of Pennsylvania Health System were assessed using several well-validated general and ICD-specific QOL instruments. Results: Between primary and secondary prevention patients, there were no significant differences in EuroQol 5D (medians: 0.84 vs 0.84, P = 0.71), Health Utilities Index (medians: 0.88 vs 0.85, P = 0.95), Short Form-12 aggregate physical summary (means: 45 vs 46, P = 0.64), and Short Form-12 aggregate mental summary (means: 46 vs 47, P = 0.93) scores. Both primary and secondary prevention patients viewed their devices favorably according to the Florida Patient Acceptance Survey scale, with no significant differences between group means (80 vs 83, P = 0.71). However, substantial fractions of both primary and secondary prevention recipients had particular concerns about lifting (40%), sexual activity (19%), and driving (14%). Conclusions: QOL does not significantly differ between primary prevention and secondary prevention ICD recipients. Device recipients had comparable QOL to published, nationwide QOL estimates among non-ICD patients of similar age. The ICD was highly acceptable to most primary and secondary prevention patients. C1 Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Groeneveld, PW (reprint author), 1229 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM peter.groeneveld@va.gov NR 32 TC 35 Z9 35 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD APR PY 2007 VL 30 IS 4 BP 463 EP 471 DI 10.1111/j.1540-8159.2007.00694.x PG 9 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 156IZ UT WOS:000245642600004 PM 17437568 ER PT J AU Moss, A Beggs, S Vega-Avelaira, D Costigan, M Hathway, GJ Salter, MW Fitzgerald, M AF Moss, Andrew Beggs, Simon Vega-Avelaira, David Costigan, Michael Hathway, Gareth J. Salter, Michael W. Fitzgerald, Maria TI Spinal microglia and neuropathic pain in young rats SO PAIN LA English DT Article DE microglia; Iba-1; lipopolysaccharide; neuropathic pain; neonatal; dorsal horn ID PERIPHERAL-NERVE INJURY; DORSAL-HORN; POSTNATAL-DEVELOPMENT; ADULT-RAT; MECHANICAL ALLODYNIA; CENTRAL TERMINALS; GLIAL ACTIVATION; CORD; MACROPHAGES; RESPONSES AB Neuropathic pain behaviour is not observed in neonatal rats and tactile allodynia does not develop in the spared nerve injury (SNI) model until rats are 4 weeks of age at the time of surgery. Since activated spinal microglia are known to play a key role in neuropathic pain, we have investigated whether the microglial response to nerve injury in young rats differs from that in adults. Here we show that dorsal horn microglial activation, visualised with IBA-1 immunostaining, is significantly less in postnatal day (P) 10 rat pups than in adults, 7 days after SNI. This was confirmed by qPCR analysis of IBA-1 mRNA and mRNA of other microglial markers, integrin-alpha M, MHC-II DM alpha and MHC-II DM beta. Dorsal horn IBA-1+ve microglia could be activated, however, by intraspinal injections of lipopolysaccharide (LPS) or N-methyl-D-aspartate (NMDA) at P10, although the increase in the levels of mRNA for all microglial markers was less than in the adult rat. In addition, P10 rats developed a small but significant mechanical allodynia in response to intrathecal LPS. Intrathecal injection of cultured ATP-activated microglia, known to cause mechanical allodynia in adult rats, had no behavioural effect at P10 and only began to cause allodynia if injections were performed at P16. The results clearly demonstrate immaturity of the microglial response triggered by nerve injury in the first postnatal weeks which may explain the absence of tactile allodynia following peripheral nerve injury in young rats. (c) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 UCL, Dept Anat & Dev Biol, London WC1E 6BT, England. Univ Toronto, Ctr Study Pain, Toronto, ON, Canada. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plastic Res Grp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Moss, A (reprint author), UCL, Dept Anat & Dev Biol, Mortimer St, London WC1E 6BT, England. EM a9813963@hotmail.com RI Fitzgerald, Maria/C-5760-2008; Vega-Avelaira, David/K-5639-2014; OI Vega-Avelaira, David/0000-0002-8551-710X; Hathway, Gareth/0000-0003-4347-9667 FU Medical Research Council [G0400572] NR 44 TC 56 Z9 58 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD APR PY 2007 VL 128 IS 3 BP 215 EP 224 DI 10.1016/j.pain.2006.09.018 PG 10 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 160AH UT WOS:000245908700005 PM 17110040 ER PT J AU Quinones, MP Estrada, CA Jimenez, F Martinez, H Willmon, O Kuziel, WA Ahuja, SK Ahuja, SS AF Quinones, M. P. Estrada, C. A. Jimenez, F. Martinez, H. Willmon, O. Kuziel, W. A. Ahuja, S. K. Ahuja, S. S. TI CCL2-independent role of CCR2 in immune responses against Leishmania major SO PARASITE IMMUNOLOGY LA English DT Article DE chemokine; immunology; infection; parasite ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CHEMOKINE RECEPTOR 2; RHEUMATOID-ARTHRITIS; DEFICIENT MICE; RECRUITMENT; INFECTION; DISEASE; CELLS; ATHEROSCLEROSIS AB The chemokine CCL2 (MCP-1) and its receptor CCR2 modulate leucocyte migration and T helper differentiation. CCL2 or CCR2 knockout (KO) mice have divergent phenotypes following infection with the intracellular parasite Leishmania major (L. major). Compared to wild-type (WT) mice, intra-dermally infected CCR2 KO mice in the L. major-resistant C57BL/6j background become susceptible and fail to generate protective Th1 responses. In contrast, subcutaneously infected CCL2 KO mice in the L. major-susceptible BALB/c background are resistant and exhibit reduced pathogenic Th2 responses. Here we explore two variables that may account for this contrasting outcome, namely background strain and route of infection. We found that the CCR2-null state, both in the BALB/c and the C57BL/6j background, was associated with increased susceptibility to intradermal or subcutaneous L. major infection. Notably, the CCL2-null state did not change the ability of C57BL/6j mice to mount protective responses following intradermal infection. Dual genetic inactivation of CCR2 and CCL2 in the L. major-resistant C57BL/6j background resulted in a shift to a susceptible phenotype analogous to that of CCR2 KO in the C57BL/6j background. We concluded that CCL2-independent effects of CCR2 are indispensable for the control of L. major infection and the generation of protective immune responses. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Prot Design Labs Inc, Fremont, CA USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Vet Adm Ctr Res AIDS & HIV Infect 1, San Antonio, TX USA. RP Ahuja, SS (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, MC 7870,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM ahuja@uthscsa.edu FU NIAID NIH HHS [AI48644]; OMH OASH HHS [D52MP03115-01-0] NR 34 TC 14 Z9 14 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0141-9838 J9 PARASITE IMMUNOL JI Parasite Immunol. PD APR PY 2007 VL 29 IS 4 BP 211 EP 217 DI 10.1111/j.1365-3024.2006.00935.x PG 7 WC Immunology; Parasitology SC Immunology; Parasitology GA 147ER UT WOS:000244986700005 PM 17371458 ER PT J AU Kelly, PA Haidet, P AF Kelly, P. Adam Haidet, Paul TI Physician overestimation of patient literacy: A potential source of health care disparities SO PATIENT EDUCATION AND COUNSELING LA English DT Article; Proceedings Paper CT Annual Research and Teaching Forum of the American-Academy-on-Physician-and-Patient CY OCT, 2004 CL Indianapolis, IN SP Amer Acad Phys & Patient DE literacy; health disparities; patient-provider relationship; health knowledge; minority groups; measurement ID DIABETES PATIENTS; COMMUNICATION; ASSOCIATION AB Objective: To investigate physician overestimation of patient literacy level in a primary care setting. Methods: The study sample consisted of 12 non-academic primary care physicians and 100 patients from a U.S. Department of Veterans Affairs Hospital in Houston, Texas. Patient literacy level was measured on a 1-4 scale using the Rapid Estimate of Adult Literacy in Medicine (REALM). Physicians rated each patient's literacy level on a corresponding scale. Chi-square was used to test for association of patient race/ ethnicity and gender with: (1) patient REALM level and (2) discrepancy between patient REALM level and physician rating of patient literacy level. Results: Patient REALM level was not statistically significantly associated with patient race/ethnicity or gender. Physicians overestimated the REALM level for 54% of African American, 11% of white non-Hispanic, and 36% of other race/ethnicity patients (p < .01). Conclusion: Physicians commonly overestimate patients' literacy levels, and this apparently occurs more often with minority patients, and particularly with African Americans, than with white non-Hispanic patients. This discordance in estimation of patient's literacy level may be a source of disparities in health care. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Baylor Coll Med, US Dept Vet Affairs, Houston, TX 77030 USA. RP Kelly, PA (reprint author), Michael E DeBakey VA Med Ctr, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM pakelly@bcm.edu NR 17 TC 106 Z9 108 U1 3 U2 14 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD APR PY 2007 VL 66 IS 1 BP 119 EP 122 DI 10.1016/j.pec.2006.10.007 PG 4 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 154DR UT WOS:000245487500017 PM 17140758 ER PT J AU Chan, PLS Nutt, JG Holford, NHG AF Chan, Phylinda L. S. Nutt, John G. Holford, Nicholas H. G. TI Levodopa slows progression of Parkinson's disease. External validation by clinical trial simulation SO PHARMACEUTICAL RESEARCH LA English DT Article DE clinical trial simulation; DATATOP; disease progress model; ELLDOPA; Parkinson's disease; protective treatment ID BENEFIT FOLLOWING WITHDRAWAL; 1ST 4 YEARS; SINEMET CR; L-DOPA; PHARMACOKINETICS; STANDARD; BROMOCRIPTINE; MULTICENTER; MORTALITY; CARBIDOPA AB To externally validate the model predictions of a DATATOP cohort analysis through application of clinical trial simulation with the study design of the ELLDOPA trial. The stochastic pharmacokinetic-pharmacodynamic and disease progress model was developed from the large DATATOP cohort of patients followed for 8 years. ELLDOPA was designed to detect a difference between placebo and levodopa treated arms in the total Unified Parkinson's Disease Rating Scale (UPDRS) taken at baseline and following 2 weeks levodopa washout after 40 weeks of treatment. The total UPDRS response was simulated with different assumptions on levodopa effect (symptomatic with/without disease modifying capability) and washout speed of symptomatic effect. The observed results of ELLDOPA were similar to the model predictions assuming levodopa slows disease progression and has a slow washout of symptomatic effect. This simulation work confirmed the conclusion of the DATATOP analysis finding that levodopa slows disease progression. The simulation results also showed that a dose-related increased rate of progression in Parkinson's disease, obscured by symptomatic benefit, is very unlikely. Finally, the simulation results also shown that 2 weeks washout period was not adequate to completely eliminate the symptomatic benefits of levodopa. C1 Univ Auckland, Dept Pharmacol & Clin Pharmacol, Fac Med & Hlth Sci, Auckland 1, New Zealand. Portland VA Med Ctr, Dept Neurol & Physiol & Pharmacol, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. RP Holford, NHG (reprint author), Univ Auckland, Dept Pharmacol & Clin Pharmacol, Fac Med & Hlth Sci, Private Bag 92019, Auckland 1, New Zealand. EM n.holford@auckland.ac.nz OI Holford, Nick/0000-0002-4031-2514 NR 33 TC 38 Z9 39 U1 0 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES JI Pharm. Res. PD APR PY 2007 VL 24 IS 4 BP 791 EP 802 DI 10.1007/s11095-006-9202-3 PG 12 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 145UF UT WOS:000244890100018 PM 17308968 ER PT J AU Borello-France, DF Handa, VL Brown, MB Goode, P Kreder, K Scheufele, LL Weber, AM AF Borello-France, Diane F. Handa, Victoria L. Brown, Morton B. Goode, Patricia Kreder, Karl Scheufele, Laura L. Weber, Anne M. CA Pelvic Floor Disorders Network TI Pelvic-floor muscle function in women with pelvic organ prolapse SO PHYSICAL THERAPY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the American-Urogynecologic-Society CY SEP 15-17, 2005 CL Atlanta, GA SP Amer Urogynecol Soc ID LOWER URINARY-TRACT; CONTINENCE-SOCIETY; SEXUAL FUNCTION; INCONTINENCE; STRENGTH; POPULATION; STANDARDIZATION; TERMINOLOGY; SYMPTOMS AB Background and Purpose The purpose of this study was to determine whether pelvic organ prolapse severity, pelvic symptoms, quality of life, and sexual function differ based on pelvic-floor muscle function in women planning to have prolapse surgery. Subjects and Methods Three hundred seventeen women without urinary stress incontinence who were enrolled in a multicenter surgical trial were examined to determine pelvic-floor muscle function (by Brink scale score). The subjects were 61.6 +/- 10.2 ((X) over bar +/- - SD) years of age. Thirteen percent of the subjects had stage II (to the hymen) pelvic organ prolapse, 68% had stage III (beyond the hymen) prolapse, and 19% had stage IV (complete vaginal eversion) prolapse. Subjects with lowest (3-6) and highest (10-12) Brink scale scores were compared on prolapse severity, pelvic symptoms and bother, quality of life, and sexual function. Results Subjects with the highest Brink scores (n=75) had less advanced prolapse, smaller genital hiatus measurements, and less urinary symptom burden compared with those with the lowest Brink scores (n=56). The results indicated that pelvic-floor muscle function was not associated with condition-specific quality of life or sexual function. Discussion and Conclusion Although modestly clinically significant, better pelvic-floor muscle function was associated with less severe prolapse and urinary symptoms. C1 Duquesne Univ, Dept Phys Therapy, Pittsburgh, PA 15282 USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Alabama, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Clin Program, Birmingham, AL USA. Univ Iowa, Dept Urol, Iowa City, IA 52242 USA. Johns Hopkins Bayview Med Ctr, Baltimore, MD USA. NICHHD, Pelv Floor Disorders Network, NIH, Bethesda, MD 20892 USA. RP Borello-France, DF (reprint author), Duquesne Univ, Dept Phys Therapy, 111 Hlth Sci Bldg, Pittsburgh, PA 15282 USA. EM borellofrance@duq.edu FU NICHD NIH HHS [U10 HD41261, U01 HD41249, U10 HD041261, U10 HD41250, U10 HD41263, U10 HD41267, U10 HD41269, U10 HD41248, U10 HD41268] NR 32 TC 11 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 APR PY 2007 VL 87 IS 4 BP 399 EP 407 DI 10.2522/ptj.20060160 PG 9 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA 150NM UT WOS:000245223500004 PM 17341510 ER PT J AU Ly, H Kawase, Y Yoneyama, R Hajjar, RJ AF Ly, Hung Kawase, Yoshiaki Yoneyama, Ryuichi Hajjar, Roger J. TI Gene therapy in the treatment of heart failure SO PHYSIOLOGY LA English DT Review ID ADENOASSOCIATED VIRUS VECTORS; TRANSDUCTION IN-VIVO; FAILING HUMAN HEARTS; LENTIVIRAL VECTORS; CARDIOVASCULAR-DISEASE; CARDIAC DYSFUNCTION; HIGH-EFFICIENCY; VIRAL VECTORS; AAV VECTORS; DELIVERY AB Heart failure is a major cause of morbidity and mortality in contemporary societies. Although progress in conventional treatment modalities is making steady and incremental gains to reduce this disease burden, there remains a need to explore new and potentially therapeutic approaches. Gene therapy, for example, was initially envisioned as a treatment strategy for inherited monogenic disorders. It is now apparent that gene therapy has broader potential that also includes acquired polygenic diseases, such as heart failure. Advances in the understanding of the molecular basis of conditions such as these, together with the evolution of increasingly efficient gene transfer technology, has placed congestive heart failure within reach of gene-based therapy. C1 Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Res Ctr, Cardiol Lab Integrat Physiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ly, H (reprint author), Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Res Ctr, Cardiol Lab Integrat Physiol, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL 057263, HL 071763, R01 HL 078691, HL 080498, HL 083156] NR 85 TC 32 Z9 35 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1548-9213 J9 PHYSIOLOGY JI Physiology PD APR PY 2007 VL 22 BP 81 EP 96 DI 10.1152/physiol.00037.2006 PG 16 WC Physiology SC Physiology GA 193EK UT WOS:000248256900003 PM 17420300 ER PT J AU Chun, YS Lalonde, DH May, JW AF Chun, Yoon S. Lalonde, Donald H. May, James W., Jr. TI Internal pedicle shaping to improve aesthetic results in reduction mammaplasty SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Editorial Material ID SCAR BREAST REDUCTION; T-SCAR; INFERIOR C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Dalhousie Univ, St John Reg Hosp, Dept Plast Surg, Halifax, NS B3H 3J5, Canada. RP Chun, YS (reprint author), Brigham & Womens Hosp, Div Plast & Reconstruct Surg, 75 Francis St, Boston, MA 02115 USA. EM ychun@partners.org NR 13 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD APR 1 PY 2007 VL 119 IS 4 BP 1183 EP 1189 DI 10.1097/01.prs.00002447.41379.5c PG 7 WC Surgery SC Surgery GA 150CX UT WOS:000245194300007 PM 17496589 ER PT J AU Yu, HY Kim, PM Sprecher, E Trifonov, V Gerstein, M AF Yu, Haiyuan Kim, Philip M. Sprecher, Emmett Trifonov, Valery Gerstein, Mark TI The importance of bottlenecks in protein networks: Correlation with gene essentiality and expression dynamics SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID TRANSCRIPTIONAL REGULATORY NETWORKS; SACCHAROMYCES-CEREVISIAE; MOLECULAR NETWORKS; COMPLEX NETWORKS; GENOMIC ANALYSIS; BUDDING YEAST; DATABASE; BETWEENNESS; CENTRALITY; RELIABILITY AB It has been a long-standing goal in systems biology to find relations between the topological properties and functional features of protein networks. However, most of the focus in network studies has been on highly connected proteins ("hubs''). As a complementary notion, it is possible to define bottlenecks as proteins with a high betweenness centrality (i.e., network nodes that have many "shortest paths'' going through them, analogous to major bridges and tunnels on a highway map). Bottlenecks are, in fact, key connector proteins with surprising functional and dynamic properties. In particular, they are more likely to be essential proteins. In fact, in regulatory and other directed networks, betweenness (i.e., "bottleneck-ness'') is a much more significant indicator of essentiality than degree (i.e., "hub-ness''). Furthermore, bottlenecks correspond to the dynamic components of the interaction network-they are significantly less well coexpressed with their neighbors than nonbottlenecks, implying that expression dynamics is wired into the network topology. C1 Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA. Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA. RP Gerstein, M (reprint author), Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. EM Mark.Gerstein@yale.edu FU NHGRI NIH HHS [P50 HG002357, P50 HG02357] NR 52 TC 358 Z9 365 U1 5 U2 18 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD APR PY 2007 VL 3 IS 4 BP 713 EP 720 AR e59 DI 10.1371/journal.pcbi.0030059 PG 8 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 163VM UT WOS:000246191300011 PM 17447836 ER PT J AU Curran, SP Ruvkun, G AF Curran, Sean P. Ruvkun, Gary TI Lifespan regulation by evolutionarily conserved genes essential for viability SO PLOS GENETICS LA English DT Article ID NEMATODE CAENORHABDITIS-ELEGANS; SYSTEMATIC RNAI SCREEN; AGE-1 PI3 KINASE; C-ELEGANS; INSULIN-RECEPTOR; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTION FACTOR; CALORIC RESTRICTION; DIETARY RESTRICTION; ADIPOSE-TISSUE AB Evolutionarily conserved mechanisms that control aging are predicted to have prereproductive functions in order to be subject to natural selection. Genes that are essential for growth and development are highly conserved in evolution, but their role in longevity has not previously been assessed. We screened 2,700 genes essential for Caenorhabditis elegans development and identified 64 genes that extend lifespan when inactivated postdevelopmentally. These candidate lifespan regulators are highly conserved from yeast to humans. Classification of the candidate lifespan regulators into functional groups identified the expected insulin and metabolic pathways but also revealed enrichment for translation, RNA, and chromatin factors. Many of these essential gene inactivations extend lifespan as much as the strongest known regulators of aging. Early gene inactivations of these essential genes caused growth arrest at larval stages, and some of these arrested animals live much longer than wild-type adults. daf-16 is required for the enhanced survival of arrested larvae, suggesting that the increased longevity is a physiological response to the essential gene inactivation. These results suggest that insulin-signaling pathways play a role in regulation of aging at any stage in life. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu FU NIA NIH HHS [F32 AG026207, F32 AG026207-01, F32 AG026207-02, F32 AG026207-03, F32-AG026207, R00 AG032308, R01 AG016636, R01-AG016636] NR 66 TC 232 Z9 284 U1 2 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD APR PY 2007 VL 3 IS 4 AR e56 DI 10.1371/journal.pgen.0030056 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 161UM UT WOS:000246041700003 PM 17411345 ER PT J AU Kim, S Namekawa, SH Niswander, LM Ward, JO Lee, JT Bardwell, VJ Zarkower, D AF Kim, Shinseog Namekawa, Satoshi H. Niswander, Lisa M. Ward, Jeremy O. Lee, Jeannie T. Bardwell, Vivian J. Zarkower, David TI A mammal-specific Doublesex homolog associates with male sex chromatin and is required for male meiosis SO PLOS GENETICS LA English DT Article ID HISTONE H2AX PHOSPHORYLATION; TESTICULAR GERM-CELLS; CHROMOSOME INACTIVATION; XY BODY; SYNAPTONEMAL COMPLEXES; PACHYTENE CHECKPOINT; DOSAGE-COMPENSATION; LATERAL ELEMENTS; MEIOTIC PROPHASE; Y-CHROMOSOME AB Gametogenesis is a sexually dimorphic process requiring profound differences in germ cell differentiation between the sexes. In mammals, the presence of heteromorphic sex chromosomes in males creates additional sex-specific challenges, including incomplete X and Y pairing during meiotic prophase. This triggers formation of a heterochromatin domain, the XY body. The XY body disassembles after prophase, but specialized sex chromatin persists, with further modification, through meiosis. Here, we investigate the function of DMRT7, a mammal-specific protein related to the invertebrate sexual regulators Doublesex and MAB-3. We find that DMRT7 preferentially localizes to the XY body in the pachytene stage of meiotic prophase and is required for male meiosis. In Dmrt7 mutants, meiotic pairing and recombination appear normal, and a transcriptionally silenced XY body with appropriate chromatin marks is formed, but most germ cells undergo apoptosis during pachynema. A minority of mutant cells can progress to diplonema, but many of these escaping cells have abnormal sex chromatin lacking histone H3K9 di- and trimethylation and heterochromatin protein 1 beta accumulation, modifications that normally occur between pachynema and diplonema. Based on the localization of DMRT7 to the XY body and the sex chromatin defects observed in Dmrt7 mutants, we conclude that DMRT7 plays a role in the sex chromatin transformation that occurs between pachynema and diplonema. We suggest that DMRT7 may help control the transition from meiotic sex chromosome inactivation to postmeiotic sex chromatin in males. In addition, because it is found in all branches of mammals, but not in other vertebrates, Dmrt7 may shed light on evolution of meiosis and of sex chromatin. C1 Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. Univ Minnesota, Biochem Mol Biol & Biophys Grad Program, Minneapolis, MN 55455 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Middlebury Coll, Dept Biol, Middlebury, VT USA. RP Zarkower, D (reprint author), Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. EM zarko001@umn.edu FU NIGMS NIH HHS [GM059152, R01 GM059152] NR 65 TC 32 Z9 34 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD APR PY 2007 VL 3 IS 4 AR e62 DI 10.1371/journal.pgen.0030062 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 161UM UT WOS:000246041700011 PM 17447844 ER PT J AU DeMonaco, HJ von Hippel, E AF DeMonaco, Harold J. von Hippel, Eric TI Reducing medical costs and improving quality via self-management tools SO PLOS MEDICINE LA English DT Article ID RATING DEPRESSION SCALE; ANTICOAGULANT-THERAPY; ORAL ANTICOAGULATION; CONTROLLED-TRIAL; CHRONIC DISEASE; HEALTH-CARE; INTERVENTION; OUTPATIENT; PROGRAM C1 Massachusetts Gen Hosp, Qual Management Unit, Boston, MA 02114 USA. MIT, Sloan Sch Management, Innovat & Entrepreneurship Grp, Cambridge, MA 02139 USA. RP DeMonaco, HJ (reprint author), Massachusetts Gen Hosp, Qual Management Unit, Boston, MA 02114 USA. EM hdemonaco@partners.org NR 28 TC 4 Z9 4 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD APR PY 2007 VL 4 IS 4 BP 609 EP 611 AR e104 DI 10.1371/journal.pmed.0040104 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 160MX UT WOS:000245947000003 PM 17439292 ER PT J AU Begun, J Gaiani, JM Rohde, H Mack, D Calderwood, SB Ausubel, FM Sifri, CD AF Begun, Jakob Gaiani, Jessica M. Rohde, Holger Mack, Dietrich Calderwood, Stephen B. Ausubel, Frederick M. Sifri, Costi D. TI Staphylococcal biofilm exopolysaccharide protects against Caenorhabditis elegans immune defenses SO PLOS PATHOGENS LA English DT Article ID POLYSACCHARIDE INTERCELLULAR ADHESIN; DEVICE-RELATED INFECTION; FOREIGN-BODY INFECTION; INNATE IMMUNITY; C-ELEGANS; GENE-EXPRESSION; MICROBIAL VIRULENCE; TRANSPOSON MUTANTS; STRESS RESISTANCE; SIGNALING PATHWAY AB Staphylococcus epidermidis and Staphylococcus aureus are leading causes of hospital-acquired infections that have become increasingly difficult to treat due to the prevalence of antibiotic resistance in these organisms. The ability of staphylococci to produce biofilm is an important virulence mechanism that allows bacteria both to adhere to living and artificial surfaces and to resist host immune factors and antibiotics. Here, we show that the icaADBC locus, which synthesizes the biofilm-associated polysaccharide intercellular adhesin (PIA) in staphylococci, is required for the formation of a lethal S. epidermidis infection in the intestine of the model nematode Caenorhabditis elegans. Susceptibility to S. epidermidis infection is influenced by mutation of the C. elegans PMK-1 p38 mitogen-activated protein (MAP) kinase or DAF-2 insulin-signaling pathways. Loss of PIA production abrogates nematocidal activity and leads to reduced bacterial accumulation in the C. elegans intestine, while overexpression of the icaADBC locus in S. aureus augments virulence towards nematodes. PIA-producing S. epidermidis has a significant survival advantage over ica-deficient S. epidermidis within the intestinal tract of wild-type C. elegans, but not in immunocompromised nematodes harboring a loss-of-function mutation in the p38 MAP kinase pathway gene sek-1. Moreover, sek-1 and pmk-1 mutants are equally sensitive to wild-type and icaADBC-deficient S. epidermidis. These results suggest that biofilm exopolysaccharide enhances virulence by playing an immunoprotective role during colonization of the C. elegans intestine. These studies demonstrate that C. elegans can serve as a simple animal model for studying host pathogen interactions involving staphylococcal biofilm exopolysaccharide and suggest that the protective activity of biofilm matrix represents an ancient conserved function for resisting predation. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA USA. Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA. Univ Virginia Hlth Syst, Div Infect Dis & Int Hlth, Charlottesville, VA USA. Univ Klinikum Hamburg, Inst Med Mikrobiol Virol & Hyg, Hamburg, Germany. Univ Coll Swansea, Sch Med, Swansea, W Glam, Wales. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA USA. RP Sifri, CD (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA USA. EM csifri@virginia.edu RI Begun, Jakob/J-6793-2014 OI Begun, Jakob/0000-0001-5256-7672 FU NIAID NIH HHS [K08 AI053677, R01 AI064332] NR 86 TC 90 Z9 99 U1 2 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2007 VL 3 IS 4 BP 526 EP 540 AR e57 DI 10.1371/journal.ppat.0030057 PG 15 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 196VP UT WOS:000248510600008 PM 17447841 ER PT J AU Ling, W Yi, YP Xuan, L Kufe, D Cheng, C AF Ling, Wei Yi Yan-Ping Xuan, Liu Kufe, Donald Cheng, Cao TI MUC1 C-terminal heterodimer and its tumorigenicity SO PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS LA Chinese DT Article DE MUC1; C-ter; CQC motif; heterodimer ID CYTOPLASMIC DOMAIN; BETA-CATENIN; CARCINOMA; PROTEIN; GENE; PHOSPHORYLATION; RECEPTOR; ANTIGEN; KINASE; CELLS AB The MUC1 protein is expressed as a stable heterodimer from a single polypeptide, which was cleaved into two subunits in endoplasmic reticulum. It localizes at the cell membrane as an alpha/beta-complex, tethered by the beta-subunit transmembrane domain. Previous studies implicated that the three amino acids of the transmembrane domain adjacent to the cytoplasmic domain in MUC1 beta-subunit are the residues Cys-Gln-Cys (CQC). Therein, site-directed mutagenesis of the CQC motif was performed and the cell lines were established. These cell lines include HCT116/MUC1, HCT116/MUC1 (CQC -> AQA), HCT116/MUC1 (Delta CQCRRK), HCT116/MUC1C-ter (CQC -> AQA), which can express wild type or mutant MUC1 on the cell surface, or its cytoplasmic domain. The effects of CQC -> AQA mutation or CQCRRK deletion were investigated in vitro and in vivo. Compared with wild type MUC1, the mutants depressed soft agar colony formation and showed abrogated tumorigenicity in nude mice. These findings implicate that CQCRRK motif mediate the formation of WC I protein complex. As a result of this research, disruption of MUC1-C-terminal subunit-associated dimerization by mutation of CQC -> AQA might represent a novel therapeutic approach for tumor. C1 Acad Mil Med Sci, Beijing Inst Biotechnol, Beijing 100850, Peoples R China. Chinese Acad Sci, Grad Sch, Beijing 100049, Peoples R China. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cheng, C (reprint author), Acad Mil Med Sci, Beijing Inst Biotechnol, Beijing 100850, Peoples R China. EM caoc@nic.bmi.ac.cn NR 18 TC 0 Z9 0 U1 0 U2 8 PU SCIENCE CHINA PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1000-3282 J9 PROG BIOCHEM BIOPHYS JI Prog. Biochem. Biophys. PD APR PY 2007 VL 34 IS 4 BP 375 EP 381 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 160AC UT WOS:000245908200007 ER PT J AU Bromley, E AF Bromley, Elizabeth TI Barriers to the appropriate clinical use of medications that improve the cognitive deficits of schizophrenia SO PSYCHIATRIC SERVICES LA English DT Review ID QUALITY-OF-LIFE; FOLLOW-UP; ECOLOGICAL VALIDITY; ALZHEIMERS-DISEASE; NEUROPSYCHOLOGICAL DEFICITS; 1ST-EPISODE SCHIZOPHRENIA; VOCATIONAL-REHABILITATION; NEUROCOGNITIVE DEFICITS; COMPROMISED INTELLECT; SUPPORTED EMPLOYMENT AB A high priority has been placed on developing medications to treat the cognitive deficits associated with schizophrenia, but less attention has been given to planning for appropriate use of these medications in practice. The cognitive deficits of schizophrenia present several complexities as a treatment target that may limit a clinician's ability to prescribe cognitive enhancers to the patients who need them and to monitor for improvements in outcomes. In this review the neuropsychological evidence regarding cognition and functioning is discussed with a view toward how this evidence might guide clinicians' prescribing practices. Three challenges regarding the use of cognitive enhancers in schizophrenia are discussed. First, laboratory constructs of cognition are not equivalent to cognitive skills and behaviors seen in the clinic. The evidence generated in clinical trials of cognitive enhancers may have uncertain ecological validity. Second, objective scores on cognitive tests often do not match clinicians' and patients' perceptions of cognitive deficits. Mismatch between objective and subjective assessments of cognition may complicate the monitoring of medication. Third, although reductions in disability are desired outcomes of cognitive enhancement, clinicians may not be able to rely on assessments of patients' functional status to determine whether cognition medications are effective. In summary, data on the clinical meaning of neuropsychological constructs, careful selection of outcome measures for randomized clinical trials, and effectiveness trials could help ensure that cognition-enhancing medications can be appropriately prescribed in usual practice settings to the patients who can benefit from them. C1 Univ Calif Los Angeles, Semel Inst, Hlth Serv Res Ctr, Los Angeles, CA 90024 USA. RP Bromley, E (reprint author), W Los Angeles Vet Affairs Med Ctr, MIRECC, 11301 Wilshire Blvd,Bldg 210A, Los Angeles, CA 90073 USA. EM ebromley@ucla.edu NR 106 TC 7 Z9 7 U1 4 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD APR PY 2007 VL 58 IS 4 BP 475 EP 481 DI 10.1176/appi.ps.58.4.475 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 154JQ UT WOS:000245503400010 PM 17412848 ER PT J AU Shi, LZ Ascher-Svanum, H Zhu, BJ Faries, D Montgomery, W Marder, SR AF Shi, Lizheng Ascher-Svanum, Haya Zhu, Baojin Faries, Douglas Montgomery, William Marder, Stephen R. TI Characteristics and use patterns of patients taking first-generation depot antipsychotics or oral antipsychotics for schizophrenia SO PSYCHIATRIC SERVICES LA English DT Article ID MEDICATION COMPLIANCE; ADHERENCE; CARE; STRATEGIES; DISORDERS; GUIDELINE; OUTCOMES; SYSTEM; COSTS; SCALE AB Objective: Investigators compared patient characteristics and antipsychotic use patterns between individuals with schizophrenia treated in usual care with first-generation depot antipsychotics and those treated with oral antipsychotics (first- or second-generation or both). Methods: Analyses used data from the U. S. Schizophrenia Care and Assessment Program, a large, prospective study of treatment for schizophrenia conducted July 1997 through September 2003. Participants were assessed at enrollment and every six months thereafter with patient self-report, validated psychiatric measures, and systematic extraction of medical records. Individuals treated with a first- generation depot antipsychotic at any time during the three-year study (N=569) were compared with those treated with only oral antipsychotics (N=1,617) on characteristics at enrollment and medication use pattern during the year after enrollment. Results: Compared with patients receiving only oral antipsychotics, participants treated with depot medications ( haloperidol or fluphenazine decanoate) were more likely to be African American (p <.001); less likely to be a veteran (p=. 005); had more psychiatric hospitalizations in the year before enrollment (p <.001); and were more likely to have been arrested (p <.001), to use alcohol and illicit substances (p <.001), and to show higher psychopathology, particularly psychotic symptoms and disorganized thinking (p <.01 for both). In the year after enrollment, participants treated with depot medications had a high mean medication possession ratio (91%), and most of the medication regimens (68%) were augmented with oral antipsychotics for prolonged durations (median of 144 days). Conclusion: Patients with schizophrenia treated with first-generation depot antipsychotics differed from those treated with only oral antipsychotics. Findings suggest that first- generation depot antipsychotics might address some unmet needs of a unique subgroup of patients with schizophrenia. C1 Tulane Univ, Sch Publ Hlth & Trop Med, Dept Hlth Syst Management, New Orleans, LA 70112 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Shi, LZ (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Dept Hlth Syst Management, 1440 Canal St,Suite 1900, New Orleans, LA 70112 USA. EM lshi1@tulane.edu NR 34 TC 59 Z9 59 U1 0 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD APR PY 2007 VL 58 IS 4 BP 482 EP 488 DI 10.1176/appi.ps.58.4.482 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 154JQ UT WOS:000245503400011 PM 17412849 ER PT J AU Niv, N Cohen, AN Sullivan, G Young, AS AF Niv, Noosha Cohen, Amy N. Sullivan, Greer Young, Alexander S. TI The MIRECC version of the global assessment of functioning scale: Reliability and validity SO PSYCHIATRIC SERVICES LA English DT Article ID IV AXIS-V; DSM-IV; QUALITY-ASSURANCE; OUTCOMES; GAF; SCHIZOPHRENIA; INTERVIEW; RATINGS; SYSTEM; CARE AB Objective: This study examined the reliability and convergent, discriminant, and predictive validity of the Mental Illness Research, Education, and Clinical Center (MIRECC) version of the Global Assessment of Functioning (GAF) scale. The MIRECC GAF measures occupational functioning, social functioning, and symptom severity on three subscales. Methods: MIRECC GAF ratings were obtained for 398 individuals with schizophrenia or schizoaffective disorder who were receiving treatment at three Veterans Affairs mental health clinics. Assessments were completed by using the Positive and Negative Syndrome Scale and the Quality of Life Interview at baseline and nine months later. Results: All three MIRECC GAF subscales exhibited very high levels of reliability. The occupational and symptom subscales showed good convergent and discriminant validity. The social subscale was related to measures of social functioning and, to a greater degree, symptom severity. The occupational and social subscales significantly predicted their respective domains at the nine-month follow-up. The symptom subscale predicted negative symptoms at follow-up; however, it did not predict positive symptoms or cognitive disorientation. Instead, the social subscale was predictive of cognitive disorientation at follow-up. When the standard GAF was routinely administered by clinicians, scores demonstrated little validity. Conclusions: The three MIRECC GAF subscales can be scored reliably, and they have good concurrent and predictive validity. Further work is needed on brief measures of patient functioning, especially measures of social functioning. C1 W Los Angeles VA, Vet Affairs Desert Pacific Mental Illness Res Edu, MIRECC, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. MIRECC, Vet Affairs S Cent, Little Rock, AR USA. Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. RP Niv, N (reprint author), W Los Angeles VA, Vet Affairs Desert Pacific Mental Illness Res Edu, MIRECC, 11301 Wilshire Blvd210A, Los Angeles, CA 90073 USA. EM noosha23@yahoo.com RI Young, Alexander/A-1523-2009 OI Young, Alexander/0000-0002-9367-9213 FU NIMH NIH HHS [MH-068639] NR 22 TC 29 Z9 29 U1 2 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD APR PY 2007 VL 58 IS 4 BP 529 EP 535 DI 10.1176/appi.ps.58.4.529 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 154JQ UT WOS:000245503400018 PM 17412856 ER PT J AU Hirose, M Regenbogen, SE Lipsitz, S Imanaka, Y Ishizaki, T Sekimoto, M Oh, EH Gawande, AA AF Hirose, Masahiro Regenbogen, Scott E. Lipsitz, Stuart Imanaka, Yuichi Ishizaki, Tatsuro Sekimoto, Miho Oh, Eun-Hwan Gawande, Atul A. TI Lag time in an incident reporting system at a university hospital in Japan SO QUALITY & SAFETY IN HEALTH CARE LA English DT Article ID HEALTH-CARE; ERROR; BARRIERS; QUALITY; SAFETY AB Background: Delays and underreporting limit the success of hospital incident reporting systems, but little is known about the causes or implications of delayed reporting. Setting and methods: The authors examined 6880 incident reports filed by physicians and nurses for three years at a national university hospital in Japan and evaluated the lag time between each incident and the submission of a report. Results: Although physicians and nurses reported nearly equal numbers of events resulting in major injury ( 32 v 31), physicians reported far fewer minor incidents ( 430 v 6387) and far fewer incidents overall ( 462 v 6418). In univariate analyses, lag time was significantly longer for physicians than nurses (3.79 v 2.20 days; p < 0.001). In multivariate analysis, physicians had adjusted reporting lag time 75% longer than nurses ( p < 0.001) and lag time for major injuries was 18% shorter than for minor injuries ( p = 0.011). Adjusted lag time in 2002 and 2004 were 34% longer than in 2003 ( p < 0.001). Conclusions: Physicians report fewer incidents than nurses and take longer to report them. Quantitative evaluation of lag time may facilitate improvements in incident reporting systems by distinguishing institutional obstacles to physician reporting from physicians' lesser willingness to report. C1 Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Kyoto Univ Hosp, Patient Safety Div, Kyoto 606, Japan. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Kyoto Univ, Grad Sch Med, Sch Publ Hlth, Dept Healthcare Econ & Qual Management, Kyoto, Japan. RP Hirose, M (reprint author), Kyoto Univ, Grad Sch Med, Sch Publ Hlth, Dept Healthcare Econ,Sakyou Ku, Yoshida Konoe Chou, Kyoto 6068501, Japan. EM mhirose@kuhp.kyoto-u.ac.jp OI Gawande, Atul/0000-0002-1824-9176 NR 23 TC 9 Z9 9 U1 1 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1475-3898 J9 QUAL SAF HEALTH CARE JI Qual. Saf. Health Care PD APR PY 2007 VL 16 IS 2 BP 101 EP 104 DI 10.1136/qshc.2006.019851 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 152WV UT WOS:000245393800005 PM 17403754 ER PT J AU Balshi, SF Wolfinger, GJ Balshi, TJ AF Balshi, Stephen F. Wolfinger, Glenn J. Balshi, Thomas J. TI An examination of immediately loaded dental implant stability in the diabetic patient using resonance frequency analysis (RFA) SO QUINTESSENCE INTERNATIONAL LA English DT Article DE bone-implant interface; diabetes; immediate loading; implant stability; resonance frequency analysis; Teeth in a Day ID MELLITUS AB Objectives: To evaluate the stability of 18 immediately loaded Branemark System dental implants in an insulin-controlled, diabetic, 71-year old patient over the first 30 months after surgery, and to correlate this data with implant stability in healthy patients. Method and Materials: Stability measurements were taken using resonance frequency analysis on all implants at surgery placement and at 5 postsurgical examinations (1, 2, 3, 6, and 30 months). Results: All 18 implants remained in function after 2.5 years of follow-up. The mean stability of the implants decreased 12.7% during the first 30 days, a value twice as much as seen in the general population. After the first 30 days, the stability of the implants increased slightly over the next 60 days. After 30 months of follow-up, the mean implant stability continued to increase, however, not to a value equal to that of the initial measurement taken at the time of implant placement. Conclusion: Despite the metabolic differences seen in diabetic patients, an immediate loading protocol can be successful and result in osseointegration. C1 Prosthodont Intermedica, Inst Facial Esthet, Ft Washington, PA 19034 USA. CM Ceram USA, Mahwah, NJ USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Balshi, SF (reprint author), Prosthodont Intermedica, Inst Facial Esthet, 467 Penn Ave,Suite 201, Ft Washington, PA 19034 USA. EM balshi2@aol.com NR 26 TC 10 Z9 11 U1 0 U2 0 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA SN 0033-6572 J9 QUINTESSENCE INT JI Quintessence Int. PD APR PY 2007 VL 38 IS 4 BP 271 EP 279 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 157BU UT WOS:000245694400002 PM 17432781 ER PT J AU Thrall, JH AF Thrall, James H. TI Building research programs in diagnostic radiology. Part III. Clinical and translational research SO RADIOLOGY LA English DT Editorial Material ID RESEARCH ENTERPRISE C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Massachusetts Gen Hosp, Dept Radiol, MZ FND 216,Box 9657,14 Fruit st, Boston, MA 02114 USA. EM thrall.james@mgh.harvard.edu NR 9 TC 7 Z9 7 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2007 VL 243 IS 1 BP 5 EP 9 DI 10.1148/radiol.2431062154 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 151TA UT WOS:000245312500003 PM 17392243 ER PT J AU MacMorris, M Kumar, M Lasda, E Larsen, A Kraemer, B Blumenthal, T AF MacMorris, Margaret Kumar, Madhur Lasda, Erika Larsen, Alison Kraemer, Brian Blumenthal, Thomas TI A novel family of C. elegans snRNPs contains proteins associated with trans-splicing SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE trans-splicing; operons; Caenorhabditis; SL snRNP; SmY ID SPLICED LEADER RNA; NUCLEAR RIBONUCLEOPROTEIN-PARTICLES; CAENORHABDITIS-ELEGANS; SL2; ORGANIZATION; EXPRESSION; OPERONS; CSTF-64; FORM; SUUM AB In many Caenorhabditis elegans pre-mRNAs, the RNA sequence between the 5' cap and the first 3' splice site is replaced by trans-splicing a short spliced leader (SL) from the Sm snRNP, SL1. C. elegans also utilizes a similar Sm snRNP, SL2, to trans-splice at sites between genes in polycistronic pre-mRNAs from operons. How do SL1 and SL2 snRNPs function in different contexts? Here we show that the SL1 snRNP contains a complex of SL75p and SL21p, which are homologs of novel proteins previously reported in the Ascaris SL snRNP. Interestingly, we show that the SL2 snRNP does not contain these proteins. However, SL75p and SL26p, a paralog of SL21p, are components of another Sm snRNP that contains a novel snRNA species, Sm Y. Knockdown of SL75p is lethal. However, knockdown of either SL21p or SL26p alone leads to cold-sensitive sterility, whereas knockdown of both SL21p and SL26p is lethal. This suggests that these two proteins have overlapping functions even though they are associated with different classes of snRNP. These phenotypic relationships, along with the association of SL26p with SL75p, imply that, like the SL1 RNA/Sm/SL75p/SL21p complex, the Sm Y/Sm/SL75p/SL26p complex is associated with trans-splicing. C1 Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA. Univ Colorado, Sch Med, Dept Biochem & Mol Genet, Aurora, CO 80045 USA. Univ Colorado, Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Boulder, CO 80309 USA. RP Blumenthal, T (reprint author), Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA. EM tom.blumenthal@colorado.edu FU NIA NIH HHS [P01 AG017586, P01 AG17586]; NIGMS NIH HHS [R01 GM042432, R01 GM42432] NR 27 TC 28 Z9 32 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD APR PY 2007 VL 13 IS 4 BP 511 EP 520 DI 10.1261/rna.426707 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 149QI UT WOS:000245161300008 PM 17283210 ER PT J AU Pyati, UJ Look, AT Hammerschmidt, M AF Pyati, Ujwal J. Look, A. Thomas Hammerschmidt, Matthias TI Zebrafish as a powerful vertebrate model system for in vivo studies of cell death SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE zebrafish; apoptosis; development; cancer; degenerative diseases; genetics ID FLUORESCENT PROTEIN GFP; ROHON-BEARD NEURONS; TRANSGENIC ZEBRAFISH; DANIO-RERIO; SUBCELLULAR-LOCALIZATION; P53-DEPENDENT APOPTOSIS; LATERAL-LINE; SURVIVAL; GENES; DIFFERENTIATION AB Understanding and manipulating cell death pathways are critical to our ability to treat human degenerative diseases and cancer. The zebrafish Danio rerio, a common aquatic pet, has evolved as a powerful tool for the discovery of genes regulating cellular suicide both during normal vertebrate development and after genetic or environmental insult. In this review, we describe the techniques that can be applied to studying cell death in zebrafish as well as highlighting what has been discovered so far. Finally, we discuss future perspectives in the field and how they relate to human disease. (c) 2006 Elsevier Ltd. All rights reserved. C1 Max Planck Inst Immunobiol, D-79108 Freiburg, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hammerschmidt, M (reprint author), Max Planck Inst Immunobiol, Stubeweg 51, D-79108 Freiburg, Germany. EM hammerschmid@immunbio.mpg.de FU NCI NIH HHS [CA119066-01]; NHLBI NIH HHS [5T32 HL07623-20]; NIGMS NIH HHS [2R01-GM063904] NR 96 TC 53 Z9 57 U1 2 U2 13 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD APR PY 2007 VL 17 IS 2 BP 154 EP 165 DI 10.1016/j.semcancer.2006.11.007 PG 12 WC Oncology SC Oncology GA 150IQ UT WOS:000245209900008 PM 17210257 ER PT J AU DeAngelo, DJ AF DeAngelo, Daniel J. TI Role of imatinib-sensitive tyrosine kinases in the pathogenesis of chronic myeloproliferative disorders SO SEMINARS IN HEMATOLOGY LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOMONOCYTIC LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; FACTOR RECEPTOR-BETA; COLONY-STIMULATING FACTOR; GROWTH-FACTOR RECEPTORS; COILED-COIL DOMAIN; BCR-ABL; C-KIT; FUSION PARTNER C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP DeAngelo, DJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. EM ddeangelo@partners.org NR 80 TC 1 Z9 1 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 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD APR PY 2007 VL 44 IS 2 SU 2 BP S17 EP S30 DI 10.1053/j.seminhematol.2007.02.001 PG 14 WC Hematology SC Hematology GA 158UC UT WOS:000245819400003 ER PT J AU Taher, A Nathan, D Porter, J AF Taher, Ali Nathan, David Porter, John TI Evaluation of iron levels to avoid the clinical sequelae of iron overload SO SEMINARS IN HEMATOLOGY LA English DT Article; Proceedings Paper CT 11th Congress of the European-Haematology-Association CY JUN 15-18, 2006 CL Amsterdam, NETHERLANDS SP European Haematol Assoc ID THALASSEMIA MAJOR; CHELATION-THERAPY; MYOCARDIAL IRON; MAGNETIC-RESONANCE; SERUM FERRITIN; PLASMA IRON; DIAGNOSIS; DISEASE; DESFERRIOXAMINE; METABOLISM AB The success of transfusion therapy for the treatment of chronic anemia has resulted in the additional clinical challenge of managing iron overload and related morbidity and mortality issues. Effective chelation therapy can control iron levels, and regular assessment of body iron burden is crucial to guide initiation and ensure correct dosing of treatment. A range of techniques are now available that allow accurate assessment of iron burden through evaluation of serum ferritin levels, or the concentration of iron in key organs such as the liver and heart. Studies have enabled threshold values to be identified, above which the risk of serious clinical sequelae is increased. C1 Amer Univ Beirut, Dept Internal Med, Beirut 11072020, Lebanon. Dana Farber Canc Inst, Boston, MA 02115 USA. UCL, Dept Haematol, London, England. RP Taher, A (reprint author), Amer Univ Beirut, Dept Internal Med, POB 11-0236, Beirut 11072020, Lebanon. EM ataher@aub.edu.lb OI Porter, John/0000-0003-3000-9359; Taher, Ali/0000-0001-8515-2238 NR 36 TC 1 Z9 2 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 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD APR PY 2007 VL 44 IS 2 SU 3 BP S2 EP S6 DI 10.1053/j.seminhematol.2007.03.002 PG 5 WC Hematology SC Hematology GA 173ZO UT WOS:000246911200002 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Biological basis of breast cancer: An introduction SO SEMINARS IN ONCOLOGY LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2007 VL 34 IS 2 SU 3 BP S1 EP S3 DI 10.1053/j.seminoncol.2007.03.018 PG 3 WC Oncology SC Oncology GA 175JI UT WOS:000247009500001 PM 17512430 ER PT J AU Cunningham, MT Brandt, JT Chandler, WL Eby, CS Hayes, TE Krishnan, J Lefkowitz, JB Olson, JD Stasik, CJ Teruya, J Van Cott, EM AF Cunningham, Mark T. Brandt, John T. Chandler, Wayne L. Eby, Charles S. Hayes, Timothy E. Krishnan, Jayashree Lefkowitz, Jerry B. Olson, John D. Stasik, Christopher J. Teruya, Jun Van Cott, Elizabeth M. TI Quality assurance in hemostasis: The perspective from the College of American Pathologists proficiency testing program SO SEMINARS IN THROMBOSIS AND HEMOSTASIS LA English DT Article DE coagulation; hemostasis testing; proficiency testing; quality assurance; quality control ID PARTIAL THROMBOPLASTIN TIME; CAP SURVEY PROGRAM; FACTOR-VIII ASSAYS; PROTHROMBIN TIME; PERFORMANCE; COAGULATION; HEPARIN; STANDARDS; IX AB External quality assurance (EQA) is an important component of the total quality assurance program of a clinical hemostasis laboratory. The College of American Pathologists (CAP) helps meet this requirement by providing a proficiency testing program that evaluates a broad range of hemostasis methods and analytes. This article reviews the published experience of the CAP proficiency testing program in hemostasis. The purpose is to formulate general conclusions about the benefits of EQA. Between 1963 and 2006, the performance characteristics of a variety of tests have been evaluated, including the prothrombin time, activated partial thromboplastin time, coagulation factor activity assays (e.g., fibrinogen, factor [F] VIII, FIX, FXI), von Willebrand factor assays, unfractionated heparin monitoring, lupus anticoagulant testing, and platelet function. Based on the results of these evaluations, the major benefits of EQA are to (1) enhance patient care and safety through improved laboratory testing; (2) characterize test accuracy and precision across multiple methods; (3) correlate specific method variables with accuracy and precision; (4) identify interfering substances and quantify their effects across multiple methods; (5) identify clinical laboratories that are at risk for poor performance so that their performance can improve; and (6) satisfy accreditation and regulatory requirements. C1 Univ Kansas, Med Ctr, Dept Pathol, Kansas City, KS 66160 USA. Eli Lilly Corp Ctr, Indianapolis, IN USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. Maine Med Ctr, Dept Pathol & Lab Med, Portland, ME 04102 USA. Washington Hosp Ctr, Dept Pathol, Washington, DC 20010 USA. Univ Colorado, Hlth Sci Ctr, Dept Pathol, Aurora, CO USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78285 USA. Texas Childrens Hosp, Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Cunningham, MT (reprint author), Univ Kansas, Med Ctr, Dept Pathol, 3901 Rainbow Blvd,Mail Stop 4049, Kansas City, KS 66160 USA. EM mcunningham@kumc.edu NR 30 TC 21 Z9 21 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0094-6176 J9 SEMIN THROMB HEMOST JI Semin. Thromb. Hemost. PD APR PY 2007 VL 33 IS 3 BP 250 EP 258 DI 10.1055/s-2007-971811 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 155PS UT WOS:000245591000006 PM 17427059 ER PT J AU Shetty, SK Nelson, EN Lawrimore, TM Palmer, WE AF Shetty, Sanjay K. Nelson, Erik N. Lawrimore, Tara M. Palmer, William E. TI Use of gadolinium chelate to confirm epidural needle placement in patients with an iodinated contrast reaction SO SKELETAL RADIOLOGY LA English DT Article DE epidural; spine; spinal; gadolinium; injections ID LOW-BACK-PAIN; STEROID INJECTIONS; ANGIOGRAPHY; EXPERIENCE; MANAGEMENT; SCIATICA; EFFICACY; MEDIA; BLOCK AB Objective When performing epidural steroid injections for the management of chronic back pain, imaging guidance and a limited epidurogram improve accuracy of needle placement and ensure appropriate delivery of the injectate into the epidural space. We describe our experience using a gadolinium chelate as an alternative contrast agent for limited epidurography in patients with a history of an iodinated contrast reaction. Design Thirty-eight of 2,067 (1.8%) epidural steroid injections performed in our department over a 25-month period (December 2003-January 2006) employed gadolinium. All injections were performed in the lumbar spine employing a paramedian interlaminar approach. Procedural notes and patient charts were reviewed to evaluate for immediate or delayed complications related to incorrect intrathecal or intravascular needle placement. A retrospective analysis of selected fluoroscopic spot images was performed to evaluate confidence of epidural needle placement; this analysis compared these spot images against those obtained from age- and gender-matched control patients in whom iodinated contrast was used to confirm needle placement. Results Real-time fluoroscopic guidance permitted confident visualization of an epidurogram at the time of procedure in all 38 cases as documented in the procedural report, and no procedure resulted in a complication due to incorrect needle placement. Retrospective review of fluoroscopic spot images revealed at least moderate confidence of epidural needle placement by both readers in 29/38 cases (76.3%). Fluoroscopic spot images obtained using gadolinium yielded significantly less confidence than images obtained in control patients whose procedures were performed using iodinated contrast (P < 0.01). However, operators were sufficiently confident in needle placement based on real-time fluoroscopic images (not available in our subsequent review) to inject anesthestic in all 38 cases, despite the immediate consequences that could result from intrathecal administration. During the same time period, there were 11/2,067 (0.5%) instances of intrathecal needle placement discovered during attempted epidurography despite the use of fluoroscopy for needle guidance and reliance on loss-of-resistance technique. Conclusion Gadolinium chelate represents a safe and useful alternative contrast agent for confirmation of epidural needle placement in patients with an iodinated contrast allergy. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Musculoskeletal Radiol, Boston, MA 02114 USA. RP Shetty, SK (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. EM shetty@post.harvard.edu NR 27 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD APR PY 2007 VL 36 IS 4 BP 301 EP 307 DI 10.1007/s00256-006-0228-8 PG 7 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 140EE UT WOS:000244486200005 PM 17187289 ER PT J AU Morgenthaler, T Alessi, C Friedman, L Owens, J Kapur, V Boehlecke, B Brown, T Chesson, A Coleman, J Lee-Chiong, T Pancer, J Swick, TJ AF Morgenthaler, Timothy Alessi, Cathy Friedman, Leah Owens, Judith Kapur, Vishesh Boehlecke, Brian Brown, Terry Chesson, Andrew, Jr. Coleman, Jack Lee-Chiong, Teofilo Pancer, Jeffrey Swick, Todd J. TI Practice parameters for the use of actigraphy in the assessment of sleep and sleep disorders: An update for 2007 SO SLEEP LA English DT Review DE circadian rhythms; actigraphy; advanced sleep phase syndrome; delayed sleep phase syndrome; shift work disorder ID NURSING-HOME RESIDENTS; PLACEBO-CONTROLLED TRIAL; BRIGHT LIGHT TREATMENT; RESTLESS LEGS SYNDROME; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; FULL-TERM INFANTS; ALZHEIMERS-DISEASE; CIRCADIAN-RHYTHMS; MORNINGNESS-EVENINGNESS; POSTMENOPAUSAL WOMEN AB Background: Actigraphy is increasingly used in sleep research and the clinical care of patients with sleep and circadian rhythm abnormalities. The following practice parameters update the previous practice parameters published in 2003 for the use of actigraphy in the study of sleep and circadian rhythms. Methods: Based upon a systematic grading of evidence, members of the Standards of Practice Committee, including those with expertise in the use of actigraphy, developed these practice parameters as a guide to the appropriate use of actigraphy, both as a diagnostic tool in the evaluation of sleep disorders and as an outcome measure of treatment efficacy in clinical settings with appropriate patient populations. Recommendations: Actigraphy provides an acceptably accurate estimate of sleep patterns in normal, healthy adult populations and inpatients suspected of certain sleep disorders. More specifically, actigraphy is indicated to assist in the evaluation of patients with advanced sleep phase syndrome (ASPS), delayed sleep phase syndrome (DSPS), and shift work disorder. Additionally, there is some evidence to support the use of actigraphy in the evaluation of patients suspected of jet lag disorder and non-24hr sleep/wake syndrome (including that associated with blindness). When polysomnography is not available, actigraphy is indicated to estimate total sleep time in patients with obstructive sleep apnea. In patients with insomnia and hypersomnia, there is evidence to support the use of actigraphy in the characterization of circadian rhythms and sleep patterns/ disturbances. In assessing response to therapy, actigraphy has proven useful as an outcome measure in patients with circadian rhythm disorders and insomnia. In older adults (including older nursing home residents), in whom traditional sleep monitoring can be difficult, actigraphy is indicated for characterizing sleep and circadian patterns and to document treatment responses. Similarly, in normal infants and children, as well as special pediatric populations, actigraphy has proven useful for delineating sleep patterns and documenting treatment responses. Conclusions: Recent research utilizing actigraphy in the assessment and management of sleep disorders has allowed the development of evidence-based recommendations for the use of actigraphy in the clinical setting. Additional research is warranted to further refine and broaden its clinical value. C1 Mayo Clin, Rochester, MN USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst Sepulveda, Los Angeles, CA USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Brown Univ, Rhode Isl Hosp, Providence, RI 02903 USA. Univ Washington, Seattle, WA 98195 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. St Joseph Mem Hosp, Murphysboro, IL USA. LSU Hlth Sci Ctr, Shreveport, LA USA. Murfreesboro Med Ctr, Murfreesboro, TN USA. Natl Jewish Med & Res Ctr, Denver, CO USA. Houston Sleep Ctr, Houston, TX USA. RP Morgenthaler, T (reprint author), Amer Acad Sleep Med, Stand Practice Comm, 1 Westbrook Corp Ctr,Suite 920, Westchester, IL 60154 USA. EM aasm@aasmnet.org RI Kapur, Vishesh/K-1054-2014; OI Kapur, Vishesh/0000-0002-5417-1097; Morgenthaler, Timothy/0000-0002-2614-3793 NR 117 TC 454 Z9 461 U1 10 U2 55 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 1 PY 2007 VL 30 IS 4 BP 519 EP 529 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 160UA UT WOS:000245966600018 PM 17520797 ER PT J AU Peteet, JR AF Peteet, John R. TI Should clinicians prescribe forgiveness? SO SOUTHERN MEDICAL JOURNAL LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Peteet, JR (reprint author), Dana Farber Canc Inst, 44 Binney St,Gossman 411, Boston, MA 02115 USA. EM John_Peteet@dfci.harvard.edu NR 6 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD APR PY 2007 VL 100 IS 4 BP 339 EP 340 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 172AX UT WOS:000246777600001 PM 17458387 ER PT J AU Basile, JN AF Basile, Jan N. TI Fixed-dose combination therapy in the treatment of hypertension: Ready for prime time SO SOUTHERN MEDICAL JOURNAL LA English DT Editorial Material ID BLOOD-PRESSURE C1 Med Univ S Carolina, Div Gen Internal Med Geriatr, Ralph H Johnson VA Med Ctr, Primary Care Serv Line, Charleston, SC 29401 USA. RP Basile, JN (reprint author), Med Univ S Carolina, Div Gen Internal Med Geriatr, Ralph H Johnson VA Med Ctr, Primary Care Serv Line, 109 Bee St, Charleston, SC 29401 USA. EM jan.basile@med.va.gov NR 7 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD APR PY 2007 VL 100 IS 4 BP 343 EP 344 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 172AX UT WOS:000246777600003 PM 17458389 ER PT J AU LaRaia, AV Waxman, AB AF LaRaia, Anne V. Waxman, Aaron B. TI Pulmonary arterial hypertension: Evaluation and management SO SOUTHERN MEDICAL JOURNAL LA English DT Review DE pulmonary hypertension; pulmonary vascular disease; prostacyclin; endothelin ID DOPPLER-ECHOCARDIOGRAPHY; TRICUSPID REGURGITATION; INHALED ILOPROST; THERAPY; DISEASE; EPOPROSTENOL; PROSTACYCLIN; ULTRASOUND; DIAGNOSIS; SURVIVAL AB Pulmonary arterial hypertension (PAH), a rare disease involving the pulmonary vascular circuit, is defined as an elevation in pulmonary arterial pressures and is characterized by symptoms of dyspnea, chest pain, and syncope. If left untreated, the disease carries a high mortality rate, with the most common cause of death being decompensated right heart failure. Over the past 5 years, there have been significant advances in this field in regards to understanding the pathogenesis, diagnosis, and classification of PAH. The availability of newer drugs has resulted in a radical change in the management of this disease with significant improvement in both quality of life and mortality. Ongoing research promises to lead to a more comprehensive understanding of the genetics, etiology, and pathogenesis of pulmonary arterial hypertension, which may ultimately translate into more effective therapeutic options. C1 Harvard Univ, Massachusetts Gen Hosp, Pulm Vasc Dis Program, Pulm Crit Care Unit,Med Sch, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Crit Care Unit, Sch Med, Boston, MA 02114 USA. RP Waxman, AB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Pulm Vasc Dis Program, Pulm Crit Care Unit,Med Sch, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. EM abwaxman@partners.org NR 49 TC 8 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD APR PY 2007 VL 100 IS 4 BP 393 EP 399 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 172AX UT WOS:000246777600014 PM 17458400 ER PT J AU Muller, AC Diestelhorst, A Kuhnt, T Kuhn, R Fornara, P Scholz, HJ Dunst, J Zietman, AL AF Mueller, Arndt-Christian Diestelhorst, Andrea Kuhnt, Thomas Kuehn, Reinhard Fornara, Paolo Scholz, Hans-Joerg Dunst, Juergen Zietman, Anthony Laurence TI Organ-sparing treatment of advanced bladder cancer - Paclitaxel as a radiosensitizer SO STRAHLENTHERAPIE UND ONKOLOGIE LA English DT Article DE bladder cancer; radiotherapy; chemotherapy; bladder preservation ID TRANSITIONAL-CELL CARCINOMA; COMBINED-MODALITY TREATMENT; RADIATION-THERAPY; DEFINITIVE RADIOTHERAPY; CONCURRENT CISPLATIN; RADICAL RADIOTHERAPY; IN-VITRO; PRESERVATION; CHEMOTHERAPY; COMBINATION AB Background and Purpose: Transurethral resection of bladder tumor (TUR-BT) and radiochemotherapy with cisplatin achieve high rates of bladder preservation and survival figures identical to radical cystectomy in muscle-invasive bladder cancers. The authors have investigated the potential use of paclitaxel in a radiochemotherapy protocol for patients with inoperable bladder carcinomas and mainly contraindications to cisplatin. Patients and Methods: Between October 1997 to August 2004, 42 patients (median age 71 years) suffering from muscle-invasive (n = 32) or recurrent (n = 10) bladder cancers were treated with a paclitaxel-containing radiochemotherapy (paclitaxel 25-35 mg/m(2) twice weekly) after TUR-BT (R0/1/2/x in n = 18/4/14/3) or cystectomy with residual tumor (n = 3). Five patients received additional cisplatin. Radiation treatment was administered to a total dose of 45-60 Gy. Results: 76.2% completed the planned regimen. Adaptations of treatment were mainly required due to diarrhea. Grade 3/4 toxicities occurred in 15/1 patients. Severe renal toxicities did not occur. 28 patients underwent restaging TUR-BT 6 weeks after radiochemotherapy (complete remission/partial remission/progressive disease: n = 24/3/1). Three patients developed a local recurrence and four distant metastases. Seven patients died from tumor, six of other reasons. Conclusions: Radiochemotherapy with paclitaxel was feasible and this bladder approach needs further investigation to evaluate whether paclitaxel could become a substitute for cisplatin. C1 Univ Halle, Dept Radiat Oncol, Halle, Germany. Univ Tubingen, Dept Radiooncol, D-72076 Tubingen, Germany. Martha Maria Hosp Halle, Dept Urol, Halle, Germany. Univ Halle, Dept Urol, Halle, Germany. Univ Lubeck, Dept Radiat Oncol, Lubeck, Germany. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Muller, AC (reprint author), Univ Tubingen, Klin Radioonkol, Hoppe Seyler Str 3, D-72076 Tubingen, Germany. RI Dunst, Juergen/D-2138-2010 NR 28 TC 15 Z9 16 U1 0 U2 2 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0179-7158 J9 STRAHLENTHER ONKOL JI Strahlenther. Onkol. PD APR PY 2007 VL 183 IS 4 BP 177 EP 183 DI 10.1007/s00066-007-1651-z PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 153RK UT WOS:000245452600003 PM 17406798 ER PT J AU Cramer, SC Koroshetz, WJ Finklestein, SP AF Cramer, Steven C. Koroshetz, Walter J. Finklestein, Seth P. TI The case for modality-specific outcome measures in clinical trials of stroke recovery-promoting agents SO STROKE LA English DT Article DE clinical trials; outcome measures; stroke recovery ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; MOTOR RECOVERY; FUNCTIONAL RECOVERY; THERAPY; APHASIA; GROWTH; RATS; STIMULATION; INFARCTION AB Clinical trials for acute stroke treatments have often used composite clinical rating scales as primary outcome measures of treatment efficacy. Recent preclinical and clinical studies highlight the opportunity to administer treatments in the subacute and chronic phase of stroke to promote neurological recovery. Because different neurological deficits recover to different extents at different rates after stroke, putative stroke recovery-promoting treatments may exert differential effects on various functional aspects of stroke recovery. For this reason, we propose that the use of modality-specific outcome measures may be best suited as primary end points in clinical trials of stroke recovery-promoting agents. The use of such end points may result in a more selective labeling of stroke recovery treatments. C1 Biotrofix Inc, Needham, MA 02494 USA. Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA. Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92717 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Finklestein, SP (reprint author), Biotrofix Inc, 604 Webster St, Needham, MA 02494 USA. EM seth.finklestein@biotrofix.com FU AHRQ HHS [1 R01 HS11392-01A1]; NINDS NIH HHS [1P50 NS051343] NR 39 TC 35 Z9 36 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2007 VL 38 IS 4 BP 1393 EP 1395 DI 10.1161/01.STR.0000260087.67462.80 PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 150JD UT WOS:000245211400055 PM 17332455 ER PT J AU Ryon, M Pai, R Sauer, J Rattner, D Thompson, C AF Ryon, M. Pai, R. Sauer, J. Rattner, D. Thompson, C. TI Evaluating an optimal gastric closure method for transgastric surgery SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE transgastric surgery; gastric closure; gastrotomy closure; pursestring suture ID PORCINE MODEL; PARTIAL HYSTERECTOMY; SURVIVAL; OOPHORECTOMY; TUBECTOMY AB Background: The transgastric approach is currently being studied as a potentially less invasive alternative to conventional laparoscopy for intra-abdominal surgery. A major obstacle to overcome is the closure of the transgastric incision in a rapid, reproducible, and safe manner. The effectiveness of various techniques for gastrotomy closure were compared by assessing leak pressures in an ex vivo porcine stomach model. Methods: Whole stomachs from adult white pigs were suspended in a Plexiglas box to facilitate endoscopic technique. Standard gastrotomies were made by needle knife incision and dilation with a controlled radial expansion (CRE) balloon. The first arm used standard QuickClips (TM); the second, a prototype device developed by LSI Solutions; the third, hand-sewn by a senior surgeon; the final, a control with open gastrotomy. Five stomachs were tested per study arm. After closure, each stomach was inflated by an automated pressure gauge. The pressures to achieve air leakage and liquid leakage were recorded. Results: The unclosed controls demonstrated air leakage at a median pressure of 15 mmHg, representing baseline system resistance. The QuickClip closures leaked air at a median pressure of 33 mmHg. The prototype gastrotomy device yielded the highest median air leak pressure of 85 mmHg while dramatically diminishing time for incision and gastrotomy closure to approximately 5 min. The hand-sewn closures leaked air at a median pressure of 47 mmHg. Using Kruskal-Wallis statistical analysis, the comparisons were significant (p = 0.0019). Post hoc paired comparisons using MULTTEST procedure with both Bonferroni and bootstrap adjustments revealed that the difference between prototype and clips was significant; prototype versus hand-sewn was not. Liquid-leak pressures produced similar results. Conclusions: The prototype device decreases procedure time and yields leak-resistant gastrotomy closures that are superior to clips and rival hand-sewn interrupted stitches. C1 Brigham & Womens Hosp, Dept Gastroenterol, Boston, MA 02115 USA. LSI Solut, New York, NY 14564 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Thompson, C (reprint author), Brigham & Womens Hosp, Dept Gastroenterol, 75 Francis St, Boston, MA 02115 USA. NR 11 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD APR PY 2007 VL 21 IS 4 BP 677 EP 680 DI 10.1007/s00464-006-9075-x PG 4 WC Surgery SC Surgery GA 155QO UT WOS:000245593200033 ER PT J AU Armstrong, AW Dorer, DJ Lugn, NE Kvedar, JC AF Armstrong, April W. Dorer, David J. Lugn, Nancy E. Kvedar, Joseph C. TI Economic evaluation of interactive teledermatology compared with conventional care SO TELEMEDICINE JOURNAL AND E-HEALTH LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; STORE-AND-FORWARD; REALTIME TELEDERMATOLOGY; COST-BENEFIT; NEW-ZEALAND; TIME; DERMATOLOGY; TECHNOLOGY AB Teledermatology offers a means of providing specialist care to underserved patients. The objectives of this study were to compare the costs of interactive teledermatology with conventional care, and to evaluate from a healthcare provider perspective whether interactive teledermatology is economically viable in the northeastern region of the United States. We studied the interactive teledermatology practice at Nantucket Cottage Hospital on Nantucket Island and the ambulatory clinics at the Massachusetts General Hospital in Boston, Massachusetts. The cost-minimization analysis compared the costs of an interactive teledermatology practice with that of a face-to-face dermatology clinic. One-way sensitivity analyses examined the effect of varying the costs of technology, physician compensation, or clinic space on the overall cost of interactive teledermatology. We also assessed the economic viability of the interactive teledermatology practice by comparing the operating costs with reimbursements. The total hourly operating costs for the interactive teledermatology practice on Nantucket Island and the face-to-face clinic in Boston were $274 and $346, respectively. Three separate one-way sensitivity analyses showed that, for the cost of the teledermatology practice to equal that of the conventional clinic, the cost of teledermatology technology could increase by 9.3-fold, dermatologists working at the teledermatology practice could be compensated up to $197 an hour, or the cost of teledermatology clinic space could reach $57 an hour. Our analysis also showed that the hourly reimbursement for the teledermatology practice was $487, which exceeded its hourly operating cost of $274. The cost of operating an interactive teledermatology practice in a remote region may be less than that of a conventional clinic in a nearby urban center in the northeastern area of the United States. From a healthcare provider perspective, interactive teledermatology can be an economically viable means of providing dermatological care to remote regions. C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Percept Informat Inc, Waltham, MA USA. RP Armstrong, AW (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 55 Fruit St,Bartlett Hall 616, Boston, MA 02114 USA. EM awarmstrong@partners.org NR 21 TC 29 Z9 29 U1 0 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED J E-HEALTH JI Telemed. J. e-Health PD APR PY 2007 VL 13 IS 2 BP 91 EP 99 DI 10.1089/tmj.2006.0035 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 165JO UT WOS:000246302000018 PM 17489695 ER PT J AU Wong, E Rosen, LS Mulay, M VanVugt, A Dinolfo, M Tomoda, C Sugawara, M Hershman, JM AF Wong, Elaine Rosen, Lee S. Mulay, Marilyn VanVugt, Andy Dinolfo, Melissa Tomoda, Chisato Sugawara, Masahiro Hershman, Jerome M. TI Sunitinib induces hypothyroidism in advanced cancer patients and may inhibit thyroid peroxidase activity SO THYROID LA English DT Article ID TYROSINE KINASE INHIBITOR; ENDOTHELIAL GROWTH-FACTOR; IN-VIVO; ANGIOGENESIS; SU11248 AB Objective: Sunitinib is a novel tyrosine kinase inhibitor with antitumor and antiangiogenic effects. An observed higher than expected rate of hypothyroidism in sunitinib-treated patients prompted assessment of the incidence of hypothyroidism. Design: Patients taking sunitinib had their thyroid function tests (TFTs) assessed via chart review. To explore potential effects on the thyroid, we examined the antiperoxidase activity of sunitinib by in vitro testing its effect on guaiacol oxidation and protein iodination by lactoperoxidase. Main outcome: Of the 89 patients who took sunitinib, 49 patients were excluded from analysis for several reasons. Of the remaining 40 patients, 21 (53%, 24% of the original 89) developed elevated thyrotropin (TSH) after a median of 5 months ( range 1 - 36 months). Median TSH was 21.4 mU/L ( range 4.6 - 174 mU/L). In vitro, sunitinib had antiperoxidase activity that was about one-fourth the potency of propylthiouracil. Conclusions: Of the 40 patients who had TFTs assessed after starting sunitinib, 53% developed elevated TSH. We recommend that all patients treated with sunitinib be monitored for hypothyroidism. The mechanism of the antithyroid effect appears to be inhibition of peroxidase activity. Further research is needed to confirm the mechanism by which sunitinib induces hypothyroidism. C1 Vet Adm Greater Los Angeles Healthcare Syst, Dept Endocrinol & Diabet, Los Angeles, CA USA. Premiere Oncol, Los Angeles, CA USA. RP Hershman, JM (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,111-D, Los Angeles, CA 90073 USA. EM jerome.hershman@va.gov NR 14 TC 112 Z9 114 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD APR PY 2007 VL 17 IS 4 BP 351 EP 355 DI 10.1089/thy.2006.0308 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 165AN UT WOS:000246276300010 PM 17465866 ER PT J AU Weinand, C Gupta, R Huang, AY Weinberg, E Madisch, I Qudsi, RA Neville, CM Pomerantseva, I Vacanti, JP AF Weinand, Christian Gupta, Rajiv Huang, Albert Y. Weinberg, Eli Madisch, Ijad Qudsi, Rameez A. Neville, Craig M. Pomerantseva, Irina Vacanti, Joseph P. TI Comparison of hydrogels in the in vivo formation of tissue-engineered bone using mesenchymal stem cells and beta-tricalcium phosphate SO TISSUE ENGINEERING LA English DT Article ID MARROW STROMAL CELLS; MECHANICAL-PROPERTIES; BIOCHEMICAL MARKERS; ALGINATE HYDROGELS; CALVARIAL DEFECTS; VOLUME CT; SCAFFOLD; CARTILAGE; VITRO; DIFFERENTIATION AB Availability of grafts and morbidity at the donor site limit autologous transplantation in patients requiring bone reconstruction. A tissue-engineering approach can overcome these limitations by producing bone-like tissue of custom shape and size from isolated cells. Several hydrogels facilitate osteogenesis on porous scaffolds; however, the relative suitability of various hydrogels has not been rigorously assessed. Fibrin glue, alginate, and collagen I hydrogels were mixed with swine bone marrow-derived differentiated mesenchymal stem cells (MSCs), applied to 3-dimensionally printed porous beta-tricalcium phosphate (b-TCP) scaffolds and implanted subcutaneously in nude mice. Although noninvasive assessment of osteogenesis in 3 dimensions is desirable for monitoring new bone formation in vivo, correlations with traditional histological and mechanical testing need to be established. High-resolution volumetric computed tomography (VCT) scanning, histological examination, biomechanical compression testing, and osteonectin (ON) expression were performed on excised scaffolds after 1, 2, 4, and 6 weeks of subcutaneous implantation in mice. Statistical correlation analyses were performed between radiological density, stiffness, and ON expression. Use of collagen I as a hydrogel carrier produced superior bone formation at 6 weeks, as demonstrated using VCT scanning with densities similar to native bone and the highest compression values. Continued contribution of the seeded MSCs was demonstrated using swine-specific messenger ribonucleic acid probes. Radiological density values correlated closely with the results of histological and biomechanical testing and ON expression. High-resolution VCT is a promising method for monitoring osteogenesis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Surg, Warren 1151,55 Fruit St, Boston, MA 02114 USA. EM jvacanti@partners.org NR 54 TC 39 Z9 39 U1 0 U2 11 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD APR PY 2007 VL 13 IS 4 BP 757 EP 765 DI 10.1089/ten.2006.0083 PG 9 WC Cell & Tissue Engineering SC Cell Biology GA 156WP UT WOS:000245680900011 PM 17223744 ER PT J AU Merino, JJ Aller, MA Sanchez-Patan, F Rubio, S Loscertales, M Arias, JL Arias, J AF Merino, J. J. Aller, M. A. Sanchez-Patan, F. Rubio, S. Loscertales, M. Arias, J. L. Arias, J. TI Regulation of chemokines levels upon liver encephalopathy induction through portal stenosis in hypertensive rats: Does SDF1 alpha play a role in repair mechanisms in the hippocampus? SO TISSUE ENGINEERING LA English DT Meeting Abstract CT 2nd International Congress on Regenerative Biology/2nd International Congress on Bio-Nano-Interface CY OCT 09-11, 2006 CL Stuttgart, GERMANY SP Soc Promot Biotechnol, BioRegioSTERN, BIOPRO Baden Wurttemberg GmbH, Fraunhofer Inst Grenzflachen & Bioverfahrenstechnik C1 UNED Neurobiol Lab, Dept Psychobiol, Madrid, Spain. Univ Complutense, Coll Med, Dept Surg, E-28040 Madrid, Spain. Univ Autonoma Madrid, Biol Psychol Dept, Madrid, Spain. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Oviedo, Dept Psychobiol, Oviedo, Spain. RI Rubio, Sandra/C-1290-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD APR PY 2007 VL 13 IS 4 BP 894 EP 895 PG 2 WC Cell & Tissue Engineering SC Cell Biology GA 156WP UT WOS:000245680900097 ER PT J AU Albers, AB Siegel, M Cheng, DM Biener, L Rigotti, NA AF Albers, Alison B. Siegel, Michael Cheng, Debbie M. Biener, Lois Rigotti, Nancy A. TI Effect of smoking regulations in local restaurants on smokers' anti-smoking attitudes and quitting behaviours SO TOBACCO CONTROL LA English DT Article ID ENVIRONMENTAL TOBACCO-SMOKE; FREE WORKPLACES; CESSATION; MASSACHUSETTS; PREVALENCE; EXPOSURE; YOUTHS; ADULTS; IMPACT; TOWN AB Objective: To examine the effect of smoking regulations in local restaurants on anti-smoking attitudes and quitting behaviours among adult smokers. Design: Hierarchical linear modelling (HLM) was used to assess the relationship between baseline strength of town-level restaurant smoking regulation and follow-up (1) perceptions of the social acceptability of smoking and ( 2) quitting behaviours. Setting: Each of the 351 Massachusetts towns was classified as having strong (complete smoking ban) or weak (all other and no smoking restrictions) restaurant smoking regulations. Subjects: 1712 adult smokers of Massachusetts aged >= 18 years at baseline who were interviewed via random-digit-dial telephone survey in 2001-2 and followed up 2 years later. Main outcome measures: Perceived social acceptability of smoking in restaurants and bars, and making a quit attempt and quitting smoking. Results: Among adult smokers who had made a quit attempt at baseline, living in a town with a strong regulation was associated with a threefold increase in the odds of making a quit attempt at follow-up (OR = 3.12; 95% CI 1.51 to 6.44). Regulation was found to have no effect on cessation at follow-up. A notable, although marginal, effect of regulation was observed for perceiving smoking in bars as socially unacceptable only among smokers who reported at baseline that smoking in bars was socially unacceptable. Conclusions: Although local restaurant smoking regulations did not increase smoking cessation rates, they did increase the likelihood of making a quit attempt among smokers who had previously tried to quit, and seem to reinforce anti-social smoking norms among smokers who already viewed smoking in bars as socially unacceptable. C1 Boston Univ, Sch Publ Hlth, Social & Behav Sci Dept, Boston, MA 02118 USA. Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02215 USA. Univ Massachusetts, Ctr Survey Res, Boston, MA 02125 USA. Massachusetts Gen Hosp, Gen Med Div, Boston, MA 02114 USA. Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Albers, AB (reprint author), Boston Univ, Sch Publ Hlth, Social & Behav Sci Dept, 715 Albany St,TW2, Boston, MA 02118 USA. EM aalbers@bu.edu OI Biener, Lois/0000-0002-4130-8138 FU NCI NIH HHS [R01 CA086257, 5 R01 CA86257-04, R01 CA086257-06] NR 25 TC 29 Z9 29 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PD APR PY 2007 VL 16 IS 2 BP 101 EP 106 DI 10.1136/tc.2006.017426 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 152GR UT WOS:000245350100014 PM 17400947 ER PT J AU Thomson, CC Hamilton, WL Siegel, MB Biener, L Rigotti, NA AF Thomson, Carey Conley Hamilton, William L. Siegel, Michael B. Biener, Lois Rigotti, Nancy A. TI Effect of local youth-access regulations on progression to established smoking among youths in Massachusetts SO TOBACCO CONTROL LA English DT Article ID TOBACCO SALES LAWS; ADOLESCENT SMOKING; UNITED-STATES; CIGARETTES; ENFORCEMENT; MINORS; IMPACT; INTERVENTIONS; ACQUISITION; INITIATION AB Objective: To test whether community-level restrictions on youth access to tobacco (including both ordinances and enforcement) are associated with less smoking initiation or less progression to established smoking among adolescents. Design: Prospective cohort study of a random sample of adolescents in Massachusetts whose smoking status was assessed by telephone interviews at baseline and 2-year follow-up, and linked to a state-wide database of town-level youth-access ordinances and enforcement practices. Participants: A random sample of 2623 adolescents aged 12-17 years who lived in 295 towns in Massachusetts in 2001-2 and were followed in 2003-4. Main outcome measures: The relationship between the strength of local youth access restrictions ( including both ordinances and level of enforcement) and (1) never-smokers' smoking initiation rates and (2) experimenters' rate of progression to established smoking was tested in a multilevel analysis that accounted for town-level clustering and adjusted for potential individual, household and town-level confounders. Results: Over 2 years, 21% of 1986 never-smokers initiated smoking and 25% of 518 experimenters became established smokers. The adjusted odds ratio (OR) for smoking initiation was 0.89 (95% CI 0.61 to 1.31) for strong versus weak youth-access policies and 0.93 (95% CI 0.67 to 1.29) for medium versus weak policies. The adjusted OR for progression to established smoking among adolescents who had experimented with smoking was 0.79 (95% CI 0.45 to 1.39) for strong versus weak local smoking restrictions and 0.85 (95% CI 0.50 to 1.45) for medium versus weak restrictions. Conclusions: This prospective cohort study found no association between community-level youth-access restrictions and adolescents' rate of smoking initiation or progression to established smoking over 2 years. C1 Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Mt Auburn Hosp, Dept Med, Cambridge, MA USA. CNU Associates, Lincoln, MA USA. Boston Univ, Sch Publ Hlth, Social & Behav Sci Dept, Boston, MA 02215 USA. Univ Massachusetts, Ctr Survey Res, Boston, MA 02125 USA. RP Rigotti, NA (reprint author), Tobacco Res & Treatment Ctr, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM nrigotti@partners.org OI Biener, Lois/0000-0002-4130-8138 FU NCI NIH HHS [R01 CA086257-06, R01 CA86257, R01 CA086257]; PHS HHS [K24-04440] NR 40 TC 3 Z9 3 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PD APR PY 2007 VL 16 IS 2 BP 119 EP 126 DI 10.1136/tc.2006.018002 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 152GR UT WOS:000245350100017 PM 17400950 ER PT J AU Saidman, SL AF Saidman, S. L. TI Histocompatibility testing for highly sensitized transplant candidates SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the Indian-Society-for-Organ-Transplantation CY OCT 04-08, 2006 CL Ahmedabad, INDIA SP Indian Soc Organ Transplantat ID FLOW-CYTOMETRIC DETECTION; RENAL-TRANSPLANTATION; HLA ANTIBODIES; RECIPIENTS AB HLA antibodies can develop for many different reasons and are often present in the serum of patients awaiting renal transplantation. These antibodies can limit the patient's ability to find a compatible donor and are a risk factor for poor graft outcome. Detection of HLA antibodies is important for identifying compatible donors, assessing the pretransplantation risk for rejection, and diagnosing humoral rejection posttransplantation. The results of antibody screens are also useful when interpreting crossmatch results. Assays used for detecting panel-reactive and donor-specific HLA antibodies, including cytotoxicity, flow cytometry, and solid phase assays, are described in this review. C1 Massachusetts Gen Hosp, Histocompatibil Lab, Boston, MA 02114 USA. RP Saidman, SL (reprint author), Massachusetts Gen Hosp, Histocompatibil Lab, Room GRJ 220,55 Fruit St, Boston, MA 02114 USA. EM ssaidman@partners.org NR 13 TC 10 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPL P JI Transplant. Proc. PD APR PY 2007 VL 39 IS 3 BP 673 EP 675 DI 10.1016/j.transproceed.2007.01.053 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 161XK UT WOS:000246050100021 PM 17445570 ER PT J AU Saidman, SL AF Saidman, S. L. TI Mixed chimerism approach to induction of transplant tolerance: A review of the Massachusetts general hospital experience SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the Indian-Society-for-Organ-Transplantation CY OCT 04-08, 2006 CL Ahmedabad, INDIA SP Indian Soc Organ Transplantat ID BONE-MARROW; LYMPHOHEMATOPOIETIC CHIMERISM; PREPARATIVE REGIMEN; ALLOGRAFT TOLERANCE; OUTCOMES; MYELOMA; KIDNEY C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Histocompatibil Lab, Boston, MA 02114 USA. RP Saidman, SL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Histocompatibil Lab, GRJ220,55 Fruit St, Boston, MA 02114 USA. EM ssaidman@partners.org NR 13 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPL P JI Transplant. Proc. PD APR PY 2007 VL 39 IS 3 BP 676 EP 677 DI 10.1016/j.transproceed.2007.01.054 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 161XK UT WOS:000246050100022 PM 17445571 ER PT J AU Saidman, S AF Saidman, S. TI Significance of anti-HLA and donor-specific antibodies in long-term renal graft survival SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the Indian-Society-for-Organ-Transplantation CY OCT 04-08, 2006 CL Ahmedabad, INDIA SP Indian Soc Organ Transplantat ID CHRONIC ALLOGRAFT NEPHROPATHY; CHRONIC REJECTION; KIDNEY-TRANSPLANTATION; ANTIDONOR ANTIBODY; HUMORAL REJECTION; FLOW-CYTOMETRY; IMMUNITY; ALLOANTIBODY; CAPILLARIES; RECIPIENTS AB Numerous studies have demonstrated an association of posttransplant HLA antibodies with decreased long-term graft survival. The presence of C4d deposition in these cases supports the hypothesis that antibody and complement deposition are involved in the pathogenesis of graft failure. Development of HLA antibodies may predate the clinical manifestation of chronic rejection (CR). However, frequency of donor-specific antibody is low when all patients are screened regardless of their graft function, and it may be more valuable to look for antibody only in patients with mild dysfunction. Effective treatment for CR has not been identified, although increased immunosuppression has been shown to decrease antibody levels and stabilize graft function. Many patients have been identified with good graft function despite the presence of circulating donor-specific HLA antibody. Additional studies focusing on the mechanism behind the apparent protection from the detrimental effects of antibody in such patients are needed. C1 Massachusetts Gen Hosp, Histocompatibil Lab, Boston, MA 02114 USA. RP Saidman, S (reprint author), Massachusetts Gen Hosp, Histocompatibil Lab, Room GRJ 220,55 Fruit St, Boston, MA 02114 USA. EM ssaidman@partners.org NR 24 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPL P JI Transplant. Proc. PD APR PY 2007 VL 39 IS 3 BP 744 EP 746 DI 10.1016/j.transproceed.2007.01.050 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 161XK UT WOS:000246050100038 PM 17445587 ER PT J AU Markland, AD Thompson, IM Ankerst, DP Higgins, B Kraus, SR AF Markland, Alayne D. Thompson, Ian M. Ankerst, Donna P. Higgins, Betsy Kraus, Stephen R. TI Lack of disparity in lower urinary tract symptom severity between community-dwelling non-Hispanic white, Mexican-American, and African-American men SO UROLOGY LA English DT Article ID BENIGN PROSTATIC HYPERPLASIA; NUTRITION EXAMINATION SURVEY; CHRONIC-RENAL-FAILURE; 3RD NATIONAL-HEALTH; NATURAL-HISTORY; ASSOCIATION; PROGRESSION; PREVALENCE; DISEASE; BLACK AB OBJECTIVES To determine whether disparities exist in the reporting of lower urinary tract symptoms (LUTS) in non-Hispanic white (NHW), Mexican-American (MA), and African-American (AA) men. METHODS Data were collected from a prospective, community-based cohort assembled to study risk factors associated with prostate cancer. Measures included demographics, pros tate-specific antigen (PSA), body mass index (BMI), and family history of prostate cancer. Lower urinary tract symptom severity was assessed in 2804 men (1485 NHW, 964 MA, 355 AA) without prostate cancer according to the American Urological Association Symptom Index. RESULTS No significant difference (P = 0.998) was seen in the prevalence of moderate or severe LUTS in NHW (34%), MA (34%), and AA (33%) men. No differences were found in either obstructive or irritative symptoms among the three groups. Age, PSA level, BMI, and family history did not affect symptom severity. CONCLUSIONS Rates of moderate to severe LUTS symptoms in this cohort were similar to those in other community-based populations of NHW men. Lower rates of moderate or severe symptoms were noted in AA men than previously reported. Mexican-American men had similar degrees of LUTS as the general population, and with their increased risk for diabetes and renal disease, in-depth study of this population is warranted. C1 Univ Texas, Hlth Sci Ctr, Dept Urol, San Antonio, TX 78229 USA. Univ Alabama, Dept Med, Div Gerontol & Geriatr Med, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. San Antonio Canc Inst, San Antonio Ctr Biomarkers Risk Prostate Canc, San Antonio, TX USA. RP Kraus, SR (reprint author), Univ Texas, Hlth Sci Ctr, Dept Urol, 7703 Floyd Curl Dr,MC 7845, San Antonio, TX 78229 USA. EM krauss@uthscsa.edu FU NCI NIH HHS [U01 CA086402-05, 5U01CA86402-04, U01 CA086402] NR 20 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD APR PY 2007 VL 69 IS 4 BP 697 EP 702 DI 10.1016/j.urology.2007.01.024 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 167TK UT WOS:000246474800023 PM 17445654 ER PT J AU King, CR Freedland, SJ Terris, MK Aronson, WJ Kane, CJ Amling, CL Presti, JC AF King, Christopher R. Freedland, Stephen J. Terris, Martha K. Aronson, William J. Kane, Christopher J. Amling, Christopher L. Presti, Joseph C., Jr. TI Optimal timing, cutoff, and method of calculation of preoperative prostate-specific antigen velocity to predict relapse after prostatectomy: A report from SEARCH SO UROLOGY LA English DT Article ID RADICAL PROSTATECTOMY; PSA VELOCITY; DOUBLING TIME; CANCER; INTERVAL AB OBJECTIVES Preoperative prostate-specific antigen (PSA) velocity (PSAV), the rate of PSA rise preceding diagnosis, predicts for relapse and cancer death after prostatectomy or radiotherapy. We studied the timing, cutoff levels, and method of calculation to better define its usefulness. METHODS The rates of biochemical relapse were examined in 471 patients who underwent radical prostatectomy (RP) with previous PSA history available. PSAV was calculated by two methods, as the difference between two PSAs divided by time, or as the slope of all available PSAs within that interval. Kaplan-Meier relapse-free survival was compared among the groups with various intervals and cutoff levels in their preoperative PSAV definition. Univariate and multivariate analysis examined all preoperative factors and PSAV for their association with relapse. RESULTS The two methods of PSAV calculation yielded values within 5% of each other (R-2 = 0.91). A PSA history that precedes RP by at least 12 months is necessary. A PSAV cutoff level of 2 ng/mL/yr or less versus greater than 2 ng/mL/yr appeared optimal for a PSA interval spanning 12 to 24 months before RP (P = 0.008). PSAV using a longer interval (24 to 36 months) before RP appeared more sensitive, with a cutoff of I ng/mL/yr or less versus greater than 1 ng/mL/yr (P = 0.029) and 2 ng/mL/yr or less versus greater than 2 ng/mL/yr (P = 0.0041) associated with relapse. A preoperative PSAV of 2 ng/mL/yr or less versus greater than 2 ng/mL/yr was an independent factor associated with the risk of relapse after RP. CONCLUSIONS The results of our study have shown that preoperative PSAV is independently associated with relapse after RP. However, a minimum interval of 12 months before RP is needed, and a PSAV cutoff level of 2 ng/mL/yr appears optimal. A simple two-point method of calculating PSAV is reliable. UROLOGY 69: 732-737, 2007.(C) 2007 Elsevier Inc. C1 Stanford Univ, Sch Med, Dept Radiat Oncol, Div Urol Oncol, Stanford, CA 94305 USA. Vet Affairs Med Ctr, Dept Surg, Urol Sect, Durham, NC USA. Duke Univ, Sch Med, Div Urol Surg, Durham, NC USA. Med Coll Georgia, Urol Sect, Augusta, GA 30912 USA. Vet Affairs Med Ctr, Dept Surg, Augusta, GA USA. Univ Calif Los Angeles, Dept Urol, Sch Med, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Urol Sect, Dept Surg, Los Angeles, CA USA. Univ Calif San Francisco, Dept Urol, Sch Med, San Francisco, CA 94143 USA. Vet Affairs Med Ctr, Urol Sect, Dept Surg, San Francisco, CA 94121 USA. Univ Alabama, Dept Urol, Birmingham, AL USA. San Diego Naval Hosp, Dept Urol, San Diego, CA USA. Stanford Univ, Sch Med, Dept Urol, Div Urol Oncol, Stanford, CA 94305 USA. Vet Affairs Med Ctr, Dept Surg, Urol Sect, Palo Alto, CA 94304 USA. RP King, CR (reprint author), Stanford Univ, Sch Med, Dept Radiat Oncol, Div Urol Oncol, 875 Blake Wilbur Dr, Stanford, CA 94305 USA. EM crking@stanford.edu OI Terris, Martha/0000-0002-3843-7270 NR 12 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD APR PY 2007 VL 69 IS 4 BP 732 EP 737 DI 10.1016/j.urology.2007.01.019 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 167TK UT WOS:000246474800029 PM 17445660 ER PT J AU Eisner, BH Feldman, AS Chapin, BF Dretler, SP AF Eisner, Brian H. Feldman, Adam S. Chapin, Brian F. Dretler, Stephen P. TI "Blind coning" - Using the stone cone for removal of intramural ureteral calculi SO UROLOGY LA English DT Article ID PERCUTANEOUS NEPHROLITHOTOMY; MIGRATION; URETEROSCOPY AB INTRODUCTION To describe the otherwise heretical technique of "blind" nonureteroscopic extraction of calculi from the intramural ureter using a 7-mm-diameter tapered coil called the "Stone Cone." TECHNICAL CONSIDERATIONS After bypassing the stone and deploying the Stone Cone, stow traction was exerted. The Stone Cone's 5, 6, and 7-mm diameter coils and unique rotary action dilated the tunnel distal to the calculus and the 2, 3, and 4-mm stiffer coils caught the calculus and propelled it out of the transiently dilated intramural ureter. A safety feature is that the coils of the Stone Cone wilt unwind at greater than 0.2-lb tension. Unlike the baskets, if a pressure greater than this is encountered, the Stone Cone will release the stone, preventing entrapment. CONCLUSIONS In selected cases, use of the Blind-Cone to remove an intramural calculus can be a rapid, effective, and safe alternative to ureteroscopic management. UROLOGY 69: 773-775, 2007.(C) 2007 Elsevier Inc. C1 Harvard Univ, Dept Urol, Kidney Stone Ctr, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. RP Eisner, BH (reprint author), Harvard Univ, Dept Urol, Kidney Stone Ctr, Massachusetts Gen Hosp,Med Sch, 55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org NR 9 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD APR PY 2007 VL 69 IS 4 BP 773 EP 775 DI 10.1016/j.urology.2007.02.007 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 167TK UT WOS:000246474800039 PM 17445670 ER PT J AU Sharma, A Masri, J Jo, OD Bernath, A Martin, J Funk, A Gera, J AF Sharma, Anushree Masri, Janine Jo, Oak D. Bernath, Andrew Martin, Jheralyn Funk, Alexander Gera, Joseph TI Protein kinase C regulates internal initiation of translation of the GATA-4 mRNA following vasopressin-induced hypertrophy of cardiac myocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RIBOSOME ENTRY SITES; TRANS-ACTING FACTORS; GENE-EXPRESSION; TRANSCRIPTION FACTORS; MEDIATED TRANSLATION; IN-VITRO; PRESSURE-OVERLOAD; AKT ACTIVITY; CYCLIN D1; PHOSPHORYLATION AB GATA-4 is a key member of the GATA family of transcription factors involved in cardiac development and growth as well as in cardiac hypertrophy and heart failure. Our previous studies suggest that GATA-4 protein synthesis may be translationally regulated. We report here that the 518-nt long 5'-untransiated region (5'-UTR) of the GATA-4 mRNA, which is predicted to form stable secondary structures (-65 kcal/mol) such as to be inhibitory to cap-dependent initiation, confers efficient translation to monocistronic reporter mRNAs in cell-free extracts. Moreover, uncapped GATA-4 5'-UTR containing monocistronic reporter mRNAs continue to be well translated while capped reporters are insensitive to the inhibition of initiation by cap-analog, suggesting a capin-dependent mechanism of initiation. Utilizing a dicistronic luciferase mRNA reporter containing the GATA-4 5'-UTR within the intercistrionic region, we demonstrate that this leader sequence confers functional internal ribosome entry site (IRES) activity. The activity of the GATA-4 IRES is unaffected in trans - differentiating P19CL6 cells, however, is strongly stimulated immediately following arginine-vasopressin exposure of H9c2 ventricular myocytes. IRES activity is then maintained at submaximal levels during hypertrophic growth of these cells. Supraphysiological Ca(2+) levels diminished stimulation of IRES activity immediately following exposure to vasopressin and inhibition of protein kinase C activity utilizing a pseudosubstrate peptide sequence blocked IRES activity during hypertrophy. Thus, our data suggest a mechanism for GATA-4 protein synthesis under conditions of reduced global cap-dependent translation, which is maintained at a submaximal level during hypertrophic growth and point to the regulation of GATA-4 IRES activity by sarco(ER)reticular Ca(2+) stores and PKC. C1 Greater Los Angels Vet Affairs Healthcare Syst, Dept Res & Dev, Los Angeles, CA 91343 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90048 USA. RP Gera, J (reprint author), Greater Los Angels Vet Affairs Healthcare Syst, Dept Res & Dev, Los Angeles, CA 91343 USA. EM gera@ucla.edu FU NCI NIH HHS [CA109312] NR 57 TC 13 Z9 15 U1 2 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 MAR 30 PY 2007 VL 282 IS 13 BP 9505 EP 9516 DI 10.1074/jbc.M608874200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 153HA UT WOS:000245421700023 PM 17284439 ER PT J AU Thompson, BD Jin, YZ Wu, KH Colvirl, RA Luster, AD Birnbaumer, L Wu, MX AF Thompson, Brian D. Jin, Yongzhu Wu, Kevin H. Colvirl, Richard A. Luster, Andrew D. Birnbaumer, Lutz Wu, Mei X. TI Inhibition of G alpha(i2) activation by G alpha(i3) in CXCR3-mediated signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; ACUTE ALLOGRAFT-REJECTION; PERTUSSIS-TOXIN; T-CELLS; G-ALPHA-I2(-/-) MICE; MULTIGENE FAMILY; ALPHA-SUBUNIT; BINDING; CXCR3; LYMPHOCYTES AB G protein-coupled receptors (GPCRs) convey extracellular stimulation into dynamic intracellular action, leading to the regulation of cell migration and differentiation. T lymphocytes express G alpha(12), and G alpha(i3), two members of the G alpha(i/o). protein family, but whether these two G alpha(i) proteins have distinguishable roles guiding T cell migration remains largely unknown because of a lack of member-specific inhibitors. This study details distinct G alpha(i2) and G alpha(i3) effects on chemokine receptor CXCR3-mediated signaling. Our data showed that Gai, was indispensable for T cell responses to three CXCR3 ligands, CXCL9, CXCL10, and CXCL11, as the lack of G alpha(i2) abolished CXCR3-stimulated migration and guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) incorporation. In sharp contrast, T cells isolated from G alpha(i3) knock-out mice displayed a significant increase in both GTP gamma S incorporation and migration as compared with wild type T cells when stimulated with CXCR3 agonists. The increased GTP gamma S incorporation was blocked by G alpha(i3) protein in a dose-dependent manner. G alpha(i3)-mediated blockade of Gai, activation did not result from Gai3 activation, but instead resulted from competition or steric hindrance of Gai, interaction with the CXCR3 receptor via the N terminus of the second intracellular loop. A mutation in this domain abrogated not only G alpha(i2) activation induced by a CXCR3 agonist but also the interaction of Gai3 to the CXCR3 receptor. These findings reveal for the first time an interplay of Gai proteins in transmitting G protein-coupled receptor signals. This interplay has heretofore been masked by the use of pertussis toxin, a broad inhibitor of the G alpha(i/o) protein family. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, Boston, MA 02114 USA. NIEHS, Transmembrane Signaling Grp, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Wu, MX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, 55 Fruit St,Edwards 222, Boston, MA 02114 USA. EM mwu2@partners.org FU Intramural NIH HHS [Z01 ES101643-05]; NIAID NIH HHS [AI070785, AI050822, R01 AI050822, K02 AI070785]; NIAMS NIH HHS [T32 AR007098, T32 AR07098-31]; NIDDK NIH HHS [R01 DK074449, P30 DK043351, DK074449, DK43351] NR 46 TC 32 Z9 34 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 MAR 30 PY 2007 VL 282 IS 13 BP 9547 EP 9555 DI 10.1074/jbc.M610931200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 153HA UT WOS:000245421700027 PM 17289675 ER PT J AU Ma, YM Boucrot, E Villen, J Affar, E Gygi, SP Gottlinger, HG Kirchhausen, T AF Ma, Yu May Boucrot, Emmanuel Villen, Judit Affar, El Bachir Gygi, Steven P. Goettlinger, Heinrich G. Kirchhausen, Tomas TI Targeting of AMSH to endosomes is required for epidermal growth factor receptor degradation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SRC HOMOLOGY-3 DOMAIN; DEUBIQUITINATING ENZYMES; UBIQUITIN ISOPEPTIDASE; ESCRT-III; MAMMALIAN-CELLS; SACCHAROMYCES-CEREVISIAE; ENDOCYTIC PATHWAYS; DOWN-REGULATION; VPS PROTEIN; COMPLEX AB To reach the lysosomes, down-regulated receptors such as the epidermal growth factor receptor must first be sorted into internal vesicles of late endosomes (multivesicular bodies), a ubiquitin-dependent event that requires the coordinated function of the endosome sorting complex required for transport (ESCRT) proteins. Here we report that CHMP3, an ESCRT-III complex component, and associated molecule of SH3 domain of STAM (AMSH), a deubiquitinating enzyme, interact with each other in cells. A dominant-negative version of CHMP3, which specifically prevents targeting of AMSH to endosomes, inhibits degradation but not internalization of EGFR, suggesting that endosomal AMSH is a functional component of the multivesicular body pathway. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM Kirchhausen@crystal.harvard.edu OI Villen, Judit/0000-0002-1005-1739 FU NIAID NIH HHS [R37 AI029873, AI29873]; NIGMS NIH HHS [GM036548] NR 43 TC 50 Z9 55 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 MAR 30 PY 2007 VL 282 IS 13 BP 9805 EP 9812 DI 10.1074/jbc.M611635200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 153HA UT WOS:000245421700055 PM 17261583 ER PT J AU Kim, SY Levenson, JM Korsmeyer, S Sweatt, JD Schumacher, A AF Kim, Se Young Levenson, Jonathan M. Korsmeyer, Stanley Sweatt, J. David Schumacher, Armin TI Developmental regulation of Eed complex composition governs a switch in global histone modification in brain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROUP PROTEIN EED; H3 LYSINE-27 METHYLATION; INACTIVE X-CHROMOSOME; EMBRYONIC STEM-CELLS; POLYCOMB-GROUP GENE; MLL-MUTANT MICE; METHYLTRANSFERASE ACTIVITY; MAMMALIAN TRITHORAX; RESPONSE ELEMENTS; BINDING PROTEIN AB Originally discovered as epigenetic regulators of developmental gene expression, the Polycomb (PcG) and trithorax (trxG) group of proteins form distinct nuclear complexes governing post-translational modification of histone tails. This study identified a novel, developmentally regulated interface between Eed and Mll, pivotal constituents of PcG and trxG pathways, respectively, in mouse brain. Although the PcG proteins Eed and EzH2 (Enhancer of Zeste protein-2) engaged in a common complex during neurodevelopment, Eed associated with the trxG protein Mll upon brain maturation. Comprehensive analysis of multiple histone modifications revealed differential substrate specificity of the novel Eed-Mll complex in adult brain compared with the developmental Eed-EzH2 complex. Newborn brain from eed heterozygotes and eed;Mll double heterozygotes exhibited decreased trimethylation at lysine 27 of histone H3, as well as hyperacetylation of histone H4. In contrast, adult hippocampus from Mll heterozygotes was remarkable for decreased acetylation of histone H4, which restored to wild-type levels in eed;Mll double heterozygotes. A physiological role for the Eed-Mll complex in adult brain was evident from complementary defects in synaptic plasticity in eed and Mll mutant hippocampi. These results support the notion that developmental regulation of complex composition bestows the predominant Eed complex with the chromatin remodeling activity conducive for gene regulation during neurodevelopment and adult brain function. Thus, this study suggests dynamic regulation of chromatin complex composition as a molecular mechanism to coopt constituents of developmental pathways into the regulation of neuronal memory formation in adult brain. C1 Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Pathol & Med,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Schumacher, A (reprint author), Baylor Coll Med, Dept Mol & Human Genet, 1 Baylor Plaza, Houston, TX 77030 USA. EM armins@bcm.tmc.edu OI Sweatt, J. David/0000-0003-3567-485X NR 60 TC 46 Z9 48 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 MAR 30 PY 2007 VL 282 IS 13 BP 9962 EP 9972 DI 10.1074/jbc.M608722200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 153HA UT WOS:000245421700071 PM 17259173 ER PT J AU Zhang, GL Bozic, I Kwoh, CK August, JT Brusic, V AF Zhang, Guang Lan Bozic, Ivana Kwoh, Chee Keong August, J. Thomas Brusic, Vladimir TI Prediction of supertype-specific HLA class I binding peptides using support vector machines SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE T-cell epitope; human leukocyte antigen supertype; promiscuous binding peptide; support vector machines ID T-CELL-EPITOPES; VACCINE DEVELOPMENT; QUANTITATIVE PREDICTION; CTL EPITOPES; MHC; MOLECULES; SEQUENCE; LIGANDS; MODELS; IDENTIFICATION AB Experimental approaches for identifying T-cell epitopes are time-consuming, costly and not applicable to the large scale screening. Computer modeling methods can help to minimize the number of experiments required, enable a systematic scanning for candidate major histocompatibility complex (MHC) binding peptides and thus speed up vaccine development. We developed a prediction system based on a novel data representation of peptide/MHC interaction and support vector machines (SVM) for prediction of peptides that promiscuously bind to multiple Human Leukocyte Antigen (HLA, human MHC) alleles belonging to a HLA supertype. Ten-fold cross-validation results showed that the overall performance of SVM models is improved in comparison to our previously published methods based on hidden Markov models (HMM) and artificial neural networks (ANN), also confirmed by blind testing. At specificity 0.90, sensitivity values of SVM models were 0.90 and 0.92 for HLA-A2 and -A3 dataset respectively. Average area under the receiver operating curve (A(ROC)) Of SVM models in blind testing are 0.89 and 0.92 for HLA-A2 and -A3 datasets. A(ROC) of HLA-A2 and -A3 SVM models were 0.94 and 0.95, validated using a full overlapping study of 9-mer peptides from human papillomavirus type 16 E6 and E7 proteins. In addition, a large-scale experimental dataset has been used to validate HLA-A2 and -A3 SVM models. The SVM prediction models were integrated into a web-based computational system MULTIPRED1, accessible at antigen.i2r.a-star.edu.sg/multipred1/. (c) 2007 Elsevier B.V All rights reserved. C1 Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. Inst Infocomm Res, Singapore 119613, Singapore. Nanyang Technol Univ, Sch Comp Engn, Singapore 639798, Singapore. Univ Belgrade, Fac Math, Belgrade, Serbia. Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. RP Brusic, V (reprint author), Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. EM Vladimir_Brusic@DFCI.HARVARD.EDU RI Bozic, Ivana/C-5003-2008 FU NIAID NIH HHS [5U19AI56541, U19 AI056541, U19 AI056541-05] NR 62 TC 27 Z9 27 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD MAR 30 PY 2007 VL 320 IS 1-2 BP 143 EP 154 DI 10.1016/j.jim.2006.12.011 PG 12 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 156EP UT WOS:000245631200013 PM 17303158 ER PT J AU Zhao, JB Wecht, JM Zhang, YF Wen, XL Zeman, R Bauman, WA Cardozo, C AF Zhao, Jingbo Wecht, Jill M. Zhang, Yuanfei Wen, Xialing Zeman, Richard Bauman, William A. Cardozo, Christopher TI iNOS expression in rat aorta is increased after spinal cord transection: A possible cause of orthostatic hypotension in man SO NEUROSCIENCE LETTERS LA English DT Article DE orthostatic hypotension; nitric oxide; inducible nitric oxide synthase; spinal cord injury ID NITRIC-OXIDE SYNTHASE; HEAD-UP TILT; SIMULATED MICROGRAVITY; TETRAPLEGIC MAN; INJURY; GENE; INTOLERANCE AB Orthostatic hypotension commonly occurs in persons with spinal cord injury (SCI), limiting rehabilitation and independence. Findings of increased production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) after exposure to simulated microgravity suggest that increased iNOS expression contributes to OH in persons with SCI. To test this possibility, male Wistar rats underwent surgical transection of the spinal cord (T 10) or sham-SCI surgery followed by euthanasia 3, 7 or 14 days later. Expression in thoracic aortic of inducible (iNOS), endothelial (eNOS) and neuronal (nNOS) NOS was then determined. In SCI rats, expression of iNOS mRNA was decreased at 3 days, had returned to normal levels of expression at 7 days and was increased at 14 days post-SCI (1.8-fold). In contrast, levels of eNOS mRNA were increased at 3 days (1.4-fold), then declined over time reaching levels by day 14 that were reduced compared to sham-SCI (0.23-fold). There were no significant effects of SCI on nNOS expression. These findings suggest a possible role for increased iNOS expression in the pathogenesis of OH in persons with SCI. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 James J Peters VA Med Ctr, VA RR&D Ctr Excellence, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Med, New York, NY USA. Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. New York Med Coll, Dept Cell Biol & Anat, Valhalla, NY 10595 USA. RP Cardozo, C (reprint author), James J Peters VA Med Ctr, VA RR&D Ctr Excellence, Ctr Excellence Med Consequences Spinal Cord Injur, Room 1E-02, Bronx, NY 10468 USA. EM chris.cardozo@mssm.edu RI Zeman, Richard/A-9295-2009 NR 30 TC 5 Z9 6 U1 1 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAR 30 PY 2007 VL 415 IS 3 BP 210 EP 214 DI 10.1016/j.neulet.2007.01.025 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 158CM UT WOS:000245768600004 PM 17287083 ER PT J AU Reichenberg, A Smith, C Schmeidler, J Silverman, JM AF Reichenberg, Abraham Smith, Christopher Schmeidler, James Silverman, Jeremy M. TI Birth order effects on autism symptom domains SO PSYCHIATRY RESEARCH LA English DT Article DE pervasive developmental disorders; autism diagnostic interview; speech; siblings; first vs. second born ID PERVASIVE DEVELOPMENTAL DISORDER; MULTIPLEX FAMILIES; NONVERBAL IQ; INDIVIDUALS; INTERVIEW; PARENTS AB Autism is predominantly genetically determined. Evidence supports familiality of the main sets of behavioral characteristics that define the syndrome of autism; however, possible non-genetic effects have also been suggested. The present study compared levels of autism symptom domains, as measured by the Autism Diagnostic Interview, and useful phrase speech scores between 106 pairs of first- and second-born siblings from multiply affected families. In addition, the intercorrelations between the measures were compared between siblings. The overall mean repetitive behavior total score was significantly higher (worse) in first-born than in second-born siblings. In contrast, first-born siblings had significantly lower (better) useful phrase speech than their younger siblings. Autism social and non-verbal communication scores were significantly correlated in first- and in second-born siblings. However, there was a significant difference in the coefficients between first- and second-born siblings. Performance on the non-verbal communication domain was also significantly and positively correlated with useful phrase speech score in both first- and second-born siblings. It is unclear at this time whether these results are of biologic origin. Nevertheless, the findings suggest that genetic studies in autism using specific levels of familial autism traits as phenotypes should take into account their intercorrelations and birth order effects embedded in the instrument. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Bronx Vet Adm Med Ctr, Psychiat Serv, Bronx, NY USA. Mt Sinai Sch Med, Dept Biomath Sci, New York, NY USA. RP Reichenberg, A (reprint author), Mt Sinai Sch Med, Dept Psychiat, Box 1230,1 Gustave L Levy Pl, New York, NY 10029 USA. EM avi.reichenberg@mssm.edu NR 16 TC 12 Z9 12 U1 1 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD MAR 30 PY 2007 VL 150 IS 2 BP 199 EP 204 DI 10.1016/j.psychres.2004.09.012 PG 6 WC Psychiatry SC Psychiatry GA 157HH UT WOS:000245708900011 PM 17289158 ER PT J AU Scandella, E Lattmann, E Luther, SA Junt, T Miller, S Ludewig, B AF Scandella, E. Lattmann, E. Luther, S. A. Junt, T. Miller, S. Ludewig, B. TI Role for CD4(+) CD3(-) lymphoid tissue inducer cells in the restoration of immunopathological damage of lymphoid organ structure following lymphocytic choriomenigitis virus infection SO SWISS MEDICAL WEEKLY LA English DT Meeting Abstract C1 Kantonsspital, LFA, CH-9007 St Gallen, Switzerland. Univ Lausanne, Dept Biochem, CH-1015 Lausanne, Switzerland. CBR, Biomed Res Inst, Boston, MA USA. RI Luther, Sanjiv/B-4380-2016 OI Luther, Sanjiv/0000-0002-8758-957X NR 0 TC 0 Z9 0 U1 0 U2 0 PU E M H SWISS MEDICAL PUBLISHERS LTD PI MUTTENZ PA FARNSBURGERSTR 8, CH-4132 MUTTENZ, SWITZERLAND SN 1424-7860 J9 SWISS MED WKLY JI Swiss Med. Wkly. PD MAR 30 PY 2007 VL 137 SU 157 BP 5S EP 5S PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 152IN UT WOS:000245355800009 ER PT J AU Stein, J Nombela-Arrieta, C Mempel, T Soriano, S Mazo, I Wymann, M Hirsch, E Martinez-A, C Fukui, Y von Andrian, U AF Stein, J. Nombela-Arrieta, C. Mempel, T. Soriano, S. Mazo, I. Wymann, M. Hirsch, E. Martinez-A, C. Fukui, Y. von Andrian, U. TI Distinct roles of DOCK2 and phosphoinositide-3-kinase gamma in interstitial lymphocyte motility and sphingosine-1-phosphate-mediated lymphocyte egress SO SWISS MEDICAL WEEKLY LA English DT Meeting Abstract C1 Univ Bern, Theodor Kocher Inst, CH-3012 Bern, Switzerland. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Basel, Inst Biochem & Genet, Dept Clin Biol Sci, CH-4003 Basel, Switzerland. Univ Turin, Dept Genet Biol & Biochem, I-10124 Turin, Italy. CSIC, Natl Biotechnol Ctr, Dept Immunol & Oncol, Madrid, Spain. Kyushu Univ, Med Inst Bioregulat, Dept Immunobiol & Neurosci, Kyushu, Japan. RI Wymann, Matthias/C-3227-2008; Hirsch, Emilio/F-4848-2013 OI Hirsch, Emilio/0000-0002-9073-6024 NR 0 TC 0 Z9 0 U1 0 U2 0 PU E M H SWISS MEDICAL PUBLISHERS LTD PI MUTTENZ PA FARNSBURGERSTR 8, CH-4132 MUTTENZ, SWITZERLAND SN 1424-7860 J9 SWISS MED WKLY JI Swiss Med. Wkly. PD MAR 30 PY 2007 VL 137 SU 157 BP 11S EP 11S PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 152IN UT WOS:000245355800031 ER PT J AU Koido, S Tanaka, Y Tajiri, H Gong, JL AF Koido, Shigeo Tanaka, Yasuhiro Tajiri, Hisao Gong, Jianlin TI Generation and functional assessment of antigen-specific T cells stimulated by fusions of dendritic cells and allogeneic breast cancer cells SO VACCINE LA English DT Article DE adoptive immunotherapy; allogeneic breast cancer cells; DC-breast cancer fusion cells; SCID mice ID TUMOR-INFILTRATING LYMPHOCYTES; MAJOR HISTOCOMPATIBILITY COMPLEX; METASTATIC MELANOMA; CARCINOMA-CELLS; ANTITUMOR IMMUNITY; IN-VIVO; VACCINATION; MICE; INTERLEUKIN-2; INDUCTION AB We have reported that fusions of patient-derived dendritic cells (DC) and autologous breast cancer cells induce T-cell responses against autologous tumors. However, the preparation of fusion cells requires patient-derived tumor cells, and these are not always available in the clinical setting. In the present study, we explore an alternative approach to constructing DC-breast cancer fusion vaccine by using breast caner-cell lines. DC generated from HLA-A*0201 -positive donor were fused to HLA-A*0201(+) allogeneic MCF7 breast cancer cells. These fusion cells co-expressed tumor-associated antigens and DC-derived costimulatory and MHC molecules. Both CD4 and CD8 T cells were activated by the fusion cells as demonstrated by the production of IFN-gamma. The fusion cells induced strong antigen-specific cytotoxic T lymphocytes (CTL) activity against their parent cells. The lysis of targets was restricted by HLA-A*0201, since killing was blocked by the anti-HLA-A2 mAb. Similar CTL activity against HLA-A*0201 -positive targets was induced when T cells were cocultured with fusions of DC and HLA-A*0201 -negative allogeneic BT20 breast cancer cells. In addition, administration of T cells stimulated by DC-breast cancer fusion cells regressed 7-day-old tumors and rendered mice free of disease up to 90 days. These results suggest that tumor-cell lines can be used as a fusion partner in the construction of DC-tumor fusion vaccine. Such fusion cells hold promise since they can be used as a vaccine for active immunotherapy or as stimulators to activate and expand T cells for adoptive immunotherapy. (c) 2006 Elsevier Ltd. All rights reserved. C1 Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Jikei Univ, Dept Internal Med, Sch Med, Div Gastroenterol & Hepatol, Tokyo 201, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gong, JL (reprint author), Boston Univ, Sch Med, Dept Med, 650 Albany St,Room 309, Boston, MA 02118 USA. EM jgong@bu.edu FU NCI NIH HHS [R01 CA087057-04] NR 31 TC 25 Z9 26 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 MAR 30 PY 2007 VL 25 IS 14 BP 2610 EP 2619 DI 10.1016/j.vaccine.2006.12.035 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 157PO UT WOS:000245732700010 PM 17239504 ER PT J AU Raghavendra, NK Engelman, A AF Raghavendra, Nidhanapati K. Engelman, Alan TI LEDGF/p75 interferes with the formation of synaptic nucleoprotein complexes that catalyze full-site HIV-1 DNA integration in vitro: Implications for the mechanism of viral cDNA integration SO VIROLOGY LA English DT Article DE integrase; full-site integration; HIV-1; LEDGF/p75 ID HUMAN-IMMUNODEFICIENCY-VIRUS; PREINTEGRATION COMPLEXES; CONCERTED INTEGRATION; TYPE-1 INTEGRASE; HUMAN-CELLS; PROTEIN; REPLICATION; CHROMATIN; IDENTIFICATION; REVEALS AB An integrase dimer can process and integrate a single HIV-1 DNA end in vitro, whereas a tetramer is required to integrate two ends. LEDGF/p75 can potently stimulate integrase activity, but its effects on half- versus full-site integration have not been investigated. Stimulation of half-site but inhibition of full-site integration is revealed here. LEDGF/p75 seems to interfere with integrase oligomerization, but does not inhibit the catalytic activity of pre-assembled complexes. We therefore speculate that LEDGF/p75 function is restricted to a point in the viral lifecycle that occurs after the formation of the preintegration synaptic complex, for example, as a chroinatin-associated tethering factor. (c) 2006 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM alan_engelman@dfci.harvard.edu FU NIAID NIH HHS [AI39394, AI60354, AI70042, P30 AI060354, R01 AI039394, R01 AI070042, R37 AI039394] NR 22 TC 31 Z9 34 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 MAR 30 PY 2007 VL 360 IS 1 BP 1 EP 5 DI 10.1016/j.virol.2006.12.022 PG 5 WC Virology SC Virology GA 149JB UT WOS:000245142100001 PM 17258258 ER PT J AU Thomas, ER Dunfee, RL Stanton, J Bogdan, D Taylor, J Kunstman, K Bell, JE Wolinsky, SM Gabuzda, D AF Thomas, Elaine R. Dunfee, Rebecca L. Stanton, Jennifer Bogdan, Derek Taylor, Joann Kunstman, Kevin Bell, Jeanne E. Wolinsky, Steven M. Gabuzda, Dana TI Macrophage entry mediated by HIV Envs from brain and lymphoid tissues is determined by the capacity to use low CD4 levels and overall efficiency of fusion SO VIROLOGY LA English DT Review DE human immunodeficiency virus type 1 (HIV); envelope; brain; lymph node; CD4; neurotropism ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; ACTIVE ANTIRETROVIRAL THERAPY; AIDS DEMENTIA COMPLEX; NEUTRALIZING ANTIBODY-RESPONSE; MONOCYTE-DERIVED MACROPHAGES; MOLECULE CCR5 INHIBITOR; CORECEPTOR BINDING-SITE; IN-VIVO; V3 LOOP AB HIV infects macrophages and microglia in the central nervous system (CNS), which express lower levels of CD4 than CD4+ T cells in peripheral blood. To investigate mechanisms of HIV neurotropism, full-length env genes were cloned from autopsy brain and lymphoid tissues from 4 AIDS patients with HIV-associated dementia (HAD). Characterization of 55 functional Env clones demonstrated that Envs with reduced dependence on CD4 for fusion and viral entry are more frequent in brain compared to lymphoid tissue. Envs that mediated efficient entry into macrophages were frequent in brain but were also present in lymphoid tissue. For most Envs, entry into macrophages correlated with overall fusion activity at all levels of CD4 and CCR5. gp160 nucleotide sequences were compartmentalized in brain versus lymphoid tissue within each patient. Proline at position 308 in the V3 loop of gp120 was associated with brain compartmentalization in 3 patients, but mutagenesis studies suggested that P308 alone does not contribute to reduced CD4 dependence or macrophage-tropism. These results suggest that HIV adaptation to replicate in the CNS selects for Envs with reduced CD4 dependence and increased fusion activity. Macrophage-tropic Envs are frequent in brain but are also present in lymphoid tissues of AIDS patients with HAD, and entry into macrophages in the CNS and other tissues is dependent on the ability to use low receptor levels and overall efficiency of fusion. (c) 2006 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Medford, MA 02155 USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. Univ Edinburgh, Dept Pathol, Western Gen Hosp, Edinburgh, Midlothian, Scotland. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, JFB 816,44 Binney St, Medford, MA 02155 USA. EM dana_gabuzda@dfci.harvard.edu RI Wolinsky, Steven/B-2893-2012; OI Wolinsky, Steven/0000-0002-9625-6697 FU Medical Research Council [G0500863]; NINDS NIH HHS [NS37277, R01 NS037277] NR 113 TC 78 Z9 79 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 0042-6822 J9 VIROLOGY JI Virology PD MAR 30 PY 2007 VL 360 IS 1 BP 105 EP 119 DI 10.1016/j.virol.2006.09.036 PG 15 WC Virology SC Virology GA 149JB UT WOS:000245142100011 PM 17084877 ER PT J AU Sacknoff, R Sheridan, RL Smith, RM Velmahos, G Schnitzer, JJ Harris, NL AF Sacknoff, Richard Sheridan, Robert L. Smith, R. Malcolm Velmahos, George Schnitzer, Jay J. Harris, Nancy Lee TI A 55-year-old man impaled in a rowing accident - Traumatic lacerations of the abdominal wall and viscera, with pelvic fracture. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SYSTEMS C1 Massachusetts Gen Hosp, Dept Trauma, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthoped, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Orthoped Surg, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. RP Sacknoff, R (reprint author), Massachusetts Gen Hosp, Dept Trauma, Boston, MA 02114 USA. NR 9 TC 2 Z9 2 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 29 PY 2007 VL 356 IS 13 BP 1353 EP 1360 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 150MN UT WOS:000245221000011 PM 17392306 ER PT J AU Durand, M Kolpak, A Farrell, T Elliott, NA Shao, WL Brown, M Volkert, MR AF Durand, Mathieu Kolpak, Adrianne Farrell, Timothy Elliott, Nathan A. Shao, Wenlin Brown, Myles Volkert, Michael R. TI The OXR domain defines a conserved family of eukaryotic oxidation resistance proteins SO BMC CELL BIOLOGY LA English DT Article ID ESTROGEN-RECEPTOR-ALPHA; COLI ENDONUCLEASE-VIII; DNA-DAMAGE; ESCHERICHIA-COLI; MITOCHONDRIAL-DNA; NTH MUTANTS; REPAIR; TRANSCRIPTION; GLYCOSYLASE; NUCLEAR AB Background: The NCOA7 gene product is an estrogen receptor associated protein that is highly similar to the human OXR1 gene product, which functions in oxidation resistance. OXR genes are conserved among all sequenced eukaryotes from yeast to humans. In this study we examine if NCOA7 has an oxidation resistance function similar to that demonstrated for OXR1. We also examine NCOA7 expression in response to oxidative stress and its subcellular localization in human cells, comparing these properties with those of OXR1. Results: We find that NCOA7, like OXR1 can suppress the oxidative mutator phenotype when expressed in an E. coli strain that exhibits an oxidation specific mutator phenotype. Moreover, NCOA7's oxidation resistance function requires expression of only its carboxyl-terminal domain and is similar in this regard to OXR1. We find that, in human cells, NCOA7 is constitutively expressed and is not induced by oxidative stress and appears to localize to the nucleus following estradiol stimulation. These properties of NCOA7 are in striking contrast to those of OXR1, which is induced by oxidative stress, localizes to mitochondria, and appears to be excluded, or largely absent from nuclei. Conclusion: NCOA7 most likely arose from duplication. Like its homologue, OXR1, it is capable of reducing the DNA damaging effects of reactive oxygen species when expressed in bacteria, indicating the protein has an activity that can contribute to oxidation resistance. Unlike OXR1, it appears to localize to nuclei and interacts with the estrogen receptor. This raises the possibility that NCOA7 encodes the nuclear counterpart of the mitochondrial OXR1 protein and in mammalian cells it may reduce the oxidative by-products of estrogen metabolite-mediated DNA damage. C1 Univ Massachusetts, Sch Med, Dept Mol Genet & Microbiol, Worcester, MA 01655 USA. Univ Quebec, Dept Chem & Biol, Trois Rivieres, PQ GA9 5H7, Canada. Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA. RP Volkert, MR (reprint author), Univ Massachusetts, Sch Med, Dept Mol Genet & Microbiol, Worcester, MA 01655 USA. EM math_dur@hotmail.com; Adrianne.Kolpak@umassmed.edu; tfarrell14@yahoo.com; nae2@u.washington.edu; wenlin.shao@novartis.com; myles_brown@dfci.harvard.edu; Michael.Volkert@umassmed.edu OI Brown, Myles/0000-0002-8213-1658; Volkert, Michael/0000-0002-0045-0912 FU NCI NIH HHS [CA100122, R01 CA100122] NR 35 TC 31 Z9 33 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2121 J9 BMC CELL BIOL JI BMC Cell Biol. PD MAR 28 PY 2007 VL 8 AR 13 DI 10.1186/1471-2121-8-13 PG 10 WC Cell Biology SC Cell Biology GA 154BF UT WOS:000245481100001 PM 17391516 ER PT J AU Hashimoto, M Sun, DM Rittling, SR Denhardt, DT Young, W AF Hashimoto, Masayuki Sun, Dongming Rittling, Susan R. Denhardt, David T. Young, Wise TI Osteopontin-deficient mice exhibit less inflammation, greater tissue damage, and impaired locomotor recovery from spinal cord injury compared with wild-type controls SO JOURNAL OF NEUROSCIENCE LA English DT Article DE osteopontin; BMS; NYU impactor; Bcl-2; knock-out mice; spinal cord injury ID FORMATION IN-VITRO; MACROPHAGE INFILTRATION; INTERSTITIAL FIBROSIS; FUNCTIONAL RECOVERY; GRANULOMA-FORMATION; DENDRITIC CELLS; MESSENGER-RNA; EXPRESSION; APOPTOSIS; MOUSE AB Osteopontin (OPN) is expressed in many tissues during inflammatory responses. After spinal cord injury, microglia expresses OPN at the site of injury during the early to subacute stages. However, the function of OPN in spinal cord injury is not well understood. This study examines the responses of OPN knock-out (K0) and wild-type (WT) mice to spinal cord contusion injury. K0 and WT mice were injured with a modified New York University impactor. Weights of 10 or 5.6 g were dropped 6.25 mm onto the T13 spinal cord under isoflurane anesthesia. At 24 h, homogenized spinal cords were analyzed for total potassium concentration to estimate lesion volumes. Expression of apoptotic genes, proinflammatory cytokines, and nerve growth factors was measured by reverse transcription (RT)-PCR and Western blot. In a series of animals, locomotor recovery was assessed with the Basso mouse scale (BMS) for 6 weeks, and histological analyses was performed to determine tissue preservation. Lesion volume showed no significant differences between K0 and WT mice at 24 h. RT-PCR indicated that K0 mice had significantly less Bcl-2, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 mRNA compared with WT controls. Western blot also showed that K0 had significantly less Bcl-2 7 d after spinal cord injury. K0 mice had significantly worse BMS locomotor scores than WT at 6 weeks. K0 mice also had a significantly reduced area of spared white matter and fewer neuronal-specific nuclear protein-positive neurons in the spinal cord surrounding the impact site. This result supports a potential neuroprotective role for OPN in the inflammatory response to spinal cord injury. C1 Togane Prefectural Hosp, Chiba 2838588, Japan. Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ 08854 USA. Forsyth Inst, Boston, MA 02115 USA. RP Young, W (reprint author), Nelson Biol Labs, Room D251,604 Allison Rd, Piscataway, NJ 08854 USA. EM wisey@mac.com NR 45 TC 51 Z9 51 U1 0 U2 1 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 MAR 28 PY 2007 VL 27 IS 13 BP 3603 EP 3611 DI 10.1523/JNEUROSCI.4805-06.2007 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 153WT UT WOS:000245468200027 PM 17392476 ER PT J AU Hewitt, AW Samples, JR Allingham, RR Jarvela, I Kitsos, G Krishnadas, SR Richards, JE Lichter, PR Petersen, MB Sundaresan, P Wiggs, JL Mackey, DA Wirtz, MK AF Hewitt, Alex W. Samples, John R. Allingham, R. Rand Jarvela, Irma Kitsos, George Krishnadas, Subbaiah R. Richards, Julia E. Lichter, Paul R. Petersen, Michael B. Sundaresan, Periasamy Wiggs, Janey L. Mackey, David A. Wirtz, Mary K. TI Investigation of founder effects for the Thr377Met Myocilin mutation in glaucoma families from differing ethnic backgrounds SO MOLECULAR VISION LA English DT Article ID OPEN-ANGLE GLAUCOMA; HUMAN GENOME; HAPLOTYPE; GENE; AGE; TIGR/MYOCILIN; INDIVIDUALS; PREVALENCE; PHENOTYPE AB PURPOSE: The aim of this study was to determine if there is a common founder for the Thr377Met myocilin mutation in primary open angle glaucoma (POAG) families with various ethnic backgrounds. METHODS: Genomic DNA of 24 POAG-affected individuals from nine pedigrees with the Thr377Met mutation and 104 unaffected family members was genotyped with six microsatellite markers and four single nucleotide polymorphisms. The families were from Greece, India, Finland, the USA, and Australia. To assess the degree of linkage disequilibrium across MYOC in the general population we also investigated data generated from the HapMap consortium. RESULTS: Three distinct haplotypes associated with the Thr377Met myocilin mutation were identified. The families from the USA and Greece, as well as the three Australian families originating from Greece and the former Yugoslavian Republic of Macedonia had one common haplotype. Interestingly, however, HapMap data suggest that linkage disequilibrium across MYOC was not strong. CONCLUSIONS: The Thr377Met myocilin mutation has arisen at least three separate times. Evidence for genetic founder effects in this prevalent age-related, yet heterogeneous, disease has important implications for future gene identification strategies. C1 Oregon Hlth & Sci Univ, Casey Eye Inst, Dept Ophthalmol, Portland, OR 97201 USA. Flinders Univ S Australia, Dept Ophthalmol, Adelaide, SA 5001, Australia. Duke Univ, Ctr Eye, Dept Ophthalmol, Durham, NC 27710 USA. Univ Helsinki, Dept Ophthalmol, FIN-00014 Helsinki, Finland. Univ Ioannina, Dept Ophthalmol, GR-45110 Ioannina, Greece. Aravind Med Res Fdn, Dept Genet, Madurai, Tamil Nadu, India. Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Cambridge, MA 02138 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia. RP Wirtz, MK (reprint author), Oregon Hlth & Sci Univ, Casey Eye Inst, Dept Ophthalmol, 3375 SW Terwilliger Blvd, Portland, OR 97201 USA. EM wirtzm@ohsu.edu RI Jarvela, Irma/L-5836-2013; Hewitt, Alex/D-1936-2013; Mackey, David/H-5340-2014; Petersen, Michael Bjorn/D-1483-2017 OI Hewitt, Alex/0000-0002-5123-5999; Mackey, David/0000-0001-7914-4709; Petersen, Michael Bjorn/0000-0003-0316-8207 FU NEI NIH HHS [R01 EY011650, 5P30EY010572, EY010886, EY015543, EY11650, P30 EY010572, R01 EY010886, R01 EY015543] NR 26 TC 10 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 MAR 28 PY 2007 VL 13 IS 50-51 BP 487 EP 492 PG 6 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 154LV UT WOS:000245509800002 PM 17417609 ER PT J AU Addo, MM Draenert, R Rathod, A Verrill, CL Davis, BT Gandhi, RT Robbins, GK Basgoz, NO Stone, DR Cohen, DE Johnston, MN Flynn, T Wurcel, AG Rosenberg, ES Altfeld, M Walker, BD AF Addo, Marylyn M. Draenert, Rika Rathod, Almas Verrill, Cori L. Davis, Benjamin T. Gandhi, Rajesh T. Robbins, Gregory K. Basgoz, Nesli O. Stone, David R. Cohen, Daniel E. Johnston, Mary N. Flynn, Theresa Wurcel, Alysse G. Rosenberg, Eric S. Altfeld, Marcus Walker, Bruce D. TI Fully Differentiated HIV-1 Specific CD8+T Effector Cells Are More Frequently Detectable in Controlled than in Progressive HIV-1 Infection SO PLOS ONE LA English DT Article AB Background. CD8+ T cells impact control of viral infections by direct elimination of infected cells and secretion of a number of soluble factors. In HIV-1 infection, persistent HIV-1 specific IFN-gamma+ CD8+ T cell responses are detected in the setting of disease progression, consistent with functional impairment in vivo. Recent data suggest that impaired maturation, as defined by the lineage markers CD45RA and CCR7, may contribute to a lack of immune control by these responses. Methodology/Principal Findings. We investigated the maturation phenotype of epitope-specific CD8+ T cell responses directed against HIV-1 in 42 chronically infected, untreated individuals, 22 of whom were "Controllers'' (median 1140 RNA copies/ml plasma, range, 50 to 2520), and 20 "progressors'' of whom had advanced disease and high viral loads (median 135,500 RNA copies/ml plasma, range 12100 to >750000). Evaluation of a mean of 5 epitopes per person revealed that terminally differentiated CD8+ T cells directed against HIV-1 are more often seen in HIV-1 Controllers (16/22; 73%) compared to HIV-1 progressors (7/20; 35%)(p = 0.015), but the maturation state of epitope-specific responses within a given individual was quite variable. Maturation phenotype was independent of the HLA restriction or the specificity of a given CD8+ T cell response and individual epitopes associated with slow disease progression were not more likely to be terminally differentiated. Conclusions/Significance. These data indicate that although full maturation of epitope-specific CD8+ T cell responses is associated with viral control, the maturation status of HIV-1 specific CD8+ T cell responses within a given individual are quite heterogeneous, suggesting epitope-specific influences on CD8+ T cell function. C1 [Draenert, Rika; Verrill, Cori L.; Walker, Bruce D.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Partners AIDS Res Ctr, Boston, MA 02114 USA. [Addo, Marylyn M.; Draenert, Rika; Rathod, Almas; Verrill, Cori L.; Davis, Benjamin T.; Gandhi, Rajesh T.; Robbins, Gregory K.; Basgoz, Nesli O.; Johnston, Mary N.; Flynn, Theresa; Wurcel, Alysse G.; Rosenberg, Eric S.; Altfeld, Marcus; Walker, Bruce D.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Addo, Marylyn M.; Draenert, Rika; Rathod, Almas; Verrill, Cori L.; Davis, Benjamin T.; Gandhi, Rajesh T.; Robbins, Gregory K.; Basgoz, Nesli O.; Johnston, Mary N.; Flynn, Theresa; Wurcel, Alysse G.; Rosenberg, Eric S.; Altfeld, Marcus; Walker, Bruce D.] Harvard Univ, Sch Med, Div Aids, Boston, MA 02115 USA. [Stone, David R.; Wurcel, Alysse G.] Lemuel Shattuck Hosp, Boston, MA USA. [Cohen, Daniel E.] Fenway Community Hlth Ctr, Boston, MA USA. RP Walker, BD (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Partners AIDS Res Ctr, Boston, MA 02114 USA. EM Bwalker@partners.org RI Robbins, Gregory/F-7988-2011 FU National Institutes of Health [RO1 AI28568, AI054178-01, NO1-A1-15442]; Deutsche Forschungsgemeinschaft [DR424/1-1]; Howard Hughes Medical Institute; Doris Duke Charitable Foundation (BDW); Partners/Fenway/Shattuck CFAR; Claflin Distinguished Scholar Award (MMA); Concerned Parents for AIDS Research (CPFA); AmfAR [70577-31-RFT] FX This study was supported by the National Institutes of Health (RO1 AI28568 and AI054178-01, contract # NO1-A1-15442), the Deutsche Forschungsgemeinschaft DR424/1-1 (RD), the Howard Hughes Medical Institute (RD and BDW), the Doris Duke Charitable Foundation (BDW), the Partners/Fenway/Shattuck CFAR, the Claflin Distinguished Scholar Award (MMA), Concerned Parents for AIDS Research (CPFA) (MMA) and AmfAR (70577-31-RFT) (MMA). NR 34 TC 63 Z9 65 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 28 PY 2007 VL 2 IS 3 AR e321 DI 10.1371/journal.pone.0000321 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10DR UT WOS:000207445200004 PM 17389912 ER PT J AU Fox, JH Kama, JA Lieberman, G Chopra, R Dorsey, K Chopra, V Volitakis, I Cherny, RA Bush, AI Hersch, S AF Fox, Jonathan H. Kama, Jibrin A. Lieberman, Gregory Chopra, Raman Dorsey, Kate Chopra, Vanita Volitakis, Irene Cherny, Robert A. Bush, Ashley I. Hersch, Steven TI Mechanisms of Copper Ion Mediated Huntington's Disease Progression SO PLOS ONE LA English DT Article AB Huntington's disease (HD) is caused by a dominant polyglutamine expansion within the N-terminus of huntingtin protein and results in oxidative stress, energetic insufficiency and striatal degeneration. Copper and iron are increased in the striata of HD patients, but the role of these metals in HD pathogenesis is unknown. We found, using inductively-coupled-plasma mass spectroscopy, that elevations of copper and iron found in human HD brain are reiterated in the brains of affected HD transgenic mice. Increased brain copper correlated with decreased levels of the copper export protein, amyloid precursor protein. We hypothesized that increased amounts of copper bound to low affinity sites could contribute to pro-oxidant activities and neurodegeneration. We focused on two proteins:huntingtin, because of its centrality to HD, and lactate dehydrogenase (LDH), because of its documented sensitivity to copper, necessity for normoxic brain energy metabolism and evidence for altered lactate metabolism in HD brain. The first 171 amino acids of wild-type huntingtin, and its glutamine expanded mutant form, interacted with copper, but not iron. N171 reduced Cu(2+) in vitro in a 1:1 copper:protein stoichiometry indicating that this fragment is very redox active. Further, copper promoted and metal chelation inhibited aggregation of cell-free huntingtin. We found decreased LDH activity, but not protein, and increased lactate levels in HD transgenic mouse brain. The LDH inhibitor oxamate resulted in neurodegeneration when delivered intra-striatially to healthy mice, indicating that LDH inhibition is relevant to neurodegeneration in HD. Our findings support a role of pro-oxidant copper-protein interactions in HD progression and offer a novel target for pharmacotherapeutics. C1 [Fox, Jonathan H.; Kama, Jibrin A.; Lieberman, Gregory; Chopra, Raman; Dorsey, Kate; Chopra, Vanita; Hersch, Steven] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Bush, Ashley I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Bush, Ashley I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA 02129 USA. [Volitakis, Irene; Cherny, Robert A.; Bush, Ashley I.] Univ Melbourne, Oxidat Disorders Lab, Mental Hlth Res Inst Victoria, Parkville, Vic 3052, Australia. [Volitakis, Irene; Cherny, Robert A.; Bush, Ashley I.] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. RP Hersch, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. EM HERSCH@HELIX.MGH.HARVARD.EDU RI Bush, Ashley/A-1186-2007; OI Bush, Ashley/0000-0001-8259-9069; Volitakis, Irene/0000-0003-0766-817X FU Huntington's Disease Society of America (HDSA); HighQ Foundation; NIH/NINDS [NS35255, NS045242]; NIH/NCCAM [AT00613]; Australian Research Council; National Health and Research Council of Australia FX Support was provided by the Huntington's Disease Society of America (HDSA), The HighQ Foundation, NIH/NINDS (NS35255 and NS045242) and NIH/NCCAM (AT00613). The Australian Research Council and the National Health and Research Council of Australia supported RAC, IV and AIB. NR 51 TC 73 Z9 75 U1 2 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 28 PY 2007 VL 2 IS 3 AR e334 DI 10.1371/journal.pone.0000334 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10DR UT WOS:000207445200017 PM 17396163 ER PT J AU Fox, CS Coady, S Sorlie, PD D'Agostino, RB Pencina, MJ Vasan, RS Meigs, JB Levy, D Savage, PJ AF Fox, Caroline S. Coady, Sean Sorlie, Paul D. D'Agostino, Ralph B. Pencina, Michael J. Vasan, Ramachandran S. Meigs, James B. Levy, Daniel Savage, Peter J. TI Increasing cardiovascular disease burden due to diabetes mellitus - The Framingham Heart Study SO CIRCULATION LA English DT Article DE diabetes mellitus; cardiovascular diseases; epidemiology; risk factors ID ACUTE MYOCARDIAL-INFARCTION; US ADULTS; NATIONAL-HEALTH; TEMPORAL TRENDS; ELUTING STENTS; RISK-FACTORS; MORTALITY; PREVALENCE; IMPACT; CHOLESTEROL AB Background-Marked reductions in cardiovascular disease (CVD) morbidity and mortality have occurred in the United States over the last 50 years. We tested the hypothesis that the relative burden of CVD attributable to diabetes mellitus (DM) has increased over the past 5 decades. Methods and Results-Participants aged 45 to 64 years from the Framingham Heart Study, who attended examinations in an "early" time period (1952 to 1974), were compared with those who attended examinations in a later time period (1975 to 1998). The risk of CVD events (n = 133 among those with and 1093 among those without DM) attributable to DM in the 2 time periods was assessed with Cox proportional hazards models; population attributable risk of DM as a CVD risk factor was calculated for each time period. The age-and sex-adjusted hazard ratio for DM as a CVD risk factor was 3.0 (95% CI, 2.3 to 3.9) in the earlier time period and 2.5 (95% CI, 1.9 to 3.2) in the later time period. The population attributable risk for DM as a CVD risk factor increased from 5.4% (95% CI, 3.8% to 6.9%) in the earlier time period to 8.7% (95% CI, 5.9% to 11.4%) in the later time period (P for attributable risk ratio = 0.04), although multivariable adjustment resulted in attenuation of these findings (P = 0.12); most of these observations were found among men. Conclusions-The proportion of CVD attributable to DM has increased over the past 50 years in Framingham. These findings emphasize the need for increased efforts to prevent DM and to aggressively treat and control CVD risk factors among those with DM. C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Diabet Endocrinol & Hypertens, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Fox, CS (reprint author), Framingham Heart Dis Epidemiol Study, NHLBI, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [N01-HC-25195]; PHS HHS [5K24H004334] NR 38 TC 276 Z9 285 U1 1 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 27 PY 2007 VL 115 IS 12 BP 1544 EP 1550 DI 10.1161/CIRCULATIONAHA.106.658948 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 150JC UT WOS:000245211300007 PM 17353438 ER PT J AU Inglessis, I Landzberg, MJ AF Inglessis, Ignacio Landzberg, Michael J. TI Interventional catheterization in adult congenital heart disease SO CIRCULATION LA English DT Article ID VENTRICULAR SEPTAL-DEFECTS; TRANSCATHETER CLOSURE; DEVICE CLOSURE; PERCUTANEOUS CLOSURE; BALLOON ANGIOPLASTY; COARCTATION; EXPERIENCE; STENOSIS; REPAIR; VALVULOPLASTY C1 Harvard Univ, Boston Childrens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston Adult Congenital Heart Grp, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Hosp, Sch Med, Boston, MA 02115 USA. RP Landzberg, MJ (reprint author), Harvard Univ, Boston Childrens Hosp, Sch Med, 300 Longwood Ave, Boston, MA 02115 USA. EM michael.landzberg@cardio.chboston.org NR 44 TC 27 Z9 32 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 MAR 27 PY 2007 VL 115 IS 12 BP 1622 EP 1633 DI 10.1161/CIRCULATIONAHA.105.592428 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 150JC UT WOS:000245211300016 PM 17389281 ER PT J AU Poh, KK Cury, RC Solis, J Fischman, AJ Wood, MJ AF Poh, Kian Keong Cury, Ricardo C. Solis, Jorge Fischman, Alan J. Wood, Malissa J. TI Complementary role of multimodality imaging in the evaluation of intracardiac lymphoma in an HIV-infected man SO CIRCULATION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. RP Poh, KK (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiac Ultrasound Lab, Blake2,55 Fruit St, Boston, MA 02114 USA. EM doctorpoh@yahoo.com 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 MAR 27 PY 2007 VL 115 IS 12 BP E339 EP E341 DI 10.1161/CIRCULATIONAHA.106.664177 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 150JC UT WOS:000245211300025 PM 17389272 ER PT J AU Mensah, GA Grant, AO Pepine, CJ AF Mensah, George A. Grant, Augustus O. Pepine, Carl J. TI ACCF/AHA/CDC Conference Report on Emerging Infectious Diseases and Biological Terrorism threats - The clinical and public health implications for the prevention and control of cardiovascular diseases SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review ID ACUTE MYOCARDIAL-INFARCTION; WEST-NILE-VIRUS; NEW-YORK-CITY; CORONARY-ARTERY-DISEASE; AMERICAN-HEART-ASSOCIATION; ACUTE RESPIRATORY SYNDROME; NEGATIVE BLOOD CULTURES; SUDDEN CARDIAC DEATH; Q-FEVER ENDOCARDITIS; TRADE-CENTER ATTACK C1 Mayo Clin & Mayo Fdn, Coll Med, Rochester, MN 55905 USA. Michigan Dept Community Hlth, Publ Hlth Adm, Lansing, MI 48913 USA. Cambridge Dept Hlth, Cambridge, MA 02139 USA. Emory Univ, Sch Nursing, Atlanta, GA 30322 USA. Univ Calif San Francisco, Sch Nursing & Med, Dept Epidemiol & Biostat, Dept Physiol Nursing, San Francisco, CA 94143 USA. Duke Univ, Med Ctr, Durham, NC 27702 USA. Ctr Dis Control & Prevent, Div Heart Dis & Stroke Prevent, Atlanta, GA 30341 USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Univ So Calif, Keck Sch Med, Hosp Good Samaritan, Inst Heart, Los Angeles, CA 90017 USA. Assoc Black Cardiol Inc, Atlanta, GA 30349 USA. Ctr Dis Control & Prevent, Div Heart Dis & Stroke Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. Univ Minnesota, Div Epidemiol, Dept Med, Minneapolis, MN 55454 USA. Univ Texas, Hlth Sci Ctr, Houston, TX 77030 USA. Texas Heart Inst, Houston, TX 77030 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Ctr Dis Control & Prevent, Coordinating Ctr Infect Dis, Atlanta, GA 30333 USA. VA Commonwlth Univ Hlth Syst, Dept Emergency Med, Richmond, VA USA. Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL 32608 USA. DHHS, Div Publ Hlth, Raleigh, NC 27699 USA. Amer Heart Assoc, Dallas, TX 75231 USA. Uniformed Serv Univ Hlth Sci, Div Mil Internal Med, Bethesda, MD 20814 USA. Chron Dis Prevent Program, Richmond, VA 23219 USA. Cedars Sinai Med Ctr, Div Cardiol, Los Angeles, CA 90048 USA. NHLBI, NIH, Bethesda, MD 20817 USA. RP Mensah, GA (reprint author), Mayo Clin & Mayo Fdn, Coll Med, 200 1st St SW, Rochester, MN 55905 USA. OI Mensah, George/0000-0002-0387-5326 NR 269 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 27 PY 2007 VL 49 IS 12 BP 1373 EP 1412 DI 10.1016/j.jacc.2007.01.017 PG 40 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 152TL UT WOS:000245384600023 PM 17394977 ER PT J AU Jefferson, AL Massaro, JM Wolf, PA Seshadri, S Au, R Vasan, RS Larson, MG Meigs, JB Keaney, JF Lipinska, I Kathiresan, S Benjamin, EJ DeCarli, C AF Jefferson, A. L. Massaro, J. M. Wolf, P. A. Seshadri, S. Au, R. Vasan, R. S. Larson, M. G. Meigs, J. B. Keaney, J. F., Jr. Lipinska, I. Kathiresan, S. Benjamin, E. J. DeCarli, C. TI Inflammatory biomarkers are associated with total brain volume - The Framingham Heart Study SO NEUROLOGY LA English DT Article ID C-REACTIVE PROTEIN; STROKE RISK PROFILE; ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; ROTTERDAM SCAN; ATROPHY; MRI; RATES; AD; QUANTIFICATION AB Background: Systemic inflammation is associated with ischemia and Alzheimer disease (AD). We hypothesized that inflammatory biomarkers would be associated with neuroimaging markers of ischemia (i. e., white matter hyperintensities [WMH]) and AD (i. e., total brain volume [TCB]). Methods: MRI WMH and TCB were quantified on 1,926 Framingham Offspring participants free from clinical stroke, TIA, or dementia (mean age 60 +/- 9 years; range 35 to 85 years; 54% women) who underwent measurement of a circulating inflammatory marker panel, including CD40 ligand, C-reactive protein, interleukin-6 (IL-6), soluble intracellular adhesion molecule-1, monocyte chemoattractant protein-1, myeloperoxidase, osteoprotegerin (OPG), P-selectin, tumor necrosis factor-alpha (TNF alpha), and tumor necrosis factor receptor II. To account for head size, both TCB (TCBV) and WMH (WMH/TCV) were divided by total cranial volume. We used multivariable linear regression to relate 10 log-transformed inflammatory biomarkers to brain MRI measures. Results: In multivariable models, inflammatory markers as a group were associated with TCBV (p < 0.0001) but not WMH/TCV (p = 0.28). In stepwise models adjusted for clinical covariates with backwards elimination of markers, IL-6 and OPG were inversely associated with TCBV; TNF alpha was inversely related to TCBV in a subset of 1,430 participants. Findings were similar in analyses excluding individuals with prevalent cardiovascular disease. The relations between TCBV and inflammatory markers were modified by both sex and age, and generally were more pronounced in men and in older individuals. Conclusions: Although our observational cross-sectional data cannot establish causality, they are consistent with the hypothesis that higher inflammatory markers are associated with greater atrophy than expected for age. C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Dis Prevent Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Calif Davis, Dept Neurol, Ctr Neurosci, Davis, CA 95616 USA. Univ Calif Davis, Imaging Dementia & Aging Lab, Davis, CA 95616 USA. RP Jefferson, AL (reprint author), Boston Univ, Sch Med, Dept Neurol, 715 Albany St,B-7800, Boston, MA 02118 USA. EM angelaj@bu.edu RI DeCarli, Charles/B-5541-2009; OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NCRR NIH HHS [M01 RR001066, M01-RR-01066]; NHLBI NIH HHS [HL064753, HL076784, HL083102, K23 HL083102, K24 HL004334, N01-HC-25195, N01HC25195, N01HV28178, P01 HL081587, R01 HL067266, R01 HL067288, R01 HL076784, R01 HL077447]; NIA NIH HHS [P30 AG013846, AG010129, AG021028, AG022773, AG028321, AG08122, AG16495, F32 AG022773, K23 AG030962, K23 AG030962-01, K23 AG030962-02, K23 AG030962-03, P30 AG010129, P30 AG013846-06, R01 AG008122, R01 AG016495, R01 AG021028, R01 AG027081, R01 AG028321]; NICHD NIH HHS [HD043444, K12 HD043444, K12 HD043444-06]; NINDS NIH HHS [NS017950, R01 NS017950] NR 36 TC 106 Z9 108 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 27 PY 2007 VL 68 IS 13 BP 1032 EP 1038 DI 10.1212/01.wnl.0000257815.20548.df PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 150JF UT WOS:000245211600012 PM 17389308 ER PT J AU Parmar, K Mauch, P Vergilio, JA Sackstein, R Down, JD AF Parmar, Kalindi Mauch, Peter Vergilio, Jo-Anne Sackstein, Robert Down, Julian D. TI Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Hoechst perfusion; stem cell niche; oxygen gradient; pimonidazole; tirapazamine ID MEASURING TUMOR HYPOXIA; SIDE POPULATION CELLS; PROGENITOR CELLS; IN-VIVO; REGULATORY FACTOR; NICHE; ARCHITECTURE; OSTEOPONTIN; ENGRAFTMENT; TELOMERASE AB The interaction of stem cells with their bone marrow microenvironment is a critical process in maintaining normal hematopoiesis. We applied an approach to resolve the spatial organization that underlies these interactions by evaluating the distribution of hematopoietic cell subsets along an in vivo Hoechst 33342 (Ho) dye perfusion gradient. Cells isolated from different bone marrow regions according to Ho fluorescence intensity contained the highest concentration of hematopoietic stem cell (HSC) activity in the lowest end of the Ho gradient (i.e., in the regions reflecting diminished perfusion). Consistent with the ability of Ho perfusion to simulate the level of oxygenation, bone marrow fractions separately enriched for HSCs were found to be the most positive for the binding of the hypoxic marker pimonidazole. Moreover, the in vivo administration of the hypoxic cytotoxic agent tirapazamine exhibited selective toxicity to the primitive stem cell subset. These data collectively indicate that HSCs and the supporting cells of the stem cell niche are predominantly located at the lowest end of an oxygen gradient in the bone marrow with the implication that regionally defined hypoxia plays a fundamental role in regulating stem cell function. C1 Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Genetix Pharmaceut Inc, Cambridge, MA 02139 USA. RP Mauch, P (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, Jimmy Fund Bldg,Room 518B,44 Binney St, Boston, MA 02115 USA. EM pmauch@lroc.harvard.edu FU NCI NIH HHS [R01 CA010941, R01CA10941]; NHLBI NIH HHS [R01HL073714, R01 HL073714]; NIAID NIH HHS [U19 AI067751, U19AI067751] NR 46 TC 433 Z9 457 U1 5 U2 28 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 MAR 27 PY 2007 VL 104 IS 13 BP 5431 EP 5436 DI 10.1073/pnas.0701152104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 152AE UT WOS:000245331700033 PM 17374716 ER PT J AU Colvin, RB AF Colvin, Robert B. TI CADI, canti, cavi SO TRANSPLANTATION LA English DT Editorial Material ID CHRONIC ALLOGRAFT NEPHROPATHY; PROTOCOL BIOPSIES; RENAL-ALLOGRAFTS; REJECTION; CLASSIFICATION; PROGRESSION; BIOMARKERS; DECLINE C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Colvin, RB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM colvin@helix.mgh.harvard.edu NR 14 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAR 27 PY 2007 VL 83 IS 6 BP 677 EP 678 DI 10.1097/01.tp.000262011.05196.a1 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 153DH UT WOS:000245411400002 PM 17414694 ER PT J AU Adams, SG Smith, PK Allan, PF Anzueto, A Pugh, JA Cornell, JE AF Adams, Sandra G. Smith, Paulla K. Allan, Patrick F. Anzueto, Antonio Pugh, Jacqueline A. Cornell, John E. TI Systematic review of the chronic care model in chronic obstructive pulmonary disease prevention and management SO ARCHIVES OF INTERNAL MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED TRIAL; RESPIRATORY HEALTH WORKER; SELF-MANAGEMENT; PATIENT EDUCATION; COPD PATIENTS; CLINICAL-TRIALS; CHRONIC ILLNESS; PROGRAM; METAANALYSIS; IMPACT AB Background: Implementation of the chronic care model (CCM) has been shown to be an effective preventative strategy to improve outcomes in diabetes mellitus, depression, and congestive heart failure, but data are lacking regarding the effectiveness of this model in preventing complications in patients with chronic obstructive pulmonary disease. Methods: We searched the MEDLINE, CINAHL, and Cochrane databases from inception to August 2005 and included English-language articles that enrolled adults with chronic obstructive pulmonary disease and (1) contained intervention(s) with CCM component(s), (2) included a comparison group or measures at 2 points (before/after), and (3) had relevant outcomes. Two reviewers independently extracted data. Results: Symptoms, quality of life, lung function, and functional status were not significantly different between the intervention and control groups. However, pooled relative risks (95% confidence intervals) for emergency/unscheduled visits and hospitalizations for the group that received at least 2 CCM components were 0.58 (0.42-0.79) and 0.78 (0.66-0.94), respectively. The weighted mean difference (95% confidence interval) for hospital stay was -2.51 (-3.40 to -1.61) days shorter for the group that received 2 or more components. There were no significant differences for those receiving only 1 CCM component. Conclusions: Limited published data exist evaluating the efficacy of CCM components in chronic obstructive pulmonary disease management. However, pooled data demonstrated that patients with chronic obstructive pulmonary disease who received interventions with 2 or more CCM components had lower rates of hospitalizations and emergency/unscheduled visits and a shorter length of stay compared with control groups. The results of this review highlight the need for well-designed trials in this population. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78285 USA. Univ Texas, Hlth Sci Ctr, Div Pulm Dis Crit Care Med, San Antonio, TX 78285 USA. VERDICT, San Antonio, TX USA. Wilford Hall USAF Med Ctr, S Texas Vet Hlth Care Syst & Pulm Med, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. RP Adams, SG (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, Pulm Dis Sect, 111E,7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM adamssg@uthscsa.edu OI Pugh, Jacqueline/0000-0003-4933-141X NR 63 TC 166 Z9 171 U1 1 U2 19 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 MAR 26 PY 2007 VL 167 IS 6 BP 551 EP 561 DI 10.1001/archinte.167.6.551 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 149UQ UT WOS:000245172800005 PM 17389286 ER PT J AU Chan, AT Manson, JE Feskanich, D Stampfer, MJ Colditz, GA Fuchs, CS AF Chan, Andrew T. Manson, JoAnn E. Feskanich, Diane Stampfer, Meir J. Colditz, Graham A. Fuchs, Charles S. TI Long-term aspirin use and mortality in women SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID LOW-DOSE ASPIRIN; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CORONARY-ARTERY-DISEASE; PREVENT COLORECTAL ADENOMAS; NATIONAL DEATH INDEX; RANDOMIZED-TRIAL; CARDIOVASCULAR-DISEASE; BREAST-CANCER; POSTMENOPAUSAL WOMEN; PHYSICIANS HEALTH AB Background: The influence of long-term use of aspirin on total mortality in women remains uncertain. Methods: We conducted a prospective, nested, case-control study of 79 439 women enrolled in the Nurses' Health Study who had no history of cardiovascular disease or cancer. Women provided data on medication use biennially since 1980. We assessed relative risk (RR) of death according to aspirin use before diagnosis of incident cardiovascular disease or cancer and during the corresponding period for each control subject. Results: During 24 years, we documented 9477 deaths from all causes. in women who reported current aspirin use, the multivariate RR of death from all causes was 0.75 (95% confidence interval, 0.71-0.81) compared with women who never used aspirin regularly. The risk reduction was more apparent for death from cardiovascular disease (RR, 0.62; 95% confidence interval, 0.55-0.71) than for death from cancer (RR, 0.88; 95% confidence interval, 0.81-0.96). Use of aspirin for 1 to 5 years was associated with significant reductions in cardiovascular mortality (RR, 0.75; 95% confidence interval, 0.61-0.92). In contrast, a significant reduction in risk of cancer deaths was not, observed until after 10 years of aspirin use (P-linear trend = .005). The benefit associated with aspirin was confined to low and moderate doses and was significantly greater in older participants (P-interaction < .001) and those with more cardiac risk factors (P-interaction = .02). Conclusions: In women, low to moderate doses of aspirin are associated with significantly lower risk of all-cause mortality, particularly in older women and those with cardiac risk factors. A significant benefit is evident within 5 years for cardiovascular disease, whereas a modest benefit for cancer is not apparent until after 10 years of use. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,Gray Jackson 728A, Boston, MA 02114 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA 107412, CA 87969]; NHLBI NIH HHS [HL 34594] NR 51 TC 51 Z9 56 U1 0 U2 1 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 MAR 26 PY 2007 VL 167 IS 6 BP 562 EP 572 DI 10.1001/archinte.167.6.562 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 149UQ UT WOS:000245172800006 PM 17389287 ER PT J AU Ho, NH Weissleder, R Tung, CH AF Ho, Nan-Hui Weissleder, Ralph Tung, Ching-Hsuan TI A self-immolative reporter for beta-galactosidase sensing SO CHEMBIOCHEM LA English DT Article DE chromogenic substrates; cleavage reactions; enzymatic assay; fluorescent probes; galactosidases ID ESCHERICHIA-COLI; GENE-EXPRESSION; LACZ; PURIFICATION; GLUCOSIDASE; SUBSTRATE; ASSAY AB A dual fluorogenic and chromogenic probe, Gal-2SBPO, has been developed based on a synthesized water-soluble dye, 9-di-3-sulfonyt-propylaminobenzo[a]phenoxazonium perchloride (2SPBO, lambda(ex/em) = 630/670 nm). beta-D-Golactopyronoside, the substrate of beta-galactosidase, was conjugated to 2SBPO through a para-substituted benzyloxycorbonyl group and a glycine residue, which serve as a self-immolative spacer and as a molecular blocker to mask the optical signal of 2SBPO, respectively. Gal-25BPO was soluble and stable under physiological conditions. Enzymatic cleavage of the P-D-galactopyranoside triggered a series of spontaneous reactions that resulted in a release of optically active 2SBPO. The beta-galactosidase activity was assayed by monitoring the absorbance at 630 nm and fluorescence at 670 nm. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Tung, CH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St,Room 5406, Charlestown, MA 02129 USA. EM tung@helix.mgh.harvard.edu FU NCI NIH HHS [P50 CA 86355, R01 CA 99385] NR 23 TC 37 Z9 37 U1 2 U2 23 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1439-4227 J9 CHEMBIOCHEM JI ChemBioChem PD MAR 26 PY 2007 VL 8 IS 5 BP 560 EP 566 DI 10.1002/cbic.200600386 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 151ZZ UT WOS:000245331100014 PM 17300128 ER PT J AU Iwasa, JH Morse, MJ Szostak, JW AF Iwasa, Janet H. Morse, M. J. Szostak, Jack W. TI Using molecular animation to visualize the chemical origins of life SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Szostak, Jack W.] Harvard Univ, Dept Mol Biol, Simches Res Ctr, Boston, MA 02114 USA. [Iwasa, Janet H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Morse, M. J.] Museum Sci, Current Sci & Technol Ctr, Boston, MA 02114 USA. EM jiwasa@gmail.com; szostak@molbio.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 25 PY 2007 VL 233 MA 1647-CHED BP 488 EP 488 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V14GL UT WOS:000207722804486 ER PT J AU Estiu, G Harrison, C Wiest, O Mazitschek, R Bradner, J AF Estiu, Guillermina Harrison, Chris Wiest, Olaf Mazitschek, Ralph Bradner, James TI Design of class selective HDAC inhibitors SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Estiu, Guillermina; Harrison, Chris; Wiest, Olaf] Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA. [Mazitschek, Ralph] Harvard Univ, Broad Inst, Chem Biol Program, Cambridge, MA 02142 USA. [Mazitschek, Ralph] MIT, Cambridge, MA 02142 USA. [Bradner, James] Dana Farber Canc Inst, Boston, MA 02115 USA. EM gestiu@nd.edu; charris5@nd.edu; owiest@nd.edu; ralph@broad.harvard.edu; James_Bradner@dfci.harvard.edu RI Mazitschek, Ralph/E-3741-2013 OI Mazitschek, Ralph/0000-0002-1105-689X NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 25 PY 2007 VL 233 MA 447-MEDI BP 615 EP 615 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V14GL UT WOS:000207722806457 ER PT J AU Park, JY Arnaout, MA Gupta, V AF Park, Jun Y. Arnaout, M. Amin Gupta, Vineet TI Discovery of novel small molecule regulators of the integrin CD11b/CD18 SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Park, Jun Y.; Arnaout, M. Amin; Gupta, Vineet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Nephrol Div, Boston, MA 02129 USA. EM vineet_gupta@hms.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 25 PY 2007 VL 233 MA 458-MEDI BP 646 EP 646 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V14GL UT WOS:000207722806488 ER PT J AU Kallmerten, A Rowland, B Pomerantz, M Oh, W Glick, J AF Kallmerten, Amy Rowland, Brittany Pomerantz, Mark Oh, William Glick, James TI MEDI 316-Discovery and SAR of furan piperazines as sodium channel blockers for the treatment of neuropathic pain SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Kallmerten, Amy; Rowland, Brittany] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. [Pomerantz, Mark; Oh, William] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. EM kallmerten.a@neu.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 25 PY 2007 VL 233 MA 374-MEDI BP 943 EP 943 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V14GL UT WOS:000207722806785 ER PT J AU Sheesley, RJ Schauer, JJ Smith, TJ Garshick, E Laden, F Blicharz, D DeMinter, J AF Sheesley, Rebecca J. Schauer, James J. Smith, Thomas J. Garshick, Eric Laden, Francine Blicharz, Drew DeMinter, Jeff TI Tracking personal exposure to diesel exhaust in a diesel freight terminal using organic tracer analysis by thermal desorption GCMS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Sheesley, Rebecca J.; Schauer, James J.] Univ Wisconsin, Environm Chem & Technol Program, Madison, WI 53706 USA. [Smith, Thomas J.; Blicharz, Drew] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Garshick, Eric] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. [Laden, Francine] Harvard Univ, Sch Publ Hlth, VA Boston Healthcare Syst, Boston, MA 02115 USA. [DeMinter, Jeff] Univ Wisconsin, Wisconsin State Lab Hyg, Madison, WI 53706 USA. EM rjsheesley@wisc.edu; jschauer@engr.wisc.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 25 PY 2007 VL 233 MA 61-FUEL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V14GL UT WOS:000207722801755 ER PT J AU Verdine, GL AF Verdine, Gregory L. TI Drugging the undruggable SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Verdine, Gregory L.] Harvard Univ, Dept Chem & Chem Biol Mol & Cellular Biol, Program Canc Chem Biol, Dana Farber Canc Inst, Cambridge, MA 02138 USA. EM gregory_verdine@harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 25 PY 2007 VL 233 MA 576-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V14GL UT WOS:000207722808802 ER PT J AU Lee-Huang, S Huang, PL Zhang, DW Lee, JW Bao, J Sun, YT Chang, YT Zhang, J Huang, PL AF Lee-Huang, Sylvia Huang, Philip Lin Zhang, Dawei Lee, Jae Wook Bao, Ju Sun, Yongtao Chang, Young Tae Zhang, John Huang, Paul Lee TI Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol: Part I. Integrase inhibition SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE HIV-1; AIDS; natural product; small-molecule HIV-1 inhibitors; HIV-1 entry inhibitor; olive leaf extract (OLE); oleuropein (Ole); hydroxytyrosol (HT); structure-function; molecular modeling ID ENVELOPE GLYCOPROTEIN; CRYSTAL-STRUCTURE; ATOMIC-STRUCTURE; MEMBRANE-FUSION; INFECTION; CORE; GP41; RECEPTOR; ENTRY; CD4 AB We have identified oleuropein (Ole) and hydroxytyrosol (HT) as a unique class of HIV-1 inhibitors from olive leaf extracts effective against viral fusion and integration. We used molecular docking simulation to study the interactions of Ole and HT with viral targets. We find that Ole and HT bind to the conserved hydrophobic pocket on the surface of the HTV-gp41 fusion domain by hydrogen bonds with Q577 and hydrophobic interactions with 1573, G572, and L568 on the gp41 N-terminal heptad repeat peptide N36, interfering with formation of the gp41 fusion-active core. To test and confirm modeling predications, we examined the effect of Ole and HT on HIV-1 fusion complex formation using native polyacrylamide gel electrophoresis and circular dichroism spectroscopy. Ole and HT exhibit dose-dependent inhibition on HIV-1 fusion core formation with EC(50)S of 66-58 nM, with no detectable toxicity. Our findings on effects of HIV-1 integrase are reported in the subsequent article. (c) 2007 Elsevier Inc. All rights reserved. C1 NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. Amer Biosci, Boston, MA 02114 USA. NYU, Dept Chem, New York, NY 10003 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lee-Huang, S (reprint author), NYU, Sch Med, Dept Biochem, 550 1St Ave, New York, NY 10016 USA. EM sylvia.lee-huang@med.nyu.edu RI Zhang, Dawei/C-5981-2008; Chang, Young-Tae/B-2780-2010; Bao, Ju/E-6242-2012; OI Chang, Young-Tae/0000-0002-1927-3688; Lee-Huang, Sylvia/0000-0003-3302-241X FU NCCIH NIH HHS [R01 AT001383, R01-AT01383] NR 35 TC 54 Z9 64 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 23 PY 2007 VL 354 IS 4 BP 872 EP 878 DI 10.1016/j.bbrc.2007.01.071 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 139DF UT WOS:000244411800006 PM 17275783 ER PT J AU Lee-Huang, S Huang, PL Zhang, DW Lee, JW Bao, J Sun, YT Chang, YT Zhang, J Huang, PL AF Lee-Huang, Sylvia Huang, Philip Lin Zhang, Dawei Lee, Jae Wook Bao, Ju Sun, Yongtao Chang, Young-Tae Zhang, John Huang, Paul Lee TI Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol: Part II. Integrase inhibition SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE HIV-1; AIDS; natural product; small molecule HIV-1 inhibitors; HIV-1 integrase inhibitor; olive leaf extract (OLE); oleuropein (Ole); hydroxytyrosol (HT); structure-function; molecular modeling ID HUMAN-IMMUNODEFICIENCY-VIRUS; ESCHERICHIA-COLI; TYPE-1; MUTATIONS; MUTANT; SITE AB We report molecular modeling and functional confirmation of Ole and HT binding to HIV-1 integrase. Docking simulations identified two binding regions for Ole within the integrase active site. Region I encompasses the conserved D64-116-E152 motif, while region II involves the flexible loop region formed by amino acid residues 140-149. HT, on the other hand, binds to region II. Both Ole and HT exhibit favorable interactions with important amino acid residues through strong H-bonding and van der Waals contacts, predicting integrase inhibition. To test and confirm modeling predictions, we examined the effect of Ole and HT on HIV-1 integrase activities including 3'-processing, strand transfer, and disintegration. Ole and HT exhibit dose-dependent inhibition on all three activities, with EC(50)s in the nanomolar range. These studies demonstrate that molecular modeling of target-ligand interaction coupled with structural-activity analysis should facilitate the design and identification of innovative integrase inhibitors and other therapeutics. (c) 2007 Elsevier Inc. All rights reserved. C1 NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. Amer Biosci, Boston, MA 02114 USA. NYU, Dept Chem, New York, NY 10003 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lee-Huang, S (reprint author), NYU, Sch Med, Dept Biochem, 550 1St Ave, New York, NY 10016 USA. EM sylvia.lee-huang@med.nyu.edu RI Zhang, Dawei/C-5981-2008; Chang, Young-Tae/B-2780-2010; Bao, Ju/E-6242-2012; OI Chang, Young-Tae/0000-0002-1927-3688; Lee-Huang, Sylvia/0000-0003-3302-241X FU NCCIH NIH HHS [R01-AT01383, R01 AT001383] NR 24 TC 38 Z9 40 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 23 PY 2007 VL 354 IS 4 BP 879 EP 884 DI 10.1016/j.bbrc.2007.01.058 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 139DF UT WOS:000244411800007 PM 17261269 ER PT J AU Griffin, WC Middaugh, LD Becker, HC AF Griffin, William C., III Middaugh, Lawrence D. Becker, Howard C. TI Voluntary ethanol drinking in mice and ethanol concentrations in the nucleus accumbens SO BRAIN RESEARCH LA English DT Article DE alcohol; mouse; self-administration; lick; nucleus accumbens ID C57BL/6J MICE; EXTRACELLULAR DOPAMINE; MICRODIALYSIS PROBES; CONSUMPTION; NALTREXONE; REINFORCEMENT; WITHDRAWAL; GLUTAMATE; EXPOSURE; CUES AB The present study determined ethanol concentrations in the nucleus accumbens (NAcc) of C57BL/6J (136) mice voluntarily drinking ethanol using an established limited access paradigm. Lickometer circuits were employed to monitor the temporal pattern of consummatory behavior, and serial samples were collected from the NAcc using in vivo microdialysis techniques. Ethanol in the dialysate was measured by gas chromatography with flame ionization detection. During dialysis, mice preferentially consumed sufficient amounts of sweetened ethanol (similar to 3 g/kg ethanol) to produce low millimolar levels of ethanol in dialysates from the NAcc; water intake was negligible. overall, there was a positive relationship between total amount of ethanol consumed during the 2 h drinking session and cumulative (as well as peak) ethanol levels in NAcc. Additionally, and the total number of licking responses was positively correlated with the total amount of ethanol consumed. Moreover, the change in NAcc ethanol levels was temporally linked to the pattern of ethanol drinking, with periods of high licking responses on the ethanol tube preceding peak brain ethanol levels. The results indicate that the voluntary consumption of ethanol by B6 mice in a limited access time frame elevates ethanol concentration in NAcc dialysates in a manner consistent with the pattern of ethanol consumption. (c) 2007 Elsevier B.V. All rights reserved. C1 Med Univ S Carolina, Ctr Drug & Alcohol Program, Charleston Alcohol Res Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Griffin, WC (reprint author), Med Univ S Carolina, Ctr Drug & Alcohol Program, Charleston Alcohol Res Ctr, POB 250861, Charleston, SC 29425 USA. EM griffinw@musc.edu FU NIAAA NIH HHS [P50AA10761] NR 29 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 23 PY 2007 VL 1138 BP 208 EP 213 DI 10.1016/j.brainres.2006.12.071 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 150QI UT WOS:000245230900022 PM 17275791 ER PT J AU Iwase, S Lan, F Bayliss, P de la Torre-Ubieta, L Huarte, M Qi, HH Whetstine, JR Bonni, A Roberts, TM Shi, Y AF Iwase, Shigeki Lan, Fei Bayliss, Peter de la Torre-Ubieta, Luis Huarte, Maite Qi, Hank H. Whetstine, Johnathan R. Bonni, Azad Roberts, Thomas M. Shi, Yang TI The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases SO CELL LA English DT Article ID DOMAIN-CONTAINING PROTEINS; METHYLATION PATTERNS; ANDROGEN-RECEPTOR; MAMMALIAN-CELLS; ARID PROTEINS; BREAST-CANCER; JARID1C GENE; JMJD2 FAMILY; TRANSCRIPTION; CHROMATIN AB Histone methylation regulates chromatin structure and transcription. The recently identified histone demethylase lysine-specific demethylase 1 (LSD1) is chemically restricted to demethylation of only mono- and di- but not tri-methylated histone H3 lysine 4 (H3K4me3). We show that the X-linked mental retardation (XLMR) gene SMCX (JARID1C), which encodes a JmjC-domain protein, reversed H3K4me3 to di- and mono- but not unmethylated products. Other SMCX family members, including SMCY, RBP2, and PLU-1, also demethylated H3K4me3. SMCX bound H3K9me3 via its N-terminal PHD (plant homeodomain) finger, which may help coordinate H3K4 demethylation and H3K9 methylation in transcriptional repression. Significantly, several XLMR-patient point mutations reduced SMCX demethylase activity and binding to H3K9me3 peptides, respectively. Importantly, studies in zebrafish and primary mammalian neurons demonstrated a role for SMCX in neuronal survival and dendritic development and a link to the demethylase activity. Our findings thus identify a family of H3K4me3 demethylases and uncover a critical link between histone modifications and XLMR. C1 Harvard Univ, Sch Med, Dana Farber Inst, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Shi, Y (reprint author), Harvard Univ, Sch Med, Dana Farber Inst, Dept Pathol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM yang_shi@hms.harvard.edu RI Perez , Claudio Alejandro/F-8310-2010; Huarte, Maite/J-6903-2014 OI Perez , Claudio Alejandro/0000-0001-9688-184X; Huarte, Maite/0000-0003-3753-6493 FU NIGMS NIH HHS [GM 071004, GM 58012, GM 70095]; NINDS NIH HHS [NS051255, NS41021]; PHS HHS [NCI118487] NR 50 TC 374 Z9 389 U1 5 U2 36 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 23 PY 2007 VL 128 IS 6 BP 1077 EP 1088 DI 10.1016/j.cell.2007.02.017 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 152XS UT WOS:000245396200015 PM 17320160 ER PT J AU Haapasalo, A Kim, DY Carey, BW Turunen, MK Pettingell, WH Kovacs, DM AF Haapasalo, Annakaisa Kim, Doo Yeon Carey, Bryce W. Turunen, Mari K. Pettingell, Warren H. Kovacs, Dora M. TI Presenilin/gamma-secretase-mediated cleavage regulates association of leukocyte-common antigen-related (LAR) receptor tyrosine phosphatase with beta-catenin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; HIPPOCAMPAL CHOLINERGIC INNERVATION; GAMMA-SECRETASE; INTRACELLULAR DOMAIN; DISINTEGRIN-METALLOPROTEASE; NEURITE OUTGROWTH; NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; CYTOPLASMIC DOMAIN; TERMINAL FRAGMENTS AB Leukocyte-common antigen-related (LAR) receptor tyrosine phosphatase regulates cell adhesion and formation of functional synapses and neuronal networks. Here we report that LAR is sequentially cleaved by alpha- and presenilin (PS)/gamma-secretases, which also affect signaling and/or degradation of type-I membrane proteins including the Alzheimer disease-related beta-amyloid precursor protein. Similar to the previously characterized PS/gamma-secretase substrates, inhibition of gamma-secretase activity resulted in elevated LAR C-terminal fragment (LAR-CTF) levels in stably LAR-overexpressing Chinese hamster ovary (CHO) cells, human neuroglioma cells, and mouse cortical neurons endogenously expressing LAR. Furthermore, LAR-CTF levels increased in cells lacking functional PS, indicating that gamma-secretase-mediated cleavage of LAR was PS-dependent. Inhibition of alpha-secretase activity by TAPI-1 treatment blocked LAR-CTF accumulation, demonstrating that prior ectodomain shedding was prerequisite for PS/gamma-secretase-mediated cleavage of LAR. Moreover, we identified the product of PS/gamma-secretase cleavage, LAR intracellular domain (LICD), both in vitro and in cells over-expressing full-length (FL) LAR or LAR-CTFs. LAR localizes to cadherin-beta-catenin-based cellular junctions. Assembly and disassembly of these junctions are regulated by tyrosine phosphorylation. We found that endogenous tyrosine-phosphorylated beta-catenin coimmunoprecipitated with LAR in CHO cells. However, when PS/gamma-secretase activity was inhibited, the association between LAR and beta-catenin significantly diminished. In addition to cell adhesion, beta-catenin is involved in transcriptional regulation. We observed that LICD significantly decreased transcription of cyclin D1, one of the beta-catenin target genes. Thus, our results show that PS/gamma-secretase-mediated cleavage of LAR controls LAR-beta-catenin interaction, suggesting an essential role for PS/gamma-secretase in the regulation of LAR signaling. C1 Massachusetts Gen Hosp, Neurobiol Dis Lab, Genet & Aging Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Kuopio, Dept Neurol & Neurosci, FIN-70211 Kuopio, Finland. RP Kovacs, DM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,MIND, Neurobiol Dis Lab,Genet & Agine Res Unit,Dept Neu, 114 16th St, Charlestown, MA 02129 USA. EM dora_kovacs@hms.harvard.edu NR 72 TC 37 Z9 38 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 MAR 23 PY 2007 VL 282 IS 12 BP 9063 EP 9072 DI 10.1074/jbc.M611324200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 158GS UT WOS:000245780300053 PM 17259169 ER PT J AU Ong, HL Cheng, KT Liu, XB Bandyopadhyay, BC Paria, BC Soboloff, J Pani, B Gwack, Y Srikanth, S Singh, BB Gill, D Ambudkar, IS AF Ong, Hwei Ling Cheng, Kwong Tai Liu, Xibao Bandyopadhyay, Bidhan C. Paria, Biman C. Soboloff, Jonathan Pani, Biswaranjan Gwack, Yousang Srikanth, Sonal Singh, Brij B. Gill, Donald Ambudkar, Indu S. TI Dynamic assembly of TRPC1-STIM1-Orai1 ternary complex is involved in store-operated calcium influx - Evidence for similarities in store-operated and calcium release-activated calcium channel components SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CAPACITATIVE CA2+ ENTRY; SALIVARY-GLAND CELLS; SMOOTH-MUSCLE-CELLS; PLASMA-MEMBRANE; CRAC CHANNEL; T-LYMPHOCYTES; STIM1; PROTEIN; TRPC1; DEPLETION AB Store-operated calcium entry (SOCE) is a ubiquitous mechanism that is mediated by distinct SOC channels, ranging from the highly selective calcium release-activated Ca2+ (CRAG) channel in rat basophilic leukemia and other hematopoietic cells to relatively Ca2+-selective or non-selective SOC channels in other cells. Although the exact composition of these channels is not yet established, TRPC1 contributes to SOC channels and regulation of physiological function of a variety of cell types. Recently, Orai1 and STIM1 have been suggested to be sufficient for generating CRAC channels. Here we show that Orai1 and STIM1 are also required for TRPC1-SOC channels. Knockdown of TRPC1, Orai1, or STIM1 attenuated, whereas overexpression of TRPC1, but not Orai1 or STIM1, induced an increase in SOC entry and I-SOC in human salivary gland cells. All three proteins were co-localized in the plasma membrane region of cells, and thapsigargin increased co-immunoprecipitation of TRPC1 with STIM1, and Orai1 in human salivary gland cells as well as dispersed mouse submandibular gland cells. In aggregate, the data presented here reveal that all three proteins are essential for generation of I-SOC in these cells and that dynamic assembly of TRPC1-STIM1-Orai1 ternary complex is involved in activation of SOC channel in response to internal Ca2+ store depletion. Thus, these data suggest a common molecular basis for SOC and CRAC channels. C1 NIDCR, Secret Physiol Sect, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. Univ N Dakota, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Grand Forks, ND 58203 USA. Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. CBR, Biomed Res Inst, Boston, MA 02115 USA. RP Ambudkar, IS (reprint author), NIDCR, Secret Physiol Sect, Gene Therapy & Therapeut Branch, NIH, Bldg 10,Rm 1N-113,10 Ctr Dr, Bethesda, MD 20892 USA. EM indu.ambudkar@nih.gov RI Soboloff, Jonathan/I-6995-2012; OI Soboloff, Jonathan/0000-0001-5192-1297; Singh, Brij/0000-0003-0535-5997 FU NCRR NIH HHS [P20 RR017699, P20 RR017699-077011]; NIDCR NIH HHS [DE017102, R01 DE017102, R01 DE017102-01A1, R01 DE017102-02, R01 DE017102-03, R01 DE017102-05, R01 DE017102-06A1]; NIGMS NIH HHS [GM07525] NR 46 TC 251 Z9 257 U1 2 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 MAR 23 PY 2007 VL 282 IS 12 BP 9105 EP 9116 DI 10.1074/jbc.M608942200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 158GS UT WOS:000245780300058 PM 17224452 ER PT J AU Radom, CT Banerjee, A Verdine, GL AF Radom, Christopher T. Banerjee, Anirban Verdine, Gregory L. TI Structural characterization of human 8-oxoguanine DNA glycosylase variants bearing active site mutations SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OXIDATIVELY DAMAGED DNA; BASE EXCISION-REPAIR; BIOCHEMICAL EXPLORATION; SUBSTRATE RECOGNITION; FPG PROTEIN; ENZYME; CLONING; 7,8-DIHYDRO-8-OXOGUANINE; MUTAGENESIS; SYSTEM AB The human 8-oxoguanine DNA glycosylase (hOGG1) protein is responsible for initiating base excision DNA repair of the endogenous mutagen 8-oxoguanine. Like nearly all DNA glycosylases, hOGG1 extrudes its substrate from the DNA helix and inserts it into an extrahelical enzyme active site pocket lined with residues that participate in lesion recognition and catalysis. Structural analysis has been performed on mutant versions of hOGG1 having changes in catalytic residues but not on variants having altered 7,8-dihydro-8-oxoguanine (oxoG) contact residues. Here we report high resolution structural analysis of such recognition variants. We found that Ala substitution at residues that contact the phosphate 5' to the lesion (H270A mutation) and its Watson-Crick face (Q315A mutation) simply removed key functionality from the contact interface but otherwise had no effect on structure. Ala substitution at the only residue making an oxoG-specific contact (G42A mutation) introduced torsional stress into the DNA contact surface of hOGG1, but this was overcome by local interactions within the folded protein, indicating that this oxoG recognition motif is "hardwired." Introduction of a side chain intended to sterically obstruct the active site pocket (Q315F mutation) led to two different structures, one of which (Q315F*(149)) has the oxoG lesion in an exosite flanking the active site and the other of which (Q315F*(292)) has the oxoG inserted nearly completely into the lesion recognition pocket. The latter structure offers a view of the latest stage in the base extrusion pathway yet observed, and its lack of catalytic activity demonstrates that the transition state for displacement of the lesion base is geometrically demanding. C1 Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. Harvard Univ, Dept Mol & Cell Biol, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. RP Verdine, GL (reprint author), Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. EM gregory_verdine@harvard.edu FU NCI NIH HHS [CA100742, R01 CA100742] NR 41 TC 43 Z9 46 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 MAR 23 PY 2007 VL 282 IS 12 BP 9182 EP 9194 DI 10.1074/jbc.M608989200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 158GS UT WOS:000245780300065 PM 17114185 ER PT J AU Roy, J Li, HM Hogan, PG Cyert, MS AF Roy, Jagoree Li, Huiming Hogan, Patrick G. Cyert, Martha S. TI A conserved docking site modulates substrate affinity for calcineurin, signaling output, and in vivo function SO MOLECULAR CELL LA English DT Article ID SACCHAROMYCES-CEREVISIAE; TRANSCRIPTION FACTOR; GENE-EXPRESSION; STRESS RESPONSES; PROTEIN-KINASE; CYCLOSPORINE-A; BINDING-SITE; YEAST; NFAT; ACTIVATION AB Calcineurin, the conserved Ca2+/calmodulin-regulated protein phosphatase, mediates diverse aspects of Ca2+-dependent signaling. We show that substrates bind calcineurin with varying strengths and examine the impact of this affinity on signaling. We altered the calcineurin-docking site, or PxIxIT motif, in Crz1, the calcineurin-regulated transcription factor in S. cerevisiae, to decrease (Crz1(PVIAVN)) or increase (Crz1(PVIVIT)) its affinity for calcineurin. As a result, the Ca2+-dependent dephosphorylation and activation of Crz1(PVIAVN) are decreased, whereas Crz1(PVIVIT) is constitutively dephosphorylated and hyperactive. Surprisingly, the physiological consequences of altering calcineurin-Crz1 affinity depend on the growth conditions. Crz1(PVIVIT) improves yeast growth under several environmental stress conditions but causes a growth defect during alkaline stress, most likely by titrating calcineurin away from other substrates or regulators. Thus, calcineurin-substrate affinity determines the Ca2+ concentration dependence and output of signaling in vivo as well as the balance between different branches of calcineurin signaling in an overall biological response. C1 Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Cyert, MS (reprint author), Stanford Univ, Dept Biol Sci, 371 Serra Mall, Stanford, CA 94305 USA. EM mcyert@stanford.edu FU NIAID NIH HHS [R01 AI040127, AI40127]; NIGMS NIH HHS [GM-48728, R01 GM048729, R01 GM048729-17, R01 GM048729-18] NR 46 TC 53 Z9 54 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAR 23 PY 2007 VL 25 IS 6 BP 889 EP 901 DI 10.1016/j.molcel.2007.02.014 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 154NI UT WOS:000245513900013 PM 17386265 ER PT J AU Kales, SN Soteriades, ES Christophi, CA Christiani, DC AF Kales, Stefanos N. Soteriades, Elpidoforos S. Christophi, Costas A. Christiani, David C. TI Emergency duties and deaths from heart disease among firefighters in the United States SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; BODY-MASS INDEX; RISK-FACTORS; CARDIOVASCULAR-DISEASE; FIRE FIGHTERS; HEALTH; ASSOCIATION; RESPONSES; FITNESS; PROFILE AB Background: Heart disease causes 45% of the deaths that occur among U.S. firefighters while they are on duty. We examined duty-specific risks of death from coronary heart disease among on-duty U.S. firefighters from 1994 to 2004. Methods: We reviewed summaries provided by the Federal Emergency Management Agency of the deaths of all on-duty firefighters between 1994 and 2004, except for deaths associated with the September 11, 2001, terrorist attacks. Estimates of the proportions of time spent by firefighters each year performing various duties were obtained from a municipal fire department, from 17 large metropolitan fire departments, and from a national database. Odds ratios and 95% confidence intervals for death from coronary heart disease during specific duties were calculated from the ratios of the observed odds to the expected odds, with nonemergency duties as the reference category. Results: Deaths from coronary heart disease were associated with suppressing a fire (32.1% of all such deaths), responding to an alarm (13.4%), returning from an alarm (17.4%), engaging in physical training (12.5%), responding to nonfire emergencies (9.4%), and performing nonemergency duties (15.4%). As compared with the odds of death from coronary heart disease during nonemergency duties, the odds were 12.1 to 136 times as high during fire suppression, 2.8 to 14.1 times as high during alarm response, 2.2 to 10.5 times as high during alarm return, and 2.9 to 6.6 times as high during physical training. These odds were based on three estimates of the time that firefighters spend on their duties. Conclusions: Certain emergency firefighting duties were associated with a risk of death from coronary heart disease that was markedly higher than the risk associated with nonemergency duties. Fire suppression was associated with the highest risk, which was approximately 10 to 100 times as high as that for nonemergency duties. C1 Harvard Univ, Sch Med, Cambridge Hlth Alliance, Employee Hlth & Ind Med, Cambridge, MA 02139 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Kindred Hosp NE, Ctr Occupat & Environm Med, Braintree, MA USA. Harvard Univ, Sch Publ Hlth, Cyprus Inst Inst Environm & Publ Hlth, Nicosia, Cyprus. RP Kales, SN (reprint author), Harvard Univ, Sch Med, Cambridge Hlth Alliance, Employee Hlth & Ind Med, Lee B Macht Bldg,Rm 427,1493 Cambridge St, Cambridge, MA 02139 USA. EM skales@challiance.org FU PHS HHS [T42/CCT122961-02] NR 39 TC 177 Z9 180 U1 1 U2 19 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 22 PY 2007 VL 356 IS 12 BP 1207 EP 1215 DI 10.1056/NEJMoa060357 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 148UP UT WOS:000245101900005 PM 17377158 ER PT J AU Vallat, J Cros, DP Harris, NL Siao, P Hedley-Whyte, ET Costenbader, KH AF Vallat, Jean-Michel Cros, Didier P. Harris, Nancy Lee Siao, Peter Hedley-Whyte, E. Tessa Costenbader, Karen H. TI A 27-year-old woman with pain and swelling of the legs - Axonal neuropathy due to lymphoplasmacytic small-vessel vasculitis, associated with connective-tissue disease with features of Sjogren's syndrome, associated with autoimmune thyroiditis and autoimmune gastritis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PERNICIOUS-ANEMIA; REVISED CRITERIA; CLASSIFICATION; MANIFESTATIONS C1 Univ Limoges, Dept Neurol & Neuropathol, Limoges, France. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Div Neuropathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Vallat, J (reprint author), Univ Limoges, Dept Neurol & Neuropathol, Limoges, France. NR 18 TC 3 Z9 3 U1 1 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 22 PY 2007 VL 356 IS 12 BP 1252 EP 1259 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 148UP UT WOS:000245101900012 PM 17377164 ER PT J AU Ross, JS Lackner, JE Lurie, P Gross, CP Wolfe, S Krumholz, HM AF Ross, Joseph S. Lackner, Josh E. Lurie, Peter Gross, Cary P. Wolfe, Sidney Krumholz, Harlan M. TI Pharmaceutical company payments to physicians - Early experiences with disclosure laws in Vermont and Minnesota SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACADEMIC MEDICAL-CENTERS; INDUSTRY; DRUG; HOUSESTAFF AB Context Recent legislation in 5 states and the District of Columbia mandated state disclosure of payments made to physicians by pharmaceutical companies. In 2 of these states, Vermont and Minnesota, payment disclosures are publicly available. Objectives To determine the accessibility and quality of the data available in Vermont and Minnesota and to describe the prevalence and magnitude of disclosed payments. Design and Setting Cross-sectional analysis of publicly available data from July 1, 2002, through June 30, 2004, in Vermont and from January 1, 2002, through December 31, 2004, in Minnesota. Main Outcome Measures Accessibility and quality of disclosure data and the number, value, and type of payments of $100 or more to physicians. Results Access to payment data required extensive negotiation with the Office of the Vermont Attorney General and manual photocopying of individual disclosure forms at Minnesota's State Board of Pharmacy. In Vermont, 61% of payments were not released to the public because pharmaceutical companies designated them as trade secrets and 75% of publicly disclosed payments were missing information necessary to identify the recipient. In Minnesota, 25% of companies reported in each of the 3 years. In Vermont, among 12 227 payments totaling $2.18 million publicly disclosed, there were 2416 payments of $100 or more to physicians; total, $1.01 million; median payment, $177 (range, $100-$20 000). In Minnesota, among 6946 payments totaling $30.96 million publicly disclosed, there were 6238 payments of $100 or more to physicians; total, $22.39 million; median payment, $1000 (range, $100-$922239). Physician-specific analyses were possible only in Minnesota, identifying 2388 distinct physicians who received payment of $100 or more; median number of payments received, 1 (range, 1-88) and the median amount received, $1000 (range, $100-$1178203). Conclusions The Vermont and Minnesota laws requiring disclosure of payments do not provide easy access to payment information for the public and are of limited quality once accessed. However, substantial numbers of payments of $100 or more were made to physicians by pharmaceutical companies. C1 Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY 10029 USA. James J Peters VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. Publ Citizen, Hlth Res Grp, Washington, DC USA. Yale Univ, Sch Med, Dept Internal Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Med, Gen Internal Med Sect, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, Sect Hlth Policy & Adv, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Internal Med, Sect Cardiovasc Med, New Haven, CT 06510 USA. Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. RP Ross, JS (reprint author), Mt Sinai Sch Med, Dept Geriatr & Adult Dev, 1 Gustave L Levy Pl,POB 1070, New York, NY 10029 USA. EM joseph.ross@mssm.edu NR 17 TC 50 Z9 50 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 MAR 21 PY 2007 VL 297 IS 11 BP 1216 EP 1223 DI 10.1001/jama.297.11.1216 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 147XO UT WOS:000245039300025 PM 17374816 ER PT J AU Casarett, DJ Quill, TE AF Casarett, David J. Quill, Timothy E. TI "I'm not ready for hospice": Strategies for timely and effective hospice discussions SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; MALIGNANT BOWEL OBSTRUCTION; TERMINALLY-ILL PATIENTS; PATIENT PREFERENCES; PALLIATIVE CARE; ADVANCED CANCER; NURSING-HOMES; HEART-FAILURE; SURVIVAL; LIFE AB Hospice programs offer unique benefits for patients who are near the end of life and their families, and growing evidence indicates that hospice can provide high-quality care. Despite these benefits, many patients do not enroll in hospice, and those who enroll generally do so very late in the course of their illness. Some barriers to hospice referral arise from the requirements of hospice eligibility, which will be difficult to eliminate without major changes to hospice organization and financing. However, the challenges of discussing hospice create other barriers that are more easily remedied. The biggest communication barrier is that physicians are often unsure of how to talk with patients clearly and directly about their poor prognosis and limited treatment options (both requirements of hospice referral) without depriving them of hope. This article describes a structured strategy for discussing hospice, based on techniques of effective communication that physicians use in other "bad news" situations. This strategy can make hospice discussions both more compassionate and more effective. C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Rochester, Med Ctr, Ctr Eth Humanities & Palliat Care, Rochester, NY 14642 USA. RP Casarett, DJ (reprint author), 3615 Chestnut St, Philadelphia, PA 19104 USA. EM casarett@mail.med.upenn.edu NR 52 TC 54 Z9 55 U1 2 U2 9 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 20 PY 2007 VL 146 IS 6 BP 443 EP 449 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 150CC UT WOS:000245192200006 PM 17371889 ER PT J AU Nathan, DM Berkwits, M AF Nathan, David M. Berkwits, Michael TI Trials that matter: Rosiglitazone, ramipril, and the prevention of type 2 diabetes SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE INTERVENTION; CARDIOVASCULAR EVENTS; MELLITUS; REDUCTION; METFORMIN C1 Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. RP Nathan, DM (reprint author), Massachusetts Gen Hosp, Diabet Unit, 50 Staniford St,3rd Floor,S503, Boston, MA 02114 USA. EM dnathan@partners.org NR 17 TC 8 Z9 8 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 20 PY 2007 VL 146 IS 6 BP 461 EP 463 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 150CC UT WOS:000245192200010 PM 17371892 ER PT J AU Wang, TJ Larson, MG Keyes, MJ Levy, D Benjamin, EJ Vasan, RS AF Wang, Thomas J. Larson, Martin G. Keyes, Michelle J. Levy, Daniel Benjamin, Emelia J. Vasan, Ramachandran S. TI Association of plasma natriuretic peptide levels with metabolic risk factors in ambulatory individuals SO CIRCULATION LA English DT Article DE atrial natriuretic factor; epidemiology; natriuretic peptides; risk factors ID BODY-MASS INDEX; INSULIN-RESISTANCE; ANGIOTENSIN-II; HEART-FAILURE; ESSENTIAL-HYPERTENSION; LIPID MOBILIZATION; CIRCULATING LEVELS; DIABETES-MELLITUS; INHIBITION; OBESITY AB Background-Experimental studies suggest that the natriuretic peptides influence lipid and fatty acid metabolism. Although it has been shown that obese individuals have reduced natriuretic peptide levels, conflicting data exist on the relation of natriuretic peptide levels to other metabolic risk factors. Methods and Results-We examined the association of plasma levels of B-type natriuretic peptide and N-terminal pro-atrial natriuretic peptide with metabolic risk factors, the metabolic syndrome, and insulin resistance in 3333 Framingham study participants free of heart failure (mean age, 58 years; 54% women). Regression analyses were performed, with adjustment for clinical and echocardiographic variables. Plasma natriuretic peptide levels were inversely associated with all components of the metabolic syndrome except for elevated blood pressure. Adjusted natriuretic peptide levels were lower in persons with the metabolic syndrome compared with those without the metabolic syndrome: In men, B-type natriuretic peptide was 24% lower (P < 0.001) and N-terminal pro-atrial natriuretic peptide was 16% lower (P < 0.001); in women, B-type natriuretic peptide was 29% lower (P < 0.001) and N-terminal pro-atrial natriuretic peptide was 18% lower (P < 0.001). Individuals with insulin resistance, as indicated by an elevated homeostasis model assessment (HOMA-IR) index, had lower levels of B-type natriuretic peptide (P=0.009 in men, P < 0.001 in women) and N-terminal pro-atrial natriuretic peptide (P < 0.001 in men, P < 0.001 in women). Conclusions-Having several metabolic risk factors is associated with low circulating natriuretic peptide levels, even after adjustment for body mass index. These findings raise the possibility that reduced natriuretic peptide activity is a manifestation of the metabolic syndrome, which may have important clinical and pathophysiological implications. C1 Massachusetts Gen Hosp, Cardiol Div, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Natl Heart Lung & Blood Inst, Bethesda, MD USA. Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. RP Wang, TJ (reprint author), Massachusetts Gen Hosp, Cardiol Div, Dept Med, GRB-800,55 Fruit St, Boston, MA 02114 USA. EM tjwang@partners.org OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [2K24-HL-04334, K23-HL-074077, N01-HC-25195] NR 48 TC 112 Z9 116 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 MAR 20 PY 2007 VL 115 IS 11 BP 1345 EP 1353 DI 10.1161/CIRCULATIONAHA.106.655142 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 147WK UT WOS:000245034300004 PM 17339551 ER PT J AU Sosnovik, DE Nahrendorf, M Deliolanis, N Novikov, M Aikawa, E Josephson, L Rosenzweig, A Weissleder, R Ntziachristos, V AF Sosnovik, David E. Nahrendorf, Matthias Deliolanis, Nikolaos Novikov, Mikhail Aikawa, Elena Josephson, Lee Rosenzweig, Anthony Weissleder, Ralph Ntziachristos, Vasilis TI Fluorescence tomography and magnetic resonance imaging of myocardial macrophage infiltration in infarcted myocardium in vivo SO CIRCULATION LA English DT Article DE fluorescence; inflammation; magnetic resonance imaging; myocardium; tomography ID COLONY-STIMULATING FACTOR; CARDIAC ALLOGRAFT-REJECTION; NONINVASIVE DETECTION; CELL-DEATH; ATHEROSCLEROSIS; INFLAMMATION; NANOPARTICLES; IMPROVEMENT; DEFICIENCY; ACCURACY AB Background-Fluorescence imaging of the heart is currently limited to invasive ex vivo or in vitro applications. We hypothesized that the adaptation of advanced transillumination and tomographic techniques would allow noninvasive fluorescence images of the heart to be acquired in vivo and be coregistered with in vivo cardiac magnetic resonance images. Methods and Results-The uptake of the magnetofluorescent nanoparticle CLIO-Cy5.5 by macrophages in infarcted myocardium was studied. Ligation of the left coronary artery was performed in 12 mice and sham surgery in 7. The mice were injected, 48 hours after surgery, with 3 to 20 mg of iron per kilogram of CLIO-Cy5.5. Magnetic resonance imaging and fluorescence molecular tomography were performed 48 hours later. An increase in magnetic resonance imaging contrast-to-noise ratio, indicative of myocardial probe accumulation, was seen in the anterolateral walls of the infarcted mice but not in the sham-operated mice (23.0 +/- 2.7 versus 5.43 +/- 2.4; P < 0.01). Fluorescence intensity over the heart was also significantly greater in the fluorescence molecular tomography images of the infarcted mice (19.1 +/- 5.2 versus 5.3 +/- 1.4; P < 0.05). The uptake of CLIO-Cy5.5 by macrophages infiltrating the infarcted myocardium was confirmed by fluorescence microscopy and immunohistochemistry. Conclusions-Noninvasive imaging of myocardial macrophage infiltration has been shown to be possible by both fluorescence tomography and magnetic resonance imaging. This could be of significant value in both the research and clinical settings. The techniques developed could also be used to image other existing fluorescent and magnetofluorescent probes and could significantly expand the role of fluorescence imaging in the heart. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02138 USA. RP Sosnovik, DE (reprint author), Ctr Mol Imaging Res, 149 13th St, Charlestown, MA 02129 USA. EM sosnovik@nmr.mgh.harvard.edu OI Deliolanis, Nikolaos/0000-0002-6392-3035 FU NHLBI NIH HHS [K08 HL079984, U01 HL080731]; NIBIB NIH HHS [R01EB000750] NR 39 TC 118 Z9 122 U1 1 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 20 PY 2007 VL 115 IS 11 BP 1384 EP 1391 DI 10.1161/CIRCULATIONAHA.106.663351 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 147WK UT WOS:000245034300009 PM 17339546 ER PT J AU Michaelson, MD Kaufman, DS Lee, H McGovern, FJ Kantoff, PW Fallon, MA Finkelstein, JS Smith, MR AF Michaelson, M. Dror Kaufman, Donald S. Lee, Hang McGovern, Francis J. Kantoff, Philip W. Fallon, Mary Anne Finkelstein, Joel S. Smith, Matthew R. TI Randomized controlled trial of annual zoledronic acid to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ANDROGEN-DEPRIVATION THERAPY; MINERAL DENSITY; RISK-FACTORS; CARCINOMA; JAWS; BISPHOSPHONATES; OSTEONECROSIS; PAMIDRONATE; BLOCKADE; FRACTURE AB Purpose Gonadotropin-releasing hormone (GnRH) agonists decrease bone mineral density (BMD) and increase fracture risk in men with prostate cancer. Annual zoledronic acid increases BMD in postmenopausal women, but its efficacy in hypogonadal men is not known. Patients and Methods In a 12-month study, 40 men with nonmetastatic prostate cancer who were receiving a GnRH agonist and had T scores more than -2.5 were randomly assigned to zoledronic acid (4 mg intravenously on day 1 only) or placebo. BMD of the posteroanterior lumbar spine and proximal femur were measured by dual-energy x-ray absorptiometry. Results Mean (+/- SE) BMD of the posteroanterior lumbar spine decreased by 3.1% +/- 1.0% in men assigned to placebo and increased by 4.0% +/- 1.0% in men assigned to zoledronic acid (P < .001). BMD of the total hip decreased by 1.9% +/- 0.7% in men assigned to placebo and increased by 0.7% +/- 0.5% in men assigned to zoledronic acid (P = .004). Similar between-group differences were observed for the femoral neck and trochanter. Serum N-telopeptide, a marker of osteoclast activity, decreased significantly after zoledronic acid treatment. Conclusion In men receiving a GnRH agonist, a single treatment with zoledronic acid significantly increased BMD and durably suppressed serum N-telopeptide levels for 12 months. Annual zoledronic acid may be a convenient and effective strategy to prevent bone loss in hypogonadal men. C1 Massachusetts Gen Hosp, Dept Hematol Oncol, Div Hematol & Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, Div Hematol & Oncol, 100 Blossom St,Cox 640, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu OI Michaelson, Dror/0000-0001-9249-6338 FU NCI NIH HHS [K24 CA121990, K24 CA121990-02] NR 19 TC 166 Z9 168 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 MAR 20 PY 2007 VL 25 IS 9 BP 1038 EP 1042 DI 10.1200/JCO.2006.07.3361 PG 5 WC Oncology SC Oncology GA 152GD UT WOS:000245348600006 PM 17369566 ER PT J AU Keating, NL Landrum, MB Guadagnoli, E Winer, EP Ayanian, JZ AF Keating, Nancy L. Landrum, Mary Beth Guadagnoli, Edward Winer, Eric P. Ayanian, John Z. TI Surveillance testing among survivors of early-stage breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; OF-CLINICAL-ONCOLOGY; ROUTINE FOLLOW-UP; AMERICAN-SOCIETY; SPECIALIST CARE; CLAIMS DATA; LINKED MEDICARE; QUALITY; GUIDELINES; PHYSICIAN AB Purpose Guidelines recommend against routine surveillance testing for women who have had breast cancer. We described follow-up care for breast cancer survivors, examined how surveillance testing varies by the types of physicians seen, and assessed changes in testing rates over time. Methods Using Surveillance, Epidemiology, and End Results-Medicare data, we studied a population-based cohort of 44,511 women age >= 65 years diagnosed with stage I/II breast cancer during 1992 to 1999 and observed through 2001. We measured bone scans, tumor antigen tests, chest x-rays, and other chest/abdominal imaging during 3 consecutive surveillance years. We described physicians seen in follow-up and used repeated-measures logistic regression to assess the relationship with testing and to assess testing trends over time. Results Nearly half of breast cancer survivors saw a medical oncologist in surveillance year 1, but only 27% saw a medical oncologist annually for 3 years. In adjusted analyses, women seeing medical oncologists had more bone scans, tumor antigen testing, chest x-rays, and chest/abdominal imaging than other women (all P < .001). Nevertheless, rates of testing decreased over time (all P < .001). Rates of tumor antigen testing and chest x-rays decreased faster and chest/abdominal imaging increased slower among women seeing medical oncologists than among other women (all P < .05). Conclusion Nonrecommended testing for early-stage breast cancer patients has decreased over time. Although most breast cancer survivors did not see oncologists annually, those who did had substantially higher rates of testing than others; whether such testing in this low-risk population was due to more symptoms or excessive surveillance is an important question for additional study. C1 Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM keating@hcp.med.harvard.edu NR 41 TC 65 Z9 68 U1 2 U2 4 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 MAR 20 PY 2007 VL 25 IS 9 BP 1074 EP 1081 DI 10.1200/JCO.2006.08.6876 PG 8 WC Oncology SC Oncology GA 152GD UT WOS:000245348600012 PM 17369571 ER PT J AU Weyman, AE AF Weyman, Arthur E. TI The year in echocardiography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID MYOCARDIAL CONTRAST ECHOCARDIOGRAPHY; TIME 3-DIMENSIONAL ECHOCARDIOGRAPHY; CARDIAC RESYNCHRONIZATION THERAPY; EMISSION COMPUTED-TOMOGRAPHY; GRADIENT AORTIC-STENOSIS; LEFT-VENTRICULAR VOLUME; PATENT FORAMEN OVALE; MAGNETIC-RESONANCE; 2-DIMENSIONAL SPECKLE; EJECTION FRACTION C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Weyman, AE (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St,Yawkey 506, Boston, MA 02114 USA. EM aweyman@partners.org NR 44 TC 5 Z9 6 U1 0 U2 0 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 MAR 20 PY 2007 VL 49 IS 11 BP 1212 EP 1219 DI 10.1016/j.jacc.2007.01.016 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 148HF UT WOS:000245064600011 PM 17367666 ER PT J AU Goldstein, JN Fazen, LE Snider, R Schwab, K Greenberg, SM Smith, EE Lev, MH Rosand, J AF Goldstein, J. N. Fazen, L. E. Snider, R. Schwab, K. Greenberg, S. M. Smith, E. E. Lev, M. H. Rosand, J. TI Contrast extravasation on CT angiography predicts hematoma expansion in intracerebral hemorrhage SO NEUROLOGY LA English DT Article ID EARLY HEMOSTATIC THERAPY; RECOMBINANT FACTOR VIIA; ACTIVATED FACTOR-VII; ANTICOAGULANT-THERAPY; WARFARIN; THROMBOLYSIS; ENLARGEMENT; GROWTH; WINDOW; RISK AB Background: Patients with acute intracerebral hemorrhage ( ICH) presenting within 3 hours of symptom onset are known to be at increased risk of expansion. However, only a minority arrive within this time frame. Therefore, alternative markers for expansion risk are needed. Objective: To examine whether contrast extravasation on CT angiography ( CTA) at presentation predicts subsequent hematoma expansion. Methods: Consecutive patients with primary ICH presenting to an urban tertiary care hospital were prospectively captured in a database. We retrospectively reviewed images for all patients receiving a CTA and at least one further CT scan within 48 hours. Results: Complete data were available for 104 patients. Contrast extravasation at the time of CTA was present in 56% of patients, and associated with an increased risk of hematoma expansion ( 22% vs 2%, p = 0.003). Patients who received a baseline CTA within 3 hours were more likely to have subsequent expansion ( 27%, vs 13% for those presenting later, p = 0.1). However, after multivariable analysis, contrast extravasation was the only significant predictor of hematoma expansion ( OR 18, 95% CI 2.1 to 162). This effect was independent of time to presentation. Conclusions: Contrast extravasation is independently associated with hematoma expansion. Patients presenting within the first few hours after symptom onset have traditionally been considered those at highest risk of expansion. However, for those presenting later, the presence of contrast may be a useful marker to guide therapies aimed at decreasing this risk. C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Goldstein, JN (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Clin 115,55 Fruit St, Boston, MA 02114 USA. EM jgoldstein@partners.org RI Goldstein, Joshua/H-8953-2016; OI Smith, Eric/0000-0003-3956-1668 FU NINDS NIH HHS [1 K23 NS42695-01, R01 NS04217] NR 30 TC 158 Z9 160 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 20 PY 2007 VL 68 IS 12 BP 889 EP 894 DI 10.1212/01.wnl.0000257087.22852.21 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 147WL UT WOS:000245034400004 PM 17372123 ER PT J AU Ullrich, NJ Robertson, R Kinnamon, DD Kieran, MW Turner, CD Chi, SN Goumnerova, L Proctor, M Tarbell, NJ Marcus, KJ Pomeroy, SL AF Ullrich, N. J. Robertson, R. Kinnamon, D. D. Kieran, M. W. Turner, C. D. Chi, S. N. Goumnerova, L. Proctor, M. Tarbell, N. J. Marcus, K. J. Pomeroy, S. L. TI Moyamoya following cranial irradiation for primary brain tumors in children SO NEUROLOGY LA English DT Article ID VESSEL OCCLUSIVE VASCULOPATHY; RADIATION-THERAPY; IVY SIGN; SURGICAL-TREATMENT; PIAL SYNANGIOSIS; OPTIC GLIOMA; YOUNG-ADULTS; DISEASE; CHILDHOOD; NEUROFIBROMATOSIS AB Objective: To study the risk factors for the development of moyamoya syndrome after cranial irradiation for primary brain tumors in children. Methods: We reviewed neuroimaging studies and dosimetry data for 456 children who were treated with radiation for a primary brain tumor and who were prospectively evaluated with serial neuroimaging studies and neurologic evaluations. A total of 345 patients had both adequate neuroimaging and radiation dosimetry data for further analysis. We used survival analysis techniques to examine the relationship of clinically important variables as risk factors for the development of moyamoya over time. Results: Overall, 12 patients ( 3.5%) developed evidence of moyamoya. The onset of moyamoya was more rapid for patients with neurofibromatosis type 1 ( NF1) ( median of 38 vs 55 months) and for patients who received > 5,000 cGy of radiation ( median of 42 vs 67 months). In a multiple Cox proportional hazards regression analysis controlling for age at start of radiation, each 100- cGy increase in radiation dose increased the rate of moyamoya by 7% ( hazard ratio [ HR] = 1.07, 95% CI: 1.02 to 1.13, p = 0.01) and the presence of NF1 increased the rate of moyamoya threefold ( HR = 3.07, 95% CI: 0.90 to 10.46, p = 0.07). Conclusions: Moyamoya syndrome is a potentially serious complication of cranial irradiation in children, particularly for those patients with tumors in close proximity to the circle of Willis, such as optic pathway glioma. Patients who received higher doses of radiation to the circle of Willis and with neurofibromatosis type 1 have increased risk of the development of moyamoya syndrome. C1 Childrens Hosp, Dept Neurol, Boston, MA 02446 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Childrens Hosp, Clin Res Program, Boston, MA 02115 USA. Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Childrens Hosp, Dept Radiat Therapy, Boston, MA 02115 USA. Dana Farber Canc Inst, Pediat Brain Tumor Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Miami, Miller Sch Med, Div Pediat Clin Res, Dept Pediat, Miami, FL 33152 USA. RP Ullrich, NJ (reprint author), Childrens Hosp, Dept Neurol, 300 Longwood Ave, Boston, MA 02446 USA. EM nicole.ullrich@childrens.harvard.edu RI Kinnamon, Daniel/J-4207-2013; OI Kieran, Mark/0000-0003-2184-7692; Robertson, Richard/0000-0001-8811-4405 NR 54 TC 91 Z9 95 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 20 PY 2007 VL 68 IS 12 BP 932 EP 938 DI 10.1212/01.wnl.0000257095.33125.48 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 147WL UT WOS:000245034400012 PM 17372129 ER PT J AU Chou, SHY Singhal, AB AF Chou, Sherry H. -Y. Singhal, Aneesh B. TI Multiple punctate cerebral hemorrhages in acute leukemia with blast crisis SO NEUROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. RP Singhal, AB (reprint author), Massachusetts Gen Hosp, Philip Kistler Stroke Res Ctr, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM asinghal@partners.org RI Chou, Sherry/G-5779-2015 NR 2 TC 5 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 20 PY 2007 VL 68 IS 12 BP 953 EP 953 DI 10.1212/01.wnl.0000257151.61125.51 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 147WL UT WOS:000245034400016 PM 17372133 ER PT J AU Chheda, MG Drappatz, J Greenberger, NJ Kesari, S Weiss, SE Gigas, DC Doherty, LM Wen, PY AF Chheda, M. G. Drappatz, J. Greenberger, N. J. Kesari, S. Weiss, S. E. Gigas, D. C. Doherty, L. M. Wen, P. Y. TI Hepatitis B reactivation during glioblastoma treatment with temozolomide: A cautionary note SO NEUROLOGY LA English DT Editorial Material ID CYTOTOXIC CHEMOTHERAPY; CANCER-PATIENTS; VIRUS REACTIVATION; RISK-FACTORS; RECOMMENDATIONS; PREVENTION C1 Brigham & Womens Hosp, Div Canc Neurol, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Ctr Canc, Dana Farber Canc Inst, Ctr Neurooncol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Chheda, MG (reprint author), Brigham & Womens Hosp, Div Canc Neurol, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. EM mchheda@partners.org RI Kesari, Santosh/E-8461-2013 NR 7 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 20 PY 2007 VL 68 IS 12 BP 955 EP 956 DI 10.1212/01.wnl.0000259430.48835.b5 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 147WL UT WOS:000245034400018 PM 17372135 ER PT J AU Ide, K Wang, H Tahara, H Liu, JX Wang, XY Asahara, T Sykes, M Yang, YG Ohdan, H AF Ide, Kentaro Wang, Hui Tahara, Hiroyuki Liu, Jianxiang Wang, Xiaoying Asahara, Toshimasa Sykes, Megan Yang, Yong-Guang Ohdan, Hideki TI Role for CD47-SIRP alpha signaling in xenograft rejection by macrophages SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE xenotransplantation; phagocytosis; reticuloendothelial system ID HUMAN T-CELL; SIRP-ALPHA; NEGATIVE REGULATION; PROTEIN-ALPHA; KNOCKOUT PIGS; CD47; XENOTRANSPLANTATION; TRANSPLANTATION; PHAGOCYTOSIS; RECOGNITION AB We have previously proven that human macrophages can phagocytose porcine cells even in the absence of Ab or complement opsonization, indicating that macrophages present a pivotal immunological obstacle to xenotransplantation. A recent report indicates that the signal regulatory protein (SIRP)alpha is a critical immune inhibitory receptor on macrophages, and its interaction with CD47, a ligand for SIRP alpha, prevents autologous phagocytosis. Considering the limited compatibility (73%) in amino acid sequences between pig and human CD47, we hypothesized that the interspecies incompatibility of CD47 may contribute to the rejection of xenogeneic cells by macrophages. In the present study, we have demonstrated that porcine CD47 does not induce SIRPa tyrosine phosphorylation in human macrophage-like cell line, and soluble human CD47-Fc fusion protein inhibits the phagocytic activity of human macrophages toward porcine cells. In addition, we have verified that manipulation of porcine cells for expression of human CD47 radically reduces the susceptibility of the cells to phagocytosis by human macrophages. These results indicate that the interspecies incompatibility of CD47 significantly contributes to the rejection of xenogeneic cells by macrophages. Genetic induction of human CD47 on porcine cells could provide inhibitory signaling to SIRPa on human macrophages, providing a novel approach to preventing macrophage-mediated xenograft rejection. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr,Bone Marrow Transplanta, Boston, MA 02129 USA. Hiroshima Univ, Grad Sch Biomed Sci, Dept Surg, Div Frontier Med Sci,Programs Biomed Res, Hiroshima 7348551, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol & Neurol,Neuroprotect Res Lab, Boston, MA 02129 USA. RP Yang, YG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr,Bone Marrow Transplanta, E Bldg 149,13th St, Boston, MA 02129 USA. EM yongguang.yang@tbrc.mgh.harvard.edu; hohdan@hiroshima-u.ac.jp FU NIAID NIH HHS [2P01 AI 045897, P01 AI045897, R01 AI064569] NR 29 TC 111 Z9 125 U1 1 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 20 PY 2007 VL 104 IS 12 BP 5062 EP 5066 DI 10.1073/pnas.0609661104 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 150YY UT WOS:000245256700054 PM 17360380 ER PT J AU Caperton, L Murphey, P Yamazaki, Y McMahan, CA Walter, CA Yanagimachi, R McCarrey, JR AF Caperton, Lee Murphey, Patricia Yamazaki, Yukiko McMahan, C. Alex Walter, Christi A. Yanagimachi, Ryuzo McCarrey, John R. TI Assisted reproductive technologies do not alter mutation frequency or spectrum SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE genetic integrity; in vitro fertilization; infertility; mutagenesis; embryology ID INTRACYTOPLASMIC SPERM INJECTION; IN-VITRO FERTILIZATION; PREIMPLANTATION MOUSE EMBRYOS; BECKWITH-WIEDEMANN-SYNDROME; LACI GENE; TESTICULAR SPERMATOZOA; IMPRINTING DEFECTS; MUTANT FREQUENCIES; ROUND SPERMATIDS; TRANSGENIC MICE AB Assisted reproductive technologies (ARTs) have now contributed to the birth of > 3 million babies worldwide, but concerns remain regarding the safety of these methods. We have used a transgenic mouse model to examine the effects of ARTs on the frequency and spectrum of point mutations in midgestation mouse fetuses produced by either natural reproduction or various methods of ART, including preimplantation culture, embryo transfer, in vitro fertilization, intracytoplasmic sperm injection, and round spermatid injection. Our results show that there is no significant difference in the frequency or spectrum of de novo point mutations found in naturally conceived fetuses and fetuses produced by in vitro fertilization, intracytoplasmic sperm injection, or round spermatid injection. These results, based on analyses of a transgenic mouse system, indicate that with respect to maintenance of genetic integrity, ARTs appear to be safe. C1 Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. Univ Texas San Antonio, San Antonio, TX 78249 USA. Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96813 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Yanagimachi, R (reprint author), Univ Texas Hlth Sci Ctr San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM yana@hawaii.edu; john.mccarrey@utsa.edu FU NICHD NIH HHS [R01 HD042772, HD 42772] NR 47 TC 28 Z9 29 U1 0 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 MAR 20 PY 2007 VL 104 IS 12 BP 5085 EP 5090 DI 10.1073/pnas.0611642104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 150YY UT WOS:000245256700058 PM 17360354 ER PT J AU Perez, GI Jurisicova, A Wise, L Lipina, T Kanisek, M Bechard, A Takai, Y Hunt, P Roder, J Grynpas, M Tilly, JL AF Perez, Gloria I. Jurisicova, Andrea Wise, Lisa Lipina, Tatiana Kanisek, Marijana Bechard, Allison Takai, Yasushi Hunt, Patricia Roder, John Grynpas, Marc Tilly, Jonathan L. TI Absence of the proapoptotic Bax protein extends fertility and alleviates age-related health complications in female mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE aging; apoptosis; menopause; ovary ID ADIPOSE-TISSUE; BREAST-CANCER; BOWEL-DISEASE; C57BL/6J MICE; WOMEN; AROMATASE; OOCYTE; TRANSITION; EXHAUSTION; ESTROGEN AB The menopausal transition in human females, which is driven by a loss of cyclic ovarian function, occurs around age 50 and is thought to underlie the emergence of an array of health problems in aging women. Although mice do not undergo a true menopause, female mice exhibit ovarian failure long before death because of chronological age and subsequently develop many of the same age-associated health complications observed in postmenopausal women. Here we show in mice that inactivation of the proapoptotic Bax gene, which sustains ovarian lifespan into advanced age, extends fertile potential and minimizes many age-related health problems, including bone and muscle loss, excess fat deposition, alopecia, cataracts, deafness, increased anxiety, and selective attention deficit. Further, ovariectomy studies show that the health benefits gained by aged females from Bax deficiency reflect a complex interplay between ovary-dependent and -independent pathways. Importantly, and contrary to popular belief, prolongation of ovarian function into advanced age by Bax deficiency did not lead to an increase in tumor incidence. Thus, the development of methods for postponing ovarian failure at menopause may represent an attractive option for improving the quality of life in aging females. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent Obstet & Gynecol, Boston, MA 02114 USA. Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. Washington State Univ, Ctr Reprod Biol, Pullman, WA 99164 USA. Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent Obstet & Gynecol, Boston, MA 02114 USA. EM jtilly@partners.org RI Grynpas, Marc/E-4576-2013; Jurisicova, Andrea/E-4580-2013; Roder, John/G-6468-2013; Lipina, Tatiana/G-9148-2014 FU NIA NIH HHS [R01/R37-AG012279, R37 AG012279, R01 AG012279] NR 36 TC 53 Z9 58 U1 1 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 MAR 20 PY 2007 VL 104 IS 12 BP 5229 EP 5234 DI 10.1073/pnas.0608557104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 150YY UT WOS:000245256700082 PM 17360389 ER PT J AU Liston, A Farr, AG Chen, Z Benoist, C Mathis, D Manley, NR Rudensky, AY AF Liston, Adrian Farr, Andrew G. Chen, Zhibin Benoist, Christophe Mathis, Diane Manley, Nancy R. Rudensky, Alexander Y. TI Lack of Foxp3 function and expression in the thymic epithelium SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID SCURFY SF MOUSE; TRANSCRIPTION FACTOR FOXP3; LYMPHORETICULAR DISEASE; T-CELLS; POLYENDOCRINOPATHY; IMMUNODEFICIENCY; TRANSPLANTATION; ENTEROPATHY; MUTATION; MUTANT AB Foxp3 is essential for the commitment of differentiating thymocytes to the regulatory CD4(+) T ( T reg) cell lineage. In humans and mice with a genetic Foxp3 deficiency, absence of this critical T reg cell population was suggested to be responsible for the severe autoimmune lesions. Recently, it has been proposed that in addition to T reg cells, Foxp3 is also expressed in thymic epithelial cells where it is involved in regulation of early thymocyte differentiation and is required to prevent autoimmunity. Here, we used genetic tools to demonstrate that the thymic epithelium does not express Foxp3. Furthermore, we formally showed that genetic abatement of Foxp3 in the hematopoietic compartment, i.e. in T cells, is both necessary and sufficient to induce the autoimmune lesions associated with Foxp3 loss. In contrast, deletion of a conditional Foxp3 allele in thymic epithelial cells did not result in detectable changes in thymocyte differentiation or pathology. Therefore, in mice the only known role for Foxp3 remains promotion of T reg cell differentiation within the T cell lineage, whereas there is no role for Foxp3 in thymic epithelial cells. C1 Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Biol Struct, Seattle, WA 98195 USA. Univ Washington, Sch Med, Howard Hughes Med Inst, Seattle, WA 98195 USA. Univ Georgia, Dept Genet, Athens, GA 30602 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Joslin Diabet Ctr, Boston, MA 02215 USA. RP Rudensky, AY (reprint author), Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98195 USA. EM aruden@u.washington.edu RI Liston, Adrian/A-2478-2008; Liston, Adrian/G-8606-2013 OI Liston, Adrian/0000-0002-6272-4085 NR 22 TC 41 Z9 44 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 19 PY 2007 VL 204 IS 3 BP 475 EP 480 DI 10.1084/jem.20062465 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 150IX UT WOS:000245210800009 PM 17353370 ER PT J AU Worbs, T Mempel, TR Bolter, J von Andrian, UH Forster, R AF Worbs, Tim Mempel, Thorsten R. Boelter, Jasmin von Andrian, Ulrich H. Foerster, Reinhold TI CCR7 ligands stimulate the intranodal motility of T lymphocytes in vivo SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID DENDRITIC CELLS; LYMPH-NODES; ANTIGEN; MIGRATION; BEHAVIOR; DETERMINES; CHEMOKINE; DYNAMICS; IMMUNITY; TISSUES AB In contrast to lymphocyte homing, little is known about molecular cues controlling the motility of lymphocytes within lymphoid organs. Applying intravital two-photon microscopy, we demonstrate that chemokine receptor CCR7 signaling enhances the intranodal motility of CD4(+) T cells. Compared to wild-type (WT) cells, the average velocity and mean motility coefficient of adoptively transferred CCR7-deficient CD4(+) T lymphocytes in T cell areas of WT recipients were reduced by 33 and 55%, respectively. Both parameters were comparably reduced for WT T lymphocytes migrating in T cell areas of plt/plt mice lacking CCR7 ligands. Importantly, systemic application of the CCR7 ligand CCL21 was sufficient to rescue the motility of WT T lymphocytes inside T cell areas of plt/plt recipients. Comparing the movement behavior of T cells in subcapsular areas that are devoid of detectable amounts of CCR7 ligands even in WT mice, we failed to reveal any differences between WT and plt/plt recipients. Furthermore, in both WT and plt/plt recipients, highly motile T cells rapidly accumulated in the subcapsular region after subcutaneous injection of the CCR7 ligand CCL19. Collectively, these data identify CCR7 and its ligands as important chemokinetic factors stimulating the basal motility of CD4(+) T cells inside lymph nodes in vivo. C1 Hannover Med Sch, Inst Immunol, D-30625 Hannover, Germany. Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Pathol, Boston, MA 02115 USA. RP Forster, R (reprint author), Hannover Med Sch, Inst Immunol, D-30625 Hannover, Germany. EM Foerster.Reinhold@mh-hannover.de RI Forster, Reinhold/D-6770-2011; von Andrian, Ulrich/A-5775-2008 NR 23 TC 188 Z9 191 U1 1 U2 8 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 MAR 19 PY 2007 VL 204 IS 3 BP 489 EP 495 DI 10.1084/jem.20061706 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 150IX UT WOS:000245210800011 PM 17325198 ER PT J AU Nombela-Arrieta, C Mempel, TR Soriano, SF Mazo, I Wymann, MP Hirsch, E Martinez, C Fukui, Y von Andrian, UH Stein, JV AF Nombela-Arrieta, Cesar Mempel, Thorsten R. Soriano, Silvia F. Mazo, Irina Wymann, Matthias P. Hirsch, Emilio Martinez-A., Carlos Fukui, Yoshinori von Andrian, Ulrich H. Stein, Jens V. TI A central role for DOCK2 during interstitial lymphocyte motility and sphingosine-1-phosphate-mediated egress SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID SPHINGOSINE 1-PHOSPHATE RECEPTORS; HIGH ENDOTHELIAL VENULES; T-CELLS; DENDRITIC CELLS; CUTTING EDGE; TRANSENDOTHELIAL MIGRATION; PHOSPHOINOSITIDE 3-KINASES; CHEMOKINE RECEPTOR; PROTEIN DOCK2; B-LYMPHOCYTES AB Recent observations using multiphoton intravital microscopy (MP-IVM) have uncovered an unexpectedly high lymphocyte motility within peripheral lymph nodes (PLNs). Lymphocyte-expressed intracellular signaling molecules governing interstitial movement remain largely unknown. Here, we used MP-IVM of murine PLNs to examine interstitial motility of lymphocytes lacking the Rac guanine exchange factor DOCK2 and phosphoinositide-3-kinase (PI3K)gamma, signaling molecules that act downstream of G protein-coupled receptors, including chemokine receptors (CKRs). T and B cells lacking DOCK2 alone or DOCK2 and PI3K gamma displayed markedly reduced motility inside T cell area and B cell follicle, respectively. Lack of PI3K.. alone had no effect on migration velocity but resulted in increased turning angles of T cells. As lymphocyte egress from PLNs requires the sphingosine-1-phosphate (S1P) receptor 1, a G alpha i protein-coupled receptor similar to CKR, we further analyzed whether DOCK2 and PI3K.. contributed to S1P-triggered signaling events. S1P-induced cell migration was significantly reduced in T and B cells lacking DOCK2, whereas T cell-expressed PI3K.. contributed to F-actin polymerization and protein kinase B phosphorylation but not migration. These findings correlated with delayed lymphocyte egress from PLNs in the absence of DOCK2 but not PI3K gamma, and a markedly reduced cell motility of DOCK2-deficient T cells in close proximity to efferent lymphatic vessels. In summary, our data support a central role for DOCK2, and to a lesser extent T cell-expressed PI3K gamma, for signal transduction during interstitial lymphocyte migration and S1P-mediated egress. C1 Univ Bern, Theodor Kocher Inst, CH-3012 Bern, Switzerland. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Basel, Inst Biochem & Genet, Dept Clin Biol Sci, CH-4003 Basel, Switzerland. Univ Turin, Dept Genet Biol & Biochem, I-10060 Turin, Italy. CSIC, Natl Biotechnol Ctr, Dept Immunol & Oncol, E-28049 Madrid, Spain. Kyushu Univ, Med Inst Bioregulat, PRESTO, Japan Sci & Technol Agcy, Fukuoka 8128582, Japan. Kyushu Univ, Med Inst Bioregulat, Dept Immunobiol & Neurosci, Div Immunogenet, Fukuoka 8128582, Japan. RP Stein, JV (reprint author), Univ Bern, Theodor Kocher Inst, CH-3012 Bern, Switzerland. EM jstein@tki.unibe.ch RI Wymann, Matthias/C-3227-2008; von Andrian, Ulrich/A-5775-2008; Hirsch, Emilio/F-4848-2013; OI Hirsch, Emilio/0000-0002-9073-6024; Nombela-Arrieta, Cesar/0000-0003-0415-259X FU NHLBI NIH HHS [T32 HL066987, T32-HL-066987-04] NR 62 TC 91 Z9 93 U1 1 U2 4 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 MAR 19 PY 2007 VL 204 IS 3 BP 497 EP 510 DI 10.1084/jem.20061780 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 150IX UT WOS:000245210800012 PM 17325199 ER PT J AU Bilenca, A Lasser, T Ozcan, A Leitgeb, RA Bouma, BE Tearney, GJ AF Bilenca, A. Lasser, T. Ozcan, A. Leitgeb, R. A. Bouma, B. E. Tearney, G. J. TI Image formation in fluorescence coherence-gated imaging through scattering media SO OPTICS EXPRESS LA English DT Article ID TOMOGRAPHY; MICROSCOPY; RESOLUTION; LIGHT AB Recently, we have experimentally demonstrated a new form of cross-sectional, coherence-gated fluorescence imaging referred to as SDFCT ('spectral-domain fluorescence coherence tomography'). Imaging in SD-FCT is accomplished by spectrally detecting self-interference of the spontaneous emission of fluorophores, thereby providing depth-resolved information on the axial positions of fluorescent probes. Here, we present a theoretical investigation of the factors affecting the detected SD-FCT signal through scattering media. An imaging equation for SD-FCT is derived that includes the effects of defocusing, numerical-aperture, and the optical properties of the medium. A comparison between the optical sectioning capabilities of SD-FCT and confocal microscopy is also presented. Our results suggest that coherence gating in fluorescence imaging may provide an improved approach for depth-resolved imaging of fluorescently labeled samples; high axial resolution (a few microns) can be achieved with low numerical apertures (NA < 0.09) while maintaining a large depth of field (a few hundreds of microns) in a relatively low scattering medium (6 mean free paths), whereas moderate NA's can be used to enhance depth selectivity in more highly scattering biological samples. (c) 2007 Optical Society of America. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Ecole Polytech Fed Lausanne, Lab Opt Biomed, CH-1015 Lausanne, Switzerland. Med Univ Vienna, Ctr Biomed Engn & Phys, A-1090 Vienna, Austria. RP Bilenca, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 50 Blossom St,BAR 7, Boston, MA 02114 USA. EM abilenca@partners.org RI Lasser, Theo/A-1006-2013; Ozcan, Aydogan/I-2608-2013; OI Lasser, Theo/0000-0002-4948-7580; Ozcan, Aydogan/0000-0002-0717-683X; Leitgeb, Rainer/0000-0002-0131-4111 NR 14 TC 7 Z9 7 U1 0 U2 2 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD MAR 19 PY 2007 VL 15 IS 6 BP 2810 EP 2821 DI 10.1364/OE.15.002810 PG 12 WC Optics SC Optics GA 148LN UT WOS:000245076200007 PM 19532519 ER PT J AU Shouse, MN Scordato, JC Farber, PR de Lanerolle, N AF Shouse, Margaret N. Scordato, John C. Farber, Paul R. de Lanerolle, Nihal TI The alpha 2 adrenoreceptor agonist clonidine suppresses evoked and spontaneous seizures, whereas the alpha 2 adrenoreceptor antagonist idazoxan promotes seizures in amygdala-kindled kittens SO BRAIN RESEARCH LA English DT Article DE norepinephrine; clonidine; idazoxan; spontaneous seizures; microinfusion; amygdala kindling; kittens ID TEMPORAL-LOBE EPILEPSY; LOCUS-COERULEUS; NOREPINEPHRINE DEPLETION; AUDIOGENIC-SEIZURES; BINDING-SITES; RAT-BRAIN; SLEEP; MICROINFUSION; NORADRENALINE; STIMULATION AB Microinfusion of alpha 2 adrenoreceptor agonists and antagonists into amygdala has contrasting effects on evoked and spontaneous seizure susceptibility in amygdala-kindled kittens. Subjects were 14 preadolescent kittens between 3 and 4 months old at the beginning of kindling. The same protocol was followed except that half the kittens received microinfusions (1 mu l) of the alpha 2 agonist clonidine (CLON; 1.32 nmol), and half received the alpha 2 antagonist idazoxan (IDA; 0.33 nmol). Infusions were made over 1 min through needles inserted into cannulae adjacent to stimulating electrodes in the kindled amygdala, and evoked seizures were tested 10-12 min later. The results were: (1) CLON elevated seizure thresholds obtained once at the beginning and end of kindling, but only when compared to sham control values (needle insertion only) in the same animals; IDA significantly reduced thresholds. (2) CLON retarded and IDA accelerated kindling rate, defined as the number of afterdischarges (ADs) required to achieve the first stage 6 seizure or generalized tonic-clonic convulsion (GTC). These effects were most pronounced on the emergence of seizure "generalization" stages (36) from "focal" seizure stages (1-2). (3) CLON prevented onset of spontaneous seizures, whereas IDA precipitated onset of spontaneous seizures in 100% of the animals before or during the 5-week post-kindling follow-up during which seizures were evoked once each work day. The study confirms previous findings in kindled rodents to show that CLON and IDA can have opposing effects on kindling development in kittens and is the first report to show contrasting effects on spontaneous epileptogenesis in kindled animals as well. (c) 2006 Elsevier B.V. All rights reserved. C1 VA Greater Los Angeles Healthcare Syst, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Dept Neurobiol, Los Angeles, CA 90024 USA. Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06520 USA. RP Shouse, MN (reprint author), VA Greater Los Angeles Healthcare Syst, Sepulveda, CA 91343 USA. EM nshouse@ucla.edu NR 47 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 16 PY 2007 VL 1137 IS 1 BP 58 EP 68 DI 10.1016/j.brainres.20006.12.033 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 145EY UT WOS:000244849300007 PM 17214976 ER PT J AU Kim, M Hersh, LB Leissring, MA Ingelsson, M Matsui, T Farris, W Lu, A Hyman, BT Selkoe, DJ Bertram, L Tanzi, RE AF Kim, Minji Hersh, Louis B. Leissring, Malcolm A. Ingelsson, Martin Matsui, Toshifumi Farris, Wesley Lu, Alice Hyman, Bradley T. Selkoe, Dennis J. Bertram, Lars Tanzi, Rudolph E. TI Decreased catalytic activity of the insulin-degrading enzyme in chromosome 10-linked Alzheimer disease families SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMYLOID BETA-PROTEIN; NEURODEGENERATIVE DISEASES; EXTRACELLULAR LEVELS; APOLIPOPROTEIN-E; PEPTIDE LEVELS; IN-VIVO; BRAIN; DEGRADATION; PROTEOLYSIS; INSULYSIN AB Insulin-degrading enzyme (IDE) is a zinc metalloprotease that degrades the amyloid beta-peptide, the key component of Alzheimer disease (AD)-associated senile plaques. We have previously reported evidence for genetic linkage and association of AD on chromosome 10q23-24 in the region harboring the IDE gene. Here we have presented the first functional assessment of IDE in AD families showing the strongest evidence of the genetic linkage. We have examined the catalytic activity and expression of IDE in lymphoblast samples from 12 affected and unaffected members of three chromosome 10-linked AD pedigrees in the National Institute of Mental Health AD Genetics Initiative family sample. We have shown that the catalytic activity of cytorsolic IDE to degrade insulin is reduced in affected versus unaffected subjects of these families. Further, we have shown the decrease in activity is not due to reduced IDE expression, suggesting the possible defects in IDE function in these AD families. In attempts to find potential mutations in the IDE gene in these families, we have found no coding region substitutions or alterations in splicing of the canonical exons and exon 15b of IDE. We have also found that total IDE mRNA levels are not significantly different in sporadic AD versus age-matched control brains. Collectively, our data suggest that the genetic linkage of AD in this set of chromosome 10-linked AD families may be the result of systemic defects in IDE activity in the absence of altered IDE expression, further supporting a role for IDE in AD pathogenesis. C1 Massachusetts Gen Hosp, Inst Neurodegenerat, Genet & Aging Res Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02129 USA. Univ Kentucky, Dept Mol & Cellular Biochem, Lexington, KY 40536 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Inst Neurodegenerat, Alzheimer Res Unit, Boston, MA 02129 USA. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp, Inst Neurodegenerat, Genet & Aging Res Unit, Bldg 114,16th St,C3009, Boston, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X NR 47 TC 56 Z9 57 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 MAR 16 PY 2007 VL 282 IS 11 BP 7825 EP 7832 DI 10.1074/jbc.M609168200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 148ND UT WOS:000245081000011 PM 17244626 ER PT J AU Block, K Gorin, Y Hoover, P Williams, P Chelmicki, T Clark, RA Yoneda, T Abboud, HE AF Block, Karen Gorin, Yves Hoover, Paul Williams, Paul Chelmicki, Tomasz Clark, Robert A. Yoneda, Toshiyuki Abboud, Hanna E. TI NAD(P)H Oxidases regulate HIF-2 alpha protein expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-SUPPRESSOR GENE; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; RENAL-CARCINOMA CELLS; GROWTH SUPPRESSION; NADPH OXIDASES; UP-REGULATION; CANCER CELLS; OXYGEN; ACTIVATION; NOX4 AB Biallelic inactivation of the von Hippel-Lindau tumor suppressor gene (VHL) is linked to the development of hereditary and sporadic renal cell carcinoma (RCC). In the absence of VHL, the alpha subunits of heterodimeric hypoxia-inducible transcription factors (HIT-1 alpha and HIF-2 alpha) are stabilized. Reactive oxygen species, generated by NAD(P)H oxidases, are involved in signaling cascades of malignant growth. We show that in VHL-deficient cells p22(phox), Nox4 protein levels and NADPH-dependent superoxide generation are increased. Reintroduction of VHL into the VHL-deficient cells down-regulates the expression of p22(phox) and NADPH-dependent superoxide generation. Inhibition of the 26 S proteasome in VHL-expressing cells increased p22(phox) protein levels, which correlated with an increase of NADPH-dependent superoxide generation. We also show that p22(phox) co-immunoprecipitates with VHL in vivo. Moreover, p22(phox) is a target of ubiquitination. Importantly, in VHL-deficient cells, diphenyleneiodonium chloride (DPI), an inhibitor of Nox oxidases, decreased the expression of HIF-2a. Down-regulation of Nox1, Nox4, and p22(phox) expression by small interfering RNA also decreased HIF-2 alpha protein expression and inhibited Akt and 4E-BP1 phosphorylation, suggesting that a translational mechanism is involved in maintaining HIF-2 alpha in VHL-deficient cells. Colony formation by RCC 786-O in soft agar was markedly inhibited by DPI. Moreover, DPI significantly inhibited RCC 786-O tumor formation in athymic mice. Collectively, the data demonstrate that VHL protein exerts its tumor suppressor action, at least partially, via inhibition of p22(phox)-based Nox4/Nox1 NADPH oxidase-dependent reactive oxygen species generation. C1 Univ Texas, Hlth Sci Ctr, George OBrien Kidney Res Ctr, Dep Med,Div Nephrol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, George OBrien Kidney Res Ctr, Dep Med,Div Endocrinol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Block, K (reprint author), Univ Texas, Hlth Sci Ctr, George OBrien Kidney Res Ctr, Dep Med,Div Nephrol, MC 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM block@uthscsa.edu RI Bell, Tiffany/F-4403-2010; OI Gorin, Yves/0000-0003-4048-6925 NR 31 TC 64 Z9 68 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 MAR 16 PY 2007 VL 282 IS 11 BP 8019 EP 8026 DI 10.1074/jbc.M611569200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 148ND UT WOS:000245081000033 PM 17200123 ER PT J AU Bhattacharya, T Daniels, M Heckerman, D Foley, B Frahm, N Kadie, C Carlson, J Yusim, K McMahon, B Gaschen, B Mallal, S Mullins, JI Nickle, DC Herbeck, J Rousseau, C Learn, GH Miura, T Brander, C Walker, B Korber, B AF Bhattacharya, Tanmoy Daniels, Marcus Heckerman, David Foley, Brian Frahm, Nicole Kadie, Carl Carlson, Jonathan Yusim, Karina McMahon, Ben Gaschen, Brian Mallal, Simon Mullins, James I. Nickle, David C. Herbeck, Joshua Rousseau, Christine Learn, Gerald H. Miura, Toshiyuki Brander, Christian Walker, Bruce Korber, Bette TI Founder effects in the assessment of HIV polymorphisms and HLA allele associations SO SCIENCE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ESCAPE; RESPONSES; CTL; EPITOPES; FITNESS; GAG; MUTATIONS; DIVERSITY; VARIANTS AB Escape from T cell-mediated immune responses affects the ongoing evolution of rapidly evolving viruses such as HIV. By applying statistical approaches that account for phylogenetic relationships among viral sequences, we show that viral lineage effects rather than immune escape often explain apparent human leukocyte antigen (HLA)-mediated immune-escape mutations defined by older analysis methods. Phylogenetically informed methods identified immune-susceptible locations with greatly improved accuracy, and the associations we identified with these methods were experimentally validated. This approach has practical implications for understanding the impact of host immunity on pathogen evolution and for defining relevant variants for inclusion in vaccine antigens. C1 Los Alamos Natl Lab, Los Alamos, NM 87545 USA. Santa Fe Inst, Santa Fe, NM 87501 USA. Microsoft Corp, Res, Machine Learning & Appl Stat Grp, Redmond, WA 98052 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA 02129 USA. Univ Washington, Dept Comp Sci & Engn, Seattle, WA 98195 USA. Royal Perth Hosp, Ctr Clin Immunol & Biomed Stat, Perth, WA, Australia. Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Korber, B (reprint author), Los Alamos Natl Lab, POB 1663, Los Alamos, NM 87545 USA. EM btk@lanl.gov RI Bhattacharya, Tanmoy/J-8956-2013; OI Bhattacharya, Tanmoy/0000-0002-1060-652X; Brander, Christian/0000-0002-0548-5778; Foley, Brian/0000-0002-1086-0296; Korber, Bette/0000-0002-2026-5757 FU NIAID NIH HHS [AI27757, AI57005] NR 20 TC 171 Z9 178 U1 1 U2 14 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 MAR 16 PY 2007 VL 315 IS 5818 BP 1583 EP 1586 DI 10.1126/science.1131528 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146LB UT WOS:000244934800055 PM 17363674 ER PT J AU Smith, JP Dong, MH Kaunitz, JD AF Smith, Jason P. Dong, Mamie H. Kaunitz, Jonathan D. TI Evaluation of a pharmacist-managed hepatitis C care clinic SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE ambulatory care; antivirals; clinical pharmacists; combined therapy; economics; hematopoietic agents; hepatitis C; peginterferon alfa 2-a; peginterferon alfa 2-b; ribavirin; toxicity ID UNITED-STATES VETERANS; PLUS RIBAVIRIN; ANTIVIRAL THERAPY; VIRUS-INFECTION AB Purpose. A description of an effort to create a more time, labor, and cost-efficient method for the management of patients with hepatitis C virus (HCV) infection in Department of Veterans Affairs (VA) hospitals is provided; this pilot study also revealed the outcomes of a pharmacist-managed clinic for these patients in comparison to established standards of care. Methods. A retrospective analysis was performed on data obtained from patients who were referred to the clinic between October 2002 and March 2004 and who had a clinical pharmacist as their primary treatment provider. The patients' medical records were searched for demographic information, disease characteristics, treatment information, treatment and safety information, and virological response. Results. Thirty-one patients were evaluated, and 27 were offered antiviral therapy in the hepatitis C care clinic between October 2002 and March 2004. Of the 27 patients who had sufficient data for analysis, there was a sustained response rate of 63% (17 of 27) overall after treatment with peginterferon and ribavirin combination therapy. Only 3 patients (11%) stopped therapy early secondary to adverse effects, whereas 8 (30%) were managed with growth factors. Conclusion. VA patients managed by a clinical pharmacist for the treatment of chronic HCV infection demonstrated similar treatment outcomes compared with the results from earlier studies with VA patients managed with traditional care. Further studies are warranted to investigate the role of the pharmacist in the management of patients with HCV infection. C1 W Los Angeles Vet Affairs Med Ctr, Greater Los Angeles Vet Affairs VA Healthcare Sys, Dept Pharm, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RP Smith, JP (reprint author), W Los Angeles Vet Affairs Med Ctr, Greater Los Angeles Vet Affairs VA Healthcare Sys, Dept Pharm, 11301 Wilshire Blvd,Bldg 500,Suite 4046A, Los Angeles, CA 90073 USA. EM jason.smith2@va.gov NR 23 TC 13 Z9 14 U1 0 U2 1 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD MAR 15 PY 2007 VL 64 IS 6 BP 632 EP 636 DI 10.2146/ajhp060153 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 152OR UT WOS:000245371800014 PM 17353572 ER PT J AU Quintero-Rivera, F Chan, A Donovan, DJ Gusella, JF Ligon, AH AF Quintero-Rivera, Fabiola Chan, Alicia Donovan, Diana J. Gusella, James F. Ligon, Azra H. TI Disruption of a synaptotagmin (SYT14) associated with neurodevelopmental abnormalities SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE reciprocal translocation; neurodevelopment; seizures; synaptotagmin ID PROTEIN-KINASE-C; CA2+ SENSOR; EXOCYTOSIS; DROSOPHILA; RELEASE; COMPLEX; REARRANGEMENTS; MEMBRANES; HOMOLOG; CLONING AB We report cytogenetic and molecular studies of a de novo, apparently balanced t(1;3)(q32.1;q25.1) identified in a 12-year-old female (designated DGAP128) with cerebral atrophy, rnacrocephaly seizures, and developmental delay. A combination of fluorescence in situ hybridization (FISH) and Southern blot analysis demonstrated disruption of a synaptotagmin gene (SYT14) at the 1q32 breakpoint. Expression of SYT14 in human brain was confirmed using Northern analysis. Because members of the synaptotagmin family of proteins function as sensors that link changes in calcium levels with a variety of biological processes, including neuro-transmission and hormone-responsiveness, SYT14 is an intriguing candidate gene for the abnormal development in this child. This is the first known constitutional rearrangement of S)714, and further systematic genetic analysis and clinical studies of DGAP128 may offer unique insights into the role of SYT14 in neurodevelopment. (c) 2007 Wiley-Liss, Inc. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Univ Alberta, Dept Med Genet, Edmonton, AB, Canada. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA USA. RP Ligon, AH (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM aligon@rics.bwh.harvard.edu RI Donovan, Diana/A-1256-2010 NR 27 TC 4 Z9 5 U1 0 U2 0 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 MAR 15 PY 2007 VL 143A IS 6 BP 558 EP 563 DI 10.1002/ajmg.a.31618 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 142PI UT WOS:000244661600006 PM 17304550 ER PT J AU Duda, DG AF Duda, Dan G. TI Endothelial cell-based therapy for hematopoiesis SO BLOOD LA English DT Editorial Material ID STEM-CELLS; ANGIOGENESIS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Duda, DG (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 4 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 MAR 15 PY 2007 VL 109 IS 6 BP 2272 EP 2273 DI 10.1182/blood-2006-12-064568 PG 2 WC Hematology SC Hematology GA 147LO UT WOS:000245004700004 ER PT J AU Hochhaus, A Kantarjian, HM Baccarani, M Lipton, JH Apperley, JF Druker, BJ Facon, T Goldberg, SL Cervantes, F Niederwieser, D Silver, RT Stone, RM Hughes, TP Muller, MC Ezzeddine, R Countouriotis, AM Shah, NP AF Hochhaus, Andreas Kantarjian, Hagop M. Baccarani, Michele Lipton, Jeffrey H. Apperley, Jane F. Druker, Brian J. Facon, Thierry Goldberg, Stuart L. Cervantes, Francisco Niederwieser, Dietger Silver, Richard T. Stone, Richard M. Hughes, Timothy P. Muller, Martin C. Ezzeddine, Rana Countouriotis, Athena M. Shah, Neil P. TI Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy SO BLOOD LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; BCR-ABL; CLINICAL RESISTANCE; POSITIVE LEUKEMIAS; KINASE INHIBITOR; MESYLATE; MUTATIONS; STI571; CELLS; INTERFERON AB Although imatinib induces marked responses in patients with chronic myeloid leukemia (CML), resistance is increasingly problematic, and treatment options for imatinib-resistant or -intolerant CML are limited. Dasatinib, a novel, highly potent, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases, induced cytogenetic responses in a phase 1 study in imatinib-resistant or -intolerant CML and was well tolerated. Initial results are presented from a phase 2 study of 186 patients with imatinib-resistant or -intolerant chronic-phase CML (CML-CP) designed to further establish the efficacy and safety of dasatinib (70 mg twice daily). At 8-months' follow-up, dasatinib induced notable responses, with 90% and 52% of patients achieving complete hematologic and major cytogenetic responses (MCyR), respectively. Responses were long lasting: only 2% of patients achieving MCyR progressed or died. Importantly, comparable responses were achieved by patients carrying BCR-ABL mutations conferring imatinib resistance. Dasatinib also induced molecular responses, reducing BCR-ABL/ABL transcript ratios from 66% at baseline to 2.6% at 9 months. Nonhematologic adverse events were generally mild to moderate, and most cytopenias were effectively managed with dose modifications. Cross-intolerance with imatinib was not evident. To conclude, dasatinib induces notable responses in imatinib-resistant or -intolerant CML-CP, is well tolerated, and represents a promising therapeutic option for these patients. This trial was registered at www.clinicaltrials.gov as CA180013. C1 Univ Heidelberg, Med Fak Mannheim, Med Klin 3, D-68167 Mannheim, Germany. Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. Univ Bologna, Dept Hematol Oncol, S Orsola Malpighi Univ Hosp, Bologna, Italy. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Hammersmith Hosp, Dept Haematol, London, England. Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Portland, OR 97201 USA. Hop Claude Huriez, Lille, France. Hosp Clin Barcelona, Dept Hematol, Barcelona, Spain. Univ Klinikum Leipzig, Med Klin & Poliklin 2, Leipzig, Germany. Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, New York, NY USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Inst Med & Vet Sci, Div Hematol, Adelaide, SA 5000, Australia. Bristol Myers Squibb Co, Wallingford, CT 06492 USA. Univ Coll San Francisco, Sch Med, Div Hematol & Oncol, San Francisco, CA USA. RP Hochhaus, A (reprint author), Univ Heidelberg, Med Fak Mannheim, Med Klin 3, Theodor Kutzer Ufer 1-3, D-68167 Mannheim, Germany. EM hochhaus@uni-hd.de RI FACON, THIERRY/M-9736-2014; OI FACON, THIERRY/0000-0001-7705-8460; Hochhaus, Andreas/0000-0003-0626-0834 NR 29 TC 380 Z9 407 U1 0 U2 11 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 2007 VL 109 IS 6 BP 2303 EP 2309 DI 10.1182/blood-2006-09-047266 PG 7 WC Hematology SC Hematology GA 147LO UT WOS:000245004700011 PM 17138817 ER PT J AU Cariappa, A Chase, C Liu, HY Russell, P Pillai, S AF Cariappa, Annaiah Chase, Catharine Liu, Haoyuan Russell, Paul Pillai, Shiv TI Naive recirculating B cells mature simultaneously in the spleen and bone marrow SO BLOOD LA English DT Article ID INDEPENDENT RESPONSES; CD22-DEFICIENT MICE; LYMPHOTOXIN-ALPHA; LYMPHOID ORGANS; DEFICIENT MICE; IN-VIVO; MATURATION; CD22; ALYMPHOPLASIA; LYMPHOCYTES AB We have recently demonstrated that IgD(hi) B cells can occupy an extravascular perisinusoidal niche in the bone marrow in addition to the well-established follicular niche in conventional secondary lymphoid organs. The spleen has long been considered to be the site at which newly formed B lymphocytes mature into IgD(hi) naive recirculating B cells, but the existence of mutant mice that have selectively lost mature B cells in the bone marrow prompted an examination of B-cell maturation at this latter site. Following a single pulse of BrdU in intact mice, sequential labeling of more mature B-cell populations in the bone marrow suggested ongoing maturation at this site. Further evidence for B-cell maturation in the bone marrow was obtained from analyses of transitional B cells in splenectomized lymphotoxin alpha-deficient mice that lack all secondary lymphold organs. In these mice, antibody-secreting cells recognizing multivalent antigens were also observed in the bone marrow following an intravenous microbial challenge. These data suggest that newly formed B cells mature into IgD(hi) B cells simultaneously in the spleen and the bone marrow and establish in a stringent manner that humoral immune responses can be initiated in situ in the bone marrow. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Pillai, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St,Charlestown Navy Yard, Boston, MA 02129 USA. EM pillai@helix.mgh.harvard.edu FU NCI NIH HHS [CA102793]; NHLBI NIH HHS [HL43340, HL071932]; NIAID NIH HHS [AI064930] NR 43 TC 49 Z9 50 U1 1 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 MAR 15 PY 2007 VL 109 IS 6 BP 2339 EP 2345 DI 10.1182/blood-2006-05-021089 PG 7 WC Hematology SC Hematology GA 147LO UT WOS:000245004700017 PM 17119110 ER PT J AU Chauhan, AK Kisucka, J Lamb, CB Bergmeier, W Wagner, DD AF Chauhan, Anil K. Kisucka, Janka Lamb, Colin B. Bergmeier, Wolfgang Wagner, Denisa D. TI von Willebrand factor and factor VIII are independently required to form stable occlusive thrombi in injured veins SO BLOOD LA English DT Article ID VON-WILLEBRAND-FACTOR; PLASMA VONWILLEBRAND-FACTOR; PLATELET-ADHESION; THROMBOCYTOPENIC PURPURA; HEMOPHILIA-A; MOUSE MODEL; DISEASE; ARTERIOLES; PROTEASE; MICE AB von Willebrand factor (VWF) protects factor Vill (FVIII) from proteolysis and mediates the initial contact of platelets with the injured vessel wall, thus playing an important role in hemostasis and thrombosis. VWF is crucial for the formation of occlusive thrombi at arterial shear rates. However, with only a few conflicting studies published, the role of VWF in venous thrombosis is still unclear. Using gene-targeted mice, we show that in ferric chloride-injured veins platelet adhesion to subendothelium is decreased and thrombus growth is impaired in VWF-/- mice when compared with wild type (WT). We also observed increased embolization in the VWF-/- mice, which was due to lower FVIII levels in these mice as recombinant factor Vill (r-FVIII) restored thrombus stability. Despite normalization of blood clotting time and thrombus stability after r-FVIII infusion, the VWF-/- venules did not occlude. Transgenic platelets lacking the VWF receptor GPlb alpha extra-cellular domain showed decreased adhesion to injured veins. But, after a delay, all the injured venules occluded in these transgenic mice. Thus, VWIF likely uses other adhesion receptors besides GPIb alpha in thrombus growth under venous shear conditions. Our studies document crucial roles for VWIF and FVIII in experimental thrombosis under venous flow conditions in vivo. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM wagner@cbr.med.harvard.edu FU NHLBI NIH HHS [R37 HL41002, R37 HL041002] NR 32 TC 45 Z9 45 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 MAR 15 PY 2007 VL 109 IS 6 BP 2424 EP 2429 DI 10.1182/blood-2006-06-028241 PG 6 WC Hematology SC Hematology GA 147LO UT WOS:000245004700028 PM 17119108 ER PT J AU Chanan-Khan, AA Kaufman, JL Mehta, J Richardson, PG Miller, KC Lonial, S Munshi, NC Schlossman, R Tariman, J Singhal, S AF Chanan-Khan, Asher A. Kaufman, Jonathan L. Mehta, Jayesh Richardson, Paul G. Miller, Kena C. Lonial, Sagar Munshi, Nikhil C. Schlossman, Robert Tariman, Joseph Singhal, Seema TI Activity and safety of bortezomib in multiple myeloma patients with advanced renal failure: a multicenter retrospective study SO BLOOD LA English DT Article ID HIGH-DOSE DEXAMETHASONE; PRESENTING FEATURES; REFRACTORY MYELOMA; THALIDOMIDE; THERAPY; TRANSPLANTATION; COMBINATION; MELPHALAN; DIALYSIS; PHASE-2 AB Patients with multiple myeloma (MM) frequently present with concomitant renal dysfunction, and those requiring dialysis have particularly poor outcomes. Bortezomib is a reversible proteasome inhibitor with significant activity in MM. This retrospective case analysis evaluated the feasibility and activity of bortezomib-based therapy in MM patients (n = 24) requiring dialysis support for advanced renal failure. All but 1 patient were undergoing dialysis at the time of therapy. Patients received bortezomib alone or bortezomib-based combination therapy. Among 20 patients with available response data, overall response rate (complete response [CR] + partial response) was 75%, with 30% CR + near CR. One patient was spared dialysis, and 3 other patients became independent of dialysis following bortezomib-based treatment. These encouraging results suggest that bortezomib or bortezomib-based regimens can be used in MM patients requiring dialysis, with manageable toxicities. Further studies will more formally evaluate the impact of bortezomib-based regimens in this patient population. C1 Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Emory Univ, Atlanta, GA 30322 USA. Northwestern Univ, Chicago, IL 60611 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chanan-Khan, AA (reprint author), Roswell Pk Canc Inst, Elm & Carlton Sts, Buffalo, NY 14263 USA. EM asher.chanan-khan@roswellpark.org NR 25 TC 150 Z9 167 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 MAR 15 PY 2007 VL 109 IS 6 BP 2604 EP 2606 DI 10.1182/blood-2006-09-046409 PG 3 WC Hematology SC Hematology GA 147LO UT WOS:000245004700052 PM 17138816 ER PT J AU Doh, ST Zhang, YY Temple, MH Cai, L AF Doh, Sung Tae Zhang, Yunyu Temple, Matthew H. Cai, Li TI Non-coding sequence retrieval system for comparative genomic analysis of gene regulatory elements SO BMC BIOINFORMATICS LA English DT Article ID DNA-SEQUENCES; ALIGNMENTS; REGIONS; RESOURCES; ENHANCERS; DISCOVERY; MOTIFS; TOOLS AB Background: Completion of the human genome sequence along with other species allows for greater understanding of the biochemical mechanisms and processes that govern healthy as well as diseased states. The large size of the genome sequences has made them difficult to study using traditional methods. There are many studies focusing on the protein coding sequences, however, not much is known about the function of non-coding regions of the genome. It has been demonstrated that parts of the non-coding region play a critical role as gene regulatory elements. Enhancers that regulate transcription processes have been found in intergenic regions. Furthermore, it is observed that regulatory elements found in non-coding regions are highly conserved across different species. However, the analysis of these regulatory elements is not as straightforward as it may first seem. The development of a centralized resource that allows for the quick and easy retrieval of non-coding sequences from multiple species and is capable of handing multi-gene queries is critical for the analysis of non-coding sequences. Here we describe the development of a web-based non-coding sequence retrieval system. Results: This paper presents a Non-Coding Sequences Retrieval System (NCSRS). The NCSRS is a web-based bioinformatics tool that performs fast and convenient retrieval of non-coding and coding sequences from multiple species related to a specific gene or set of genes. This tool has compiled resources from multiple sources into one easy to use and convenient web based interface. With no software installation necessary, the user needs only internet access to use this tool. Conclusion: The unique features of this tool will be very helpful for those studying gene regulatory elements that exist in non-coding regions. The web based application can be accessed on the internet at: http://cell.rutgers.edu/ncsrs/. C1 Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Doh, ST (reprint author), Rutgers State Univ, Dept Biomed Engn, 599 Taylor Rd, Piscataway, NJ 08854 USA. EM sungtae@rci.rutgers.edu; yunyu_zhang@dfci.harvard.edu; mht@research.dfci.harvard.edu; lcai@rutgers.edu NR 33 TC 9 Z9 9 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD MAR 15 PY 2007 VL 8 AR 94 DI 10.1186/1471-2105-8-94 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 154CC UT WOS:000245483400002 PM 17362514 ER PT J AU Oh, WK Proctor, K Nakabayashi, M Evan, C Tormey, LK Daskivich, T Antras, L Smith, M Neary, MP Duh, MS AF Oh, William K. Proctor, Kevin Nakabayashi, Mari Evan, Carolyn Tormey, Lauren K. Daskivich, Timothy Antras, Lucia Smith, Michael Neary, Maureen P. Duh, Mei Sheng TI The risk of renal impairment in hormone-refractory prostate cancer patients with bone metastases treated with zoledronic acid SO CANCER LA English DT Article DE renal impairment; hormone-refractory prostate cancer; zoledronic acid; pamidronate; bisphosphonates; risk factors ID SKELETAL COMPLICATIONS; PAMIDRONATE; FAILURE AB BACKGROUND. Bisphosphonates have been used to treat bone metastases in hormone-refractory prostate cancer (HRPC), but certain agents have been associated with renal toxicity. For this observational study, the authors assessed the risk of renal impairment in patients with HRPC who received zoledronic acid from December 1999 to April 2005. METHODS. A comprehensive medical records review was performed in a major tertiary oncology center (n = 122 patients). The primary outcome of renal impairment was defined as an increase >= 0.5 mg/dL or >= 1.0 mg/dL over baseline creatinine value if the baseline value was < 1.4 mg/dL or >= 1.4 mg/dL, respectively. A risk factor analysis was conducted using the Andersen-Gill extension to the Cox proportional hazards model. RESULTS. Renal impairment was observed in 23.8% of patients. The risk of renal impairment increased with an extended duration of zoledronic acid therapy (< 6 months, 11.1%; >= 24 months, 26.3%) and previous pamidronate treatment (45.5% vs 19.0% for patients with no prior pamidronate). A significantly greater risk of renal impairment was associated with increasing age at zoledronic acid initiation, prior pamidronate use, and a history of renal disease, hypertension, or smoking (P < 0.05). CONCLUSIONS. in an outpatient clinic setting, the risk of renal impairment among patients with HRPC who received zoledronic acid was greater than the risk reported previously in clinical trials. Cancer 2007;109:1090-6. (c) 2007 American Cancer Society. C1 Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Med Oncol, Boston, MA 02115 USA. Anal Grp Inc, Boston, MA USA. Hoffmann La Roche Inc, Nutley, NJ 07110 USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Med Oncol, 44 Binney St,Dana 1230, Boston, MA 02115 USA. EM william_oh@dfci.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 16 TC 22 Z9 22 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 15 PY 2007 VL 109 IS 6 BP 1090 EP 1096 DI 10.1002/cncr.22504 PG 7 WC Oncology SC Oncology GA 149RF UT WOS:000245163600012 PM 17311345 ER PT J AU Jain, RK Tong, RT Munn, LL AF Jain, Rakesh K. Tong, Ricky T. Munn, Lance L. TI Effect of vascular normalization, by antiangiogenic therapy on interstitial hypertension, peritumor edema, and lymphatic metastasis: Insights from a mathematical model SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TUMOR VASCULATURE; FLUID PRESSURE; CANCER-CELLS; HYDRAULIC CONDUCTIVITY; NODE METASTASIS; RECTAL-CANCER; SOLID TUMORS; IN-VIVO; TRANSPORT AB Preclinical and clinical evidence shows that antiangiogenic agents can decrease tumor vessel permeability and interstitial fluid pressure (IFP) in a process of vessel "normalization." The resulting normalized vasculature has more efficient perfusion, but little is known about how tumor IFP and interstitial fluid velocity (IFV) are affected by changes in transport properties of the vessels and interstitium that are associated with antiangiogenic therapy. By using a mathematical model to simulate IFP and IFV profiles in tumors, we show here that antiangiogenic therapy can decrease IFP by decreasing the tumor size, vascular hydraulic permeability, and/or the surface area per unit tissue volume of tumor vessels. Within a certain window of antiangiogenic effects, interstitial convection within the tumor can increase dramatically, whereas fluid convection out of the tumor margin decreases. This would result in increased drug convection within the tumor and decreased convection of drugs, growth factors, or metastatic cancer cells from the tumor margin into the peritumor fluid or tissue. Decreased convection of growth factors, such as vascular endothelial growth factor-C (VEGF-C), would limit peritumor hyperplasia, and decreased VEGF-A would limit angiogenesis in sentinel lymph nodes. Both of these effects would reduce the probability of lymphatic metastasis. Finally, decreased fluid convection into the peritumor tissue would decrease peritumor edema associated with brain tumors and ascites accumulation in the peritoneal or pleural cavity, a major complication with a number of malignancies. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, EL Steele Lab Tumor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, EL Steele Lab Tumor Biol, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NCI NIH HHS [P01 CA080124, P01 CA080124-080006, P01 CA080124-089001, R01 CA085140, R01 CA85140] NR 52 TC 277 Z9 290 U1 5 U2 33 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 MAR 15 PY 2007 VL 67 IS 6 BP 2729 EP 2735 DI 10.1158/0008-5472.CAN-06-4102 PG 7 WC Oncology SC Oncology GA 147RC UT WOS:000245019100043 PM 17363594 ER PT J AU Gupta, V Yeo, G Kawakubo, H Rangnekar, V Ratnaswamy, P Hayashida, T MacLaughlin, DT Donahoe, PK Maheswaran, S AF Gupta, Vandana Yeo, Giminna Kawakubo, Hirofumi Rangnekar, Vivek Ratnaswamy, Preethi Hayashida, Tetsu MacLaughlin, David T. Donahoe, Patricia K. Maheswaran, Shyamala TI Mullerian-inhibiting substance induces gro-beta expression in breast cancer cells through a nuclear factor-kappa B-dependent and Smad1-dependent mechanism SO CANCER RESEARCH LA English DT Article ID MAMMARY EPITHELIAL-CELLS; INDUCED GENE-EXPRESSION; RAY CRYSTAL-STRUCTURE; TRANSCRIPTION FACTOR; INDEPENDENT MECHANISM; HUMAN-FIBROBLASTS; ACTIVATION; PROTEINS; INDUCTION; CYTOKINE AB Mullerian-inhibiting substance (MIS), a transforming growth factor-beta family member, activates the nuclear factor-kappa B (NF-kappa B) pathway and induces the expression of B-cell translocation gene 2 (BTG2), IFN regulatory factor-1 (IRF-1), and the chemokine Gro-beta. Inhibiting NF-kappa B activation with a phosphorylation-deficient I kappa B alpha, mutant abrogated MIS-mediated induction of all three genes. Expression of dominant-negative Smad1, in which serines at the COOH-terminal SSVS motif are converted to alanines, suppressed MIS-induced Smad1 phosphorylation and impaired MIS-stimulated Gro-beta promoter-driven reporter expression and Gro-beta mRNA. Suppressing Smad1 expression using small interfering RNA also mitigated MIS-induced Gro-beta mRNA, suggesting that regulation of Gro-beta expression by MIS was dependent on activation of NF-kappa B as well as Smad1. However, induction of IRF-1 and BTG2 mRNAs by MIS was independent of Smad1 activation. Characterization of kappa B-binding sequences within Gro-beta, BTG2, and IRF-1 promoters showed that MIS stimulated binding of p50 and p65 subunits to all three sites, whereas phosphorylated Smad1 (phospho-Smad1) protein was detectable only in the NF-kappa B complex bound to the kappa B site of the Gro-beta promoter. Consistent with these observations, chromatin immunoprecipitation assays showed recruitment of both phospho-Smad1 and P65 to the Gro-beta promoter in vivo, whereas p65, but not phospho-Smad1, was recruited to the BTG2 promoter. These results show a novel interaction between MIS-stimulated Smad1 and NF-kappa B signaling in which enhancement of NF-kappa B DNA binding and gene expression by phospho-Smad1 is dependent on the sequence of the kappa B consensus site within the promoter. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Dept Surg Oncol, Charlestown, MA 02129 USA. Univ Kentucky, Dept Radiat Med, Lexington, KY 40506 USA. Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. RP Maheswaran, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Dept Surg Oncol, Bldg 149,13th St, Charlestown, MA 02129 USA. EM maheswaran@helix.mgh.harvard.edu FU NCI NIH HHS [CA89138, CA17393]; NICHD NIH HHS [HD32112] NR 52 TC 7 Z9 9 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2007 VL 67 IS 6 BP 2747 EP 2756 DI 10.1158/0008-5472.CAN-06-2312 PG 10 WC Oncology SC Oncology GA 147RC UT WOS:000245019100045 PM 17363596 ER PT J AU Lin, NU Winer, EP AF Lin, Nancy U. Winer, Eric P. TI Brain metastases: The HER2 paradigm SO CLINICAL CANCER RESEARCH LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; BREAST-CANCER PATIENTS; CELL LUNG-CANCER; PROPHYLACTIC CRANIAL IRRADIATION; COMBINED BIOLOGICAL THERAPY; TYROSINE KINASE INHIBITOR; TRASTUZUMAB-BASED THERAPY; GROWTH-FACTOR VEGF; PHASE-II TRIAL; SOLID TUMORS AB Between 100,000 and 170,000 patients with cancer develop central nervous system (CNS) metastases each year in the U.S., of which similar to 20% carry a primary diagnosis of breast cancer. As a consequence of improvements in systemic therapy, which have allowed patients to live longer with advanced cancer, CNS metastases are emerging as an important sanctuary site, and the incidence may be increasing in patients with particular tumor subtypes. Unless there are improvements in the treatment of CNS disease, a growing proportion of patients may be at risk of experiencing both morbidity and mortality as a result of uncontrolled CNS progression, often at a time when their extra-CNS disease is apparently under control. This article reviews changes in the epidemiology and natural history of women with brain metastases from HER2-positive breast cancer over the last decade and presents the therapeutic challenges and opportunities that have arisen in this setting. First, the apparent increase in CNS disease among women with HER2-positive breast cancer, relative to historical controls, is discussed, followed by consideration of potential causes of this observation. Next, the implications of CNS disease, in terms of prognosis and the potential development of preventive strategies are considered. Finally, new developments in systemic approaches to the treatment of CNS disease, including cytotoxic chemotherapy and targeted therapy, are explored. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM ewiner@partners.org NR 91 TC 184 Z9 189 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 15 PY 2007 VL 13 IS 6 BP 1648 EP 1655 DI 10.1158/1078-0432.CCR-06-2478 PG 8 WC Oncology SC Oncology GA 147VV UT WOS:000245031800008 PM 17363517 ER PT J AU Baumgart, E Cohen, MS Neto, BS Jacobs, MA Wotkowicz, C Rieger-Christ, KM Biolo, A Zeheb, R Loda, M Libertino, JA Summerhayes, IC AF Baumgart, Egbert Cohen, Michael S. Neto, Brasil Silva Jacobs, Micah A. Wotkowicz, Chad Rieger-Christ, Kimberly M. Biolo, Andreia Zeheb, Ron Loda, Massimo Libertino, John A. Summerhayes, Ian C. TI Identification and prognostic significance of an epithelial-mesenchymal transition expression profile in human bladder tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID SUPERFICIAL UROTHELIAL TUMORS; BETA-CATENIN; NEOPLASTIC PROGRESSION; CARCINOMA CELLS; N-CADHERIN; PANCREATIC-CARCINOMA; SIGNALING PATHWAY; GAMMA-CATENIN; CANCER; METASTASIS AB Purpose: Epithelial to mesenchymal transition (EMT) is reportedly an important transition in cancer progression in which the underlying cellular changes have been identified mainly using in vitro models. In this study, we examined the expression pattern of EMT markers in vivo and determined the occurrence and clinical significance of these events in a series of bladder carcinomas. Experimental Design: Eight hundred and twenty-five tumor samples from 572 bladder cancer patients were assembled in 10 tissue microarrays. Paraffin sections from each tissue microarray were subjected to antigen retrieval and processed by immunohistochemistry for the expression of E-cadherin, plakoglobin, beta-catenin, N-cadherin, and vimentin. Results: Pathologic expression of E-cadherin, beta-catenin, plakoglobin, and vimentin were associated with the clinicopathologic variables of grade and stage with only the cytoplasmic localization of plakoglobin found associated with lymph node status. Associations between the aforementioned markers were found significant as determined by the Spearman correlation coefficient with N-cadherin showing no associations in this analysis. In univariate survival analysis involving patients who underwent cystectomy, the reduction or loss of plakoglobin significantly influenced overall survival (P = 0.02) in which the median time to death was 2 years compared with 4 years when a normal level of plakoglobin was recorded. When the analysis was done for cancer-specific survival, low levels of both plakoglobin (P = 0.02) and P-catenin (P = 0.02) significantly influenced survival. Conclusion: The putative markers of EMT defined within a panel of bladder carcinoma cell lines were recorded in vivo, frequently associated with tumors of high grade and stage. Although multivariate analysis showed no significant influence of the EMT biomarkers on survival, alterations associated with plakoglobin were identified as significant prognostic features in these tumors. C1 Lahey Clin Fdn, Robert E Wise MD Res & Educ Inst, Cell & Mol Biol Lab, Burlington, MA 01805 USA. Lahey Clin Fdn, Dept Urol, Burlington, MA 01805 USA. Lahey Clin Fdn, Dept Pathol, Burlington, MA 01805 USA. Hosp Clin Porto Alegre, Dept Internal Med & Cardiol, Porto Alegre, RS, Brazil. Dana Farber Canc Ctr, Dept Pathol, Boston, MA USA. RP Summerhayes, IC (reprint author), Lahey Clin Fdn, Robert E Wise MD Res & Educ Inst, Cell & Mol Biol Lab, 31 Mall Rd, Burlington, MA 01805 USA. EM Ian.C.Summerhayes@lahey.org RI Biolo, Andreia/E-9860-2013 NR 40 TC 83 Z9 97 U1 0 U2 5 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 MAR 15 PY 2007 VL 13 IS 6 BP 1685 EP 1694 DI 10.1158/1078-0432.CCR-06-2330 PG 10 WC Oncology SC Oncology GA 147VV UT WOS:000245031800012 PM 17363521 ER PT J AU Feng, S Agoulnik, IU Bogatcheva, NV Kamat, AA Kwabi-Addo, B Li, R Ayala, G Ittmann, MM Agoulnik, AI AF Feng, Shu Agoulnik, Irina U. Bogatcheva, Natalia V. Kamat, Aparna A. Kwabi-Addo, Bernard Li, Rile Ayala, Gustavo Ittmann, Michael M. Agoulnik, Alexander I. TI Relaxin promotes prostate cancer progression SO CLINICAL CANCER RESEARCH LA English DT Article ID TRANSGENIC MOUSE; UP-REGULATION; H2 RELAXIN; GROWTH; RECEPTORS; CELLS; DIFFERENTIATION; TUMOR; MICE; OVEREXPRESSION AB Purpose: To understand the role of relaxin peptide in prostate cancer, we analyzed the expression of relaxin and its receptor in human prostate cancer samples, the effects of relaxin signaling on cancer cell phenotype in vitro, and the effects of increased serum relaxin concentrations on cancer progression in vivo. Experimental Design: The relaxin and its receptor leucine-rich repeat containing G protein coupled receptor 7 (LGR7) expression were studied by quantitative reverse transcription-PCR (11 benign and 44 cancer tissue samples) and by relaxin immunohistochemistry using tissue microarrays containing 10 normal and 69 cancer samples. The effects of relaxin treatment and enclogenous relaxin/LGR7 suppression via short interfering RNA in PC-3 and LNCaP cells were analyzed in vitro. The effect of transgenic relaxin overexpression [Tg(Rln1)] on cancer growth and survival was evaluated in autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP). Results:The relaxin mRNA expression was significantly higher in recurrent prostate cancer samples. In tissue microarrays of the 10 normal tissues, 8 had low staining in epithelial cells, whereas only 1 of 9 high-grade prostatic intraepithelial neoplasia lesions had low expression (P = 0.005) and only 29 of 65 cancers had low expression (P = 0.047). Stimulation with relaxin increased cell proliferation, invasiveness, and adhesion in vitro. The suppression of relaxin/LGR7 via short interfering RNAs decreased cell invasiveness by 90% to 95% and growth by 10% to 25% and increased cell apoptosis 0.6 to 2.2 times. The Tg (Rln1) TRAMP males had shorter median survival time, associated with the decreased apoptosis of tumor cells, compared with non-Tg(R/n1) TRAMP animals. Conclusions: Relaxin signaling plays a role in prostate cancer progression. C1 Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA. RP Agoulnik, AI (reprint author), Baylor Coll Med, Dept Obstet & Gynecol, 1 Baylor Plaza,Suite 207D, Houston, TX 77030 USA. EM agoulnik@bcm.edu RI Kwabi-Addo, Bernard/A-6993-2016; OI Kwabi-Addo, Bernard/0000-0003-3692-6350; Agoulnik, Irina/0000-0003-4889-0324; Agoulnik, Alexander/0000-0001-6587-6845 FU NCI NIH HHS [R21 CA118362-01A1, 5 P50 CA58204, R21 CA118362] NR 32 TC 63 Z9 65 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 15 PY 2007 VL 13 IS 6 BP 1695 EP 1702 DI 10.1158/1078-0432.CCR-06-2492 PG 8 WC Oncology SC Oncology GA 147VV UT WOS:000245031800013 PM 17363522 ER PT J AU Butler, MO Lee, JS Ansen, S Neuberg, D Hodi, FS Murray, AP Drury, L Berezovskaya, A Mulligan, RC Nadler, LM Hirano, N AF Butler, Marcus O. Lee, Jeng-Shin Ansen, Sascha Neuberg, Donna Hodi, F. Stephen Murray, Andrew P. Drury, Linda Berezovskaya, Alla Mulligan, Richard C. Nadler, Lee M. Hirano, Naoto TI Long-lived antitumor CD8(+) lymphocytes for adoptive therapy generated using an artificial antigen-presenting cell SO CLINICAL CANCER RESEARCH LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; IN-VIVO PERSISTENCE; DENDRITIC CELLS; NASOPHARYNGEAL CARCINOMA; METASTATIC MELANOMA; TUMOR-REGRESSION; EXPRESS CD83; IMMUNOTHERAPY; EXPANSION; MEMORY AB Purpose: Antitumor lymphocytes can be generated ex vivo unencumbered by immunoregulation found in vivo. Adoptive transfer of these cells is a promising therapeutic modality that could establish long-term antitumor immunity. However, the widespread use of adoptive therapy has been hampered by the difficulty of consistently generating potent antitumor lymphocytes in a timely manner for every patient. To overcome this, we sought to establish a clinical grade culture system that can reproducibly generate antigen-specific cytotoxic T lymphocytes (CTL). Experimental Design: We created an off-the-shelf, standardized, and renewable artificial antigen-presenting cell (aAPC) line that coexpresses HLA class I, CD54, CD58, CD80, and the dendritic cell maturation marker CD83. We tested the ability of aAPC to generate tumor antigen-specific CTL under optimal culture conditions. The number, phenotype, effector function, and in vitro longevity of generated CTL were determined. Results: Stimulation of CD8(+) T cells with peptide-pulsed aAPC generated large numbers of functional CTL that recognized a variety of tumor antigens. These CTLs, which possess a phenotype consistent with in vivo persistence, survived ex vivo for prolonged periods of time. Clinical grade aAPC(33), produced under current Good Manufacturing Practices guidelines, generated sufficient numbers of CTL within a short period of time. These CTL specifically lysed a variety of melanoma tumor lines naturally expressing a target melanoma antigen. Furthermore, antitumor CTL were easily generated in all melanoma patients examined. Conclusions: With clinical grade aAPC(33) in hand, we are now poised for clinical translation of ex vivo generated antitumor CTL for adoptive cell transfer. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Childrens Hosp, Div Mol Med, Boston, MA 02115 USA. RP Butler, MO (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM Marcus_Butler@dfci.harvard.edu FU NCI NIH HHS [CA87720, CA92625-04]; NHLBI NIH HHS [HL54785-08] NR 49 TC 67 Z9 67 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 15 PY 2007 VL 13 IS 6 BP 1857 EP 1867 DI 10.1158/1078-0432.CCR-06-1905 PG 11 WC Oncology SC Oncology GA 147VV UT WOS:000245031800035 PM 17363542 ER PT J AU Johnson, S Schriever, C Galang, M Kelly, CP Gerding, DN AF Johnson, Stuart Schriever, Christopher Galang, Minerva Kelly, Ciaran P. Gerding, Dale N. TI Interruption of recurrent Clostridium difficile - Associated diarrhea episodes by serial therapy with vancomycin and rifaximin SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID IN-VITRO ACTIVITY; DISEASE AB Eight women who each experienced 4-8 episodes of Clostridium difficile-associated diarrhea were given a 2-week course of rifaximin therapy when they were asymptomatic, immediately after completing their last course of vancomycin therapy. Seven of the 8 patients experienced no further diarrhea recurrence. The patient who had a recurrence responded to a second course of rifaximin therapy, but rifaximin-resistant C. difficile was recovered after treatment. A controlled trial for treating recurrent Clostridium difficile associated diarrhea appears to be warranted. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Beth Israel Deaconess Hosp, Boston, MA USA. Harvard Univ, Boston, MA 02115 USA. RP Johnson, S (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. EM sjohnson@lumc.edu NR 12 TC 176 Z9 184 U1 2 U2 4 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 MAR 15 PY 2007 VL 44 IS 6 BP 846 EP 848 DI 10.1086/511870 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 136RT UT WOS:000244242500015 PM 17304459 ER PT J AU Kotton, CN AF Kotton, Camille N. TI Zoonoses in solid-organ and hematopoietic stem cell transplant recipients SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID BONE-MARROW-TRANSPLANTATION; ORTHOTOPIC LIVER-TRANSPLANTATION; MYCOBACTERIUM-MARINUM INFECTION; CAT-SCRATCH DISEASE; OF-THE-LITERATURE; TRYPANOSOMA-CRUZI INFECTION; ACUTE RESPIRATORY SYNDROME; YELLOW-FEVER VACCINE; RENAL-TRANSPLANT; HEART-TRANSPLANT AB Numerous reports exist of the transmission of zoonoses to humans during and after solid-organ and hematopoietic stem cell transplantation. Donor-derived infections of numerous etiologies, including West Nile virus infection, Chagas disease, toxoplasmosis, rabies, lymphocytic choriomeningitis virus infection, and infection due to Brucella species have been reported. Most zoonoses occur as a primary infection after transplantation, and immunocompromised patients are more likely to experience significant morbidity and mortality from these infections. Risks of zoonotic infection in the posttransplantation period could be reduced by patient education. Increased recognition of the risks of zoonoses, as well as the advent of molecular biology-based testing, will potentially augment diagnostic aptitude. Documented zoonotic infection as it affects transplantation will be the primary focus of this review. C1 Massachusetts Gen Hosp, Transplant & Immunocompromised Host Sect, Div Infect Dis, Boston, MA 02114 USA. RP Kotton, CN (reprint author), Massachusetts Gen Hosp, Transplant & Immunocompromised Host Sect, Div Infect Dis, 55 Fruit St,Cox 5, Boston, MA 02114 USA. EM ckotton@partners.org NR 168 TC 58 Z9 62 U1 0 U2 3 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 MAR 15 PY 2007 VL 44 IS 6 BP 857 EP 866 DI 10.1086/511859 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 136RT UT WOS:000244242500018 PM 17304461 ER PT J AU Liu, Y Pathak, N Kramer-Zucker, A Drummond, IA AF Liu, Yan Pathak, Narendra Kramer-Zucker, Albrecht Drummond, Iain A. TI Notch signaling controls the differentiation of transporting epithelia and multiciliated cells in the zebrafish pronephros SO DEVELOPMENT LA English DT Article DE pronephros; jagged 2; multiciliated cell; Notch3; double bubble; mind bomb; zebrafish ID POLYCYSTIC KIDNEY-DISEASE; RIGHT AXIS DETERMINATION; INTRAFLAGELLAR TRANSPORT; C-ELEGANS; DEVELOPING MOUSE; GENE-EXPRESSION; PRIMARY CILIUM; TUBULAR CELLS; HOMOLOG; MUTATIONS AB Epithelial tubules consist of multiple cell types that are specialized for specific aspects of organ function. In the zebrafish pronephros, multiciliated cells (MCCs) are specialized for fluid propulsion, whereas transporting epithelial cells recover filtered-blood solutes. These cell types are distributed in a 'salt-and-pepper' fashion in the pronephros, suggesting that a lateral inhibition mechanism may play a role in their differentiation. We find that the Notch ligand Jagged 2 is expressed in MCCs and that notch3 is expressed in pronephric epithelial cells. Morpholino knockdown of either jagged 2 or notch3, or mutation in mind bomb (in which Notch signaling is impaired), dramatically expands ciliogenic gene expression, whereas ion transporter expression is lost, indicating that pronephric cells are transfated to MCCs. Conversely, ectopic expression of the Notch1a intracellular domain represses MCC differentiation. Gamma-secretase inhibition using DAPT demonstrated a requirement for Notch signaling early in pronephric development, before the pattern of MCC differentiation is apparent. Strikingly, we find that jagged 2 knockdown generates extra cilia and is sufficient to rescue the kidney cilia mutant double bubble. Our results indicate that Jagged 2/Notch signaling modulates the number of multiciliated versus transporting epithelial cells in the pronephros by way of a genetic pathway involving repression of rfx2, a key transcriptional regulator of the ciliogenesis program. C1 Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA 02129 USA. Univ Hosp Freiburg, Div Renal, Zent Klin Forsch, D-79106 Freiburg, Germany. RP Drummond, IA (reprint author), Massachusetts Gen Hosp, Div Nephrol, 149 13th St, Charlestown, MA 02129 USA. EM idrummon@receptor.mgh.harvard.edu FU NIDDK NIH HHS [R01 DK53093] NR 67 TC 106 Z9 110 U1 1 U2 10 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAR 15 PY 2007 VL 134 IS 6 BP 1111 EP 1122 DI 10.1242/dev.02806 PG 12 WC Developmental Biology SC Developmental Biology GA 144YJ UT WOS:000244832200010 PM 17287248 ER PT J AU Shaw, AT Meissner, A Dowdle, JA Crowley, D Magendantz, M Ouyang, C Parisi, T Rajagopal, J Blank, LJ Bronson, RT Stone, JR Tuveson, DA Jaenisch, R Jacks, T AF Shaw, Alice T. Meissner, Alexander Dowdle, James A. Crowley, Denise Magendantz, Margaret Ouyang, Chensi Parisi, Tiziana Rajagopal, Jayaraj Blank, Leah J. Bronson, Roderick T. Stone, James R. Tuveson, David A. Jaenisch, Rudolf Jacks, Tyler TI Sprouty-2 regulates oncogenic K-ras in lung development and tumorigenesis SO GENES & DEVELOPMENT LA English DT Article DE K-ras; mouse models; lung development; lung cancer; Sprouty ID FACIO-CUTANEOUS SYNDROME; BRANCHING MORPHOGENESIS; GERMLINE MUTATIONS; SOMATIC ACTIVATION; KINASE PATHWAY; N-RAS; MOUSE; CANCER; CELLS; MICE AB Somatic activation of Ras occurs frequently in human cancers, including one-third of lung cancers. Activating Ras mutations also occur in the germline, leading to complex developmental syndromes. The precise mechanism by which Ras activation results in human disease is uncertain. Here we describe the phenotype of a mouse engineered to harbor a germline oncogenic K-ras(G12D) mutation. This mouse exhibits early embryonic lethality due to a placental trophoblast defect. Reconstitution with a wild-type placenta rescues the early lethality, but mutant embryos still succumb to cardiovascular and hematopoietic defects. In addition, mutant embryos demonstrate a profound defect in lung branching morphogenesis associated with striking up-regulation of the Ras/mitogen-activated protein kinase (MAPK) antagonist Sprouty-2 and abnormal localization of MAPK activity within the lung epithelium. This defect can be significantly suppressed by lentiviral short hairpin RNA (shRNA)-mediated knockdown of Sprouty-2 in vivo. Furthermore, in the context of K-ras(G12D)-mediated lung tumorigenesis, Sprouty-2 is also up-regulated and functions as a tumor suppressor to limit tumor number and overall tumor burden. These findings indicate that in the lung, Sprouty-2 plays a critical role in the regulation of oncogenic K-ras, and implicate counter-regulatory mechanisms in the pathogenesis of Ras-based disease. C1 MIT, Ctr Canc Res, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Tufts Univ, Sch Med & Vet Med, Dept Pathol, Boston, MA 02111 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Cambridge Res Inst, Cambridge CB2 0RE, England. RP Jacks, T (reprint author), MIT, Ctr Canc Res, Cambridge, MA 02139 USA. EM tjacks@mit.edu FU NCI NIH HHS [K08 CA111634, 5-U01-CA84306-06, P30 CA014051, 5K08CA111634-2, U01 CA084306, P30-CA14051] NR 50 TC 91 Z9 95 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAR 15 PY 2007 VL 21 IS 6 BP 694 EP 707 DI 10.1101/gad.1526207 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 147HB UT WOS:000244992900009 PM 17369402 ER PT J AU Touma, M Sun, ZYJ Clayton, LK Marissen, WE Kruisbeek, AM Wagner, G Reinherz, EL AF Touma, Maki Sun, Zhen-Yu J. Clayton, Linda K. Marissen, Wilfred E. Kruisbeek, Ada M. Wagner, Gerhard Reinherz, Ellis L. TI Importance of the CD3 gamma ectodomain terminal beta-strand and membrane proximal stalk in thymic development and receptor assembly SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL-RECEPTOR; ANTIGEN RECEPTOR; ALPHA-BETA; ZETA-CHAIN; CD3-EPSILON-GAMMA HETERODIMER; SIGNAL-TRANSDUCTION; KINASE ACTIVATION; ALLELIC EXCLUSION; CRYSTAL-STRUCTURE; TCR/CD3 COMPLEX AB CD3 epsilon gamma and CD3 epsilon delta are noncovalent heterodimers; each consists of Ig-like extracellular domains associated side-to-side via paired terminal beta-strands that are linked to individual subunit membrane proximal stalk segments. CD3 epsilon, CD3 gamma, and CD3 delta stalks contain the RxCxxCxE motif. To investigate the functional importance of a CD3 stalk and terminal beta-strand, we created a CD3 gamma double mutant CD3 gamma(C82S/C85S) and a CD3 gamma beta-strand triple mutant CD3 gamma(Q76S/Y78A/Y79A) for use in retroviral transduction of lymphoid progenitors for comparison with CD3 gamma wt. Although both mutant CD3 gamma molecules reduced association with CD3 epsilon in CD3 epsilon gamma heterodimers, CD3 gamma(Q76S/Y78A/Y79A) abrogated surface TCR expression whereas CD3 gamma(C82S/C85S) did not. Furthermore, CD3 gamma(C82S/C85S) rescued thymic development in CD3 gamma(-/-) fetal thymic organ culture. However, the numbers of double-positive and single-positive thymocytes after CD3 gamma(C82S/C85S) transduction were significantly reduced despite surface pre-TCR and TCR expression comparable to that of CD3 gamma(-/-) thymocytes transduced in fetal thymic organ culture with a retrovirus harboring CD3 gamma wt cDNA. Furthermore, double-negative thymocyte development was perturbed with attenuated double-negative 3/double-negative 4 maturation and altered surface-expressed CD3 epsilon gamma, as evidenced by the loss of reactivity with CD3 gamma N terminus-specific antisera. Single histidine substitution of either CD3 gamma stalk cysteine failed to restore CD3 epsilon gamma association and conformation in transient COS-7 cell transfection studies. Thus, CD3 gamma(C82) and CD3 gamma(C85) residues likely are either reduced or form a tight intrachain disulfide loop rather than contribute to a metal coordination site in conjunction with CD3 epsilon(C80) and CD3 epsilon(C83). The implications of these results for CD3 epsilon gamma and TCR structure and signaling function are discussed. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Netherlands Canc Inst, Div Immunol, NL-1066 CX Amsterdam, Netherlands. RP Reinherz, EL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM ellis_reinherz@dfci.harvard.edu FU NIAID NIH HHS [AI 19807, AI 37581] NR 51 TC 14 Z9 15 U1 0 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2007 VL 178 IS 6 BP 3668 EP 3679 PG 12 WC Immunology SC Immunology GA 146NX UT WOS:000244942400039 PM 17339464 ER PT J AU Montalbetti, N Li, Q Wu, YL Chen, XZ Cantiello, HF AF Montalbetti, Nicolas Li, Qiang Wu, Yuliang Chen, Xing-Zhen Cantiello, Horacio F. TI Polycystin-2 cation channel function in the human syncytiotrophoblast is regulated by microtubular structures SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID HUMAN PLACENTAL SYNCYTIOTROPHOBLAST; EPITHELIAL CA2+ CHANNEL; KIDNEY-DISEASE; CALCIUM-CHANNELS; HUMAN TROPHOBLAST; PRIMARY CILIUM; ALPHA-ACTININ; INTRACELLULAR CA2+; ENTRY CHANNELS; KIF3A SUBUNIT AB Polycystin-2 (PC2), encoded by PKD2, which is one of the genes whose mutations cause polycystic kidney disease, is abundantly produced in the apical domain of the syncytiotrophoblast (hST) of term human placenta. PC2, a TRP-type (TRPP2) non-selective cation channel, is present in primary cilia of renal epithelial cells, a microtubule-based ancillary structure with sensory function. The hST has abundant cytoskeletal structures, and actin filament dynamics regulate PC2 channel function in this epithelium. However, it is expected that the apical hST excludes microtubular structures. Here, we demonstrated by Western blot and immunocytochemical analyses that hST apical vesicles indeed contain microtubule structural components, including tubulin isoforms, acetylated alpha-tubulin, and the kinesin motor proteins KIF3A and KIF3B. PC2 and tubulin were substantially colocalized in hST vesicles. Treatment of hST vesicles with either the microtubular disrupter colchicine (15 mu M) or the microtubular stabilizer paclitaxel (taxol, 15 mu M) resulted in distinct patterns of microtubular re-organization and PC2 redistribution. We also observed that changes in microtubular dynamics regulate PC2 channel function. Addition of colchicine rapidly inhibited PC2 channel activity in lipid-bilayer reconstituted hST membranes. Addition of either tubulin and GTP, or taxol, however, stimulated PC2 channel activity in control hST membranes. Interestingly, we found that the kinesin motor protein KIF3A was capable of increasing PC2 channel activity in hST. We believe that the data are the first to provide a direct demonstration of a microtubular interaction with PC2 in the hST. This interaction thus plays an important regulatory role in the control of ion transport in the human placenta. C1 Massachusetts Gen Hosp, Renal Unit, Dept Med, Charlestown, MA 02129 USA. Univ Alberta, Dept Physiol, Edmonton, AB, Canada. Fac Farm & Bioquim, Lab Canales Ion, Dept Fisicoquim & Quim Analit, Buenos Aires, DF, Argentina. RP Cantiello, HF (reprint author), Massachusetts Gen Hosp, Renal Unit, Dept Med, Bldg 149,13th St, Charlestown, MA 02129 USA. EM cantiello@helix.mgh.harvard.edu OI Montalbetti, Nicolas/0000-0003-2897-9540 NR 68 TC 22 Z9 22 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD MAR 15 PY 2007 VL 579 IS 3 BP 717 EP 728 DI 10.1113/jphysiol.2006.125583 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 145TH UT WOS:000244886900018 PM 17204494 ER PT J AU Cheng, EM Swarztrauber, K Siderowf, AD Eisa, MS Lee, M Vassar, S Jacob, E Vickrey, BG AF Cheng, Eric M. Swarztrauber, Kari Siderowf, Andrew D. Eisa, Mahmood S. Lee, Martin Vassar, Stefanie Jacob, Erin Vickrey, Barbara G. TI Association of specialist involvement and quality of care for Parkinson's disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; quality of care; indicators; movement-disorder specialist ID VULNERABLE ELDERS/; STANDARDS SUBCOMMITTEE; PRACTICE PARAMETER; MEDICAL-CARE; INDICATORS; LIFE; MANAGEMENT; AGREEMENT; VARIABLES; NEUROLOGY AB Because Parkinson's disease (PD) has multiple neurological symptoms and often complex treatments, the quality of PD care may be higher when a specialist is involved. We examined the medical records, from 1998 to 2004, of 401 Los Angeles veterans with Parkinson's disease to determine whether care met key indicators of PD care quality. All care following a visit to a movement-disorder specialist or general neurologist was classified as specialty care. We compared adherence to each indicator by level of specialist involvement through logistic regression models. Over the study period, 10 indicators of PD care quality were triggered 2,227 times. Overall, movement disorder specialist involvement (78%) was associated with higher adherence to indicators than did general neurologist involvement (70%, P = 0.006) and nonneurologist involvement (52%, P < 0.001). The differences between movement disorder specialist and nonneurologist involvement were especially large for four indicators: treatment of wearing-off, assessments of falls, depression, and hallucinations. There is significant room for improving aspects of PD care quality among patients who do not have the involvement of a specialist. Quality of care interventions should involve specialists in management of motor symptoms and incorporate methods for routine assessment of nomnotor PD symptoms. (c) 2007 Movement Disorder Society. C1 VA Greater Los Angeles Healthcare Syst, Dept Neurol, Parkinsons Dis Res Educ & Clin Ctr PADRECC, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Prov Hlth Syst, Prov Med Grp, Newberg, OR USA. Philadelphia VA Med Ctr, PADRECC, Philadelphia, PA USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Yale Univ, Dept Neurol, New Haven, CT USA. Neurol Neurosurg & Spine Clin S Georgia, Valdosta, GA USA. VA Greater Los Angeles Healthcare Syst, VA Ctr Study Healthcare Provider Behav, Los Angeles, CA 90073 USA. RP Cheng, EM (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Neurol, Parkinsons Dis Res Educ & Clin Ctr PADRECC, 11301 Wilshire Blvd,B500,ML 127, Los Angeles, CA 90073 USA. EM Eric.Cheng@va.gov NR 26 TC 29 Z9 29 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAR 15 PY 2007 VL 22 IS 4 BP 515 EP 522 DI 10.1002/mds.21311 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 153CG UT WOS:000245408700013 PM 17260340 ER PT J AU Erkko, H Xia, B Nikkilae, J Schleutker, J Syrjaekoski, K Mannermaa, A Kallioniemi, A Pylkas, K Karppinen, SM Rapakko, K Miron, A Sheng, Q Li, GL Mattila, H Bell, DW Haber, DA Grip, M Reiman, M Jukkola-Vuorinen, A Mustonen, A Kere, J Aaltonen, LA Kosma, VM Kataja, V Soini, Y Drapkin, RI Livingston, DM Winqvist, R AF Erkko, Hannele Xia, Bing Nikkilae, Jenni Schleutker, Johanna Syrjaekoski, Kirsi Mannermaa, Arto Kallioniemi, Anne Pylkas, Katri Karppinen, Sanna-Maria Rapakko, Katrin Miron, Alexander Sheng, Qing Li, Guilan Mattila, Henna Bell, Daphne W. Haber, Daniel A. Grip, Mervi Reiman, Mervi Jukkola-Vuorinen, Arja Mustonen, Aki Kere, Juha Aaltonen, Lauri A. Kosma, Veli-Matti Kataja, Vesa Soini, Ylermi Drapkin, Ronny I. Livingston, David M. Winqvist, Robert TI A recurrent mutation in PALB2 in Finnish cancer families SO NATURE LA English DT Article ID SENSITIVE GEL-ELECTROPHORESIS; BREAST-CANCER; SUSCEPTIBILITY ALLELES; FANCONI-ANEMIA; OVARIAN-CANCER; BRCA2 AB BRCA1, BRCA2 and other known susceptibility genes account for less than half of the detectable hereditary predisposition to breast cancer(1-3). Other relevant genes therefore remain to be discovered. Recently a new BRCA2-binding protein, PALB2, was identified(4). The BRCA2-PALB2 interaction is crucial for certain key BRCA2 DNA damage response functions as well as its tumour suppression activity(4). Here we show, by screening for PALB2 mutations in Finland that a frameshift mutation, c.1592delT, is present at significantly elevated frequency in familial breast cancer cases compared with ancestry-matched population controls. The truncated PALB2 protein caused by this mutation retained little BRCA2-binding capacity and was deficient in homologous recombination and crosslink repair. Further screening of c.1592delT in unselected breast cancer individuals revealed a roughly fourfold enrichment of this mutation in patients compared with controls. Most of the mutation-positive unselected cases had a familial pattern of disease development. In addition, one multigenerational prostate cancer family that segregated the c.1592delT truncation allele was observed. These results indicate that PALB2 is a breast cancer susceptibility gene that, in a suitably mutant form, may also contribute to familial prostate cancer development. C1 Univ Kuopio, Inst Clin Med, FIN-70211 Kuopio, Finland. Karolinska Inst, Dept Biosci, SE-17177 Huddinge, Sweden. Karolinska Inst, Clin Res Ctr, SE-17177 Huddinge, Sweden. Univ Helsinki, Dept Med Genet, FIN-00014 Helsinki, Finland. Biomedicum Helsinki, FIN-00014 Helsinki, Finland. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Kuopio Univ Hosp, Dept Clin Pathol, FIN-70211 Kuopio, Finland. Univ Kuopio, Inst Clin Med Pathol & Forens Med, FIN-70211 Kuopio, Finland. Univ Tampere, Inst Med technol, Canc Genet Lab, FIN-33520 Tampere, Finland. Tampere Univ Hosp, Tampere, Finland. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Oulu Univ Hosp, FIN-90029 OYS, Finland. Univ Oulu, Dept Pathol, Oulu, Finland. Univ Oulu, Dept Oncol, Oulu, Finland. Univ Oulu, Dept Surg, Oulu, Finland. Univ Oulu, Dept Clin Genet, Oulu, Finland. RP Winqvist, R (reprint author), Kuopio Univ Hosp, Dept Oncol, FIN-70211 Kuopio, Finland. EM david_livingston@dfci.harvard.edu; robert.winqvist@oulu.fi RI Kere, Juha/A-9179-2008; Aaltonen, Lauri/A-5375-2010; Drapkin, Ronny/E-9944-2016; OI Kere, Juha/0000-0003-1974-0271; Aaltonen, Lauri/0000-0001-6839-4286; Drapkin, Ronny/0000-0002-6912-6977; Kallioniemi, Anne/0000-0003-3552-8158 NR 16 TC 225 Z9 229 U1 3 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 MAR 15 PY 2007 VL 446 IS 7133 BP 316 EP 319 DI 10.1038/nature05609 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 145VC UT WOS:000244892900045 PM 17287723 ER PT J AU Peng, CY Yajima, H Burns, CE Zon, LI Sisodia, SS Pfaff, SL Sharma, K AF Peng, Chian-Yu Yajima, Hiroshi Burns, Caroline Erter Zon, Leonard I. Sisodia, Sangram S. Pfaff, Samuel L. Sharma, Kamal TI Notch and MAML signaling drives scl-dependent interneuron diversity in the spinal cord SO NEURON LA English DT Article ID ELEGANS VULVAL DEVELOPMENT; PROGENITOR-CELL IDENTITY; MOTOR-NEURON; TRANSCRIPTION FACTORS; SUBTYPE IDENTITY; V2 INTERNEURONS; POSITIONAL IDENTITY; LOCOMOTOR CIRCUITS; SONIC HEDGEHOG; XENOPUS RETINA AB The ventral spinal cord generates multiple inhibitory and excitatory interneuron subtypes from four cardinal progenitor domains (p0, p1,, p2, p3). Here we show that cell-cell interactions mediated by the Notch receptor play a critical evolutionarily conserved role in the generation of excitatory v2aIN and inhibitory v2bIN interneurons. Lineage-tracing experiments show that the v2aIN and v2bIN develop from genetically identical p2 progenitors. The p2 daughter cell fate is controlled by Delta4 activation of Notch receptors together with MAML factors. Cells receiving Notch signals activate a transcription factor code that specifies the v2bIN fate, whereas cells deprived of Notch signaling express another code for v2aIN formation. Thus, our study provides insight into the cell-extrinsic signaling that controls combinatorial transcription factor profiles involved in regulating the process of interneuron subtype diversification. C1 Univ Chicago, Dept Neurobiol, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Harvard Stem Cell Inst, Boston, MA 02115 USA. Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA. RP Sharma, K (reprint author), Univ Chicago, Dept Neurobiol, Chicago, IL 60637 USA. EM ksharma@bsd.uchicago.edu FU NINDS NIH HHS [R01-NS045106, R01 NS045106-04, R01 NS045106] NR 57 TC 94 Z9 94 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD MAR 15 PY 2007 VL 53 IS 6 BP 813 EP 827 DI 10.1016/j.neuron.2007.02.019 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 151LV UT WOS:000245292800007 PM 17359917 ER PT J AU Jiang, X Bradley, E Rini, RA Zeffiro, T VanMeter, J Riesenhuber, M AF Jiang, Xiong Bradley, Evan Rini, Regina A. Zeffiro, Thomas VanMeter, John Riesenhuber, Maximilian TI Categorization training results in shape- and category-selective human neural plasticity SO NEURON LA English DT Article ID LATERAL OCCIPITAL COMPLEX; INFERIOR TEMPORAL CORTEX; EVENT-RELATED FMRI; VISUAL CATEGORIZATION; OBJECT RECOGNITION; PREFRONTAL CORTEX; TASK-DIFFICULTY; FUNCTIONAL MRI; ATTENTION; AREA AB Object category learning is a fundamental ability, requiring the combination of "bottom-up" stimulus-driven with "top-down" task-specific information. It therefore may be a fruitful domain for study of the general neural mechanisms underlying cortical plasticity. A simple model predicts that category learning involves the formation of a task-independent shape-selective representation that provides input to circuits learning the categorization task, with the computationally appealing prediction of facilitated learning of additional, novel tasks over the same stimuli. Using fMRI rapid-adaptation techniques, we find that categorization training (on morphed "cars") induced a significant release from adaptation for small shape changes in lateral occipital cortex irrespective of category membership, compatible with the sharpening of a representation coding for physical appearance. In contrast, an area in lateral prefrontal cortex, selectively activated during categorization, showed sensitivity posttraining to explicit changes in category membership. Further supporting the model, categorization training also improved discrimination performance on the trained stimuli. C1 Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20007 USA. Massachusetts Gen Hosp, Neural Syst Grp, Charlestown, MA 02129 USA. Georgetown Univ, Med Ctr, Ctr Funct & Mol Imaging, Washington, DC 20007 USA. RP Riesenhuber, M (reprint author), Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20007 USA. EM mr287@georgetown.edu RI Bradley, Evan/H-9037-2012; OI Bradley, Evan/0000-0001-6887-671X; Riesenhuber, Maximilian/0000-0002-5744-0408 FU NCRR NIH HHS [M01 RR020359]; NICHD NIH HHS [P30 HD040677, P30 HD40677]; NIMH NIH HHS [P20 MH066239, P20 MH066239-04, P20MH66239, R01 MH076281, R01 MH076281-02, R01MH076281] NR 48 TC 142 Z9 144 U1 1 U2 20 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD MAR 15 PY 2007 VL 53 IS 6 BP 891 EP 903 DI 10.1016/j.neuron.2007.02.015 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 151LV UT WOS:000245292800013 PM 17359923 ER PT J AU Lewis, GD Holmes, CB Holmvang, G Butterton, JR Harris, NL Bazari, H AF Lewis, Gregory D. Holmes, Charles B. Holmvang, Godtfred Butterton, Joan R. Harris, Nancy Lee Bazari, Hasan TI Case 8-2007: A 48-year-old man with chest pain followed by cardiac arrest - Helicobacter cinaedi myopericarditis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; HUMAN-IMMUNODEFICIENCY-VIRUS; ACUTE AORTIC DISSECTION; ACUTE PERICARDITIS; ENDOMYOCARDIAL BIOPSY; CAMPYLOBACTER-CINAEDI; SEPTIC SHOCK; LYMPHOCYTIC MYOCARDITIS; DILATED CARDIOMYOPATHY; GIANT-CELL C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. RP Lewis, GD (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 50 TC 11 Z9 11 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 15 PY 2007 VL 356 IS 11 BP 1153 EP 1162 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 145PO UT WOS:000244877200010 PM 17360994 ER PT J AU Ozcan, A Tewary, A Digonnet, MJF Kino, GS AF Ozcan, Aydogan Tewary, Anuranjita Digonnet, Michel J. F. Kino, Gordon S. TI Observation of mode coupling in bitapered air-core photonic bandgap fibers SO OPTICS COMMUNICATIONS LA English DT Article ID OPTICAL-FIBER; CONVERSION; DEVICES; TAPERS AB We report the fabrication and characterization of the first bitapers in air-core photonic bandgap fibers. Like conventional fiber bitapers, these devices are found to exhibit quasi-sinusoidally modulated transmission spectra, the signature of resonant coupling to a dominant cladding mode. However, unlike in conventional tapers of comparable length, the modulation period is very short (0.5-3.3 nm), which suggests that coupling takes place to a very high order cladding mode. Such coupling is observed even in comparatively weak bitapers (diameter reduction as low as similar to 2%), indicating that air-core fibers are highly sensitive to tapering. The loss of weak tapers is observed to be small (< 0.3 dB), which suggests possible applications of this simple technology as in-line filters of high resolution. (c) 2006 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA. Stanford Univ, Edward L Ginzton Lab, Stanford, CA 94305 USA. RP Ozcan, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM aozcan@mgh.harvard.edu RI Ozcan, Aydogan/I-2608-2013 OI Ozcan, Aydogan/0000-0002-0717-683X NR 10 TC 9 Z9 10 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0030-4018 J9 OPT COMMUN JI Opt. Commun. PD MAR 15 PY 2007 VL 271 IS 2 BP 391 EP 395 DI 10.1016/j.optcom.2006.10.039 PG 5 WC Optics SC Optics GA 140FD UT WOS:000244488900014 ER PT J AU Joo, C Kim, KH de Boer, JF AF Joo, Chuhnin Kim, Ki Hean de Boer, Johannes F. TI Spectral-domain optical coherence phase and multiphoton microscopy SO OPTICS LETTERS LA English DT Article ID FLUORESCENCE MICROSCOPY; DYNAMICS; CELLS AB We describe simultaneous quantitative phase contrast and multiphoton fluorescence imaging by combined spectral-domain optical coherence phase and multiphoton microscopy. The instrument employs two light sources for efficient optical coherence microscopic and multiphoton imaging and can generate structural and functional images of transparent specimens in the epidirection. Phase contrast imaging exhibits spatial and temporal phase stability in the subranometer range. We also demonstrate the visualization of actin filaments in a fixed cell specimen, which is confirmed by simultaneous multiphoton fluorescence imaging. (c) 2007 Optical Society of America C1 MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Joo, C (reprint author), MIT, Dept Mech Engn, Cambridge, MA 02139 USA. EM cmjoo@mit.edu; deboer@helix.mgh.harvard.edu RI de Boer, Johannes/B-7590-2012; OI de Boer, Johannes/0000-0003-1253-4950; Joo, Chulmin/0000-0002-1812-2976 FU NCRR NIH HHS [R01 RR19768]; NEI NIH HHS [EY14975] NR 16 TC 31 Z9 31 U1 0 U2 3 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD MAR 15 PY 2007 VL 32 IS 6 BP 623 EP 625 DI 10.1364/OL.32.000623 PG 3 WC Optics SC Optics GA 143MR UT WOS:000244726900014 PM 17308581 ER PT J AU Biss, DP Sumorok, D Burns, SA Webb, RH Zhou, YP Bifano, TG Cote, D Veilleux, I Zamiri, P Lin, CP AF Biss, David P. Sumorok, Daniel Burns, Stephen A. Webb, Robert H. Zhou, Yaopeng Bifano, Thomas G. Cote, Daniel Veilleux, Israel Zamiri, Parisa Lin, Charles P. TI In vivo fluorescent imaging of the mouse retina using adaptive optics SO OPTICS LETTERS LA English DT Article ID SCANNING LASER OPHTHALMOSCOPY; GANGLION-CELLS; HUMAN EYE; ABERRATIONS AB In vivo imaging of the mouse retina using visible and near infrared wavelengths does not achieve diffraction-limited resolution due to wavefront aberrations induced by the eye. Considering the pupil size and axial dimension of the eye, it is expected that unaberrated imaging of the retina would have a transverse resolution of 2 mu m. Higher-order aberrations in retinal imaging of human can be compensated for by using adaptive optics. We demonstrate an adaptive optics system for in vivo imaging of fluorescent structures in the retina of a mouse, using a microelectromechanical system membrane mirror and a Shack-Hartmann wavefront sensor that detects fluorescent wavefront. (c) 2007 Optical Society of America. C1 Schepens Eye Res Inst, Boston, MA 02114 USA. Boston Univ, Brookline, MA 02446 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Adv Microscopy Program, Boston, MA 02114 USA. RP Biss, DP (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM david.biss@schepens.harvard.edu RI Cote, Daniel/D-5185-2011; Bifano, Thomas/E-6412-2013; Burns, Stephen/D-9259-2011 OI Bifano, Thomas/0000-0003-4952-2515; Burns, Stephen/0000-0001-5348-035X FU NEI NIH HHS [EY-014375, EY-14106, R01 EY004395, R01 EY004395-25, R01 EY014106, R01 EY014375]; NIBIB NIH HHS [R01 EB000664, R01 EB000664-02] NR 14 TC 33 Z9 33 U1 1 U2 10 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD MAR 15 PY 2007 VL 32 IS 6 BP 659 EP 661 DI 10.1364/OL.32.000659 PG 3 WC Optics SC Optics GA 143MR UT WOS:000244726900026 PM 17308593 ER PT J AU Meena Sam, M Pierce, K Szostak, JW McLaughlin, LW AF Meena Sam, Mui Pierce, Kathryn Szostak, Jack W. McLaughlin, Larry W. TI 2 ',3 '-Dideoxy-3 '-thionucleoside triphosphates: Syntheses and polymerase substrate activities SO ORGANIC LETTERS LA English DT Article ID DEPENDENT RNA-POLYMERASE; ESCHERICHIA-COLI; 3'-S-PHOSPHOROTHIOLATE LINKAGES; DNA-SYNTHESIS; OLIGODEOXYNUCLEOTIDES; 5'-TRIPHOSPHATES; TERMINATORS AB All four 2',3'-dideoxy-3'-thio-nucleosides (ddtNTPs) function as substrates for the Y410F mutant of Deep Vent (exo(-)) DNA polymerase. Not only are the ddtNTPs incorporated to form the N + 1 product, but further elongations are observed in which the key step is attack of the 3'-thiol on the 5'-triphosphate. Although other polymerases are likely to differ in their use of the ddtNTPs, there does not appear to be a fundamental prohibition against using a thiol nucleophile on a phosphate anhydride electrophile. The syntheses of four ddtNTPs (C, T, A, G) are described. C1 Boston Coll, Merkert Chem Ctr, Dept Chem, Chestnut Hill, MA 02467 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP McLaughlin, LW (reprint author), Boston Coll, Merkert Chem Ctr, Dept Chem, Chestnut Hill, MA 02467 USA. EM mclaughl@bc.edu NR 16 TC 0 Z9 0 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD MAR 15 PY 2007 VL 9 IS 6 BP 1161 EP 1163 DI 10.1021/ol070147w PG 3 WC Chemistry, Organic SC Chemistry GA 143PV UT WOS:000244735900054 ER PT J AU Pree, I Bigenzahn, S Fuchs, D Koporc, Z Nierlich, P Winkler, C Brandacher, G Sykes, M Muehlbacher, F Langer, F Wekerle, T AF Pree, Ines Bigenzahn, Sinda Fuchs, Dietmar Koporc, Zvonimir Nierlich, Patrick Winkler, Christiana Brandacher, Gerald Sykes, Megan Muehlbacher, Ferdinand Langer, Felix Wekerle, Thomas TI CTLA4Ig promotes the induction of hematopoietic chimerism and tolerance independently of indoleamine-2,3-dioxygenase SO TRANSPLANTATION LA English DT Article DE tolerance; mixed chimerism; costimulation blockade; CTLA4Ig; indoleamine-2,3-dioxygenase ID BONE-MARROW-TRANSPLANTATION; T-CELL TOLERANCE; LONG-TERM ACCEPTANCE; TRYPTOPHAN CATABOLISM; DENDRITIC CELLS; INDOLEAMINE 2,3-DIOXYGENASE; COSTIMULATORY BLOCKADE; CARDIAC ALLOGRAFTS; MIXED CHIMERISM; MECHANISMS AB Bone marrow transplantation (BMT) under costimulation blockade induces mixed chimerism and tolerance in rodent models. Recent data, predominantly from in vitro studies, suggest that in addition to blocking the CD28 costimulation pathway CTLA4Ig also acts through upregulating the tryptophan-catabolizing enzyme indoleamine-2,3-dioxygenase (IDO). Here we demonstrate that even though CTLA4Ig is critically required for the induction of chimerism and tolerance in a murine model of nonmyeloablative BMT, IDO activity is not. No significant differences were detectable in the kynurenine to tryptophan ratios (indicative of IDO activity) in sera of BMT recipients treated with CTLA4Ig (tolerant group) versus BMT recipients treated without CTLA4Ig (nontolerant group) versus naive controls. In vivo inhibition of IDO immediately after BMT with CTLA4Ig or several months thereafter did not block achievement of chimerism and tolerance. Thus, IDO does not play a critical role in the induction or maintenance of chimerism and tolerance in a CTLA4Ig-based BMT model. C1 Vienna Gen Hosp, Dept Surg, Div Transplantat, A-1090 Vienna, Austria. Innsbruck Med Univ, Dept Gen & Transplant Surg, Innsbruck, Austria. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplant Biol Res, Boston, MA 02115 USA. RP Wekerle, T (reprint author), Vienna Gen Hosp, Dept Surg 21A, Waehringer Guertel 18, A-1090 Vienna, Austria. EM thomas.wekerle@meduniwien.ac.at RI Brandacher, Gerald/L-7540-2016; OI Wekerle, Thomas/0000-0001-5159-2796 FU Austrian Science Fund FWF [F 2310] NR 29 TC 27 Z9 29 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAR 15 PY 2007 VL 83 IS 5 BP 663 EP 667 DI 10.1097/01.tp.0000255594.23445.29 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 146PD UT WOS:000244945600025 PM 17353791 ER PT J AU Kirschner, KL Breslin, ML Iezzoni, LI AF Kirschner, Kristi L. Breslin, Mary Lou Iezzoni, Lisa I. TI Structural impairments that limit access to health care for patients with disabilities SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID PREVENTIVE SERVICES; BARRIERS C1 Northwestern Univ, Feinberg Sch Med, Rehabil Inst Chicago, Chicago, IL 60611 USA. Disabil Rights Educ & Def Fund, Berkeley, CA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, Boston, MA USA. RP Kirschner, KL (reprint author), Northwestern Univ, Feinberg Sch Med, Rehabil Inst Chicago, 345 E Super St,Room 1136, Chicago, IL 60611 USA. EM kkirschner@ric.org NR 23 TC 35 Z9 36 U1 1 U2 5 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 MAR 14 PY 2007 VL 297 IS 10 BP 1121 EP 1125 DI 10.1001/jama.297.10.1121 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 145KZ UT WOS:000244865200028 PM 17356035 ER PT J AU Aryana, A d'Avila, A Heist, EK Mela, T Singh, JP Ruskin, JN Reddy, VY AF Aryana, Arash d'Avila, Andre Heist, E. Kevin Mela, Theofanie Singh, Jagmeet P. Ruskin, Jeremy N. Reddy, Vivek Y. TI Remote magnetic navigation to guide endocardial and epicardial catheter mapping of scar-related ventricular tachycardia SO CIRCULATION LA English DT Article DE ablation; catheter ablation; electrophysiology; magnetic resonance imaging; mapping; tachycardia; tomography ID MULTIDETECTOR COMPUTED-TOMOGRAPHY; HEALED MYOCARDIAL-INFARCTION; PORCINE MODEL; FIBRILLATION ABLATION; HEART-DISEASE; SINUS RHYTHM; GUIDANCE; SYSTEM AB Background - The present study examines the safety and feasibility of using a remote magnetic navigation system to perform endocardial and epicardial substrate-based mapping and radiofrequency ablation in patients with scar-related ventricular tachycardia (VT). Methods and Results - Using the magnetic navigation system, we performed 27 procedures on 24 consecutive patients with a history of VT related to myocardial infarction, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy, or sarcoidosis. Electroanatomic mapping of the left ventricular, right ventricular, and ventricular epicardial surfaces was constructed in 24, 10, and 12 patients, respectively. Complete-chamber VT activation maps were created in 4 patients. A total of 77 VTs were inducible, of which 21 were targeted during VT with the remotely navigated radiofrequency ablation catheter alone. With a combination of entrainment and activation mapping, 17 of 21 VTs (81%) were successfully terminated in a mean of 8.4 +/- 8.2 seconds; for the remainder, irrigated radiofrequency ablation was necessary. The mean fluoroscopy times for endocardial and epicardial mapping were 27 +/- 23 seconds (range, 0 to 105 seconds) and 18 +/- 18 seconds (range, 0 to 49 seconds), respectively. In concert with a manually navigated irrigated ablation catheter, 75 of 77 VTs (97%) were ultimately ablated. Four patients underwent a second procedure for recurrent VT, 3 with the magnetic navigation system. After 1.2 procedures per patient, VT did not recur during a mean follow-up of 7 +/- 3 months (range, 2 to 12 months). Conclusions - The present study demonstrates the safety and feasibility of remote catheter navigation to perform substrate mapping of scar-related VT in a wide range of disease states with a minimal amount of fluoroscopy exposure. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Reddy, VY (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB-109, Boston, MA 02114 USA. EM vreddy@partners.org RI d'Avila, Andre/A-7693-2009; d'Avila, Andre Luiz/F-8009-2010 OI d'Avila, Andre Luiz/0000-0001-8769-1411 FU NHLBI NIH HHS [K23 HL68064] NR 20 TC 64 Z9 66 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 MAR 13 PY 2007 VL 115 IS 10 BP 1191 EP 1200 DI 10.1161/CIRCULATIONAHA.106.672162 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 145KQ UT WOS:000244864100007 PM 17296855 ER PT J AU Givertz, MM Andreou, C Conrad, CH Colucci, WS AF Givertz, Michael M. Andreou, Costa Conrad, Chester H. Colucci, Wilson S. TI Direct myocardial effects of levosimendan in humans with left ventricular dysfunction - Alteration of force-frequency and relaxation-frequency relationships SO CIRCULATION LA English DT Article DE calcium; contractility; heart failure; levosimendan; myocardium ID FAILING HUMAN MYOCARDIUM; SENSITIVE K+ CHANNEL; SEVERE HEART-FAILURE; DIASTOLIC FUNCTION; CA2+ SENSITIZER; TROPONIN-C; PHOSPHODIESTERASE INHIBITION; INTRAVENOUS LEVOSIMENDAN; DILATED CARDIOMYOPATHY; CALCIUM SENSITIZATION AB Background - Enthusiasm for the development of Ca2+ sensitizers as inotropic agents for heart failure has been tempered by reports of impaired relaxation. Levosimendan, which increases myofilament Ca2+ sensitivity via Ca2+-dependent binding to troponin C, exerts positive inotropic and lusitropic effects in failing human myocardium in vitro. We sought to determine the direct effects of levosimendan on failing human myocardium in vivo, and in particular whether levosimendan exerts heart rate - dependent effects on systolic or diastolic function. Methods and Results - Ten patients with left ventricular dysfunction caused by nonischemic dilated cardiomyopathy ( mean left ventricular ejection fraction, 27 +/- 2%) were instrumented with an infusion catheter in the left main coronary artery, a high-fidelity micromanometer-tipped catheter in the left ventricle, and a bipolar pacing wire in the right atrium. Inotropic (peak + dP/dt) and lusitropic (Tau) responses were assessed during continuous intracoronary drug infusion in sinus rhythm followed by atrial pacing at 20, 40, and 60 beats per minute above the sinus rate. Under control conditions (intracoronary 5% dextrose in water), atrial-pacing tachycardia decreased Tau by 13% (P < 0.05), but did not increase + dP/dt. Intracoronary levosimendan (3.75 and 12.5 mu g/min for 15 minutes each) increased +dP/dt dose-dependently and decreased Tau over a range of heart rates, but did not alter the slope of the force-frequency or relaxation-frequency relationship. Conclusions - Myocardial calcium sensitization with levosimendan exerts mild inotropic and lusitropic effects in humans with left ventricular dysfunction, but does not alter the force-frequency or relaxation-frequency relationship. C1 Boston Univ, Med Ctr, Cardiomyopathy Program, Boston, MA USA. Boston Univ, Med Ctr, Cardiovasc Sect, Boston, MA USA. VA Boston Healthcare, Cardiol Sect, Boston, MA USA. RP Givertz, MM (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM mgivertz@partners.org NR 41 TC 36 Z9 42 U1 0 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 MAR 13 PY 2007 VL 115 IS 10 BP 1218 EP 1224 DI 10.1161/CIRCULATIONAHA.106.668640 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 145KQ UT WOS:000244864100010 PM 17339544 ER PT J AU Elkind, MSV Prabhakaran, S Pittman, J Koroshetz, W Jacoby, M Johnston, KC AF Elkind, M. S. V. Prabhakaran, S. Pittman, J. Koroshetz, W. Jacoby, M. Johnston, K. C. CA GAIN Am Investigators TI Sex as a predictor of outcomes in patients treated with thrombolysis for acute stroke SO NEUROLOGY LA English DT Article ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; RANDOMIZED CONTROLLED-TRIAL; CEREBROVASCULAR-DISEASE; GENDER-DIFFERENCES; POOLED ANALYSIS; METAANALYSIS; CLASSIFICATION; FIBRINOLYSIS; PROUROKINASE AB Objective: To determine the association between sex and functional outcomes after thrombolytic treatment for acute ischemic stroke in the context of a clinical trial. Methods: We analyzed predictors of outcome among patients treated with recombinant tissue plasminogen activator (rtPA) in the Glycine Antagonist in Neuroprotection for Patients with Acute Stroke Americas trial, a multicenter, randomized, double-blind, placebo-controlled study of a putative neuroprotectant. Results: Among 1,367 trial patients, 333 (24%) were treated with rtPA within 3 hours. The proportion of patients achieving good functional outcomes at 3 months differed by sex (47.5% of men vs 30.3% of women had Barthel Index [BI] >= 95; 32.2% of men vs 23.4% of women had modified Rankin Score [mRS] <= 1). NIH Stroke Score was similar by sex. Men were more likely to have good functional outcomes after adjusting for relevant covariates: for BI >= 95, adjusted odds ratio ( OR) 3.28 ( 1.74 to 6.17); for mRS <= 1, adjusted OR 2.12 ( 1.11 to 4.03). Survival was worse among men: adjusted OR 0.45 (0.20 to 1.01). Other predictors of functional outcomes included age, stroke side, severity, complications, and infections. Conclusions: Among tissue plasminogen activator - treated patients in this clinical trial population, men were approximately three times as likely to have good functional outcomes, despite elevated mortality. Thrombolysis for stroke may not reverse the tendency for women to have worse functional outcomes after stroke. C1 Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. Columbia Presbyterian Med Ctr, Presbyterian Hosp, New York, NY 10032 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Des Moines Univ, Sch Med, Dept Neurol, Des Moines, IA USA. Univ Virginia, Hlth Syst, Dept Neurol & Publ Hlth Sci, Charlottesville, VA USA. RP Elkind, MSV (reprint author), Columbia Univ, Coll Phys & Surg, Dept Neurol, 710 W 168 St, New York, NY 10032 USA. EM mse13@columbia.edu NR 44 TC 43 Z9 44 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 13 PY 2007 VL 68 IS 11 BP 842 EP 848 DI 10.1212/01.wnl.0000256748.28281.ad PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 145KP UT WOS:000244864000008 PM 17353472 ER PT J AU Chen-Plotkin, AS Vossel, KA Samuels, MA Chen, MH AF Chen-Plotkin, Alice S. Vossel, Keith A. Samuels, Martin A. Chen, Ming Hui TI Encephalopathy, stroke, and myocardial infarction with DMSO use in stem cell transplantation SO NEUROLOGY LA English DT Article ID INFUSION AB Stem cell transplants are established therapy for hematologic and solid tumor malignancies. Known neurological complications of stem cell transplantation include CNS infection, seizures, strokes, metabolic encephalopathy, and hemorrhage. We report two cases of autologous stem cell transplantation complicated by cerebral infarction and myocardial injury. We postulate that the cryopreservative dimethyl sulfoxide may be responsible. C1 Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Cardiol & Womens Hlth, Boston, MA 02115 USA. RP Chen-Plotkin, AS (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. EM aschen@partners.org NR 10 TC 22 Z9 25 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 13 PY 2007 VL 68 IS 11 BP 859 EP 861 DI 10.1212/01.wnl.0000256716.04218.5b PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 145KP UT WOS:000244864000011 PM 17353475 ER PT J AU Liu, XQ Bulgakov, OV Darrow, KN Pawlyk, B Adamian, M Liberman, MC Li, TS AF Liu, Xiaoqing Bulgakov, Oleg V. Darrow, Keith N. Pawlyk, Basil Adamian, Michael Liberman, M. Charles Li, Tiansen TI Usherin is required for maintenance of retinal photoreceptors and normal development of cochlear hair cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE photoreceptor degeneration; retina; retinitis pigmentosa ID SYNDROME-TYPE IIA; RECESSIVE RETINITIS-PIGMENTOSA; SYNDROME TYPE 1D; HEARING-LOSS; USH2A GENE; PROTEIN NETWORK; MOUSE MODEL; SYNDROME 1B; MUTATIONS; IDENTIFICATION AB Usher syndrome type IIA (USH2A), characterized by progressive photoreceptor degeneration and congenital moderate hearing loss, is the most common subtype of Usher syndrome. In this article, we show that the USH2A protein, also known as usherin, is an exceptionally large (approximate to 600-kDa) matrix protein expressed specifically in retinal photoreceptors and developing cochlear hair cells. In mammalian photoreceptors, usherin is localized to a spatially restricted membrane microdomain at the apical inner segment recess that wraps around the connecting cilia, corresponding to the periciliary ridge complex described for amphibian photoreceptors. In sensory hair cells of the cochlea, it is associated transiently with the hair bundles during postnatal development. Targeted disruption of the Ush2a gene in mice leads to progressive photoreceptor degeneration and a moderate but nonprogressive hearing impairment, mimicking the visual and hearing deficits in USH2A patients. These data suggest that usherin is required for the long-term maintenance of retinal photoreceptors and for the development of cochlear hair cells. We propose a model in which usherin in photoreceptors is tethered via its C terminus to the plasma membrane and its large extracellular domain projecting into the periciliary matrix, where they may interact with the connecting cilium to fulfill important structural or signaling roles. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Li, TS (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. EM tli@meei.harvard.edu FU NEI NIH HHS [P30 EY 14104, P30 EY014104, R01 EY 10309, R01 EY010309]; NIDCD NIH HHS [P30 DC 05209, P30 DC005209, R01 DC 00188, R01 DC000188, R01 DC000188-27] NR 48 TC 95 Z9 96 U1 1 U2 7 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 MAR 13 PY 2007 VL 104 IS 11 BP 4413 EP 4418 DI 10.1073/pnas.0610950104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146ZH UT WOS:000244972700032 PM 17360538 ER PT J AU Strobel, O Dor, Y Stirman, A Trainor, A Fernandez-del Castillo, C Warshaw, AL Thayer, SP AF Strobel, Oliver Dor, Yuval Stirman, Amy Trainor, Amanda Fernandez-del Castillo, Carlos Warshaw, Andrew L. Thayer, Sarah P. TI beta cell transdifferentiation does not contribute to preneoplastic/metaplastic ductal lesions of the pancreas by genetic lineage tracing in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE metaplasia; pancreatitis; pancreatic intraepithelial neoplasia ID TUBULAR COMPLEXES; ACINAR-CELLS; RAT PANCREAS; MALIGNANT-TRANSFORMATION; LANGERHANS ISLETS; GROWTH-FACTOR; ADULT-RATS; MOUSE; HAMSTER; INSULIN AB Inflammatory injury to the pancreas results in regeneration of normal tissue and formation of metaplastic lesions of a ductal phenotype. These metaplastic ductal lesions (MDL) are called tubular complexes (TC), mucinous metaplasia, or pancreatic intra-epithelial neoplasia. Because they are regularly found in chronic pancreatitis and pancreatic cancer, their formation is thought to represent a step in inflammation-mediated carcinogenesis. Despite these lesions' ductal character, their origin is controversial. All known pancreatic cell lineages have been suggested as the origin. In vitro studies suggest that differentiated cells in the pancreas remain highly plastic and can transdifferentiate as a mechanism of regeneration and metaplasia. In vivo studies suggest that islets, specifically is cells, may be the cell of origin. However, in vitro studies are subject to ductal cell contamination, and previous in vivo studies interpret static data rather than direct evidence. Using genetic lineage tracing in vivo, we investigate whether transdifferentiation of beta cells contributes to regeneration or metaplasia in pancreatitis. RIP-CreER;Z/AP mice were used to heritably tag beta cells in the adult pancreas. Injury by cerulein pancreatitis resulted in regeneration of normal tissue and metaplasia with formation of two distinct types of TC and mucinous lesions. Lineage tracing revealed that none of these MDL are of beta cell origin; nor do beta cells contribute to regeneration of normal acinar and ductal tissue, which indicates that the plasticity of differentiated pancreatic islet cells, suggested by earlier static and in vitro studies, plays no role in regeneration, metaplasia, and carcinogenesis in vivo. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Cellular Biochem & Human Genet, IL-91120 Jerusalem, Israel. RP Thayer, SP (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,WACC 460, Boston, MA 02114 USA. EM sthayer@partners.org RI Dor, Yuval/C-2405-2011 NR 48 TC 38 Z9 39 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 MAR 13 PY 2007 VL 104 IS 11 BP 4419 EP 4424 DI 10.1073/pnas.06052488104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146ZH UT WOS:000244972700033 PM 17360539 ER PT J AU Zha, S Alt, FW Cheng, HL Brush, JW Li, G AF Zha, Shan Alt, Frederick W. Cheng, Hwei-Ling Brush, James W. Li, Gang TI Defective DNA repair and increased genomic instability in Cernunnos-XLF-deficient murine ES cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE nonhomologous DNA end-joining; severe combined immunodeficiency; V(D)J recombination ID DOUBLE-STRAND BREAKS; END-JOINING FACTOR; V(D)J RECOMBINATION; SACCHAROMYCES-CEREVISIAE; MAMMALIAN TELOMERES; IV-COMPLEX; PROTEIN; STABILITY; PHENOTYPE; INTERACTS AB Nonhomologous DNA end-joining (NHEJ) is a major pathway of DNA double-strand break (DSB) repair in mammalian cells, and it functions to join both specifically programmed DSBs that occur in the context of V(D)J recombination during early lymphocyte development as well as general DSBs that occur in all cells. Thus, defects in NHEJ impair V(D)J recombination and lead to general genomic instability. In human patients, mutations of Cernunnos-XLF (also called NHEJ1), a recently identified NHEJ factor, underlie certain severe combined immune deficiencies associated with defective V(D)J recombination and radiosensitivity. To characterize Cernunnos-XLF function in mouse cells, we used gene-targeted mutation to delete exons 4 and 5 from both copies of the Cernunnos-XLF gene in ES cell (referred to as Cer(Delta/Delta) ES cells). Analyses of Cer(Delta/Delta) ES cells showed that they produce no readily detectable Cernunnos-XLF protein. Based on transient V(D)J recombination assays, we find that Cer(Delta/Delta) ES cells have dramatic impairments in ability to form both V(D)J coding joins and joins of their flanking recombination signal sequences (RS joins). Cer(Delta/Delta) ES cells are highly sensitive to ionizing radiation and have intrinsic DNA DSB repair defects as measured by pulse field gel electrophoresis. Finally, the Cernunnos-XLF mutations led to increased spontaneous genomic instability, including translocations. We conclude that, in mice, Cernunnos-XLF is essential for normal NHEJ-mediated repair of DNA DSBs and that Cernunnos-XLF acts as a genomic caretaker to prevent genomic instability. C1 Harvard Univ, Sch Med, Childrens Hosp, CBR Inst Biomed Res,Howard Hughes Med Inst, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Childrens Hosp, CBR Inst Biomed Res,Howard Hughes Med Inst, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu FU NCI NIH HHS [CA 92625, P01 CA092625]; NIAID NIH HHS [AI 35714, P01 AI035714] NR 32 TC 76 Z9 80 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 13 PY 2007 VL 104 IS 11 BP 4518 EP 4523 DI 10.1073/pnas.0611734104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146ZH UT WOS:000244972700050 PM 17360556 ER PT J AU Gavanescu, I Kessler, B Ploegh, H Benoist, C Mathis, D AF Gavanescu, Irina Kessler, Benedikt Ploegh, Hidde Benoist, Christophe Mathis, Diane TI Loss of Aire-dependent thymic expression of a peripheral tissue antigen renders it a target of autoimmunity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE central tolerance; self-antigen; inflammation ID T-CELL REPERTOIRE; CANDIDIASIS-ECTODERMAL DYSTROPHY; PROMISCUOUS GENE-EXPRESSION; NEGATIVE SELECTION; DEFICIENT MICE; REGULATOR PROTEIN; EPITHELIAL-CELLS; SELF-ANTIGEN; TOLERANCE; MOUSE AB Both humans and mice with a mutation in the autoimmune regulator (aire) gene develop multiorgan autoimmune disease. Aire was shown to exert its critical function in medullary epithelial cells of the thymus by promoting ectopic expression of peripheral tissue antigens. It was hypothesized that the widespread autoimmunity of Aire-deficient individuals reflects a lack of tolerance induction to the repertoire of peripheral tissue antigens expressed in the thymus of normal individuals. Here, we substantiate this hypothesis by identifying Mucin 6 as a stomach-specific antigen targeted by autoantibodies in gastritisprone mice lacking thymic expression of aire and demonstrate that transcription of the Mucin 6 gene in thymic medullary epithelial cells is indeed Aire-dependent. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Benoist, C (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu; dm@joslin.harvard.edu OI Kessler, Benedikt/0000-0002-8160-2446 FU NCI NIH HHS [T32 CA009382, T32 CA 09382-22]; NIAID NIH HHS [F32 AI062010, F32 AI 62010-01]; NIDDK NIH HHS [R01 DK 60027, P30 DK036836, P30 DK 36836, R01 DK060027] NR 35 TC 55 Z9 56 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 MAR 13 PY 2007 VL 104 IS 11 BP 4583 EP 4587 DI 10.1073/pnas.0700259104 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146ZH UT WOS:000244972700061 PM 17360567 ER PT J AU Seal, KH Bertenthal, D Miner, CR Sen, S Marmar, C AF Seal, Karen H. Bertenthal, Daniel Miner, Christian R. Sen, Saunak Marmar, Charles TI Bringing the war back home - Mental health disorders among 103 788 US veterans returning from Iraq and Afghanistan seen at Department of Veterans Affairs facilities SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL COMORBIDITY SURVEY; CARE; VIETNAM; PREVALENCE; ATTRITION; SERVICES AB Background: Veterans of Operations Enduring Freedom and Iraqi Freedom (OEF/OIF) have endured high combat stress and are eligible for 2 years of free military service-related health care through the Department of Veterans Affairs (VA) health care system, yet little is known about the burden and clinical circumstances of mental health diagnoses among OEF/OIF veterans seen at VA facilities. Methods: US veterans separated from OEF/OIF military service and first seen at VA health care facilities between September 30, 2001 ( US invasion of Afghanistan), and September 30, 2005, were included. Mental health diagnoses and psychosocial problems were assessed using International Classification of Diseases, Ninth Revision, Clinical Modification codes. The prevalence and clinical circumstances of and subgroups at greatest risk for mental health disorders are described herein. Results: Of 103 788 OEF/OIF veterans seen at VA health care facilities, 25 658 (25%) received mental health diagnosis(es); 56% of whom had 2 or more distinct mental health diagnoses. Overall, 32 010 (31%) received mental health and/or psychosocial diagnoses. Mental health diagnoses were detected soon after the first VA clinic visit (median of 13 days), and most initial mental health diagnoses (60%) were made in nonmental health clinics, mostly primary care settings. The youngest group of OEF/OIF veterans (age, 18-24 years) were at greatest risk for receiving mental health or posttraumatic stress disorder diagnoses compared with veterans 40 years or older. Conclusions: Co-occurring mental health diagnoses and psychosocial problems were detected early and in primary care medical settings in a substantial proportion of OEF/OIF veterans seen at VA facilities. Targeted early detection and intervention beginning in primary care settings are needed to prevent chronic mental illness and disability. C1 San Francisco VA Med Ctr, Div Gen Internal Med, Hlth Serv Res & Dev Res Enhancement Award Program, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. RP Seal, KH (reprint author), San Francisco VA Med Ctr, Div Gen Internal Med, Hlth Serv Res & Dev Res Enhancement Award Program, Box 111A-1,4150 Clement St, San Francisco, CA 94121 USA. EM karen.seal@va.gov NR 27 TC 474 Z9 480 U1 5 U2 35 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 MAR 12 PY 2007 VL 167 IS 5 BP 476 EP 482 DI 10.1001/archinte.167.5.476 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 145GX UT WOS:000244854400011 PM 17353495 ER PT J AU Colston, JT Boylston, WH Feldman, MD Jenkinson, CP de la Rosa, SD Barton, A Trevino, RJ Freeman, GL Chandrasekar, B AF Colston, James T. Boylston, William H. Feldman, Marc D. Jenkinson, Chris P. de la Rosa, Sam D. Barton, Amanda Trevino, Rodolfo J. Freeman, Gregory L. Chandrasekar, Bysani TI Interleukin-18 knockout mice display maladaptive cardiac hypertrophy in response to pressure overload SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE interleukins; myocardial hypertrophy; Akt; signal transduction; mouse; pressure overload ID NF-KAPPA-B; TRANSVERSE AORTIC CONSTRICTION; TUMOR-NECROSIS-FACTOR; SIGNALING PATHWAY; HYPOXIC INJURY; IN-VIVO; EXPRESSION; IL-18; CARDIOMYOCYTES; HEART AB Interleukin (IL)-18 is a cardiotropic proinflammatory cytokine chronically elevated in the serum of patients with cardiac hypertrophy (LVH). The purpose of this study was to examine the role of IL-18 in pressure-overload hypertrophy using wild type (WT) and IL-18 -/- (null) mice. Adult male C57B1/6 mice underwent transaortic constriction (TAC) for 7 days or sham surgery. Heart weight/body weight ratios showed blunted hypertrophy in IL-18 null TAC mice compared to WT TAC animals. Microarray analyses indicated differential expression of hypertrophy-related genes in WT versus IL-18 nulls. Northern, Western, and EMSA analyses showed Akt and GATA4 were increased in WT but unchanged in IL-18 null mice. Our results demonstrate blunted hypertrophy with reduced expression of contractile-, hypertrophy-, and remodeling-associated genes following pressure overload in IL-18 null mice, and suggest that TL-18 plays a critical role in the hypertrophic response. (c) 2007 Elsevier Inc. All rights reserved. C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. RP Chandrasekar, B (reprint author), S Texas Vet Hlth Care Syst, San Antonio, TX USA. EM chandraseka@uthscsa.edu FU NHLBI NIH HHS [HL68020, R01 HL068020, R21 HL079926, HL077926]; NIA NIH HHS [T32 AG021890]; NIDDK NIH HHS [R01 DK079195] NR 31 TC 30 Z9 33 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 9 PY 2007 VL 354 IS 2 BP 552 EP 558 DI 10.1016/j.bbrc.2007.01.030 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 133YO UT WOS:000244050000037 PM 17250807 ER PT J AU Sheen, J He, P AF Sheen, Jen He, Ping TI Nuclear actions in innate immune signaling SO CELL LA English DT Editorial Material ID RESISTANCE PROTEIN AB Innate immunity in plants and animals is mediated through pattern recognition receptors, which were thought to initiate signaling in the cytoplasm to activate defense pathways. Shen et al. (2006) and Burch-Smith et al. (2007) now provide compelling evidence that certain plant disease resistance proteins, which detect specific pathogenic effectors, act in the nucleus to trigger downstream signaling and defense pathways. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. RP Sheen, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. EM sheen@molbio.mgh.harvard.edu NR 10 TC 5 Z9 6 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAR 9 PY 2007 VL 128 IS 5 BP 821 EP 823 DI 10.1016/j.cell.2007.02.019 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 148KN UT WOS:000245073400003 PM 17350565 ER PT J AU Cui, RT Widlund, HR Feige, E Lin, JY Wilensky, DL Igras, VE D'Orazio, J Fung, CY Schanbacher, CF Granter, SR Fisher, DE AF Cui, Rutao Widlund, Hans R. Feige, Erez Lin, Jennifer Y. Wilensky, Dara L. Igras, Viven E. D'Orazio, John Fung, Claire Y. Schanbacher, Carl F. Granter, Scott R. Fisher, David E. TI Central role of p53 in the suntan response and pathologic hyperpigmentation SO CELL LA English DT Article ID PROOPIOMELANOCORTIN GENE-EXPRESSION; MICROPHTHALMIA TRANSCRIPTION FACTOR; SQUAMOUS-CELL CARCINOMA; PLASMA BETA-ENDORPHIN; SKIN-CANCER; DNA-DAMAGE; MELANOCORTIN-1 RECEPTOR; ULTRAVIOLET-B; HUMAN MELANOCYTES; SV40-TRANSFORMED CELLS AB UV-induced Pigmentation (suntanning) requires induction of a-melanocyte-stimulating hormone (alpha-MSH) secretion by keratinocytes- alpha-MSH and other bioactive pepticles are cleavage products Of pro-opiomelanocortin (POMC). Here we Provide biochemical and genetic evidence demonstrating that UV induction of POMC/MSH in skin is directly controlled by p53. Whereas p53 potently stimulates the POMC promoter in response to UV, the absence of p53, as in knockout mice, is associated with absence of the UV-tanning response. The same pathway produces beta-endorphin, another POMC derivative, which potentially contributes to sun-seeking behaviors. Furthermore, several instances of UV-independent pathologic Pigmentation are shown to involve p53 "mimicking" the tanning response. P53 thus functions as a sensor/effector for UV Pigmentation, which is a nearly constant environmental exposure. Moreover, this pathway is activated in numerous conditions of pathologic pigmentation and thus mimics the tanning response. C1 Harvard Univ, Sch Med, Melanoma Program Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat Hematol Oncol, Dana Farber Canc Inst,Childrens Hosp Boston, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Harvard Univ, Sch Med, Melanoma Program Med Oncol, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM david_fisher@dfci.harvard.edu NR 85 TC 260 Z9 263 U1 0 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAR 9 PY 2007 VL 128 IS 5 BP 853 EP 864 DI 10.1016/j.cell.2006.12.045 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 148KN UT WOS:000245073400011 PM 17350573 ER PT J AU Klose, RJ Yan, Q Tothova, Z Yamane, K Erdjument-Bromage, H Tempst, P Gilliland, DG Zhang, Y Kaelin, WG AF Klose, Robert J. Yan, Qin Tothova, Zuzana Yamane, Kenichi Erdjument-Bromage, Hediye Tempst, Paul Gilliland, D. Gary Zhang, Yi Kaelin, William G., Jr. TI The retinoblastoma binding protein RBP2 is an H3K4 demethylase SO CELL LA English DT Article ID DOMAIN-CONTAINING PROTEINS; LSD1 HISTONE DEMETHYLASE; MYELOID PROGENITOR; OXIDATIVE DEMETHYLATION; LYSINE-4 METHYLATION; MENTAL-RETARDATION; ANDROGEN-RECEPTOR; ESCHERICHIA-COLI; STRUCTURAL BASIS; MOLECULAR-BASIS AB Changes in histone methylation status regulate chromatin structure and DNA-dependent processes such as transcription. Recent studies indicate that, analogous to other histone modifications, histone methylation is reversible. Retinoblastoma binding protein 2 (RBP2), a nuclear protein implicated in the regulation of transcription and differentiation by the retinoblastoma tumor suppressor protein, contains a JmjC domain recently defined as a histone demethylase signature motif. Here we report that RBP2 is a demethylase that specifically catalyzes demethylation on H3K4, whose methylation is normally associated with transcriptionally active genes. RBP2-/- mouse cells displayed enhanced transcription of certain cytokine genes, which, in the case of SDF1, was associated with increased H3K4 trimethylation. Furthermore, RBP2 specifically demethylated H3K4 in biochemical and cell-based assays. These studies provide mechanistic insights into transcriptional regulation by RBP2 and provide the first example of a mammalian enzyme capable of erasing trimethylated H3K4. C1 Howard Hughes Med Inst, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Biochem & Biophys, Linenberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol,Dept Med, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Mol Biol Program, New York, NY 10021 USA. RP Zhang, Y (reprint author), Howard Hughes Med Inst, Chapel Hill, NC 27599 USA. EM yi_zhang@med.unc.edu; william_kaelin@dfci.harvard.edu RI Yan, Qin/E-8893-2012; OI Yan, Qin/0000-0003-4077-453X; Tempst, Paul/0000-0002-6680-3987 FU NCI NIH HHS [CA 076120]; NIGMS NIH HHS [GM 68804] NR 60 TC 228 Z9 240 U1 2 U2 18 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 9 PY 2007 VL 128 IS 5 BP 889 EP 900 DI 10.1016/j.cell.2007.02.013 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 148KN UT WOS:000245073400014 PM 17320163 ER PT J AU Prall, OWJ Menon, MK Solloway, MJ Watanabe, Y Zaffran, S Bajolle, F Biben, C McBride, JJ Robertson, BR Chaulet, H Stennard, FA Wise, N Schaft, D Wolstein, O Furtado, MB Shiratori, H Chien, KR Hamada, H Black, BL Saga, Y Robertson, EJ Buckingham, ME Harvey, RP AF Prall, Owen W. J. Menon, Mary K. Solloway, Mark J. Watanabe, Yusuke Zaffran, Stephane Bajolle, Fanny Biben, Christine McBride, Jim J. Robertson, Bronwyn R. Chaulet, Herve Stennard, Fiona A. Wise, Natalie Schaft, Daniel Wolstein, Orit Furtado, Milena B. Shiratori, Hidetaka Chien, Kenneth R. Hamada, Hiroshi Black, Brian L. Saga, Yumiko Robertson, Elizabeth J. Buckingham, Margaret E. Harvey, Richard P. TI An Nkx2-5/Bmp2/Smad1 negative feedback loop controls heart progenitor specification and proliferation SO CELL LA English DT Article ID HOMEOBOX GENE NKX2-5; TRANSCRIPTION FACTOR NKX2-5; OUTFLOW TRACT; ASYMMETRIC EXPRESSION; SIGNALING PATHWAY; EMBRYOS LACKING; FIELD; MUTATIONS; CELLS; DISEASE AB During heart development the second heart field (SHF) provides progenitor cells for most cardiomyocytes and expresses the homeodomain factor Nkx2-5. We now show that feedback repression of Bmp2/Smad1 signaling by Nkx2-5 critically regulates SHF proliferation and outflow tract (OFT) morphology. In the cardiac fields of Nkx2-5 mutants, genes controlling cardiac specification (including Bmp2) and maintenance of the progenitor state were upregulated, leading initially to progenitor overspecification, but subsequently to failed SHF proliferation and OFT truncation. In Smad1 mutants, SHF proliferation and deployment to the OFT were increased, while Smad1 deletion in Nkx2-5 mutants rescued SHF proliferation and OFT development. In Nkx2-5 hyponnorphic mice, which recapitulate human congenital heart disease (CHD), OFT anomalies were also rescued by Smad1 deletion. Our findings demonstrate that Nkx2-5 orchestrates the transition between periods of cardiac induction, progenitor proliferation, and OFT morphogenesis via a Smadl dependent negative feedback loop, which may be a frequent molecular target in CHD. C1 Victor Chang Cardiac Res Inst, Sydney, NSW 2010, Australia. Univ New S Wales, Fac Life Sci, Kensington, NSW 2053, Australia. Univ New S Wales, Fac Med, Kensington, NSW 2053, Australia. Inst Pasteur, Dept Dev Biol, CNRS, URA 2578, Paris, France. Garvan Inst Med Res, Sydney, NSW 2010, Australia. Univ New S Wales, Ramaciotti Ctr Gene Funct Anal, Sydney, NSW, Australia. Osaka Univ, Grad Sch Frontier Biosci, Osaka, Japan. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Natl Inst Genet, Div Mammalian Dev, Mishima, Shizuoka 4118540, Japan. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. RP Harvey, RP (reprint author), Victor Chang Cardiac Res Inst, Sydney, NSW 2010, Australia. EM r.harvey@victorchang.unsw.edu.au RI Zaffran, Stephane/I-2955-2016; OI Zaffran, Stephane/0000-0002-0811-418X; Black, Brian/0000-0002-6664-8913 FU NICHD NIH HHS [R21 HD047858, HD 047858, R21 HD047858-01]; Wellcome Trust [059312] NR 41 TC 259 Z9 272 U1 2 U2 20 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAR 9 PY 2007 VL 128 IS 5 BP 947 EP 959 DI 10.1016/j.cell.2007.01.042 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 148KN UT WOS:000245073400018 PM 17350578 ER PT J AU Silver, DP Dimitrov, SD Feunteun, J Gelman, R Drapkin, R Lu, SHD Shestakova, E Velmurugan, S DeNunzio, N Dragomir, S Mar, J Liu, XL Rottenberg, S Jonkers, J Ganesan, S Livingston, DM AF Silver, Daniel P. Dimitrov, Stoil D. Feunteun, Jean Gelman, Rebecca Drapkin, Ronny Lu, Shihua D. Shestakova, Elena Velmurugan, Soundarapandian DeNunzio, Nicholas Dragomir, Serban Mar, Jessica Liu, Xiaoling Rottenberg, Sven Jonkers, Jos Ganesan, Shridar Livingston, David M. TI Further evidence for BRCA1 communication with the inactive X chromosome SO CELL LA English DT Editorial Material ID HUMAN BREAST-CANCER; GENETIC INSTABILITY; DNA-REPAIR; CELL-CYCLE; S-PHASE; HETEROCHROMATIN; MUTATION; P53; REPLICATION; EXPRESSION AB BRCA1, a breast and ovarian cancer-suppressor gene, exerts tumor-suppressing functions that appear to be associated, at least in part, with its DNA repair, checkpoint, and mitotic regulatory activities. Earlier work from our laboratory also suggested an ability of BRCA1 to communicate with the inactive X chromosome (Xi) in female somatic cells (Ganesan et al., 2002). Xiao et al. (2007) (this issue of Cell have challenged this conclusion. Here we discuss recently published data from our laboratory and others and present new results that, together, provide further support for a role of BRCA1 in the regulation of XIST concentration on Xi in somatic cells. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Inst Canc, New Brunswick, NJ 08903 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Paris 11, Inst Gustave Roussy, Lab Genome & Canc, CNRS, F-94805 Villejuif, France. Netherlands Canc Inst, Div Mol Biol, NL-1066 CX Amsterdam, Netherlands. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Ganesan, S (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Inst Canc, 195 Little Albany St, New Brunswick, NJ 08903 USA. EM ganesash@umdnj.edu; david_livingston@dfci.harvard.edu RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 NR 36 TC 38 Z9 40 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 9 PY 2007 VL 128 IS 5 BP 991 EP 1002 DI 10.1016/j.cell.2007.02.025 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 148KN UT WOS:000245073400021 PM 17350581 ER PT J AU Pregibon, DC Toner, M Doyle, PS AF Pregibon, Daniel C. Toner, Mehmet Doyle, Patrick S. TI Multifunctional encoded particles for high-throughput biomolecule analysis SO SCIENCE LA English DT Article ID COMBINATORIAL CHEMISTRY; CHEMICAL LIBRARIES; ARRAY; IMMUNOASSAY; TECHNOLOGY; MICROCARRIERS; MICROARRAY; ASSAYS AB High-throughput screening for genetic analysis, combinatorial chemistry, and clinical diagnostics benefits from multiplexing, which allows for the simultaneous assay of several analytes but necessitates an encoding scheme for molecular identification. Current approaches for multiplexed analysis involve complicated or expensive processes for encoding, functionalizing, or decoding active substrates ( particles or surfaces) and often yield a very limited number of analyte-specific codes. We present a method based on continuous-flow lithography that combines particle synthesis and encoding and probe incorporation into a single process to generate multifunctional particles bearing over a million unique codes. By using such particles, we demonstrate a multiplexed, single-fluorescence detection of DNA oligomers with encoded particle libraries that can be scanned rapidly in a flow-through microfluidic channel. Furthermore, we demonstrate with high specificity the same multiplexed detection using individual multiprobe particles. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, BioMEMS Resource Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Doyle, PS (reprint author), MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM pdoyle@mit.edu FU NIBIB NIH HHS [P41 EB002503] NR 32 TC 428 Z9 435 U1 26 U2 194 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD MAR 9 PY 2007 VL 315 IS 5817 BP 1393 EP 1396 DI 10.1126/science.1134929 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 143UP UT WOS:000244752200028 PM 17347435 ER PT J AU Kidambi, S Sheng, LF Yarmush, ML Toner, M Lee, I Chan, C AF Kidambi, Srivatsan Sheng, Lufang Yarmush, Martin L. Toner, Mehmet Lee, Ilsoon Chan, Christina TI Patterned co-culture of primary hepatocytes and fibroblasts using polyelectrolyte multilayer templates SO MACROMOLECULAR BIOSCIENCE LA English DT Article DE adhesion; co-culture; micro-contact printing; polyelectrolyte; polyelectrolyte multilayers; primary hepatocytes; tissue engineering ID RESPONSIVE CULTURE DISHES; SELF-ASSEMBLED MONOLAYERS; ADULT-RAT HEPATOCYTES; CELL-INTERACTIONS; DIFFERENTIATED FUNCTION; LIVER-CELLS; THIN-FILMS; SURFACES; ADHESION; MAINTENANCE AB This paper describes the formation of patterned cell co-cultures using the layer-by-layer deposition of synthetic ionic polymers and without the aid of adhesive proteins/ligands such as Collagen or fibronectin. In this study, we used synthetic polymers, namely poly(diallyldi-methylammoniurn chloride) (PDAC) and sulfonated polystyrene (SPS) as the polycation and polyanion, respectively, to build the multilayer films. We formed SPS patterns on polyelectrolyte multilayer (PEM) surfaces either by microcontact printing PDAC onto SPS surfaces or vice-versa. To create patterned co-cultures on PEMs, we capitalize on the preferential attachment and spreading of primary hepatocytes on SPS as opposed to PDAC surfaces. In contrast, fibroblasts readily attached to both PDAC and SPS surfaces, and as a result, we were able to obtain patterned co-cultures of fibroblast and primary hepatocytes on synthetic PEM surfaces. We characterized the morphology and hepatic-specific functions of the patterned cell co-cultures with microscopy and biochemical assays. Our results suggest an alternative approach to fabricating controlled co-cultures with specified cell-cell and cell-surface interactions; this approach provides flexibility in designing cell-specific surfaces for tissue engineering applications. C1 Michigan State Univ, Dept Chem Engn & Mat Sci, E Lansing, MI 48824 USA. Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Dept Surg, Boston, MA USA. Shriners Burns Hosp, Boston, MA USA. RP Lee, I (reprint author), Michigan State Univ, Dept Chem Engn & Mat Sci, E Lansing, MI 48824 USA. EM leeil@egr.msu.edu; krischan@egr.msu.edu RI Lee, Ilsoon/E-7527-2011; KIDAMBI, SRIVATSAN/A-5689-2015 OI KIDAMBI, SRIVATSAN/0000-0002-0282-0411 NR 55 TC 44 Z9 45 U1 0 U2 31 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1616-5187 J9 MACROMOL BIOSCI JI Macromol. Biosci. PD MAR 8 PY 2007 VL 7 IS 3 BP 344 EP 353 DI 10.1002/mabi.200600205 PG 10 WC Biochemistry & Molecular Biology; Materials Science, Biomaterials; Polymer Science SC Biochemistry & Molecular Biology; Materials Science; Polymer Science GA 152LZ UT WOS:000245364800008 PM 17370273 ER PT J AU Haber, DA Settleman, J AF Haber, Daniel A. Settleman, Jeff TI Cancer - Drivers and passengers SO NATURE LA English DT Editorial Material ID HUMAN BREAST; LUNG-CANCER; MUTATIONS; GEFITINIB; GENE C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA 02129 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Blst 149-7,, Charlestown, MA 02129 USA. EM haber@helix.mgh.harvard.edu NR 11 TC 99 Z9 100 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 8 PY 2007 VL 446 IS 7132 BP 145 EP 146 DI 10.1038/446145a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 143JS UT WOS:000244718100026 PM 17344839 ER PT J AU Greenman, C Stephens, P Smith, R Dalgliesh, GL Hunter, C Bignell, G Davies, H Teague, J Butler, A Edkins, S O'Meara, S Vastrik, I Schmidt, EE Avis, T Barthorpe, S Bhamra, G Buck, G Choudhury, B Clements, J Cole, J Dicks, E Forbes, S Gray, K Halliday, K Harrison, R Hills, K Hinton, J Jenkinson, A Jones, D Menzies, A Mironenko, T Perry, J Raine, K Richardson, D Shepherd, R Small, A Tofts, C Varian, J Webb, T West, S Widaa, S Yates, A Cahill, DP Louis, DN Goldstraw, P Nicholson, AG Brasseur, F Looijenga, L Weber, BL Chiew, YE Defazio, A Greaves, MF Green, AR Campbell, P Birney, E Easton, DF Chenevix-Trench, G Tan, MH Khoo, SK Teh, BT Yuen, ST Leung, SY Wooster, R Futreal, PA Stratton, MR AF Greenman, Christopher Stephens, Philip Smith, Raffaella Dalgliesh, Gillian L. Hunter, Christopher Bignell, Graham Davies, Helen Teague, Jon Butler, Adam Edkins, Sarah O'Meara, Sarah Vastrik, Imre Schmidt, Esther E. Avis, Tim Barthorpe, Syd Bhamra, Gurpreet Buck, Gemma Choudhury, Bhudipa Clements, Jody Cole, Jennifer Dicks, Ed Forbes, Simon Gray, Kris Halliday, Kelly Harrison, Rachel Hills, Katy Hinton, Jon Jenkinson, Andy Jones, David Menzies, Andy Mironenko, Tatiana Perry, Janet Raine, Keiran Richardson, Dave Shepherd, Rebecca Small, Alexandra Tofts, Calli Varian, Jennifer Webb, Tony West, Sofie Widaa, Sara Yates, Andy Cahill, Daniel P. Louis, David N. Goldstraw, Peter Nicholson, Andrew G. Brasseur, Francis Looijenga, Leendert Weber, Barbara L. Chiew, Yoke-Eng deFazio, Anna Greaves, Mel F. Green, Anthony R. Campbell, Peter Birney, Ewan Easton, Douglas F. Chenevix-Trench, Georgia Tan, Min-Han Khoo, Sok Kean Teh, Bin Tean Yuen, Siu Tsan Leung, Suet Yi Wooster, Richard Futreal, P. Andrew Stratton, Michael R. TI Patterns of somatic mutation in human cancer genomes SO NATURE LA English DT Article ID KINASE GENE FAMILY; HUMAN LUNG-CANCER; COLORECTAL CANCERS; SIGNALING PATHWAY; TUMOR-SUPPRESSOR; BREAST-CANCER; BETA RECEPTOR; PROTEIN; TITIN; INACTIVATION AB Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274 megabases (Mb) of DNA corresponding to the coding exons of 518 protein kinase genes in 210 diverse human cancers. There was substantial variation in the number and pattern of mutations in individual cancers reflecting different exposures, DNA repair defects and cellular origins. Most somatic mutations are likely to be 'passengers' that do not contribute to oncogenesis. However, there was evidence for 'driver' mutations contributing to the development of the cancers studied in approximately 120 genes. Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated. C1 Wellcome Trust Sanger Inst, Canc Genome Project, Cambridge CB10 1SA, England. EMBL, European Bioinformat Inst, Cambridge CB10 1SD, England. Massachusetts Gen Hosp, Neurosurg Serv, Mol Pathol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Royal Brompton Hosp, London SW3 6NP, England. Ludwig Inst Canc Res, B-1200 Brussels, Belgium. Erasmus MC, Daniel den Hoed Canc Ctr, Josephine Nefkens Inst, Lab Pathol Expt Pathooncol, NL-3000 DR Rotterdam, Netherlands. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Westmead Hosp, Dept Gynaecol Oncol, Westmead, NSW 2145, Australia. Univ Sydney, Westmead Inst Canc Res, Westmead Millennium Inst, Westmead, NSW 2145, Australia. Inst Canc Res, Sutton SM2 5NG, Surrey, England. Addenbrookes NHS Trust, Dept Haematol, Cambridge CB2 0QQ, England. Univ Cambridge, Cambridge CB2 0QQ, England. Univ Cambridge, Canc Res UK Genet Epidemiol Unit, Cambridge CB1 8RN, England. Univ Queensland, Royal Brisbane Hosp, Queensland Inst Med Res, Herston, Qld 4029, Australia. Van Andel Res Inst, Grand Rapids, MI 49503 USA. Univ Hong Kong, Queen Mary Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China. RP Futreal, PA (reprint author), Wellcome Trust Sanger Inst, Canc Genome Project, Wellcome Trust Genome Campus, Cambridge CB10 1SA, England. EM paf@sanger.ac.uk; mrs@sanger.ac.uk RI Dalgliesh, Gillian/B-7799-2008; Choudhury, Bhudipa/D-3863-2011; deFazio, Anna/D-3939-2013; Yuen , Siu /K-6311-2014; Vastrik, Imre/C-2690-2009; Leung, Suet Yi/C-4340-2009; OI Richardson, David/0000-0003-0247-9118; Birney, Ewan/0000-0001-8314-8497; Yates, Andrew/0000-0002-8886-4772; Dalgliesh, Gillian/0000-0001-8526-5064; Gray, Kristian/0000-0002-7035-7107; Hunter, Christopher/0000-0002-1335-0881; Choudhury, Bhudipa/0000-0002-1392-6414; deFazio, Anna/0000-0003-0057-4744; Jenkinson, Andrew/0000-0002-0703-6984 FU Wellcome Trust [088340, , 077012] NR 39 TC 1571 Z9 2077 U1 10 U2 162 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 8 PY 2007 VL 446 IS 7132 BP 153 EP 158 DI 10.1038/nature05610 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 143JS UT WOS:000244718100033 PM 17344846 ER PT J AU Bazari, H Jaff, MR Mannstadt, M Yan, SF Farhat, MR AF Bazari, Hasan Jaff, Michael R. Mannstadt, Michael Yan, Shaofeng Farhat, Maha R. TI A woman with diabetic renal disease and nonhealing skin ulcers - Calciphylaxis, extensive, involving the right leg. Atherosclerotic vascular disease with ischemic ulcer on the heel and osteomyelitis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID INTRAVENOUS-SODIUM THIOSULFATE; PERITONEAL-DIALYSIS; CUTANEOUS NECROSIS; HYPERBARIC-OXYGEN; RISK-FACTORS; PROTEIN-S; CALCIFICATION; THERAPY; FAILURE; PATIENT C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Vasc Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Bazari, H (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 40 TC 23 Z9 24 U1 1 U2 2 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 MAR 8 PY 2007 VL 356 IS 10 BP 1049 EP 1057 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 143DC UT WOS:000244699200011 PM 17347459 ER PT J AU Li, W Li, Y Guan, SX Fan, JH Cheng, CF Bright, AM Chinn, C Chen, M Woodley, DT AF Li, Wei Li, Yong Guan, Shengxi Fan, Jianhua Cheng, Chieh-Fang Bright, Alexandra M. Chinn, Cindi Chen, Mei Woodley, David T. TI Extracellular heat shock protein-90 alpha: linking hypoxia to skin cell motility and wound healing SO EMBO JOURNAL LA English DT Article DE cell motility; HIF-1; hypoxia; secreted Hsp90; wound healing ID HUMAN DERMAL FIBROBLASTS; HUMAN KERATINOCYTE MOTILITY; HEAT-SHOCK PROTEINS; SIGNAL-TRANSDUCTION; INDUCIBLE FACTOR-1; GENE-EXPRESSION; CANCER-THERAPY; MIGRATION; OXYGEN; INDUCTION AB Hypoxia is a microenvironmental stress in wounded skin, where it supports wound healing by promoting cell motility. The mechanism of the hypoxia action remained speculative. Here, we provide evidence that hypoxia promotes human dermal fibroblast (HDF) migration by inducing secretion of heat shock protein-90alpha (hsp90 alpha) into the extracellular environment through hypoxia-inducible factor-1alpha (HIF-1 alpha). The secreted hsp90 alpha in turn executes hypoxia's pro-motility effect. Expression of an activated HIF-1 alpha mimicked, whereas expression of an inactive HIF-1 alpha or suppression of endogenous HIF-1 alpha blocked, hypoxia- induced hsp90a secretion and HDF migration. Interestingly, the hypoxia-HIF-1 pathway-induced hsp90a secretion required neither changes in the steady-state mRNA level nor in the promoter activity of hsp90a. Recombinant hsp90a fully duplicated the hypoxia effect on HDFs. Inhibition of extracellular hsp90a function completely blocked the hypoxia-HIF-1 pathway-stimulated HDF migration. More intriguingly, topical application of hsp90a accelerated wound healing in mice. This study has demonstrated a novel mechanism of hypoxia > HIF-1 > hsp90 alpha secretion > skin cell migration > wound healing, and identified extracellular hsp90 alpha as a potential therapeutic agent for skin wounds. C1 Univ So Calif, Keck Sch Med, Dept Dermatol, Los Angeles, CA 90033 USA. Greater Los Angeles Vet Adm Hlth Syst, Los Angeles, CA USA. Fourth Mil Med Univ, Dept Plast Surg, Xijing Hosp, Xian, Shaanxi, Peoples R China. RP Li, W (reprint author), Univ So Calif, Keck Sch Med, Dept Dermatol, 1303 N Miss Rd, Los Angeles, CA 90033 USA. EM wli@usc.edu FU NIAMS NIH HHS [R01 AR046538, AR46538, GM/AR67100-01] NR 48 TC 124 Z9 134 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 7 PY 2007 VL 26 IS 5 BP 1221 EP 1233 DI 10.1038/sj.emboj.7601579 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 143JE UT WOS:000244716000003 PM 17304217 ER PT J AU Bernal, F Tyler, AF Korsmeyer, SJ Walensky, LD Verdine, GL AF Bernal, Federico Tyler, Andrew F. Korsmeyer, Stanley J. Walensky, Loren D. Verdine, Gregory L. TI Reactivation of the p53 tumor suppressor pathway by a stapled p53 peptide SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID WILD-TYPE P53; P53-HDM2 INTERACTION; DNA DAMAGE; IN-VIVO; MDM2; ACTIVATION; TRANSACTIVATION; ANTAGONISTS; APOPTOSIS; PROTEIN AB The p53-hDM2 protein interaction is a validated therapeutic target in cancer. We report the synthesis of stabilized alpha-helix of p53 (SAH-p53) compounds that antagonize the p53-hDM2 interaction. We demonstrate that hydrocarbon stapling confers cellular permeability to a p53 peptide that is then capable of modulating transcriptional activity. The lead SAH-p53 compound triggers apoptosis in hDM2-overexpressing cancer cells by reactivating the native p53 signaling pathway. SAH-p53 is the first example of an all-hydrocarbon i, i+7 stabilized peptide that subverts cancer through direct modulation of a transcriptional pathway. C1 Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Walensky, LD (reprint author), Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. EM loren_walensky@dfci.harvard.edu; verdine@chemistry.harvard.edu FU NCI NIH HHS [F32 CA 103510]; NHLBI NIH HHS [KO8 HL 074049] NR 31 TC 260 Z9 261 U1 10 U2 96 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 MAR 7 PY 2007 VL 129 IS 9 BP 2456 EP + DI 10.1021/ja0693587 PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 143OF UT WOS:000244731300024 PM 17284038 ER PT J AU Kerlikowske, K Ichikawa, L Miglioretti, DL Buist, DSM Vacek, PM Smith-Bindman, R Yankaskas, B Carney, PA Ballard-Barbash, R AF Kerlikowske, Karla Ichikawa, Laura Miglioretti, Diana L. Buist, Diana S. M. Vacek, Pamela M. Smith-Bindman, Rebecca Yankaskas, Bonnie Carney, Patricia A. Ballard-Barbash, Rachel TI Longitudinal measurement of clinical mammographic breast density to improve estimation of breast cancer risk SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PARENCHYMAL PATTERNS; FAMILY-HISTORY; SCREENING MAMMOGRAPHY; UNITED-STATES; TAMOXIFEN; AGE; WOMEN; ASSOCIATION; POPULATION; PREVENTION AB Background Whether a change over time in clinically measured mammographic breast density influences breast cancer risk is unknown. Methods From January 1993 to December 2003, data that included American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) breast density categories (1-4 in order of increasing density) were collected prospectively on 301955 women aged 30 and older who were not using postmenopausal hormone replacement therapy and underwent at least two screening mammography examinations; 2639 of the women were diagnosed with breast cancer within 1 year of the last examination. Women's first and last BI-RADS breast density (average 3.2 years apart) and logistic regression were used to model the odds of having invasive breast cancer or ductal carcinoma in situ diagnosed within 12 months of the last examination by change in BI-RADS category. Rates of breast cancer adjusted for age, mammography registry, and time between screening examinations were estimated from this model. All statistical tests were two-sided. Results The rate (breast cancers per 1000 women) of breast cancer was higher if BI-RADS breast density category increased from 1 to 2 (5.6, 95% confidence interval [CI] = 4.7 to 6.9) or 1 to 3 (9.9, 95% Cl = 6.4 to 15.5) compared to when it remained at BI-RADS density of 1 (3.0, 95% Cl = 2.3 to 3.9; P <.001 for trend). Similar and statistically significant trends between increased or decreased density and increased or decreased risk of breast cancer, respectively, were observed for women whose breast density category was initially 2 or 3 and changed categories. BI-RADS density of 4 on the first examination was associated with a high rate of breast cancer (range 9.1-13.4) that remained high even if breast density decreased. Conclusion An increase in BI-RADS breast density category within 3 years may be associated with an increase in breast cancer risk and a decrease in density category with a decrease in risk compared to breast cancer risk in women in whom breast density category remains unchanged. Two longitudinal measures of BI-RADS breast density may better predict a woman's risk of breast cancer than a single measure. C1 Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Vet Affairs, Gen Internal Med Sect, San Francisco, CA 94143 USA. Grp Hlth Ctr Hlth Studies, Seattle, WA USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Vermont, Coll Med, Dept Med Biostat, Burlington, VT USA. Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. Univ N Carolina, Dept Radiol, Chapel Hill, NC USA. Oregon Hlth Sci Univ, Dept Family Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Kerlikowske, K (reprint author), San Francisco VA Med Ctr, Gen Internal Med Sect, 111A1,4150 Clement St, San Francisco, CA 94121 USA. EM karla.kerlikowske@ucsf.edu FU NCI NIH HHS [U01CA69976, U01CA63736, U01 CA086076-06, P01 CA107584, U01CA70040, U01CA63740, U01CA63731, R01 CA080888, U01CA70013, U01 CA086076, U01CA86082, U01CA86076, U01 CA086082] NR 51 TC 115 Z9 115 U1 1 U2 5 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 MAR 7 PY 2007 VL 99 IS 5 BP 386 EP 395 DI 10.1093/jnci/djk066 PG 10 WC Oncology SC Oncology GA 145PV UT WOS:000244877900011 PM 17341730 ER PT J AU Nakazawa, G Joner, M Ladich, E Kolodgie, F Finn, AV Gold, HK Virmani, R AF Nakazawa, Gaku Joner, Michael Ladich, Elena Kolodgie, Frank Finn, Aloke V. Gold, Herman K. Virmani, Renu TI Pathologic findings of coronary bifurcation stenting - DES vs BMS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT i2 Summit 2007 on Innovation in Intervention CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol, SCAI C1 Inst Inc, Gaithersburg, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU B BP 11B EP 11B PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LT UT WOS:000244652100043 ER PT J AU Han, JK Feliciano, Z AF Han, Janet K. Feliciano, Zenaida TI Is outpatient implantation of biventricular devices safe? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 18A EP 18A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651800072 ER PT J AU Sheth, T Dodd, J Finn, A Gold, H Cury, RC AF Sheth, Tei Dodd, Jonathan Finn, Alok Gold, Herman Cury, Ricardo C. TI Coronary stent assessability by 64 slice multi-detector computed tomography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT i2 Summit 2007 on Innovation in Intervention CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol, SCAI C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU B BP 25B EP 26B PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LT UT WOS:000244652100103 ER PT J AU Mendoza, I Marques, J Palacios, I Corrado, D Mendoza, IB Priori, SG Pulpon, L Moleiro, F Misticchio, F Matheus, A AF Mendoza, Ivan Marques, Juan Palacios, Igor Corrado, Domenico Mendoza B, Ivan Priori, Silvia G. Pulpon, Luis Moleiro, Federico Misticchio, Francesca Matheus, Alvaro TI A new familial syndrome induced by the interaction of Trypanosoma Cruzi with the cardiac sodium channel gene SCN5A SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 Cent Univ Venezuela, Caracas, Venezuela. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 56A EP 56A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651800231 ER PT J AU Moukarbel, GV Ennis, SC Moore, SA MacGillivray, TE AF Moukarbel, George V. Ennis, Stephanie C. Moore, Stephanie A. MacGillivray, Thomas E. TI New generation axial-flow left ventricular assist device can support patients with various degrees of right ventricular dysfunction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 78A EP 79A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651800324 ER PT J AU Ennis, SC Moore, SA Ennis, CA Moukarbel, GV MacGillivray, TE AF Ennis, Stephanie C. Moore, Stephanie A. Ennis, Cynthia A. Moukarbel, George V. MacGillivray, Thomas E. TI Are initial indications for left ventricular assist support necessary? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 79A EP 79A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651800325 ER PT J AU Kawase, Y Ly, HQ Prunier, F Lebeche, D Shi, Y Yoneyama, R Hoshino, K Takewa, Y Tardif, JC Levine, RA Tanguay, JF Hajjar, RJ AF Kawase, Yoshiaki Ly, Hung Q. Prunier, Fabrice Lebeche, Djamel Shi, Yanfen Yoneyama, Ryuichi Hoshino, Kozo Takewa, Yoshiaki Tardif, Jean-Claude Levine, Robert A. Tanguay, Jean-Francois Hajjar, Roger J. TI Gene transfer of SERCA2a by intracoronary delivery of adeno-associated virus type 1 vector in a pre-clinical model of heart failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 83A EP 83A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651800343 ER PT J AU Dhaliwal, A Bozkurt, B DeBakey, ME AF Dhaliwal, Amandeep Bozkurt, Biykem DeBakey, Michael E. TI Higher percent BNP reduction is required in blacks than whites to reduce event free survival in heart failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 91A EP 92A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651800376 ER PT J AU Nasir, K Sarwar, A Dannemann, N Moselewski, F Nichols, J Tawakol, A Cury, R Abbara, S Shapiro, M Brady, T Hoffmann, U AF Nasir, Khurram Sarwar, Ammar Dannemann, Nina Moselewski, Fabian Nichols, Johns Tawakol, Ahmed Cury, Ricardo Abbara, Suhny Shapiro, Micheal Brady, THomas Hoffmann, Udo TI Incidence of contrast induced nephropathy in patients with acute chest pain undergoing contrast - Enhanced coronary MDCT SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 117A EP 117A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651800477 ER PT J AU Poh, KK Solis, J Flaherty, M Kang, YJ Levine, RA Hung, J AF Poh, Kian Keong Solis, Jorge Flaherty, Mary Kang, Yue-Jian Levine, Robert A. Hung, Judy TI Novel assessment of aortic stenosis using real-time three dimensional echocardiography: Comparison of continuity equation derived aortic valve area with planimetry SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 141A EP 141A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651801018 ER PT J AU Passeri, JJ Lin, AY Ahluwalia, N Gerszten, RE Picard, MH Scherrer-Crosbie, M AF Passeri, Jonathan J. Lin, Alexander Y. Ahluwalia, Neil Gerszten, Robert E. Picard, Michael H. Scherrer-Crosbie, Marielle TI Noninvasive detection and characterization of abdominal aortic aneurysms in mice using ultrasound SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 144A EP 144A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651801031 ER PT J AU Seneviratne, SK Shapiro, M Rogers, I Moselewski, F Cury, RC Nichols, JH Hoffmann, U AF Seneviratne, Suth K. Shapiro, Michael Rogers, Ian Moselewski, Fabian Cury, Ricardo C. Nichols, John H. Hoffmann, Udo TI Diagnostic accuracy of global and regional left ventricular function measured by 64-slice multidetector computed tomography for acute coronary syndrome in patients with acute chest pain SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 157A EP 157A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651801083 ER PT J AU Shapiro, M Hsu, J Kalva, S Nasir, K Nichols, JH Kalra, M Cury, RC Brady, TJ Hoffmann, U AF Shapiro, Michael Hsu, Joe Kalva, Sanjeeva Nasir, Khurram Nichols, John H. Kalra, Mannudeep Cury, Ricardo C. Brady, Thomas J. Hoffmann, Udo TI Coronary artery image quality using multidetector computed tomography to simultaneously evaluate for coronary artery stenosis, aortic dissection, and pulmonary embolism SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 171A EP 172A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651801142 ER PT J AU Butler, J Mooyaart, EAQ Moselewski, F Shapiro, MD Brady, T Hoffmann, U AF Butler, Javed Mooyaart, Eline A. Q. Moselewski, Fabian Shapiro, Michael D. Brady, Thomas Hoffmann, Udo TI Metabolic syndrome is independently associated with increased coronary atherosclerotic plaque burden SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 182A EP 182A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651801188 ER PT J AU Shapiro, M Neilan, TG Jassal, DS Samy, B Nasir, K Hoffmann, U Brady, TJ Cury, RC AF Shapiro, Michael Neilan, Thomas G. Jassal, Davinder S. Samy, Bharat Nasir, Khurram Hoffmann, Udo Brady, Thomas J. Cury, Ricardo C. TI Multicletector computed tomography for the detection of left atrial appendage thrombus - A comparative study with transesophageal echocardiography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 182A EP 183A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651801189 ER PT J AU Mena, JL Morrow, DA Ostor, E Dorobantu, M Qin, J Antman, E Braunwald, E AF Mena, Jessica L. Morrow, David A. Ostor, Erika Dorobantu, Maria Qin, Jie Antman, Elliott Braunwald, Eugene CA TIMI Study Grp TI Enoxaparin vs unfractionated heparin in women undergoing fibrinolysis for ST-elevation myocardial infarction in ExTRACT-TIMI 25 SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 202A EP 203A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651801270 ER PT J AU Scirica, BM Morrow, DA Cannon, CP Ray, KK Sabatine, MS Ritai, N Jarolim, P Shui, A McCabe, CH Braunwald, E AF Scirica, Benjamin M. Morrow, David A. Cannon, Christopher P. Ray, Kausik K. Sabatine, Marc S. Ritai, Nader Jarolim, Petr Shui, Amy McCabe, Carolyn H. Braunwald, Eugene TI C-reactive protein and B-type natriuretic pepticle independently predict hospitalization for heart failure after acute coronary syndromes and identify patients who benefit from intensive statin therapy in the PROVE IT-TIMI 22 trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 TIMI Stdy Grp, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 204A EP 205A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651801279 ER PT J AU Mega, JL Murphy, S Morrow, DA McCabe, CH Antman, EM Braunwald, E Gibson, CM AF Mega, Jessica L. Murphy, Sabina Morrow, David A. McCabe, Carolyn H. Antman, Elliott M. Braunwald, Eugene Gibson, C. Michael TI A risk score to predict sudden cardiac death in patients with ST-elevation myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 TIMI Study Grp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 212A EP 212A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651801311 ER PT J AU Applegate, RJ Sacrinty, MT Kutcher, MA Baki, TT Gandhi, SK Santos, RM Little, WC AF Applegate, Robert J. Sacrinty, Matthew T. Kutcher, Michael A. Baki, Talal T. Gandhi, Sanjay K. Santos, Renato M. Little, William C. TI Comparison of drug-eluting versus bare metal stents: Timing of subacute thrombosis up to 2 years SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 TIMI Study Grp, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 227A EP 227A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651801377 ER PT J AU Scirica, BM Morrow, DA Karwatowska-Prokopczuk, E Cairns, R Aroesty, J McCabe, CH Braunwald, E AF Scirica, Benjamin M. Morrow, David A. Karwatowska-Prokopczuk, Ewa Cairns, Richard Aroesty, Julian McCabe, Carolyn H. Braunwald, Eugene TI Association between recurrent ischemia on continuous ECG (Holter) monitoring and short and long term mortality in patients with non-ST-elevation ACS in the MERLIN - TIMI 36 trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 TIMI Study Grp, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 227A EP 228A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651801378 ER PT J AU Jang, IK Senatore, F Weisman, N Picard, MH Zile, MR Pettigrew, V Shen, S Tatsuno, J Hibberd, M Wackers, FJT AF Jang, Ik-Kyung Senatore, Fred Weisman, Neil Picard, Michael H. Zile, Michael R. Pettigrew, Veronica Shen, Steven Tatsuno, Jun Hibberd, Mark Wackers, Frans J. Th CA EVOLVE investigators TI A randomized, double-blind, placebo-controlled study of the safety and efficacy of intravenous MCC-135 as an adjunct to primary percutaneous coronary intervention in patients with acute myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 241A EP 241A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651801436 ER PT J AU Jneid, H Moukarbel, GV Refaat, M Zardkoohi, O Maree, AO Awaida, JP Semigran, MJ Semigran, MJ Gold, HK Pomerantsev, EV Palacios, IF AF Jneid, Hani Moukarbel, George V. Refaat, Marwan Zardkoohi, Omeed Maree, Andrew O. Awaida, Jean-Pierre Semigran, Marc J. Semigran, Marc J. Gold, Herman K. Pomerantsev, Eugene V. Palacios, Igor F. TI Differences in invasive therapies and in-hospital mortality between patients with and without ST-segment elevation myocardial infarction complicated by cardiogenic shock SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 246A EP 246A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651801458 ER PT J AU Ebrahimi, R Feit, F Manoukian, S Lincoff, AM Dyke, C Gersh, B Mehran, R Moses, J Stone, G AF Ebrahimi, Ramin Feit, Frederick Manoukian, Steven Lincoff, A. Michael Dyke, Cornelius Gersh, Bernard Mehran, Roxana Moses, Jeffery Stone, Gregg TI Outcome in acute coronary syndrome patients managed surgically based on clopidogrel exposure and delay to surgery: A report from the ACUITY trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 Univ Calif Los Angeles, Greater Los Angeles VA Med Ctr, Los Angeles, CA USA. Columbia Univ, Ctr Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 252A EP 252A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651801482 ER PT J AU Ebrahimi, R Manoukian, S Feit, F Lincoff, AM Dyke, C Gersh, B Mehran, R Moses, J Stone, G AF Ebrahimi, Ramin Manoukian, Steven Feit, Frederick Lincoff, A. Michael Dyke, Cornelius Gersh, Bernard Mehran, Roxana Moses, Jeffery Stone, Gregg TI Upstream therapy with bivalirudin is as safe and effective as heparin for patients with acute coronary syndrome undergoing coronary artery bypass surgery: A report from the ACUITY trial. SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 Univ Calif Los Angeles, Greater Los Angeles VA Med Ctr, Los Angeles, CA USA. Columbia Univ, Ctr Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 253A EP 253A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651801484 ER PT J AU Jneid, H Fonarow, G Ellrodt, G Maree, AO Moukarbel, GV Palacios, IF LaBresh, K Lang, L Newby, LK Fletcher, G Peterson, E Cannon, CP Wexler, L AF Jneid, Hani Fonarow, Gregg Ellrodt, Gray Maree, Andrew O. Moukarbel, George V. Palacios, Igor F. LaBresh, Kenneth Lang, Li Newby, L. Kristin Fletcher, Gerald Peterson, Eric Cannon, Chris P. Wexler, Laura TI Gender differences in medical care and in-hospital mortality after acute myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. RI LaBresh, Kenneth/A-6995-2017 OI LaBresh, Kenneth/0000-0001-9040-1956 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 292A EP 292A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651802078 ER PT J AU Jneid, H Fonarow, G Maree, AO LaBresh, K Lang, L Bolli, R Newby, LK Fletcher, G Palacios, IF Wexler, L Peterson, E AF Jneid, Hani Fonarow, Gregg Maree, Andrew O. LaBresh, Kenneth Lang, Li Bolli, Roberto Newby, L. Krislin Fletcher, Gerald Palacios, Igor F. Wexler, Laura Peterson, Eric TI Differences in medical care in patients presenting with acute myocardial infarction during holidays and weekends vs. weekdays SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. RI Bolli, Roberto/A-6870-2010; LaBresh, Kenneth/A-6995-2017 OI LaBresh, Kenneth/0000-0001-9040-1956 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 295A EP 296A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651802089 ER PT J AU Chua, S Hung, J Chung, SY Fu, M Wu, CR Yip, HK Hang, CL Chen, MC AF Chua, Sarah Hung, Judy Chung, Sheng-Ying Fu, Morgan Wu, Chung Ren Yip, Han Kon Hang, Chi Ling Chen, Mien Chen TI Primary percutaneous coronary intervention lowers incidence of ischemic mitral regurgitation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 Chang Gung Univ, Chang Gung Memorial Hosp, Kaohsiung Med Ctr, Coll Med, Kaohsiung, 02114, Taiwan. Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 309A EP 309A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651802147 ER PT J AU Forman, DE Cohen, RA Hoth, KF Poppas, A Moser, DJ Gunstad, J Paul, RH Jefferson, AL Haley, A Tate, DF Ono, M Wake, N Gerhard-Herman, M AF Forman, Daniel E. Cohen, Ronald A. Hoth, Karin F. Poppas, Athena Moser, David J. Gunstad, John Paul, Robert H. Jefferson, Angela L. Haley, Andreana Tate, David F. Ono, Makoto Wake, Nicole Gerhard-Herman, Marie TI Cognition and brachial endothelial responses in older adults with cardiovascular disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Va Boston Hlth Care Syst, Boston, MA USA. RI Tate, David/G-5166-2011 OI Tate, David/0000-0003-0213-1920 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 352A EP 352A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651802328 ER PT J AU Zabalgoitia, M Reagan, RF Stec, DE Rimoldi, JM Valente, AJ Chandrasekar, B AF Zabalgoitia, Miguel Reagan, Raymond F. Stec, David E. Rimoldi, John M. Valente, Anthony J. Chandrasekar, Bysani TI Carbon monoxide donors or heme oxygenase-1 overexpression block interleukin-18-mediated NF-kB-PTEN-dependent human cardiac endothelial cell death SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 So Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 378A EP 378A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651802434 ER PT J AU Raffel, OC Takano, M Tearney, GJ DeJoseph Gauthier, DA Bouma, BE Jang, IK AF Raffel, Owen Christopher Takano, Masanori Tearney, Guillermo J. DeJoseph Gauthier, Denise A. Bouma, Brett E. Jang, Ik-Kyung TI Fibrous cap thickness of culprit plaque in subjects with acute coronary syndromes is related to individual plaque characteristics and not to the presence of systemic cardiovascular risk factors: An intravascular optical coherence tomography study. SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 400A EP 400A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651802527 ER PT J AU Kuhn, B del Monte, F Hajjar, RJ Arab, S Keating, MT AF Kuhn, Bernhard del Monte, Federica Hajjar, Roger J. Arab, Shima Keating, Mark T. TI Myocardial regeneration through periostin-induced cardiomyocyte proliferation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 56th Annual Scientific Session of the American-College-of-Cardiology CY MAR 24-27, 2007 CL New Orleans, LA SP Amer Coll Cardiol C1 Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2007 VL 49 IS 9 SU A BP 421A EP 421A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 142LQ UT WOS:000244651802616 ER PT J AU Thacker, EL O'Reilly, EJ Weisskopf, MG Chen, H Schwarzschild, MA McCullough, ML Calle, EE Thun, MJ Ascherio, A AF Thacker, E. L. O'Reilly, E. J. Weisskopf, M. G. Chen, H. Schwarzschild, M. A. McCullough, M. L. Calle, E. E. Thun, M. J. Ascherio, A. TI Temporal relationship between cigarette smoking and risk of Parkinson disease SO NEUROLOGY LA English DT Article ID ASSOCIATION; COHORT; DIAGNOSIS; MORTALITY; NICOTINE; ACCURACY; CAFFEINE; ALCOHOL; TRAITS; COFFEE AB Objective: To characterize further the relationship between smoking history and Parkinson disease (PD) risk by considering temporal and qualitative features of smoking exposure, including duration, average intensity, and recentness, as well as the relative importance of smoking during different periods of life. Methods: We prospectively assessed incident PD from 1992 to 2001 among 79,977 women and 63,348 men participating in the Cancer Prevention Study II Nutrition Cohort, according to their cigarette smoking status and lifetime smoking histories. Results: During follow-up, 413 participants had definite or probable PD confirmed by their treating neurologists or medical record review. Compared with never smokers, former smokers had a relative risk (RR) of 0.78 (95% CI 0.64 to 0.95) and current smokers had an RR of 0.27 (95% CI 0.13 to 0.56). On average, participants with more years smoked, more cigarettes per day, older age at quitting smoking, and fewer years since quitting smoking had lower PD risk. The relative risks and trends did not vary significantly by sex. The cumulative incidence of PD was lowest among participants who quit smoking at later ages. A 30% to 60% decreased risk of PD was apparent for smoking as early as 15 to 24 years before symptom onset, but not for smoking 25 or more years before onset. Conclusions: The lower risk of Parkinson disease among current and former smokers varied with smoking duration, intensity, and recentness. The dependence of this association on the timing of smoking during life is consistent with a biologic effect. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Amer Canc Soc, Epidemiol & Surveillance Res Dept, Atlanta, GA 30329 USA. RP Thacker, EL (reprint author), 655 Huntington Ave,Bldg 2, Boston, MA 02115 USA. EM ethacker@post.harvard.edu OI Thacker, Evan/0000-0002-3813-0885; Chen, Honglei/0000-0003-3446-7779 FU Intramural NIH HHS; NINDS NIH HHS [NS048517, R01 NS048517, R01 NS048517-03] NR 20 TC 73 Z9 75 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 6 PY 2007 VL 68 IS 10 BP 764 EP 768 DI 10.1212/01.wnl.0000256374.50227.4b PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 142VX UT WOS:000244679900009 PM 17339584 ER PT J AU Greenberg, SM Parisi, JE Keegan, BM AF Greenberg, Steven M. Parisi, Joseph E. Keegan, B. Mark TI A 63-year-old man with headaches and behavioral deterioration SO NEUROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; CEREBRAL AMYLOID ANGIOPATHY; OF-THE-LITERATURE; PRIMARY ANGIITIS; GRANULOMATOUS-ANGIITIS; MR; VASCULITIS; DISEASE; IMMUNIZATION; ANGIOGRAPHY C1 Mayo Clin & Mayo Fdn, Dept Neurol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Rochester, MN 55905 USA. Mayo Clin Scottsdale, Coll Med, Dept Neurol, Scottsdale, AZ USA. Mayo Clin Scottsdale, Coll Med, Dept Pathol & Lab Med, Scottsdale, AZ USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. RP Keegan, BM (reprint author), Mayo Clin & Mayo Fdn, Dept Neurol, 200 1st St SW, Rochester, MN 55905 USA. EM keegan.bmark@mayo.edu NR 23 TC 9 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 6 PY 2007 VL 68 IS 10 BP 782 EP 787 DI 10.1212/01.wnl.0000258985.31455.13 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 142VX UT WOS:000244679900014 PM 17339589 ER PT J AU Schmelzle, T Mailleux, AA Overholtzer, M Carroll, JS Solimini, NL Lightcap, ES Veiby, OP Brugge, JS AF Schmelzle, Tobias Mailleux, Arnaud A. Overholtzer, Michael Carroll, Jason S. Solimini, Nicole L. Lightcap, Eric S. Veiby, Ole P. Brugge, Joan S. TI Functional role and oncogene-regulated expression of the BH3-only factor Bmf in mammary epithelial anoikis and morphogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE apoptosis; breast; cancer; extracellular matrix ID BREAST-CANCER; INDUCED APOPTOSIS; CELL-MIGRATION; BIM; DEATH; PROTEINS; ACINI; LIFE; BAD; PROGRESSION AB The formation of a lumen in three-dimensional mammary epithelial acinar structures in vitro involves selective apoptosis of centrally localized cells that lack matrix attachment. Similarly, apoptosis is induced by forced detachment of mammary epithelial cells from matrix, a process referred to as anoikis. Through microarray analysis, we found that mRNA levels of the proapoptotic BH3-only protein Bmf are up-regulated during both anoikis and acinar morphogenesis. Importantly, down-regulation of Bmf expression by small interfering RNAs is sufficient to prevent anoikis and acinar cell death and promote anchorage-independent growth to a similar extent as down-regulation of another BH3-only protein, Bim, which was previously shown to be required for these processes. Knockdown of the BH3-only proteins Bad or Bid does not suppress anoikis or luminal apoptosis or promote anchorage-independent growth, but protects from other defined apoptotic stimuli, indicating specificity of BH3-only function. Bmf mRNA is significantly up-regulated upon loss of matrix attachment or disruption of the actin cytoskeleton, but not in response to several other stresses. Interestingly, constitutive activation of the Mek/Erk or phosphatidylinositol 3-kinase/Akt pathways suppresses the transcriptional up-regulation of Bmf during anoikis. Thus, Bmf is a central mediator of anoikis in mammary cells and a target of oncogenes that contribute to the progression of glandular epithelial tumors. Finally, Bmf is expressed during involution of the mouse mammary gland, suggesting that Bmf may also critically contribute to developmental processes in vivo. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Millennium Pharmaceut Inc, Dept Mol & Cellular Oncol, Cambridge, MA 02139 USA. RP Brugge, JS (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. EM joan_brugge@hms.harvard.edu FU NCI NIH HHS [CA 080111, CA 105134, P01 CA080111, R01 CA105134, T32 CA 09361, T32 CA009361] NR 35 TC 85 Z9 86 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 MAR 6 PY 2007 VL 104 IS 10 BP 3787 EP 3792 DI 10.1073/pnas.0700115104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146ZE UT WOS:000244972400024 PM 17360431 ER PT J AU Khoo, CM Carrasco, DR Bosenberg, MW Paik, JH DePinho, RA AF Khoo, Christine M. Carrasco, Daniel R. Bosenberg, Marcus W. Paik, Ji-Hye DePinho, Ronald A. TI Ink4a/Arf tumor suppressor does not modulate the degenerative conditions or tumor spectrum of the telomerase-deficient mouse SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE telomere; cancer aging; checkpoint; p53 ID HUMAN-DIPLOID FIBROBLASTS; DNA-DAMAGE; P53-DEPENDENT APOPTOSIS; DYSFUNCTIONAL TELOMERES; G(1) ARREST; P53; P19(ARF); CANCER; MICE; TUMORIGENESIS AB The Rb/p16(lnk4a) and p53/p19Arf tumor suppressor pathways have been linked to diverse cancer-relevant processes, including those governing the cellular responses to telomere dysfunction. in this study, we sought to provide direct genetic evidence of a role for the Ink4a/Arf tumor suppressor gene, encoding both p16(lnk4a) and p19(Arf), in modulating the cellular and tissue phenotypes associated with telomere dysfunction by using the mTerc Ink4a/Arf mouse model. In contrast to the rescue associated with p53 deficiency, Ink4a/Arf deficiency did not attenuate the degenerative phenotypes elicited by telomere dysfunction in the late-generation mTerc(-/-) mice. Furthermore, in contrast to accelerated cancer onset and increased epithelial cancers of late-generation mTerc(-/-) p53 mutant mice, late-generation mTerc(-/-) lnk4a/Arf mutant mice experienced a delayed tumor onset and maintained the lymphoma and sarcoma spectrum. Consistent with the negligible role of Ink4a/Arf in the telomere checkpoint response in vivo, late-generation mTerc-/- lnk4a/Arf-/- tissues show activated p53, and derivative tumor cell lines sustain frequent loss of p53 function, whereas all early generation mTerc lnk4a/Arf-/- tumor cell lines remain intact for p53. In addition, the late-generation mTerc-/- lnk4a/Arf-/- tumors showed activation of the alternative lengthening of telomere mechanism, underscoring the need for adaptation to the presence of telomere dysfunction in the absence of p16(lnk4a) and p19(Arf). These observations highlight the importance of genetic context in dictating whether telomere dysfunction promotes or suppresses age-related degenerative conditions as well as the rate of initiation and type of spontaneous cancers. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Fdn Inst Innovat Canc Sci,Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Fdn Inst Innovat Canc Sci,Ctr Appl Canc Sc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Fdn Inst Innovat Canc Sci,Dept Med Oncol, Mayer Bldg,Room 413,44 Binney St, Boston, MA 02115 USA. EM ron_depinho@dfci.harvard.edu FU NCI NIH HHS [U01 CA 84313, U01 CA084313, R01 CA084628, R01 CA 84628] NR 54 TC 28 Z9 35 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 MAR 6 PY 2007 VL 104 IS 10 BP 3931 EP 3936 DI 10.1073/pnas.0700093104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146ZE UT WOS:000244972400048 PM 17360455 ER PT J AU Suber, F Carroll, MC Moore, FD AF Suber, Freeman Carroll, Michael C. Moore, Francis D., Jr. TI Innate response to self-antigen significantly exacerbates burn wound depth SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE complement; natural IgM; trauma; wound physiology ID COMPLEMENT RECEPTOR TYPE-1; REPERFUSION INJURY; LEUKOCYTE ADHESION; NATURAL ANTIBODY; SKELETAL-MUSCLE; ISCHEMIA/REPERFUSION INJURY; ISCHEMIA-REPERFUSION; MONOCLONAL-ANTIBODY; THERMAL-INJURY; ACTIVATION AB A major component of burn injury is caused by additional local damage from acute inflammation. Using a scald burn model in mice, we find that this part of the injury is dependent on recognition of self-antigen by specific natural IgM, leading to activation of the complement system. We propose that the depth of a burn wound is a sum of the thermal energy applied and of the degree of host inflammatory response. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. CBR Inst Biomed Res, Dept Pathol, Boston, MA 02115 USA. CBR Inst Biomed Res, Dept Pediat, Boston, MA 02115 USA. RP Moore, FD (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM fmoore@partners.org FU PHS HHS [P50 52585] NR 32 TC 25 Z9 26 U1 0 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 MAR 6 PY 2007 VL 104 IS 10 BP 3973 EP 3977 DI 10.1073/pnas.0609026104 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146ZE UT WOS:000244972400055 PM 17360462 ER PT J AU Wu, C Ranganath, S Gleason, M Woodman, BB Borjeson, TM Alt, FW Bassing, CH AF Wu, Cherry Ranganath, Sheila Gleason, Megan Woodman, Barbara B. Borjeson, Tiffany M. Alt, Frederick W. Bassing, Craig H. TI Restriction of endogenous T cell antigen receptor beta rearrangements to V beta 14 through selective recombination signal sequence modifications SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE V(D)J recombination ID CHROMOSOMAL V(D)J RECOMBINATION; ALLELIC EXCLUSION; 12/23 RULE; LYMPHOCYTE DEVELOPMENT; IMMATURE THYMOCYTES; SYNAPTIC COMPLEX; V-BETA; DIFFERENTIATION; EXPRESSION; GENES AB T cell antigen receptor (TCR)beta V(D)J variable region exon assembly is ordered, with D beta to J beta rearrangements occurring before joining of V beta s to a DJ beta complex. Germ-line V(D)J segments are flanked by recombination signal (RS) sequences, which consist of heptamers and nonamers separated by a spacer of 12 (12-RS) or 23 (23-RS) bp. V(D)J recombination is restricted by the 12/23 rule; joining occurs only between gene segments flanked by 12-RSs and 23-RSs. V beta segments have 23-RSs and J beta segments 12-RSs, which based on the 12/23 rule should allow direct joining. However, V beta segments rearrange only to DJ beta complexes and not JP segments, because of restrictions beyond 12/23 (B12/23) that make the V beta 23-RS incompatible with the J beta 12-IRS. To determine whether direct V beta to JP joining occurs if flanking RSs are B12/23 compatible, we generated mice whose lymphocytes contained replacement of the V beta 1412-RS with the 3'D beta 112-RS on a TCR beta allele lacking D beta segments (the J beta 1(M6) allele). Mice heterozygous for the J beta 1(M6) allele had dramatically increased VP14+ thymocyte and T cell numbers and decreased numbers of cells expressing other V beta s. This altered V beta repertoire resulted from direct V beta 14 to J beta 1 rearrangements on the J beta 1(M6) allele. Mice harboring lymphocytes homozygous for J beta 1(m6) allele developed normal thymocyte and T cell numbers with all expressing V beta 14. Our findings show that selective RS modifications enforce rearrangement of a specific V beta gene segment and demonstrate the importance of B12/23 mechanisms for ensuring generation of diverse B12/13 repertoires. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,CBR Inst Biomed Res, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu FU NIAID NIH HHS [R01 AI020047, R01 AI020047-26, AI 20047] NR 25 TC 9 Z9 9 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 MAR 6 PY 2007 VL 104 IS 10 BP 4002 EP 4007 DI 10.1073/pnas.0700081104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146ZE UT WOS:000244972400060 PM 17360467 ER PT J AU Peer, D Zhu, PC Carman, CV Lieberman, J Shimaoka, M AF Peer, Dan Zhu, Pengcheng Carman, Christopher V. Lieberman, Judy Shimaoka, Motomu TI Selective gene silencing in activated leukocytes by targeting siRNAs to the integrin lymphocyte function-associated antigen-1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE affinity up-regulation; antiinflammation; cell adhesion molecule; drug delivery; AL-57 and TS1/22 ID IN-VIVO; IMMUNE-SYSTEM; HIGH-AFFINITY; ANTIBODY; DOMAIN; CELLS; ALPHA; ADHESIVENESS; EXPRESSION; ADHESION AB Silencing gene expression by RNAi is a powerful method for exploring gene function and validating drug targets and potentially for therapy. Lymphocytes and other primary blood cells are resistant to lipid-based transfection in vitro and are difficult to target in vivo. We show here that antibody-protamine fusion proteins targeting the human integrin lymphocyte function-associated antigen-1 (LFA-1) efficiently deliver siRNAs and specifically induce silencing in primary lymphocytes, monocytes, and dendritic cells. Moreover, a fusion protein constructed from an antibody that preferentially recognizes activation-dependent conformational changes in LFA-1 selectively targets activated leukocytes and can be used to suppress gene expression and cell proliferation only in activated lymphocytes. The siRNA-fusion protein complexes do not cause lymphocyte activation or induce IFN responses. K562 cells expressing latent WT or constitutively activated LFA-1 engrafted in the lungs of SCID mice are selectively targeted by intravenously injected fusion protein-siRNA complexes, demonstrating the potential in vivo applicability of LFA-1-directed siRNA delivery. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM lieberman@cbr.med.harvard.edu; shimaoka@cbrinstitute.org RI Peer, Dan/A-1785-2011; Lieberman, Judy/A-2717-2015; Carman, Christopher/L-8108-2016 OI Peer, Dan/0000-0001-8238-0673; Carman, Christopher/0000-0001-7358-2548 FU NIAID NIH HHS [AI 45587, AI 58695, AI 63421, R01 AI045587, R01 AI063421, R21 AI058695, R56 AI045587] NR 41 TC 172 Z9 181 U1 0 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 6 PY 2007 VL 104 IS 10 BP 4095 EP 4100 DI 10.1073/pnas.0608491104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146ZE UT WOS:000244972400076 PM 17360483 ER PT J AU Escamilla, MA Ontiveros, A Nicolini, H Raventos, H Mendoza, R Medina, R Munoz, R Levinson, D Peralta, JM Dassori, A Almasy, L AF Escamilla, M. A. Ontiveros, A. Nicolini, H. Raventos, H. Mendoza, R. Medina, R. Munoz, R. Levinson, D. Peralta, J. M. Dassori, A. Almasy, L. TI A genome-wide scan for schizophrenia and psychosis susceptibility loci in families of Mexican and Central American ancestry SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE schizophrenia; genetics; Mexico; Latino; Mexican-American; Central American ID COSTA-RICAN POPULATION; LINKAGE DISEQUILIBRIUM; DIAGNOSTIC INTERVIEW; VULNERABILITY LOCUS; BIPOLAR DISORDER; GENE; HETEROGENEITY; CHROMOSOME-18; RELIABILITY; PEDIGREES AB Schizophrenia is a complex psychiatric disorder, likely to be caused in part by multiple genes. In this study, linkage analyses were performed to identify chromosomal regions most likely to be associated with schizophrenia and psychosis in multiplex families of Mexican and Central American origin. Four hundred and fifty-nine individuals from 99 families, containing at least two siblings with hospital diagnoses of schizophrenia or schizoaffective disorder, were genotyped. Four hundred and four microsatellite markers were genotyped for all individuals and multipoint non-parametric linkage analyses were performed using broad (any psychosis) and narrow (schizophrenia and schizoaffective disorder) models. Under the broad model, three chromosomal regions (1pter-p36, 5q35, and 18p11) exhibited evidence of linkage with non-parametric lod (NPL) scores greater than 2.7 (equivalent to empirical P values of less than 0.001) with the peak multipoint NPL = 3.42 (empirical P value 0.00003), meeting genomewide evidence for significant linkage in the 1pter-p36 region. Under the narrow model, the same three loci showed (nonsignificant) evidence of linkage. These linkage findings (lpter-p36, 18p11, and 5q35) highlight where genes for psychosis and schizophrenia are most likely to be found in persons of Mexican and Central American ancestry, and correspond to recent linkages of schizophrenia or psychosis in other populations which were formed in part from emigrants from the Spanish empire of the 15th and 16th centuries. (c) 2006 Wiley-Liss, Inc. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. Inst Informat Invest Mental Hlth, INFOSAME, Sch Med, Ctr Invest,Div Hlth Sci,ITESM, Monterrey, NL, Mexico. Med & Family Res Grp, Mexico City, DF, Mexico. Univ Costa Rica, Ctr Res Mol Biol, San Jose, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Torrance, CA 90509 USA. S Texas Vet Hlth Syst, Dept Psychiat, San Antonio, TX USA. Family Hlth Ctr San Diego, San Diego, CA USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. SW Fdn Biomed Res, San Antonio, TX 78284 USA. RP Escamilla, MA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM escamillam@uthsesa.edu OI Raventos, Henriette/0000-0001-9423-8308; Nicolini, Humberto/0000-0003-2494-0067 FU NIMH NIH HHS [MH60881] NR 41 TC 27 Z9 27 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD MAR 5 PY 2007 VL 144B IS 2 BP 193 EP 199 DI 10.1002/ajmg.b.30411 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 143NL UT WOS:000244729000006 PM 17044102 ER PT J AU Perry, RT Wiener, H Harrell, LE Blacker, D Tanzi, RE Bertram, L Bassett, SS Go, RCP AF Perry, Rodney T. Wiener, Howard Harrell, Lindy E. Blacker, Deborah Tanzi, Rudolph E. Bertram, Lars Bassett, Susan S. Go, Rodney C. P. TI Follow-up mapping supports the evidence for linkage in the candidate region 9q22 in the NIMH Alzheimer's Disease genetics initiative cohort SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE chromosome; neurodegenerative; STR; genomic scan; SNPs ID SINGLE-NUCLEOTIDE POLYMORPHISMS; FAMILY-BASED ASSOCIATION; ADRDA WORK GROUP; GENOME SCAN; COMPLEX TRAITS; NEUROTROPHIC FACTOR; AMYLOID DEPOSITION; CLINICAL-DIAGNOSIS; TGF-BETA; ONSET AB Other than the APOE peak at 19q13, the 9q22 region was identified in our original genomic scan as the candidate region with the highest multipoint lod score (MLS) in the subset of late onset Alzheimer's Disease (AD) families (MLS = 2.9 at 101 cM) from the NIMH Genetics Initiative sample. We have now genotyped an additional 12 short tandem repeats (STR) in this region. Multipoint analysis shows the region remains significant with an increase in the peak AILS from 2.9 to 3.8 at 95 cM near marker D9S1815, and the 1 LOD interval narrows from 21.5 to 11 cM. HLOD scores also provide evidence for significant linkage (4.5 with an alpha = 31%) with a further narrowing of the region to 6.6 cM (92.2-98.8 cM). Single nucleotide polymorphisms (SNPs) in the Ubiquilin1 gene (UBQLN1), located at 83.3 cM, have been reported to be significantly associated to AD, accounting for a substantial portion of the original linkage signal [Bertram et al., 2005]. Our analyses of the higher resolution genotype data generated here provide further support for the existence of a least one additional locus on chromosome 9q22. In an effort to pinpoint this putative AD susceptibility gene, we have begun to analyze SNPs in other candidate genes in and around this narrowed region to test for additional associations to AD. (c) 2006 Wiley-Liss, Inc. C1 Univ Alabama, Dept Epidemiol & Int Hlth, Birmingham, AL 35294 USA. Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Unit, Charlestown, MA USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. RP Perry, RT (reprint author), Univ Alabama, Dept Epidemiol & Int Hlth, 210H Ryals Bldg,1665 Univ Blvd, Birmingham, AL 35294 USA. EM rperry@uab.edu RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X FU NIA NIH HHS [U24 AG021886]; NINDS NIH HHS [R01 NS045934-05] NR 78 TC 10 Z9 10 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD MAR 5 PY 2007 VL 144B IS 2 BP 220 EP 227 DI 10.1002/ajmg.b.30433 PG 8 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 143NL UT WOS:000244729000010 PM 17034007 ER PT J AU DaSilva, AFM Granziera, C Tuch, DS Snyder, J Vincent, M Hadjikhani, N AF DaSilva, Alexandre F. M. Granziera, Cristina Tuch, David S. Snyder, Josh Vincent, Maurice Hadjikhani, Nouchine TI Interictal alterations of the trigeminal somatosensory pathway and periaqueductal gray matter in migraine SO NEUROREPORT LA English DT Article DE brain; diffusion tersor imaging; imaging; migraine; periaqueductal grey; trigeminal somatosensory system ID DIFFUSION; HEADACHE; BRAIN; SENSITIVITY; DEPRESSION; ATTACKS; RISK; PAIN AB Migraine has been traditionally considered a nonprogressive, paroxysmal disorder with no brain abnormalities between attacks. We used diffusion tensor imaging to examine interictal diffusion properties of the brains of migraineurs with aura, migraineurs without aura and matched healthy controls. Areas of lower fractional anisotropy were present in migraineurs along the thalamocortical tract. In addition, migraineurs with aura had lower fractional anisotropy in the ventral trigeminothalamic tract, and migraineurs without aura had lower fractional anisotropy in the ventrolateral periaqueductal grey matter. Our results indicate the presence of permanent interictal changes in migraineurs, pointing to an effect of migraine on the trigeminal somatosensory and modulatory pain systems. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. UFRJ, Fac Med, Dept Neurol, Rio De Janeiro, Brazil. RP Hadjikhani, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Bldg 120,110 6th St,Room 217, Charlestown, MA 02129 USA. EM nouchine@nmr.mgh.harvard.edu RI Hadjikhani, Nouchine/C-2018-2008; Vincent, Maurice/B-1415-2009 OI Hadjikhani, Nouchine/0000-0003-4075-3106; FU NIBIB NIH HHS [U54 EB05149, U54 EB005149]; NINDS NIH HHS [5P01 NS 35611-09, P01 NS035611] NR 24 TC 66 Z9 71 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAR 5 PY 2007 VL 18 IS 4 BP 301 EP 305 DI 10.1097/WNR.0b013e32801776bb PG 5 WC Neurosciences SC Neurosciences & Neurology GA 146BN UT WOS:000244909600001 PM 17435592 ER PT J AU Magnee, MJCM Stekelenburg, JJ Kemner, C de Gelder, B AF Magnee, Maurice J. C. M. Stekelenburg, Jeroen J. Kemner, Chantal de Gelder, Beatrice TI Similar facial electromyographic responses to faces, voices, and body expressions SO NEUROREPORT LA English DT Article DE affective prosody; audiovisual perception; body language; electromyogram; face expression; mirror neurons ID SOCIAL COGNITION; PERCEPTION; STIMULI; EMOTION; FEAR AB Observing facial expressions automatically prompts imitation, as can be seen with facial electromyography. To investigate whether this reaction is driven by automatic mimicry or by recognition of the emotion displayed we recorded electromyograph responses to presentations of facial expressions, face-voice combinations and bodily expressions, which resulted from happy and fearful stimuli. We observed emotion-specific facial muscle activity (zygomaticus for happiness, corrugator for fear) for all three stimulus categories. This indicates that spontaneous facial expression is more akin to an emotional reaction than to facial mimicry and imitation of the seen face stimulus. We suggest that seeing a facial expression, an emotional body expression or hearing an emotional tone of voice all activate the affect program corresponding to the emotion displayed. C1 Univ Utrecht, Ctr Med, Rudolf Magnus Inst Neurosci, Dept Child & Adolescent Psychiat, Utrecht, Netherlands. Tilburg Univ, Lab Cognit & Affect Neurosci, NL-5000 LE Tilburg, Netherlands. Maastricht Univ, Fac Psychol, Sect Biol Dev Psychol, Maastricht, Netherlands. Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP de Gelder, B (reprint author), Athinous MGH NMR Ctr, Bldg 36,1st St,Room 417, Charlestown, MA 02129 USA. EM degelder@nmr.mgh.harvard.edu NR 17 TC 46 Z9 46 U1 0 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAR 5 PY 2007 VL 18 IS 4 BP 369 EP 372 DI 10.1097/WNR.0b013e32801776e6 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 146BN UT WOS:000244909600014 PM 17435605 ER PT J AU Cense, B Mujat, M Chen, TC Park, BH de Boer, JF AF Cense, Barry Mujat, Mircea Chen, Teresa C. Park, B. Hyle de Boer, Johannes F. TI Polarization-sensitive spectral-domain optical coherence tomography using a single line scan camera SO OPTICS EXPRESS LA English DT Article ID NERVE-FIBER LAYER; HUMAN RETINA; HUMAN SKIN; BIREFRINGENCE; INTERFEROMETRY; THICKNESS; TISSUE AB Polarization- sensitive optical coherence tomography can be used to measure the birefringence of biological tissue such as the human retina. Previous measurements with a time- domain polarization- sensitive optical coherence tomography system revealed that the birefringence of the human retinal nerve fiber layer is not constant, but varies as a function of location around the optic nerve head. Here we present a spectral- domain polarization- sensitive optical coherence tomography system that uses a spectrometer configuration with a single line scan camera and a Wollaston prism in the detection arm. Since only one camera has to be synchronized with other components in the system, the design is simplified considerably. This system is 60 times faster than a time- domain polarization- sensitive optical coherence tomography system. Data was acquired using concentric circular scans around the optic nerve head of a young healthy volunteer and the acquisition time for 12 circular scans was reduced from 72 s to 1.2 s. The acquired data sets demonstrate variations in retinal thickness and double pass phase retardation per unit depth that were similar to data from the same volunteer taken with a time- domain polarization- sensitive system. The double pass phase retardation per unit depth of the retinal nerve fiber layer varied between 0.18 and 0.40 degrees/mu m, equivalent to a birefringence of 2.2(.)10(-4) and 4.8(.)10(-4) respectively, measured at 840 nm. (c) 2007 Optical Society of America. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Cense, B (reprint author), Indiana Univ, Sch Optometry, 800 E Atwater Ave, Bloomington, IN 47405 USA. EM bcense@indiana.edu; deboer@helix.mgh.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 NR 27 TC 49 Z9 50 U1 0 U2 10 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD MAR 5 PY 2007 VL 15 IS 5 BP 2421 EP 2431 DI 10.1364/OE.15.002421 PG 11 WC Optics SC Optics GA 142WW UT WOS:000244682600044 PM 19532479 ER PT J AU Yelin, D White, WM Motz, JT Yun, SH Bouma, BE Tearney, GJ AF Yelin, Dvir White, W. Matthew Motz, Jason. T. Yun, Seok H. Bouma, Brett E. Tearney, Guillermo J. TI Spectral-domain spectrally-encoded endoscopy SO OPTICS EXPRESS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; INTRADUCTAL LESIONS; MINIATURE ENDOSCOPY; CURRENT STATE; DIAGNOSIS; SURGERY; INTERFEROMETRY; BREAST; FIBER AB Spectrally-encoded miniature endoscopy uses a single optical fiber and wavelength division multiplexing to obtain macroscopic images through miniature, flexible probes. In turn, it has the potential to enable two-and three-dimensional imaging within the body at locations that are currently difficult to access with conventional endoscopes. Here we present a novel detection scheme for spectrally-encoded endoscopy using spectral-domain interferometry. Compared to previous time-domain configurations, this new detection method results in greater than 1000-fold increase in sensitivity (77 dB), a 6-fold increase in imaging speed (30 volumes per second), and a 2-fold increase in depth range (2.8 mm). We demonstrate spectrally-encoded, spectral-domain detection by conducting video-rate, three-dimensional imaging in a variety of specimens, including the paws of a mouse embryo and excised human ear bones. Our results show that this new technology enables video rate spectrally-encoded endoscopy and will therefore be useful for a variety of minimally invasive medical applications. (c) 2007 Optical Society of America. C1 Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Yelin, D (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, 55 Fruit St,BAR 703, Boston, MA 02114 USA. EM dyelin@partners.org NR 31 TC 37 Z9 38 U1 0 U2 7 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD MAR 5 PY 2007 VL 15 IS 5 BP 2432 EP 2444 DI 10.1364/OE.15.002432 PG 13 WC Optics SC Optics GA 142WW UT WOS:000244682600045 PM 19532480 ER PT J AU Zraika, S Hull, RL Udayasankar, J Utzschneider, KM Tong, J Gerchman, F Kahn, SE AF Zraika, Sakeneh Hull, Rebecca L. Udayasankar, Jayalakshmi Utzschneider, Kristina M. Tong, Jenny Gerchman, Fernando Kahn, Steven E. TI Glucose- and time-dependence of islet amyloid formation in vitro SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE islet amyloid; human islet amyloid polypeptide; islets; beta-cell; insulin secretion; cell viability; amylin; mouse model; diabetes ID TRANSGENIC MOUSE MODEL; BETA-CELL APOPTOSIS; DIABETES-MELLITUS; POLYPEPTIDE IAPP; MICE; PATHOGENESIS; SECRETION; PANCREAS; FIBRILS AB Islet amyloid contributes to the loss of beta-cell mass in type 2 diabetes. To examine the roles of glucose and time on amyloid formation, we developed a rapid in vitro model using isolated islets from human islet amyloid polypeptide (hIAPP) transgenic mice. Islets from hIAPP transgenic and non-transgenic mice were cultured for up to 7 days with either 5.5, 11.1, 16.7 or 33.3 mmol/l glucose. At various time-points throughout the culture period, islets were harvested for determination of amyloid and beta-cell areas, and for measures of cell viability, insulin content, and secretion. Following culture of hIAPP transgenic islets in 16.7 or 33.3 mmol/l glucose, amyloid formation was significantly increased compared to 5.5 or 11.1 mmol/l glucose culture. Amyloid was detected as early as day 2 and increased in a time-dependent manner so that by day 7, a decrease in the proportion of beta-cell area in hIAPP transgenic islets was evident. When compared to non-transgenic islets after 7-day culture in 16.7 mmol/l glucose, hIAPP transgenic islets were 24% less viable, had decreased beta-cell area and insulin content, but displayed no change in insulin secretion. Thus, we have developed a rapid in vitro model of light microscopy-visible islet amyloid formation that is both glucose- and time-dependent. Formation of amyloid in this model is associated with reduced cell viability and beta-cell loss but adequate functional adaptation. It thus enables studies investigating the mechanism(s) underlying the amyloid-associated loss of beta-cell mass in type 2 diabetes. (c) 2007 Elsevier Inc. All rights reserved. C1 VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98108 USA. RP Zraika, S (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. EM zraikas@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002; Hull, Rebecca/0000-0001-9690-4087 FU NIDDK NIH HHS [DK-17047, DK-74404, K01 DK074404, P30 DK017047] NR 27 TC 23 Z9 25 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 2 PY 2007 VL 354 IS 1 BP 234 EP 239 DI 10.1016/j.bbrc.2006.12.187 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 135DH UT WOS:000244133800039 PM 17222388 ER PT J AU Schillace, RV Pisenti, N Pattamanuch, N Galligan, S Marracci, GH Bourdette, DN Carr, DW AF Schillace, R. V. Pisenti, N. Pattamanuch, N. Galligan, S. Marracci, G. H. Bourdette, D. N. Carr, D. W. TI Lipoic acid stimulates cAMP production in T lymphocytes and NK cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE lipoic acid; cAMP; lymphocyte; NK cell ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS; PROSTANOID RECEPTORS; SPINAL-CORD; MIGRATION; BLOOD; ACTIVATION; EXPRESSION; EP2 AB The anti-oxidant lipoic acid (LA) potently suppresses clinical and pathologic disease in the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis, by inhibiting the migration of pathogenic T cells to the spinal cord. The mechanism by which this occurs is largely unknown. In this report we demonstrate that LA induces increases in cyclic AMP, a known immunosuppressant, in human T cells. The increase in cAMP is associated with increased adenylyl eyclase activity and is partially blocked by prostanoid receptor antagonists. We present evidence that LA also stimulates cAMP production in natural killer (NK) cells. This novel mechanism of action is highly relevant to the immunomodulatory effects of LA and provides further support for the study of LA as a therapeutic agent for multiple sclerosis and other autoimmune diseases. (c) 2007 Elsevier Inc. All rights reserved. C1 Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Endocrinol, Portland, OR 97239 USA. RP Carr, DW (reprint author), VAMC, RD-8 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM carrd@ohsu.edu FU NCCIH NIH HHS [P50AT00066-01, P50 AT000066] NR 18 TC 27 Z9 29 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 2 PY 2007 VL 354 IS 1 BP 259 EP 264 DI 10.1016/j.bbrc.2006.12.195 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 135DH UT WOS:000244133800043 PM 17210133 ER PT J AU Fujikawa, DG Shinmei, SS Zhao, SP Aviles, ER AF Fujikawa, Denson G. Shinmei, Steve S. Zhao, Shuangping Aviles, Ernesto R., Jr. TI Caspase-dependent programmed cell death pathways are not activated in generalized seizure-induced neuronal death SO BRAIN RESEARCH LA English DT Article DE caspase-8; caspase-9; cell death; DNA laddering; necrosis; seizures ID INTERNUCLEOSOMAL DNA CLEAVAGE; INDUCED STATUS EPILEPTICUS; NMDA RECEPTOR ANTAGONIST; ACUTE NECROTIC INSULTS; HYPOXIA-ISCHEMIA; ENDONUCLEASE-G; APOPTOTIC NEURODEGENERATION; CYSTEINE PROTEASES; LIMBIC SEIZURES; MUTANT MICE AB Activation of the caspase-dependent cell death pathways has been shown in focal seizures, but whether this occurs in prolonged generalized seizures is not known. We investigated whether the initiator caspase in the extrinsic pathway, caspase-8, or the intrinsic pathway, caspase-9, is activated during the first 24 h following lithium-pilocarpine-induced status epilepticus, when neuronal death is maximal and widespread. The thymuses of rats given methamphetamine were used as positive controls for caspase-3-activated cellular apoptosis. Following methamphetamine treatment, caspase-9 but not caspase-8 was activated in thymocytes. However, 6 or 24 h following status epilepticus, none of 26 brain regions studied showed either caspase-8 or -9 activation by immunohistochemistry, western blotting and enzyme activity assays. Our results provide evidence against the activation of the extrinsic and intrinsic caspase pathways in generalized seizures, which produce morphologically necrotic neurons with internucleosomal DNA cleavage (DNA laddering), a programmed process. In contrast, there is increasing evidence that caspase-independent programmed mechanisms play a prominent role in seizure-induced neuronal death. Published by Elsevier B.V. C1 VA Greater Los Angeles Healthcare Syst, Expt Neurol Lab, North Hills, CA 91343 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. RP Fujikawa, DG (reprint author), VA Greater Los Angeles Healthcare Syst, Expt Neurol Lab, 151B4,16111 Plummer St, North Hills, CA 91343 USA. EM dfujikaw@ucla.edu NR 76 TC 25 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 2 PY 2007 VL 1135 IS 1 BP 206 EP 218 DI 10.1016/j.brainres.2006.12.029 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 141BR UT WOS:000244551900024 PM 17204252 ER PT J AU Eto, K Kaur, V Thomas, MK AF Eto, Kazuhiro Kaur, Varinderpal Thomas, Melissa K. TI Regulation of pancreas duodenum homeobox-1 expression by early growth response-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEAR FACTOR 3-BETA; CELL-SPECIFIC TRANSCRIPTION; INSULIN GENE-TRANSCRIPTION; PROMOTER FACTOR-I; PDX-1 GENE; BETA-CELLS; MICROARRAY ANALYSIS; DIABETES-MELLITUS; TARGET GENES; EGR-1 AB The homeodomain transcription factor pancreas duodenum homeobox-1 (PDX-1) is a key regulator of pancreatic beta-cell development, function, and survival. Deficits in PDX-1 expression result in insulin deficiency and hyperglycemia. We previously found that the glucose-responsive transcription factor early growth response-1 (Egr-1) activates the insulin promoter in part by increasing expression levels of PDX-1. We now report that Egr-1 binds and activates multiple regulatory sites within the pdx-1 promoter. We identified consensus Egr-1 recognition sequences within proximal and distal. regions of the mouse pdx-1 promoter and demonstrated specific binding of Egr-1 by chromatin immunoprecipitation and electrophoretic mobility shift assays. Overexpression of Egr-1 increased transcriptional activation of the -4500 proximal pdx-1 promoter and of the highly conserved regulatory Areas I, II, and Ill. Mutagenesis of a specific Egr-1 binding site within Area III substantially decreased Egr-1-mediated activation. Egr-1 increased the transcriptional activation of Areas I and II, despite the absence of Egr-1 recognition sequences within this promoter segment, suggesting that Egr-1 also can regulate the pdx-1 promoter indirectly. Egr-1 increased, and a dominant-negative Egr-1 mutant repressed, the transcriptional activation of distal pdx-1 promoter sequences. Mutagenesis of a specific Egr-1 binding site within regulatory Area IV reduced basal and Egr-1-mediated transcriptional activation. Our data indicate that Egr-1 regulates expression of PDX-1 in pancreatic P-cells by both direct and indirect activation of the pdx-1 promoter. We propose that Egr-1 expression levels may act as a sensor in pancreatic P-cells to translate extracellular signals into changes in PDX-1 expression levels and pancreatic beta-cell function. C1 Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Thomas, MK (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, Thier 340,50 Blossom St, Boston, MA 02114 USA. EM mthomas1@partners.org FU NIDDK NIH HHS [P30DK057521] NR 64 TC 17 Z9 17 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 MAR 2 PY 2007 VL 282 IS 9 BP 5973 EP 5983 DI 10.1074/jbc.M607288200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 145LS UT WOS:000244867200002 PM 17150967 ER PT J AU Lu, H Wu, JY Beswick, EJ Ohno, T Odenbreit, S Haas, R Reyes, VE Kita, M Graham, DY Yamaoka, Y AF Lu, Hong Wu, Jeng Yih Beswick, Ellen J. Ohno, Tomoyuki Odenbreit, Stefan Haas, Rainer Reyes, Victor E. Kita, Masakazu Graham, David Y. Yamaoka, Yoshio TI Functional and intracellular signaling differences associated with the Helicobacter pylori AlpAB adhesin from Western and East Asian strains SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GASTRIC EPITHELIAL-CELLS; NF-KAPPA-B; OUTER-MEMBRANE PROTEINS; CAG PATHOGENICITY ISLAND; HISTIDINE-DECARBOXYLASE PROMOTER; INFLAMMATION-ASSOCIATED CANCER; INTERLEUKIN-8 PRODUCTION; TYROSINE PHOSPHORYLATION; ACTIVATOR PROTEIN-1; EXPRESSION AB Following adhesion of Helicobacterpylori to gastric epithelial cells, intracellular signaling leads to cytokine production, which causes H. pylori-related gastric injury. Two adjacent homologous genes (alpA and alpB), which encode H. pylori outer membrane proteins, are thought to be associated with adhesion and cytokine induction. We co-cultured gastric epithelial cells with wild type H. pylori strains and their corresponding alpA/alpB-deleted mutants (Delta alpAB). Results were confirmed by complementation. Flow cytometry confirmed that AlpAB was involved in cellular adhesion. Deletion of alpAB reduced interleukin (IL)-6 induction in gastric epithelial cells. Deletion of alpAB reduced IL-8 induction with East Asian but not with Western strains. All AlpAB-positive strains tested activated the extracellular signal-regulated kinase, c-Fos, and cAMP-responsive element-binding protein. Activation of the Jun-N-terminal kinase, c-Jun, and NF-kappa B was exclusive to AlpAB from East Asian strains. Delta alpAB mutants poorly colonized the stomachs of C57BL/6 mice and were associated with lower mucosal levels of KC and IL-6. Our results suggest that AlpAB may induce gastric injury by mediating adherence to gastric epithelial cells and by modulating proinflammatory intracellular signaling cascades. Known geographical differences in H. pylori-related clinical outcomes may relate to differential effects of East Asian and Western types of AlpAB on NF-kappa B-related proinflammatory signaling pathways. C1 Baylor Coll Med, Dept Med Gastroenterol, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Digest Dis, Dept Gastroenterol,Renji Hosp, Shanghai 200001, Peoples R China. Kaohsiung Med Univ Hosp, Div Gastroenterol, Dept Internal Med, Kaohsiung 807, Taiwan. Univ Texas, Med Branch, Dept Pediat, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. Univ Munich, Max Von Pettenkofer Inst Hyg & Med Microbiol, D-80336 Munich, Germany. Kyoto Prefectural Univ Med, Dept Microbiol, Kyoto 6028566, Japan. RP Yamaoka, Y (reprint author), Baylor Coll Med, Dept Med Gastroenterol, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM yyamaoka@bcm.tmc.edu RI Wu, Jeng-Yih/D-4520-2009 FU NIDDK NIH HHS [R01 DK062813-03, DK50669, DK56338, DK62813, P30 DK056338, R01 DK050669, R01 DK062813] NR 41 TC 35 Z9 40 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 MAR 2 PY 2007 VL 282 IS 9 BP 6242 EP 6254 DI 10.1074/jbc.M611178200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 145LS UT WOS:000244867200030 PM 17202133 ER PT J AU Levine, JB Youngs, RM MacDonald, ML Chu, M Leeder, AD Berthiaume, F Konradi, C AF Levine, J. B. Youngs, R. M. MacDonald, M. L. Chu, M. Leeder, A. D. Berthiaume, F. Konradi, C. TI Isolation rearing and hyperlocomotion are associated with reduced immediate early gene expression levels in the medial prefrontal cortex SO NEUROSCIENCE LA English DT Article DE open field; isolation rearing; adolescence; immediate early gene; neuroplasticity; hyperactivity ID DEFICIT HYPERACTIVITY DISORDER; MESSENGER-RNA EXPRESSION; NUCLEUS-ACCUMBENS; RAT-BRAIN; NEUROTROPHIC FACTOR; HOMER PROTEINS; MOUSE-BRAIN; ARC GENE; IN-VIVO; C-FOS AB Environmental deprivation contributes in important ways to the development of a wide range of psychiatric disorders. Isolation rearing of rodents, a model for environmental deprivation in humans, consistently produces hyperlocomotion, which provides a measurable parameter to study the underlying mechanisms of early adverse psychosocial stressors. Male Sprague-Dawley rat pups were separated from dams at postnatal (PN) day 20 and reared either in groups of three or in isolation. On PN 38, locomotion was assessed in the open field. On PN 46, rats were killed and gene expression patterns examined in the medial prefrontal cortex (mPFC). Isolation-reared rats displayed increased locomotor activity and decreased resting time in the open field. Specific gene expression patterns in the mPFC were associated with both isolation rearing and hyperlocomotive behavior in the open field. Genes involved in these expression patterns included immediate early genes (IEGs) and genes that regulate cell differentiation and apoptosis. The study of these genes could provide important insights into how abnormal early psychosocial events affect brain function and behavior. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved. C1 McLean Hosp, Lab Neuroplastic, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Engn & Med, Boston, MA 02114 USA. Shriners Burn Hosp Children, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Levine, JB (reprint author), McLean Hosp, Lab Neuroplastic, Belmont, MA 02478 USA. EM jblevine@partners.org RI Levine, John/G-6221-2015 FU NIMH NIH HHS [5T32MH016259] NR 86 TC 42 Z9 46 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD MAR 2 PY 2007 VL 145 IS 1 BP 42 EP 55 DI 10.1016/j.neuroscience.2006.11.063 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 140FE UT WOS:000244489100006 PM 17239545 ER PT J AU Moye, PK Pesik, N Terndrup, T Roe, J Weissman, N Kiefe, C Houston, TK AF Moye, Philip Kevin Pesik, Nicki Terndrup, Thomas Roe, Jedd Weissman, Norman Kiefe, Catarina Houston, Thomas K. TI Bioterrorism training in US emergency medicine residencies: Has it changed since 9/11? SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT 12th Annual National Research Service Award Trainees Conference CY JUN, 2006 CL Seattle, WA DE bioterrorism; residency; education; emergency medicine; experiential learning ID CARDIAC LIFE-SUPPORT; FACULTY-DEVELOPMENT; SKILLS; PROGRAMS AB Objectives: To assess the change in prevalence of bioterrorism training among emergency medicine (EM) residencies from 1998 to 2005, to characterize current training, and to identify characteristics of programs that have implemented more intensive training methods. Methods: This was a national cross sectional survey of the 133 U.S. EM residencies participating in the 2005 National Resident Matching Program; comparison with a baseline survey from 1998 was performed. Types of training provided were assessed, and programs using experiential methods were identified. Results: Of 112 programs (84.2%) responding, 98% reported formal training in bioterrorism, increased from 53% (40/76) responding in 1998. In 2005, most programs with bioterrorism training (65%) used at least three methods of instruction, mostly lectures (95%) and disaster drills (80%). Fewer programs used experiential methods such as field exercises or bioterrorism-specific rotations (35% and 13%, respectively). Compared with other programs, residency programs with more complex, experiential methods were more likely to teach bioterrorism-related topics at least twice a year (83% vs. 59%; p = 0.018), to teach at least three topics (60% vs. 40%; p = 0.02), and to report funding for bioterrorism research and education (74% vs. 45%; p = 0.007). Experiential and nonexperiential programs were similar in program type (university or nonuniversity), length of program, number of residents, geographic location, and urban or rural setting. Conclusions: Training of EM residents in bioterrorism preparedness has increased markedly since 1998. However, training is often of low intensity, relying mainly on nonexperiential instruction such as lectures. Although current recommendations are that training in bioterrorism include experiential learning experiences, the authors found the rate of these experiences to be low. C1 Univ Alabama, Dept Emergency Med, Birmingham, AL 35294 USA. Univ Alabama, Ctr Outcomes & Effectiveness Res & Educ, Birmingham, AL USA. Univ Alabama, Dept Med, Div Prevent Med, Birmingham, AL USA. Emory Univ, Sch Med, Dept Emergency Med, Atlanta, GA USA. William Beaumont Hosp, Dept Emergency Med, Royal Oak, MI 48072 USA. Birmingham VA Med Ctr, Deep S Ctr Effectiveness Res, Birmingham, AL USA. Univ Alabama, Dept Med, Hlth Serv & Outcomes Res Training Program, Birmingham, AL 35294 USA. RP Moye, PK (reprint author), Univ Alabama, Dept Emergency Med, Birmingham, AL 35294 USA. EM kmoye@uabmc.edu RI Houston, Thomas/F-2469-2013 NR 25 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAR PY 2007 VL 14 IS 3 BP 221 EP 227 DI 10.1197/j.aem.2006.10.102 PG 7 WC Emergency Medicine SC Emergency Medicine GA 142FS UT WOS:000244635400006 PM 17264202 ER PT J AU Richman, IB Clark, S Sullivan, AF Camargo, CA AF Richman, Ilana B. Clark, Sunday Sullivan, Ashley F. Camargo, Carlos A., Jr. TI National study of the relation of primary care shortages to emergency department utilization SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE primary care shortage; utilization ID PUBLIC HOSPITAL EMERGENCY; HEALTH AB Background: Emergency department (ED) visit volumes are increasing nationwide. Objectives: To determine whether states with primary care shortages have higher rates of ED use Methods: Populations residing in primary care shortage areas were abstracted from the Health Resources and Services Administration Geospatial Database. Annual ED visit volumes were available from the 2001 National ED Inventory. Population data and potential confounders were abstracted from federal data sets. All analyses were conducted at the state level. Results: Primary care shortage densities varied greatly across states, ranging from 3 (New Jersey) to 28 (Mississippi) medically underserved individuals per 100 people. States also varied in their annual ED visit densities, ranging from 23 visits (Hawaii) to 65 visits (Washington, DC) per 100 people. Of the 17 states in the top tertile for primary care shortage, 7 also were in the top tertile for ED visits. Primary care shortage density was positively associated with ED visit density. An increase of 10 medically underserved individuals per 100 people was associated with an annual increase of 4.2 ED visits per 100 people (p = 0.04). The association remained after controlling for six factors, with an increase of 10 medically underserved individuals per 100 people associated with an annual increase of 3.3 ED visits per 100 people (p = 0.04). Nevertheless, five states had high ED visit densities despite comparatively low primary care shortage densities (Maine, Massachusetts, New Hampshire, Rhode Island, and Vermont), whereas five others had low ED visit densities despite high primary care shortage densities (Arizona, Idaho, Montana, New Mexico, and South Dakota). Conclusions: A positive association between primary care shortage densities and ED visit densities was found. Although most states adhere to this pattern, some states do not. Further investigation of this dissociation may yield additional explanations for rising ED visit volumes. C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. EM ccamargo@partners.org FU AHRQ HHS [R01 HS13099] NR 10 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAR PY 2007 VL 14 IS 3 BP 279 EP 282 DI 10.1197/j.aem.2006.10.093 PG 4 WC Emergency Medicine SC Emergency Medicine GA 142FS UT WOS:000244635400017 PM 17242383 ER PT J AU Nappi, J Yoshida, H AF Nappi, Janne Yoshida, Hiroyuki TI Fully automated three-dimensional detection of polyps in fecal-tagging CT colonography SO ACADEMIC RADIOLOGY LA English DT Article DE computer-aided detection; CAD; fecal tagging; CT colonography; virtual colonoscopy ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; AIDED DIAGNOSIS SCHEME; CATHARTIC PREPARATION; REDUCTION; CAD; SEGMENTATION; PERFORMANCE; COLONOSCOPY; CENTERLINE; BARIUM AB Rationale and Objectives. The presence of opacified materials presents several technical challenges for automated detection of polyps in fecal-tagging computed tomography colonography (ftCTC), such as pseudo-enhancement and the distortion of the density, size, and shape of the observed lesions. We developed a fully automated computer-aided detection (CAD) scheme that addresses these issues in automated detection of polyps in ftCTC. Materials and Methods. Pseudo-enhancement was minimized by use of an adaptive density correction (ADC) method. The presence of tagging was minimized by use of an adaptive density mapping (ADM) method. We also developed a new method for automated extraction of the colonic wall within air-filled and tagged regions. The ADC and ADM parameters were optimized by use of an anthropomorphic phantom. The CAD scheme was evaluated with 32+32 cases from two types of clinical ftCTC databases. The cases in database I had full cathartic cleansing and 40 polyps >= 6 mm, and the cases in database 11 had reduced cathartic cleansing and 44 polyps >= 6 mm. The by-polyp detection performance of the CAD scheme was evaluated by use of a leave-one-patient-out method with five features, and the results were compared with those of a conventional CAD scheme by use of free-response receiver operating characteristic curves. Results. The CAD scheme detected 95% and 86% of the polyps >= 6 mm with 3.6 and 4.2 false positives per scan on average in databases I and II, respectively. For polyps 10 mm, the detection sensitivity was 94% in database I (with one missed hyperplastic polyp) and 100% in database II at the same false-positive rate. The detection sensitivity of the new CAD scheme was approximately 20% higher than that of the conventional CAD scheme. Conclusions. The results show that the CAD scheme developed in this study resolves the technical challenges introduced by fecal tagging, is applicable to a variety of colon preparation regimens, and provides a performance superior to that of conventional CAD schemes. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Nappi, J (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. EM jnappi@partners.org FU NCI NIH HHS [CA095279, R01 CA095279-04, R01 CA131718, R01 CA095279-05, R01 CA095279, R56 CA095279] NR 33 TC 47 Z9 48 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD MAR PY 2007 VL 14 IS 3 BP 287 EP 300 DI 10.1016/j.acra.2006.11.007 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 173GI UT WOS:000246861100006 PM 17307661 ER PT J AU Kuebler, D Illingworth, A Blenc, A Wilbur, D AF Kuebler, D. Illingworth, A. Blenc, A. Wilbur, D. TI A peer comparison program for the quality assurance of HPV DNA detection using the digene hybrid capture II/surepath method shows excellent analytic interlaboratory correlation SO ACTA CYTOLOGICA LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dahl Chase Diagnost Serv, Bangor, ME USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD MAR-APR PY 2007 VL 51 IS 2 SU S BP 280 EP 280 PG 1 WC Pathology SC Pathology GA 149VI UT WOS:000245174600082 ER PT J AU Cummings, DE Naleid, AM Lattemann, DPF AF Cummings, David E. Naleid, Amy M. Lattemann, Dianne P. Figlewicz TI Ghrelin: a link between energy homeostasis and drug abuse? SO ADDICTION BIOLOGY LA English DT Editorial Material ID STIMULATES LOCOMOTOR-ACTIVITY; CONDITIONED PLACE PREFERENCE; TRANSPORTER MESSENGER-RNA; RAT NUCLEUS-ACCUMBENS; DOPAMINE RELEASE; INTRAVENTRICULAR INSULIN; COCAINE-SEEKING; ALCOHOL; LEPTIN; FOOD C1 Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. RP Cummings, DE (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, 1660 S Columbian Way,S-111 Endo, Seattle, WA 98108 USA. EM davidec@u.washington.edu FU NIDDK NIH HHS [DK40963, P01 DK68384, R01 DK61516] NR 37 TC 18 Z9 19 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1369-1600 J9 ADDICT BIOL JI Addict. Biol. PD MAR PY 2007 VL 12 IS 1 BP 1 EP 5 DI 10.1111/j.1369-1600.2007.00053.x PG 5 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA 139FF UT WOS:000244417000001 PM 17407491 ER PT J AU Bugg, JM DeLosh, EL Davalos, DB Davis, HP AF Bugg, Julie M. DeLosh, Edward L. Davalos, Deana B. Davis, Hasker P. TI Age differences in Stroop interference: Contributions of general slowing and task-specific deficits SO AGING NEUROPSYCHOLOGY AND COGNITION LA English DT Article ID OLDER-ADULTS; COLOR-WORD; WORKING-MEMORY; PERFORMANCE; INHIBITION; ATTENTION; SPEED AB This study examined the contributions of general slowing and task-specific deficits to age-related changes in Stroop interference. Nine hundred thirty-eight participants aged 20 to 89 years completed an abbreviated Stroop color-naming task and a subset of 281 participants also completed card-sorting, simple reaction time, and choice reaction time tasks. Age-related increases in incongruent color-naming latency and card-sorting perseverative errors were observed. Hierarchical regression analyses showed that the processing speed measures accounted for significant variance on both dependent measures, but that there was also a significant residual effect of age. An additional regression analysis showed that some of the variance in incongruent color-naming, after controlling for processing speed, was shared with the variance in perseverative errors. Overall, findings suggest that the age difference in Stroop interference is partially attributable to general slowing, but is also attributable to age-related changes in task-specific processes such as inhibitory control. C1 Colorado State Univ, Ft Collins, CO 80523 USA. Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Denver, CO USA. Univ Colorado, Colorado Springs, CO 80907 USA. RP Bugg, JM (reprint author), Washington Univ, Dept Psychol, Campus Box 1125,1 Brooking Dr, St Louis, MO 63130 USA. EM jbugg@artsci.wustl.edu NR 28 TC 31 Z9 31 U1 4 U2 12 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1382-5585 J9 AGING NEUROPSYCHOL C JI Aging Neuropsychol. Cogn. PD MAR PY 2007 VL 14 IS 2 BP 155 EP 167 DI 10.1080/138255891007065 PG 13 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA 155QA UT WOS:000245591800004 ER PT J AU Hinkin, CH Barclay, TR Castellon, SA Levine, AJ Durvasula, RS Marion, SD Myers, HF Longshore, D AF Hinkin, Charles H. Barclay, Terry R. Castellon, Steven A. Levine, Andrew J. Durvasula, Ramani S. Marion, Sarah D. Myers, Hector F. Longshore, Douglas TI Drug use and medication adherence among HIV-1 infected individuals SO AIDS AND BEHAVIOR LA English DT Article DE HIV infection; AIDS; medication adherence; drug use; methamphetamine; cocaine ID ACTIVE ANTIRETROVIRAL THERAPY; SELF-REPORTED ADHERENCE; HIV-INFECTED PERSONS; CRACK COCAINE USE; METHAMPHETAMINE DEPENDENCE; PROTEASE INHIBITORS; VIRAL SUPPRESSION; PATIENT-ADHERENCE; SUBSTANCE USE; ADULTS AB This longitudinal study examined the impact of drug use and abuse on medication adherence among 150 HIV-infected individuals, 102 who tested urinalysis positive for recent illicit drug use. Medication adherence was tracked over a 6-month period using an electronic monitoring device (MEMS caps). Over the 6-month study drug-positive participants demonstrated significantly worse medication adherence than did drug-negative participants (63 vs. 79%, respectively). Logistic regression revealed that drug use was associated with over a fourfold greater risk of adherence failure. Stimulant users were at greatest risk for poor adherence. Based upon within-participants analyses comparing 3-day adherence rates when actively using versus not using drugs, this appears to be more a function of state rather than trait. These data suggest that it is the acute effects of intoxication, rather than stable features that may be characteristic of the drug-using populace, which leads to difficulties with medication adherence. C1 Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Calif State Univ Los Angeles, Los Angeles, CA 90032 USA. Point Loma Univ, San Diego, CA USA. Charles R Drew Univ Med & Sci, Res Ctr Ethn Hlth & Behav, Los Angeles, CA 90059 USA. RP Hinkin, CH (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, 760 Westwood Plaza,Room C8-747, Los Angeles, CA 90024 USA. EM chinkin@ucla.edu FU NIDA NIH HHS [R01 DA013799, R01 DA013799-04, R01 DA13799]; NIMH NIH HHS [T32 MH019535] NR 58 TC 129 Z9 134 U1 2 U2 12 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS behav. PD MAR PY 2007 VL 11 IS 2 BP 185 EP 194 DI 10.1007/s10461-006-9152-0 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 140CO UT WOS:000244480700003 PM 16897351 ER PT J AU Mayben, JK Kramer, JR Kallen, MA Franzini, L Lairson, DR Giordano, TP AF Mayben, Jennifer K. Kramer, Jennifer R. Kallen, Michael A. Franzini, Luisa Lairson, David R. Giordano, Thomas P. TI Predictors of delayed HIV diagnosis in a recently diagnosed cohort SO AIDS PATIENT CARE AND STDS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; FUNCTIONAL HEALTH LITERACY; UNITED-STATES; ANTIRETROVIRAL THERAPY; COST-EFFECTIVENESS; CARE; INFECTION; URBAN; SEX; ADHERENCE AB Delayed diagnosis of HIV is associated with a worse prognosis despite highly active anti-retroviral therapy. Many persons with HIV infection are diagnosed late in the disease process. We conducted a study of 119 persons recently diagnosed with HIV infection to determine the association of health literacy and other factors with delayed diagnosis. Patients were recruited from four publicly funded facilities in Houston, Texas. Health literacy was measured with the Test of Functional Health Literacy in Adults (TOFHLA). Delayed diagnosis was assessed by CD4 cell count at diagnosis. Sixty-five percent of patients had CD4 cell counts 350 cells/mm(3) or less. Twenty-eight percent had inadequate health literacy, but literacy was not associated with CD4 cell count. Thirty-eight percent were tested because they "felt sick." In multivariable analysis, female gender (p = 0.005), reason tested other than "felt sick" (p < 0.001), and marijuana use (p = 0.004) and other illicit drug use (p = 0.01) were predictors of having a higher CD4 cell count at diagnosis. These results confirm that late diagnosis of HIV is common among users of public health care facilities. Expanded routine testing for HIV infection is needed with attention directed to men and persons who may not recognize that they are at risk for contracting HIV infection. C1 Baylor Coll Med, Dept Family & Community Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Houston Ctr Qual Care & Utilizat Studies, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, Houston, TX USA. RP Giordano, TP (reprint author), Baylor Coll Med, Dept Family & Community Med, Houston, TX 77030 USA. EM tpg@bcm.tmc.edu FU NIMH NIH HHS [K23MH067505]; PHS HHS [T32HP10031] NR 36 TC 25 Z9 25 U1 2 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD MAR PY 2007 VL 21 IS 3 BP 195 EP 204 DI 10.1089/apc.2006.0097 PG 10 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 156LX UT WOS:000245651100006 PM 17428187 ER PT J AU Williams, EC Horton, NJ Samet, JH Saitz, R AF Williams, Emily C. Horton, Nicholas J. Samet, Jeffrey H. Saitz, Richard TI Do brief measures of readiness to change predict alcohol consumption and consequences in primary care patients with unhealthy alcohol use? SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med DE alcohol; alcohol use; readiness to change ID BEHAVIORAL-COUNSELING INTERVENTIONS; CHANGE QUESTIONNAIRE; EXCESSIVE DRINKERS; SMOKING-CESSATION; SELF-EFFICACY; CAGE; METAANALYSIS; VALIDATION; DRINKING; SAMPLE AB Background: Assessing readiness to change is recommended as part of brief interventions for patients with unhealthy alcohol use. However, the utility and predictive validity of readiness measures have not been well established. Methods: In a prospective cohort study, we assessed primary care patients with unhealthy alcohol use (past-month drinking of risky amounts, or any amount and an affirmative response to CAGE alcohol screening questionnaire) and reassessed them 6 months later. At study entry, we assessed readiness to change using 1 multi-item measure of stage of change, and 5 single-item measures (readiness per se, importance of changing, confidence in ability to change, intention to cut down, intention to abstain). Outcomes included alcohol consumption and alcohol-related consequences. Multivariable regression models were fit for each measure of readiness and each outcome. Results: Of 312 patients with unhealthy alcohol use, 228 (73%) were assessed at study entry and 6 months later and had complete data. Among readiness measures, only confidence and intention to abstain (1 point changes on single-item measures) were associated with consumption 6 months later: less heavy episodic drinking [adjusted odds ratio (AOR) 0.88, 95% CI 0.80-0.98 and AOR 0.79, 0.64-0.98, respectively], and less drinking of risky amounts (AOR 0.89, 0.79-1.00 and AOR 0.78, 0.62-0.98, respectively). Intention to abstain was also associated with more abstinence (AOR 1.43, 1.09-1.88). Single-item measures of readiness, importance, and intention to cut down were significantly associated with higher odds of alcohol consequences. Greater confidence (single item) was associated with a lower odds of any consequences (AOR 0.88, 0.79-0.98). Conclusions: Greater readiness, as measured by several brief assessments, was associated with more consequences and was not predictive of consumption. However, assessing confidence in the ability to change one's alcohol use may have a role in predicting subsequent decreases in both consumption and consequences in primary care patients. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98101 USA. VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98101 USA. Univ Washington, Dept Med, Grad Sch Publ Hlth, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Grad Sch Publ Hlth, Seattle, WA 98195 USA. Smith Coll, Dept Math & Stat, Northampton, MA 01063 USA. Boston Univ, Sch Med, Clin Addict Res & Educ Unit, Sect Gen Internal Med,Dept Med, Boston, MA 02118 USA. Med Ctr, Boston, MA USA. Boston Univ, Sch Publ Hlth, Youth Alcohol Prevent Ctr, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA. RP Williams, EC (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM emwilli@u.washington.edu RI Horton, Nicholas/A-2493-2008; OI Samet, Jeffrey/0000-0002-0897-3400; Horton, Nicholas/0000-0003-3332-4311; /0000-0002-2535-1427 NR 66 TC 34 Z9 34 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAR PY 2007 VL 31 IS 3 BP 428 EP 435 DI 10.1111/j.1530-0277.2006.00324.x PG 8 WC Substance Abuse SC Substance Abuse GA 134QE UT WOS:000244097900009 PM 17295727 ER PT J AU Au, DH Kivlahan, DR Bryson, CL Blough, D Bradley, KA AF Au, David H. Kivlahan, Daniel R. Bryson, Chris L. Blough, David Bradley, Katharine A. TI Alcohol screening scores and risk of hospitalizations for GI conditions in men SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcoholism; alcohol screening; epidemiology; hemorrhage; pancreatitis; hepatitis ID PRIMARY-CARE PATIENTS; BEHAVIORAL-COUNSELING INTERVENTIONS; IDENTIFICATION TEST AUDIT; PROBLEM DRINKING; USE DISORDERS; GENERAL-POPULATION; LIVER-DISEASE; HEALTH-STATUS; SELF-REPORTS; CONSUMPTION AB Background: Alcohol misuse is a common cause of liver disease, upper gastrointestinal (GI) bleeding, and pancreatitis, but it is not known whether alcohol screening questionnaires can identify patients at increased risk for hospitalizations due to these conditions. Objective: To evaluate the association of alcohol screening scores with the risk of subsequent hospitalization for alcohol-related GI conditions. Design: Retrospective cohort study. Participants: Male general medicine outpatients from 7 Veterans Affairs (VA) medical centers who returned mailed questionnaires. Measurements: The CAGE questionnaire (0-4 points) and the Alcohol Use Disorders Identification Test-Consumption questions (AUDIT-C; 0-12 points) were included on mailed surveys. The main outcome, "GI hospitalization," was a primary VA or Medicare discharge diagnosis indicating liver disease, upper GI bleeding, or pancreatitis. Results: Among 31,311 patients followed, a median of 3.75 years, patients with CAGE scores >= 2 points or AUDIT-C scores >= 6 points were at a significantly increased risk for GI hospitalizations. Adjusted hazard ratios (HRadj) ranged from 1.6 (95% CI 1.2-2.0) for CAGE score 2, to 1.7 (1.4-2.2) for CAGE 4, and from 1.4 (1.01-2.0) for AUDIT-C scores from 6 to 7, to 2.7 (1.9-3.8) for AUDIT-C scores from 10 to 12. Secondary analyses demonstrated that the association was the strongest among patients less than 50 years of age who reported drinking in the past year. Conclusions: Brief alcohol screening questionnaires predict subsequent hospitalizations for alcohol-related GI conditions. C1 Ctr Excellence Subst Abuse Treatment & Educ, VA Puget Sound Hlth Care Syst, Seattle, WA 98101 USA. Hlth Serv Res & Dev, Seattle, WA USA. Primary & Specialty Med Care Serv, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Pharm, Seattle, WA 98195 USA. RP Bradley, KA (reprint author), Ctr Excellence Subst Abuse Treatment & Educ, VA Puget Sound Hlth Care Syst, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM willi@u.washington.edu FU NIAAA NIH HHS [K23 AA00313] NR 56 TC 39 Z9 39 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAR PY 2007 VL 31 IS 3 BP 443 EP 451 DI 10.1111/j.1530-0277.2006.00325.x PG 9 WC Substance Abuse SC Substance Abuse GA 134QE UT WOS:000244097900011 PM 17295729 ER PT J AU Butler, J Shapiro, M Reiber, J Sheth, T Ferencik, M Kurtz, EG Nichols, J Pena, A Cury, RC Brady, TJ Hoffmann, U AF Butler, Javed Shapiro, Michael Reiber, Johannes Sheth, Tej Ferencik, Maros Kurtz, Emily G. Nichols, John Pena, Antonio Cury, Ricardo C. Brady, Thomas J. Hoffmann, Udo TI Extent and distribution of coronary artery disease: A comparative study of invasive versus noninvasive angiography with computed angiography SO AMERICAN HEART JOURNAL LA English DT Article ID INTRAVASCULAR ULTRASOUND; ATHEROSCLEROTIC PLAQUE; MYOCARDIAL-INFARCTION; RISK PREDICTION; STABLE ANGINA; HEART-DISEASE; TOMOGRAPHY; LESIONS; INTERVENTION; PROGRESSION AB Background The extent and nature of overall coronary artery disease (CAD), defined as the cumulative stenotic and nonstenotic, calcified and noncalcified atherosclerosis burden, are underestimated by invasive coronary angiography (ICA) and more accurately quantified with intravascular ultrasound. Multidetector row computed tomography (MDCT) is inferior to intravascular ultrasound but may constitute an attractive noninvasive alternative to assess overall CAD burden. Methods To compare ICA with MDCT for detection of CAD (defined as luminal narrowing of any degree or calcification by ICA and any atherosclerotic plaque detection by MDCT using the 17-segment model), we studied 37 patients (age, 63 11 years) who underwent both tests. Results A total of 508 of 586 (87%) segments were assessable, and CAD was detected in 121 of 508 (24%) segments by ICA versus 338 of 508 (67%) by MDCT (P <.01). Of the 121 segments positive for CAD by ICA, MDCT detected plaques in 117 segments (97%). In the 387 of 508 (76%) segments that were free of CAD by ICA, MDCT detected CAD in 221 (57%) segments. Overall, ICA detected CAD in only 20%, 48%, and 46% of segments with noncalcified, calcified, and mixed plaques, respectively, seen by MDCT (P =.01). Of the 221 segments negative for CAD by ICA, 119 (54%) were positively remodeled on MDCT. Overall correlation between ICA and MDCT for detection of CAD was poor (kappa =0.25). Conclusions Invasive coronary angiography and MDCT differ significantly in estimating the presence and nature of CAD. Multidetector row computed tomography may provide an attractive noninvasive alternative to ICA to assess the effects of medical therapy. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, Cambridge, MA 02138 USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, 165 Cambridge St,4th Floor,Suite 400, Boston, MA 02114 USA. EM uhoffman@partners.org NR 38 TC 30 Z9 30 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2007 VL 153 IS 3 BP 378 EP 384 DI 10.1016/j.ahj.2006.11.022 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 143ZF UT WOS:000244764200007 PM 17307416 ER PT J AU Rieber, J Jung, P Koenig, A Schiele, T Shapiro, M Hoffmann, U Klauss, V AF Rieber, Johannes Jung, Philip Koenig, Andreas Schiele, Thomas Shapiro, Michael Hoffmann, Udo Klauss, Volker TI Five-year follow-up in patients after therapy stratification based on intracoronary pressure measurement SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-ARTERY-DISEASE; FRACTIONAL FLOW RESERVE; DRUG-ELUTING STENTS; ACUTE MYOCARDIAL-INFARCTION; LONG-TERM SAFETY; MEDICAL THERAPY; RANDOMIZED-TRIAL; INTRAVASCULAR ULTRASOUND; FUNCTIONAL SEVERITY; BALLOON ANGIOPLASTY AB Background Invasive coronary angiography (ICA) alone fails to accurately select patients with intermediate stenoses who should be treated by percutaneous coronary intervention (PC]). Previous studies have demonstrated the usefulness of fractional flow reserve (FFR) for identifying patients in whom deferring an intended PC] would be more beneficial than performing the planned procedure. The long-term safety of FFR-based therapy stratification, however, remains unknown. Therefore, the aim of this study was to retrospectively evaluate the long-term safety of an FFR-based therapy stratification in patients with intermediate coronary lesions detected by ICA. Methods We included 56 patients presenting with a 50% to 75% angiographic stenosis by visual assessment on ICA, with negative, inconclusive, or no stress test, and in whom the intended PCI was deferred based on the result of the FFR measurement (ie, FFR >= 0.75). The occurrence of major adverse cardiac events during a 5-year follow-up period was recorded. Results A complete 5-year follow-up was available in all patients. Mean follow-up was 1868 +/- 380 days. During follow-up, 16 events (1 cardiac death, 4 noncardiac deaths, 11 revascularization procedures) occurred. The combined rate of cardiac death and nonfatal myocardial infarction was 1.8% over 5 years. Nine PCI procedures (5 target vessel, 4 nontarget vessel) were performed during follow-up based on objective signs of ischemia. The angina status was not different between inclusion and the 5-year follow-up. Conclusion Deferring PCI in patients without critical reduction in FFR may be a safe option during long-term follow-up. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Cambridge, MA 02138 USA. Univ Munich, Dept Cardiol, Med Poliklin, Munich, Germany. RP Rieber, J (reprint author), Massachusetts Gen Hosp, Dept Radiol, 165 Cambridge St, Boston, MA 02114 USA. EM j.r@lmu.de NR 41 TC 12 Z9 14 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2007 VL 153 IS 3 BP 403 EP 409 DI 10.1016/j.ahj.2006.11.013 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 143ZF UT WOS:000244764200011 PM 17307420 ER PT J AU Kressin, NR Glickman, ME Peterson, ED Whittle, J Orner, MB Petersen, LA AF Kressin, Nancy R. Glickman, Mark E. Peterson, Eric D. Whittle, Jeff Orner, Michelle B. Petersen, Laura A. TI Functional status outcomes among white and African-American cardiac patients in an equal access system SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-ARTERY BYPASS; HEALTH-CARE-SYSTEM; QUALITY-OF-LIFE; RACIAL-DIFFERENCES; VETERANS-AFFAIRS; DISEASE; REVASCULARIZATION; ANGIOGRAPHY; DISPARITIES; SURGERY AB Background Racial disparities exist in invasive cardiac procedure use and, sometimes, in subsequent functional status outcomes. We explored whether racial differences in functional outcomes occur in settings where differences in access and treatment are minimized. Methods We conducted a prospective observational cohort study of 1022 white and African-American cardiac patients with positive nuclear imaging studies in 5 VA hospitals. Patients' functional status was assessed at baseline, 6, and 12 months later using the Seattle Angina Questionnaire and the SF-12, controlling for, treatment received, clinical, sociodemographic, and psychological, characteristics. Results There were no significant baseline effects of race on functional status, after adjusting for sociodemographics, comorbid conditions, maximal medical therapy, severity of ischemia on nuclear imaging study, personal attitudes, and beliefs. Although there were no race differences in percutaneous transluminal coronary angioplasty use, there was a trend of African Americans being less likely to undergo coronary artery bypass graft, after 6 months (1.4% vs 6.5%) and I year (1.9 vs 6.9%). After adjustment, the decline in the SF 12 Physical Component Summary from baseline to 6 months was, on average, 2.4 points less for African Americans than for whites, and at 12 months, Anginal Stability improved 8.4 points more for African Americans. The relative strength and direction of both findings persisted after removing covariates that might be confounded with race, and African Americans decreased less than whites on Physical Limitations, and improved more on Treatment Satisfaction, Anginal Frequency, and Disease Perceptions. Conclusions in a setting where differences in access are minimized, so are racial differences in functional status outcomes. C1 VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02215 USA. Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC 27706 USA. Zablocki Vet Adm Med Ctr, Primary Care Div, Milwaukee, WI 53295 USA. Med Coll Wisconsin, Dept Med, Div Gen Internal Med, Milwaukee, WI 53226 USA. Houston VA Med Ctr, Div Hlth Policy & Qual, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Baylor Coll Med, Sect Hlth Serv Res, Dept Med, Houston, TX 77030 USA. RP Kressin, NR (reprint author), VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, 200 Springs Rd,Bldg 70,152, Bedford, MA 01730 USA. EM nkressin@bu.edu OI Kressin, Nancy/0000-0003-2767-4286; Glickman, Mark/0000-0003-3993-2801 NR 39 TC 10 Z9 10 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2007 VL 153 IS 3 BP 418 EP 425 DI 10.1016/j.ahj.2006.11.019 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 143ZF UT WOS:000244764200013 PM 17307422 ER PT J AU Camargo, CA Rifas-Shiman, SL Litonjua, AA Rich-Edwards, JW Weiss, ST Gold, DR Kleinman, K Gillman, MW AF Camargo, Carlos A., Jr. Rifas-Shiman, Sheryl L. Litonjua, Augusto A. Rich-Edwards, Janet W. Weiss, Scott T. Gold, Diane R. Kleinman, Ken Gillman, Matthew W. TI Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE vitamin D; pregnancy; dietary intake; childhood wheeze; asthma ID REGULATORY T-CELLS; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; D-RECEPTOR GENE; 25-HYDROXYVITAMIN-D LEVELS; PULMONARY-FUNCTION; HYPOVITAMINOSIS-D; D INSUFFICIENCY; DIETARY-INTAKE; BIRTH COHORT AB Background: Vitamin D deficiency and asthma are common at higher latitudes. Although vitamin D has important immunologic effects, its relation with asthma is unknown. Objective: We hypothesized that a higher maternal intake of vitamin D during pregnancy is associated with a lower risk of recurrent wheeze in children at 3 y of age. Design: The participants were 1194 mother-child pairs in Project Viva-a prospective prebirth cohort study in Massachusetts. We assessed the maternal intake of vitamin D during pregnancy from a validated food-frequency questionnaire. The primary outcome was recurrent wheeze, ie, a positive asthma predictive index ( >= 2 wheezing attacks among children with a personal diagnosis of eczema or a parental history of asthma). Results: The mean (+/- SD) total vitamin D intake during pregnancy was 548 167 IU/d. By age 3 y, 186 children (16%) had recurrent wheeze. Compared with mothers in the lowest quartile of daily intake (median: 356 IU), those in the highest quartile (724 IU) had a lower risk of having a child with recurrent wheeze [odds ratio (OR): 0.39; 95% CI: 0.25, 0.62; P for trend < 0.001]. A 100-IU increase in vitamin D intake was associated with lower risk (OR: 0.81; 95% CI: 0.74, 0.89), regardless of whether vitamin D was from the diet (OR: 0.81; 95% CI: 0.69, 0.96) or supplements (OR: 0.82; 95% CI: 0.73, 0.92). Adjustment for 12 potential confounders, including maternal intake of other dietary factors, did not change the results. Conclusion: In the northeastern United States, a higher maternal intake of vitamin D during pregnancy may decrease the risk of recurrent wheeze in early childhood. C1 Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Sch Med,Ctr D Receptor Activat Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Univ, Pilgrim Hlth Care, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Dept Med,Brigham & Womens Hosp, Boston, MA USA. RP Camargo, CA (reprint author), Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Sch Med,Ctr D Receptor Activat Res, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org RI Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 FU NHLBI NIH HHS [HL64925, HL68041, HL75504, K24 HL068041, R01 HL064925, R01 HL075504]; NICHD NIH HHS [R01 HD034568, HD34568, R37 HD034568]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-11] NR 55 TC 370 Z9 383 U1 9 U2 41 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAR PY 2007 VL 85 IS 3 BP 788 EP 795 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 146ES UT WOS:000244917900019 PM 17344501 ER PT J AU Bresnahan, S Eastwood, JA AF Bresnahan, Sandra Eastwood, Jo-Ann TI Confounding T-wave inversion SO AMERICAN JOURNAL OF CRITICAL CARE LA English DT Article ID NONCARDIAC SURGERY; COMMITTEE; MORTALITY; UPDATE AB In the medical community, the nonspecific finding of T-wave inversion warrants further investigation. An electrocardiogram may be an essential component of a surgical risk evaluation. Patients who show a T-wave inversion on a preoperative electrocardiogram require further investigation to distinguish between pathological and benign T-wave inversion. Optimizing patients' safety during the perioperative experience is the ultimate clinical outcome. C1 [Eastwood, Jo-Ann] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. [Bresnahan, Sandra] Univ Calif Los Angeles, Anesthesia Preop Clin, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Bresnahan, S (reprint author), Mail Code 111,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM sandra.bresnahan@va.gov NR 14 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CRITICAL CARE NURSES PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 1062-3264 J9 AM J CRIT CARE JI Am. J. Crit. Care PD MAR PY 2007 VL 16 IS 2 BP 137 EP 140 PG 4 WC Critical Care Medicine; Nursing SC General & Internal Medicine; Nursing GA 271SS UT WOS:000253809600008 PM 17322013 ER PT J AU Thakkar, K Gilger, MA Shulman, RJ El Serag, HB AF Thakkar, Kalpesh Gilger, Mark A. Shulman, Robert J. El Serag, Hashem B. TI EGD in children with abdominal pain: A systematic review SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID HELICOBACTER-PYLORI INFECTION; UPPER GASTROINTESTINAL ENDOSCOPY; FIBEROPTIC ENDOSCOPY; ADOLESCENTS; CHILDHOOD; INFANTS; DISEASE; REFLUX; DYSPEPSIA; DIAGNOSIS AB BACKGROUND: We performed a systematic review to examine the diagnostic yield (endoscopic and histologic) of esophagogastroduodenoscopy (EGD) for the evaluation of abdominal pain of unclear etiology in children. We also examined the effect of EGD on change in treatment, quality of life, change in abdominal pain, and cost-effectiveness. METHODS: All full-length articles published in English during 1966-2005 were included if: (a) participants had abdominal pain without known underlying gastrointestinal disease, (b) participants underwent EGD primarily for the evaluation of abdominal pain, (c) findings of the EGD were reported, (d) participants were under 18 yr, and (e) sample size greater than 50. RESULTS: Eighteen articles examining 1,871 patients fulfilled the inclusion and exclusion criteria. All were observational and most (13) were prospective. Only three studies were performed in the United States and of those two were prospective. The largest study examined about 400 procedures and 13 studies examined less than 100 procedures. One case of inflammatory bowel disease and 67 duodenal or gastric ulcers were reported, thus diagnostic yield was achieved in 3.6% of cases. The prevalence of nonspecific histological gastrointestinal inflammatory lesions varied between 23% and 93%. Six articles attempted to correlate endoscopic or histologic findings with treatment management decisions. No articles attempted to describe quality of life or cost-effectiveness. None of the studies analyzed the association of alarm symptoms or signs to diagnostic yield. CONCLUSIONS: The diagnostic yield of EGD in children with unclear abdominal pain is low; however, existing studies are inadequate. The effect of EGD on change in treatment, quality of life, improvement of abdominal pain, and cost-effectiveness is unknown. The predictors of significant findings are unclear. Our findings suggest that a large multicenter study examining clinical factors, biopsy reports, and addressing patient outcomes is needed to further clarify the value of EGD in children with abdominal pain. C1 Baylor Coll Med, Sect Pediat Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA. Baylor Coll Med, USDA ARS, Childrens Nutr Res Ctr, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX USA. Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Thakkar, K (reprint author), 6621 Fannin St CCC 1010, Houston, TX 77030 USA. NR 49 TC 14 Z9 14 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAR PY 2007 VL 102 IS 3 BP 654 EP 661 DI 10.1111/j.1572-0241.2007.01051.x PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 140PF UT WOS:000244517000029 PM 17222318 ER PT J AU Ahmed, A Lefante, CM Alam, N AF Ahmed, Ali Lefante, Christina M. Alam, Nazmul TI Depression and nursing home admission among hospitalized older adults with coronary artery disease: A propensity score analysis SO AMERICAN JOURNAL OF GERIATRIC CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; HEART-FAILURE; MAJOR DEPRESSION; ELDERLY PATIENTS; COMMON OUTCOMES; RELATIVE RISK; MORTALITY; HEALTH; PREDICTORS; SYMPTOMS AB Admission to a nursing home is considered a Poor outcome for community-dwelling older adults. The objective of this study was to determine whether depression increased the risk of nursing home admission. Using the National Hospital Discharge Survey 2001-2003 datasets, the authors identified 28,172 community-dwelling older adults, 65 years and older, discharged alive with a primary discharge diagnosis of coronary artery disease. The objective of this study was to determine the association between depression and subsequent nursing home admissions in these patients. Propensity scores for depression, calculated for each patient using a multivariable logistic. regression model, were used to match 686 depressed patients with 2058 nondepressed patients who had similar propensity scores. Logistic regression analyses were used to determine the association between depression and nursing home admission. Patients had a mean age SD of 77 +/- 8 years, and 61% were women. Compared with 9% of nondepressed patients, 13% of depressed patients were admitted to nursing homes (relative risk, 1.42; 95% confidence interval, 1.12-1.78). When adjusted for various demographic, clinical, and care-related covariates, the association became somewhat stronger (adjusted relative risk, 1.55; 95% confidence interval, 1.21-1.99). In ambulatory older adults hospitalized with coronary artery disease, a secondary diagnosis of depression was associated with a significantly increased risk of nursing home admission. C1 Univ Alabama, Div Gerontol & Geriatr Med, Sch Med, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. Univ Alabama, Ctr Heart Failure Res, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Sect Geriatr, Birmingham, AL USA. Louisiana State Univ, Hlth Sci Ctr, New Orleans Sch Publ Hlth, Dept Epidemiol, New Orleans, LA USA. RP Ahmed, A (reprint author), Univ Alabama, Div Gerontol & Geriatr Med, Sch Med, Dept Med, 1530 3rd Ave S,CH-19,Suite 219, Birmingham, AL 35294 USA. EM aahmed@uab.edu RI Ahmed, Ali/A-2934-2008 OI Ahmed, Ali/0000-0002-6832-6424 FU NHLBI NIH HHS [P50-HL077100, 1-R01-HL085561-01, R01 HL085561-01, R01 HL085561, P50 HL077100]; NIA NIH HHS [K23 AG019211, K23 AG019211-01A2, 1-K23-AG19211-04, K23 AG019211-04, 1-K23-AG19211-01] NR 44 TC 5 Z9 5 U1 0 U2 0 PU LE JACQ LTD PI DARIEN PA 3 PARKLANDS DRIVE, DARIEN, CT 06820 USA SN 1076-7460 J9 AM J GERIATR CARDIOL JI Am. J. Geriatr. Cardiol. PD MAR-APR PY 2007 VL 16 IS 2 BP 76 EP 83 DI 10.1111/j.1076-7460.2007.05519.x PG 8 WC Cardiac & Cardiovascular Systems; Geriatrics & Gerontology SC Cardiovascular System & Cardiology; Geriatrics & Gerontology GA 144WE UT WOS:000244826300003 PM 17380615 ER PT J AU Kaphingst, KA Lobb, R Fay, ME Hunt, MK Suarez, EG Fletcher, RH Emmons, KM AF Kaphingst, Kimberly A. Lobb, Rebecca Fay, Martha E. Hunt, Mary K. Suarez, Elizabeth Gonzalez Fletcher, Robert H. Emmons, Karen M. TI Impact of intervention dose on cancer-related health behaviors among working-class, multiethnic, community health center patients SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE intervention dose; process evaluation; multiethnic patients; health centers ID PREVENTION; POPULATIONS; DIRECTIONS AB Purpose. To examine the relationship between intervention dose and health behavior change in Healthy Directions-Health Centers, an intervention designed to reduce cancer risk factors. Design. Analysis of intervention condition participant data from a randomized controlled trial. Setting. Community health centers in Massachusetts. Subjects. Patients residing in low-income, working-class, multiethnic neighborhoods. Intervention. Components were clinician endorsement, in-person counseling session and four telephone counseling sessions with a trained health advisor, and social-contextual tailored materials. Measures. Intervention dose was number of six possible intervention components completed by each participant. Changes in fruit and vegetable consumption, red meat consumption, physical activity, and multivitamin intake between baseline (n = 1088) and 8-month follow-up (n = 967; 89% of baseline sample) were determined. Analysis. Bivariate and multivariate associations between intervention dose and change in health behaviors were examined. Results. In multivaiiate analysis, the association between intervention dose and increase in multivitamin intake approached significance (p < .07). Seventy Percent of Participants completed all intervention activities. In bivariate analysis, completion of four telephone counseling calls was associated with decrease in red meat consumption (p < .05). Conclusion. These findings indicate that future studies should examine the number, content, and length of contacts needed for behavior change. The results also suggest that health centers are a channel for reaching diverse populations, as shown by the high Level of intervention implementation. C1 NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. Harvard Univ, Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kaphingst, KA (reprint author), NHGRI, Social & Behav Res Branch, 2 Ctr Dr,MSC 0249,Bldg 2,Room 4E30, Bethesda, MD 20892 USA. EM kkaphing@mail.nih.gov OI Lobb, Rebecca/0000-0003-3503-0675 FU NCI NIH HHS [5 P01 CA75308] NR 9 TC 1 Z9 1 U1 2 U2 5 PU AMER J HEALTH PROMOTION INC PI KEEGO HARBOR PA 1660 CASS LAKE RD, STE 104, KEEGO HARBOR, MI 48320 USA SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD MAR-APR PY 2007 VL 21 IS 4 BP 262 EP 266 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 150QO UT WOS:000245231500007 PM 17375492 ER PT J AU Simpson, L Dougherty, D Krause, D Ku, CM Perrin, JM AF Simpson, Lisa Dougherty, Denise Krause, David Ku, Cindy M. Perrin, James M. TI Measuring children's health care quality SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article ID MEDICAID C1 Cincinnati Childrens Hosp Med Ctr, Child Policy Res Ctr, Cincinnati, OH 45229 USA. Natl Initiat Childrens Healthcare Qual, Child Hlth Policy, Cincinnati, OH USA. Agcy Healthcare Res & Qual, Child Hlth & Qual Improvement, Rockville, MD USA. Amer Canc Soc, Florida Div, Tampa, FL USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Child & Adolescent Hlth Policy, Boston, MA USA. RP Simpson, L (reprint author), Cincinnati Childrens Hosp Med Ctr, Child Policy Res Ctr, 333 Burnet Ave, Cincinnati, OH 45229 USA. EM lisa.simpson@cchmc.org NR 15 TC 9 Z9 9 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1062-8606 J9 AM J MED QUAL JI Am. J. Med. Qual. PD MAR-APR PY 2007 VL 22 IS 2 BP 80 EP 84 DI 10.1177/1062860606298549 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 147TS UT WOS:000245026000002 PM 17395962 ER PT J AU Martin, BK Breitner, JCS Evans, D Lyketsos, CG Meinert, CL AF Martin, Barbara K. Breitner, John C. S. Evans, Denis Lyketsos, Constantine G. Meinert, Curtis L. TI The trialist, meta-analyst, and journal editor: Lessons from ADAPT SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Rush Univ, Med Ctr, Dept Internal Med, Chicago, IL 60612 USA. Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Martin, BK (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAR PY 2007 VL 120 IS 3 BP 192 EP 193 DI 10.1016/j.amjmed.2006.12.010 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 143WF UT WOS:000244756400002 PM 17349436 ER PT J AU Rosman, AS Korsten, MA AF Rosman, Alan S. Korsten, Mark A. TI Meta-analysis comparing CT colonography, air contrast barium enema, and colonoscopy SO AMERICAN JOURNAL OF MEDICINE LA English DT Review DE CT colonography; barium enema; colonoscopy; summary receiver operating characteristic curve; meta-analysis ID COMPUTED-TOMOGRAPHIC COLONOGRAPHY; VIRTUAL COLONOSCOPY; COLORECTAL-CANCER; CONVENTIONAL COLONOSCOPY; DIAGNOSTIC-TEST; COLON-CANCER; PATIENT ACCEPTANCE; AVERAGE-RISK; POLYPS; NEOPLASIA AB INTRODUCTION: Published studies have reported a wide range of sensitivities and specificities for computed tomographic (CT) colonography for polyp detection, generating controversy regarding its diagnostic accuracy. METHODS: A meta-analysis of published studies comparing the accuracies of CT colonography and colonoscopy for polyp detection was performed. The pooled per-patient sensitivities and specificities were calculated at various thresholds for polyp size. Summary receiver operating characteristic (sROC) curves were also constructed. RESULTS: Thirty studies were included in the meta-analysis of CT colonography. The pooled per-patient sensitivity of CT colonography was higher for polyps greater than 10 mm (0.82, 95% confidence interval [CI], 0.76- 0.88) compared with polyps 6 to 10 mm (0.63, 95% CI, 0.52- 0.75) and polyps 0 to 5 mm (0.56, 95% CI, 0.42- 0.70). Similarly, the exact area under the sROC curve (area +/- standard error) was higher using a threshold greater than 10 mm (0.898 +/- 0.063) compared with thresholds of greater than 5 mm and any size (0.884 +/- 0.033 and 0.822 +/- 0.059, respectively). There were no significant differences in the diagnostic characteristics of 2-dimensional versus 3-dimensional CT colonography. At a threshold greater than 5 mm, the exact area under the sROC curve was significantly higher for endoscopic colonoscopy compared with CT colonography (0.998 +/- 0.006 vs 0.884 +/- 0.033, P <.005). CONCLUSIONS: CT colonography has a reasonable sensitivity and specificity for detecting large polyps but was less accurate than endoscopic colonoscopy for smaller polyps. Thus, CT colonography may not be a reasonable alternative in situations in which a small polyp may be clinically relevant. (c) 2007 Elsevier Inc. All rights reserved. C1 James J Peters VA Med Ctr, Gastroenterol Sect, Bronx, NY 10468 USA. James J Peters VA Med Ctr, Program Med, Bronx, NY 10468 USA. Mt Sinai Sch Med, New York, NY USA. RP Rosman, AS (reprint author), James J Peters VA Med Ctr, Gastroenterol Sect, Suite F,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Alan.Rosman@Med.VA.Gov NR 74 TC 68 Z9 71 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAR PY 2007 VL 120 IS 3 BP 203 EP U4 DI 10.1016/j.amjmed.2006.05.061 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 143WF UT WOS:000244756400004 PM 17349438 ER PT J AU Parikh, NI Pencina, MJ Wang, TJ Lanier, KJ Fox, CS D'Agostino, RB Vasan, RS AF Parikh, Nisha I. Pencina, Michael J. Wang, Thomas J. Lanier, Katherine J. Fox, Caroline S. D'Agostino, Ralph B. Vasan, Ramachandran S. TI Increasing trends in incidence of overweight and obesity over 5 decades SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE body mass index; obesity; overweight; trends; epidemiology ID BODY-MASS INDEX; UNITED-STATES; US ADULTS; PHYSICAL-ACTIVITY; SECULAR TRENDS; HEART-DISEASE; WEIGHT CHANGE; RISK-FACTORS; PREVALENCE; FRAMINGHAM AB PURPOSE: We evaluated trends in the incidence of overweight and obesity over the past 50 years. METHODS: We evaluated trends in the incidence of overweight (25 <= body mass index [BMI] < 30 kg/m(2)), obesity (BMI >= 30 kg/m(2)) and stage 2 obesity (BMI >= 35 kg/m(2)) from 1950 to 2000 in Framingham Study participants (n = 6798, 54% women). Individuals aged 40-55 years who attended 2 examinations 8 years apart in each decade were eligible. RESULTS: The incidences of overweight, obesity, and stage 2 obesity increased across the decades in both sexes (P for trend <.001). For men, the incidence of overweight rose from 21.8% (95% confidence interval [CI], 17.6- 26.5) in the 1950s to 35.2% (95% CI, 28.6- 42.5) in the 1990s; of obesity from 5.8% (95% CI, 4.4-7.6) to 14.8% (95% CI, 12.2-17.9); and of stage 2 obesity from 0.2% (95% CI, 0.1-0.9) to 5.4% (95% CI, 4.0-7.2). For women, incidence rates of overweight increased from 15.0% (95% CI, 12.3-18.1) to 33.1% (95% CI, 29.0- 37.4); of obesity from 3.9% (95% CI, 2.9- 5.3) to 14% (95% CI, 11.6- 16.7); and of stage 2 obesity from 1.7% (95% CI, 1.1- 2.6) to 4.4% (95% CI, 3.2- 6.0). Overall, incidence rates of overweight increased 2-fold and that of obesity more than 3-fold over 5 decades, findings that remained robust upon additional adjustment for baseline BMI in each decade. CONCLUSIONS: The incidence of overweight and obesity increased progressively over the last 5 decades, suggesting that the rising trend in prevalence is not a recent phenomenon. (c) 2007 Elsevier Inc. All rights reserved. C1 Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02215 USA. Boston Univ, Sch Med, Cardiol Sect, Boston Med Ctr, Boston, MA 02215 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [N01-HC-25195, 2K24HL04334, K23HL074077] NR 46 TC 94 Z9 97 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAR PY 2007 VL 120 IS 3 BP 242 EP U6 DI 10.1016/j.amjmed.2006.06.004 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 143WF UT WOS:000244756400013 PM 17349447 ER PT J AU Driver, JA Gaziano, JM Gelber, RP Lee, IM Buring, JE Kurth, T AF Driver, Jane A. Gaziano, J. Michael Gelber, Rebecca P. Lee, I-Min Buring, Julie E. Kurth, Tobias TI Development of a risk score for colorectal cancer in men SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE colon cancer; rectal cancer; risk score; risk prediction; behavioral risk factors ID UNITED-STATES; PHYSICIANS HEALTH; BREAST-CANCER; RECTAL-CANCER; INDEX; COLON; PREDICTION; VALIDATION; SMOKING; WEIGHT AB BACKGROUND: Colorectal cancer is a common and preventable disease for which screening rates remain unacceptably low. METHODS: We developed a risk scoring system for the development of colorectal cancer among participants in the Physician's Health Study, a prospective cohort of 21,581 US male physicians who were all free of cancer. Predictors of colorectal cancer were self-reported and identified from the baseline questionnaire. Logistic regression was used to determine the independent predictors of incident colorectal cancer over the follow-up period. Risk scores were created from the sum of the odds ratios of the final predictors and used to divide the cohort into categories of increasing relative risk. RESULTS: During 20 years of follow-up, 381 cases of colon cancer and 104 cases of rectal cancer developed in the cohort. Age, alcohol use, smoking status, and body mass index were independent significant predictors of colorectal cancer. The point scores were used to define 10 risk groups. Those in the highest risk group (9-10 points) had an odds ratio of 15.29 (6.19-37.81) for colorectal cancer compared with those with the lowest risk. We further stratified scores into 3 risk classes. Compared with those at the lowest relative risk, the odds ratio for colorectal cancer was 3.07 (2.46-3.83) in the intermediate risk group and 5.75 (4.44-7.44) in the highest risk group. CONCLUSIONS: We developed a simple scoring system for colorectal cancer that identifies men at increased relative risk on the basis of age and modifiable factors. This tool should be validated in other populations. (c) 2007 Elsevier Inc. All rights reserved. C1 Brigham & Womens Hosp, Div Aging, Boston, MA 02120 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Boston VA Healthcare Syst, Massachusetts Vet Epidemiol Res Informat Ctr, Boston, MA USA. RP Kurth, T (reprint author), Brigham & Womens Hosp, Div Aging, 1620 Tremont St, Boston, MA 02120 USA. EM tkurth@rics.bwh.harvard.edu RI Kurth, Tobias/A-9243-2012 OI Kurth, Tobias/0000-0001-7169-2620 FU NCI NIH HHS [CA 40360, R01 CA097193, CA 34944]; NHLBI NIH HHS [HL-26490, HL-34595] NR 25 TC 61 Z9 62 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAR PY 2007 VL 120 IS 3 BP 257 EP 263 DI 10.1016/j.amjmed.2006.05.055 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 143WF UT WOS:000244756400015 PM 17349449 ER PT J AU Campos, NG Salomon, JA Servoss, JC Nunes, DP Samet, JH Freedberg, KA Goldie, SJ AF Campos, Nicole G. Salomon, Joshua A. Servoss, Julie C. Nunes, David P. Samet, Jeffrey H. Freedberg, Kenneth A. Goldie, Sue J. TI Cost-effectiveness of treatment for hepatitis C in an urban cohort co-infected with HIV SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE hepatitis C virus (HCV); human immunodeficiency virus (HIV); cost-effectiveness; peginterferon-alfa and ribavirin; clinical guidelines; treatment eligibility ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; ALPHA-2A PLUS RIBAVIRIN; LIVER FIBROSIS; INITIAL TREATMENT; PROGRESSION; INTERFERON-ALPHA-2B; COINFECTION; DISEASE; ERA AB PURPOSE: Recent clinical trials have evaluated treatment strategies for chronic infection with hepatitis C virus (HCV) in patients co-infected with human immunodeficiency virus (HIV). Our objective was to use these data to examine the cost-effectiveness of treating HCV in an urban cohort of co-infected patients. METHODS: A computer-based model, together with available published data, was used to estimate lifetime costs ( 2004 US dollars), life expectancy, and incremental cost per year of life saved (YLS) associated with 3 treatment strategies: (1) interferon-alfa and ribavirin; (2) pegyllated interferon-alfa; and (3) pegylated interferon-alfa and ribavirin. The target population included treatment-eligible patients, based on an actual urban cohort of HIV-HCV co-infected subjects, with a mean age of 44 years, of whom 66% had genotype 1 HCV, 16% had cirrhosis, and 98% had CD4 cell counts > 200 cells/mm(3). RESULTS: Pegylated interferon- alfa and ribavirin was consistently more effective and cost-effective than other treatment strategies, particularly in patients with non-genotype 1 HCV. For patients with CD4 counts between 200 and 500 cells/mm(3), survival benefits ranged from 5 to 11 months, and incremental costeffectiveness ratios were consistently less than $75,000 per YLS for men and women of both genotypes. Due to better treatment efficacy in non-genotype 1 HCV patients, this group experienced greater life expectancy gains and lower incremental cost-effectiveness ratios. CONCLUSIONS: Combination therapy with pegylated interferon- alfa and ribavirin for HCV in eligible co-infected patients with stable HIV disease provides substantial life-expectancy benefits and appears to be cost-effective. Overcoming barriers to HCV treatment eligibility among urban co-infected patients remains a critical priority. (c) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Program Hlth Decis Sci, Boston, MA 02115 USA. Harvard Univ, Program Hlth Policy, Cambridge, MA 02138 USA. Harvard Univ, Initiat Global Hlth, Dept Populat & Int Hlth, Sch Publ Hlth, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA. Boston Univ, Sch Med, Boston Med Ctr, Dept Med,Sect Gen Internal Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Gastroenterol Sect, Boston, MA 02118 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Harvard Ctr AIDS Res, Boston, MA 02115 USA. RP Campos, NG (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Program Hlth Decis Sci, 718 Huntington Ave,2nd Floor, Boston, MA 02115 USA. EM gastin@post.harvard.edu RI Salomon, Joshua/D-3898-2009; OI Salomon, Joshua/0000-0003-3929-5515; Samet, Jeffrey/0000-0002-0897-3400 FU NIAAA NIH HHS [R01-AA13216, R01 AA013216, R01 AA013216-05]; NIAID NIH HHS [K24 AI062476, K24 AI062476-03] NR 38 TC 16 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAR PY 2007 VL 120 IS 3 BP 272 EP 279 DI 10.1016/j.amjmed.2006.06.036 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 143WF UT WOS:000244756400017 PM 17349451 ER PT J AU Spanos, GK Wilde, EA Bigler, ED Cleavinger, HB Fearing, MA Levin, HS Li, X Hunter, JV AF Spanos, G. K. Wilde, E. A. Bigler, E. D. Cleavinger, H. B. Fearing, M. A. Levin, H. S. Li, X. Hunter, J. V. TI Cerebellar atrophy after moderate-to-severe pediatric traumatic brain injury SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID DIFFUSE AXONAL INJURY; PREFRONTAL CORTEX; HEAD-INJURY; CHILDREN; VULNERABILITY; PROJECTIONS; PROTEIN; IMPACT; RAT; MRI AB BACKGROUND AND PURPOSE: Although the cerebellum has not attracted the same degree of attention as cortical areas and the hippocampus in traumatic brain injury (TBI) literature, there is limited structural and functional imaging evidence that the cerebellum is also vulnerable to insult. The cerebellum is emerging as part of a frontocerebellar system that, when disrupted, results in significant cognitive and behavioral consequences, We hypothesized that cerebellar volume would be reduced in children following TBI and wished to examine the relation between the cerebellum and known sites of projection, including the prefrontal cortex, thalamus, and pons. MATERIALS AND METHODS: Quantitative MR imaging was used to measure cerebellar white and gray matter and lesion volumes 1-10 years following TBI in 16 children 9-16 years of age and 16 demographically matched typically developing children 9-16 yeas of age. Cerebellar volumes were also compared with volumetric data from other brain regions to which the cerebellum projects. RESULTS: A significant group difference was found in cerebellar white and gray matter volume, with children in the TBI group consistently exhibiting smaller volumes, Repeating the analysis after excluding children with focal cerebellar lesions revealed that significant group differences still remained for cerebellar white matter (WM). We also found a relation between the cerebellum and projection areas, including the dorsolateral prefrontal cortex, thalamus, and pons in 1 or both groups. CONCLUSION: Our finding of reduced cerebellar WM volume in children with TBI is consistent with evidence from experimental studies suggesting that the cerebellum and its related projection areas are highly vulnerable to fiber degeneration following traumatic insult. C1 Texas Childrens Hosp, Dept Diagnost Imaging, Houston, TX 77030 USA. Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. Brigham Young Univ, Dept Neurosci, Provo, UT 84602 USA. Univ Utah, Dept Radiol, Salt Lake City, UT 84132 USA. Univ Utah, Dept Psychiat, Salt Lake City, UT 84132 USA. Dartmouth Coll Sch Med, Dept Psychiat, W Lebanon, NH USA. Boston VA Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Wilde, EA (reprint author), Baylor Coll Med, Cognit Neurosci Lab, 1790 Dryden Rd,Ste 725, Houston, TX 77030 USA. EM ewilde@bcm.tmc.edu FU NICHD NIH HHS [U19 HD35476]; NINDS NIH HHS [NS-21889] NR 29 TC 40 Z9 40 U1 0 U2 2 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAR PY 2007 VL 28 IS 3 BP 537 EP 542 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 149PW UT WOS:000245160100035 PM 17353332 ER PT J AU Klein, R Deng, YZ Klein, BEK Hyman, L Seddon, J Frank, RN Wallace, RB Hendrix, SL Kuppermann, BD Langer, RD Kuller, L Brunner, R Johnson, KC Thomas, AM Haan, M AF Klein, Ronald Deng, Yingzi Klein, Barbara E. K. Hyman, Leslie Seddon, Johanna Frank, Robert N. Wallace, Robert B. Hendrix, Susan L. Kuppermann, Baruch D. Langer, Robert D. Kuller, Lewis Brunner, Robert Johnson, Karen C. Thomas, Asha M. Haan, Mary TI Cardiovascular disease, its risk factors and treatment, and age-related macular degeneration: Women's health initiative sight exam ancillary study SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID BEAVER-DAM EYE; POOLED FINDINGS; 3 CONTINENTS; STATIN USE; CHOROIDAL NEOVASCULARIZATION; 5-YEAR INCIDENCE; MEDICATION USE; MACULOPATHY; ASSOCIATION; PREVALENCE AB center dot PURPOSE: To examine the association of cardiovascular disease (CVD), CVD risk factors, and CVD treatment with age related macular degeneration (AMD). center dot DESIGN: Observational analysis of a randomized clinical trial. center dot METHODS: SETTINGS: The Women's Health Initiative Sight Examination (WHISE), an ancillary study to the Women's Health Initiative's clinical trial of hormone replacement therapy. STUDY POPULATION: A total of 4,288 women age 63 years and older. OBSERVATION PROCEDURES: Information on CVD and its risk factors were obtained from a standardized questionnaire and examination. MAIN OUTCOME MEASURE: AMD as deter, mined by standardized grading of fundus photographs. center dot RESULTS: Prevalence of any AMD was 21.4% (n = 919). Of those with AMD, 5.8% (n = 53) had signs of exudative AMD (n = 39) or pure geographic atrophy (n = 14), limiting the power to examine associations. Significant associations between late AMD and CVD risk factors were (odds ratio [OR], 95% confidence interval [CI]) older age (1.19, 1.13 to 1.27, P < .0001), more pack years smoked (1.02 per pack,year smoked, 1.003 to 1.03, P = .01), systolic blood pressure (0.84 per 10 mm Hg, 0.71 to 0.995, P = .04), report of taking calcium channel blockers (2.49, 1.21 to 5.12, P = .04), self-reported history of diabetes (2.00, 1.01 to 3.96, P = .05), and greater body mass index (1.05 per 1 kg/m(2), 1.001 to 1.10, P = .05). History of myocardial infarction, stroke, use of statins, or white blood cell count was not associated with AMD. center dot CONCLUSIONS: Results suggest that smoking, use of calcium channel blockers, diabetes, and obesity are risk factors for late AMD in women. However, the association of late AMD with systolic blood pressure and the effects of other CVD risk factors on early AMD need to be further explored. C1 Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI 53726 USA. Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. SUNY Stony Brook, Div Epidemiol, Dept Prevent Med, Stony Brook, NY 11794 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Wayne State Univ, Kresge Eye Inst, Detroit, MI USA. Univ Iowa, Dept Epidemiol, Iowa City, IA USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Hutzel Hosp, Detroit, MI 48201 USA. Univ Calif Irvine, Dept Ophthalmol, Irvine, CA USA. Geisinger Hlth Syst, Outcomes Res Inst, Ctr Hlth Res, Danville, PA USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Nevada, Sch Med, Reno, NV 89557 USA. Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. MedStar Res Inst, Washington, DC USA. RP Klein, R (reprint author), Univ Wisconsin, Dept Ophthalmol & Visual Sci, 610 N Walnut St,4th Floor WARF, Madison, WI 53726 USA. EM kleinr@epi.ophth.wisc.edu FU WHI NIH HHS [N01 WH022110, N01 WH022110-024, N01 WH032113] NR 50 TC 62 Z9 67 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAR PY 2007 VL 143 IS 3 BP 473 EP 483 DI 10.1016/j.ajo.2006.11.058 PG 11 WC Ophthalmology SC Ophthalmology GA 141CZ UT WOS:000244555700013 PM 17317391 ER PT J AU Brockhurst, RJ Sandberg, MA AF Brockhurst, Robert J. Sandberg, Michael A. TI Optical coherence tomography findings in occult macular dystrophy SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID THICKNESS; ACUITY AB PURPOSE: To determine the basis for unexplained visual acuity loss in selected patients. DESIGN: Observational study of patients with unexplained reduced visual acuity. METHODS: We used optical coherence tomography (OCT) to evaluate foveal structure in eight patients. These patients had corrected visual acuities of 20/25 to count fingers in one or both eyes and a normal ocular examination. We recorded foveal cone electroretinograms (ERGs) as an objective measure of foveal function. RESULTS: Seven patients showed reduced foveal thickness associated with thinning of the outer nuclear layer (ONL), and five of these patients also had reduced foveal cone ERGs. One patient had normal tomograms and reduced foveal ERGs. CONCLUSIONS: Unexplained reductions in visual acuity may result from photoreceptor loss or foveal malfunction without photoreceptor loss, which are indicators of occult macular dystrophy. OCT and the foveal cone ERG together appear to be sufficient to identify the basis for visual acuity loss in these patients. C1 Harvard Univ, Berman Gund Lab, Massachusetts Eye & Ear Infirm, Sch Med,Study Retinal Degenerat, Boston, MA 02114 USA. RP Brockhurst, RJ (reprint author), Harvard Univ, Berman Gund Lab, Massachusetts Eye & Ear Infirm, Sch Med,Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. EM linda_berard@meei.harvard.edu NR 7 TC 20 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAR PY 2007 VL 143 IS 3 BP 516 EP 518 DI 10.1016/j.ajo.2006.10.025 PG 3 WC Ophthalmology SC Ophthalmology GA 141CZ UT WOS:000244555700024 PM 17317401 ER PT J AU Tam, DY Vagefi, MR Naseri, A AF Tam, Diamond Y. Vagefi, M. Reza Naseri, Ayman TI The clear corneal tongue: A mechanism for wound incompetence after phacoemulsification SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CATARACT-SURGERY; ENDOPHTHALMITIS; INCISION; TUNNEL AB PURPOSE: To describe a mechanism for wound incompe, tence after phacoemulsification with corneal incisions resulting in early postoperative wound leakage. DESIGN: Observational case series. METHODS: Three patients who had uneventful phacoemulsification through a clear corneal incision were identified because of a postoperative wound leak. A corneal tongue, consisting of an everted triangular flap of posterior corneal stroma, the Descemet membrane, and endothelium, was observed in the wounds of all cases. RESULTS: One wound leak resolved after pressure patching. The other two necessitated wound revisions. None of the patients developed endophthalmitis. CONCLUSIONS: In phacoemulsification with corneal incisions, an everted flap of posterior corneal tissue, a corneal tongue, may prevent normal anatomical apposition of the surgical wound edges leading to potential wound incompetence. This event may increase the risk of endophthalmitis after clear corneal phacoemulsification. C1 San Francisco VA Med Ctr, Dept Ophthalmol, San Francisco, CA 94121 USA. RP Naseri, A (reprint author), San Francisco VA Med Ctr, Dept Ophthalmol, San Francisco, CA 94121 USA. EM Ayman.Naseri@va.gov NR 7 TC 7 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAR PY 2007 VL 143 IS 3 BP 526 EP 528 DI 10.1016/j.ajo.2006.09.061 PG 3 WC Ophthalmology SC Ophthalmology GA 141CZ UT WOS:000244555700029 PM 17317406 ER PT J AU Boseley, ME Gherson, S Hartnick, CJ AF Boseley, Mark E. Gherson, Shirley Hartnick, Christopher J. TI Spasmodic dysphonia in an adolescent patient with an autoimmune neurologic disorder SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID BOTULINUM TOXIN; NEUROPSYCHIATRIC DISORDERS; STREPTOCOCCAL INFECTIONS; PANDAS AB Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) has been primarily described in the neurology and psychiatry literature. The symptoms of this syndrome typically are a range of obsessive compulsive disorders and neuromuscular tics. The otolaryngologist occasionally becomes involved with these children when it is deemed that chronic tonsil infections are the source. We report here on a child diagnosed with PANDAS who presented with severe ventricular hyperfunction and adductor spasmodic dysphonia. She was treated with botulinum toxin, which resulted in a significant improvement in subjective voice as well as reduced jitter and shimmer on objective voice measurements. (C) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Madigan Army Med Ctr, Tacoma, WA 98431 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM christopher_hartnick@meei.harvard.edu OI Gherson, Shirley/0000-0001-7773-5089 NR 10 TC 0 Z9 1 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 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD MAR-APR PY 2007 VL 28 IS 2 BP 140 EP 142 DI 10.1016/j.amjoto.2007.01.002 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA 149QU UT WOS:000245162500016 PM 17362824 ER PT J AU Arystarkhova, E Donnet, C Munoz-Matta, A Specht, SC Sweadner, KJ AF Arystarkhova, Elena Donnet, Claudia Munoz-Matta, Ana Specht, Susan C. Sweadner, Kathleen J. TI Multiplicity of expression of FXYD proteins in mammalian cells: dynamic exchange of phospholemman and gamma-subunit in response to stress SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE Na-K-ATPase; cellular stress; regulation ID NA-K-ATPASE; HORMONE-INDUCED FACTOR; RENAL NA,K-ATPASE; IMMUNOCYTOCHEMICAL LOCALIZATION; PHOSPHATIDYLINOSITOL 3-KINASE; DIFFERENTIAL REGULATION; SPLICE VARIANTS; PLASMA-MEMBRANE; XENOPUS OOCYTES; FUNCTIONAL-ROLE AB Functional properties of Na-K-ATPase can be modified by association with FXYD proteins, expressed in a tissue-specific manner. Here we show that expression of FXYDs in cell lines does not necessarily parallel the expression pattern of FXYDs in the tissue(s) from which the cells originate. While being expressed only in lacis cells in the juxtaglomerular apparatus and in blood vessels in kidney, FXYD1 was abundant in renal cell lines of proximal tubule origin (NRK-52E, LLC-PK1, and OK cells). Authenticity of FXYD1 as a part of Na-K-ATPase in NRK-52E cells was demonstrated by co-purification, co-immunoprecipitation, and co-localization. Induction of FXYD2 by hypertonicity (500 mosmol/kgH(2)O with NaCl for 48 h or adaptation to 700 mosmol/kgH(2)O) correlated with downregulation of FXYD1 at mRNA and protein levels. The response to hypertonicity was influenced by serum factors and entailed, first, dephosphorylation of FXYD1 at Ser68 (1-5 h) and, second, induction of FXYD2a and a decrease in FXYD1 with longer exposure. FXYD1 was completely replaced with FXYD2a in cells adapted to 700 mosmol/kgH(2)O and showed a significantly decreased sodium affinity. Thus dephosphorylation of FXYD1 followed by exchange of regulatory subunits is utilized to make a smooth transition of properties of Na-K-ATPase. We also observed expression of mRNA for multiple FXYDs in various cell lines. The expression was dynamic and responsive to physiological stimuli. Moreover, we demonstrated expression of FXYD5 protein in HEK-293 and HeLa cells. The data imply that FXYDs are obligatory rather than auxiliary components of Na-K-ATPase, and their interchangeability underlies responses of Na-K-ATPase to cellular stress. C1 Massachusetts Gen Hosp, Lab Membrane Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Puerto Rico, Sch Med, Dept Pharmacol & Toxicol, San Juan, PR 00936 USA. RP Arystarkhova, E (reprint author), Massachusetts Gen Hosp, Lab Membrane Biol, 415 Thier Res Bldg,55 Fruit St, Boston, MA 02114 USA. EM earistarkhova@yahoo.com FU NCRR NIH HHS [G12-RR-03051]; NHLBI NIH HHS [HL-036271]; NICHD NIH HHS [G11-HD-046326]; NIDDK NIH HHS [DK-44351]; NINDS NIH HHS [NS-45083] NR 72 TC 15 Z9 15 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 EI 1522-1563 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD MAR PY 2007 VL 292 IS 3 BP C1179 EP C1191 DI 10.1152/ajpcell.00328.2006 PG 13 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 144HO UT WOS:000244787300021 PM 17050615 ER PT J AU Barre, L Richardson, C Hirshman, MF Brozinick, J Fiering, S Kemp, BE Goodyear, LJ Witters, LA AF Barre, Laura Richardson, Christine Hirshman, Michael F. Brozinick, Joseph Fiering, Steven Kemp, Bruce E. Goodyear, Laurie J. Witters, Lee A. TI Genetic model for the chronic activation of skeletal muscle AMP-activated protein kinase leads to glycogen accumulation SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE glycogen synthase; exercise; transgenic mice ID PARKINSON-WHITE-SYNDROME; TRANSGENIC MICE; GLUCOSE-TRANSPORT; UPSTREAM KINASE; CARRIER PIGS; SYNTHASE; SUBUNIT; METABOLISM; OVEREXPRESSION; CARBOHYDRATE AB The AMP- activated protein kinase ( AMPK) is an important metabolic sensor/ effector that coordinates many of the changes in mammalian tissues during variations in energy availability. We have sought to create an in vivo genetic model of chronic AMPK activation, selecting murine skeletal muscle as a representative tissue where AMPK plays important roles. Muscleselective expression of a mutant noncatalytic gamma 1 subunit ( R70Q gamma) of AMPK activates AMPK and increases muscle glycogen content. The increase in glycogen content requires the presence of the endogenous AMPK catalytic alpha- subunit, since the offspring of cross- breeding of these mice with mice expressing a dominant negative AMPK alpha subunit have normal glycogen content. In R70Q gamma 1-expressing mice, there is a small, but significant, increase in muscle glycogen synthase ( GSY) activity associated with an increase in the muscle expression of the liver isoform GSY2. The increase in glycogen content is accompanied, as might be expected, by an increase in exercise capacity. Transgene expression of this mutant AMPK gamma 1 subunit may provide a useful model for the chronic activation of AMPK in other tissues to clarify its multiple roles in the regulation of metabolism and other physiological processes. C1 Dartmouth Coll Sch Med, Dept Med, Hanover, NH 03755 USA. Dartmouth Coll Sch Med, Dept Biochem, Hanover, NH 03755 USA. Dartmouth Coll Sch Med, Dept Microbiol & Immunol, Hanover, NH 03755 USA. Dartmouth Coll, Dept Biol Sci, Hanover, NH 03755 USA. Harvard Univ, Sch Med, Div Res, Joslin Diabetes Ctr, Cambridge, MA 02138 USA. Eli Lilly & Co, Indianapolis, IN USA. St Vincents Inst, Fitzroy, Vic, Australia. CSIRO Mol & hlth Technol, Fitzroy, Vic, Australia. RP Witters, LA (reprint author), Dartmouth Coll Sch Med, Dept Med, Remsen 322,N Coll St, Hanover, NH 03755 USA. EM lee.a.witters@dartmouth.edu RI Kemp, Bruce/L-2633-2014 OI Kemp, Bruce/0000-0001-6735-5082 FU NIAMS NIH HHS [AR-45670]; NIDDK NIH HHS [DK-35712] NR 39 TC 40 Z9 42 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD MAR PY 2007 VL 292 IS 3 BP E802 EP E811 DI 10.1152/ajpendo.00369.2006 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 143LB UT WOS:000244722000019 PM 17106064 ER PT J AU Fischer, L Gukovskaya, AS Penninger, JM Mareninova, OA Friess, H Gukovsky, I Pandol, SJ AF Fischer, L. Gukovskaya, A. S. Penninger, J. M. Mareninova, O. A. Friess, H. Gukovsky, I. Pandol, S. J. TI Phosphatidylinositol 3-kinase facilitates bile acid-induced Ca2+ responses in pancreatic acinar cells SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE sarco( endo) plasmic reticulum Ca2+-ATPase; taurolithocholic acid 3-sulfate; taurochenodeoxycholate; cholecystokinin; pancreatitis ID RAT HEPATOCYTES; ENZYME ACTIVATION; CALCIUM; RELEASE; OBSTRUCTION; CA2+-ATPASE; RETICULUM; SEVERITY; SIGNALS; STORES AB Bile acids are known to induce Ca2+ signals in pancreatic acinar cells. We have recently shown that phosphatidylinositol 3-kinase (PI3K) regulates changes in free cytosolic Ca2+ concentration ([Ca2+](i)) elicited by CCK by inhibiting sarco(endo) plasmic reticulum Ca2+-ATPase (SERCA). The present study sought to determine whether PI3K regulates bile acid-induced [Ca2+](i) responses. In pancreatic acinar cells, pharmacological inhibition of PI3K with LY-294002 or wortmannin inhibited [Ca2+](i) responses to taurolithocholic acid 3-sulfate (TLC-S) and taurochenodeoxycholate (TCDC). Furthermore, genetic deletion of the PI3K gamma-isoform also decreased [Ca2+](i) responses to bile acids. Depletion of CCK-sensitive intracellular Ca2+ pools or application of caffeine inhibited bile acid-induced [Ca2+](i) signals, indicating that bile acids release Ca2+ from agonist-sensitive endoplasmic reticulum (ER) stores via an inositol (1,4,5)-trisphosphate-dependent mechanism. PI3K inhibitors increased the amount of Ca2+ in intracellular stores during the exposure of acinar cells to bile acids, suggesting that PI3K negatively regulates SERCA-dependent Ca2+ reloading into the ER. Bile acids inhibited Ca2+ reloading into ER in permeabilized acinar cells. This effect was augmented by phosphatidylinositol (3,4,5)-trisphosphate (PIP3), suggesting that both bile acids and PI3K act synergistically to inhibit SERCA. Furthermore, inhibition of PI3K by LY-294002 completely inhibited trypsinogen activation caused by the bile acid TLC-S. Our results indicate that PI3K and its product, PIP3, facilitate bile acid-induced [Ca2+](i) responses in pancreatic acinar cells through inhibition of SERCA-dependent Ca2+ reloading into the ER and that bile acid- induced trypsinogen activation is mediated by PI3K. The findings have important implications for the mechanism of acute pancreatitis since [Ca2+](i) increases and trypsinogen activation mediate key pathological processes in this disorder. C1 W Los Angeles Vet Affairs Healthcare Ctr, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA. Austrian Acad Sci, Inst Mol Biotechnol, Vienna, Austria. RP Gukovskaya, AS (reprint author), W Los Angeles Vet Affairs Healthcare Ctr, Vet Affairs Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 258,Rm 340, Los Angeles, CA 90073 USA. EM agukovsk@ucla.edu RI Penninger, Josef/I-6860-2013 OI Penninger, Josef/0000-0002-8194-3777 FU NIAAA NIH HHS [P50-AA-11999]; NIDDK NIH HHS [DK-59508, DK-59936] NR 37 TC 27 Z9 29 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAR PY 2007 VL 292 IS 3 BP G875 EP G886 DI 10.1152/ajpgi.00558.2005 PG 12 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 144HN UT WOS:000244787200020 PM 17158252 ER PT J AU Armoundas, AA Rose, J Aggarwal, R Stuyvers, BD O'Rourke, B Kass, DA Marban, E Shorofsky, SR Tomaselli, GF Balke, CW AF Armoundas, Antonis A. Rose, Jochen Aggarwal, Rajesh Stuyvers, Bruno D. O'Rourke, Brian Kass, David A. Marban, Eduardo Shorofsky, Stephen R. Tomaselli, Gordon F. Balke, C. William TI Cellular and molecular determinants of altered Ca2+ handling in the failing rabbit heart: primary defects in SR Ca2+ uptake and release mechanisms SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE calcium; ion channels; sarcoplasmic reticulum; pacing tachycardia ID CARDIAC SARCOPLASMIC-RETICULUM; LEFT-VENTRICULAR MYOCARDIUM; ADENOVIRAL GENE-TRANSFER; DILATED CARDIOMYOPATHY; NA+-CA2+ EXCHANGER; CALCIUM-RELEASE; MESSENGER-RNA; RYANODINE RECEPTORS; PROTEIN-LEVELS; CONTRACTILE RESERVE AB Myocytes from the failing myocardium exhibit depressed and prolonged intracellular Ca2+ concentration ([ Ca2+](i)) transients that are, in part, responsible for contractile dysfunction and unstable repolarization. To better understand the molecular basis of the aberrant Ca2+ handling in heart failure ( HF), we studied the rabbit pacing tachycardia HF model. Induction of HF was associated with action potential ( AP) duration prolongation that was especially pronounced at low stimulation frequencies. L- type calcium channel current ( I-Ca,I- L) density ( - 0.964 +/- 0.172 vs. -0.745 +/- 0.128 pA/ pF at + 10 mV) and Na+/Ca2+ exchanger ( NCX) currents ( 2.1 +/- 0.8 vs. 2.3 +/- 0.8 pA/ pF at +30 mV) were not different in myocytes from control and failing hearts. The amplitude of peak [ Ca2+](i) was depressed ( at +10 mV, 0.72 +/- 0.07 and 0.56 +/- 0.04 mu M in normal and failing hearts, respectively; P < 0.05), with slowed rates of decay and reduced Ca2+ spark amplitudes ( P < 0.0001) in myocytes isolated from failing vs. control hearts. Inhibition of sarco( endo) plasmic reticulum Ca2+-ATPase ( SERCA) 2a revealed a greater reliance on NCX to remove cytosolic Ca2+ in myocytes isolated from failing vs. control hearts ( P < 0.05). mRNA levels of the alpha(1C)-subunit, ryanodine receptor ( RyR), and NCX were unchanged from controls, while SERCA2a and phospholamban ( PLB) were significantly downregulated in failing vs. control hearts ( P < 0.05). alpha(1C) protein levels were unchanged, RyR, SERCA2a, and PLB were significantly downregulated ( P < 0.05), while NCX protein was significantly upregulated ( P < 0.05). These results support a prominent role for the sarcoplasmic reticulum ( SR) in the pathogenesis of HF, in which abnormal SR Ca2+ uptake and release synergistically contribute to the depressed [ Ca2+](i) and the altered AP profile phenotype. C1 Johns Hopkins Univ, Dept Med, Div Mol Cardiobiol, Baltimore, MD 21205 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA USA. Univ Maryland, Dept Med, Div Cardiol, Baltimore, MD 21201 USA. Univ Calgary, Dept Med, Div Cardiol, Calgary, AB, Canada. Univ Kentucky, Coll Med, Dept Med, Lexington, KY USA. Univ Kentucky, Coll Med, Dept Physiol, Lexington, KY USA. Univ Kentucky, Coll Med, Inst Mol Med, Lexington, KY USA. RP Armoundas, AA (reprint author), Johns Hopkins Univ, Div Cardiol, 844 Ross Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. EM gtomasel@jhmi.edu FU NHLBI NIH HHS [1 R01 HL-071865, P01 HL081427, P50-HL-52307, R01 HL061711-08, R01 HL061711, R01 HL071865, P01 HL081427-040001, 2 R01-HL-50435] NR 84 TC 37 Z9 42 U1 0 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAR PY 2007 VL 292 IS 3 BP H1607 EP H1618 DI 10.1152/ajpheart.00525.2006 PG 12 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 142VS UT WOS:000244679300046 PM 17122195 ER PT J AU Sullivan, CN Raboin, SJ Gulley, S Sinzobahamvya, NT Green, GM Reeve, JR Sayegh, AI AF Sullivan, Cherese N. Raboin, Shannon J. Gulley, Stephen Sinzobahamvya, Ntwenzi T. Green, Gary M. Reeve, Joseph R., Jr. Sayegh, Ayman I. TI Endogenous cholecystokinin reduces food intake and increases Fos-like immunoreactivity in the dorsal vagal complex but not in the myenteric plexus by CCK1 receptor in the adult rat SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE camostat; vagotomy; devazepide ID GLUCAGON-LIKE PEPTIDE-1; BRAIN-STEM; C-FOS; GASTROINTESTINAL-TRACT; INTESTINAL NUTRIENTS; CENTRAL ORGANIZATION; EXOCRINE PANCREAS; BINDING-SITES; NEURONS; EXPRESSION AB Endogenous cholecystokinin reduces food intake and increases Fos-like immunoreactivity in the dorsal vagal complex but not in the myenteric plexus by CCK1 receptor in the adult rat. Am J Physiol Regul Integr Comp Physiol 292: R1071 - R1080, 2007. First published November 2, 2006; doi:10.1152/ajpregu. 00490.2006. - We hypothesized that endogenous CCK reduces food intake by activating the dorsal vagal complex (DVC) and the myenteric neurons of the gut. To test this hypothesis, adult rats were given camostat mesilate; a nonnutrient releaser of endogenous CCK, by orogastric gavage, and Fos-like immunoreactivity (Fos-LI) was quantified in the DVC and the myenteric plexus. The results for endogenous CCK were compared with those for exogenous CCK-8. Exogenous CCK-8 reduced food intake and stimulated Fos-LI in the DVC and in myenteric neurons of the duodenum and jejunum. In comparison, endogenous CCK reduced food intake and increased DVC Fos-LI but did not increase Fos-LI in the myenteric plexus. Similar to CCK-8, devazepide, a specific CCK1 receptor antagonist, and not L365,260, a specific CCK2 receptor antagonist, attenuated the reduction of food intake by camostat. In addition, Fos-LI in the DVC in response to both exogenous CCK-8 and camostat administration was significantly attenuated by vagotomy, as well as by blocking CCK1 receptors. These results demonstrate for the first time that reduction of food intake in adult rats by endogenous CCK released by a nonnutrient mechanism requires CCK1 receptors, the vagus nerve, and activation of the DVC, but not the myenteric plexus. C1 Tuskegee Univ, Coll Vet Med, Dept Biomed Sci, Gastroenterol Lab, Tuskegee, AL 36088 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. Univ Calif Los Angeles, CURE, Los Angeles, CA USA. Univ Calif Los Angeles, Digest Dis Res Ctr, Vet Adm Greater Los Angeles Healthcare Syst, Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Div Digest Dis, Sch Med, Los Angeles, CA USA. RP Sullivan, CN (reprint author), Tuskegee Univ, Coll Vet Med, Dept Biomed Sci, Gastroenterol Lab, Tuskegee, AL 36088 USA. EM sayeghai@tuskegee.edu FU NIDDK NIH HHS [DK 41301, R01 DK 33850]; NIGMS NIH HHS [S06 GM 08091-31] NR 55 TC 25 Z9 26 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD MAR PY 2007 VL 292 IS 3 BP R1071 EP R1080 DI 10.1152/ajpregu.00490.2006 PG 10 WC Physiology SC Physiology GA 143LC UT WOS:000244722100003 PM 17082351 ER PT J AU Zhang, WK Meng, H Li, ZH Shu, ZJ Ma, XY Zhang, BX AF Zhang, Wanke Meng, Hua Li, Zhen-Hua Shu, Zhenju Ma, Xiuye Zhang, Bin-Xian TI Regulation of STIM1, store-operated Ca2+ influx, and nitric oxide generation by retinoic acid in rat mesangial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE diabetes; protein downregulation; glomerular hyperfiltration; proteasome; lactacystin; eNOS ID PROTEIN-KINASE-C; GLOMERULAR ENDOTHELIAL-CELLS; ACTIVATED RECEPTOR-GAMMA; DIABETIC-NEPHROPATHY; HIGH GLUCOSE; TGF-BETA; EXTRACELLULAR-MATRIX; PLASMA-MEMBRANE; CALCIUM INFLUX; EXPRESSION AB It has been shown that store- operated Ca2+ influx ( SOC) plays critical roles in the activation of endothelial nitric oxide ( NO) synthase ( eNOS) and generation of NO in endothelial cells. Recent studies indicate stromal interaction molecule 1 ( STIM1) is the molecule responsible for SOC activation following Ca2+ depletion in the ER. Retinoic acids ( RA) have beneficial effects in the treatment of renal diseases. The mechanism of the RA action is still largely unknown. In the current study, we used primary cultured rat mesangial cells to examine the effect of RA on SOC and STIM1. In these cells, BK caused concentration- dependent [ Ca2+](i) mobilization. Treatment of the cells with RA, while it had no effect on the initial peak, reduced the plateau phase of BK- mediated [ Ca2+](i) response, indicating the inhibition of SOC by RA. The level of STIM1 protein but not mRNA in RA- treated cells was significantly reduced. RA treatment did not affect TGF-beta- mediated gradual Ca2+ influx which occurred by superoxide anion- mediated mechanism, indicating RA treatment specifically inhibited SOC in mesangial cells. RT- PCR and Western blot analysis demonstrated that eNOS was expressed in rat mesangial cells grown in media containing 11 and 30 but not 5.5 mM glucose. Downregulation of STIM1 protein and BK- induced SOC by RA treatment or STIM1 dsRNA were associated with abolished NO production. The 26S proteasome inhibitor lactacystin blocked the RA- mediated downregulation of BK- induced SOC, suggesting that ubiquitin- proteasome pathway may be involved in RA- mediated STIM1 protein downregulation in rat mesangial cells. Our data suggest that glucose- induced eNOS expression and NO production in mesangial cells may contribute to hyperfiltration in diabetes and RA may exert beneficial effects by downregulation of STIM1 and SOC in mesangial cells. C1 S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78285 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78285 USA. RP Zhang, BX (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr, GRECC 182,7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM zhangb2@uthscsa.edu FU NHLBI NIH HHS [R01-HL-75011] NR 55 TC 15 Z9 15 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAR PY 2007 VL 292 IS 3 BP F1054 EP F1064 DI 10.1152/ajprenal.00286.2006 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 143LE UT WOS:000244722300018 PM 17090780 ER PT J AU Samuels, J Shugart, YY Grados, MA Willour, VL Bienvenu, OJ Greenberg, BD Knowles, JA McCracken, JT Rauch, SL Murphy, DL Wang, Y Pinto, A Fyer, AJ Piacentini, J Pauls, DL Cullen, B Rasmussen, SA Hoehn-Saric, R Valle, D Liang, KY Riddle, MA Nestadt, G AF Samuels, Jack Shugart, Yin Yao Grados, Marco A. Willour, Virginia L. Bienvenu, O. Joseph Greenberg, Benjamin D. Knowles, James A. McCracken, James T. Rauch, Scott L. Murphy, Dennis L. Wang, Ying Pinto, Anthony Fyer, Abby J. Piacentini, John Pauls, David L. Cullen, Bernadette Rasmussen, Steven A. Hoehn-Saric, Rudolf Valle, David Liang, Kung-Yee Riddle, Mark A. Nestadt, Gerald TI Significant linkage to compulsive hoarding on chromosome 14 in families with obsessive-compulsive disorder: Results from the OCD collaborative genetics study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID COMPLEX SEGREGATION ANALYSIS; PEDIATRIC PROBANDS; SYMPTOM DIMENSIONS; SCAN; HETEROGENEITY; PREDICTORS; PHENOTYPES; TRAITS; MODEL AB Objective: Individuals with obsessive-compulsive disorder (OCD) who have compulsive hoarding behavior are clinically different from other OCD-affected individuals. The objective of this study was to determine whether there are chromosomal regions specifically linked to compulsive hoarding behavior in families with obsessive-compulsive disorder. Methods: The authors used multipoint allele-sharing methods to assess for linkage in 219 multiplex OCD families collected as part of the OCD Collaborative Genetics Study. The authors treated compulsive hoarding as the phenotype of interest and also stratified families into those with and without two or more relatives affected with compulsive hoarding. Results: Using compulsive hoarding as the phenotype, there was suggestive linkage to chromosome 14 at marker D14S588 (Kong and Cox logarithm of the odds ratio [LOD] [KAC(all)=2.9]). In families with two or more hoarding relatives, there was significant linkage of OCD to chromosome 14 at marker C14S1937 (KAC(all)= 3.7), whereas in families with fewer than two hoarding relatives, there was suggestive linkage to chromosome 3 at marker D3S2398 (KAC(all)= 2.9). Conclusions: The findings suggest that a region on chromosome 14 is linked with compulsive hoarding behavior in families with OCD. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21287 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21287 USA. Brown Univ, Sch Med, Butler Hosp, Dept Psychiat & Human Behav, Providence, RI 02912 USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Samuels, J (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 600 N Wolfe St,Meyer 4-181, Baltimore, MD 21287 USA. EM jacks@jhmi.edu RI Piacentini, John/C-4645-2011; Liang, Kung-Yee/F-8299-2011; Pinto, Anthony/D-2718-2017; OI Pinto, Anthony/0000-0002-6078-7242; Samuels, Jack/0000-0002-6715-7905 FU NCRR NIH HHS [RR00052]; NIMH NIH HHS [K23-MH-64543, R01-MH-50214] NR 40 TC 85 Z9 90 U1 0 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2007 VL 164 IS 3 BP 493 EP 499 DI 10.1176/appi.ajp.164.3.493 PG 7 WC Psychiatry SC Psychiatry GA 141DN UT WOS:000244557800020 PM 17329475 ER PT J AU Colen, RR Singer, AE McLoud, TC AF Colen, Rivka R. Singer, Amad Eldin McLoud, Theresa C. TI Cryptococcal pneumonia in an immunocompetent patient SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE chest; correlation; infectious diseases; lung diseases; radiologic-pathologic ID PULMONARY CRYPTOCOCCOSIS; CT FINDINGS C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Colen, RR (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND Bldg 2, Boston, MA 02114 USA. EM rrcolen@partners.org NR 7 TC 0 Z9 0 U1 1 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2007 VL 188 IS 3 BP W281 EP W282 DI 10.2214/AJR.06.0614 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 156QE UT WOS:000245663300052 PM 17312037 ER PT J AU Mino-Kenudson, M Ban, S Ohana, M Puricelli, W Deshpande, V Shimizu, M Nishioka, NS Lauwers, GY AF Mino-Kenudson, Mari Ban, Shinichi Ohana, Masaya Puricelli, William Deshpande, Vikrain Shimizu, Michio Nishioka, Norman S. Lauwers, Gregory Y. TI Buried dysplasia and early adenocarcinoma arising in Barrett esophagus after porfimer-photodynamic therapy SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE Barrett esophagus; dysplasia; carcinoma; buried; photodynamic therapy; histopathology; porfimer ID HIGH-GRADE DYSPLASIA; ACID SUPPRESSION; SQUAMOUS REEPITHILIALIZATION; EARLY CANCER; FOLLOW-UP; ABLATION; ERADICATION; CARCINOMA; REGRESSION; TRIAL AB The restoration of squamous epithelium after photodynamic therapy (PDT) for Barrett esophagus (BE) and its related neoplasms has been noted. It may result in the development of buried neoplasms and/or BE underneath restored squamous epithelium which maintain their potential for malignant transformation. The purpose of this study was to evaluate the prevalence, endoscopic, and histologic characteristics and also response to further treatment of buried neoplastic epithelium developing after PDT. Fifty-two BE patients with high-grade dysplasia (n = 19), intramucosal adenocarcinoma (n = 28), and invasive adenocarcinoma (n = 5) were treated with portimer PDT. Buried neoplasms completely covered by squamous epithelium were seen in I patient before and in 13 patients after PDT. Their prevalence was 0.6% and 7.4% of pre and post-PDT biopsy levels positive for neoplasia (P = 0.001). Buried neoplasms, representing the highest grade of residual neoplasm, were noted in a series of I I post-PDT endoscopies (7.1% of 155 post-PDT endoscopies with neoplastic diagnoses) of 8 patients. Their occurrence after PDT was neither associated with the length of BE, the diffuseness of neoplasms nor the presence of buried lesions before treatment. There was no prevalent location for these lesions in relation to the original segment of BE, although the majority of both surface and buried neoplasms were found in the prior neoplastic sites. Patients with buried neoplasms responded to further treatment similarly to those with only surface neoplasms (8 of 13 vs. 17 of 24) (P = 0.33). In conclusion, buried neoplasms are not uncommon after PDT. Thorough endoscopic surveillance with extensive biopsies, especially of the sites previously positive for neoplasia is important to avoid overlooking buried neoplasms that may progress. C1 Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. Tenri Hosp, Dept Gastroenterol, Tenri, Nara 632, Japan. RP Lauwers, GY (reprint author), Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, WRN 2,55 Fruit St, Boston, MA 02114 USA. EM glauwers@partners.org NR 41 TC 47 Z9 47 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 2007 VL 31 IS 3 BP 403 EP 409 DI 10.1097/01.pas.0000213407.03064.37 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 141JN UT WOS:000244574700009 PM 17325482 ER PT J AU Mengel, M Chapman, JR Cosio, FG Cavaille-Coll, MW Haller, H Halloran, PF Kirk, AD Mihatsch, MJ Nankivell, BJ Racusen, LC Roberts, IS Rush, DN Schwarz, A Seron, D Stegall, MD Colvin, RB AF Mengel, M. Chapman, J. R. Cosio, F. G. Cavaille-Coll, M. W. Haller, H. Halloran, P. F. Kirk, A. D. Mihatsch, M. J. Nankivell, B. J. Racusen, L. C. Roberts, I. S. Rush, D. N. Schwarz, A. Seron, D. Stegall, M. D. Colvin, R. B. TI Protocol biopsies in renal transplantation: Insights into patient management and pathogenesis SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material DE biopsy; kidney; protocol; rejection; subclinical; surrogate ID CHRONIC ALLOGRAFT NEPHROPATHY; EARLY CYCLOSPORINE WITHDRAWAL; SUBCLINICAL REJECTION; KIDNEY-TRANSPLANTATION; DIAGNOSIS; CRITERIA; INJURY; CELLS AB A 1-day symposium on the application of protocol biopsies in renal transplantation was held in Boston, 21 July 2006. Representatives from centers with extensive experience in the use of protocol biopsies for routine patient care and research reported results on the pathological findings and their value in patient management. The consensus was that protocol biopsies, in experienced hands, are a safe and valuable means of detecting subclinical disease that can benefit from modification of therapy. Furthermore, molecular studies reveal evidence of activity or progression not readily appreciated by histological techniques. Wider application is expected in multicenter clinical trials to predict and validate outcomes. The principal barrier to wider use of protocol biopsies is knowledge of the benefits of intervention. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Hannover Med Sch, Inst Pathol, D-3000 Hannover, Germany. Westmead Hosp, Ctr Transplant Res & Renal Res, Sydney, NSW, Australia. Mayo Clin & Mayo Fdn, Div Nephrol & Hypertens, Rochester, MN 55905 USA. US FDA, CDER, Div Special Pathogen & Transplantat Prod, Rockville, MD 20857 USA. Hannover Med Sch, Dept Nephrol, D-3000 Hannover, Germany. Univ Alberta, Alberta Transplant Appl Genom Ctr, Edmonton, AB, Canada. Natl Inst Digest & Kidney Dis, Transplantat Branch, NIH, Bethesda, MD USA. Univ Basel, Inst Pathol, CH-4003 Basel, Switzerland. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. Oxford Radcliffe Hosp, Dept Pathol, Oxford, England. Univ Manitoba, Dept Nephrol, Winnipeg, MB, Canada. Univ Bellvitge, Dept Nephrol, Hosp, Barcelona, Spain. Mayo Clin & Mayo Fdn, Dept Surg, Rochester, MN 55905 USA. RP Colvin, RB (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM Colvin@helix.mgh.harvard.edu RI Kirk, Allan/B-6905-2012; Halloran, Philip/J-1390-2012 OI Halloran, Philip/0000-0003-1371-1947 NR 26 TC 64 Z9 66 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAR PY 2007 VL 7 IS 3 BP 512 EP 517 DI 10.1111/j.1600-6143.2006.01677.x PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 143JD UT WOS:000244715800006 PM 17250556 ER PT J AU Solez, K Colvin, RB Racusen, LC Sis, B Halloran, PF Birk, PE Campbell, PM Cascalho, M Collins, AB Demetris, AJ Drachenberg, CB Gibson, IW Grimm, PC Haas, M Lerut, E Liapis, H Mannon, RB Marcus, PB Mengel, M Mihatsch, MJ Nankivell, BJ Nickeleit, V Papadimitriou, JC Platt, JL Randhawa, P Roberts, I Salinas-Madriga, L Salomon, DR Seron, D Sheaff, M Weening, JJ AF Solez, K. Colvin, R. B. Racusen, L. C. Sis, B. Halloran, P. F. Birk, P. E. Campbell, P. M. Cascalho, M. Collins, A. B. Demetris, A. J. Drachenberg, C. B. Gibson, I. W. Grimm, P. C. Haas, M. Lerut, E. Liapis, H. Mannon, R. B. Marcus, P. B. Mengel, M. Mihatsch, M. J. Nankivell, B. J. Nickeleit, V. Papadimitriou, J. C. Platt, J. L. Randhawa, P. Roberts, I. Salinas-Madriga, L. Salomon, D. R. Seron, D. Sheaff, M. Weening, J. J. TI Banff '05 Meeting report: Differential diagnosis of chronic allograft injury and elimination of chronic allograft nephropathy ('CAN') SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material DE Banff classification; central slide review; scoring ID INTERTUBULAR CAPILLARY CHANGES; INCOMPATIBLE RENAL-ALLOGRAFTS; POSITIVE CROSS-MATCH; TRANSPLANT GLOMERULOPATHY; PERITUBULAR CAPILLARIES; C4D DEPOSITS; HISTOLOGIC-FINDINGS; CYCLOSPORINE NEPHROTOXICITY; KIDNEY-TRANSPLANTATION; HUMORAL REJECTION AB The 8th Banff Conference on Allograft Pathology was held in Edmonton, Canada, 15-21 July 2005. Major outcomes included the elimination of the non-specific term 'chronic allograft nephropathy' (CAN) from the Banff classification for kidney allograft pathology, and the recognition of the entity of chronic antibody-mediated rejection. Participation of B cells in allograft rejection and genomics markers of rejection were also major subjects addressed by the conference. C1 Univ Alberta, Edmonton, AB, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Manitoba, Winnipeg, MB, Canada. Mayo Clin, Rochester, MN USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Maryland, Baltimore, MD 21201 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Univ Hosp, Louvain, Belgium. Washington Univ, Sch Med, St Louis, MO USA. NIDDK, NIH, Bethesda, MD 20892 USA. Methodist Hlth Syst, Dallas, TX USA. Hannover Med Sch, Inst Pathol, Hannover, Germany. Univ Basel, Basel, Switzerland. Univ Sydney, Sydney, NSW 2006, Australia. Univ N Carolina, Chapel Hill, NC USA. John Radcliffe Hosp, Dept Cellular Pathol, Oxford OX3 9DU, England. St Louis Univ, Hlth Sci Ctr, St Louis, MO 63103 USA. Scripps Inst, La Jolla, CA USA. Univ Barcelona, Barcelona, Spain. Royal London Hosp, London E1 1BB, England. Univ Amsterdam, Amsterdam, Netherlands. RP Solez, K (reprint author), Univ Alberta, Edmonton, AB, Canada. EM Kim.Solez@ualberta.ca RI Salomon, Daniel/E-9380-2012; Halloran, Philip/J-1390-2012; OI Halloran, Philip/0000-0003-1371-1947; Cascalho, Marilia/0000-0002-2695-3921 NR 54 TC 662 Z9 718 U1 0 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAR PY 2007 VL 7 IS 3 BP 518 EP 526 DI 10.1111/j.1600-6143.2006.01688.x PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 143JD UT WOS:000244715800007 PM 17352710 ER PT J AU Papas, KK Colton, CK Nelson, RA Rozak, PR Avgoustiniatos, ES Scott, WE Wildey, GM Pisania, A Weir, GC Hering, BJ AF Papas, K. K. Colton, C. K. Nelson, R. A. Rozak, P. R. Avgoustiniatos, E. S. Scott, W. E., III Wildey, G. M. Pisania, A. Weir, G. C. Hering, B. J. TI Human islet oxygen consumption rate and DNA measurements predict diabetes reversal in nude mice SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE islet potency; oxygen consumption rate; nude mice; quality assessment ID VIABILITY ASSAY; TRANSPLANTATION; PRESERVATION; PANCREAS AB There is a need for simple, quantitative and prospective assays for islet quality assessment that are predictive of islet transplantation outcome. The current state-of-the-art athymic nude mouse bioassay is costly, technically challenging and retrospective. In this study, we report on the ability of 2 parameters characterizing human islet quality: (1) oxygen consumption rate (OCR), a measure of viable volume; and (2) OCR/DNA, a measure of fractional viability, to predict diabetes reversal in nude mice. Results demonstrate that the probability for diabetes reversal increases as the graft's OCR/DNA and total OCR increase. For a given transplanted OCR dose, diabetes reversal is strongly dependent on OCR/DNA. The OCR and OCR/DNA (the 'OCR test') data exhibit 89% sensitivity and 77% specificity in predicting diabetes reversal in nude mice (n = 86). We conclude that the prospective OCR test can effectively replace the retrospective athymic nude mouse bioassay in assessing human islet quality prior to islet transplantation. C1 Univ Minnesota, Dept Surg, Diabet Inst Immunol & Transplantat, Minneapolis, MN 55455 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. City Hope Natl Med Ctr, ABCC, ICR Ctr Consortium, Duarte, CA 91010 USA. City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Papas, KK (reprint author), Univ Minnesota, Dept Surg, Diabet Inst Immunol & Transplantat, Box 242 UMHC, Minneapolis, MN 55455 USA. EM papas006@umn.edu RI Nelson, Rebecca/C-4438-2014 FU NCRR NIH HHS [U42 RR 016598-01, U42 RR 016606, U42 RR016598, U42 RR016598-05, U42 RR016598-06, U42 RR016606]; NIDDK NIH HHS [P30 DK036836, P30 DK 36836-16] NR 24 TC 75 Z9 75 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAR PY 2007 VL 7 IS 3 BP 707 EP 713 DI 10.1111/j.1600-6143.2006.01655.x PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA 143JD UT WOS:000244715800030 PM 17229069 ER PT J AU Adams, MS Alston, TA AF Adams, Mark S. Alston, Theodore A. TI Echocardiographic reflections on a pericardium SO ANESTHESIA AND ANALGESIA LA English DT Article C1 Harvard Univ, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Cardiac Anesthesia Grp,Sch Med, Boston, MA 02114 USA. RP Adams, MS (reprint author), Harvard Univ, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Cardiac Anesthesia Grp,Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM MAdams2@partners.org NR 3 TC 4 Z9 4 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAR PY 2007 VL 104 IS 3 BP 506 EP 506 DI 10.1213/01.ane.0000255056.78259.3c PG 1 WC Anesthesiology SC Anesthesiology GA 139KU UT WOS:000244431500011 PM 17312198 ER PT J AU Sun, BC Hoffman, JR Mower, WR AF Sun, Benjamin C. Hoffman, Jerome R. Mower, William R. TI Evaluation of a modified prediction instrument to identify significant pediatric intracranial injury after blunt head trauma SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID NEW-ORLEANS CRITERIA; COMPUTED-TOMOGRAPHY; CLINICAL PREDICTORS; DECISION INSTRUMENT; CHILDREN; RULE; CT; CONSCIOUSNESS; ABNORMALITY; INDICATORS AB Study objective: We evaluate the effect of a modification of the University of California-Davis Pediatric Head Injury Rule on the ability of the decision instrument for pediatric head injury to predict clinically important intracranial injury in an external cohort. Methods: We analyzed data prospectively recorded in 1,666 pediatric patients enrolled in the derivation set of the National Emergency X-Radiography Utilization Study II (NEXUS II). Treating physicians at 21 emergency departments recorded the presence or absence of clinical predictors on all patients who received a head computed tomography (CT) scan after experiencing blunt head trauma. Predictors included 3 exact elements of the University of California-Davis Rule (abnormal mental status, signs of skull fracture, and scalp hematoma in children : 2 years of age), some with different wording, and 2 modified elements with new definitions (the presence of high-risk vomiting or severe headache, rather than any vomiting or headache). Results: A significant intracranial injury was identified by CT in 138 (8.3%) patients. Sensitivity of the modified instrument to detect significant intracranial injury was 90.4% (95% confidence interval [CI] 85.4% to 95.4%); 13 children with such an injury were misclassified as low risk, Specificity of the modified instrument was 42.7% (95% Cl 40.1% to 45.3%). Conclusion: In the NEXUS II cohort, a modified version of the University of California-Davis Rule misclassified a substantial proportion of pediatric patients with clinically important blunt head injury. Although we cannot evaluate the exact University of California-Davis Rule, we demonstrate that using stricter definitions of "headache" and "vomiting" and different wording than in the original study may have unintended or negative consequences. We emphasize the importance of careful attention to precise definitions of clinical predictors when a decision instrument is used. C1 Univ Calif Los Angeles, Ctr Emergency Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Robert Wood Johnson Clin Scolars Program, Los Angeles, CA 90024 USA. RP Sun, BC (reprint author), W Los Angeles VA Med Ctr, MAil Stop 111,Bldg 500,Wing 3E,11301 Wilshire Blv, Los Angeles, CA 90073 USA. EM bsun@post.harvard.edu FU AHRQ HHS [R01 HS09699] NR 27 TC 24 Z9 24 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAR PY 2007 VL 49 IS 3 BP 325 EP 332 DI 10.1016/j.annemergmed.2006.08.032 PG 8 WC Emergency Medicine SC Emergency Medicine GA 142GI UT WOS:000244637000014 PM 17210207 ER PT J AU Gaynes, BN Rush, AJ Trivedi, MH Wisniewski, SR Balasubramani, GK Spencer, DC Petersen, T Klinkman, M Warden, D Nicholas, L Fava, M AF Gaynes, Bradley N. Rush, A. John Trivedi, Madhukar H. Wisniewski, Stephen R. Balasubramani, G. K. Spencer, Donald C. Petersen, Timothy Klinkman, Michael Warden, Diane Nicholas, Linda Fava, Maurizio TI Major depression symptoms in primary care and psychiatric care settings: A cross-sectional analysis SO ANNALS OF FAMILY MEDICINE LA English DT Article DE primary care; depression; suicide; psychiatric comorbidity ID DIAGNOSTIC SCREENING QUESTIONNAIRE; STAR-ASTERISK-D; ANTIDEPRESSANT EFFICACY TRIALS; RANDOMIZED CONTROLLED-TRIALS; QUALITY-OF-LIFE; MOOD DISORDERS; ANXIETY DISORDERS; CLINICAL-PRACTICE; RATING SCALE; SUICIDE RISK AB PURPOSE We undertook a study to confirm and extend preliminary findings that participants with major depressive disorder (MDD) in primary care and specialty care settings have with equivalent degrees of depression severity and an indistinguishable constellation of symptoms. METHODS Baseline data were collected for a distinct validation cohort of 2,541 participants (42% primary care) from 14 US regional centers comprised of 41 clinic sites (18 primary care, 23 specialty care). Participants met broadly inclusive eligibility criteria requiring a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of MDD and a minimum depressive symptom score on the 17-item Hamilton Rating Scale for Depression. The main outcome measures were the 30-item Inventory of Depressive Symptomatology - Clinician Rated and the Psychiatric Diagnostic Screening Questionnaire. RESULTS Primary care and specialty care participants had identical levels of moderately severe depression and identical distributions of depressive severity scores. Both primary care and specialty care participants showed considerable suicide risk, with specialty care participants even more likely to report prior suicide attempts. Core depressive symptoms or concurrent psychiatric disorders were not substantially different between settings. One half of participants in each setting had an anxiety disorder (48.6% primary care vs 51.6% specialty care, P = .143), with social phobia being the most common (25.3% primary care vs 32.1% specialty care, P = .002). CONCLUSIONS For outpatients with nonpsychotic MDD, depressive symptoms and severity vary little between primary care and specialty care settings. in this large, broadly inclusive US sample, the risk factors for chronic and recurrent depressive illness were frequently present, highlighting a clear risk for treatment resistance and the need for aggressive management strategies in both settings. C1 Univ N Carolina, Dept Psychiat, Sch Med, Chapel Hill, NC 27599 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75230 USA. Univ Pittsburgh, Epidemiol Data Ctr, Grad Sch Publ Hlth, Pittsburgh, PA USA. Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Univ Michigan, Dept Family Med, Ann Arbor, MI 48109 USA. RP Gaynes, BN (reprint author), Univ N Carolina, Dept Psychiat, Sch Med, CB 7160, Chapel Hill, NC 27599 USA. EM bngaynes@med.unc.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Gaynes, Bradley/0000-0002-8283-5030; Rush, Augustus/0000-0003-2004-2382; Goundappa K, Balasubramani/0000-0001-7221-1825 FU NIMH NIH HHS [MH01951-03, N01MH90003] NR 63 TC 48 Z9 50 U1 3 U2 6 PU ANNALS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672, UNITED STATES SN 1544-1709 J9 ANN FAM MED JI Ann. Fam. Med. PD MAR-APR PY 2007 VL 5 IS 2 BP 126 EP 134 DI 10.1370/afm.641 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 161FU UT WOS:000246000700006 PM 17389536 ER PT J AU Werner, RM Asch, DA AF Werner, Rachel M. Asch, David A. TI Clinical concerns about clinical performance measurement SO ANNALS OF FAMILY MEDICINE LA English DT Editorial Material DE health care quality; access; and evaluation; quality improvement; primary health care; patient-centered care ID QUALITY-OF-CARE; HEALTH-CARE; PHYSICIANS; VA AB Performance measurement has become one of the foundations of current efforts.,, to improve health care quality and has successfully increased compliance with practice guidelines in many settings. Despite the successes of performance measurement, many physicians remain apprehensive about its use because performance measurement "gets in the way of" delivering good care. There are several reasons clinicians might feel this way. First, performance measurement is increasingly being extended to areas that have only a small clinical benefit and thus risk diverting attention from other more important but unmeasured aspects of care. Second, most performance measurement systems provide no priority for following guidelines likely to yield a large clinical benefit compared with guidelines likely to yield at best a small clinical benefit. Third, performance measures focus physicians' attention narrowly on compliance with those measures rather than more broadly on the needs of the individual patient. Because performance measures are evaluated at the level of the indicator, they may crowd out quality at the level of the patient that is equally important but that cannot be easily measured. Performance measures play an important role in improving health care quality and will undoubtedly continue to do so; however, they are only one part of the solution to improving health care quality. Good performance is not necessarily good care, and pressure to improve performance can come at the sacrifice of good care. in its current state, performance measurement is better suited to improving measured care than improving the care of individual patients. C1 Univ Penn, Div Gen Internal Med, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Werner, RM (reprint author), Univ Penn, Div Gen Internal Med, Sch Med, 1230 Blockley Hall 423 Guardian Dr, Philadelphia, PA 19104 USA. EM rwerner@mail.med.upenn.edu NR 22 TC 29 Z9 29 U1 2 U2 4 PU ANNALS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672, UNITED STATES SN 1544-1709 J9 ANN FAM MED JI Ann. Fam. Med. PD MAR-APR PY 2007 VL 5 IS 2 BP 159 EP 163 DI 10.1370/afm.645 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 161FU UT WOS:000246000700011 PM 17389541 ER PT J AU Haidet, P AF Haidet, Paul TI Jazz and the 'art' of medicine: Improvisation in the medical encounter SO ANNALS OF FAMILY MEDICINE LA English DT Editorial Material DE physician-patient relations; primary health care; patient-centered care; education; medical; humanities; music; communication; curriculum; theoretical models; behavioral medicine; health care delivery; health services research ID DOCTOR-PATIENT COMMUNICATION; PRIMARY-CARE PHYSICIANS; BAD-NEWS; INTERVIEW; SATISFACTION; BEHAVIOR; SKILLS; CLUES AB Improvisation is an important aspect of patient-physician communication. It is also a defining feature of jazz music performance. This essay uses examples from jazz to illustrate principles of improvisation that relate to an individual communication act (ie, building space into one's communication), a physician's communicative style (ie, developing one's voice), and the communicative process of the medical encounter (ie, achieving ensemble). At all 3 levels, the traditions of jazz improvisation can inform efforts to research and teach medical interviewing by fostering a contextualized view of patient-physician communication. C1 Baylor Coll Med, Houston, TX 77030 USA. RP Haidet, P (reprint author), VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM phaidet@bcm.tmc.edu NR 55 TC 38 Z9 38 U1 6 U2 13 PU ANNALS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672, UNITED STATES SN 1544-1709 J9 ANN FAM MED JI Ann. Fam. Med. PD MAR-APR PY 2007 VL 5 IS 2 BP 164 EP 169 DI 10.1370/afm.624 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 161FU UT WOS:000246000700012 PM 17389542 ER PT J AU Yeo, TW De Jager, PL Gregory, SG Barcellos, LF Walton, A Goris, A Fenoglio, C Ban, M Taylor, CJ Goodman, RS Walsh, E Wolfish, CS Horton, R Traherne, J Beck, S Trowsdale, J Caillier, SJ Ivinson, AJ Green, T Pobywajlo, S Lander, ES Pericak-Vance, MA Haines, JL Daly, MJ Oksenberg, JR Hauser, SL Compston, A Hafler, DA Rioux, JD Sawcer, S AF Yeo, Tai Wai De Jager, Philip L. Gregory, Simon G. Barcellos, Lisa F. Walton, Amie Goris, An Fenoglio, Chiara Ban, Maria Taylor, Craig J. Goodman, Reyna S. Walsh, Emily Wolfish, Cara S. Horton, Roger Traherne, James Beck, Stephan Trowsdale, John Caillier, Stacy J. Ivinson, Adrian J. Green, Todd Pobywajlo, Susan Lander, Eric S. Pericak-Vance, Margaret A. Haines, Jonathan L. Daly, Mark J. Oksenberg, Jorge R. Hauser, Stephen L. Compston, Alastair Hafler, David A. Rioux, John D. Sawcer, Stephen CA Int Multiple Sclerosis Genetics TI A second major histocompatibility complex susceptibility locus for multiple sclerosis SO ANNALS OF NEUROLOGY LA English DT Article ID POLYMORPHIC MICROSATELLITE MARKERS; CLASS-I REGION; HUMAN MHC; HLA-DR; GENETIC SUSCEPTIBILITY; DIAGNOSTIC-CRITERIA; AUTOIMMUNE-DISEASE; LINKAGE; ASSOCIATION; HAPLOTYPES AB Objective: Variation in the major histocompatibility complex (MHC) on chromosome 6p21 is known to influence susceptibility to multiple sclerosis with the strongest effect originating from the HL4-DPB1 gene in the class 11 region. The possibility that other genes in the MHC independently influence susceptibility to multiple sclerosis has been suggested but remains unconfirmed. Methods: Using a combination of microsatellite, single nucleotide polymorphism, and human leukocyte antigen (HLA) typing, we screened the MHC in trio families looking for evidence of residual association above and beyond that attributable to the established DRB1*1501 risk haplotype. We then refined this analysis by extending the genoryping of classical HLA loci into independent cases and control subjects. Results: Screening confirmed the presence of residual association and suggested that this was maximal in the region of the HLA-C gene. Extending analysis of the classical loci confirmed that this residual association is partly due to allelic heterogeneity at the HLA-DRB1 locus, but also reflects an independent effect from the HLA-C gene. Specifically, the HLA-C*05 allele, or a variant in tight linkage disequilibrium with it, appears to exert a protective effect (p = 3.3 x 10(-5)). Interpretation: Variation in the HLA-C gene influences susceptibility to multiple sclerosis independently of any effect attributable to the nearby HLA-DRB1 gene. C1 Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England. Brigham & Womens Hosp, Dept Neurol, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. MIT, Program Med & Populat Genet, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02138 USA. Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC USA. Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif Berkeley, Sch Publ Hlth, Div Epidemiol, Berkeley, CA 94720 USA. Univ Milan, Dept Neurol Sci, Dino Ferrari Ctr, IRCCS Osped Maggiore Policlin, Milan, Italy. Addenbrookes Hosp, Tissue Typing Lab, Hinxton, England. Wellcome Trust Sanger Inst, Hinxton, England. Univ Cambridge, Dept Pathol, Div Immunol, Cambridge CB2 1QP, England. Massachusetts Gen Hosp, Ctr Genome Res, Boston, MA 02114 USA. Harvard Univ, Ctr Neurodegenerat & Repair, Boston, MA 02115 USA. Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN USA. Univ Calif San Francisco, Inst Human Genet, Sch Med, San Francisco, CA 94143 USA. Univ Montreal, Montreal, PQ, Canada. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. RP Sawcer, S (reprint author), Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Hills Rd, Cambridge CB2 2QQ, England. EM sjs1016@mole.bio.cam.ac.uk RI Rioux, John/A-9599-2015; Hauser, Stephen/J-2978-2016; Haines, Jonathan/C-3374-2012; Goris, An/F-2943-2010 OI Rioux, John/0000-0001-7560-8326; Goris, An/0000-0002-1276-6682 FU Medical Research Council [G0401569]; Multiple Sclerosis Society [588]; NINDS NIH HHS [K08 NS46341, K08 NS046341, NS026799, NS032830, NS049477, R01 NS026799, R01 NS032830, R01 NS049477]; Wellcome Trust [048880, 057097] NR 57 TC 108 Z9 109 U1 1 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAR PY 2007 VL 61 IS 3 BP 228 EP 236 DI 10.1002/ana.21063 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 153EZ UT WOS:000245416100009 PM 17252545 ER PT J AU Bahmad, F Merchant, SN AF Bahmad, Fayez, Jr. Merchant, Saumil N. TI Histopathology of ossicular grafts and implants in chronic otitis media SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE histopathology; implant; middle ear; ossicular graft ID MIDDLE-EAR; REPLACEMENT PROSTHESIS; HISTOLOGICAL FATE; CARTILAGE; SURGERY; BONE; OSSICULOPLASTY; TYMPANOPLASTY; AUTOGRAFTS; PATHOLOGY AB Objectives: We describe the histopathology of ossicular grafts and implants so as to provide insight into factors that may influence functional results after surgery for chronic otitis media. Methods: Histopathologic observations were made on 56 cases: 50 surgical specimens and 6 temporal bone cases in which the graft was sectioned in situ. Results and Conclusions: Autogenous malleus, incus, and cortical bone grafts behaved in a similar manner and maintained their morphological size, shape, and contour for extended periods of time, at least up to 30 years. These histopathologic observations support the continued use of autograft ossicular and cortical bone grafts for middle ear reconstruction. Cartilage grafts developed chondromalacia with resulting loss of stiffness and showed a tendency to undergo resorption. Synthetic prostheses made of porous plastic (Plastipore, Polycel) elicited foreign body giant cell reactions with various degrees of biodegradation of the implants. Prostheses made of hydroxyapatite and Bioglass were enveloped by a lining of connective tissue and mucosal epithelium. The Bioglass material was broken down into small fragments and partially resorbed by a host response within the middle car. These results warrant caution in the use of prostheses made of porous plastic or Bioglass. C1 Massachusetts Eye & Ear Infirm, Otopathol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Otopathol Lab, 243 Charles, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC04798, R01 DC004798, U24 DC008559, U24 DC008559-01] NR 35 TC 11 Z9 11 U1 0 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD MAR PY 2007 VL 116 IS 3 BP 181 EP 191 PG 11 WC Otorhinolaryngology SC Otorhinolaryngology GA 147TC UT WOS:000245024400004 PM 17419521 ER PT J AU Enzinger, PC Benedetti, JK Meyerhardt, JA Mccoy, S Hundahl, SA Macdonald, JS Fuchs, CS AF Enzinger, Peter C. Benedetti, Jacqueline K. Meyerhardt, Jeffrey A. McCoy, Sheryl Hundahl, Scott A. Macdonald, John S. Fuchs, Charles S. TI Impact of hospital volume on recurrence and survival after surgery for gastric cancer SO ANNALS OF SURGERY LA English DT Article ID SURGICAL VOLUME; OPERATIVE MORTALITY; RANDOMIZED TRIAL; 5-YEAR SURVIVAL; STOMACH-CANCER; UNITED-STATES; OUTCOMES; CARCINOMA; RESECTION; CHEMORADIOTHERAPY AB Background: Some, but not all, studies using registry data have suggested a small but significant long-term survival advantage following a curative surgical resection of gastric cancer at hospitals where the volume of such surgeries is high. However, because such data may be significantly influenced by the impact of postoperative mortality, and may be imbalanced for factors important to survival, the true nature of this relationship remains uncertain. Methods: We conducted a nested volume-outcome study in a sample of 448 surgical survivors with stage IB through IV (M0) gastric and gastroesophageal junction adenocarcinoma, previously randomized to adjuvant chemoradiation after surgery or surgery alone, to measure the effect of hospital surgical volume, as assessed by Medicare claims data, on overall survival and gastric cancer recurrence. Results: In this selected sample of postoperative survivors, hospital surgical volume was not predictive of overall survival (P = 0.46) or disease-free survival (P = 0.43) at a median follow-up of 8.9 years. However, patients who underwent either a D1 or D2 dissection at a high- or moderate-volume center experienced an adjusted hazard ratio of 0.80 (95% CI, 0.53-1.20) for overall survival and 0.78 (95% CI, 0.53-1.14) for disease-free survival compared with those patients resected at a low-volume hospital; these results were not statistically significant. When a DO resection was performed, hospital procedure volume showed no impact on survival. Conclusions: Excluding the impact of perioperative mortality by utilizing prospectively recorded data from a large postoperative adjuvant trial, hospital procedure volume had no overall effect on long-term gastric cancer survival. The potential benefit of moderate- to high-volume centers for patients who underwent a D1 or D2 dissection requires confirmation in larger studies. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. SW Oncol Grp, Ctr Stat, Seattle, WA USA. Univ Calif Davis, Davis, CA 95616 USA. VA No Calif Hlth Care Syst, Sacramento, CA USA. St Vincents Comprehens Canc Ctr, New York, NY USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Enzinger, PC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM peter_enzinger@dfci.harvard.edu NR 42 TC 47 Z9 53 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAR PY 2007 VL 245 IS 3 BP 426 EP 434 DI 10.1097/01.sla.0000245469.35088.42 PG 9 WC Surgery SC Surgery GA 140OO UT WOS:000244515300014 PM 17435550 ER PT J AU Kay, J AF Kay, J. TI Educational challenges for rheumatology in the United States SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT 27th European Workshop for Rheumatology Research CY FEB 22-24, 2007 CL Florence, ITALY C1 Massachusetts Gen Hosp, Dept Med, Rheumatol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD MAR 1 PY 2007 VL 66 SU 1 BP A1 EP A2 PG 2 WC Rheumatology SC Rheumatology GA 138BN UT WOS:000244337600003 ER PT J AU Kim, ND Chou, RC Tager, AM Luster, AD AF Kim, N. D. Chou, R. C. Tager, A. M. Luster, A. D. TI A non-cell autonomous requirement for the leukotriene B-4 receptor BLT1 on neutrophils in inflammatory arthritis SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT 27th European Workshop for Rheumatology Research CY FEB 22-24, 2007 CL Florence, ITALY C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD MAR 1 PY 2007 VL 66 SU 1 MA 004 BP A7 EP A7 PG 1 WC Rheumatology SC Rheumatology GA 138BN UT WOS:000244337600020 ER PT J AU Makrygiannakis, D Hermansson, M Ulfgren, AK Nicholas, AP Zendman, AJ Eklund, A Grunewald, J Skold, M Klareskog, L Catrina, AI AF Makrygiannakis, D. Hermansson, M. Ulfgren, A-K. Nicholas, A. P. Zendman, A. J. Eklund, A. Grunewald, J. Skold, M. Klareskog, L. Catrina, A. Irinel TI Smoking upregulates peptidylarginine 2 enzyme expression and citrullination SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT 27th European Workshop for Rheumatology Research CY FEB 22-24, 2007 CL Florence, ITALY C1 Karolinska Univ Hosp, Dept Rheumatol, Stockholm, Sweden. Karolinska Univ Hosp, Dept Resp Med, Stockholm, Sweden. Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL USA. Radboud Univ Nijmegen, Dept Biochem, Nijmegen, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD MAR 1 PY 2007 VL 66 SU 1 MA 035 BP A16 EP A16 PG 1 WC Rheumatology SC Rheumatology GA 138BN UT WOS:000244337600051 ER PT J AU Wright, CD Edwards, FH AF Wright, Cameron D. Edwards, Fred H. TI The society of thoracic surgeons general thoracic surgery database SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material RP Wright, CD (reprint author), Massachusetts Gen Hosp, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM wright.cameron@mgh.harvard.edu NR 0 TC 12 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAR PY 2007 VL 83 IS 3 BP 893 EP 894 DI 10.1016/j.athoracsur.2006.09.078 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 142KJ UT WOS:000244648100001 PM 17307428 ER PT J AU Grillo, HC Wright, CD AF Grillo, Hermes C. Wright, Cameron D. TI Tracheal compression with "hairpin" right aortic arch: Management by aortic division and aortopexy by right thoracotomy guided by intraoperative bronchoscopy SO ANNALS OF THORACIC SURGERY LA English DT Article ID LEFT SUBCLAVIAN ARTERY; KOMMERELLS DIVERTICULUM; ESOPHAGEAL COMPRESSION; SURGICAL-TREATMENT; VASCULAR RING AB Background. Four patients with severe tracheal obstruction due to right aortic arch, aberrant left subclavian artery, diverticulum of Kommerell, ligamentum or ductus arteriosum, and, additionally, right descending aorta, mild pectus excavatum, and high aortic arch apex, with narrow space between the ascending and descending aortic limbs, underwent division of ligamentum, excision of diverticulum and division (and reimplantation) of aberrant subclavian, either in multiple or single operations, but failed to achieve relief of obstruction. Methods. In addition to the procedures noted, fabric sling aortopexy of ascending and descending aortic limbs around adjacent ribs, with or without aortic division after prosthetic graft between ascending and descending aortic limbs was required, all performed through a right thoracotomy and adjunctive cervical incision, and with flexible bronchoscopic monitoring of each step. Results. Three patients obtained full relief of airway obstruction, which has persisted in follow-up from eight to over 12 years. One who had persistent severe tracheal malacia after prior tracheal resection and resultant chronic pulmonary sepsis died from these complications. Conclusions. In this unusual subset of a rare vascular ring anomaly, radical methods were necessary for correction of airway obstruction after failure of prior conventional procedures. C1 Massachusetts Gen Hosp, Thorac Surg Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Wright, CD (reprint author), Massachusetts Gen Hosp, Thorac Surg Div, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM wright.cameron@mgh.harvard.edu NR 13 TC 5 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAR PY 2007 VL 83 IS 3 BP 1152 EP 1157 DI 10.1016/j.athoracsur.2006.11.006 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 142KJ UT WOS:000244648100039 PM 17307479 ER PT J AU Illuminati, G LaMuraglia, G Nigri, G Vietri, F AF Illuminati, Giulio LaMuraglia, Glenn Nigri, Giuseppe Vietri, Francesco TI Surgical repair of an aberrant splenic artery aneurysm: Report of a case SO ANNALS OF VASCULAR SURGERY LA English DT Article ID ANOMALOUS SPLENOMESENTERIC TRUNK AB Aneurysms of the splenic artery are the most common splanchnic aneurysms. Aneurysms of a splenic artery with an anomalous origin from the superior mesenteric artery are however rare, with eight previously reported cases. Their indications for treatment are superposable to those of aneurysms affecting an orthotopic artery. Methods of treatment of this condition include endovascular, minimally invasive techniques and surgical resection. We report one more case of aneurysm of an aberrant splenic artery, treated with surgical resection, and preservation of the spleen. C1 [Illuminati, Giulio; Nigri, Giuseppe; Vietri, Francesco] Univ Roma La Sapienza, Francesco Durante Dept Surg, Rome, Italy. [LaMuraglia, Glenn] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg, Boston, MA 02115 USA. RP LaMuraglia, G (reprint author), Via Vincenzo Bellini 14, I-00198 Rome, Italy. EM giulio.illuminati@uniromal.it OI ILLUMINATI, Giulio/0000-0001-8773-8523 NR 10 TC 9 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD MAR-APR PY 2007 VL 21 IS 2 BP 216 EP 218 DI 10.1016/j.avsg.2006.06.014 PG 3 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 277IU UT WOS:000254206700018 PM 17349366 ER PT J AU Kaneki, M Shimizu, N Yamada, D Chang, KH AF Kaneki, Masao Shimizu, Nobuyuki Yamada, Daisuke Chang, Kyungho TI Nitrosative stress and pathogenesis of insulin resistance SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID NITRIC-OXIDE SYNTHASE; ALPHA-LIPOIC ACID; NF-KAPPA-B; ENDOPLASMIC-RETICULUM STRESS; INCREASED OXIDATIVE STRESS; ACTIVATED PROTEIN-KINASE; MUSCLE GLUCOSE-TRANSPORT; CENTRAL-NERVOUS-SYSTEM; ESTER L-NAME; SKELETAL-MUSCLE AB Insulin resistance is a major causative factor for type 2 diabetes and is associated with increased risk of cardiovascular disease. Despite intense investigation for a number of years, molecular mechanisms underlying insulin resistance remain to be determined. Recently, chronic inflammation has been highlighted as a culprit for obesity-induced insulin resistance. Nonetheless, upstream regulators and downstream effectors of chronic inflammation in insulin resistance remain unclarified. Inducible nitric oxide synthase (iNOS), a mediator of inflammation, has emerged as an important player in insulin resistance. Obesity is associated with increased iNOS expression in insulin-sensitive tissues in rodents and humans. Inhibition of MOS ameliorates obesity-induced insulin resistance. However, molecular mechanisms by which iNOS mediates insulin resistance remain largely unknown. Protein S-nitrosylation, a covalent attachment of NO moiety to thiol sulfhydryls, has emerged as a major mediator of a broad array of NO actions. S-nitrosylation is elevated in patients with type 2 diabetes, and increased S-nitrosylation of insulin signaling molecules, including insulin receptor, insulin receptor substrate-1, and Akt/PKB, has been shown in skeletal muscle of obese, diabetic mice. Akt/PKB is reversibly inactivated by S-nitrosylation. Based on these findings, S-nitrosylation has recently been proposed to play an important role in the pathogenesis of insulin resistance. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. Harvard Univ, Shriners Hosp Children, Sch Med, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. RP Kaneki, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 149 13th St,Rm 6604, Charlestown, MA 02129 USA. EM mkaneki@partners.org FU NIDDK NIH HHS [R01DK058127] NR 120 TC 76 Z9 80 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD MAR PY 2007 VL 9 IS 3 BP 319 EP 329 DI 10.1089/ars.2006.1464 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 130NL UT WOS:000243806200005 PM 17184170 ER PT J AU Wagner, MT Wymer, JH Carlozzi, NE Bachman, D Walker, A Mintzer, J AF Wagner, Mark T. Wymer, Joy H. Carlozzi, Noelle E. Bachman, David Walker, Aljoeson Mintzer, Jacobo CA Alzheimer Study Grp TI Preliminary examination of progression of Alzheimer's disease in a rural Southern African American cohort SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE African American; Alzheimer disease; dementia; neuropsychological assessment; cerebrovascular disease ID NEUROPSYCHOLOGICAL TEST-PERFORMANCE; MILD COGNITIVE IMPAIRMENT; NEUROPSYCHIATRIC INVENTORY; ISCHEMIC SCORE; UNITED-STATES; RISK-FACTORS; DEMENTIA; DIAGNOSIS; ADULTS; CERAD AB African Americans are at significantly increased risk for the development of Alzheimer's disease (AD), yet are seriously underrepresented in research trials. Preliminary experiences on a large scale, multi-site, 5-year longitudinal trial investigating the psychometric expression and progression of AD targeting an aging Southern rural cohort of African Americans are reported. Sixty-five participants, ranging from asymptomatic to severely demented, underwent extensive individual diagnostic and psychometric evaluation. Results indicated that cultural factors strongly influenced the data. Recruitment with asymptomatic volunteers were found to have greater educational attainment than other participant groups. Psychomotor measures showed greater impairment in African Americans compared to Caucasians suggesting increased cerebrovascular burden. African Americans' performance on the Boston Naming Test and the Wechsler Test of Adult Reading tests were significantly different than performance of Caucasian groups. The findings demonstrated that a better understanding of sociocultural factors associated with AD in the African American population may facilitate the development of primary and secondary preventions, especially when considering the role of cerebrovascular comorbidity which is a modifiable risk factor. (C) 2007 National Academy of Neuropsychology. Published by Elsevier Ltd. All rights reserved. C1 Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Wagner, MT (reprint author), Med Univ S Carolina, Dept Neurosci, CSB Room 307,96 Jonathon Lucas St, Charleston, SC 29425 USA. EM wagnermt@musc.edu NR 69 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD MAR PY 2007 VL 22 IS 3 BP 405 EP 414 DI 10.1016/j.acn.2007.01.014 PG 10 WC Psychology, Clinical; Psychology SC Psychology GA 196IO UT WOS:000248475100014 PM 17296283 ER PT J AU Gliklich, RE White, M Slayton, MH Barthe, PG Makin, IRS AF Gliklich, Richard E. White, Matthew Slayton, Michael H. Barthe, Peter G. Makin, Inder Raj S. TI Clinical pilot study of intense ultrasound therapy to deep dermal facial skin and subcutaneous tissues SO ARCHIVES OF FACIAL PLASTIC SURGERY LA English DT Article ID THERMAL-INJURY; LASER; FACE AB Objective: To evaluate the clinical safety of intense ultrasound in the treatment of the dermis and subcutaneous tissues of the face and neck in terms of skin inflammation, pain, adverse events, and histologic features. Design: In an open-label, phase 1 study, patients scheduled to undergo a rhytidectomy were enrolled into immediate (face-lift surgery within 24 hours of intense ultrasound treatment) and delayed (face-lift surgery 4-12 weeks after treatment) treatment groups. Intense ultrasound treatments were performed as a series of several linear exposures delivered 1.5 to 2.0 mm apart with the use of 1 of 3 available handpieces with different focal depths. Subject pain ratings and standardized digital photographs were obtained at uniform points. Photographs were blindly rated for inflammation. Histologic evaluation of treated tissues was performed with nitroblue tetrazolium chloride viability stain. Results: Fifteen subjects with a mean +/- SD age of 53 +/- 7 years were enrolled. Seven subjects were nonrandomly assigned to the immediate group and 8 were in the delayed group. On histologic examination, thermal injury zones were consistently identified in the dermis at exposure levels greater than 0.5 J as focal areas of denatured collagen. At this threshold level or above, most patient exposures were associated with transient superficial skin erythema and slight to mild discomfort on a standardized pain scale. No other adverse effects were noted in any case. Thermal injury zones were produced in the expected linear pattern and were consistent in size and depth from zone to zone. Increasing source power did not increase the depth of the epicenter of the thermal injury zone. Epidermis was spared in all cases. Conclusion: In this first clinical study of intense ultrasound therapy to facial tissues, the intense ultrasound system allowed for the safe and well-tolerated placement of targeted, precise, and consistent thermal injury zones in the dermis and subcutaneous tissues with sparing of the epidermis. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol,Div Facial Plast & Reconstru, Boston, MA USA. Ulthera Inc, Mesa, AZ USA. RP Gliklich, RE (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Facial Plast & Reconstruct Surg, 243 Charles St, Boston, MA 02114 USA. EM Richard_Gliklich@meei.harvard.edu NR 16 TC 33 Z9 34 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1521-2491 J9 ARCH FACIAL PLAST S JI Arch. Facial Plast. Surg. PD MAR-APR PY 2007 VL 9 IS 2 BP 88 EP 95 DI 10.1001/archfaci.9.2.88 PG 8 WC Surgery SC Surgery GA 147OI UT WOS:000245011900002 PM 17372061 ER PT J AU Kremen, WS Koenen, KC Boake, C Purcell, S Eisen, SA Franz, CE Tsuang, MT Lyons, MJ AF Kremen, William S. Koenen, Karestan C. Boake, Corwin Purcell, Shaun Eisen, Seth A. Franz, Carol E. Tsuang, Ming T. Lyons, Michael J. TI Pretrauma cognitive ability and risk for posttraumatic stress disorder - A twin study SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID TRAUMA EXPOSURE; REGISTRY; INTELLIGENCE; VETERANS; MEMORY; VULNERABILITY; ADOLESCENCE; DEPENDENCE; CHILDHOOD; SYMPTOMS AB Context: Cognitive deficits are associated with post-traumatic stress disorder (PTSD), but whether such deficits reflect sequelae or risk factors is not fully resolved. Objective: To determine, in a representative sample, whether preexposure cognitive ability is associated with risk for PTSD, and whether that risk is genetically mediated. Design, Setting, and Participants: The co-twin control study involved 2386 male Vietnam-era twin veterans with a mean (SD) age of 41.9 (2.7) years, a population-based sample of men who were in military service during this era. Cognitive ability scores were obtained just before military induction at a mean (SD) age of 19.7 (1.5) years. Participants included only individuals who were exposed to potentially traumatic events and underwent preexposure cognitive testing. Main Outcome Measures: Armed Forces Qualification Test (of cognitive ability) percentile scores and PTSD diagnosed by means of structured interviews. Results: We found a significant dose-response relationship between preexposure cognitive ability and risk for PTSD. After controlling for confounders, the highest cognitive ability quartile had a 48% lower risk than the lowest ability quartile (P < .001). Non-PTSD-concordant pairs had the highest scores; PTSD-concordant pairs had the lowest scores; and PTSD-discordant pairs had intermediate scores. Differences in Armed Forces Qualification Test scores within twin pairs were significant only in PTSD-discordant pairs (P = .04) and were accounted for specifically by the discordant dizygotic pairs (P = .002). Genetic influences on preexposure cognitive ability explained 5% of the variation in PTSD, but 100% of that relationship was explained by common genes. Conclusions: Preexposure cognitive ability is a risk or a protective factor for PTSD. The variance in PTSD explained by preexposure cognitive ability is accounted for entirely by common genetic factors. Lower cognitive ability may be a marker of less adaptive coping against adverse mental health consequences of exposure to potentially traumatic events. Further study of the potential mechanisms through which cognitive ability confers risk is needed. C1 Univ Calif San Diego, Ctr Behav Genom, Dept Psychiat, La Jolla, CA 92093 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Harvard Univ, Harvard Inst Psychait Epidemiol & Genet, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Harvard Inst Psychait Epidemiol & Genet, Dept Genet, Boston, MA 02115 USA. Inst Rehabil & Res, Houston, TX USA. Washington Univ, Sch Med, St Louis Vet Affairs Med Ctr, Res & Med Serv, St Louis, MO 63130 USA. Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63130 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63130 USA. RP Kremen, WS (reprint author), Univ Calif San Diego, Ctr Behav Genom, Dept Psychiat, 9500 Gilman Dr,Mail Code 0738, La Jolla, CA 92093 USA. EM wkremen@ucsd.edu RI Lyons, Michael/B-6119-2011; OI Lyons, Michael/0000-0001-6516-9219 FU NIA NIH HHS [AG 022982, R01 AG018384, R01 AG018386, R01 AG022381, AG 018384, AG 018386, AG 022381]; NIAAA NIH HHS [AA 010586]; NIDA NIH HHS [DA 04604]; NIMH NIH HHS [K08 MH070627-04, MH 070627, K08 MH070627] NR 44 TC 66 Z9 66 U1 3 U2 15 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAR PY 2007 VL 64 IS 3 BP 361 EP 368 DI 10.1001/archpsyc.64.3.361 PG 8 WC Psychiatry SC Psychiatry GA 142LB UT WOS:000244650200013 PM 17339525 ER PT J AU Bacskai, BJ Frosch, MP Freeman, SH Raymond, SB Augustinack, JC Johnson, KA Irizarry, MC Klunk, WE Mathis, CA DeKosky, ST Greenberg, SM Hyman, BT Growdon, JH AF Bacskai, Brian J. Frosch, Matthew P. Freeman, Stefanie H. Raymond, Scott B. Augustinack, Jean C. Johnson, Keith A. Irizarry, Michael C. Klunk, William E. Mathis, Chester A. DeKosky, Steven T. Greenberg, Steven M. Hyman, Bradley T. Growdon, John H. TI Molecular imaging with Pittsburgh compound B confirmed at autopsy - A case report SO ARCHIVES OF NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; AMYLOID BINDING; BRAIN; HUMANS AB Objective: To determine the correspondence between uptake of Pittsburgh Compound B (PiB) in life and measures of beta-amyloid (A beta) in postmortem tissue analysis. Patient: A 76-year-old man with a clinical diagnosis of dementia with Lewy bodies underwent fluorodeoxyglucose F-18 and PiB positron emission tomographic brain scans. Imaging revealed marked region specific binding of PiB and abnormal fluorodeoxyglucose uptake. Intervention: Autopsy was performed 3 months after the PiB scan. Results: Autopsy confirmed the clinical diagnosis; in addition, there was severe cerebral amyloid angiopathy and only moderate numbers of parenchymal A beta plaques. Biochemical measures revealed a positive correlation between A beta levels and regional PiB binding. Conclusion: This report confirms that PiB detects A beta in the living patient and demonstrates that amyloid deposited as cerebral amyloid angiopathy can be the dominant source of signal. C1 Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, CS Kubik Lab Nueropathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. RP Bacskai, BJ (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, 114 16th St, Charlestown, MA 02129 USA. EM bbacskai@partners.org RI Mathis, Chester/A-8607-2009; OI Klunk, William/0000-0001-5512-0251 FU NIA NIH HHS [AG05134]; NIBIB NIH HHS [EB00768]; NINDS NIH HHS [NS038372] NR 14 TC 190 Z9 195 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAR PY 2007 VL 64 IS 3 BP 431 EP 434 DI 10.1001/archneur.64.3.431 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 145GZ UT WOS:000244854600019 PM 17353389 ER PT J AU Anderson, CA Bosque, P Filley, CM Arciniegas, DB Kleinschmidt-DeMasters, BK Pape, WJ Tyler, KL AF Anderson, C. Alan Bosque, Patrick Filley, Christopher M. Arciniegas, David B. Kleinschmidt-DeMasters, B. K. Pape, W. John Tyler, Kenneth L. TI Colorado surveillance program for chronic wasting disease transmission to humans - Lessons from 2 highly suspicious but negative cases SO ARCHIVES OF NEUROLOGY LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; MULE DEER; PRIONS; ELK; BARRIERS AB Objective: To describe 2 patients with rapidly progressive dementia and risk factors for exposure to chronic wasting disease (CWD) in whom extensive testing negated the possible transmission of CWD. Design/Methods: We describe the evaluation of 2 young adults with initial exposure histories and clinical presentations that suggested the possibility of CWD transmission to humans. Patients: A 52-year-old woman with possible laboratory exposure to CWD and a 25-year-old man who had consumed meat from a CWD endemic area. Interventions: Clinical evaluation, neuropathological examination, and genetic testing. Results: Neuropathological and genetic assessment in the 2 patients proved the diagnoses of early-onset Alzheimer disease and a rare genetic prion disease. Conclusion: No convincing cases of CWD transmission to humans have been detected in our surveillance program. C1 Univ Colorado, Sch Med, Dept Neurol, Denver, CO 80202 USA. Univ Colorado, Sch Med, Dept Psychiat, Denver, CO 80202 USA. Univ Colorado, Sch Med, Dept Pathol, Denver, CO 80202 USA. Univ Colorado, Sch Med, Dept Med, Denver, CO 80202 USA. Univ Colorado, Sch Med, Dept Microbiol, Denver, CO 80202 USA. Univ Colorado, Sch Med, Dept Immunol, Denver, CO 80202 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Denver Hlth Med Ctr, Denver, CO USA. Colorado Dept Publ Hlth & Environm, Denver, CO USA. RP Anderson, CA (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol, B-182,4200 E 9th Ave, Denver, CO 80262 USA. EM al.anderson@uchsc.edu RI Arciniegas, David/A-3792-2009; OI Tyler, Kenneth/0000-0003-3294-5888 NR 19 TC 10 Z9 12 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAR PY 2007 VL 64 IS 3 BP 439 EP 441 DI 10.1001/archneur.64.3.439 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 145GZ UT WOS:000244854600021 PM 17353391 ER PT J AU Aiello, LP Ai, E Aiello, LM Anand, R Blumenkranz, M Boyer, D Brucker, AJ Chandler, T Chong, L Connor, T Danis, R Dehning, D Dodson, P Eaton, A Faber, D Finkelstein, D Forrester, JV Frank, RN Garcia, C Gardner, TW Gehrs, KM Goodart, RA Gottlieb, J Greven, CM Guyer, DR Hainsworth, D Hooper, P Jackson, WE Kinyoun, JL Kipnes, M Klein, ML Kohner, EM Kuppermann, B Lewis, H Li, HK Lund-Anderson, H Ma, C Martin, DF Orellana, J Paden, PY Polak, B Ross, SA Sharuk, G Singerman, LJ Smiddy, WE Trese, M Tweeten, JP Vine, A Vora, J Wolffenbuttel, B AF Aiello, Lloyd Paul Ai, Everett Aiello, Lloyd M. Anand, Rajiv Blumenkranz, Mark Boyer, David Brucker, Alexander J. Chandler, Thomas Chong, Lawrence Connor, Thomas Danis, Ron Dehning, Doug Dodson, Paul Eaton, Alexander Faber, David Finkelstein, Dan Forrester, John V. Frank, Robert N. Garcia, Charles Gardner, Thomas W. Gehrs, Karen M. Goodart, Roy A. Gottlieb, Justin Greven, Craig M. Guyer, David R. Hainsworth, Dean Hooper, Philip Jackson, Willliam E. Kinyoun, James L. Kipnes, Mark Klein, Michael L. Kohner, Eva M. Kuppermann, Baruch Lewis, Hilel Li, Helen K. Lund-Anderson, Henrik Ma, Colin Martin, Daniel F. Orellana, Juan Paden, Philip Y. Polak, Bettine Ross, Stuart A. Sharuk, George Singerman, Lawrence J. Smiddy, William E. Trese, Michael Tweeten, James P. Vine, Andrew Vora, Jiten Wolffenbuttel, Bruce CA PKC-DMES Study Grp TI Effect of ruboxistaurin in patients with diabetic macular edema - Thirty-month results of the randomized PKC-DMES clinical trial SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID PROTEIN-KINASE-C; ENDOTHELIAL GROWTH-FACTOR; BETA INHIBITOR; COMPLICATIONS; PROGRESSION; RATS; NEOVASCULARIZATION; AMELIORATION; RETINOPATHY; WISCONSIN AB Objective: To evaluate the safety and efficacy of orally administered ruboxistaurin (RBX) as a mesylate salt in patients with diabetic macular edema (DME). 1 Design: Multicenter, double-masked, randomized, placebo-controlled study of 686 patients receiving placebo or RBX orally ( 4, 16, or 32 mg/d) for 30 months. At baseline, patients had DME farther than 300 mu m from the center of the macula, an Early Treatment Diabetic Retinopathy Study retinopathy severity level from 20 to 47A without prior photocoagulation, and an Early Treatment Diabetic Retinopathy Study visual acuity of 75 or more letters in the study eye. The primary study outcome was progression to sight-threatening DME or application of focal/grid photocoagulation for DME. Main Outcome Measure: Masked grading of stereoscopic fundus photographs. Results: The delay in progression to the primary outcome was not statistically significant ( 32 mg of RBX vs placebo, P=.14 [unadjusted]; Cox proportional hazards model adjusted for covariates, hazards ratio=0.73; 95% confidence interval, 0.53-1.0; P=.06). However, application of focal/ grid photocoagulation prior to progression to sight-threatening DME varied by site, and a secondary analysis of progression to sight-threatening DME alone showed that 32 mg of RBX per day reduced progression, compared with placebo (P=.054 [ unadjusted]; Cox proportional hazards model, hazards ratio= 0.66; 95% confidence interval, 0.47-0.93; P=.02). Conclusions: Although progression to the primary outcome was not delayed, daily oral administration of RBX may delay progression of DME to a sight-threatening stage. Ruboxistaurin was well tolerated in this study. C1 Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. RP Aiello, LP (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM lloydpaul.aiello@joslin.harvard.edu RI Wolffenbuttel, Bruce/A-8419-2011 OI Wolffenbuttel, Bruce/0000-0001-9262-6921 NR 26 TC 83 Z9 86 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAR PY 2007 VL 125 IS 3 BP 318 EP 324 PG 7 WC Ophthalmology SC Ophthalmology GA 145DR UT WOS:000244846000003 ER PT J AU Boulos, PR Knoepp, SM Rubin, PAD AF Boulos, Patrick Roland Knoepp, Stewart M. Rubin, Peter A. D. TI Green bone SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID TETRACYCLINE; FLUORESCENCE; BILIRUBIN; GROWTH; TEETH; PHOTOSENSITIVITY; DISCOLORATION; ONYCHOLYSIS; ENAMEL AB Objective: To describe the unusual finding of yellow-green colored bone during routine orbital surgery, to detail its investigation, and to demonstrate its benign nature. Methods: When green bone was found, specimens were sent for light and fluorescent microscopy, ultraviolet photography, and spectrophotometry. Results: Yellow-green bone was encountered in 3 patients during orbital tumor excision or orbital fracture repair procedures. The only common cause was prior use of tetracycline during adolescence. All patients had healthy white dentition. In all cases, absence of neoplasia was demonstrated histologically. The bone fluoresced with a bright yellow-green color when exposed to 365-nm ultraviolet light. Histologic analysis demonstrated fluorescence located near the haversian canals. Spectrophotometry revealed absorption at 4 wavelengths specific to tetracycline: 230, 275, 380, and 440 nm. Conclusions: Fixation of tetracycline and ensuing fluorescence occurs mostly in areas of new bone growth and mineralization. This happens during childhood but also with bone remodeling associated with tumors or fractures. Once mineralized, teeth should therefore not be affected if tetracycline exposure occurs after ages 8 to 10 years. This paucity of external clues can lead to the surprising but innocuous surgical finding of green bone. Careful history and proper investigation can confirm its origin. C1 Eye Plast Consultants, Brookline, MA 02146 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Rubin, PAD (reprint author), Eye Plast Consultants, 44 Washington St, Brookline, MA 02146 USA. EM padrmd@aol.com NR 45 TC 2 Z9 2 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAR PY 2007 VL 125 IS 3 BP 380 EP 386 DI 10.1001/archopht.125.3.380 PG 7 WC Ophthalmology SC Ophthalmology GA 145DR UT WOS:000244846000012 PM 17353410 ER PT J AU McLaughlin, ME Pepin, SM MacCollin, M Choopong, P Lessell, S AF McLaughlin, Margaret E. Pepin, Susan M. MacCollin, Mia Choopong, Pitipol Lessell, Simmons TI Ocular pathologic findings of neurofibromatosis type 2 SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; NF2 TUMOR-SUPPRESSOR; LENS OPACITIES; MERLIN; NERVE; GENE AB Objective: To gain insight into the pathogenesis of neurofibromatosis type 2 (NF2) by investigating the ocular manifestations of this disease. Methods: Using standard histologic techniques, immunohistochemistry, and electron microscopy, we described the ocular pathologic findings of a 34-year-old woman who died from complications of NF2. Results: We identified 3 types of NF2-associated lesions: juvenile posterior subcapsular cataracts, epiretinal membranes, and an intrascleral schwannoma. Conclusions: Our analysis indicated that dysplastic lens cells accumulate just anterior to the posterior lens capsule in juvenile posterior subcapsular cataracts and that dysplastic Muller cells may be a major component of NF2-associated epiretinal membranes. C1 MIT, Ctr Canc Res, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP McLaughlin, ME (reprint author), MIT, Ctr Canc Res, E17-517,40 Ames St, Cambridge, MA 02139 USA. EM memclaughlin@partners.org NR 17 TC 15 Z9 15 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAR PY 2007 VL 125 IS 3 BP 389 EP 394 DI 10.1001/archopht.125.3.389 PG 6 WC Ophthalmology SC Ophthalmology GA 145DR UT WOS:000244846000013 PM 17353411 ER PT J AU Green, SM Redmond, P Januzzi, JL Aleryani, S Lee-Lewindrowski, C Sluss, P Lewandrowski, KB AF Green, Sandy M. Redmond, Patrick Januzzi, James L. Aleryani, Sarnir Lee-Lewindrowski, Cizabeth Sluss, Patrick Lewandrowski, Kent B. TI The impact of amino-terminal pro-brain natriuretic peptide testing on hospital length of stay and morbidity in patients with acute decompensated heart failure SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID OUTPATIENT TRIAL REDHOT; EMERGENCY-DEPARTMENT; DYSPNEIC PATIENTS; PLASMA-LEVELS; DIAGNOSIS; MANAGEMENT; PROGNOSIS; RISK AB center dot Context.-In clinical trials, N-terminal pro-brain natriuretic peptide (NT-proBNP) testing has been shown to be valuable for diagnosis and triage of patients with acute decompensated heart failure. It is not yet clear what benefits might be expected from the initiation of NT-proBNP testing in an everyday clinical setting. Objective.-To determine the effects of NT-proBNP testing on hospital length of stay as well as on 60-day morbidily and mortality in patients with acute decompensated heart failure before and after the test was implemented in the clinical laboratory. Design.-We measured hospital length of stay and 60-day morbidity and mortality rates among patients with acute decompensated heart failure admitted before and after initiation of NT-proBNP testing in our hospital. Differences in demographics between preimplementation and postimplementation groups were compared with the chi(2) test for categorical variables and the Wilcoxon rank sum test for continuous variables. Comparison between the hospital length of stay for each group was evaluated using the Mann-Whitney U test. Differences in rates of rehospitalization or death at 60 days following presentation were assessed using chi(2) cross-tabulation. Results.-Patients in the postimplementation group had similar clinical features as those in the preimplementation group. The hospital length of stay for patients in the postimplementation study group decreased both with respect to mean (1.86-day reduction) and median (1.3-day reduction) hospital stay (both, P = .03). Additionally, significantly lower rates of death (6.6% absolute risk reduction, P = .01), rehospitalization (12.1% absolute risk reduction, P = .005), and the composite of the 2 rates (18.7% absolute risk reduction, P = .008) were found following initiation of NT-proBNP testing. Conclusions.-Implementation of NT-proBNP testing may result in significant reductions in hospital length of stay as well as improvements in rates of morbidity and mortality in patients with acute decompensated heart failure. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol & Lab Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Lewandrowski, KB (reprint author), Massachusetts Gen Hosp, Dept Med, Gray 5,Fruit St, Boston, MA 02114 USA. EM Klewandrowski@partneis.org NR 23 TC 9 Z9 12 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAR PY 2007 VL 131 IS 3 BP 473 EP 476 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 142NJ UT WOS:000244656400022 PM 17516751 ER PT J AU van Drongelen, S Boninger, ML Impink, BG Khalaf, T AF van Drongelen, Stefan Boninger, Michael L. Impink, Bradley G. Khalaf, Tagreed TI Ultrasound imaging of acute biceps tendon changes after wheelchair sports SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE rehabilitation; shoulder; tendon injuries; ultrasonography; wheelchairs ID ROTATOR CUFF TEARS; UPPER EXTREMITY; SHOULDER JOINT; 2 SPEEDS; ULTRASONOGRAPHY; PARAPLEGIA; PROPULSION; PATHOLOGY; USERS; PAIN AB Objectives: To investigate acute changes in the biceps tendon after a high-intensity wheelchair propulsion activity and to determine whether these changes are related to subject characteristics. Design: The biceps tendon was imaged with ultrasound before and after wheelchair basketball or quad rugby. The average diameter of the tendon was calculated as well as the echogenicity ratio (the pixel intensity ratio of the biceps tendon to a reference just superficial to the tendon sheath). Setting: National Veterans Wheelchair Games in 2004 and 2005. Participants: Forty-two subjects who participated in wheelchair basketball or quad rugby at the Veterans Games. Interventions: Not applicable. Main Outcome Measures: Biceps tendon diameter and biceps echogenicity. Results: The echogenicity ratio of the tendon significantly decreased from 1.97 to 1.73 after the event (P=.038). The diameter of the biceps tendon increased from 4.60 to 4.82mm (P=.178). Also, it was found that the change in tendon diameter positively correlated with the time of play (P=.004). Conclusions: Acute changes in biceps tendon properties after exercise were found and likely represent edema, a first sign of overuse injury. The significance of continuous activity was shown by the fact that subjects who had more playing time showed a larger increase in tendon diameter. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. Swiss Parapleg Res, Nottwil, Switzerland. Mayo Clin, Coll Med, Dept Phys Med & Rehabil, Rochester, MN USA. RP Boninger, ML (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. EM boninger@pitt.edu RI van Drongelen, Stefan/J-4983-2015; OI van Drongelen, Stefan/0000-0001-5961-1015; Boninger, Michael/0000-0001-6966-919X NR 32 TC 19 Z9 19 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2007 VL 88 IS 3 BP 381 EP 385 DI 10.1016/j.apmr.2006.11.024 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 142AU UT WOS:000244621600018 PM 17321833 ER PT J AU Protopapas, MG Bundock, E Westmoreland, S Nero, C Graham, WA Nesathurai, S AF Protopapas, Marina G. Bundock, Elizabeth Westmoreland, Susan Nero, Christopher Graham, W. Andrew Nesathurai, Shanker TI The complications of scar formation associated with intrathecal pump placement SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE case report; intrathecal injections; muscle spasticity; spinal injections; rehabilitation ID NITRIC-OXIDE; MORPHINE; MONOCYTES AB A 40-year-old man had an intrathecal morphine-baclofen pump inserted for the treatment of severe dystonia affecting all limbs and severe low back pain. The etiology of his dystonic symptoms, despite thorough investigations, was uncertain. At age 45, the patient fell resulting in a cervical spinal cord injury. He underwent C2 through C5 instrumentation and fusion for cervical spine stabilization. Subsequently, an intrathecal morphine-baclofen pump was implanted to control pain and decrease spasticity. The patient ultimately died at age 48 from complications of pneumonia, and an autopsy was performed. Gross pathologic examination revealed that the intrathecal catheter entered the posterior aspect of the lumbar thecal sac, but coursed superiorly in the anterior intradural space. The catheter tip exited the thecal sac in the upper thoracic spine and became embedded in a fibrotic scar. Displacement of the catheter tip of the intrathecal morphine-baclofen pump and subsequent formation of scar tissue resulted in decreased drug delivery, contributing to diminished pain control and functional status. Catheter displacement and epidural scar formation must be considered as a potential cause of ineffective pain control and decreased functional status in patients with intrathecal morphine-baclofen pumps. C1 Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Nesathurai, S (reprint author), Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, 125 Nashua St, Boston, MA 02114 USA. EM snesathurai@partners.org NR 9 TC 6 Z9 6 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2007 VL 88 IS 3 BP 389 EP 390 DI 10.1016/j.apmr.2006.12.023 PG 2 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 142AU UT WOS:000244621600020 PM 17321835 ER PT J AU Wilson, CT Woloshin, S Schwartz, LM AF Wilson, Chad T. Woloshin, Steven Schwartz, Lisa M. TI Choosing where to have major surgery - Who makes the decision? SO ARCHIVES OF SURGERY LA English DT Article ID PERFORMANCE DATA; PUBLIC RELEASE AB Hypothesis: Efforts are under way to distribute hospital performance data directly to patients to inform their decisions about where to go for major surgery, but patients are not always involved in making the decision of where they will have surgery. Design: Telephone interviews. Participants: Five hundred ten randomly selected Medicare patients who had undergone 1 of 5 elective high-risk operations approximately 3 years earlier: abdominal aneurysm repair (n = 103), heart valve replacement surgery (n = 96), or resections for bladder (n = 119), lung (n = 128), or stomach (n = 64) cancer. Main Outcome Measure: Proportion of patients who responded that their physician was the main decision maker of where they would have surgery. Results: Thirty-one percent of patients said their physician was the main decision maker about where the patient would have surgery (42% said they decided equally with their physician, 22% said they were the main decision maker, and 5% said their family helped make the decision for them). This proportion was similar across patient age, income, and educational attainment. Men were more likely to say the physician was the main decision maker (34% vs 24%; P = .02), as were patients in poor to fair health compared with those in good to excellent health (37% vs; 28%; P = .05). The physician was significantly more likely to be the main decision maker for cardiovascular operations compared with cancer operations (39% vs 26%; P = .001). Conclusion: Although most patients participated in the decision of where they would have major surgery, one third said the decision was made mainly by their physician. C1 Dept Vet Affairs Med Ctr, VA Outcomes Grp, White River Jct, VT USA. Dartmouth Coll Sch Med, Ctr Evaluat Clin Sci, Hanover, NH USA. Dartmouth Hitchcock Med Ctr, Dept Med, Lebanon, NH 03766 USA. RP Wilson, CT (reprint author), Massachusetts Gen Hosp, Div Gen Surg, 55 Fruit St, Boston, MA 02114 USA. EM ctwilson@partners.org FU AHRQ HHS [R03HS1304901] NR 12 TC 27 Z9 27 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAR PY 2007 VL 142 IS 3 BP 242 EP 246 DI 10.1001/archsurg.142.3.242 PG 5 WC Surgery SC Surgery GA 143JO UT WOS:000244717700008 PM 17372048 ER PT J AU Zhang, YY Gottardo, L Mlynarski, W Frazier, W Nolan, D Duffy, J Marescotti, MC Gervino, EV Johnstone, MT Mantzoros, CS Avogaro, A Doria, A AF Zhang, Yuan-Yuan Gottardo, Lucia Mlynarski, Wojciech Frazier, Winfred Nolan, David Duffy, Jill Marescotti, Maria Cristina Gervino, Ernest V. Johnstone, Michael T. Mantzoros, Christos S. Avogaro, Angelo Doria, Alessandro TI Genetic variability at the leptin receptor (LEPR) locus is a determinant of plasma fibrinogen and C-reactive protein levels SO ATHEROSCLEROSIS LA English DT Article DE inflammation; leptin; genetics; fibrinogen; CRP ID CARDIOVASCULAR-DISEASE; RISK-FACTORS; OB-R; ASSOCIATION; OBESITY; HUMANS; CLONING; CELLS; MICE AB Objective: Cellular and animal studies suggest that leptin has proinflammatory and prothrombotic effects that could link increased adipose mass directly to atherogenesis. To investigate this hypothesis, we examined the effect of genetic variability at the leptin receptor (LEPR) locus on the plasma levels of fibrinogen and CRP-two markers of inflammation and susceptibility to atherosclerosis. Methods and results: Linkage disequilibrium analysis of 71 single-nucleotide polymorphisms (SNPs) spanning the LEPR locus revealed four haplotype blocks that could be tagged by 11 SNPs. In 630 healthy Caucasian individuals, variability in block #4 was significantly associated with plasma fibrinogen (p = 0.005), accounting for 3% of its variance (r(2) = 0.030). The same block was also associated with CRP levels (p = 0.049, r(2) = 0.022). The effect was strongest for two of the SNPs in this block. At rs3790432, fibrinogen was 10% higher in minor allele homozygotes than in major allele homozygotes and intermediate in heterozygotes (p = 0.015). At rs1805096, it was 5% higher (p = 0.007) and CRP 32% higher (p = 0.011) in major allele homozygotes than in minor allele carriers. This pattern of association was also evident in the haplotype analysis. Conclusions: Association of leptin receptor variability with inflammatory traits supports the hypothesis that leptin may play a role in atherogenesis. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Univ Padua, Dept Clin & Expt Med, I-35100 Padua, Italy. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. RP Doria, A (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM alessandro.doria@joslin.harvard.edu FU NHLBI NIH HHS [HL73168, HL71981]; NIDDK NIH HHS [DK36836] NR 30 TC 28 Z9 29 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAR PY 2007 VL 191 IS 1 BP 121 EP 127 DI 10.1016/j.atherosclerosis.2006.02.043 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 146OO UT WOS:000244944100015 PM 16580675 ER PT J AU Miller, MW Resick, PA AF Miller, Mark W. Resick, Patricia A. TI Internalizing and externalizing subtypes in female sexual assault survivors: Implications for the understanding of complex PTSD SO BEHAVIOR THERAPY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL COMORBIDITY SURVEY; BORDERLINE PERSONALITY-DISORDER; COMMON MENTAL-DISORDERS; DSM-III-R; PSYCHIATRIC-DISORDERS; ALEXITHYMIA CONSTRUCT; MAJOR DEPRESSION; TRAUMATIC EVENTS; CLINICAL-SAMPLE AB This study replicated and extended findings of internalizing and externalizing subtypes of posttraumatic psychopathology (Miller, M. W., Greif, J. L., & Smith, A. A. (2003). Multidimensional Personality Questionnaire profiles of veterans with traumatic combat exposure: Internalizing and externalizing subtypes. Psychological Assessment, 15, 205-215; Miller, M. W., Kaloupek, D. G., Dillon, A. L., & Keane, T.M. (2004). Externalizing and internalizing subtypes of combat-related PTSD: A replication and extension using the PSY-5 Scales. Journal of Abnormal Psychology, 113, 636-645) to a female sample of rape survivors with chronic PTSD. Cluster analyses of Schedule for Nonadaptive and Adaptive Personality (Clark, L. A. (1996). SNAP-Schedule for Nonadaptive and Adaptive Personality: Manual for administration, scoring, and interpretation. Minneapolis: University of Minnesota Press.) temperament scale profiles from 143 women with PTSD partitioned the sample into a simple PTSD cluster, defined by normal range personality scores and moderate symptomatology, and 2 more "complex" clusters distinguished by more severe tendencies towards externalizing or internalizing psychopathology. Externalizers were characterized by disinhibition, substance dependence, and Cluster B personality disorder features; internalizers by low positive temperament, high rates of major depressive disorder, and elevations on measures of schizoid and avoidant personality disorder. C1 [Miller, Mark W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Miller, Mark W.; Resick, Patricia A.] Boston Univ, Boston, MA 02215 USA. RP Miller, MW (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave,116B-2, Boston, MA 02130 USA. EM mark.miller5@va.gov RI Miller, Mark/G-7322-2011 OI Miller, Mark/0000-0001-6393-8563 FU NIMH NIH HHS [MH51509, MH66324, R01 MH051509, R01 MH051509-10, R03 MH066324] NR 78 TC 84 Z9 84 U1 7 U2 21 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD MAR PY 2007 VL 38 IS 1 BP 58 EP 71 DI 10.1016/j.beth.2006.04.003 PG 14 WC Psychology, Clinical SC Psychology GA 323BG UT WOS:000257418400005 PM 17292695 ER PT J AU Duerr, EM Chung, DC AF Duerr, Eva-Maria Chung, Daniel C. TI Molecular genetics of neuroendocrine tumors SO BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article DE neuroendocrine tumors; NET; carcinoid; MEN1; MEN2; VHL; CGH; LOH; microarray ID PANCREATIC ENDOCRINE TUMORS; COMPARATIVE GENOMIC HYBRIDIZATION; GASTROINTESTINAL CARCINOID-TUMORS; DEPENDENT KINASE INHIBITORS; NEOPLASIA TYPE-1 GENE; BETA-CATENIN GENE; SUPPRESSOR GENE; CYCLIN D1; MEN1 GENE; MICROSATELLITE INSTABILITY AB Neuroendocrine tumors can develop either sporadically or in association with familial syndromes such as multiple endocrine neoplasia type I (MEN I), multiple endocrine neoplasia type 2 (MEN2) or von Hippel-Lindau (VHL). A variety of genetic approaches has been utilized to dissect the underlying molecular pathogenesis of these distinctive tumors, including genome-wide screens such as comparative genomic hybridization, loss of heterozygosity and DNA microarray analysis as well as targeted investigations into specific tumor suppressor gene and oncogene candidates. The identification of the MEN I tumor suppressor gene that underlies the MEN I syndrome has provided important new insights into tumor pathogenesis. In addition, a number of independent approaches has converged on a pivotal role for regulators of the cell cycle. However, our understanding of the molecular biology of these tumors remains far from complete. In this review we highlight some of the key approaches, findings and implications of these genetic studies. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit,Dept Med, Boston, MA 02114 USA. RP Chung, DC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit,Dept Med, GRJ 825,50 Blossom St, Boston, MA 02114 USA. EM dchung@partners.org NR 92 TC 31 Z9 36 U1 0 U2 2 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1521-690X J9 BEST PRACT RES CL EN JI Best Pract. Res. Clin. Endoc. Metab. PD MAR PY 2007 VL 21 IS 1 BP 1 EP 14 DI 10.1016/j.beem.2006.12.001 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 159TZ UT WOS:000245891400002 PM 17382262 ER PT J AU Scadden, DT AF Scadden, David T. TI The stem cell niche in health and leukemic disease SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Article; Proceedings Paper CT Acute Leukemia Forum 2006 CY MAR 31, 2006 CL San Francisco, CA DE leukemia; stem cells; stem cell niches; microenvironment ID HEMATOPOIETIC STEM; PARATHYROID-HORMONE; PROGENITOR CELLS; OSTEOPONTIN; EXPRESSION; RECEPTORS; COMPONENT; CALCIUM; CANCER; SIZE AB That adult stem cells live in a highly specialized complex microenvironment, also known as a niche, is a pedestrian concept about 30 years old. It may, however, represent a relatively novel approach to being able to modify either normal or abnormal stem cells. Our emphasis in the past has been focused on identifying autonomous regulators of the stem cells and in attempting to modify them through the use of exogenous agents like cytokines. The body modulates these cells largely through the complex system that is embodied in the niche. This report discusses studies in which the niche components are modified to observe their effect on stem cells. The niches being investigated lie in the gut, skin, brain and bone. Other sites for hematopoiesis. exist in the body, but these specific microenvironments can be localized and each component. can be carefully evaluated using mouse models. Studies are ongoing as to how the stem cell! microenvironment can support or propagate malignancies. By understanding the signals of this particular microenvironment, we may be able to adapt them to achieve a therapeutic benefit. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Stem Cell Inst, Cambridge, MA USA. RP Scadden, DT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med, CPZN-4265A,185 Cambridge St, Boston, MA 02114 USA. EM scadden.david@mgh.harvard.edu FU NIDDK NIH HHS [R01 DK050234, R01 DK050234-11A2] NR 21 TC 35 Z9 40 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1521-6926 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PD MAR PY 2007 VL 20 IS 1 BP 19 EP 27 DI 10.1016/j.beha.2006.11.001 PG 9 WC Hematology SC Hematology GA 149WR UT WOS:000245178100004 PM 17336251 ER PT J AU Stone, RM AF Stone, Richard M. TI Targeted agents in AML: much more to do SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Article; Proceedings Paper CT Acute Leukemia Forum 2006 CY MAR 31, 2006 CL San Francisco, CA DE acute myeloid leukemia; targeted therapy; Flt3; farnesyl transferase inhibitors ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; ACUTE MYELOGENOUS LEUKEMIA; TYROSINE KINASE INHIBITOR; COLONY-STIMULATING FACTOR; PHASE-I; HEMATOLOGIC MALIGNANCIES; GEMTUZUMAB OZOGAMICIN; CELL TRANSPLANTATION; FLT3 ANTAGONIST AB To what degree has targeted therapy succeeded in acute myeloid leukemia (AML)? Targeted therapy has become a buzzword, with its meaning lost from overuse. In chronic myeloid leukemia (CML), gastrointestinal stromal cell tumor, and a small subset of patients with non-small cell lung cancer, a validated target has been identified and a highly specific therapeutic agent has been developed. Targeted therapy generally requires a pathophysiological Achilles heel in a tumor that can be exploited by nontoxic therapy. In most cases, the validated target has been a tyrosine kinase enzyme critical for tumor growth and survival. Are similar "drugable" targets available in AML? While our understanding of the pathophysiology of AML has advanced over the past decade, and some potential targets have been identified, no single agent will likely produce a significant proportion of remissions. On the other hand, nascent attempts with mild success have been achieved, yielding hope that this strategy will bear real fruit in the future. C1 Dana Farber Canc Inst, Adult Leukemia Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Stone, RM (reprint author), Dana Farber Canc Inst, Adult Leukemia Program, 44 Binney St,D 840, Boston, MA 02115 USA. EM rstone@partners.org NR 45 TC 13 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1521-6926 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PD MAR PY 2007 VL 20 IS 1 BP 39 EP 48 DI 10.1016/j.beha.2006.11.006 PG 10 WC Hematology SC Hematology GA 149WR UT WOS:000245178100006 PM 17336253 ER PT J AU Turner, JH Garnovskaya, MN Raymond, JR AF Turner, Justin H. Garnovskaya, Maria N. Raymond, John R. TI Serotonin 5-HT1A receptor stimulates c-Jun N-terrninal kinase and induces apoptosis in Chinese hamster ovary fibroblasts SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE 5-hydroxytryptamine; serotonin; apoptosis; programmed cell death; G protein; phosphorylation ID ACTIVATED PROTEIN-KINASE; BAY X 3702; TERMINAL KINASE; MEDIATED INHIBITION; PARKINSONS-DISEASE; SIGNALING PATHWAYS; CAUSES SUPPRESSION; CULTURED NEURONS; RAT HIPPOCAMPUS; CELL-SURVIVAL AB The 5-HTlA receptor is a prototypical member of the large and diverse scrotonin receptor family. One key role of this receptor is to stimulate cell proliferation and differentiation via the extracellular signal regulated protein kinase (ERK) mitogen activated protein (MAP) kinase. There are few reports on the ability of the 5-HTlA receptor to modulate other MAP kinases such as c-Jun N-terminal kinase (JNK), which is activated by various extracellular stimuli, resulting in cell growth, differentiation, and programmed cell death. We report here for the first time that the 5-HTlA receptor stimulates JNK. JNK stimulation was Pertussis toxin-sensitive and was mediated by Rho family low molecular weight GTPases. The 5-HTlA receptor also increased apoptosis, which was mimicked by the MEK inhibitor PD98059, and blocked by the JNK inhibitor SP600125. These results suggest that the 5-HTlA receptor stimulates both ERK-dependent anti-apoptotic pathways and JNK-dependent pro-apoptotic pathways in CHO cells. (c) 2006 Published by Elsevier B.V. C1 Ralph H Johnson VA Med Ctr, Med & Res Serv, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. RP Raymond, JR (reprint author), 179 Ashley Ave,Colcock Hall Off Provost, Charleston, SC 29425 USA. EM raymondj@musc.edu FU NIDDK NIH HHS [DK52448]; NIGMS NIH HHS [GM63909, GM08716] NR 61 TC 16 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD MAR PY 2007 VL 1773 IS 3 BP 391 EP 399 DI 10.1016/j.bbamcr.2006.12.003 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 147LS UT WOS:000245005100011 PM 17208318 ER PT J AU Levin, M Palmer, AR AF Levin, Michael Palmer, A. Richard TI Left-right patterning from the inside out: widespread evidence for intracellular control SO BIOESSAYS LA English DT Review ID LEFT-RIGHT ASYMMETRY; LEFT-RIGHT AXIS; PRIMARY CILIA FORMATION; PLANAR CELL POLARITY; MIRROR-IMAGE FLOWERS; BILATERAL GYNANDROMORPH; GAP-JUNCTIONS; EARLY STEP; DORSOVENTRAL AXIS; ZEBRAFISH EMBRYO AB The field of left-right (LR) patterning-the study of molecular mechanisms that yield directed morphological asymmetries in otherwise symmetrical organisms-is in disarray. On one hand is the undeniably elegant hypothesis that rotary beating of inclined cilia is the primary symmetry-breaking step: they create an asymmetric extracellular flow across the embryonic midline. On the other hand lurk many early symmetry-breaking steps that, even in some vertebrates, precede the onset of ciliary flow. We highlight an intracellular model of LR patterning where gene expression is initiated by physiological asymmetries that arise from subcellular asymmetries (e.g. motor-protein function along oriented cytoskeletal tracks). A survey of symmetry breaking in eukaryotes ranging from protists to vertebrates suggests that intracellular cytoskeletal elements are ancient and primary LR cues. Evolutionarily, quirky effectors like ciliary motion were likely added later in vertebrates. In some species (like mice), developmentally earlier cues may have been abandoned entirely. Late-developing asymmetries pose a challenge to the intracellular model, but early mid-plane determination in many groups increases its plausibility. Multiple experimental tests are possible. C1 Harvard Univ, Sch Dent Med, Forsyth Ctr Regenerat & Dev Biol, Forsyth Inst, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. Univ Alberta, Dept Biol Sci, Systemat & Evolut Grp, Edmonton, AB, Canada. Bamfield Marine Sci Ctr, Bamfield, BC, Canada. RP Levin, M (reprint author), Harvard Univ, Sch Dent Med, Forsyth Ctr Regenerat & Dev Biol, Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. EM mlevin@forsyth.org RI Palmer, A. Richard/A-3593-2010 OI Palmer, A. Richard/0000-0002-7579-3899 FU NCRR NIH HHS [C06RR11244]; NIGMS NIH HHS [GM06227] NR 124 TC 87 Z9 89 U1 3 U2 34 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0265-9247 J9 BIOESSAYS JI Bioessays PD MAR PY 2007 VL 29 IS 3 BP 271 EP 287 DI 10.1002/bies.20545 PG 17 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 142HY UT WOS:000244641300009 PM 17295291 ER PT J AU Hasler, G Pinto, A Greenberg, BD Samuels, J Fyer, AJ Pauls, D Knowles, JA McCracken, JT Piacentini, J Riddle, MA Rauch, SL Rasmussen, SA Willour, VL Grados, MA Cullen, B Bienvenu, JO Shugart, YY Liang, KY Hoehn-Saric, R Wang, Y Ronquillo, J Nestadt, G Murphy, DL AF Hasler, Gregor Pinto, Anthony Greenberg, Benjamin D. Samuels, Jack Fyer, Abby J. Pauls, David Knowles, James A. McCracken, James T. Piacentini, John Riddle, Mark A. Rauch, Scott L. Rasmussen, Steven A. Willour, Virginia L. Grados, Marco A. Cullen, Bernadette Bienvenu, O. Joseph Shugart, Yin-Yao Liang, Kung-yee Hoehn-Saric, Rudolf Wang, Ying Ronquillo, Jonne Nestadt, Gerald Murphy, Dennis L. TI Familiality of factor analysis-derived YBOCS dimensions in OCD-affected sibling pairs from the OCD collaborative genetics study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE comorbidity; endophenotypes; epidemiology; genetics; obsessive-compulsive disorder; symptom dimensions ID OBSESSIVE-COMPULSIVE DISORDER; LA-TOURETTE-SYNDROME; SYMPTOM DIMENSIONS; SEGREGATION ANALYSIS; COMORBIDITY; SCHIZOPHRENIA; EPIDEMIOLOGY; ASSOCIATION; FAMILY; POLYMORPHISM AB Background: Identification of familial, more homogenous characteristics of obsessive-compulsive disorder (OCD) may help to define relevant subtypes and increase the power of genetic and neurobiological studies of OCD. While factor-analytic studies have found consistent, clinically meaningful OCD symptom dimensions, there have been only limited attempts to evaluate the familiality and potential genetic basis of such dimensions. Methods: Four hundred eighteen sibling pairs with OCD were evaluated using the Structured Clinical Interview for DSM-IV and the Yale-Brown Obsessive Compulsive Scale (YBOCS) Symptom Checklist and Severity scales. Results: After controlling for sex, age, and age of onset, robust sib-sib intraclass correlations were found for two of the four YBOCS factors: Factor IV (hoarding obsessions and compulsions (p = .001) and Factor I (aggressive, sexual, and religious obsessions, and checking compulsions; p = .002). Smaller, but still significant, familiality was found for Factor III (contamination/cleaning; p = .02) and Factor 11 (symmetry/ordering/arranging;p = .04). Limiting the sample to female subjects more than doubled the familiality estimates for Factor 11 (p = .003). Among potentially relevant comorbid conditions for genetic studies, bipolar I/II and major depressive disorder were strongly associated with Factor I (p < .001), whereas ADHD, alcohol dependence, and bulimia were associated with Factor 11 (p < .01). Conclusions: Factor-analyzed OCD symptom dimensions in sibling pairs with OCD are familial with some gender-dependence, exhibit relatively specific relationships to comorbid psychiatric disorders and thus may be useful as refined phenotypes for molecular genetic studies of OCD. C1 NIMH, Clin Sci Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA. Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Div Child & Adolescent Psychiat, Sch Med, Los Angeles, CA 90024 USA. Massachusetts Gen Hosp, Psychiat Neuroimaging Res Program, Charlestown, MA USA. Massachusetts Gen Hosp, Obsess Compuls Disorders Program, Dept Psychiat, Charlestown, MA USA. RP Murphy, DL (reprint author), NIMH, Clin Sci Lab, Intramural Res Program, NIH, Bldg 10,Room 3D41,10 Ctr Dr,MSC 1264, Bethesda, MD 20892 USA. EM dm30h@nih.gov RI Piacentini, John/C-4645-2011; Liang, Kung-Yee/F-8299-2011; Hasler, Gregor/E-4845-2012; Pinto, Anthony/D-2718-2017; OI Hasler, Gregor/0000-0002-8311-0138; Pinto, Anthony/0000-0002-6078-7242; Samuels, Jack/0000-0002-6715-7905 FU Intramural NIH HHS; NIMH NIH HHS [R01 MH50214]; PHS HHS [OPD-GERCRR00052] NR 56 TC 93 Z9 96 U1 3 U2 8 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 MAR 1 PY 2007 VL 61 IS 5 BP 617 EP 625 DI 10.1016/j.biopsych.2006.05.040 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140BI UT WOS:000244476800006 PM 17027929 ER PT J AU Buitelaar, JK Michelson, D Danckaerts, M Gillberg, C Spencer, TJ Zuddas, A Faries, DE Zhang, SY Biederman, J AF Buitelaar, Jan K. Michelson, David Danckaerts, Marina Gillberg, Christopher Spencer, Thomas J. Zuddas, Alessandro Faries, Douglas E. Zhang, Shuyu Biederman, Joseph TI A randomized, double-blind study of continuation treatment for attention-deficit hyperactivity disorder after 1 year SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ADHD; atomoxetine; pediatric subjects; relapse prevention ID DEFICIT/HYPERACTIVITY DISORDER; PEDIATRIC-PATIENTS; ATOMOXETINE; CHILDREN; TRIAL AB Background: The efficacy of atomoxetine in maintaining symptom response following 1 year of treatment was assessed in children and adolescents (n = 163) with DSM-IV defined attention-deficit/hyperactivity disorder (ADHD). Methods: Subjects had previously responded to atomoxetine acutely and had completed I year of double-blind atomoxetine treatment. They were then randomly assigned in double-blind fashion to continued atomoxetine or placebo substitution for 6 months. Results: Atomoxetine was superior to placebo in preventing relapse (Wilcoxon test, p = .008) and in maintaining symptom response (ADHD Rating Scale IV score, p < .001). Among subjects assigned to discontinuation, the magnitude of symptom return was generally to a level of severity less than that observed at study entry. Conclusions: Following I year of treatment with atomoxetine, continued treatment over the ensuing 6 months was associated with superior outcomes compared with placebo substitution. However, there was considerable variability between individuals in the magnitude of symptom return after drug discontinuation, suggesting that some subjects treated with atomoxetine for a year with good results may consolidate gains made during drug treatment and could benefit from a medication-free trial to assess the need for ongoing drug treatment. C1 Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. Univ St Radboud, Med Ctr, Nijmegen, Netherlands. Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. Katholieke Univ Leuven, Louvain, Belgium. Barnneuropsykiatriska Klin, Gothenburg, Sweden. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Cagliari, Cagliari, Italy. RP Michelson, D (reprint author), Lilly Corp Ctr, Lilly Res Labs, DC 1730, Indianapolis, IN 46285 USA. EM michelson@lilly.com RI Buitelaar, Jan/E-4584-2012 OI Buitelaar, Jan/0000-0001-8288-7757 NR 16 TC 50 Z9 51 U1 0 U2 0 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 MAR 1 PY 2007 VL 61 IS 5 BP 694 EP 699 DI 10.1016/j.biopsych.2006.03.066 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140BI UT WOS:000244476800015 PM 16893523 ER PT J AU Polzer, J Bangs, ME Zhang, SY Dellva, MA Tauscher-Wisniewski, S Acharya, N Watson, SB Allen, AJ Wilens, TE AF Polzer, John Bangs, Mark E. Zhang, Shuyu Dellva, Mary Anne Tauscher-Wisniewski, Sitra Acharya, Nayan Watson, Susan B. Allen, Albert J. Wilens, Timothy E. TI Meta-analysis of aggression or hostility events in randomized, controlled clinical trials of atomoxetine for ADHD SO BIOLOGICAL PSYCHIATRY LA English DT Article DE aggression; atomoxetine; hostility; incidence difference; methylpheniclate; placebo ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; ONCE-DAILY ATOMOXETINE; DEFICIT HYPERACTIVITY DISORDER; JUVENILE-DELINQUENCY; PHYSICAL AGGRESSION; CONDUCT PROBLEMS; YOUNG-ADULTS; CHILDREN; BEHAVIOR; METHYLPHENIDATE AB Background: We systematically examined potential aggression/hostility-related events in a meta-analysis of acute clinical trials of atomoxetine for attention-deficit/hyperactivity disorder (ADHD). Methods: Pediatric patients from 14 trials of atomoxetine were subdivided into a placebo-controlled (atomoxetine n = 1308, placebo n = 806) or active comparator databases (atomoxetine n = 566, methylphenidate n = 472). A third database comprised adult patients from placebo-controlled studies (atomoxetine n = 541, placebo n = 405). A computerized search of adverse events and comments identified patients with potential aggression/hostility events. Mantel-Haenszel incidence differences (MHID) were calculated. Results: In the placebo-controlled database, we observed 21 atomoxetine and 9 placebo patients with reported aggression/hostility events, MHID of .6% (95% confidence interval [Cl]: -.4,1.7). In the active comparator database, there were seven events in atomoxetine and four in methylphenidate patients, MHID = .2% (95% CI: -1.0,11.3). In the adult database, there were no events in 0 atomoxetine and one placebo patient, MHID = -.3% (95% CI: -.8,.2). Conclusions: Aggression/hostility-related events occurred in less than 2% of patients and were more frequent in pediatric patients treated with atomoxetine versus placebo (risk ratio of 1.33; not statistically significant). The risk of aggression/hostility events was similar inpatients treated with atomoxetine or methylphenidate. C1 Lilly Res Labs, Indianapolis, IN USA. Lilly Res Ctr Ltd, Windlesham GU20 6PH, Surrey, England. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Polzer, J (reprint author), Lilly Corp Ctr, Indianapolis, IN 46285 USA. EM polzer@lilly.com NR 41 TC 18 Z9 19 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 2007 VL 61 IS 5 BP 713 EP 719 DI 10.1016/j.biopsych.2006.05.044 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140BI UT WOS:000244476800018 PM 16996485 ER PT J AU Mani, G Feldman, MD Patel, D Agrawal, CM AF Mani, Gopinath Feldman, Marc D. Patel, Devang Agrawal, C. Mauli TI Coronary stents: A materials perspective SO BIOMATERIALS LA English DT Review DE stent; surface treatment; surface modification; drug delivery ID DRUG-ELUTING STENTS; MUSCLE-CELL-PROLIFERATION; BALLOON-EXPANDABLE-STENT; IMMERSION ION-IMPLANTATION; TITANIUM-NITRIDE-OXIDE; 316L STAINLESS-STEEL; CARBON-COATED STENTS; LONG-TERM STABILITY; ARTERY-DISEASE; SURFACE MODIFICATION AB The objective of this review is to describe the suitability of different biomaterials as coronary stents. This review focuses on the following topics: (1) different materials used for stents, (2) surface characteristics that influence stent-biology interactions, (3) the use of polymers in stents, and (4) drug-eluting stents, especially those that are commercially available. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Texas, Coll Engn, Dept Biomed Engn, San Antonio, TX 78249 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Cardiol, San Antonio, TX 78229 USA. Dept Vet Affairs S Texas Hlth Care Syst, San Antonio, TX 78229 USA. RP Agrawal, CM (reprint author), Univ Texas, Coll Engn, Dept Biomed Engn, 1 UTSA Circle, San Antonio, TX 78249 USA. EM mauli.agrawal@utsa.edu NR 272 TC 388 Z9 410 U1 19 U2 179 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD MAR PY 2007 VL 28 IS 9 BP 1689 EP 1710 DI 10.1016/j.biomaterials.2006.11.042 PG 22 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 135RE UT WOS:000244169900011 PM 17188349 ER PT J AU Lee, BC Rodin, DM Shah, KK Dahl, DM AF Lee, Benjamin C. Rodin, David M. Shah, Ketul K. Dahl, Douglas M. TI Laparoscopic inguinal hernia repair during laparoscopic radical prostatectomy SO BJU INTERNATIONAL LA English DT Article DE prostatectomy; prostatic neoplasms; laparoscopy; hernia ID PROSTHETIC MESH HERNIOPLASTY; RETROPUBIC PROSTATECTOMY; SURGERY AB To describe our experience of simultaneous laparoscopic radical prostatectomy (LRP) and inguinal hernia repair (LIHR) with a non-absorbable mesh, as there are few reports of simultaneous herniorrhaphy during LRP. Forty patients who had simultaneous LIHR and LRP were retrospectively reviewed. All operations were completed via antegrade techniques using a non-absorbable mesh for the LIHR, as the results with absorbable mesh were disappointing. In all, 48 clinically apparent hernias were repaired in 40 patients (mean age 60 years). Of these, 13 were left-sided, 23 right-sided, and six bilateral; 19 were direct, 14 indirect, two pantaloon, three femoral, and in 10 the type was not recorded. The mean operative duration was 172 min and the mean hospital stay was 1.5 days. Two patients had a urine leak after surgery, which resolved with no further intervention, and two developed a pelvic lymphocele, one at 4 months and the other at 2 months after surgery. Two patients required urinary catheter re-insertion for retention after surgical catheter removal at 9 and 10 days after surgery, respectively. One patient developed a deep venous thrombosis 19 days after surgery. Of the 40 patients, 36 (90%) were followed for a mean of 10 months; none had a hernia recurrence on the repaired side, while two developed a new symptomatic contralateral hernia. LIHR is a successful and reliable way to treat symptomatic patients who are treated surgically for prostate cancer. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Boston, MA 02115 USA. RP Rodin, DM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Boston, MA 02115 USA. EM drodin@partners.org NR 15 TC 12 Z9 12 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD MAR PY 2007 VL 99 IS 3 BP 637 EP 639 DI 10.1111/j.1464-410X.2006.06687.x PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 134AF UT WOS:000244054300031 PM 17407518 ER PT J AU Appelbaum, FR Rosenblum, D Arceci, RJ Carroll, WL Breitfeld, PP Forman, SJ Larson, RA Lee, SJ Murphy, SB O'Brien, S Radich, J Scher, NS Smith, FO Stone, RM Tallman, MS AF Appelbaum, Frederick R. Rosenblum, Daniel Arceci, Robert J. Carroll, William L. Breitfeld, Philip P. Forman, Stephen J. Larson, Richard A. Lee, Stephanie J. Murphy, Sharon B. O'Brien, Susan Radich, Jerald Scher, Nancy S. Smith, Franklin O. Stone, Richard M. Tallman, Martin S. TI End points to establish the efficacy of new agents in the treatment of acute leukemia SO BLOOD LA English DT Article ID ACUTE-MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; MINIMAL RESIDUAL DISEASE; BONE-MARROW-TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; QUALITY-OF-LIFE; STEM-CELL TRANSPLANTATION; ONCOLOGY-GROUP; RETROSPECTIVE ANALYSIS; GEMTUZUMAB OZOGAMICIN AB Federal regulations provide 2 pathways for approval of new agents for the treatment of acute leukemia, regular and accelerated approval. Regular approval requires evidence of clinical benefit, which is generally defined as either prolongation of life or improved quality of life, or an effect on an end point established as a surrogate for clinical benefit. Accelerated approval can be obtained based on demonstration of an effect on a surrogate measure "reasonably likely" to predict clinical benefit, but requires demonstration of clinical benefit after approval as well. The acute leukemias are a heterogeneous and relatively uncommon group of diseases. The design and execution of prospective randomized clinical trials demonstrating prolongation of life or improved quality of life for patients with these disorders can be difficult and costly and require lengthy follow-up. Thus, the development of novel trial design and inclusion of validated surrogate markers for clinical benefit are needed. To explore some of the issues pertinent to the choice of end points for drug approval in acute leukemia, the Food and Drug Administration invited the American Society of Hematology to participate in the organization and conduct of a joint workshop. In this report, we present the results of that effort. C1 Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. NIH, Bethesda, MD 20892 USA. Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Mt Sinai Sch Med, Sch Med, New York, NY USA. NYU, Sch Med, New York, NY USA. Duke Univ, Sch Med, Durham, NC USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, Hlth Sci Ctr, Childrens Canc Res Inst, San Antonio, TX 78285 USA. MD Anderson Canc Ctr, Houston, TX USA. US FDA, Rockville, MD 20857 USA. Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. RP Appelbaum, FR (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D5-310,POB 19024, Seattle, WA 98109 USA. EM fappelba@fhcrc.org OI Larson, Richard/0000-0001-9168-3203 NR 41 TC 47 Z9 50 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 MAR 1 PY 2007 VL 109 IS 5 BP 1810 EP 1816 DI 10.1182/blood-2006-08-041152 PG 7 WC Hematology SC Hematology GA 142HW UT WOS:000244641100011 PM 17095617 ER PT J AU Bellucci, R Oertelt, S Gallagher, M Li, SG Zorn, E Weller, E Porcheray, F Alyea, EP Soiffer, RJ Munshi, NC Gershwin, ME Ritz, J AF Bellucci, Roberto Oertelt, Sabine Gallagher, Meagan Li, Sigui Zorn, Emmanuel Weller, Edie Porcheray, Fabrice Alyea, Edwin P. Soiffer, Robert J. Munshi, Nikhil C. Gershwin, M. Eric Ritz, Jerome TI Differential epitope mapping of antibodies to PDG-E2 in patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation and primary biliary cirrhosis SO BLOOD LA English DT Article ID PYRUVATE-DEHYDROGENASE COMPLEX; BONE-MARROW TRANSPLANTATION; MITOCHONDRIAL AUTO-ANTIGEN; DONOR LYMPHOCYTE INFUSION; VERSUS-HOST-DISEASE; MULTIPLE-MYELOMA; DIHYDROLIPOAMIDE ACETYLTRANSFERASE; ANTIMITOCHONDRIAL AUTOANTIBODIES; AUTOEPITOPE; RESPONSES AB A unique characteristic of the autoimmune liver disease primary biliary cirrhosis (PBC) is the presence of high-titer and extremely specific autoantibodies to the E2 component of the pyruvate dehydrogenase complex (PDC-E2). Autoantibodies to PDC-E2 antigen have only been detected in patients with disease or in those who subsequently develop PBC. One exception has been a subgroup of patients with multiple myeloma (MM) who underwent allogeneic hematopoietic stem cell transplantation (HSCT) and received donor lymphocyte infusions (DLIs) after transplantation. These patients developed high-titer antibodies to a variety of myeloma-associated antigens, including PDC-E2, coincident with rejection of myeloma cells in vivo. To examine the specificity of autoantibodies to PDC in these patients, we screened sera from patients with MM, chronic leukemias, monoclonal gammopathy of unknown significance (MGUS), PBC, and healthy donors. Three of 11 patients with MM (27%) and 2 of 6 patients with chronic leukemias (33%) developed anti-PDC-E2 antibodies in association with DLI response; 2 of 12 (17%) patients in the MGUS pretreatment control population also had detectable anti-PDC responses. Interestingly, the epitope specificity of these PDC-E2 autoantibodies was distinctive, suggesting that the mechanisms leading to loss of tolerance in the transplantation patients are distinct from PBC. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Calif Davis, Dept Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St M530, Boston, MA 02115 USA. EM jerome_ritz@dfci.harvard.edu FU NCI NIH HHS [P01 CA078378, CA078378]; NIAID NIH HHS [AI29530, U19 AI029530, P01 AI029530]; NIDDK NIH HHS [DK037003, R01 DK039588, R37 DK039588, DK39588, R01 DK083352] NR 39 TC 7 Z9 7 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 MAR 1 PY 2007 VL 109 IS 5 BP 2001 EP 2007 DI 10.1182/blood-2006-06-030304 PG 7 WC Hematology SC Hematology GA 142HW UT WOS:000244641100038 PM 17068145 ER PT J AU Weisberg, E Catley, L Wright, RD Moreno, D Banerji, L Ray, A Manley, PW Mestan, J Fabbro, D Jiang, JR Hall-Meyers, E Callahan, L DellaGatta, JL Kung, AL Griffin, JD AF Weisberg, Ellen Catley, Laurie Wright, Renee D. Moreno, Daisy Banerji, Lolita Ray, Arghya Manley, Paul W. Mestan, Juergen Fabbro, Doriano Jiang, Jingrui Hall-Meyers, Elizabeth Callahan, Linda DellaGatta, Jamie L. Kung, Andrew L. Griffin, James D. TI Beneficial effects of combining nilotinib and imatinib in preclinical models of BCR-ABL(+) leukemias SO BLOOD LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; KINASE INHIBITOR STI571; ABL TYROSINE KINASE; BCR-ABL; SELECTIVE INHIBITOR; CLINICAL RESISTANCE; ACCELERATED PHASE; POINT MUTATIONS; BLAST CRISIS AB Drug resistance resulting from emergence of imatinib-resistant BCR-ABL point mutations is a significant problem in advanced-stage chronic myelogenous leukemia (CML). The BCR-ABL inhibitor, nilotinib (AMN107), is significantly more potent against BCR-ABL than imatinib, and is active against many imatinib-resistant BCR-ABL mutants. Phase 1/2 clinical trials show that nilotinib can induce remissions in patients who have previously failed imatinib, indicating that sequential therapy with these 2 agents has clinical value. However, simultaneous, rather than sequential, administration of 2 BCR-ABL kinase inhibitors is attractive for many reasons, including the theoretical possibility that this could reduce emergence of drug-resistant clones. Here, we show that exposure of a variety of BCR-ABL(+) cell lines to imatinib and nilotinib results in additive or synergistic cytotoxicity, including testing of a large panel of cells expressing BCR-ABL point mutations causing resistance to imatinib in patients. Further, using a highly quantifiable bioluminescent in vivo model, drug combinations were at least additive in antileukemic activity, compared with each drug alone. These results suggest that despite binding to the same site in the same target kinase, the combination of imatinib and nilotinib is highly efficacious in these models, indicating that clinical testing of combinations of BCR-ABL kinase inhibitors is warranted. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Novartis Inst Biomed Res, Basel, Switzerland. RP Griffin, JD (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM james_griffin@dfci.harvard.edu RI Catley, Laurence/E-5313-2013; OI Kung, Andrew/0000-0002-9091-488X FU NCI NIH HHS [P01 CA066996, CA36167, CA66996, R01 CA036167, R37 CA036167]; NIDDK NIH HHS [DK50654, P01 DK050654] NR 39 TC 70 Z9 72 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 MAR 1 PY 2007 VL 109 IS 5 BP 2112 EP 2120 DI 10.1182/BLOOD-2006-06-026377 PG 9 WC Hematology SC Hematology GA 142HW UT WOS:000244641100052 PM 17068153 ER PT J AU Woo, A Moran, TB Choe, SK Schindler, Y Sullivan, M Fujiwara, Y Paw, BH Cantor, AB AF Woo, Andrew Moran, Tyler B. Choe, Seong-Kyu Schindler, Yocheved Sullivan, Matthew Fujiwara, Yuko Paw, Barry H. Cantor, Alan B. TI Identification of zfp148 (ZBP-89) as a novel GATA-1 associated Kruppel-type zinc finger transcription factor required for megakaryopoiesis and definitive erythropoiesis SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT 15th Conference on Hemoglobin Switching CY SEP 14-18, 2006 CL St Johns Coll, Oxford, ENGLAND HO St Johns Coll C1 Harvard Univ, Childrens Hosp, Sch Med, Dana Farber Canc Inst,Div Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol, Boston, MA 02115 USA. RI Iborra, Francisco/A-2943-2009 NR 0 TC 1 Z9 1 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 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAR-APR PY 2007 VL 38 IS 2 MA 15 BP 129 EP 130 DI 10.1016/j.bcmd.2006.10.023 PG 2 WC Hematology SC Hematology GA 140OB UT WOS:000244513900025 ER PT J AU Wang, J Rao, S Chu, J Shen, X Levasseur, DN Theunissen, TW Orkin, SH AF Wang, J. Rao, S. Chu, J. Shen, X. Levasseur, D. N. Theunissen, T. W. Orkin, S. H. TI Protein interaction network for pluripotency of ES cells: Possible clues to organization of self-renewal machinery in other stem cells SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT 15th Conference on Hemoglobin Switching CY SEP 14-18, 2006 CL St Johns Coll, Oxford, ENGLAND HO St Johns Coll C1 Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAR-APR PY 2007 VL 38 IS 2 MA 92 BP 164 EP 164 DI 10.1016/j.bcmd.2006.10.103 PG 1 WC Hematology SC Hematology GA 140OB UT WOS:000244513900102 ER PT J AU Schmahmann, JD Pandya, DN Wang, R Dai, G D'Arceuil, HE de Crespigny, AJ Wedeen, VJ AF Schmahmann, Jeremy D. Pandya, Deepak N. Wang, Ruopeng Dai, Guangping D'Arceuil, Helen E. de Crespigny, Alex J. Wedeen, Van J. TI Association fibre pathways of the brain: parallel observations from diffusion spectrum imaging and autoradiography SO BRAIN LA English DT Review DE tract tracing; tractography; fibre bundles; diffusion tensor imaging; isotope; disconnection ID INFERIOR TEMPORAL CORTEX; FRONTAL-CORTEX; RHESUS-MONKEY; IN-VIVO; BUCCOFACIAL APRAXIA; AUDITORY-CORTEX; STEREOTACTIC CINGULOTOMY; UNCINATE FASCICULUS; PREFRONTAL CORTEX; MIRROR NEURONS AB Understanding the long association pathways that convey cortical connections is a critical step in exploring the anatomic substrates of cognition in health and disease. Diffusion tensor imaging (DTI) is able to demonstrate fibre tracts non-invasively, but present approaches have been hampered by the inability to visualize fibres that have intersecting trajectories (crossing fibres), and by the lack of a detailed map of the origins, course and terminations of the white matter pathways. We therefore used diffusion spectrum imaging (DSI) that has the ability to resolve crossing fibres at the scale of single MRI voxels, and identified the long association tracts in the monkey brain. We then compared the results with available expositions of white matter pathways in the monkey using autoradiographic histological tract tracing. We identified 10 long association fibre bundles with DSI that match the observations in the isotope material: emanating from the parietal lobe, the superior longitudinal fasciculus subcomponents I, II and III; from the occipital-parietal region, the fronto-occipital fasciculus; from the temporal lobe, the middle longitudinal fasciculus and from rostral to caudal, the uncinate fasciculus, extreme capsule and arcuate fasciculus; from the occipital-temporal region, the inferior longitudinal fasciculus; and from the cingulate gyrus, the cingulum bundle. We suggest new interpretations of the putative functions of these fibre bundles based on the cortical areas that they link. These findings using DSI and validated with reference to autoradiographic tract tracing in the monkey represent a considerable advance in the understanding of the fibre pathways in the cerebral white matter. By replicating the major features of these tracts identified by histological techniques in monkey, we show that DSI has the potential to cast new light on the organization of the human brain in the normal state and in clinical disorders. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02215 USA. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol, CPZS-340,55 Fruit St, Boston, MA 02114 USA. EM jschmahmann@partners.org FU NCRR NIH HHS [P41RR14075, S10RR016811]; NIMH NIH HHS [MH64044]; NINDS NIH HHS [NS41285] NR 106 TC 482 Z9 490 U1 3 U2 54 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAR PY 2007 VL 130 BP 630 EP 653 DI 10.1093/brain/awl359 PN 3 PG 24 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 145BJ UT WOS:000244840000006 PM 17293361 ER PT J AU Kuperberg, GR Kreher, DA Sitnikova, T Caplan, DN Holcomb, PJ AF Kuperberg, Gina R. Kreher, Donna A. Sitnikova, Tatiana Caplan, David N. Holcomb, Phillip J. TI The role of animacy and thematic relationships in processing active English sentences: Evidence from event-related potentials SO BRAIN AND LANGUAGE LA English DT Article DE semantics; syntax; language; P600; N400; ERP ID SYNTACTIC AMBIGUITY RESOLUTION; BRAIN POTENTIALS; LANGUAGE COMPREHENSION; SEMANTIC ANOMALIES; EYE-MOVEMENTS; TIME-COURSE; INFORMATION; MEMORY; INDEPENDENCE; INTEGRATION AB Recent event-related potential studies report a P600 effect to incongruous verbs preceded by semantically associated inanimate noun-phrase (NP) arguments, e.g., "eat" in "At breakfast the eggs would eat.....". This P600 effect may reflect the processing cost incurred when semantic-thematic relationships between critical verbs and their preceding NP argument(s) bias towards different interpretations to those dictated by their sentences' syntactic structures. We have termed such violations of alternative thematic roles, 'thematic role violations.' Semantic-thematic relationships are influenced both by semantic associations and by more basic semantic features, such as a noun's animacy. This study determined whether a P600 effect can be evoked by verbs whose thematic structures are violated by their preceding inanimate NP arguments, even in the absence of close semantic-associative relationships with these arguments or their preceding contexts. ERPs were measured to verbs under four conditions: (1) non-violated ("At breakfast the boys would eat..."); (2) preceded by introductory clauses and animate NPs that violated their pragmatic expectations but not their thematic structures ("At breakfast the boys would plant..."); (3) preceded by semantically related contexts but inanimate NPs that violated their thematic structures ("At breakfast the eggs would eat..."); (4) preceded by semantically unrelated contexts and inanimate NPs that also violated their thematic structures ("At breakfast the eggs would plant..."). Pragmatically non-thematic role violated verbs preceded by unrelated contexts and animate NPs evoked robust N400 effects and small P600 effects. Thematically violated verbs preceded by inanimate argument NPs evoked robust P600 effects but no N400 effects, regardless of whether these inanimate arguments or their preceding contexts were semantically related or unrelated to these verbs. These findings suggest that semantic-thematic relations, related to animacy constraints on verbs' arguments, are computed online and can immediately impact verb processing within active, English sentences. (C) 2006 Elsevier Inc. All rights reserved. C1 Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Kuperberg, GR (reprint author), Tufts Univ, Dept Psychol, Medford, MA 02155 USA. EM kuperber@nmr.mgh.harvard.edu FU NICHD NIH HHS [R01 HD025889-15, HD25889, R01 HD025889, R01 HD025889-17, R01 HD043251, R01 HD043251-05]; NIMH NIH HHS [K23 MH02034, R01 MH071635] NR 62 TC 88 Z9 98 U1 2 U2 21 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD MAR PY 2007 VL 100 IS 3 BP 223 EP 237 DI 10.1016/j.bandl.2005.12.006 PG 15 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 158XG UT WOS:000245828100001 PM 16546247 ER PT J AU Kurowski, KM Blumstein, SE Palumbo, CL Waldstein, RS Burton, MW AF Kurowski, Kathleen M. Blumstein, Sheila E. Palumbo, Carole L. Waldstein, Robin S. Burton, Martha W. TI Nasal consonant production in Broca's and Wernicke's aphasics: Speech deficits and neuroanatomical correlates SO BRAIN AND LANGUAGE LA English DT Article DE aphasic; speech; nasal consonants; murmur; acoustic; articulatory; laryngeal; lesion extent ID VOICE-ONSET TIME; UNILATERAL BRAIN-DAMAGE; ANTICIPATORY COARTICULATION; ACOUSTIC ANALYSIS; ARTICULATION; APRAXIA; PATIENT; PERCEPTION; INTONATION; MOVEMENTS AB The present study investigated the articulatory implementation deficits of Broca's and Wernicke's aphasics and their potential neuro-anatomical correlates. Five Broca's aphasics, two Wernicke's aphasics, and four age-matched normal speakers produced consonant-vowel-(consonant) real word tokens consisting of [m, n] followed by [i, e, a, o, u]. Three acoustic measures were analyzed corresponding to different properties of articulatory implementation: murmur duration (a measure of timing), amplitude of the first harmonic at consonantal release (a measure of articulatory coordination), and murmur amplitude over time (a measure of laryngeal control). Results, showed that Broca's aphasics displayed impairments in all of these parameters, whereas Wernicke's aphasics only exhibited greater variability in the production of two of the parameters. The lesion extent data showed that damage in either Broca's area or the insula cortex was not predictive of the severity of the speech output impairment. Instead, lesions in the upper and lower motor face areas and the supplementary motor area resulted in the most severe implementation impairments. For the Wernicke's aphasics, the posterior areas (superior marginal gyrus, parietal, and sensory) appear to be involved in the retrieval and encoding of lexical forms for speech production, resulting in increased variability in speech production. (C) 2006 Elsevier Inc. All rights reserved. C1 Brown Univ, Dept Cognit & Linguist Sci, Providence, RI 02912 USA. Dept Vet Affairs Med Ctr, Res Serv, Providence, RI 02908 USA. Boston Univ, Harold Goodglass Aphasia Res Ctr, VA Boston Healthcare Syst, Boston, MA 02130 USA. VA Boston Healthcare Syst, Res Serv, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. RP Kurowski, KM (reprint author), Brown Univ, Dept Cognit & Linguist Sci, Providence, RI 02912 USA. EM Kathleen_Kurowski@brown.edu FU NIA NIH HHS [R01 AG014345]; NIDCD NIH HHS [R01 DC000314-19, R01 DC000314-21A1, P50 DC000081-34, P50 DC000081-35, R01 DC000314-20, R01 DC000314-18, P50 DC000081, R01 DC000314, R01 DC000314-15, R01 DC000314-17, R01 DC000314-16, R01 DC000314-14, P50 DC000081-35S1]; PHS HHS [00314, 0081] NR 50 TC 3 Z9 3 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 0093-934X J9 BRAIN LANG JI Brain Lang. PD MAR PY 2007 VL 100 IS 3 BP 262 EP 275 DI 10.1016/j.bandl.2006.10.002 PG 14 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 158XG UT WOS:000245828100004 PM 17145076 ER PT J AU Baselga, J Piccart-Gebhart, MJ Gelber, RD di Cosimo, S Viale, G Koehler, M Rojo, F AF Baselga, J. Piccart-Gebhart, M. J. Gelber, R. D. di Cosimo, S. Viale, G. Koehler, M. Rojo, F. TI Neo-ALTTO (neoadjuvant lapatinib and/or trastuzumab treatment optimisation) study [BIG 1-06/SOLTI/EGF106903]: a phase III translational study for Her2-overexpressing early breast cancer (BC) SO BREAST LA English DT Meeting Abstract C1 [Baselga, J.; di Cosimo, S.; Rojo, F.] Hebron Univ Hosp, Barcelona, Spain. [Piccart-Gebhart, M. J.] Inst Jules Bordet, B-1000 Brussels, Belgium. [Gelber, R. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Viale, G.] European Inst Oncol, Milan, Italy. [Koehler, M.] GlaxoSmithKline Inc, Collegeville, PA USA. RI Rojo, Federico/S-6551-2016 NR 0 TC 2 Z9 2 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD MAR PY 2007 VL 16 SU 1 BP S48 EP S48 DI 10.1016/S0960-9776(07)70184-4 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 320ZU UT WOS:000257274600154 ER PT J AU Garber, J AF Garber, J. TI Breast cancer genetics: clues to tumor biology SO BREAST LA English DT Meeting Abstract C1 [Garber, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD MAR PY 2007 VL 16 SU 1 BP S2 EP S2 DI 10.1016/S0960-9776(07)70029-2 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 320ZU UT WOS:000257274600004 ER PT J AU Gelber, RD Goldhirsch, A AF Gelber, R. D. Goldhirsch, A. TI Using clinical trial data to tailor adjuvant treatments for individual patients SO BREAST LA English DT Meeting Abstract C1 [Gelber, R. D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Int Breast Canc Study Grp, Boston, MA 02115 USA. [Goldhirsch, A.] European Inst Oncol, Dept Med, Milan, Italy. [Goldhirsch, A.] Oncol Inst So Switzerland, Bellinzona, Switzerland. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD MAR PY 2007 VL 16 SU 1 BP S8 EP S8 DI 10.1016/S0960-9776(07)70049-8 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 320ZU UT WOS:000257274600023 ER PT J AU Harris, JR AF Harris, J. R. TI State of the art of post mastectomy radiation therapy (PMRT) SO BREAST LA English DT Meeting Abstract ID EARLY BREAST-CANCER; RANDOMIZED-TRIALS; 15-YEAR SURVIVAL; RECURRENCE C1 [Harris, J. R.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD MAR PY 2007 VL 16 SU 1 BP S6 EP S7 DI 10.1016/S0960-9776(07)70045-0 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 320ZU UT WOS:000257274600019 ER PT J AU Moy, B Maltzman, JD Goss, PE AF Moy, B. Maltzman, J. D. Goss, P. E. TI Phase III study of lapatinib after completion of adjuvant chemotherapy in trastuzumab-naive women with ErbB2-overexpressing breast cancer: Tykerb evaluation after chemotherapy (TEACH) study SO BREAST LA English DT Meeting Abstract C1 [Moy, B.; Goss, P. E.] Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Boston, MA 02114 USA. [Maltzman, J. D.] GlaxoSmithKline Inc, Collegeville, PA USA. NR 0 TC 4 Z9 4 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD MAR PY 2007 VL 16 SU 1 BP S47 EP S47 DI 10.1016/S0960-9776(07)70179-0 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 320ZU UT WOS:000257274600149 ER PT J AU Partridge, AH AF Partridge, A. H. TI Fertility and adjuvant treatment in young women with breast cancer SO BREAST LA English DT Meeting Abstract C1 [Partridge, A. H.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD MAR PY 2007 VL 16 SU 1 BP S11 EP S12 DI 10.1016/S0960-9776(07)70064-4 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 320ZU UT WOS:000257274600034 ER PT J AU Piccart-Gebhart, MJ Perez, EA Baselga, J Gelber, RD Rosa, D Azambuja, E Oliva, C Goldhirsch, A AF Piccart-Gebhart, M. J. Perez, E. A. Baselga, J. Gelber, R. D. Rosa, D. Azambuja, E. Oliva, C. Goldhirsch, A. TI ALTTO (adjuvant lapatinib and/or trastuzumab treatment optimisation) study [BIG 2-06/N063D/EGF106708]: a phase III study for HER2-overexpressing early breast cancer (BC) SO BREAST LA English DT Meeting Abstract C1 [Piccart-Gebhart, M. J.; Rosa, D.; Azambuja, E.] Inst Jules Bordet, B-1000 Brussels, Belgium. [Perez, E. A.] Mayo Clin, Jacksonville, FL 32224 USA. [Baselga, J.] Vall Hebron Univ Hosp, Barcelona, Spain. [Gelber, R. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Oliva, C.] GlaxoSmithKline Inc, Collegeville, PA USA. [Goldhirsch, A.] European Inst Oncol, Milan, Italy. NR 0 TC 5 Z9 5 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD MAR PY 2007 VL 16 SU 1 BP S46 EP S47 DI 10.1016/S0960-9776(07)70178-9 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 320ZU UT WOS:000257274600148 ER PT J AU Suter, TM Procter, M van Veldhuisen, DJ Muscholl, M Muehlbauer, S Gelber, RD Piccart-Gebhart, MJ AF Suter, T. M. Procter, M. van Veldhuisen, D. J. Muscholl, M. Muehlbauer, S. Gelber, R. D. Piccart-Gebhart, M. J. TI Cardiac side effects in the HERceptin Adjuvant (HERA) trial SO BREAST LA English DT Meeting Abstract C1 [Suter, T. M.] Swiss Cardiovasc Ctr, Bern, Switzerland. [van Veldhuisen, D. J.] Univ Groningen, Groningen, Netherlands. [Muehlbauer, S.] F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. [Gelber, R. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Piccart-Gebhart, M. J.] Inst Jules Bordet, Dept Med, B-1000 Brussels, Belgium. [Piccart-Gebhart, M. J.] Breast Int Grp, Brussels, Belgium. RI van Veldhuisen, Dirk Jan/E-8967-2014 NR 0 TC 1 Z9 1 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD MAR PY 2007 VL 16 SU 1 BP S44 EP S44 DI 10.1016/S0960-9776(07)70170-4 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 320ZU UT WOS:000257274600140 ER PT J AU Winer, E Tolaney, S AF Winer, E. Tolaney, S. TI Role of baseline staging and follow-up: between reassurance and economic constraints SO BREAST LA English DT Meeting Abstract C1 [Winer, E.; Tolaney, S.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD MAR PY 2007 VL 16 SU 1 BP S4 EP S4 DI 10.1016/S0960-9776(07)70038-3 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 320ZU UT WOS:000257274600012 ER PT J AU Marcom, PK Isaacs, C Harris, L Wong, ZW Kommarreddy, A Novielli, N Mann, G Tao, Y Ellis, MJ AF Marcom, P. Kelly Isaacs, Claudine Harris, Lyndsay Wong, Zee Wang Kommarreddy, Aruna Novielli, Nellie Mann, Gretchen Tao, Yu Ellis, Matthew J. TI The combination of letrozole and trastuzumab as first or second-line biological therapy produces durable responses in a subset of HER2 positive and ER positive advanced breast cancers SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; letrozole; trastuzumab; phase 2 clinical trial ID ENDOCRINE THERAPY; SERUM HER-2/NEU; HORMONE-THERAPY; TAMOXIFEN; EFFICACY; SAFETY; CHEMOTHERAPY; RESISTANCE; ANTIBODY; PLUS AB Background Estrogen receptor (ER) and/or progesterone receptor expression occurs in similar to 50% HER2 positive (HER2+) breast cancers and cross-talk between the estrogen and HER2 pathways promotes endocrine therapy resistance. The efficacy of the aromatase inhibitor letrozole in combination with trastuzumab was therefore tested in a Phase 2 study. Methods Patients with ER+ and/or PgR+ and HER2+ (IHC 2+ or 3+ or FISH+) advanced breast cancer were treated with trastuzumab plus letrozole until disease progression or unacceptable toxicity. Results Thirty-three patients were enrolled, of which thirty one were considered evaluable. The majority of patients (82%) had received tamoxifen and 82% had HER2 FISH+ and/or IHC 3+ tumors. Eight patients responded (1 CR and 7 PR) for an overall response rate (ORR) of 26% and a clinical benefit rate (CBR) of 52%. The median time to progression (TTP) was 5.8 months and the median duration of response (DOR) was 20.6+ months. Excluding IHC 2+, FISH- tumors, the OR was 24%, CBR 44%, TTP 5.5 months and DOR 17+ months. The combination was well tolerated with only two toxicity events requiring termination of study medication. Conclusions Combined trastuzumab and letrozole treatment for patients with HER2+ and ER+ advanced breast cancer produced durable responses consistently lasting at least 1 year in one quarter of the patients. While these data are promising for a subgroup, for half the patients, trastuzumab plus letrozole was inactive. This finding demonstrates ER+ HER2+ advanced disease is heterogeneous and additional agents will be required for optimal management based on targeted therapeutics alone. C1 Washington Univ, Sch Med, Siteman Comprehens Canc Ctr, St Louis, MO USA. Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Singapore Natl Canc Inst, Singapore, Singapore. Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Durham, NC 27710 USA. RP Ellis, MJ (reprint author), Washington Univ, Sch Med, Siteman Comprehens Canc Ctr, 660 S Euclid Ave,Campus Box 8056, St Louis, MO USA. EM mellis@wustl.edu NR 18 TC 100 Z9 103 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD MAR PY 2007 VL 102 IS 1 BP 43 EP 49 DI 10.1007/s10549-006-9307-8 PG 7 WC Oncology SC Oncology GA 137OV UT WOS:000244302800005 PM 16897431 ER PT J AU Ozanne, EM Annis, C Adduci, K Showstack, J Esserman, L AF Ozanne, Elissa M. Annis, Caroline Adduci, Kelly Showstack, Jonathan Esserman, Laura TI Pilot trial of a computerized decision aid for breast cancer prevention SO BREAST JOURNAL LA English DT Article DE breast cancer; decision aid; decision support; prevention; risk assessment; shared decision making ID PROPHYLACTIC BILATERAL MASTECTOMY; HORMONE REPLACEMENT THERAPY; RANDOMIZED-TRIAL; WOMEN; RISK; PATIENT; PERCEPTIONS; KNOWLEDGE; FRAMEWORK; SCALE AB This study sought to evaluate a shared decision-making aid for breast cancer prevention care designed to help women make appropriate prevention decisions by presenting information about risk in context. The decision aid was implemented in a high-risk breast cancer prevention program and pilot-tested in a randomized clinical trial comparing standard consultations to use of the decision aid. Physicians completed training with the decision aid prior to enrollment. Thirty participants enrolled (15 per group) and completed measures of clinical feasibility and effectiveness prior to, immediately after, and at 9 months after their consultations. The decision aid was feasible to use during the consultations as measured by consultation duration, user satisfaction, patient knowledge, and decisional conflict. The mean consultation duration was not significantly different between groups (24 minutes for intervention group versus 21 minutes for control group, p = 0.42). The majority found the decision aid acceptable and useful and would recommend it to others. Both groups showed an improvement in breast cancer prevention knowledge postvisit, which was significant in the intervention group (p = 0.01) but not the control group (p = 0.13). However, the knowledge scores returned to baseline at follow-up in both groups. Decision preference for patients who chose chemoprevention post consultations remained constant at follow-up for the intervention group, but not for the control group. The decision framework provides access to key information during consultations and facilitates the integration of emerging biomarkers in this setting. Initial results suggest that the decision aid is feasible for use in the consultation room. The tendency for the decision choices and knowledge scores to return to baseline at follow-up suggests the need for initial and ongoing prevention decision support. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Univ Calif San Francisco, Med Ctr, Carol Franc Buck Breast Care Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. Univ Calif San Francisco, Med Ctr, Dept Surg & Radiol, San Francisco, CA 94143 USA. RP Ozanne, EM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM elissa@mgh-ita.org RI Showstack, Jonathan/L-6556-2013 OI Showstack, Jonathan/0000-0002-1367-419X NR 45 TC 33 Z9 33 U1 2 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1075-122X J9 BREAST J JI Breast J. PD MAR-APR PY 2007 VL 13 IS 2 BP 147 EP 154 DI 10.1111/j.1524-4741.2007.00395.x PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 138CV UT WOS:000244341600006 PM 17319855 ER PT J AU Brusic, V AF Brusic, Vladimir TI The growth of bioinformatics SO BRIEFINGS IN BIOINFORMATICS LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Brusic, V (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1467-5463 J9 BRIEF BIOINFORM JI Brief. Bioinform. PD MAR PY 2007 VL 8 IS 2 BP 69 EP 70 DI 10.1093/bib/bbm008 PG 2 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 162WN UT WOS:000246120300001 PM 17384431 ER PT J AU Jackson, ML Bassett, K Nirmalan, PV Sayre, EC AF Jackson, M. L. Bassett, K. Nirmalan, P. V. Sayre, E. C. TI Contrast sensitivity and visual hallucinations in patients referred to a low vision rehabilitation clinic SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CHARLES-BONNET-SYNDROME; PARKINSONS-DISEASE; DISCRIMINATION AB Aim: To examine the association of reported visual hallucinations and measured visual parameters in adult patients referred for low vision rehabilitation. Methods: All patients (N=225) referred to a low vision rehabilitation clinic for a calendar year were asked a standardised question about symptoms of formed visual hallucinations. Best corrected visual acuity and contrast sensitivity using the Pelli-Robson chart were measured. We conducted multiple logistic regression analysis of the association between visual hallucinations and visual parameters. Results: Of the total cohort, 78 (35%) reported visual hallucinations. Visual acuity and contrast sensitivity were considered in four quartiles. In multiple logistic regression controlling for contrast sensitivity, age, gender, report of depression and independence, measured acuity in each of the poorer three categories (compared to the best) was not associated with reported hallucinations. Contrast sensitivity in the three poorer quartiles (compared to the best) was strongly associated with the report of hallucinations (OR 4.1, CI 1.1, 15.9; OR 10.5, CI 2.6, 42.1; OR 28.1, CI 5.6, 140.9) after controlling for acuity, age, sex, depression and independence. Conclusions: Lowest contrast sensitivity was the strongest predictor of reported hallucinations after adjusting for visual acuity. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Vis Rehabil Ctr, Boston, MA 02114 USA. USA, Vancouver Isl Hlth Author, Victoria, BC, Canada. UBC, British Columbia Ctr Epidemiol & Int Ophthalmol, Vancouver, BC, Canada. LV Prasad Eye Inst, Hyderabad, Andhra Pradesh, India. Simon Fraser Univ, Dept Stat & Actuarial Sci, Arthritis Res Ctr Canada, Burnaby, BC V5A 1S6, Canada. RP Jackson, ML (reprint author), MEEI, Vis Rehabil, 243 Charles St, Boston, MA 02114 USA. EM Marylou_jackson@meei.harvard.edu NR 15 TC 9 Z9 11 U1 2 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD MAR PY 2007 VL 91 IS 3 BP 296 EP 298 DI 10.1136/bjo.2006.104604 PG 3 WC Ophthalmology SC Ophthalmology GA 139IQ UT WOS:000244425900012 PM 17035271 ER PT J AU Davies, G Bidmead, M Lamb, C Nalder, C Seco, J AF Davies, G. Bidmead, M. Lamb, C. Nalder, C. Seco, J. TI Electron dosimetry of angular fields SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article ID OUTPUT FACTORS AB Shaping electron fields through the use of lead cut-outs may result in there being acute angles in part of the field. Using both experimental techniques and EGSnrc Monte Carlo simulations an investigation was carried out to determine the dosimetric consequences of this. Measurements were made to investigate how the field dose was related to the angle between adjacent sides in the cut-outs. The study involved two electron energies (9 MeV and 12 MeV) and source-skin distances (SSDs) in the range 1000-1100 mm. For angles less than about 120 degrees the dose received in the angular region decreased significantly, the effect being more pronounced at 12 MeV than at 9 MeV, and at longer SSDs. The planar shapes of the Monte Carlo dose distributions agreed with those experimentally determined to within +/- 1.5 mm at 9 MeV and +/- 1.0 mm at 12 MeV, demonstrating the validity of using such calculations for this purpose. Graphs are presented which may help in the prospective assessment of the dose reductions likely to be incurred. C1 Royal Marsden NHS Fdn Trust, London SW3 6JJ, England. RP Seco, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiat Oncol, Francis H Burr Proton Therapy Ctr,Med Sch, 30 Fruit St, Boston, MA 02114 USA. EM jseco@partners.present.org RI Seco, Joao/J-4451-2012 NR 10 TC 1 Z9 3 U1 0 U2 0 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD MAR PY 2007 VL 80 IS 951 BP 202 EP 208 DI 10.1259/bjr/86992777 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 181JI UT WOS:000247432600008 PM 17303615 ER PT J AU Zorzi, D Laurent, A Pawlik, TM Lauwers, GY Vauthey, JN Abdalla, EK AF Zorzi, D. Laurent, A. Pawlik, T. M. Lauwers, G. Y. Vauthey, J. -N. Abdalla, E. K. TI Chemotherapy-associated hepatotoxicity and surgery for colorectal liver metastases SO BRITISH JOURNAL OF SURGERY LA English DT Review ID NONALCOHOLIC FATTY LIVER; PORTAL-VEIN EMBOLIZATION; HEPATIC ARTERIAL INFUSION; PROSPECTIVE RANDOMIZED TRIAL; BONE-MARROW-TRANSPLANTATION; LONG-TERM SURVIVAL; VENOOCCLUSIVE DISEASE; 1ST-LINE TREATMENT; PREOPERATIVE CHEMOTHERAPY; HEPATOCELLULAR-CARCINOMA AB Background: Preoperative systemic chemotherapy is increasingly used in patients who undergo hepatic resection for colorectal liver metastases (CLM). Although chemotherapy-related hepatic injury has been reported, the incidence and the effect of such injury on patient outcome remain ill defined. Methods: A systematic review of relevant studies published before May 2006 was performed. Studies that reported on liver injury associated with preoperative chemotherapy for CLM were identified and data on chemotherapy-specific liver injury and patient outcome following hepatic resection were synthesized and tabulated. Results: Hepatic steatosis, a mild manifestation of non-alcoholic fatty liver disease (NAFLD), may occur after treatment with 5-fluorouracil and is associated with increased postoperative morbidity. Nonalcoholic steatohepatitis, a serious complication of NAFLD that includes inflammation and hepatocyte damage, can occur after treatment with irinotecan, especially in obese patients. Irinotecan-associated steatohepatitis can affect hepatic reserve and increase morbidity and mortality after hepatectomy. Hepatic sinusoidal obstruction syndrome can occur in patients treated with oxaliplatin, but does not appear to be associated with an increased risk of perioperative death. Conclusion. Preoperative chemotherapy for CLM induces regimen-specific hepatic changes that can affect patient outcome. Both response rate and toxicity should be considered when selecting preoperative chemotherapy in patients with CLM. C1 Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. Univ Paris 05, Fac Cochin, Unite Propre Rech Enseignement Super 1833, Immunol Lab, Paris, France. Univ Paris 05, Fac Cochin, Unite Propre Rech Enseignement Super 1833, Lab Rech Chirurg, Paris, France. Univ Paris 12, CHU Henri Mondor, Serv Chirurg Viscerale & Digest, Creteil, France. Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Vauthey, JN (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Unit 444,1515 Holcombe Blvd, Houston, TX 77030 USA. EM jvauthey@mdanderson.org RI Laurent, Alexis/E-9605-2011 NR 86 TC 231 Z9 238 U1 2 U2 10 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0007-1323 J9 BRIT J SURG JI Br. J. Surg. PD MAR PY 2007 VL 94 IS 3 BP 274 EP 286 DI 10.1002/bjs.5719 PG 13 WC Surgery SC Surgery GA 147LG UT WOS:000245003900004 PM 17315288 ER PT J AU DuBois, S Demetri, G AF DuBois, Steven Demetri, George TI Markers of angiogenesis and clinical features in patients with sarcoma SO CANCER LA English DT Review DE angiogenesis; sarcoma; biomarker; VEGF ID ENDOTHELIAL GROWTH-FACTOR; SOFT-TISSUE SARCOMAS; GASTROINTESTINAL STROMAL TUMOR; POOR-PROGNOSIS; SERUM-LEVELS; MATRIX METALLOPROTEINASE-1; FACTOR EXPRESSION; FACTOR VEGF; OSTEOSARCOMA; RECEPTOR AB The growth and dissemination of sarcomas depends on angiogenesis. A number of measurable markers related to tumor angiogenesis have been studied in patients with sarcoma. The available literature related to markers of angiogenesis and clinical features in patients with sarcoma was reviewed. Clinical features of interest included tumor size, tumor grade, tumor stage, presence of metastatic disease, and prognosis. In patients with soft-tissue sarcomas, tumor vascular endothelial growth factor (VEGF) expression correlates with stage, grade, and prognosis. Circulating VEGF levels also correlate with tumor grade. High circulating angiopoietin-2 levels are associated with increased tumor size in soft-tissue sarcoma. For patients with osteosarcoma, tumor VEGF expression correlates with outcome. Elevated tumor and circulating VEGF levels are associated with the development of lung metastases in osteosarcoma. Patients with Ewing sarcoma have increased circulating VEGF levels compared with controls. Angiogenesis markers correlate with important clinical features in patients with sarcomas ranging from soft-tissue sarcomas to bone sarcomas. Markers of angiogenesis may serve an important role in predicting a particular patient's clinical course and in identifying patients for possible antiangiogenic therapy. C1 Harvard Univ, Dana Farber Canc Inst, Ludwig Cr, Boston, MA 02115 USA. Ludwig Inst Canc Res, Boston, MA USA. Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. RP Demetri, G (reprint author), Harvard Univ, Dana Farber Canc Inst, Ludwig Cr, 44 Binney St, Boston, MA 02115 USA. EM gdemetri@partners.org FU NCI NIH HHS [T32 CA009172] NR 49 TC 71 Z9 77 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 1 PY 2007 VL 109 IS 5 BP 813 EP 819 DI 10.1002/cncr.22455 PG 7 WC Oncology SC Oncology GA 141MK UT WOS:000244582600001 PM 17265525 ER PT J AU Gandhi, L Harding, MW Neubauer, M Langer, CJ Moore, M Ross, HJ Johnson, BE Lynch, TJ AF Gandhi, Leena Harding, Matthew W. Neubauer, Marcus Langer, Corey J. Moore, Melvin Ross, Helen J. Johnson, Bruce E. Lynch, Thomas J. TI A phase II study of the safety and efficacy of the multidrug resistance inhibitor VX-710 combined with doxorubicin and vincristine in patients with recurrent small cell lung cancer SO CANCER LA English DT Article DE multidrug resistance; VX-710; lung neoplasm; carcinoma; small cell; clinical trials; phase II ID ADVANCED BREAST-CANCER; P-GLYCOPROTEIN; CHEMOTHERAPY RESPONSE; PROTEIN EXPRESSION; GENE-EXPRESSION; BIRICODAR; TECHNETIUM-99M-SESTAMIBI; COMBINATION; TOPOTECAN; DISEASE AB BACKGROUND. Tumors with multidrug resistance (MDR) frequently up-regulate efflux proteins, including MDR-associated protein (MRP-1) and P-glycoprotein (Pgp). MDR represents an obstacle to successful chemotherapy treatment and is reversible in Pgp- or MRP-1-expressing cells by the inhibitor VX-710. A Phase II study was designed to evaluate VX-710 in combination with doxorubicin and vincristine in patients with sensitive, recurrent small cell lung cancer (SCLC). METHODS. Eligible patients had recurrent SCLC after a response to first-line chemotherapy. Stage 1 safety evaluation was completed with planned expansion if 9 responses were confirmed in the first 35 patients. Patients were treated every 21 days until progression or intolerable adverse events (AEs). RESULTS. Thirty-six patients were enrolled from 1998 to 2000. Neutropenia was the major toxicity, occurring in 26 of 36 patients (72%). Neutropenia was more severe (30% vs 20% grade 4) and developed earlier (58% vs 38% in Cycle 1) among the 15 patients who were enrolled prior to an amendment that required neutropenia prophylaxis. Four patients died on study: 2 from infections likely related to therapy and 2 from cancer progression. Seven of 36 patients (19%) had partial responses; 6 patients sustained responses through 6 cycles of treatment, with 1 response lasting 3 years. Three additional patients had unconfirmed responses, and 4 patients had stable disease. The median survival was 6 months. No correlative Tc-99m-sestamibi uptake in tumor tissue was observed with the addition of VX-710 in this study. CONCLUSIONS. The addition of VX-710 to doxorubicin and vincristine therapy did not significantly enhance antitumor activity or survival. Although there were durable responses, criteria were not met to proceed with Stage 2 expansion. C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Vertex Pharmaceut Inc, Cambridge, MA USA. Kansas City Canc Ctr, Overland Pk, KS USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Georgia Canc Specialists, Decatur, GA USA. Providence Canc Ctr, Earle A Chiles Res Inst, Portland, OR USA. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. EM bejohnson@partners.org OI Gandhi, Leena/0000-0002-2398-9179 NR 25 TC 47 Z9 50 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 1 PY 2007 VL 109 IS 5 BP 924 EP 932 DI 10.1002/cncr.22492 PG 9 WC Oncology SC Oncology GA 141MK UT WOS:000244582600014 PM 17285598 ER PT J AU Klein, AP de Andrade, M Hruban, RH Bondy, M Schwartz, AG Gallinger, S Lynch, HT Syngal, S Rabe, KG Goggins, MG Petersen, GM AF Klein, Alison P. de Andrade, Mariza Hruban, Ralph H. Bondy, Melissa Schwartz, Ann G. Gallinger, Steven Lynch, Henry T. Syngal, Sapna Rabe, Kari G. Goggins, Michael G. Petersen, Gloria M. TI Linkage analysis of chromosome 4 in families with familial pancreatic cancer SO CANCER BIOLOGY & THERAPY LA English DT Article DE pancreatic cancer; genetics; linkage analysis; adenocarcinoma; familial pancreatic cancer; hereditary; gastrointestinal cancer ID HEREDITARY PANCREATITIS; SUSCEPTIBILITY LOCUS; MUTATIONS; GENE; GERMLINE; BRCA2; MAPS; STATISTICS; CARCINOMA; KINDREDS AB Background: Approximately 10% of pancreatic ductal adenocarcinomas have a familial basis. While a small portion of this familial clustering can be explained by inherited mutations in known genes ( BRCA2, p16/CDKN2A, PRSS1, and STK11), the genetic basis for the majority of this familial clustering remains unknown. In addition, a pancreatic cancer susceptibility locus has been reported to be linked to chromosome 4q32-34 in a single family having a high penetrance of early-onset pancreatic ductal adenocarcinoma and pancreatic insufficiency. The goal of this study is to determine if linkage to chromosome 4q exists in our series of well-characterized families with idiopathic familial pancreatic cancer enrolled in the Pancreatic Cancer Genetic Epidemiology Consortium (PACGENE). Methods: Parametric and nonparametric linkage analyses were performed using 21 microsatellite markers on chromosome 4 on affected individuals with pancreatic cancer from 42 familial pancreatic cancer kindreds. Results: Markov Chain Monte Carlo parametric and nonparametric linkage analyses using SIMWALK2 as well as nonparametric linkage analysis using MERLIN did not provide strong evidence of linkage in this region (LOD < 1.0). Only one family provided a multipoint LOD score of > 0.5 adjacent to the reported region. Conclusions: Our results do not support linkage to the 4q32-34 region in the majority of our familial pancreatic cancer kindreds. However, because multiple pancreatic cancer susceptibility genes are likely to exist, it is possible that a subset of the families in this study may be linked to this region. C1 Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21231 USA. Mayo Clin, Coll Med, Rochester, MI USA. MD Anderson Canc Ctr, Houston, TX USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Creighton Univ, Omaha, NE 68178 USA. Dana Farber Canc Inst, Boston, MA USA. RP Klein, AP (reprint author), Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Sol Goldman Pancreat Canc Res Ctr, 1550 Orleans St, Baltimore, MD 21231 USA. EM aklein1@jhmi.edu RI Gallinger, Steven/E-4575-2013 FU NCI NIH HHS [P50 CA062924, P50 CA062924-100011, P50 CA062924-110011, P50 CA062924-120011, P50 CA062924-130011, R01 CA097075, R01 CA097075-03] NR 27 TC 17 Z9 17 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD MAR PY 2007 VL 6 IS 3 BP 320 EP 323 PG 4 WC Oncology SC Oncology GA 190TF UT WOS:000248082500009 PM 17312386 ER PT J AU Dingli, D Michor, F Antal, T Pacheco, JM AF Dingli, David Michor, Franziska Antal, Tibor Pacheco, Jorge M. TI The emergence of tumor metastases SO CANCER BIOLOGY & THERAPY LA English DT Article DE tumor; metastases; mathematical modeling; dynamics; evolution ID BREAST-CANCER METASTASIS; SUPPRESSOR GENE INACTIVATION; CHROMOSOMAL INSTABILITY; COLON-CANCER; CELLS; MODEL; DYNAMICS; MICROMETASTASES; CARCINOGENESIS; MELANOMA AB The appearance of metastases is an ominous sign in the natural history of any malignant tumor. Their presence implies a high tumor burden and greatly decreases the probability of a cure. Metastasis development requires the evolution of tumor cells that can survive in an environment that is normally not supportive to their growth and such cells must leave the tumor to establish tumor niches elsewhere. The interactions between the appearance of cells with metastatic ability in the primary tumor and their exit from the tumor lead to complex dynamics that can be either beneficial or detrimental to the tumor. We develop a simple mathematical model to illustrate how the interplay between mutation rate and export probability affects the intratumoral dynamics of metastasis enabled cells and the rate of metastases formation. C1 Harvard Univ, Sch Med, Program Evolut Dynam, Cambridge, MA 02138 USA. Mayo Clin, Coll Med, Div Hematol, Rochester, MI USA. Harvard Soc Fellows, Cambridge, MA USA. Dana Farber Canc Inst, Boston, MA USA. Univ Lisbon, CFTC, Lisbon, Portugal. Univ Lisbon, Dept Fis, Lisbon, Portugal. RP Dingli, D (reprint author), Harvard Univ, Sch Med, Program Evolut Dynam, 1 Brattle Sq, Cambridge, MA 02138 USA. EM dingli@fas.harvard.edu RI Antal, Tibor/A-4512-2008; Dingli, David/B-6355-2008; Pacheco, Jorge/B-6116-2008 OI Pacheco, Jorge/0000-0002-2579-8499 NR 52 TC 12 Z9 12 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD MAR PY 2007 VL 6 IS 3 BP 383 EP 390 PG 8 WC Oncology SC Oncology GA 190TF UT WOS:000248082500019 PM 17312385 ER PT J AU Clegg, LX Reichman, ME Hankey, BF Miller, BA Lin, YD Johnson, NJ Schwartz, SM Bernstein, L Chen, VW Goodman, MT Gomez, SL Graff, JJ Lynch, CF Lin, CC Edwards, BK AF Clegg, Limin X. Reichman, Marsha E. Hankey, Benjamin F. Miller, Barry A. Lin, Yi D. Johnson, Norman J. Schwartz, Stephen M. Bernstein, Leslie Chen, Vivien W. Goodman, Marc T. Gomez, Scarlett L. Graff, John J. Lynch, Charles F. Lin, Charles C. Edwards, Brenda K. TI Quality of race, Hispanic ethnicity, and immigrant status in population-based cancer registry data: implications for health disparity studies SO CANCER CAUSES & CONTROL LA English DT Article DE National Longitudinal Mortality Study; NLMS; race; ethnicity and immigrant status; surveillance; epidemiology; End Results; SEER ID NATIONAL DEATH INDEX; END RESULTS PROGRAM; UNITED-STATES; AMERICAN-INDIANS; BREAST-CANCER; BIRTHPLACE; SURVEILLANCE; SELF; EPIDEMIOLOGY; WOMEN AB Population-based cancer registry data from the Surveillance, Epidemiology, and End Results (SEER) Program at the National Cancer Institute are based on medical records and administrative information. Although SEER data have been used extensively in health disparities research, the quality of information concerning race, Hispanic ethnicity, and immigrant status has not been systematically evaluated. The quality of this information was determined by comparing SEER data with self-reported data among 13,538 cancer patients diagnosed between 1973-2001 in the SEER-National Longitudinal Mortality Study linked database. The overall agreement was excellent on race (kappa = 0.90, 95% CI = 0.88-0.91), moderate to substantial on Hispanic ethnicity (kappa = 0.61, 95% CI = 0.58-0.64), and low on immigrant status (kappa = 0.21. 95% CI = 0.10, 0.23). The effect of these disagreements was that SEER data tended to under-classify patient numbers when compared to self-identifications, except for the non-Hispanic group which was slightly over-classified. These disagreements translated into varying racial-, ethnic-, and immigrant status-specific cancer statistics, depending on whether self-reported or SEER data were used. In particular, the 5-year Kaplan-Meier survival and the median survival time from all causes for American Indians/Alaska Natives were substantially higher when based on self-classification (59% and 140 months, respectively) than when based on SEER classification (44% and 53 months, respectively), although the number of patients is small. These results can serve as a useful guide to researchers contemplating the use of population-based registry data to ascertain disparities in cancer burden. In particular, the study results caution against evaluating health disparities by using birthplace as a measure of immigrant status and race information for American Indians/Alaska Natives. C1 US Dept Vet Affairs, Off Healthcare Inspect, Off Inspector Gen, Washington, DC 20001 USA. NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Monash Univ, Sch Med, Melbourne, Vic 3004, Australia. US Bur Census, Suitland, MD USA. Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98104 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. LSU Sch Publ Hlth, Louisiana Tumor Registry, New Orleans, LA USA. Univ Hawaii, Canc Res Ctr, Honolulu, HI 96822 USA. No Calif Canc Ctr, Fremont, CA USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48202 USA. Univ Iowa, State Hlth Registry Iowa, Iowa City, IA 52242 USA. RP Clegg, LX (reprint author), US Dept Vet Affairs, Off Healthcare Inspect, Off Inspector Gen, 801 I St,NW,Room 1018, Washington, DC 20001 USA. EM Lin.clegg@va.gov NR 43 TC 93 Z9 97 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAR PY 2007 VL 18 IS 2 BP 177 EP 187 DI 10.1007/s10552-006-0089-4 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 134EL UT WOS:000244065700007 PM 17219013 ER PT J AU Yun, CH Boggon, TJ Li, YQ Woo, MS Greulich, H Meyerson, M Eck, MJ AF Yun, Cai-Hong Boggon, Titus J. Li, Yiqun Woo, Michele S. Greulich, Heidi Meyerson, Matthew Eck, Michael J. TI Structures of lung cancer-derived EGFR mutants and inhibitor complexes: Mechanism of activation and insights into differential inhibitor sensitivity SO CANCER CELL LA English DT Article ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; CRYSTAL-STRUCTURE; IRREVERSIBLE INHIBITORS; ACQUIRED-RESISTANCE; CELL-LINES; GEFITINIB; MUTATIONS; SRC; DOMAIN AB Mutations in the EGFR kinase are a cause of non-small-cell lung cancer. To understand their mechanism of activation and effects on drug binding, we studied the kinetics of the L858R and G719S mutants and determined their crystal structures with inhibitors including gefitinib, AEE788, and a staurosporine. We find that the mutations activate the kinase by disrupting autoinhibitory interactions, and that they accelerate catalysis as much as 50-fold in vitro. Structures of inhibitors in complex with both wild-type and mutant kinases reveal similar binding modes for gefitinib and AEE788, but a marked rotation of the staurosporine in the G719S mutant. Strikingly, direct binding measurements show that gefitinib binds 20-fold more tightly to the L858R mutant than to the wild-type enzyme. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. Harvard Univ, Borad Inst, Cambridge, MA 02141 USA. MIT, Cambridge, MA 02141 USA. RP Eck, MJ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 25 Shattuck St, Boston, MA 02115 USA. EM eck@red.dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 FU NCI NIH HHS [CA080942, CA116020, R01 CA080942, R01 CA116020]; NCRR NIH HHS [P41 RR001646] NR 52 TC 461 Z9 475 U1 4 U2 53 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAR PY 2007 VL 11 IS 3 BP 217 EP 227 DI 10.1016/j.ccr.2006.12.017 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 149MU UT WOS:000245151800004 PM 17349580 ER PT J AU Shipitsin, M Campbell, LL Argani, P Werernowicz, S Bloushtain-Qimron, N Yao, J Nikolskaya, T Serebryiskaya, T Beroukhim, R Hu, M Halushka, MK Sukumar, S Parker, LM Anderson, KS Harris, LN Garber, JE Richardson, AL Schnitt, SJ Nikolsky, Y Gelman, RS Polyak, K AF Shipitsin, Michail Campbell, Lauren L. Argani, Pedram Werernowicz, Stanislawa Bloushtain-Qimron, Noga Yao, Jun Nikolskaya, Tatiana Serebryiskaya, Tatiana Beroukhim, Rameen Hu, Min Halushka, Marc K. Sukumar, Saraswati Parker, Leroy M. Anderson, Karen S. Harris, Lyndsay N. Garber, Judy E. Richardson, Andrea L. Schnitt, Stuart J. Nikolsky, Yuri Gelman, Rebecca S. Polyak, Kornelia TI Molecular definition of breast tumor heterogeneity SO CANCER CELL LA English DT Article ID GENE-EXPRESSION SIGNATURE; IN-VITRO PROPAGATION; HUMAN MAMMARY-GLAND; GROWTH-FACTOR-BETA; ADULT STEM-CELLS; TGF-BETA; CANCER-CELLS; DISTANT METASTASIS; CD24 EXPRESSION; SELF-RENEWAL AB Cells with distinct phenotypes including stem-cell-like properties have been proposed to exist in normal human mammary epithelium and breast carcinomas, but their detailed molecular characteristics and clinical significance are unclear. We determined gene expression and genetic profiles of cells purified from cancerous and normal breast tissue using markers previously associated with stem-cell-like properties. CD24+ and CD44+ cells from individual tumors were clonally related but not always identical. CD44+ cell-specific genes included many known stem-cell markers and correlated with decreased patient survival. The TGF-beta pathway was specifically active in CD44+ cancer cells, where its inhibition induced a more epithelial phenotype. Our data suggest prognostic relevance of CD44+ cells and therapeutic targeting of distinct tumor cell populations. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Dept Med, Boston, MA 02115 USA. Harvard Univ, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Program Biol & Biomed Sci, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21231 USA. GeneGo Inc, St Joseph, MI 49085 USA. NI Vavilov Gen Genet Res Inst, Moscow 117809, Russia. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM kornelia_polyak@dfci.harvard.edu RI Nikolskaya, Tatiana/M-5008-2013; OI Halushka, Marc/0000-0002-7112-7389 FU NCI NIH HHS [P50 CA088843, CA89393, CA94074, P50 CA089393, P50 CA089393-060014, P50 CA089393-070014, P50 CA089393-080014, R01 CA094074, R01 CA094074-05, R01 CA116235, R01 CA116235-01A1, R01 CA116235-02, R01 CA116235-03] NR 57 TC 776 Z9 821 U1 4 U2 63 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAR PY 2007 VL 11 IS 3 BP 259 EP 273 DI 10.1016/j.ccr.2007.01.013 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 149MU UT WOS:000245151800007 PM 17349583 ER PT J AU Zhu, AX Clark, JW Ryan, DP Meyerhardt, JA Enzinger, PC Earle, CC Fuchs, CS Regan, E Anbe, H Houghton, M Zhang, J Urrea, P Kulke, MH AF Zhu, Andrew X. Clark, JeVrey W. Ryan, David P. Meyerhardt, Jeffrey A. Enzinger, Peter C. Earle, Craig C. Fuchs, Charles S. Regan, Eileen Anbe, Hiroshi Houghton, Michele Zhang, Joshua Urrea, Peter Kulke, Matthew H. TI Phase I and pharmacokinetic study of S-1 administered for 14 days in a 21-day cycle in patients with advanced upper gastrointestinal cancer SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE S-1; 5-Fluorouracil (5-FU); gastrointestinal malignancies; antitumor activity; phase I; pharmacokinetics ID ADVANCED GASTRIC-CANCER; CELL LUNG-CANCER; PLUS CISPLATIN; SOLID TUMORS; ANTITUMOR-ACTIVITY; ORAL FLUOROURACIL; LIVER-MICROSOMES; TRACT CANCER; 5-FLUOROURACIL; TRIAL AB Purpose S-1 is a novel oral fluoropyrimidine that combines tegafur with CDHP and oxonic acid. To decrease the incidence of late onset, severe diarrhea observed in a previous study, a phase I study was conducted to determine the maximum tolerated dose (MTD) of S-1 utilizing a 14-day schedule, repeated every 21 days, in patients with chemotherapy-refractory upper gastrointestinal malignancies. Methods S-1 was administered orally, twice-daily, at an initial dose level of 30 mg/m(2)/dose; doses were escalated by 5 mg/m2 at each level. A minimum of three patients were enrolled at each dose level. S-1 toxicity, antitumor activity, and pharmacokinetics were assessed. The MTD was based on the dose limiting toxicity (DLT) during the first treatment cycle. Results At 30 mg/m2 no DLT was observed in the first three evaluable patients. Two of the first three patients at the 35 mg/m(2) dose level developed DLTs (grade 3 rash and dehydration). An additional nine patients were subsequently treated at 30 mg/m(2) without DLT and this dose was established as the MTD. Common toxicities at 30 mg/m2 included diarrhea, nausea, skin rash, anorexia, and fatigue. No grade 4 toxicities were observed. One partial response was seen in a patient with gemcitabine-refractory pancreatic adenocarcinoma and ten patients with pancreatic, gastric, or gallbladder carcinomas achieved stable disease as their best response to therapy. The AUC((0-8)) of 5-FU at the 30 and 35 mg/m(2) dose levels were 875 +/- 212 and 894 +/- 151 h ng/ml, respectively. Conclusions In a 14-day dosing schedule, the MTD of S-1 was 30 mg/m(2) and preliminary evidence of antitumor activity was seen in a North American population with refractory upper gastrointestinal malignancies. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02481 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Taiho Pharma, Princeton, NJ USA. RP Zhu, AX (reprint author), Massachusetts Gen Hosp, 100 Blossom St,Cox 640, Boston, MA 02114 USA. EM azhu@partners.org; matthew_kulke@dfci.harvard.edu FU NCI NIH HHS [K23 CA 093401]; NHLBI NIH HHS [K30 HL04095] NR 40 TC 24 Z9 24 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAR PY 2007 VL 59 IS 3 BP 285 EP 293 DI 10.1007/s00280-006-0265-y PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 119RX UT WOS:000243031900001 PM 16786333 ER PT J AU Kawano, T Agata, N Kharbanda, S Avigan, D Kufe, D AF Kawano, Takeshi Agata, Naoki Kharbanda, Surender Avigan, David Kufe, Donald TI A novel isocoumarin derivative induces mitotic phase arrest and apoptosis of human multiple myeloma cells SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE isocoumarins; NM-3 analog; multiple myeloma; mitotic arrest; apoptosis ID NM-3; ANGIOGENESIS; INHIBITOR; ACID AB Purpose The isocoumarin NM-3 reverses resistance of human multiple myeloma (MM) cells to dexamethasone and is in clinical trials. In the present work, the NM-3 analog, 185322, has been studied for activity against MM cells. Methods Human U266, RPMI8226 and primary MM cells were analyzed for the effects of 185322 on cell cycle distribution, tubulin polymerization and induction of apoptosis. Results We show that, in contrast to NM-3, treatment with 185322 is associated with a marked arrest of MM cells in M phase. The results also demonstrate that treatment with 185322 is associated with a rapid decrease in tubulin assembly and an increase in Bcl-2 phosphorylation, consistent with disruption of mitosis. Our results further demonstrate that mitotic failure induced by 185322 results in activation of an apoptotic response in MM cell lines and primary MM cells. By contrast, 185322 had little if any effect on growth and survival of human carcinoma cells. Conclusion These findings identify a novel inhibitor of microtubule assembly that induces mitotic arrest and apoptosis of MM cells. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu FU NCI NIH HHS [CA100707, CA42802] NR 17 TC 22 Z9 22 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAR PY 2007 VL 59 IS 3 BP 329 EP 335 DI 10.1007/s00280-006-0274-x PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 119RX UT WOS:000243031900006 PM 16830153 ER PT J AU MacDonald, SM Taghian, AG AF MacDonald, Shannon M. Taghian, Alphonse G. TI Is it time to use protons for breast cancer? SO CANCER JOURNAL LA English DT Editorial Material ID CONSERVING SURGERY; RADIATION-THERAPY; CLINICAL-EXPERIENCE; IRRADIATION; RADIOTHERAPY; LUMPECTOMY; MASTECTOMY; OUTCOMES; BEAMS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM ataghian@partners.org NR 20 TC 4 Z9 4 U1 0 U2 2 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD MAR-APR PY 2007 VL 13 IS 2 BP 84 EP 86 DI 10.1097/PPO.0b013e318053cdb0 PG 3 WC Oncology SC Oncology GA 162JO UT WOS:000246083300004 PM 17476135 ER PT J AU Nakabayashi, M Ling, J Xie, WL Regan, MM Oh, WK AF Nakabayashi, Mari Ling, Jonathan Xie, Wanling Regan, Meredith M. Oh, William K. TI Response to vinorelbine with or without estramustine as second-line chemotherapy in patients with hormone-refractory prostate cancer SO CANCER JOURNAL LA English DT Article DE vinorelbine; estramustine; hormone-refractory prostate cancer; second-line chemotherapy; prostate-specific antigen response ID PHASE-II; TRIAL; MITOXANTRONE; VINBLASTINE; PREDNISONE; DOCETAXEL; ANTIGEN; TUBULIN AB Background: Vinorelbine (VRL) in combination with estramustine has known efficacy in the initial chemotherapeutic management of hormone-refractory prostate cancer (HRPC). However, little is known about the efficacy of VRL as second-line chemotherapy in HRPC. Methods: We retrospectively identified patients with HRPC treated in a single institution with VRL as second-line chemotherapy with or without estramustine. Patient baseline characteristics, declines in prostate-specific antigen, performance status, toxicities, and survival were assessed. Results: Thirty-nine patients were treated with VRL between 1999 and 2005. Twenty-one patients (54%) received single-agent VRL and 18 patients (46%) had concomitant estramustine. Seven patients (17.9%, 95% confidence interval 7.5%-33.6%) treated with VRL experienced prostate-specific antigen declines >= 50%. Median duration of therapy was 1.4 months (range 0.2-14.0 months). Median overall survival was 6.9 months (range 1.4-29.9 months); it was 16.1 month in responders and 5.5 months in nonresponders. Median survival was significantly longer in patients with VRL and estramustine than in patients who received VRL alone (8.5 months versus 4.1 months, P = 0.05). The most common reversible adverse effect of VRL was grade 1 or 2 fatigue observed in 36% of patients. Conclusions: As a second-line chemotherapy, VRL demonstrated moderate activity and was well tolerated in patients with HRPC. Patients treated with the combination of VRL and estramustine experienced a longer survival than those receiving VRL alone. C1 Dana Farber Canc Inst, Dept Med Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Community Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. EM william_oh@dfci.harvard.edu RI Oh, William/B-9163-2012; OI Oh, William/0000-0001-5113-8147; Ling, Jonathan/0000-0003-1927-9729 NR 15 TC 11 Z9 12 U1 0 U2 2 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD MAR-APR PY 2007 VL 13 IS 2 BP 125 EP 129 DI 10.1097/PPO.0b013e3180465940 PG 5 WC Oncology SC Oncology GA 162JO UT WOS:000246083300010 PM 17476141 ER PT J AU Skaar, JR Florens, L Tsutsumi, T Arai, T Tron, A Swanson, SK Washburn, MP DeCaprio, JA AF Skaar, Jeffrey R. Florens, Laurence Tsutsumi, Takeya Arai, Takehiro Tron, Adriana Swanson, Selene K. Washburn, Michael P. DeCaprio, James A. TI PARC and CUL7 form atypical cullin RING ligase complexes SO CANCER RESEARCH LA English DT Article ID SCF UBIQUITIN LIGASE; SACCHAROMYCES-CEREVISIAE; CELL-CYCLE; PROTEINS; NEDD8; PROTEOME; DOMAINS; BINDS; P53; BOX AB CUL7 and the p53-associated, PARkin-like cytoplasmic protein (PARC) were previously reported to form homodimers and heterodimers, the first demonstration of cullin dimerization. Although a CUL7-based SKPI/CUL1/F-box (SCF)-like complex has been observed, little is known about the existence of a PARC-based SCF-like complex and how PARC interacts with CUL7-based complexes. To further characterize PARC- containing complexes, we examined the ability of PARC to form an SCF-like complex. PARC binds RBX1 and is covalently modified by NEDD8, defining PARC as a true cullin. However, PARC fails to bind SKP1 or F-box proteins, including the CUL7-associated FBXW8. To examine the assembly of PARC- and CUL7-containing complexes, tandem affinity purification followed by multidimensional protein identification technology were used. Multidimensional protein identification technology analysis revealed that the CUL7 interaction with FBXW8 was mutually exclusive of CUL7 binding to PARC or p53. Notably, although heterodimers of CUL7 and PARC bind p53, p53 is not required for the dimerization of CUL7 and PARC. The observed physical separation of FBXW8 and PARC is supported functionally by the generation of Pare-/-, Fbxw8-/- mice, which do not show exacerbation of the Fbxw8-/- phenotype. Finally, all of the PARC and CUL7 subcomplexes examined exhibit E3 ubiquitin ligase activity in vitro. Together, these findings indicate that the intricate assembly of PARC- and CUL7-containing complexes is highly regulated, and multiple subcomplexes may exhibit ubiquitin ligase activity. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Stowers Inst Med Res, Kansas City, MO USA. RP DeCaprio, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Mayer 440,44 Binney St, Boston, MA 02115 USA. EM james_decaprio@dfci.harvard.edu OI Florens, Laurence/0000-0002-9310-6650; Washburn, Michael/0000-0001-7568-2585 FU NCI NIH HHS [R01 CA 93804] NR 32 TC 32 Z9 39 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2007 VL 67 IS 5 BP 2006 EP 2014 DI 10.1158/0008-5472.CAN-06-3241 PG 9 WC Oncology SC Oncology GA 143QQ UT WOS:000244738100018 PM 17332328 ER PT J AU Li, WH Zhang, XP Olumi, AF AF Li, Wenhua Zhang, Xiaoping Olumi, Aria F. TI MG-132 sensitizes TRAIL-resistant prostate cancer cells by activating c-Fos/c-Jun heterodimers and repressing c-FLIP(L) SO CANCER RESEARCH LA English DT Article ID APOPTOSIS-INDUCING LIGAND; UBIQUITIN-PROTEASOME PATHWAY; RECEPTOR-INDUCED APOPTOSIS; NF-KAPPA-B; MEDIATED APOPTOSIS; CELLULAR FLIP; HEPATOMA-CELLS; LEUKEMIA CELLS; UP-REGULATION; TNF-ALPHA AB Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent because it induces apoptosis in cancer cells but not in normal cells. Unfortunately, some cancer cells develop resistance to TRAIL-induced apoptosis. Therefore, it is clinically relevant to determine the molecular mechanisms that differentiate between TRAIL-sensitive and TRAIL-resistant tumors. Previously, we have shown that the antiapoptotic molecule cellular-FLICE-inhibitory protein long isoform [c-FLIP(L)] is necessary and sufficient to maintain resistance to TRAIL-induced apoptosis. We have found that c-FLIP(L) is transcriptionally regulated by the activator protein-1 (AP-1) family member protein c-Fos. Here, we report that MG-132, a small-molecule inhibitor of the proteasome, sensitizes TRAIL-resistant prostate cancer cells by inducing c-Fos and repressing c-FLIP(L). c-Fos, which is activated by MG-132, negatively regulates c-FLIP(L) by direct binding to the putative promoter region of the c-FLIP(L) gene. In addition to activating c-Fos, MG-132 activates another AP-1 family member, c-Jun. We show that c-Fos heterodimerizes with c-Jun to repress transcription of c-FLIP(L). Therefore, MG-132 sensitizes TRAIL-resistant prostate cancer cells by activating the AP-1 family members c-Fos and c-Jun, which, in turn, repress the antiapoptotic molecule c-FLIP(L). C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Urol Surg, Boston, MA USA. RP Olumi, AF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Yawkey Bldg,Suite 7E,55 Fruit St, Boston, MA 02114 USA. EM aolumi@partners.org FU NIDDK NIH HHS [DK 64062] NR 49 TC 65 Z9 67 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2007 VL 67 IS 5 BP 2247 EP 2255 DI 10.1158/0008-5472.CAN-06-3793 PG 9 WC Oncology SC Oncology GA 143QQ UT WOS:000244738100045 PM 17332355 ER PT J AU Mulloy, R Ferrand, A Kim, Y Sordella, R Bell, DW Haber, DA Anderson, KS Settleman, J AF Mulloy, Roseann Ferrand, Audrey Kim, Youngjoo Sordella, Raffaella Bell, Daphne W. Haber, Daniel A. Anderson, Karen S. Settleman, Jeffrey TI Epidermal growth factor receptor mutants from human lung cancers exhibit enhanced catalytic activity and increased sensitivity to gefitinib SO CANCER RESEARCH LA English DT Article ID ACQUIRED-RESISTANCE; KINASE INHIBITORS; KINETIC-ANALYSIS; EGFR MUTATIONS; ERLOTINIB; ADENOCARCINOMAS; TRANSFORMATION; THERAPY; COMMON AB Somatic mutations within the epidermal growth factor receptor (EGFR) kinase domain are detected in 10% to 30% of human non-small cell lung cancers and are correlated with striking clinical responses in a subset of patients treated with EGFR kinase inhibitors, such as gefitinib and erlotinib. Cellbased studies suggest that these mutant EGFRs promote increased autophosphorylating activity on a subset of EGFR COOH-terminal tyrosines and the consequent engagement of a subset of downstream effectors. Because EGFR function is regulated at multiple levels in vivo, and it is therefore difficult to assess the direct consequences of these mutations on EGFR enzyme function, we measured EGFR catalytic activity in in vitro kinase assays using purified recombinant proteins corresponding to the cytoplasmic domain of wild-type and two frequently detected EGFR mutants (DeIL747-P753insS and L858R). Both mutants exhibit substantially increased autophosphorylating activity relative to wild-type EGFR, and they exhibit distinct reaction kinetics. In addition, the mutant kinases are more sensitive to kinase inhibition by gefitinib, which seems to reflect their increased drug affinity. These findings suggest that the altered signaling properties and drug sensitivity of these EGFR mutants that have been observed in vivo largely result from differences in the catalytic properties of the kinase. In addition, we find that the T790M secondary "drug resistance mutation" of EGFR, which frequently arises in relapsed patients that initially responded to treatment, confers enhanced kinase activity to primary activating EGFR alleles and may, therefore, be oncogenic in some contexts. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Mol Therapeut, Charlestown, MA 02129 USA. Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA. RP Settleman, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM settleman@helix.mgh.harvard.edu FU NCI NIH HHS [R01 CA 115830]; NIGMS NIH HHS [R01 GM 71805] NR 20 TC 103 Z9 106 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2007 VL 67 IS 5 BP 2325 EP 2330 DI 10.1158/0008-5472.CAN-06-4293 PG 6 WC Oncology SC Oncology GA 143QQ UT WOS:000244738100054 PM 17332364 ER PT J AU Vila-Petroff, M Salas, MA Said, M Valverde, CA Sapia, L Portiansky, E Hajjar, RJ Kranias, EG Mundina-Weilenmann, C Mattiazzi, A AF Vila-Petroff, Martin Salas, Margarita A. Said, Matilde Valverde, Carlos A. Sapia, Luciana Portiansky, Enrique Hajjar, Roger J. Kranias, Evangelia G. Mundina-Weilenmann, Cecilia Mattiazzi, Alicia TI CaMKII inhibition protects against necrosis and apoptosis in irreversible ischemia-reperfusion injury SO CARDIOVASCULAR RESEARCH LA English DT Article DE CaMKII; ischemia/reperfusion injury; apoptosis; necrosis; myocardium ID VENTRICULAR MYOCYTES; KINASE-II; PHOSPHOLAMBAN PHOSPHORYLATION; CELL-DEATH; NA+/CA2+ EXCHANGER; MYOCARDIAL REPERFUSION; CARDIAC-HYPERTROPHY; CA2+ OVERLOAD; HEART-FAILURE; RAT HEARTS AB Objectives: Ca2+/calmodulin-dependent protein kinase 11 (CaMKII) has been implicated in the regulation of cardiac excitation-contraction coupling (ECC) as well as in apoptotic signaling and adverse remodeling. The goal of the present study is to investigate the role of CaMKII in irreversible ischemia and reperfusion (I/R) injury. Methods: Isovolumic Langendorff perfused rat hearts were subjected to global no-flow I/R (45 min/120 min), and isolated myocytes were subjected to a protocol of simulated I/R (45 min simulated ischemia/60 min reoxygenation) either in the absence or presence of CaMKII inhibition [KN-93 (KN) or the CaMKII inhibitory peptide (AIP)]. Results: In I/R hearts, an increase in CaMKII activity at the beginning of reperfirsion was confirmed by the significantly increased phosphorylation of the Thr(17) site of phospholamban. In the presence of KN, contractile recovery at the end of reperfusion was almost double that of I/R hearts. This recovery was associated with a significant decrease in the extent of infarction, lactate dehydrogenase release (necrosis), TUNEL-positive cells, caspase-3 activity, and an increase in the Bcl-2/Bax ratio (apoptosis). In isolated myocytes, both KN and AIP prevented simulated I/R-induced spontaneous contractile activity and cell mortality. Similar results were obtained when inhibiting the reverse mode Na+/Ca2+ exchanger (NCX) with KB-R7943, sarcoplasmic reticulum (SR) function with ryanodine and thapsigargin, or SR Ca2+ release with tetracaine. In contrast, overexpression of CaMKII decreased cell viability from 52 +/- 3% to 26 +/- 2%. Conclusions: Taken together, the present findings are the first to establish CaMKII as a fundamental component of a cascade of events integrating the NCX, the SR, and mitochondria that promote cellular apoptosis and necrosis in irreversible I/R injury. 0 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. C1 Natl Univ La Plata, Fac Ciencias Med, Ctr Invest Cardiovasc, RA-1900 La Plata, Argentina. Fac Vet, Dept Patol, La Plata, Argentina. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Univ Cincinnati, Coll Med, Dept Pharmacol & Cell Biophys, Cincinnati, OH 45267 USA. RP Mundina-Weilenmann, C (reprint author), Natl Univ La Plata, Fac Ciencias Med, Ctr Invest Cardiovasc, 60 & 120, RA-1900 La Plata, Argentina. EM cmundweil@atlas.med.untp.edu.ar; ramattia@atlas.med.unlp.edu.ar FU FIC NIH HHS [5R03TW007713-02]; NHLBI NIH HHS [HL057263, HL071763, HL078691, HL080498, HL083156, HL26057, HL64018] NR 31 TC 117 Z9 128 U1 0 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD MAR 1 PY 2007 VL 73 IS 4 BP 689 EP 698 DI 10.1016/j.cardiores.2006.12.003 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 151PD UT WOS:000245301800011 PM 17217936 ER PT J AU Palacios, IF Condado, JA Brandi, S Rodriguez, V Bosch, F Silva, G Low, RI Rogers, JH AF Palacios, Igor F. Condado, Jose A. Brandi, Sergio Rodriguez, Victor Bosch, Fernando Silva, Gaston Low, Reginald I. Rogers, Jason H. TI Safety and feasibility of acute percutaneous septal sinus shortening: First-in-human experience SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE mitral valve; regurgitation; valves; percutaneous mitral valve repair; catheters ID FUNCTIONAL MITRAL REGURGITATION; CORONARY-SINUS; HEART-FAILURE; CARDIOMYOPATHY; MECHANISM; ECHOCARDIOGRAPHY; RECONSTRUCTION; ANNULOPLASTY; COMPLEX AB Background: Multiple percutaneous therapies for the treatment of functional and ischemic mitral regurgitation (FMR/IMR) are under development. We previously reported a novel percutaneous technique, the percutaneous septal sinus shortening [PS3] System (TM), which was effective in ameliorating FMR in an animal model. We herein report results from the first-in-human safety and feasibility pilot study involving the PS3 System. Methods and Results: The primary objective of this first-in-human study was to evaluate the safety and feasibility of acute percutaneous septal-lateral shortening by using the PS3 System in patients immediately prior to clinically-indicated surgical mitral valve repair. Two patients were enrolled. Patient One had severe aortic insufficiency with moderate functional mitral regurgitation. The PS3 System reduced the MR grade from 2+ to 1+ with a decrease in the mean septal-lateral systolic (SLS) dimension from 38 to 27 mm (29% reduction). Patient Two had severe ischemic mitral regurgitation in the setting of severe multi-vessel disease and prior infero-posterior infarct. MR grade was reduced from 3+ to 1+ with a decrease in the mean SLS dimension from 36 to 25 mm (31 % reduction). There were no procedural complications and both patients proceeded to pre-planned cardiac surgery, where the devices were explanted under direct visualization. Conclusions: The PS3 System has been safely translated from the preclinical setting to first-in-human implantation. Both patients studied experienced a reduction in MR after device implantation, with significant SLS shortening. Further clinical trials will be needed to assess long-term efficacy and durability. (c) 2007 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Ctr Med Caracas, Caracas, Venezuela. Hop Univ Caracas, Caracas, Venezuela. Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. RP Palacios, IF (reprint author), 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM ipalacios@partners.org NR 16 TC 28 Z9 28 U1 0 U2 1 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 MAR 1 PY 2007 VL 69 IS 4 BP 513 EP 518 DI 10.1002/ccd.21070 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 141ZL UT WOS:000244617700008 PM 17323357 ER PT J AU Podar, K Anderson, KC AF Podar, Klaus Anderson, Kenneth C. TI Inhibition of VEGF signaling pathways in multiple myeloma and other malignancies SO CELL CYCLE LA English DT Article DE VEGF; anti-angiogenesis; combination therapy; metronomic therapy ID BONE-MARROW ANGIOGENESIS; ENDOTHELIAL PROGENITOR CELLS; TUMOR ANGIOGENESIS; BLOOD-VESSELS; THERAPEUTIC IMPLICATIONS; METRONOMIC CHEMOTHERAPY; VASCULOGENIC MIMICRY; GROWTH-FACTORS; SOLID TUMORS; CANCER AB Due to its direct effects on endothelial cells, circulatory endothelial progenitor cells, hematopoietic stem cells, immune cells, osteoclasts, osteoblasts and neurons, vascular endothelial growth factor (VEGF) is linked to tumor cell development, progression, metastatic osteolysis and drug resistance, as well as clinical features such as metastatic osteolysis. Importantly, recent advances in the understanding of mechanisms of action of antiangiogenic drugs/VEGF-inhibitors have fundamentally changed treatment regimens in cancer. VEGF plays a key role not only in solid tumors but also in hematologic malignan cies, including multiple myeloma (MM). Despite recent advances in our understanding of MM pathogenesis and novel therapies (bortezomib and lenalidomide), it remains incur able. Our own and others' work suggest that VEGF - inhibitors e. g., the small molecule VEGF receptor inhibitor pazopanib, may also improve patient outcome in MM. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Ctr, Boston, MA 02115 USA. RP Podar, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Ctr, 44 Binney St, Boston, MA 02115 USA. EM klaus_podar@dfci.harvard.edu FU NCI NIH HHS [P0-1 CA78378, P50 CA100707, R0 CA50947] NR 48 TC 38 Z9 40 U1 0 U2 3 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAR 1 PY 2007 VL 6 IS 5 BP 538 EP 542 DI 10.4161/cc.6.5.3922 PG 5 WC Cell Biology SC Cell Biology GA 154GW UT WOS:000245495900008 PM 17351339 ER PT J AU Tefferi, A Gilliland, DG AF Tefferi, Ayalew Gilliland, D. Gary TI Oncogenes in myeloproliferative disorders SO CELL CYCLE LA English DT Review DE polycythemia; thrombocythemia; myelofibrosis; JAK2; JAK2V617F ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; JUVENILE MYELOMONOCYTIC LEUKEMIA; TRANSCRIPTION FACTOR GATA-1; JAK2 V617F MUTATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; TYROSINE KINASE INHIBITOR; ACUTE MEGAKARYOBLASTIC LEUKEMIA; CHRONIC MYELOCYTIC-LEUKEMIA; COLONY-STIMULATING FACTOR AB Myeloproliferative disorders (MPDs) constitute a group of hematopoietic malignancies that feature enhanced proliferation and survival of one or more myeloid lineage cells. William Dameshek is credited for introducing the term "MPDs" in 1951 when he used it to group chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) under one clinicopathologic category. Since then, other myeloid neoplasms have been added to the MPD member list: chronic neutrophilic (CNL), eosinophilic (CEL) and myelomonocytic (CMML) leukemias; juvenile myelomonocytic leukemia (JMML); hypereosinophilic syndrome (HES); systemic mastocytosis (SM); and others. Collectively, MPDs are stem cell-derived clonal proliferative diseases whose shared and diverse phenotypic characteristics can be attributed to dysregulated signal transduction-a consequence of acquired somatic mutations. The most recognized among the latter is BCR-ABL, the disease-causing mutation in CML. Other mutations of putative pathogenetic relevance in MPDs include: JAK2V617F in PV, ET, and PMF; JAK2 exon 12 mutations in PV; MPLW515L/K in PMF and ET; KITD816V in SM; FIP1L1-PDGFRA in CEL-SM; rearrangements of PDGFRB in CEL-CMML and FGFR1 in stem cell leukemia-lymphoma syndrome; and RAS/PTPN11/NF1 mutations in JMML. This increasing repertoire of mutant molecules has streamlined translational research and molecularly targeted drug development in MPDs. C1 Mayo Clin & Mayo Fdn, Div Hematol, Rochester, MN 55905 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Tefferi, A (reprint author), Mayo Clin & Mayo Fdn, Div Hematol, W 10A,200 1st St SW, Rochester, MN 55905 USA. EM tefferi.ayalew@mayo.edu; ggilliland@rics.bwh.harvard.edu NR 383 TC 97 Z9 108 U1 0 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAR 1 PY 2007 VL 6 IS 5 BP 550 EP 566 DI 10.4161/cc.6.5.3919 PG 17 WC Cell Biology SC Cell Biology GA 154GW UT WOS:000245495900011 PM 17351342 ER PT J AU Perez, GI Acton, BM Jurisicova, A Perkins, GA White, A Brown, J Trbovich, AM Kim, MR Fissore, R Xu, J Ahmady, A D'Estaing, SD Li, H Kagawa, W Kurumizaka, H Yokoyama, S Okada, H Mak, TW Ellisman, MH Casper, RF Tilly, JL AF Perez, G. I. Acton, B. M. Jurisicova, A. Perkins, G. A. White, A. Brown, J. Trbovich, A. M. Kim, M. -R Fissore, R. Xu, J. Ahmady, A. D'Estaing, S. D. Li, H. Kagawa, W. Kurumizaka, H. Yokoyama, S. Okada, H. Mak, T. W. Ellisman, M. H. Casper, R. F. Tilly, J. L. TI Genetic variance modifies apoptosis susceptibility in mature oocytes via alterations in DNA repair capacity and mitochondrial ultrastructure SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE apoptosis; DNA damage; mitochondria; genetic modifiers; germ cells; oocytes ID CELL-DEATH; ELECTRON TOMOGRAPHY; MOUSE; MICE; ACTIVATION; CRISTAE; ORGANIZATION; ARCHITECTURE; INSTABILITY; DISRUPTION AB Although the identification of specific genes that regulate apoptosis has been a topic of intense study, little is known of the role that background genetic variance plays in modulating cell death. Using germ cells from inbred mouse strains, we found that apoptosis in mature (metaphase II) oocytes is affected by genetic background through at least two different mechanisms. The first, manifested in AKR/J mice, results in genomic instability. This is reflected by numerous DNA double- strand breaks in freshly isolated oocytes, causing a high apoptosis susceptibility and impaired embryonic development following fertilization. Microinjection of Rad51 reduces DNA damage, suppresses apoptosis and improves embryonic development. The second, manifested in FVB mice, results in dramatic dimorphisms in mitochondrial ultrastructure. This is correlated with cytochrome c release and a high apoptosis susceptibility, the latter of which is suppressed by pyruvate treatment, Smac/DIABLO deficiency, or microinjection of 'normal' mitochondria. Therefore, background genetic variance can profoundly affect apoptosis in female germ cells by disrupting both genomic DNA and mitochondrial integrity. C1 Harvard Univ, Vincent Ctr Reprod Biol, Vincent Obstet & Gynecol Serv, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. Univ Toronto, Dept Physiol, Toronto, ON, Canada. Univ Toronto, Dept Obstet & Gynecol, Toronto, ON, Canada. Univ Toronto, Dept Obstet & Gynecol, Toronto, ON, Canada. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. Univ Calif San Diego, Natl Ctr Microscopy & Imaging Res, La Jolla, CA 92093 USA. Univ Massachusetts, Dept Vet & Anim Sci, Amherst, MA 01003 USA. RIKEN, Prot Res Grp, Genom Sci Ctr, Yokohama, Kanagawa, Japan. Univ Toronto, Univ Hlth Network, Campbell Family Inst Breast Canc Res, Toronto, ON, Canada. Ontario Canc Inst, Toronto, ON M4X 1K9, Canada. RP Tilly, JL (reprint author), Harvard Univ, Vincent Ctr Reprod Biol, Vincent Obstet & Gynecol Serv, Massachusetts Gen Hosp,Med Sch, THR 901B,55 Fruit St, Boston, MA 02114 USA. EM perezg@msu.edu; jtilly@partners.org RI Jurisicova, Andrea/E-4580-2013; Casper, Robert/E-3775-2013; Yokoyama, Shigeyuki/N-6911-2015 OI Casper, Robert/0000-0002-6249-462X; Yokoyama, Shigeyuki/0000-0003-3133-7338 FU NCRR NIH HHS [RR04050]; NIA NIH HHS [R01/R37-AG012279] NR 40 TC 29 Z9 30 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD MAR PY 2007 VL 14 IS 3 BP 524 EP 533 DI 10.1038/sj.cdd.4402050 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 137EI UT WOS:000244275400015 PM 17039249 ER PT J AU Keskin, DB Marshall, B Munn, D Mellor, AL Gearhart, DA AF Keskin, Derin B. Marshall, Brendan Munn, David Mellor, Andrew L. Gearhart, Debra A. TI Decreased protein nitration in macrophages that overexpress indoleamine 2,3-dioxygenase SO CELLULAR & MOLECULAR BIOLOGY LETTERS LA English DT Article DE RAW 264.7 macrophages; indoleamine 2; 3-dioxygenase; oxidative stress; protein oxidation; superoxide anion ID MICROVASCULAR ENDOTHELIAL-CELLS; OXIDATIVE STRESS; SUPEROXIDE ANION; GAMMA-INTERFERON; QUINOLINIC ACID; KYNURENINE PATHWAY; HUMAN-FIBROBLASTS; L-TRYPTOPHAN; ANTIOXIDANT ACTIVITIES; TOXOPLASMA-GONDII AB The activity of indoleamine 2, 3-dioxygenase ( IDO; E. C. 1.13.11.42) catalyzes the oxidative cleavage of tryptophan to form kynurenine. IDO activity consumes superoxide anions; therefore, we postulated that over- expression of IDO might mitigate superoxide- anion dependent, oxidative modification of cellular proteins in vitro. We prepared and characterized RAW 264.7 macrophages that were stably transfected with either an IDO expression vector or the control ( empty) vector. We detected IDO mRNA, protein, and enzyme activity in the IDO- transfected macrophages, but not in the macrophages transfected with the empty vector. To generate superoxide anions in situ, we treated the IDO- and control- transfected cultures with xanthine or hypoxanthine, and then used ELISA methods to quantitate the relative levels of oxidatively modified proteins in total cell lysates. The levels of protein carbonyls were similar in IDO- transfected and vector- transfected macrophages; however, protein nitration was significantly less in IDO- transfected cells compared to control transfectants. In addition, steady- state levels of superoxide anions were significantly lower in the IDO- transfected cultures compared with control transfectants. Our results are consistent with the concept that, besides degrading tryptophan, IDO activity may protect cells from oxidative damage. C1 Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA. Dept Vet Affairs Med Ctr, Med Res Serv, Augusta, GA USA. RP Keskin, DB (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Derin_keskin@dfci.harvard.edu; dgearhar@mail.mcg.edu FU NIAID NIH HHS [R01AI044219]; NICHD NIH HHS [R01HD041187]; NINDS NIH HHS [F32NS10723] NR 93 TC 8 Z9 8 U1 0 U2 1 PU CELLULAR & MOLECULAR BIOLOGY LETTERS PI WROCLAW PA UNIV WROCLAW, INST BIOCHEM, DEPT GENETIC BIOCHEMISTRY, PRZBYSZEWSKIEGO 63/77, 51-148 WROCLAW, POLAND SN 1425-8153 J9 CELL MOL BIOL LETT JI Cell. Mol. Biol. Lett. PD MAR PY 2007 VL 12 IS 1 BP 82 EP 102 DI 10.2478/s11658-006-0048-9 PG 21 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 142EN UT WOS:000244632300007 PM 17103092 ER PT J AU Snyder, JS Alain, C AF Snyder, Joel S. Alain, Claude TI Sequential auditory scene analysis is preserved in normal aging adults SO CEREBRAL CORTEX LA English DT Article DE aging; auditory cortex; auditory scene analysis; dipole source analysis; event-related potentials ID AGE-RELATED-CHANGES; HEARING-IMPAIRED LISTENERS; EVENT-RELATED POTENTIALS; STREAM SEGREGATION; EVOKED POTENTIALS; TONE SEQUENCES; PERCEPTUAL ORGANIZATION; MODULATED TONES; CORTEX; FREQUENCY AB Normal aging is accompanied by speech perception difficulties, especially in adverse listening situations such as a cocktail party. To assess whether such difficulties might be related to impairments in sequential auditory scene analysis, event-related brain potentials were recorded from normal-hearing young, middle-aged, and older adults during presentation of low (A) tones, high (B) tones, and silences (-) in repeating 3 tone triplets (ABA-). The likelihood of reporting hearing 2 streams increased as a function of the frequency difference between A and B tones (Delta f) to the same extent for all 3 age groups and was paralleled by enhanced sensory-evoked responses over the frontocentral scalp regions. In all 3 age groups, there was also a progressive buildup in brain activity from the beginning to the end of the sequence of triplets, which was characterized by an enhanced positivity that peaked at about 200 ms after the onset of each ABA- triplet. Similar Delta f- and buildup-related activity also occurred over the right temporal cortex, but only for young adults. We conclude that age-related difficulties in separating competing speakers are unlikely to arise from deficits in streaming and might instead reflect less efficient concurrent sound segregation. C1 Baycrest Ctr Geriatr Care, Rotman Res Inst, Toronto, ON, Canada. Univ Toronto, Dept Psychol, Toronto, ON M5S 1A1, Canada. RP Snyder, JS (reprint author), Harvard Univ, VA Boston Healthcare Syst, Dept Psychiat 116A, 940 Belmont St, Brockton, MA 02301 USA. EM joel_snyder@hms.harvard.edu RI Snyder, Joel/B-4675-2008 OI Snyder, Joel/0000-0002-5565-3063 NR 57 TC 30 Z9 30 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD MAR PY 2007 VL 17 IS 3 BP 501 EP 512 DI 10.1093/cercor/bhj175 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 135AD UT WOS:000244125200001 PM 16581981 ER PT J AU Yuan, H Barnes, KR Weissleder, R Cantley, L Josephson, L AF Yuan, Hushan Barnes, Katie R. Weissleder, Ralph Cantley, Lewis Josephson, Lee TI Covalent reactions of Wortmannin under physiological conditions SO CHEMISTRY & BIOLOGY LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHOINOSITIDE 3-KINASE; INHIBITOR WORTMANNIN; ANTITUMOR-ACTIVITY; GLUCOSE-TRANSPORT; IN-VITRO; PROTEIN; ANTILIPOLYSIS; ALLERGY; TARGET AB Wortmannin (Wm), a steroid-like molecule of 428.4 Da, appears to be unstable in biological fluids (apparent chemical instability), yet it exhibits an anti proliferative activity in assays employing a 48 hr incubation period (prolonged bioactivity), a situation we refer to as the "wortmannin paradox." Under physiological conditions, Wm covalently reacts with nucleophiles such as the side chains of cysteine, N-methyl hexanoic acid, lysine, or proline at the C20 position on the furan ring. Like Wm, WmC20 amino acid derivatives had significant anti proliferative activities. Three Wm derivatives, WmC20-proline, WmC20-cysteine, and a WmC20-N-methyl hexanoic acid, generated Wm that then reacted with lysine in an exchange-type reaction. This unusual, reversible, covalent reaction of Wm with nucleophiles under physiological conditions provides an explanation for the wortmannin paradox. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. RP Josephson, L (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St, Charlestown, MA 02129 USA. EM ljosephson@partners.org RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [P50CA86355, T32 CA079443]; NIBIB NIH HHS [R01EB00662]; NIGMS NIH HHS [R01 GM041890, GM041890] NR 29 TC 21 Z9 21 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD MAR PY 2007 VL 14 IS 3 BP 321 EP 328 DI 10.1016/j.chembiol.2007.02.007 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 151QU UT WOS:000245306500013 PM 17379147 ER PT J AU McCarthy, JR Weissleder, R AF McCarthy, Jason R. Weissleder, Ralph TI Model systems for fluorescence and singlet oxygen quenching by metal loporphyrins SO CHEMMEDCHEM LA English DT Article AB Next-generation photodynamic therapy agents will minimize extraneous phototoxicity by being active only at the target site. To this end, we have developed a model system to systematically investigate the excited-state quenching ability of a number of metalloporphyrins. Central metal ions that prefer four-coordinate, square planar orientations (Ag '', Cu '', Ni '', Pd '', and Zn '') were used. Porphyrin dimers based on 5-(4-aminophenyl)-10,15,20-triphenylporphyrin and comprising both a free base porphyrin and a metalloporphyrin covalently linked through a five-carbon alkyl chain were synthesized. The fluorescence and singlet oxygen quantum yields for the dimers were probed at 630 and 650 nm, respectively, resulting in the excitation of only the free base porphyrin and allowing a comparison of the quenching efficacy of each central metal ion. These results demonstrate that metalloporphyrins can serve as efficient quenchers, and may be useful in the design of novel light-activated therapeutic agents. RP McCarthy, JR (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St,Rm 5406, Charlestown, MA 02129 USA. EM jason_mccarthy@hms.harvard.edu NR 46 TC 0 Z9 0 U1 1 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1860-7179 J9 CHEMMEDCHEM JI ChemMedChem PD MAR PY 2007 VL 2 IS 3 BP 360 EP 365 DI 10.1002/cmdc.200600244 PG 6 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V43PK UT WOS:000202946800012 ER PT J AU Diaz, A Barria, P Niederman, M Restrepo, MI Dreyse, J Fuentes, G Couble, B Saldias, F AF Diaz, Alejandro Barria, Paulina Niederman, Michael Restrepo, Marcos I. Dreyse, Jorge Fuentes, Gino Couble, Bernardita Saldias, Fernando TI Etiology of community-acquired pneumonia in hospitalized patients in Chile - The increasing prevalence of respiratory viruses among classic pathogens SO CHEST LA English DT Article DE bacterial pneumonia; community; etiology; viruses ID PNEUMOCOCCAL PNEUMONIA; ADULT PATIENTS; STREPTOCOCCUS-PNEUMONIAE; PROGNOSTIC-FACTORS; EPITHELIAL-CELLS; GUIDELINES; MANAGEMENT; MULTICENTER; DIAGNOSIS; SEVERITY AB Background and study objectives: The range and relative impact of microbial pathogens, particularly viral pathogens, as a cause of community-acquired pneumonia (CAP) in hospitalized adults has not received much attention. The aim of this study was to determine the microbial etiology of CAP in adults and to identify the risk factors for various specific pathogens. Methods: We prospectively studied 176 patients (mean [+/- SD] age, 65.8 +/- 18.5 years) who had hospitalized for CAP to identify the microbial etiology. For each patient, sputum and blood cultures were obtained as well as serology testing for Mycoplasina pneumoniae and Chlamydophila pneumoniae, urinary antigen testing for Legionella pneumophila and Streptococcus pneumoniae, and a nasopharyngeal swab for seven respiratory viruses. Results: Microbial etiology was determined in 98 patients (55%). S pneumoniae (49 of 98 patients; 50%) and respiratory viruses (32%) were the most frequently isolated pathogen groups. Pneumococcal pneumonia was associated with tobacco smoking of > 10 pack-years (odds ratio [OR] 2.6; 95% confidence interval [CI], 1.2 to 5.4; p = 0.01). Respiratory viruses were isolated more often in fall or winter (28%; p = 0.011), and as an exclusive etiology tended to be isolated in patients : 65 years of age (20%; p = 0.07). Viral CAP was associated with antimicrobial therapy prior to hospital admission (OR, 4.5; 95% CI, 1.4 to 14.6). Conclusions: S pneumoniae remains the most frequent pathogen in adults with CAP and should be covered with empirical antimicrobial treatment. Viruses were the second most common etiologic agent and should be tested for, especially in fall or winter, both in young and elderly patients who are,hospitalized with CAP. C1 Pontificia Univ Catolica Chile, Dept Enfermedades Resp, Santiago, Chile. Winthrop Univ Hosp, Dept Med, Mineola, NY 11501 USA. S Texas Vet Hlth Care Syst, Dept Med, Div Pulm Crit Care Med & Infect Dis, San Antonio, TX USA. RP Diaz, A (reprint author), 20 Bonner Ave, Somerville, MA 02143 USA. EM alediazf@hotmail.com RI Restrepo, Marcos/H-4442-2014 NR 37 TC 58 Z9 68 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAR PY 2007 VL 131 IS 3 BP 779 EP 787 DI 10.1378/chest.06-1800 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 148KI UT WOS:000245072900024 PM 17356093 ER PT J AU Grinspan, ZM Olson, TR Cimino, C AF Grinspan, Z. M. Olson, T. R. Cimino, C. TI Anatomy reports on the Internet: A Web-based tool for student reports on cadaveric findings SO CLINICAL ANATOMY LA English DT Article DE multimedia education; gross anatomy; anatomical variation; web-based education ID MEDICAL-EDUCATION; DESIGN AB The difference between the idealization of anatomy atlases and the reality of human cadavers often frustrates gross anatomy students. To encourage students to celebrate rather than protest these differences, we describe a web site ARI (Anatomy Reports on the Internet) that allows students to document cadaveric findings online with photographs and text. We used several web languages for site construction, including mysql, php, html, and javascript. Faculty tools allow instructors to upload digital images of the structures, add relevant commentary, view and delete images, review submitted reports, and examine database statistics. Student tools allow dissection groups to choose and comment on images, enter and edit reports, and read reports submitted by other students. During the first two years of the site's use (2000-2001, 2002-2003), every dissection group at our institution submitted at least one report. Technical support requests were minimal. C1 Albert Einstein Coll Med, Off Comp Based Educ, Bronx, NY 10461 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10467 USA. RP Cimino, C (reprint author), Albert Einstein Coll Med, Off Comp Based Educ, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM cimino@aecom.yu.edu NR 21 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0897-3806 J9 CLIN ANAT JI Clin. Anat. PD MAR PY 2007 VL 20 IS 2 BP 215 EP 221 DI 10.1002/ca.20293 PG 7 WC Anatomy & Morphology SC Anatomy & Morphology GA 135FI UT WOS:000244139100019 PM 16617438 ER PT J AU Sakhuja, R Green, S Oestreicher, EM Sluss, PM Lee-Lewandrowski, E Lewandrowski, KB Januzz, JL AF Sakhuja, Rahul Green, Sandy Oestreicher, Eveline M. Sluss, Patrick M. Lee-Lewandrowski, Elizabeth Lewandrowski, Kent B. Januzz, James L., Jr. TI Amino-terminal pro-brain natriuretic peptide, brain natriuretic peptide, and troponin T for prediction of mortality in acute heart failure SO CLINICAL CHEMISTRY LA English DT Article ID C-REACTIVE PROTEIN; RISK STRATIFICATION; ANALYTICAL PERFORMANCE; MYOCARDIAL-INFARCTION; EMERGENCY-DEPARTMENT; ASSAY; CARDIOMYOPATHY; IMPRECISION; ELEVATION; PROGNOSIS AB Background: Combining testing for natriuretic peptides [amino-terminal pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP)l and cardiac troponin T (cTnT) may help predict mortality in patients with acute heart failure (HF). Methods: We studied 209 patients with acute HF at an urban academic center and used ROC curves and multivariate analyses to examine the relationship of outcome to natriuretic peptide and cTnT concentrations at presentation. Results: Higher concentrations of natriuretic peptides and cTnT at presentation were predictors of death at 60 days and 1 year (P < 0.001 and P < 0.01, respectively, at both time points). Optimal cutoff points for NT-proBNP, BNP, and cTnT for predicting death by 60 days or 1 year were 5562 and 3174 ng/L, 428 and 352 ng/L, and 0.01 and 0.01 mu g/L, respectively. Most decedents demonstrated increased concentrations of both natriuretic peptides and cTnT and had a 25% mortality rate at the 60-day time point (P < 0.001). Mortality rates were low (< 4%) among patients with either no increase or an increase in only 1 marker. Decedents with increases in both a natriuretic peptide and cTnT at presentation had the highest death rate at 1 year (45%, P < 0.001). This combination was strongly predictive of death [NT-proBNP plus cTnT: hazard ratio (HR), 7.66; 95% confidence interval (CD, 3.06-17.8; BNP plus cTnT: HR, 6.82; 95% Cl, 2.99-16.51. Conclusions: A dual-marker strategy incorporating a natriuretic peptide and cTnT is superior to either marker alone for estimating short- and longer-term risk in patients with acute HE (c) 2007 American Association for Clinical Chemistry. C1 Massachusetts Gen Hosp, Clin Labs, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Labs, Cardiol Div, Boston, MA 02114 USA. RP Januzz, JL (reprint author), Massachusetts Gen Hosp, Clin Labs, Dept Med, Yawkey 5984,32 Fruit St, Boston, MA 02114 USA. EM JJanuzzi@Partners.org NR 40 TC 28 Z9 31 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAR PY 2007 VL 53 IS 3 BP 412 EP 420 DI 10.1373/clinchem.2006.074047 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 141BC UT WOS:000244550300007 PM 17259237 ER EF