FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Kufer, SK Puchner, EM Gumpp, H Liedl, T Gaub, HE AF Kufer, S. K. Puchner, E. M. Gumpp, H. Liedl, T. Gaub, H. E. TI Single-molecule cut-and-paste surface assembly SO SCIENCE LA English DT Article ID ATOMIC-FORCE MICROSCOPE; SCANNING TUNNELING MICROSCOPY; DNA-MOLECULES; SPECTROSCOPY; BIOLOGY; CELLS AB We introduce a method for the bottom- up assembly of biomolecular structures that combines the precision of the atomic force microscope ( AFM) with the selectivity of DNA hybridization. Functional units coupled to DNA oligomers were picked up from a depot area by means of a complementary DNA strand bound to an AFM tip. These units were transferred to and deposited on a target area to create basic geometrical structures, assembled from units with different functions. Each of these cut- and- paste events was characterized by single- molecule force spectroscopy and single- molecule fluorescence microscopy. Transport and deposition of more than 5000 units were achieved, with less than 10% loss in transfer efficiency. C1 [Kufer, S. K.; Puchner, E. M.; Gumpp, H.; Gaub, H. E.] Univ Munich, Ctr Nanosci, D-80799 Munich, Germany. [Kufer, S. K.; Puchner, E. M.; Gumpp, H.; Gaub, H. E.] Univ Munich, Dept Phys, D-80799 Munich, Germany. [Liedl, T.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Liedl, T.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Kufer, SK (reprint author), Univ Munich, Ctr Nanosci, Amalienstr 54, D-80799 Munich, Germany. RI Liedl, Tim/O-7539-2014 OI Liedl, Tim/0000-0002-0040-0173 NR 33 TC 169 Z9 173 U1 3 U2 82 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 FEB 1 PY 2008 VL 319 IS 5863 BP 594 EP 596 DI 10.1126/science.1151424 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 257AQ UT WOS:000252772000033 PM 18239119 ER PT J AU Schlabach, MR Luo, J Solimini, NL Hu, G Xu, QK Li, MZ Zhao, ZM Smogorzewska, A Sowa, ME Ang, XLL Westbrook, TF Liang, AC Chang, K Hackett, JA Harper, JW Hannon, GJ Elledge, SJ AF Schlabach, Michael R. Luo, Ji Solimini, Nicole L. Hu, Guang Xu, Qikai Li, Mamie Z. Zhao, Zhenming Smogorzewska, Agata Sowa, Mathew E. Ang, Xiaolu L. Westbrook, Thomas F. Liang, Anthony C. Chang, Kenneth Hackett, Jennifer A. Harper, J. Wade Hannon, Gregory J. Elledge, Stephen J. TI Cancer proliferation gene discovery through functional Genomics SO SCIENCE LA English DT Article ID COLORECTAL CANCERS; HUMAN BREAST; P53 PATHWAY; SCREEN; PHOSPHATASE; CELLS; MDM2 AB Retroviral short hairpin RNA (shRNA) - mediated genetic screens in mammalian cells are powerful tools for discovering loss- of- function phenotypes. We describe a highly parallel multiplex methodology for screening large pools of shRNAs using half- hairpin barcodes for microarray deconvolution. We carried out dropout screens for shRNAs that affect cell proliferation and viability in cancer cells and normal cells. We identified many shRNAs to be antiproliferative that target core cellular processes, such as the cell cycle and protein translation, in all cells examined. Moreover, we identified genes that are selectively required for proliferation and survival in different cell lines. Our platform enables rapid and cost- effective genome-wide screens to identify cancer proliferation and survival genes for target discovery. Such efforts are complementary to the Cancer Genome Atlas and provide an alternative functional view of cancer cells. C1 [Schlabach, Michael R.; Luo, Ji; Solimini, Nicole L.; Hu, Guang; Xu, Qikai; Li, Mamie Z.; Zhao, Zhenming; Smogorzewska, Agata; Westbrook, Thomas F.; Liang, Anthony C.; Hackett, Jennifer A.; Elledge, Stephen J.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Schlabach, Michael R.; Luo, Ji; Solimini, Nicole L.; Hu, Guang; Xu, Qikai; Li, Mamie Z.; Zhao, Zhenming; Smogorzewska, Agata; Westbrook, Thomas F.; Liang, Anthony C.; Hackett, Jennifer A.; Elledge, Stephen J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Genet & Genom,Dept Genet, Boston, MA 02115 USA. [Smogorzewska, Agata] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sowa, Mathew E.; Ang, Xiaolu L.; Harper, J. Wade] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Chang, Kenneth; Hannon, Gregory J.] Cold Spring Harbor Lab, Howard Hughes Med Inst, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA. RP Elledge, SJ (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. EM selledge@genetics.med.harvard.edu RI Smogorzewska, Agata/B-8891-2011; Hu, Guang/E-7474-2016; OI Hu, Guang/0000-0003-0437-4723; Cambronne, Lulu/0000-0002-3547-448X FU Howard Hughes Medical Institute; NCI NIH HHS [P01 CA013106, T32 CA009216, T32CA09216, P01 CA013106-36, P01 CA013106-37]; NIA NIH HHS [R01 AG011085]; NINDS NIH HHS [F31 NS054507-01] NR 18 TC 243 Z9 247 U1 2 U2 27 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 FEB 1 PY 2008 VL 319 IS 5863 BP 620 EP 624 DI 10.1126/science.1149200 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 257AQ UT WOS:000252772000041 PM 18239126 ER PT J AU Peer, D Park, EJ Morishita, Y Carman, CV Shimaoka, M AF Peer, Dan Park, Eun Jeong Morishita, Yoshiyuki Carman, Christopher V. Shimaoka, Motomu TI Systemic leukocyte-directed siRNA delivery revealing cyclin D1 as an anti-inflammatory target SO SCIENCE LA English DT Article ID SMALL INTERFERING RNAS; IN-VIVO; GENE; COLITIS; CELLS AB Cyclin D1 ( CyD1) is a pivotal cell cycle - regulatory molecule and a well- studied therapeutic target for cancer. Although CyD1 is also strongly up- regulated at sites of inflammation, its exact roles in this context remain uncharacterized. To address this question, we developed a strategy for selectively silencing CyD1 in leukocytes in vivo. Targeted stabilized nanoparticles ( tsNPs) were loaded with CyD1 - small interfering RNA ( siRNA). Antibodies to beta(7) integrin ( beta(7) I) were then used to target specific leukocyte subsets involved in gut inflammation. Systemic application of beta(7) I-tsNPs silenced CyD1 in leukocytes and reversed experimentally induced colitis in mice by suppressing leukocyte proliferation and T helper cell 1 cytokine expression. This study reveals CyD1 to be a potential anti- inflammatory target, and suggests that the application of similar modes of targeting by siRNA may be feasible in other therapeutic settings. C1 [Peer, Dan; Park, Eun Jeong; Morishita, Yoshiyuki; Shimaoka, Motomu] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Peer, Dan; Park, Eun Jeong; Morishita, Yoshiyuki; Shimaoka, Motomu] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Carman, Christopher V.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Carman, Christopher V.] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Shimaoka, M (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 200 Longwood Ave, Boston, MA 02115 USA. EM shimaoka@cbrinstitute.org RI Peer, Dan/A-1785-2011; Carman, Christopher/L-8108-2016 OI Peer, Dan/0000-0001-8238-0673; Carman, Christopher/0000-0001-7358-2548 FU NHLBI NIH HHS [HL048675, P01 HL048675, P01 HL048675-150013]; NIAID NIH HHS [AI63421, R01 AI063421, R01 AI063421-04] NR 21 TC 306 Z9 317 U1 4 U2 64 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 FEB 1 PY 2008 VL 319 IS 5863 BP 627 EP 630 DI 10.1126/science.1149859 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 257AQ UT WOS:000252772000043 PM 18239128 ER PT J AU Giles, FJ DeAngeloc, DJ Baccaran, M Deininger, M Guilhot, F Hughes, T Mauro, M Radich, J Ottmann, O Cortes, J AF Giles, Francis J. DeAngeloc, Daniel J. Baccaran, Michele Deininger, Michael Guilhot, Francois Hughes, Timothy Mauro, Michael Radich, Jerald Ottmann, Oliver Cortes, Jorge TI Optimizing outcomes for patients with advanced disease in chronic myelogenous leukemia SO SEMINARS IN ONCOLOGY LA English DT Review ID CHRONIC MYELOID-LEUKEMIA; TYROSINE KINASE INHIBITOR; IMATINIB MESYLATE DISCONTINUATION; CYTOGENETIC CLONAL EVOLUTION; PATIENTS RECEIVING IMATINIB; IN-VITRO SENSITIVITY; EARLY CHRONIC-PHASE; WNT GENE FAMILY; BCR-ABL; INTERFERON-ALPHA C1 [Giles, Francis J.] Univ Texas Hlth Sci Ctr San Antonio, Div Hematol & Med Oncol, San Antonio, TX 78229 USA. [Giles, Francis J.] CTRC Inst Drug Dev, San Antonio, TX 78229 USA. [Cortes, Jorge] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX USA. [DeAngeloc, Daniel J.] Dana Faber Canc Inst, Boston, MA USA. [Baccaran, Michele] Univ Bologna, Bologna, Italy. [Deininger, Michael; Mauro, Michael] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Guilhot, Francois] CHU Poitiers, INSERM, Clin Invest Ctr, Poitiers, France. [Hughes, Timothy] Inst Med & Vet Sci, Adelaide, SA 5000, Australia. [Radich, Jerald] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Ottmann, Oliver] Univ Frankfurt, Frankfurt, Germany. RP Giles, FJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Hematol & Med Oncol, San Antonio, TX 78229 USA. EM frankgiles@aol.com RI Ottmann, Oliver/D-5007-2016 OI Ottmann, Oliver/0000-0001-9559-1330 NR 131 TC 16 Z9 16 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 2008 VL 35 IS 1 SU 1 BP S1 EP S17 DI 10.1053/j.seminoncol.2007.12.002 PG 17 WC Oncology SC Oncology GA 287XN UT WOS:000254950100001 PM 18346528 ER PT J AU Ouellette, H Bredella, M Labis, J Palmer, WE Torriani, M AF Ouellette, Hugue Bredella, Miriam Labis, John Palmer, William E. Torriani, Martin TI MR imaging of the elbow in baseball pitchers SO SKELETAL RADIOLOGY LA English DT Review DE baseball; pitcher; MR imaging; overhead throwing athlete; elbow ID ULNAR COLLATERAL LIGAMENT; POSTEROLATERAL ROTATORY INSTABILITY; OSTEOCHONDRITIS-DISSECANS; THROWING ATHLETE; VALGUS STABILITY; ARTHROGRAPHY; INJURY; RECONSTRUCTION; EPICONDYLITIS; CONSTRAINTS AB Baseball pitcher throwing biomechanics are important to understanding the pathophysiology and magnetic resonance (MR) imaging appearances of injuries in baseball pitchers. Baseball pitchers experience repetitive excessive valgus forces at the elbow. Typical injuries are secondary to medial joint distraction, lateral joint compression, and rotatory forces at the olecranon. MR imaging is useful for evaluation of the elbow in baseball pitchers. C1 [Ouellette, Hugue; Bredella, Miriam; Palmer, William E.; Torriani, Martin] Massachusetts Gen Hosp, Div Musculoskeletal Radiol, Boston, MA 02114 USA. [Labis, John] Methodist Hosp, Houston, TX 77030 USA. RP Ouellette, H (reprint author), Massachusetts Gen Hosp, Div Musculoskeletal Radiol, 55 Fruit St,Yawkey 6046, Boston, MA 02114 USA. EM haouellette@partners.org NR 40 TC 22 Z9 23 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD FEB PY 2008 VL 37 IS 2 BP 115 EP 121 DI 10.1007/s00256-007-0364-9 PG 7 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 242ND UT WOS:000251731200003 PM 17805531 ER PT J AU Ellenbogen, JM AF Ellenbogen, Jeffrey M. TI The sleeping brain's influence on memory SO SLEEP LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Sleep Med,Dept Neurol, Boston, MA 02114 USA. RP Ellenbogen, JM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Sleep Med,Dept Neurol, 55 Fruit St,Wang ACC 720, Boston, MA 02114 USA. EM jeffrey_ellenbogen@hms.harvard.edu NR 3 TC 1 Z9 5 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD FEB 1 PY 2008 VL 31 IS 2 BP 163 EP 164 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 257HZ UT WOS:000252791100002 PM 18274262 ER PT J AU Guzman-Marin, R Suntsova, N Bashir, T Nienhuis, R Szymusiak, R McGinty, D AF Guzman-Marin, Ruben Suntsova, Natalia Bashir, Tariq Nienhuis, Robert Szymusiak, Ronald McGinty, Dennis TI Rapid eye movement sleep deprivation contributes to reduction of neurogenesis in the hippocampal dentate gyrus of the adult rat SO SLEEP LA English DT Article DE adult neurogenesis; hippocampus; dentate gyrus ID LONG-TERM POTENTIATION; CELL-PROLIFERATION; EXPRESSION; PLASTICITY; RECOVERY; EXERCISE; STRESS; PERIOD; BRAIN; BDNF AB Study Objectives: The dentate gyrus (DG) of the adult hippocampus contains progenitor cells, which have potential to differentiate into neurons. Previously we reported that 96 hours of total sleep deprivation reduces neurogenesis in the DG of adult rats. Loss of either non-rapid eye movement (NREM) or rapid eye movement (REM) sleep could have contributed to the effect of total sleep deprivation. The present study assessed the effect of 4 days of REM sleep deprivation (REMD) on neurogenesis. Design: REMD was achieved by brief treadmill movement initiated by automatic online detection of REM sleep. A yoked-control (YC) rat was placed in the same treadmill and experienced the identical movement regardless the stage of the sleep-wake cycle. The thymidine analog 5-bromo-2'-deoxy-uridine and the intrinsic proliferation marker, Ki-67, were both used to label proliferating cells. Setting: Basic neurophysiology laboratory. Participants: Male Sprague-Dawley male rats (300 - 320 g) Results: REM sleep was reduced by 85% in REMD rats and by 43% in YC, compared with cage control animals and by 79% in REMD rats compared with YC. NREM sleep and slow wave activity within NREM did not differ in REMD and YC groups. Cell proliferation was reduced by 63 % in REMD compared with YC rats, and by 82% and 51 %, respectively, in REMD and YC rats compared with cage controls. Across all animals, cell proliferation exhibited a positive correlation with the percentage of REM sleep (r = 0.84, P < 0.001). Reduced cell proliferation in REMD rats was confirmed with the intrinsic proliferation marker, Ki-67. REMD also reduced the percentage of proliferating cells that later expressed a mature neuronal marker. Conclusions: The present findings support a hypothesis that REM sleep-associated processes facilitate proliferation of granule cells in the adult hippocampal DG. C1 [Guzman-Marin, Ruben; Suntsova, Natalia; Bashir, Tariq; Nienhuis, Robert; Szymusiak, Ronald; McGinty, Dennis] VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. [Guzman-Marin, Ruben; Suntsova, Natalia; Bashir, Tariq; McGinty, Dennis] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Szymusiak, Ronald] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Suntsova, Natalia] Rostov State Univ, AB Kogan Res Inst Neurocybernet, Rostov Na Donu, Russia. RP McGinty, D (reprint author), VA Greater Los Angeles Healthcare Syst, REs Serv 151A3, 16111 Plummer St, Los Angeles, CA 91343 USA. EM dmcginty@ucla.edu FU NHLBI NIH HHS [P50 HL060296, HL 60296]; NIMH NIH HHS [MH 075076, R01 MH075076] NR 35 TC 48 Z9 52 U1 1 U2 6 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD FEB 1 PY 2008 VL 31 IS 2 BP 167 EP 175 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 257HZ UT WOS:000252791100003 PM 18274263 ER PT J AU Tamaki, M Matsuoka, T Nittono, H Hori, T AF Tamaki, Masako Matsuoka, Tatsuya Nittono, Hiroshi Hori, Tadao TI Fast sleep spindle (13-15 Hz) activity correlates with sleep-dependent improvement in visuomotor performance SO SLEEP LA English DT Article DE sleep spindle; procedural memory; motor learning; fast spindle; slow spindle ID LONG-TERM POTENTIATION; PROCEDURAL MEMORY; STAGE-2 SLEEP; TIME-COURSE; NEOCORTEX; DENSITY; RATS; EEG AB Study Objectives: The relationship between memory enhancement and fast (13-16 Hz) versus slow (10-13 Hz) spindle activity during sleep was investigated. Design: Standard polysomnographic recordings were conducted during an adaptation, control nonlearning, and learning night. Automatic spindle detection and measurement was utilized with visual confirmation. Setting: Participants slept in individual, temperature-controlled bedrooms in a sleep laboratory. Participants: Twelve healthy student volunteers (9 women and 3 men, mean age: 22.3 years) participated. Interventions: On the learning night, participants completed a presleep learning session on a modified version of mirror-tracing task followed by a postsleep test session. No learning or test sessions were performed on the adaptation and nonlearning nights. Measurements and Results: Tracing time was reduced by 6.4 seconds (20.6% +/- 2.07%) from the presleep to the postsleep session. Mean amplitude and duration of fast spindles was greater on the learning night than on the nonlearning night (both P values < 0.05). Skill improvement and fast-spindle activity were positively correlated (density [r = 0.76, P < 0.01], amplitude [r = 0.69, P < 0.05], and duration [r = 0.67, P < 0.05]). Significant correlations between fast-spindle activity and mirror-tracing performance were also evident for the nonlearning night. There was no significant relationship between mirror-tracing performance and slow-spindle activity on any night. Conclusions: The thalamocortical network underlying fast-spindle generation may contribute to or reflect plasticity during sleep. C1 [Tamaki, Masako; Matsuoka, Tatsuya; Nittono, Hiroshi; Hori, Tadao] Hiroshima Univ, Grad Sch Integrated Arts, Dept Behav Sci, Hiroshima 7398521, Japan. [Tamaki, Masako] Massachusetts Gen Hosp, Atinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Boston, MA 02114 USA. RP Hori, T (reprint author), Hiroshima Univ, Grad Sch Integrated Arts, Dept Behav Sci, 1-7-1 Kagamiyama, Hiroshima 7398521, Japan. EM tdhori@hiroshima-u.ac.jp RI Nittono, Hiroshi/C-4043-2009 OI Nittono, Hiroshi/0000-0001-5671-609X NR 40 TC 71 Z9 72 U1 0 U2 2 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD FEB 1 PY 2008 VL 31 IS 2 BP 204 EP 211 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 257HZ UT WOS:000252791100007 PM 18274267 ER PT J AU McBride, CM Puleo, E Pollak, KI Clipp, EC Woolford, S Emmons, KM AF McBride, Colleen M. Puleo, Elaine Pollak, Kathryn I. Clipp, Elizabeth C. Woolford, Sam Emmons, Karen M. TI Understanding the role of cancer worry in creating a "teachable moment" for multiple risk factor reduction SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE worry; teachable moment; behavior change; USA; colon cancer ID POSSIBLE SELVES; BREAST-CANCER; SCREENING BEHAVIOR; PROJECT PREVENT; HEALTH-STATUS; COLON-CANCER; OUTCOMES; SMOKING; WOMEN; LIFE AB The manuscript examines the influence of contextual factors on whether and for whom a colon polyp diagnosis might be a teachable moment, as indicated by engagement with a proactively delivered intervention. Baseline and 8-month follow-up data were analyzed from a two-site behavioral intervention trial with patients in Massachusetts and North Carolina, USA who had recently undergone polypectomy for pre-cancerous colon polyps and were randomized to a behavior change intervention condition (N = 591). Intervention "buy-in" was used as an indicator of response consistent with the polyp identification serving as a teachable moment. Cancer worry, personal risk, health-related self-identity and other sociodemographic factors were tested to predict intervention buy-in. As predicted, those who were most worried about colon cancer were most likely to engage in the intervention. One indicator of personal risk, number of risk behaviors, was significantly and negatively associated with buy-in. Predictors of intervention buy-in and cancer worry were not consistent. We recommend that expanded measures of affect and health-related self-identity should be considered in future research to understand the motivational potential of health events for increasing engagement in effective behavior change interventions. (C) 2007 Elsevier Ltd. All rights reserved. C1 [McBride, Colleen M.] NHGRI, Social Behav Res Branch, Bethesda, MD 20892 USA. [Puleo, Elaine] Univ Massachusetts, Amherst, MA 01003 USA. [Clipp, Elizabeth C.] Duke Univ, Ctr Med, Div Geriatr, Dept Med, Durham, NC 27706 USA. [Clipp, Elizabeth C.] Duke Univ, Med Ctr, Sch Nursing, Duke Comprehens Canc Ctr, Durham, NC 27706 USA. [Woolford, Sam] Bentley Coll, Waltham, MA 02154 USA. [Emmons, Karen M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. RP McBride, CM (reprint author), NHGRI, Social Behav Res Branch, 2 Ctr Dr,Bldg 2,Room E408, Bethesda, MD 20892 USA. EM cmcbride@mail.nih.gov FU Intramural NIH HHS [Z01 HG200315-04] NR 43 TC 36 Z9 37 U1 3 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD FEB PY 2008 VL 66 IS 3 BP 790 EP 800 DI 10.1016/j.socscimed.2007.10.014 PG 11 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 261SA UT WOS:000253099100026 PM 18037204 ER PT J AU Parashurama, N Nahmias, Y Cho, CH van Poll, D Tilles, AW Berthiaume, F Yarmush, ML AF Parashurama, Natesh Nahmias, Yaakov Cho, Cheul H. van Poll, Daan Tilles, Arno W. Berthiaume, Francois Yarmush, Martin L. TI Activin afters the kinetics of endoderm induction in embryonic stem cells cultured on collagen gels SO STEM CELLS LA English DT Article DE activin; endoderm; collagen gel; embryonic stem cells (mouse); follistatin; epiblast ID DEFINITIVE ENDODERM; GENE-EXPRESSION; IN-VITRO; GUT ENDODERM; VISCERAL ENDODERM; PRIMITIVE STREAK; MOUSE EMBRYOS; DIFFERENTIATION; GASTRULATION; FOLLISTATIN AB Embryonic stem cell-derived endoderm is critical for the development of cellular therapies for the treatment of disease such as diabetes, liver cirrhosis, or pulmonary emphysema. Here, we describe a novel approach to induce endoderm from mouse embryonic stem (mES) cells using fibronectin-coated collagen gels. This technique results in a homogeneous endoderm-like cell population, demonstrating endoderm-specific gene and protein expression, which remains committed following in vivo transplantation. In this system, activin, normally an endoderm inducer, caused an 80% decrease in the Foxa2-positive endoderm fraction, whereas follistatin increased the Foxa2-positive endoderm fraction to 78%. Our work suggests that activin delays the induction of endoderm through its transient precursors, the epiblast and mesendoderm. Long-term differentiation displays a twofold reduction in hepatic gene expression and threefold reduction in hepatic protein expression of activin-treated cells compared with follistatin-treated cells. Moreover, subcutaneous transplantation of activin-treated cells in a syngeneic mouse generated a heterogeneous teratoma-like mass, suggesting that these were a more primitive population. In contrast, follistatin-treated cells resulted in an encapsulated epithelial-like mass, suggesting that these cells remained committed to the endoderm lineage. In conclusion, we demonstrate a novel technique to induce the direct differentiation of endoderm from mES cells without cell sorting. In addition, our work suggests a new role for activin in induction of the precursors to endoderm and a new endoderm-enrichment technique using follistatin. C1 [Parashurama, Natesh; Nahmias, Yaakov; Cho, Cheul H.; van Poll, Daan; Tilles, Arno W.; Berthiaume, Francois; Yarmush, Martin L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA USA. [Parashurama, Natesh; Yarmush, Martin L.] Rutgers State Univ, Dept Chem & Biochem Engn, Piscataway, NJ USA. RP Yarmush, ML (reprint author), Ctr Engn Med, 114 16th St,Room 1402, Charlestown, MA 02129 USA. EM ireis@sbi.org RI Nahmias, Yaakov/H-4725-2013 FU NIDDK NIH HHS [K01 DK080241, K01 DK080241-01] NR 62 TC 14 Z9 14 U1 0 U2 13 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD FEB PY 2008 VL 26 IS 2 BP 474 EP 484 DI 10.1634/stemcells.2007-0303 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 265PE UT WOS:000253372600020 PM 18065398 ER PT J AU Conrad, C Zeindl-Eberhart, E Moosmann, S Nelson, PJ Bruns, CJ Huss, R AF Conrad, Claudius Zeindl-Eberhart, Evelyn Moosmann, Sabine Nelson, Peter J. Bruns, Christiane J. Huss, Ralf TI Alkaline phosphatase, glutathione-S-transferase-P, and cofilin-1 distinguish multipotent mesenchymal stromal cell lines derived from the bone marrow versus peripheral blood SO STEM CELLS AND DEVELOPMENT LA English DT Article ID HEMATOPOIETIC STEM; PRECURSORS; GTPASES; ELECTROPHORESIS; PROGENITORS; ASSAY; RAC AB Multipotent mesenchymal stromal cells (MSCs) can be isolated from bone marrow or peripheral blood. To identify phenotypical and functional differences between MSCs derived from these sources, the human bone marrow-derived, fibroblast-like cell line L87/4 was compared with the peripheral blood-derived, fibroblast-like cell line V54/2. Both cell lines expressed similar levels of SH3(+), CD45(-), CD68(-), CD133(-), and HLA-DR-. The bone marrow-derived cells expressed higher surface levels of CD105, CD10, and CD117 and preferentially expressed alkaline phosphatase, glutathione S-transferase P, and cofilin-1. The peripheral blood-derived line showed a higher number of CD34(+)/CD105(+) double-positive and side population (SP) cells. The results demonstrate the more multipotent, yet quiescent, stromal phenotype of bone marrow MSCs, whereas MSCs isolated from the circulation display more hematopoietic-lineage characteristics. Importantly, potential marker genes that distinguish the two stages of MSCs are defined. C1 [Conrad, Claudius; Bruns, Christiane J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Zeindl-Eberhart, Evelyn; Moosmann, Sabine; Huss, Ralf] Univ Munich, Inst Pathol, D-80539 Munich, Germany. [Nelson, Peter J.] Univ Munich, Klinikum Innenstadt, Policlin, D-80539 Munich, Germany. [Moosmann, Sabine; Huss, Ralf] Pharma Res, Roche Diagnost, Penzberg, Germany. RP Conrad, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 55 Fruit St,GRB-425, Boston, MA 02114 USA. EM cconrad1@partners.org NR 22 TC 15 Z9 16 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1547-3287 J9 STEM CELLS DEV JI Stem Cells Dev. PD FEB PY 2008 VL 17 IS 1 BP 23 EP 27 DI 10.1089/scd.2007.0159 PG 5 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 269DB UT WOS:000253628600004 PM 18237266 ER PT J AU Sorensen, AG Heiss, WD AF Sorensen, A. Gregory Heiss, Wolf-Dieter TI Advances in imaging 2007 SO STROKE LA English DT Editorial Material DE imaging ID ACUTE STROKE; COMPUTED-TOMOGRAPHY; RADIATION-EXPOSURE; PERFUSION; MRI; CT; MANAGEMENT; DIFFUSION; RECOVERY; APHASIA C1 [Sorensen, A. Gregory] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. [Heiss, Wolf-Dieter] Max Planck Inst Neurol Res, Cologne, Germany. RP Sorensen, AG (reprint author), Martinos Ctr Biomed Imaging, 149 13th St, Boston, Boston, MA 02129 USA. EM sorensen@nmr.mgh.harvard.edu NR 35 TC 3 Z9 3 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 FEB PY 2008 VL 39 IS 2 BP 276 EP 278 DI 10.1161/STROKEAHA.107.511717 PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100010 PM 18187676 ER PT J AU Singhal, AB Lo, EH AF Singhal, Aneesh B. Lo, Eng H. TI Advances in emerging nondrug therapies for acute stroke 2007 SO STROKE LA English DT Editorial Material DE acute stroke; non-drug therapies; therapy ID FOCAL CEREBRAL-ISCHEMIA; TISSUE-PLASMINOGEN ACTIVATOR; INFRARED-LASER THERAPY; NORMOBARIC HYPEROXIA; OXYGEN-THERAPY; HYPERBARIC-OXYGEN; INFARCT VOLUME; ARTERY OCCLUSION; BRAIN ISCHEMIA; CLINICAL-TRIAL C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Program Neurosci,Neuroprotect Res L, Cambridge, MA 02138 USA. RP Singhal, AB (reprint author), Massachusetts Gen Hosp, Ctr Stroke Res, 175 Cambridge St , Suite 300, Boston, MA 02114 USA. EM asinghal@partners.org FU NINDS NIH HHS [P50 NS051343, P01 NS055104, P01-NS55104, P50 NS010828, P50-NS10828, P50-NS51343, R01 NS037074, R01 NS051412, R01 NS053560, R01 NS056458, R01-NS37074, R01-NS51412, R01-NS56458] NR 33 TC 7 Z9 12 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 BP 289 EP 291 DI 10.1161/STROKEAHA.107.511485 PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100014 PM 18187678 ER PT J AU Voetsch, B Jin, RC Bierl, C Deus-Silva, L Camargo, ECS Annichino-Bizacchi, JM Handy, DE Loscalzo, J AF Voetsch, Barbara Jin, Richard C. Bierl, Charlene Deus-Silva, Leonardo Camargo, Erica C. S. Annichino-Bizacchi, Joyce M. Handy, Diane E. Loscalzo, Joseph TI Role of promoter polymorphisms in the plasma glutathione peroxidase (GPx-3) gene as a risk factor for cerebral venous thrombosis SO STROKE LA English DT Article DE cerebral venous thrombosis; genetic risk factors; glutathione peroxidase; oxidant stress; thromboembolic disease ID HYDROPEROXIDE-REDUCING ACTIVITY; ARTERIAL ISCHEMIC-STROKE; NITRIC-OXIDE; PROTHROMBIN-GENE; VEIN-THROMBOSIS; YOUNG-ADULTS; MUTATION; PLATELET; HYPERHOMOCYSTEINEMIA; INHIBITION AB Background and Purpose-Plasma glutathione peroxidase (GPx-3) is a major antioxidant enzyme in plasma and the extracellular space that scavenges reactive oxygen species produced during normal metabolism or after oxidative insult. A deficiency of this enzyme increases extracellular oxidant stress, promotes platelet activation, and may promote oxidative posttranslational modification of fibrinogen. We recently identified a haplotype (H-2) in the GPx-3 gene promoter that increases the risk of arterial ischemic stroke among children and young adults. Methods-The aim of this study is to identify possible relationships between promoter haplotypes in the GPx-3 gene and cerebral venous thrombosis (CVT). We studied the GPx-3 gene promoter from 23 patients with CVT and 123 young controls (18 to 45 years) by single-stranded conformational polymorphism and sequencing analysis. Results-Over half of CVT patients (52.1%) were heterozygous (H1H2) or homozygous (H2H2) carriers of the H-2 haplotype compared with 12.2% of controls, yielding a more than 10-fold independent increase in the risk of CVT (OR=10.7; 95% CI, 2.70 to 42.36; P<0.0001). Among women, the interaction of the H2 haplotype with hormonal risk factors increased the OR of CVT to almost 70 (P<0.0001). Conclusions-These findings show that a novel GPx-3 promoter haplotype is a strong, independent risk factor for CVT. As we have previously shown that this haplotype is associated with a reduction in transcriptional activity, which compromises antioxidant activity and antithrombotic benefits of the enzyme, these results suggest that a deficiency of GPx-3 leads to a cerebral venous thrombophilic state. C1 [Voetsch, Barbara; Jin, Richard C.; Bierl, Charlene; Handy, Diane E.; Loscalzo, Joseph] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Evans Dept Med, Boston, MA 02215 USA. [Handy, Diane E.; Loscalzo, Joseph] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Voetsch, Barbara; Deus-Silva, Leonardo] Univ Estadual Campinas, Dept Neurol, Campinas, Brazil. [Camargo, Erica C. S.] Univ Sao Paulo, Dept Neurol, BR-05508 Sao Paulo, Brazil. [Annichino-Bizacchi, Joyce M.] Univ Estadual Campinas, Hematol & Hemotherapy Ctr, Campinas, Brazil. [Voetsch, Barbara; Camargo, Erica C. S.] Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Sch Med,Dept Neurol, Cambridge, MA 02138 USA. RP Loscalzo, J (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM jloscalzo@partners.org RI Sangue, Inct/I-1919-2013 FU NHLBI NIH HHS [HL55993, HL58976, HL61795] NR 27 TC 39 Z9 44 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 BP 303 EP 307 DI 10.1161/STROKEAHA.107.490094 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100017 PM 18096833 ER PT J AU Ay, H Arsava, EM Koroshetz, WJ Sorensen, AG AF Ay, Hakan Arsava, E. Murat Koroshetz, Walter J. Sorensen, A. Gregory TI Middle cerebral artery infarcts encompassing the insula are more prone to growth SO STROKE LA English DT Article DE cerebral infarct; diffusion-weighted imaging; heart-brain relationships; insula; MRI; neurocardiology; sympathetic nervous system ID PATHOLOGICAL SYMPATHETIC ACTIVATION; HIGH-RESOLUTION MEASUREMENT; TRACER BOLUS PASSAGES; ACUTE ISCHEMIC-STROKE; BLOOD-FLOW; SUDDEN-DEATH; CORTEX STIMULATION; BRAIN; TISSUE; HYPERGLYCEMIA AB Background and Purpose - Based on previous observations that infarcts encompassing the insula were linked to unfavorable clinical outcome, we hypothesized that insular damage was directly associated with worsened infarction in ischemic but potentially viable neighboring brain tissue. Methods - Using acute diffusion- and perfusion-weighted MRI within the first 12 hours of symptom onset and a follow-up MRI on day 5 or later, we calculated the percentage of mismatch lost (PML) in 61 consecutive patients with ischemic stroke within the middle cerebral artery territory. PML denoted the percentage of mismatch tissue between diffusion- weighted imaging and mean transit time maps that eventually underwent infarction. We explored the relationship between PML and insular location using a regression model. Results - The median PML was 17.7% (interquartile range, 3.5% to 54.2%) in insular and 2.5% (0.0% to 12.7%) in noninsular infarcts (P < 0.01). The PML correlated with the volume of abnormal regions on diffusion- weighted imaging (P < 0.01), mean transit time (P < 0.01), cerebral blood flow maps (P < 0.01), and cerebral blood volume maps (P < 0.01). A linear regression model with PML as response and with acute MRI volumes, age, and the site of vascular occlusion as covariates showed that insular involvement was an independent predictor of PML (P < 0.01). The regression model predicted an approximately 3.2-fold increase in PML with insular involvement. Conclusions - Infarction of the insula is associated with increased conversion of ischemic but potentially viable neighboring tissues into infarction. The unfavorable tissue outcome in insular infarcts may not be a mere bystander effect from proximal middle cerebral artery occlusions. C1 [Ay, Hakan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02129 USA. [Ay, Hakan; Arsava, E. Murat; Sorensen, A. Gregory] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biomed Ctr Imging,Dept Radiol, Boston, MA 02129 USA. [Koroshetz, Walter J.] NINDS, NIH, Bethesda, MD USA. RP Ay, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biomed Ctr Imging, 149 13th St,Rm 2301, Boston, MA 02129 USA. EM hay@partners.org RI Arsava, Ethem Murat/I-9197-2013 OI Arsava, Ethem Murat/0000-0002-6527-4139 FU NCRR NIH HHS [P41-RR14075]; NINDS NIH HHS [R01-NS38477-04, NS38477] NR 47 TC 24 Z9 25 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 BP 373 EP 378 DI 10.1161/STROKEAHA.107.499095 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100028 PM 18174474 ER PT J AU Kim, YR van Meer, MPA Tejima, E Murata, Y Mandeville, JB Dai, G Chuang, DM Rosen, BR Lo, EH AF Kim, Young R. van Meer, Maurits P. A. Tejima, Emiri Murata, Yoshi Mandeville, Joseph B. Dai, George Chuang, De-Maw Rosen, Bruce R. Lo, Eng H. TI Functional MRI of delayed chronic lithium treatment in rat focal cerebral ischemia SO STROKE LA English DT Article DE BOLD; CBV; fMRI; focal ischemia; neuroprotective agents; rat; treatment ID GLYCOGEN-SYNTHASE KINASE-3-BETA; ARTERY OCCLUSION; FOREPAW STIMULATION; TEMPORAL EVOLUTION; ANIMAL-MODELS; STROKE; ANGIOGENESIS; SURVIVAL; BRAIN; RECOVERY AB Background and Purpose - The use of lithium as a neuroprotective agent has been demonstrated using various models in which improvements in infarct size, DNA damage, and neurological function were reported. We further investigated neurohemodynamic aspects of the treatment-associated recovery by assessing the therapeutic efficacy of delayed chronic lithium treatment using functional MRI. Methods - Ipsilesional functional MRI activations in the somatosensory cortex, acquired 2 weeks after the 90-minute transient middle cerebral artery occlusion, were compared between lithium- and saline-treated rats. Specifically, MRI signal changes based on blood oxygenation level dependence and functional cerebral blood volume responses were examined using electrical stimulation of forelimbs. Additional immunohistochemical assays were performed. Results - The ratio of ipsilesional to contralesional blood oxygenation level dependence response magnitudes significantly improved with lithium treatments. In contrast, the increase of the functional cerebral blood volume response magnitude ratio was not statistically significant. Nonetheless, the lithium treatment induced significant enhancements of total functional MRI activation (defined as a product of activation volume and response magnitude) for both blood oxygenation level dependence and functional cerebral blood volume methods. Increased cerebral blood volume in periinfarct tissues suggests a possible stroke-induced vascular transformation in both saline- and lithium-treated rats; however, other MRI-derived vascular parameters (vascular size index and microvascular volume) and immunohistochemical staining (CD31, glia fibrillary-associated protein, and matrix metalloproteinase-9) may imply that the neoformation of vasculature was differently affected by the lithium treatment. Conclusions - The delayed chronic lithium treatment enhanced the blood oxygenation level dependence functional MRI response magnitude in the absence of neurological improvement and influenced vascular formation in poststroke animal models. C1 [Kim, Young R.; van Meer, Maurits P. A.; Mandeville, Joseph B.; Dai, George; Rosen, Bruce R.] Massachusetts Gen Hosp, Ctr Biomed Imaging, Boston, MA 02129 USA. [Kim, Young R.; van Meer, Maurits P. A.; Tejima, Emiri; Murata, Yoshi; Lo, Eng H.] Massachusetts Gen Hosp, Neuroprtect Res Lab, Boston, MA 02129 USA. [van Meer, Maurits P. A.] Univ Med Ctr Utrecht, Image Sci Inst, Utrecht, Netherlands. [Chuang, De-Maw] NIH, NIMH, Mol Neurobiol Sect, Bethesda, MD USA. RP Kim, YR (reprint author), Massachusetts Gen Hosp, Ctr Biomed Imaging, 149 13th St,Rm 2301, Boston, MA 02129 USA. EM spmn@nmr.mgh.harvard.edu FU NIBIB NIH HHS [5R01EB002066, R01 EB002066, 17 R01-EB002066]; NINDS NIH HHS [R01 NS053560, P01 NS055104, P50-NS10828, R01-NS48422, R01 NS048422, P50 NS010828, R01-NS37074, R01 NS056458, R01-NS56458, R01 NS037074, P01-NS55104] NR 24 TC 25 Z9 28 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 FEB PY 2008 VL 39 IS 2 BP 439 EP 447 DI 10.1161/STROKEAHA.107.492215 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100039 PM 18187690 ER PT J AU Greenberg, SM Nandigam, RNK Schoenfeld, D Zhang, H Betensky, RA Rosand, J Viswanathan, A Smith, EE AF Greenberg, Steven M. Nandigam, R. N. Kaveer Schoenfeld, David Zhang, Hui Betensky, Rebecca A. Rosand, Jonathan Viswanathan, Anand Smith, Eric E. TI Microbleeds versus macrobleeds: Evidence for distinct processes SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Greenberg, Steven M.; Nandigam, R. N. Kaveer; Schoenfeld, David; Zhang, Hui; Rosand, Jonathan; Viswanathan, Anand; Smith, Eric E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 NR 0 TC 2 Z9 2 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 FEB PY 2008 VL 39 IS 2 MA 2 BP 528 EP 528 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100064 ER PT J AU Levine, DA Safford, MM Allison, JJ Houston, TK Reker, DM King, PH Williams, LS Litaker, MS Kiefe, CI AF Levine, Deborah A. Safford, Monika M. Allison, Jeroan J. Houston, Thomas K. Reker, Dean M. King, Peter H. Williams, Linda S. Litaker, Mark S. Kiefe, Catarina I. TI Long-term use of secondary stroke prevention therapies among US veterans SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Levine, Deborah A.; Safford, Monika M.; Allison, Jeroan J.; Houston, Thomas K.; Litaker, Mark S.; Kiefe, Catarina I.] Univ Alabama, Birmingham, AL USA. [Reker, Dean M.] Kansas VA Med Ctr, Kansas City, MO USA. [King, Peter H.] Birmingham VA Med Ctr, Birmingham, AL USA. [Williams, Linda S.] Richard L Roudebush Vet Adm Med Ctr, Indianapolis, IN USA. RI Houston, Thomas/F-2469-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA 13 BP 531 EP 531 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100074 ER PT J AU Nogueira, RG AF Nogueira, Raul G. TI Safety and efficacy of endovascular thrombectomy in patients with abnormal hemostasis: Pooled analysis of the MERCI and Multi MERCI trials SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Nogueira, Raul G.] Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA 39 BP 537 EP 537 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100100 ER PT J AU Jouvent, E Mangin, JF Porcher, R Viswanathan, A O'Sullivan, M Guichard, JP Dichgans, M Bousser, MG Chabriat, H AF Jouvent, Eric Mangin, Jean-Francois Porcher, Raphael Viswanathan, Anand O'Sullivan, Mike Guichard, Jean-Pierre Dichgans, Martin Bousser, Marie-Germaine Chabriat, Hugues TI Morphological changes of cortical sulci in cerebral small vessel diseases: A 3D MRI study in CADASIL. SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Jouvent, Eric; Guichard, Jean-Pierre; Bousser, Marie-Germaine; Chabriat, Hugues] Hosp Larlboisiere, Dept Neurol, D-80539 Paris, France. [Mangin, Jean-Francois] I2BM, Neurospin, Salcay, France. [Porcher, Raphael] Hop St Louis, Dept Biostat, Paris, France. [Viswanathan, Anand] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Clin Trials Unit, Boston, MA USA. [O'Sullivan, Mike; Dichgans, Martin] Univ Munich, Klinikum Grosshadern, Dept Neurol, Munich, Germany. RI Jouvent, Eric/B-4320-2014; Chabriat, Hugues/G-5699-2010 OI Jouvent, Eric/0000-0001-7797-2236; Chabriat, Hugues/0000-0001-8436-6074 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA 65 BP 543 EP 543 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100126 ER PT J AU Viswanathan, A Patel, P Rahman, R Nandigam, RN Kinnecom, C Bracoud, L Rosand, J Chabriat, H Greenberg, SM Smith, EE AF Viswanathan, Anand Patel, Pratik Rahman, Rosanna Nandigam, R. N. Kinnecom, Catherine Bracoud, Luc Rosand, Jonathan Chabriat, Hugues Greenberg, Steven M. Smith, Eric E. TI Tissue microstructural changes are independently associated with pre-index cognitive impairment in survivors of lobar intracerebral hemorrhage. SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Viswanathan, Anand; Patel, Pratik; Rahman, Rosanna; Nandigam, R. N.; Kinnecom, Catherine; Rosand, Jonathan; Greenberg, Steven M.; Smith, Eric E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bracoud, Luc] Bio Imaging Technol SAS, Lyon, France. [Chabriat, Hugues] Assistance Publ Hop Paris, CHU Lariboisiere, Dept Neurol, Paris, France. RI Smith, Eric/C-5443-2012; Chabriat, Hugues/G-5699-2010 OI Smith, Eric/0000-0003-3956-1668; Chabriat, Hugues/0000-0001-8436-6074 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA 68 BP 544 EP 544 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100129 ER PT J AU Furie, KL Howard, AG Chambless, LE Campbell, S Toole, JF Elkind, MS AF Furie, Karen L. Howard, Annie G. Chambless, Lloyd E. Campbell, Stephen Toole, James F. Elkind, Mitchell S. TI C-reactive protein predicts recurrent stroke and death in a hyperhomocyst(e)inemic population SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Furie, Karen L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Howard, Annie G.; Chambless, Lloyd E.; Campbell, Stephen] Univ N Carolina, Chapel Hill, NC 27515 USA. [Toole, James F.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Elkind, Mitchell S.] Columbia Univ, New York, NY 10027 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA 93 BP 550 EP 551 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100154 ER PT J AU Wintermark, M Jawadi, SS Rapp, JH Tihan, T Tong, E Glidden, D Abedin, S Schaeffer, S Acevedo-Bolton, G Orwoll, B Pan, X Saloner, D AF Wintermark, Max Jawadi, Sumayya S. Rapp, Joseph H. Tihan, Tarik Tong, Elizabeth Glidden, David Abedin, Sami Schaeffer, Sarah Acevedo-Bolton, Gabriel Orwoll, Benjamin Pan, XianMang Saloner, David TI High-resolution CT imaging of carotid artery atherosclerotic plaques SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Wintermark, Max; Tihan, Tarik; Tong, Elizabeth; Glidden, David; Schaeffer, Sarah; Acevedo-Bolton, Gabriel; Orwoll, Benjamin; Saloner, David] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Jawadi, Sumayya S.; Abedin, Sami] Univ Missouri, Kansas City, KS USA. [Rapp, Joseph H.; Pan, XianMang] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA 105 BP 554 EP 554 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100166 ER PT J AU Singer, DE Chang, YC Fang, MC Borowsky, LH Pomernacki, NK Udaltsova, N Go, AS AF Singer, Daniel E. Chang, Yuchiao Fang, Margaret C. Borowsky, Leila H. Pomernacki, Niela K. Udaltsova, Natalia Go, Alan S. TI Assessing the net clinical benefit of warfarin by ischemic stroke risk in atrial fibrillation: The ATRIA study SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Singer, Daniel E.; Chang, Yuchiao; Borowsky, Leila H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fang, Margaret C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Pomernacki, Niela K.; Udaltsova, Natalia; Go, Alan S.] Kaiser Permanente, Div Res, Oakland, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA 117 BP 556 EP 557 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100178 ER PT J AU Goldsmith, T Cadogan, E Furie, KL Schwamm, LH Singhal, AB Vega-Barachowitz, C Lee, H Cohen, AK AF Goldsmith, Tessa Cadogan, Elizabeth Furie, Karen L. Schwamm, Lee H. Singhal, Aneesh B. Vega-Barachowitz, Carmen Lee, Hang Cohen, Audrey Kurash TI Validation of a swallow screening tool in acute neuroscience patients SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Goldsmith, Tessa; Cadogan, Elizabeth; Furie, Karen L.; Schwamm, Lee H.; Singhal, Aneesh B.; Vega-Barachowitz, Carmen; Lee, Hang; Cohen, Audrey Kurash] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA 123 BP 558 EP 558 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100184 ER PT J AU Lima, F Parides, MK Greer, DM Kelly, PJ Furie, KL AF Lima, Fabricio Parides, Michael K. Greer, David M. Kelly, Peter J. Furie, Karen L. TI Left atrial diameter predicts atrial fibrillation in ischemic stroke patients SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Lima, Fabricio; Greer, David M.; Furie, Karen L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Parides, Michael K.] Columbia Univ, New York, NY 10027 USA. [Kelly, Peter J.] Mater Misericordiae Univ Hosp, Dublin, Ireland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA 121 BP 558 EP 558 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100182 ER PT J AU Nogueira, RG Sukavaneshvar, S Rabinov, JD Dabus, G Yoo, AJ Buonanno, FS Pryor, JC Schwamm, LH Hirsch, JA AF Nogueira, Raul G. Sukavaneshvar, Sivaprasad Rabinov, James D. Dabus, Guilherme Yoo, Albert J. Buonanno, Ferdinando S. Pryor, Johnny C. Schwamm, Lee H. Hirsch, Joshua A. TI Scanning electron microscopy analysis of thromboembolic material retrieved from cerebral and cervical arteries of patients with acute ischemic stroke SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Nogueira, Raul G.; Rabinov, James D.; Dabus, Guilherme; Yoo, Albert J.; Buonanno, Ferdinando S.; Pryor, Johnny C.; Schwamm, Lee H.; Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sukavaneshvar, Sivaprasad] Med Device Evaluat Ctr, Salt Lake City, UT USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA 140 BP 562 EP 563 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100201 ER PT J AU Nogueira, RG Cury, R Pomerantz, S Hirsch, JA Buonanno, FS Schwamm, LH Abbara, S Gonzalez, RG Lev, MH AF Nogueira, Raul G. Cury, Ricardo Pomerantz, Stuart Hirsch, Joshua A. Buonanno, Ferdinando S. Schwamm, Lee H. Abbara, Suhny Gonzalez, Ramon G. Lev, Michael H. TI The neurocardiovascular CT protocol: A comprehensive analysis of stroke etiology and ischemic penumbra using 64-slice multi-detector CT in patients with acute ischemic stroke SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Nogueira, Raul G.; Cury, Ricardo; Pomerantz, Stuart; Hirsch, Joshua A.; Buonanno, Ferdinando S.; Schwamm, Lee H.; Abbara, Suhny; Gonzalez, Ramon G.; Lev, Michael H.] Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 1 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 FEB PY 2008 VL 39 IS 2 MA P8 BP 571 EP 571 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100229 ER PT J AU Copen, WA Barak, ER Schwamm, LH Reza-Gharai, L Kamalian, S Wu, O Gonzalez, RG Schaefer, PW AF Copen, William A. Barak, Elizabeth R. Schwamm, Lee H. Reza-Gharai, Leila Kamalian, Shahmir Wu, Ona Gonzalez, R. G. Schaefer, Pamela W. TI Persistence of the diffusion-perfusion mismatch up to 24 hours: Dependence upon proximal arterial occlusion SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Copen, William A.; Barak, Elizabeth R.; Schwamm, Lee H.; Reza-Gharai, Leila; Kamalian, Shahmir; Wu, Ona; Gonzalez, R. G.; Schaefer, Pamela W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P40 BP 579 EP 579 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100260 ER PT J AU Ning, M Palacios, IF Inglessis, I McNamara, ME Llevens, M Demirjian, ZN Cruz-Gonzalez, I McMullin, D Rengifo, P Buonanno, FS AF Ning, MingMing Palacios, Igor F. Inglessis, Ignacio McNamara, Mary Ellen Llevens, Mary Demirjian, Zareh N. Cruz-Gonzalez, Ignacio McMullin, David Rengifo, Pablo Buonanno, Ferdinando S. TI Gender and age associated clinical characteristics of young patients with patent foramen ovale (PFO) related strokes SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Ning, MingMing; Palacios, Igor F.; Inglessis, Ignacio; McNamara, Mary Ellen; Llevens, Mary; Demirjian, Zareh N.; Cruz-Gonzalez, Ignacio; Rengifo, Pablo; Buonanno, Ferdinando S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. [McMullin, David] NYU, New York, NY USA. 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P48 BP 581 EP 581 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100268 ER PT J AU Ferreira, RM Goldmakher, G Kamalian, S Schaefer, PW Gonzalez, RG Lev, MH AF Ferreira, Rafael M. Goldmakher, Gregory Kamalian, Shahmir Schaefer, Pamela W. Gonzalez, R. Gilberto Lev, Michael H. TI Arterial input choice in CTP map construction with acute MCA thrombus: Does side matter? Not if delay correction software is used proximal to the occlusion. SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Ferreira, Rafael M.; Goldmakher, Gregory; Kamalian, Shahmir; Schaefer, Pamela W.; Gonzalez, R. Gilberto; Lev, Michael H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P65 BP 585 EP 585 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100285 ER PT J AU Goldmakher, GV Camargo, EC Furie, KL Smith, WS Harris, GJ Chou, MJ Biagini, T Roccatagliata, L Halpern, EF Dillon, WP Gonzalez, RG Singhal, AB Koroshetz, WJ Lev, MH AF Goldmakher, Gregory V. Camargo, Erica C. Furie, Karen L. Smith, Wade S. Harris, Gordon J. Chou, Maggie J. Biagini, Trese Roccatagliata, Luca Halpern, Elkan F. Dillon, William P. Gonzalez, R. Gilberto Singhal, Aneesh B. Koroshetz, Walter J. Lev, Michael H. TI Hyperdense basilar artery sign on unenhanced CT predicts thrombus and outcome in acute posterior circulation stroke. SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Goldmakher, Gregory V.; Camargo, Erica C.; Furie, Karen L.; Smith, Wade S.; Harris, Gordon J.; Chou, Maggie J.; Roccatagliata, Luca; Halpern, Elkan F.; Gonzalez, R. Gilberto; Singhal, Aneesh B.; Koroshetz, Walter J.; Lev, Michael H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Biagini, Trese; Dillon, William P.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P63 BP 585 EP 585 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100283 ER PT J AU Verduzco, LA Yoo, AJ Mui, K Lev, MH Hirsch, JA Gonzalez, RG Schaefer, PW AF Verduzco, Luis A. Yoo, Albert J. Mui, Kit Lev, Michael H. Hirsch, Joshua A. Gonzalez, Ramon G. Schaefer, Pamela W. TI MR regional perfusion values in hyperacute ischemic stroke treated by intra-arterial thrombolysis are influenced by recanalization and time to recanalization. SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Verduzco, Luis A.; Yoo, Albert J.; Mui, Kit; Lev, Michael H.; Hirsch, Joshua A.; Gonzalez, Ramon G.; Schaefer, Pamela W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P66 BP 586 EP 586 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100286 ER PT J AU Wu, O Ay, H Arsava, EM Benner, T Melinosky, C Tiglias, VJ Holt, CA Garimella, K Wang, M Zhu, M Copen, WA Schaefer, PW Gonzalez, RG Koroshetz, WJ Singhal, AB Sorensen, AG AF Wu, Ona Ay, Hakan Arsava, E. M. Benner, Thomas Melinosky, Christopher Tiglias, Vicky J. Holt, Christian A. Garimella, Kiran Wang, Meiyun Zhu, Mingwang Copen, William A. Schaefer, Pamela W. Gonzalez, R. G. Koroshetz, Walter J. Singhal, Aneesh B. Sorensen, A. G. TI MR-Based algorithms combining DWI-PWI more accurately predicts tissue outcome than DWI or PWI individually in a large patient cohort. SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Wu, Ona; Ay, Hakan; Arsava, E. M.; Benner, Thomas; Melinosky, Christopher; Tiglias, Vicky J.; Garimella, Kiran; Wang, Meiyun; Zhu, Mingwang; Sorensen, A. G.] MGH, Athinoula A Martinos Ctr BioMed Imaging, Charlestown, MA USA. [Holt, Christian A.; Koroshetz, Walter J.; Singhal, Aneesh B.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Copen, William A.; Schaefer, Pamela W.; Gonzalez, R. G.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P74 BP 587 EP 588 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100294 ER PT J AU Masrur, S Abdullah, AR Smith, EE Hidalgo, R El-Ghandour, A Rordorf, G Schwamm, LH AF Masrur, Shihab Abdullah, Abdul R. Smith, Eric E. Hidalgo, Renzo El-Ghandour, Ahmed Rordorf, Guy Schwamm, Lee H. TI Safety of thrombolytics in patients with malignancy and acute ischemic stroke SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Masrur, Shihab; Abdullah, Abdul R.; Smith, Eric E.; Hidalgo, Renzo; El-Ghandour, Ahmed; Rordorf, Guy; Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P83 BP 590 EP 590 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100303 ER PT J AU Weinreb, DB Schwamm, LH AF Weinreb, David B. Schwamm, Lee H. TI The use of a portable CT scanner is associated with a 58% reduction in request-to-scan times for neuro CT imaging in the emergency room of a 280-bed community hospital SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Weinreb, David B.] Salem Hosp, N Shore Med Ctr, Salem, MA USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P101 BP 594 EP 595 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100321 ER PT J AU Liebeskind, DS Nogueira, RG AF Liebeskind, David S. Nogueira, Raul G. TI Improving acute stroke care in a community hospital utilizing neurohospitalists SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Liebeskind, David S.] Univ Calif Los Angeles, Los Angeles, CA USA. [Nogueira, Raul G.] Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P130 BP 602 EP 602 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100351 ER PT J AU Barak, E Romero, J Kamalian, S Gharai, LR Gonzalez, RG Schaefer, P AF Barak, Elizabeth Romero, Javier Kamalian, Shahmir Gharai, Leila R. Gonzalez, Ramon G. Schaefer, Pamela TI Does hyperacute diffusion and perfusion weighted imaging predict outcome in acute ischemic stroke? SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Barak, Elizabeth; Romero, Javier; Kamalian, Shahmir; Gharai, Leila R.; Gonzalez, Ramon G.; Schaefer, Pamela] Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P152 BP 607 EP 607 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100372 ER PT J AU Park, S Masrur, S Abdullah, AR El-Ghandour, A Hidalgo, R Schwamm, LH AF Park, Soojin Masrur, Shihab Abdullah, Abdul R. El-Ghandour, Ahmed Hidalgo, Renzo Schwamm, Lee H. TI Inpatient acute ischemic stroke: Patient characteristics, process measures and thrombolytic rates SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Park, Soojin; Masrur, Shihab; Abdullah, Abdul R.; El-Ghandour, Ahmed; Hidalgo, Renzo; Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P176 BP 613 EP 613 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100395 ER PT J AU Arsava, EM Ay, H Singhal, AB Wu, O Furie, KL Sorensen, AG AF Arsava, Ethem Murat Ay, Hakan Singhal, Aneesh B. Wu, Ona Furie, Karen L. Sorensen, A. Gregory TI An infarct volume threshold on early DWI to predict unfavorable clinical outcome SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Arsava, Ethem Murat; Ay, Hakan; Wu, Ona; Sorensen, A. Gregory] Massachusetts Gen Hosp, AA Martinos Ctr BioMed Imaging, Boston, MA 02114 USA. [Singhal, Aneesh B.; Furie, Karen L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P200 BP 619 EP 619 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100419 ER PT J AU Sorond, FA Rudolph, JL Pochay, VE Pikula, A Babikian, V AF Sorond, Farzaneh A. Rudolph, James L. Pochay, Val E. Pikula, Alexandra Babikian, Viken TI Carotid stenosis affects cerebral hemodynamics during CABG SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Sorond, Farzaneh A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Rudolph, James L.; Pochay, Val E.; Babikian, Viken] VA Boston Healthcare Syst, Boston, MA USA. [Pikula, Alexandra] Boston Univ, Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P207 BP 621 EP 621 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100426 ER PT J AU Ay, H Arsava, EM Gungor, L Furie, KL Koroshetz, WJ Sorensen, AG AF Ay, Hakan Arsava, Ethem Murat Gungor, Levent Furie, Karen L. Koroshetz, Walter J. Sorensen, A. Gregory TI Imaging-based estimation of stroke recurrence risk SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Ay, Hakan; Arsava, Ethem Murat; Gungor, Levent; Sorensen, A. Gregory] Massachusetts Gen Hosp, AA Martinos Cntr BioMed Imaging, Boston, MA 02114 USA. [Furie, Karen L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Koroshetz, Walter J.] NIH, Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P226 BP 625 EP 626 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100445 ER PT J AU Rengifo, P Palacios, IF Inglessis, I McNamara, ME Lievens, M Demirjian, ZN Cruz-Gonzalez, I Ning, M Buonanno, FS AF Rengifo, Pablo Palacios, Igor F. Inglessis, Ignacio McNamara, Mary E. Lievens, Mary Demirjian, Zareh N. Cruz-Gonzalez, Ignacio Ning, MingMing Buonanno, Ferdinando S. TI Catheter closure of patent foramen ovale improves symptom burden in migraine patients SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Rengifo, Pablo; Palacios, Igor F.; Inglessis, Ignacio; McNamara, Mary E.; Lievens, Mary; Demirjian, Zareh N.; Cruz-Gonzalez, Ignacio; Ning, MingMing; Buonanno, Ferdinando S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P229 BP 626 EP 626 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100448 ER PT J AU Sale, MM Furie, KL Hsu, FC Mychaleckyj, JC Sides, EG Howard, TD Worrall, BB Liu, Y Coull, BM Rich, SS Toole, JF AF Sale, Michele M. Furie, Karen L. Hsu, Fang-Chi Mychaleckyj, Josyf C. Sides, Elizabeth G. Howard, Timothy D. Worrall, Bradford B. Liu, Yongmei Coull, Bruce M. Rich, Stephen S. Toole, James F. TI Multiple variants in the transcobalamin 2 and cystathionine beta-synthase genes are associated with homocysteine levels in subjects from the vitamin intervention for stroke prevention (VISP) trial SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Sale, Michele M.; Mychaleckyj, Josyf C.; Worrall, Bradford B.; Rich, Stephen S.] Univ Virginia, Charlottesville, VA USA. [Furie, Karen L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hsu, Fang-Chi; Sides, Elizabeth G.; Howard, Timothy D.; Liu, Yongmei; Toole, James F.] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. [Coull, Bruce M.] Univ Arizona, Tucson, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P242 BP 630 EP 630 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100461 ER PT J AU Kohen, R Millard, SP Becker, KJ Buzaitis, A Cain, KC Teri, L Tirschwell, D Veith, R Mitchell, PH AF Kohen, Ruth Millard, Steven P. Becker, Kyra J. Buzaitis, Ann Cain, Kevin C. Teri, Linda Tirschwell, David Veith, Richard Mitchell, Pamela H. TI Polymorphisms of the serotonin transporter are associated with increased risk for post-stroke depression SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Kohen, Ruth; Becker, Kyra J.; Buzaitis, Ann; Cain, Kevin C.; Teri, Linda; Tirschwell, David; Veith, Richard; Mitchell, Pamela H.] Univ Washington, Seattle, WA 98195 USA. [Millard, Steven P.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P286 BP 641 EP 641 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100505 ER PT J AU Defilippo, D Parides, MK Besanger, A Greer, DM Bliss, S Furie, KL AF Defilippo, Donna Parides, Michael K. Besanger, Angela Greer, David M. Bliss, Susan Furie, Karen L. TI Glycosylated hemoglobin predicts stroke recurrence SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Defilippo, Donna; Besanger, Angela; Greer, David M.; Bliss, Susan; Furie, Karen L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Parides, Michael K.] Columbia Univ, New York, NY 10027 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P295 BP 643 EP 643 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100514 ER PT J AU Thompson, BB Smith, EE AF Thompson, Bradford B. Smith, Eric E. TI Antiplatelet therapy does not affect outcome following intracerebral hemorrhage: Systematic review and meta-analysis SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Thompson, Bradford B.; Smith, Eric E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P333 BP 651 EP 652 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100548 ER PT J AU Zhu, H Liu, J Yu, Z Sun, PZ Murata, Y Lu, J Lo, EH Wang, X AF Zhu, Haihao Liu, Jianxiang Yu, Zhanyang Sun, Phillip Z. Murata, Yoshihiro Lu, Jie Lo, Eng H. Wang, Xiaoying TI Annexin II combined with low dose tPA improves neurological outcomes in embolic stroke model of rats SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Neuroprotect Res Lab,Program Neurosci, Charlestown, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Neuroprotect Res Lab,Program Neurosci, Charlestown, MA USA. 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P386 BP 663 EP 664 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100599 ER PT J AU Khan, M Hoda, MN Giri, S Singh, I Singh, AK AF Khan, Mushfiquddin Hoda, Md Nasrul Giri, Shailendra Singh, Inderjit Singh, Avtar K. TI Lipid aldehydes contribute to acute stroke injury via protein carbonyl formation and glutathione depletion in a rat model of focal cerebral ischemia and reperfusion SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Khan, Mushfiquddin; Hoda, Md Nasrul; Giri, Shailendra; Singh, Inderjit] Med Univ S Carolina, Charleston, SC 29425 USA. [Singh, Avtar K.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P420 BP 671 EP 671 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100632 ER PT J AU Savitz, SI Liu, C Zhang, H Schallert, T Liu, P AF Savitz, Sean I. Liu, Christina Zhang, Huiling Schallert, Timothy Liu, Philip TI DWI as a surrogate of brain injury in global cerebral ischemia in mice: Imaging and behavioral effects of hypothermia SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Savitz, Sean I.; Zhang, Huiling] Univ Texas, Houston Med Sch, Houston, TX USA. [Liu, Christina; Liu, Philip] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schallert, Timothy] Univ Texas Austin, Austin, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P431 BP 674 EP 674 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100643 ER PT J AU Yu, Z Liu, J Guo, S Xing, C Zhu, H Yuan, JC Lo, EH Wang, X AF Yu, Zhanyang Liu, Jianxiang Guo, Shuzhen Xing, Changhong Zhu, Haihao Yuan, Juliet C. Lo, Eng H. Wang, Xiaoying TI Neuroglobin-overexpression alters hypoxic response gene expression in primary neuron culture following oxygen glucose deprivation SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Yu, Zhanyang; Liu, Jianxiang; Guo, Shuzhen; Xing, Changhong; Zhu, Haihao; Yuan, Juliet C.; Lo, Eng H.; Wang, Xiaoying] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P440 BP 676 EP 676 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100651 ER PT J AU Schwab, K Longstreth, WT Gorelick, PB Nyenhuis, DL Greenberg, SM Kim, JJ AF Schwab, Kristin Longstreth, Will T., Jr. Gorelick, Philip B. Nyenhuis, David L. Greenberg, Steven M. Kim, Jane J. TI Healthcare impact of preventive therapy for vascular cognitive impairment. SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Schwab, Kristin; Greenberg, Steven M.] Massachusetts Gen Hosp, Stroke Res Ctr, Boston, MA 02114 USA. [Longstreth, Will T., Jr.] Univ Washington, Seattle, WA 98195 USA. [Gorelick, Philip B.; Nyenhuis, David L.] Univ Illinois, Chicago, IL 60680 USA. [Kim, Jane J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P474 BP 684 EP 685 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100685 ER PT J AU Besanger, A Parides, MK Kelly, PJ Camargo, EC Dipietro, A Greer, DM Holt, C Lima, F Pinzon, S Tiglias, V Whittaker, A Furie, KL AF Besanger, Angela Parides, Michael K. Kelly, Peter J. Camargo, Erica C. Dipietro, Allison Greer, David M. Holt, Christian Lima, Fabricio Pinzon, Sandra Tiglias, Vicky Whittaker, Alexis Furie, Karen L. TI Dietary fiber intake predicts acute stroke severity and 6-month functional outcome. SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Besanger, Angela; Camargo, Erica C.; Dipietro, Allison; Greer, David M.; Holt, Christian; Lima, Fabricio; Pinzon, Sandra; Tiglias, Vicky; Whittaker, Alexis; Furie, Karen L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Parides, Michael K.] Columbia Univ, New York, NY 10027 USA. [Kelly, Peter J.] Mater Misericordiae Univ Hosp, Dublin, Ireland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P503 BP 691 EP 691 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100714 ER PT J AU Rost, NS Smith, EE Chang, Y Snider, RW Chanderraj, R Schwab, K Fitzmaurice, E Wendell, L Greenberg, SM Rosand, J AF Rost, Natalia S. Smith, Eric E. Chang, Yuchiao Snider, Ryan W. Chanderraj, Rishi Schwab, Kristin Fitzmaurice, Emily Wendell, Lauren Greenberg, Steven M. Rosand, Jonathan TI Prediction of functional outcome in primary ICH: The FUNC score SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Rost, Natalia S.; Smith, Eric E.; Chang, Yuchiao; Snider, Ryan W.; Chanderraj, Rishi; Schwab, Kristin; Fitzmaurice, Emily; Wendell, Lauren; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P523 BP 696 EP 696 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100734 ER PT J AU Reeves, MJ Schwamm, LH Yu, YL AF Reeves, Mathew J. Schwamm, Lee H. Yu, Yanglin CA GWTG Steering Comm Invest TI Off-hour admission and in-hospital mortality in hospitals participating in the get with the guidelines-stroke program SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Reeves, Mathew J.] Michigan State Univ, E Lansing, MI 48824 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yu, Yanglin] Duke Clin Res Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P540 BP 700 EP 701 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100751 ER PT J AU Furie, KL Howard, AG Chambless, LE Prince, V Toole, JF Howard, VJ AF Furie, Karen L. Howard, Annie G. Chambless, Lloyd E. Prince, Valerie Toole, James F. Howard, Virginia J. TI Early weight change after ischemic stroke SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Furie, Karen L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Howard, Annie G.; Chambless, Lloyd E.] Univ N Carolina, Chapel Hill, NC USA. [Prince, Valerie] Samford Univ, McWhorter Sch Pharm, Birmingham, AL USA. [Toole, James F.] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. [Howard, Virginia J.] Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P576 BP 710 EP 710 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100787 ER PT J AU Kim, HH Jeong, SJ You, Z Ken, N Liu, PY Hwang, SK Waeber, C Liao, JK AF Kim, Hyung-Hwan Jeong, Sung-Jin You, Zerong Ken, Noma Liu, Ping-Yen Hwang, Seo-Kyoung Waeber, Christian Liao, Jame K. TI Neuronal loss and motor function deficiency in mice with targeted disruption of Rho kinase (ROCK): Role of hippocampal p27Kip1 SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Kim, Hyung-Hwan; Ken, Noma; Liu, Ping-Yen; Hwang, Seo-Kyoung; Liao, Jame K.] Brigham & Womens Hosp, Cambridge, MA USA. [Jeong, Sung-Jin; You, Zerong; Waeber, Christian] Massachusetts Gen Hosp, Charlestown, MA USA. RI Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P655 BP 728 EP 728 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100864 ER PT J AU Muehlschlegel, S Selb, J Diamond, SG Boas, DA Schwamm, LH AF Muehlschlegel, Susanne Selb, Juliette Diamond, Solomon G. Boas, David A. Schwamm, Lee H. TI Near infrared spectroscopy assessment of dynamic cerebral autoregulation in ischemic stroke SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Muehlschlegel, Susanne] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Neurocrit Care Serv, Boston, MA USA. [Selb, Juliette; Boas, David A.] Harvard Univ, MGH Athinoula A Martinos Ctr BioMed Imaging, Charlestown, MA USA. [Diamond, Solomon G.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Schwamm, Lee H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke Serv, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P658 BP 728 EP 728 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100867 ER PT J AU Kim, HH Hwang, SK Shin, HK Blondeau, N You, Z Liao, JK Waeber, C AF Kim, Hyung-Hwan Hwang, Seo-Kyoung Shin, Hwa Kyoung Blondeau, Nicolas You, Zerong Liao, James K. Waeber, Christian TI The sphingosine-1-phosphate analogue FTY720 is neuroprotective in a rodent model of brain ischemia SO STROKE LA English DT Meeting Abstract CT 33rd International Stroke Conference CY FEB 19-21, 2008 CL New Orleans, LA SP Amer Stroke Assoc, Amer Heart Assoc C1 [Kim, Hyung-Hwan; Hwang, Seo-Kyoung; Liao, James K.] Brigham & Womens Hosp, Cambridge, MA USA. [Shin, Hwa Kyoung; Blondeau, Nicolas; You, Zerong; Waeber, Christian] Massachusetts Gen Hosp, Charlestown, MA USA. RI Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2008 VL 39 IS 2 MA P661 BP 729 EP 729 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 256JY UT WOS:000252726100870 ER PT J AU Johnson, JG Zhang, B Prigerson, HG AF Johnson, Jeffrey G. Zhang, Baohu Prigerson, Holly G. TI Investigation of a developmental model of risk for depression and suicidality following spousal bereavement SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID PARENTAL BONDING INSTRUMENT; RETROSPECTIVE REPORTS; MARITAL QUALITY; TRAUMATIC GRIEF; RATING-SCALE; ATTACHMENT; DISORDERS; ADOLESCENCE; OUTPATIENTS; DEPENDENCY AB Data from a community-based multi-wave investigation were used to examine a developmental model of risk for depression and suicidality following the death of a spouse. Measures of perceived parental affection and control during childhood were administered to 218 widowed adults 11 months after the death of the spouse. Self-esteem, spousal dependency, depression, and suicidality were assessed 9 months later. Dependency on the deceased spouse mediated a significant association between retrospectively reported parental control during childhood and post-loss depressive symptoms. Depressive symptoms mediated significant associations of dependency on the deceased spouse and low self-esteem with suicidal ideation and behavior. C1 [Johnson, Jeffrey G.] NYSPI, New York, NY 10032 USA. [Johnson, Jeffrey G.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10027 USA. [Zhang, Baohu; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psycho Oncol & Palliat Care Res, Boston, MA 02115 USA. [Prigerson, Holly G.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Psychiat, Cambridge, MA 02138 USA. RP Johnson, JG (reprint author), NYSPI, Box 60,1051 Riverside Dr, New York, NY 10032 USA. EM jjohnso@pi.cpmc.columbia.edu FU NCI NIH HHS [CA106370, R01 CA106370]; NIA NIH HHS [P30AG21342]; NIMH NIH HHS [MH56529, MH63892] NR 60 TC 7 Z9 7 U1 1 U2 9 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0363-0234 J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD FEB PY 2008 VL 38 IS 1 BP 1 EP 12 DI 10.1521/suli.2008.38.1.1 PG 12 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 270QK UT WOS:000253735100002 PM 18355104 ER PT J AU Hart, SL Latini, DM Cowan, JE Carroll, PR AF Hart, Stacey L. Latini, David M. Cowan, Janet E. Carroll, Peter R. CA CaPSURE Investigators TI Fear of recurrence, treatment satisfaction, and quality of life after radical prostatectomy for prostate cancer SO SUPPORTIVE CARE IN CANCER LA English DT Article DE prostate cancer; treatment satisfaction; fear of recurrence; quality-of-life ID SURVIVORS; UNCERTAINTY; ANXIETY; RADIATION; DATABASE; CAPSURE; SCALE; CARE AB Goals of work Fear of cancer recurrence (FOR) is common in prostate cancer patients, but little research has examined the impact of FOR on quality of life (QOL) or the mechanism by which these fears become intensified. The objective of this study was to examine treatment satisfaction (TS) as a moderator of the relationship between FOR and QOL. Patients and methods Data were drawn from the CaPSURE (TM) database, a 12,000-man national observational prostate cancer registry. Three hundred and thirty-three patients who underwent radical prostatectomy (RP) to treat their prostate cancer completed self-report measures. TS was measured 0-6 months post-RP with a nine-item scale developed for this study, FOR was measured 6-12 months post-RP with a previously validated five-item scale, and QOL was measured 12-18 months post-RP with the Short Form 36. Main results After controlling for age, education, number of comorbid medical conditions, and cancer severity, lower FOR (B=-0.12, p < 0.0001), higher TS (B=0.09, p < 0.001), and the interaction of TS x FOR (B=0.87, p < 0.05) significantly predicted higher mental health QOL scores. Furthermore, lower FOR (B=-0.08, p < 0.01), and the interaction of TS x FOR (B=-1.11, p < 0.01) significantly predicted higher physical health QOL scores. Conclusions TS levels mitigated the impact of high FOR on lower levels of QOL. Specifically, patients who reported lower TS and greater FOR endorsed significantly lower levels of QOL compared to other patients in the sample. C1 [Hart, Stacey L.] Ryerson Univ, Dept Psychol, Toronto, ON M5B 2K3, Canada. [Latini, David M.] Baylor Coll Med, Scott Dept Urol, Houston, TX USA. [Latini, David M.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX USA. [Latini, David M.] VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. [Cowan, Janet E.; Carroll, Peter R.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. [Cowan, Janet E.; Carroll, Peter R.] Univ Calif San Francisco, Programs Urol Oncol & Genitourinary Canc Epidemio, Ctr Comprehens Canc, San Francisco, CA 94143 USA. RP Hart, SL (reprint author), Ryerson Univ, Dept Psychol, 350 Victoria St, Toronto, ON M5B 2K3, Canada. EM stacey.hart@ryerson.ca RI Hart, Stacey/E-4819-2011; OI Macaluso, Joseph/0000-0001-7383-1321; Latini, David/0000-0002-6161-4861 FU NIMH NIH HHS [K08 MH 068257]; PHS HHS [P50 C89520] NR 24 TC 41 Z9 41 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD FEB PY 2008 VL 16 IS 2 BP 161 EP 169 DI 10.1007/s00520-007-0296-x PG 9 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 252TX UT WOS:000252470600008 PM 17638026 ER PT J AU Warshaw, AL Sarr, MG AF Warshaw, Andrew L. Sarr, Michael G. TI Profiting from innovation: An introduction SO SURGERY LA English DT Editorial Material C1 [Warshaw, Andrew L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sarr, Michael G.] Mayo Clin & Mayo Fdn, Dept Surg, Rochester, MN 55902 USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, 55 Fruit St,WHT506, Boston, MA 02114 USA. EM awarshaw@partners.org NR 0 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD FEB PY 2008 VL 143 IS 2 BP 157 EP 157 DI 10.1016/j.surg.2007.11.007 PG 1 WC Surgery SC Surgery GA 262UA UT WOS:000253172300001 ER PT J AU Toneguzzo, F AF Toneguzzo, Frances TI From innovation to successful commercialization: Assessing value and investment-does the equation make sense? SO SURGERY LA English DT Editorial Material C1 [Toneguzzo, Frances] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Toneguzzo, F (reprint author), 101 Huntington Ave,4th Floor, Boston, MA 02199 USA. EM ftoneguzzo@partners.org NR 0 TC 2 Z9 2 U1 2 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD FEB PY 2008 VL 143 IS 2 BP 165 EP 168 DI 10.1016/j.surg.2007.11.008 PG 4 WC Surgery SC Surgery GA 262UA UT WOS:000253172300004 PM 18242328 ER PT J AU Toner, M Tompkins, RG AF Toner, Mehmet Tompkins, Ronald G. TI Invention, innovation, entrepreneurship in academic medical centers SO SURGERY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Serv, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA USA. Shriners Hosp Children, Boston, MA USA. RP Tompkins, RG (reprint author), Massachusetts Gen Hosp, Dept Surg, Trauma & Burn Serv, 55 Fruit St,GRB1302, Boston, MA 02114 USA. EM rtompkins@partners.org FU NIBIB NIH HHS [P41 EB002503]; NIGMS NIH HHS [P50 GM021700, P50 GM021700-30, T32 GM007035, T32 GM007035-33, U54 GM062119, U54 GM062119-07] NR 11 TC 3 Z9 4 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD FEB PY 2008 VL 143 IS 2 BP 168 EP 171 DI 10.1016/j.surg.2007.11.004 PG 4 WC Surgery SC Surgery GA 262UA UT WOS:000253172300005 PM 18242329 ER PT J AU Vacanti, JP AF Vacanti, Joseph P. TI Tissue engineering: From bench to bedside via commercialization SO SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Pediat Surg, 55 Fruit St,Warren 1151, Boston, MA 02114 USA. EM jvacanti@partners.org NR 0 TC 6 Z9 7 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD FEB PY 2008 VL 143 IS 2 BP 181 EP 183 DI 10.1016/j.surg.2007.11.003 PG 3 WC Surgery SC Surgery GA 262UA UT WOS:000253172300008 PM 18242332 ER PT J AU Sachs, DH AF Sachs, David H. TI Patents and research: Friends or foes? SO SURGERY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Surg, Boston, MA 02129 USA. RP Sachs, DH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Surg, MGH East,Bldg 149-9019,13th St, Boston, MA 02129 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD FEB PY 2008 VL 143 IS 2 BP 191 EP 193 DI 10.1016/j.surg.2007.11.001 PG 3 WC Surgery SC Surgery GA 262UA UT WOS:000253172300010 PM 18242334 ER PT J AU Itani, KMF Hawn, MT AF Itani, Kamal M. F. Hawn, Mary T. TI Advances in abdominal wall hernia repair - Preface SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 [Itani, Kamal M. F.] VA Boston Hlth Care Syst, Dept Surg, Boston, MA 02132 USA. [Itani, Kamal M. F.] Boston Univ, Boston, MA 02132 USA. [Hawn, Mary T.] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. RP Itani, KMF (reprint author), VA Boston Hlth Care Syst, Dept Surg, 1400 VFW Pkwy, Boston, MA 02132 USA. EM kitani@med.va.gov; mhawn@uab.edu NR 0 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 0039-6109 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD FEB PY 2008 VL 88 IS 1 BP XVII EP XIX DI 10.1016/j.suc.2008.01.002 PG 3 WC Surgery SC Surgery GA 275PP UT WOS:000254084400002 PM 18267157 ER PT J AU Hermsen, JL Sano, Y Gomez, FE Maeshima, Y Kang, W Kudsk, KA AF Hermsen, Joshua L. Sano, Yoshifumi Gomez, F. Enrique Maeshima, Yoshinori Kang, Woodae Kudsk, Kenneth A. TI Parenteral Nutrition Inhibits Tumor Necrosis Factor-alpha-Mediated IgA Response to Injury SO SURGICAL INFECTIONS LA English DT Article AB Background: Parenteral nutrition (PN) increases the incidence of pneumonia in severely injured patients compared with enteral feeding (ENT). Injury induces an innate airway IgA response in severely injured patients; similar responses occur in mice. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) stimulate the production of polymeric immunoglobulin receptor (pIgR), the protein required to transport immunoglobulin A (IgA) to mucosal surfaces. We have shown that PN alters levels of lung and nasal passage IgA and several IgA-stimulating cytokines. We hypothesized that TNF-alpha and IL-1 beta blockade, as well as PN, would blunt the airway IgA response to injury. Methods: Male Institute of Cancer Research (ICR) mice were randomized to uninjured controls (n = 10) or to intra-peritoneal phosphate-buffered saline (PBS) (n = 9), antagonistic TNF-alpha antibody (100 mcg, n = 7), or antagonistic IL-1 beta antibody (50 mcg, n = 8) 30 min prior to surgical stress with laparotomy and neck incisions. Mice were sacrificed at 8 h for nasal and bronchoalveolar lavage (NAL, BAL) to measure IgA by enzyme-linked immunosorbent assay. In a separate experiment, 12 mice underwent intravenous cannulation followed by chow (n = 5) or PN (n = 7) feeding for 5 days prior to the same stress and IgA measurement. Results: Injury significantly increased NAL and BAL IgA (225 +/- 104 ng) compared with baseline (145 +/- 38 ng; p = 0.01). Blockade of TNF-alpha eliminated the innate airway IgA response to injury (130 +/- 47 ng; p = 0.01), whereas IL-1 beta blockade blunted and PN eliminated it completely. Conclusions: Tumor necrosis factor-alpha is involved in the respiratory IgA immune response to injury. Both TNF-alpha blockade and PN impair this innate response, and blockade of IL-1 beta impairs it to a degree. We hypothesize that these cytokines blunt this response via their known effects on the polymeric immunoglobulin receptor (pIgR), whereas the PN-induced deficit likely is multifactorial. C1 [Kudsk, Kenneth A.] Univ Wisconsin, Dept Surg, Coll Med & Publ Hlth, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. RP Kudsk, KA (reprint author), Univ Wisconsin, Dept Surg, Coll Med & Publ Hlth, 600 Highland Ave,H4-736 CSC, Madison, WI 53792 USA. EM kudsk@surgery.wisc.edu FU U.S. National Institutes of Health [2R01GM53439]; Office of Research and Development, Biomedical Laboratory R&D Service, Department of Veterans Affairs FX This research was supported by U.S. National Institutes of Health grant 2R01GM53439 and work supported in part by the Office of Research and Development, Biomedical Laboratory R&D Service, Department of Veterans Affairs. NR 42 TC 15 Z9 16 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-2964 J9 SURG INFECT JI Surg. Infect. PD FEB PY 2008 VL 9 IS 1 BP 33 EP 40 DI 10.1089/sur.2007.029 PG 8 WC Infectious Diseases; Surgery SC Infectious Diseases; Surgery GA V18FO UT WOS:000207990900005 PM 18363466 ER PT J AU Frank, JA Pittet, JF Wray, C Matthay, MA AF Frank, J. A. Pittet, J-F Wray, C. Matthay, M. A. TI Protection from experimental ventilator-induced acute lung injury by IL-1 receptor blockade SO THORAX LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; NITRIC-OXIDE SYNTHASE; TIDAL VOLUME VENTILATION; MECHANICAL VENTILATION; NEUTROPHIL INFILTRATION; CONTROLLED-TRIAL; FLUID CLEARANCE; DOUBLE-BLIND; RAT LUNGS; INTERLEUKIN-1 AB Background: Clinical studies have shown that injurious mechanical ventilation is associated with increased airspace and plasma levels of interleukin-1b (IL-1 beta); however, the potential therapeutic value of IL-1 inhibition in acute lung injury has not been thoroughly investigated. A study was undertaken to determine if IL-1 signalling is a necessary early event in the pathogenesis of experimental ventilator-induced lung injury. Methods: Mice deficient in IL-1 receptor type 1 (IL1R1) and rats treated with IL-1 receptor antagonist (IL-1Ra) were mechanically ventilated with high tidal volume (30 ml/kg) and the effect of IL-1 signalling blockade on the severity of lung injury was determined. Results: Permeability, as measured by radiolabelled albumin flux, was significantly lower in IL1R1 null mice than in wild-type mice during injurious ventilation (p<0.05). IL-1Ra significantly decreased protein permeability and pulmonary oedema in rats during injurious ventilation and also decreased airspace and plasma levels of the chemokine CXCL1 and airspace neutrophils. IL-1Ra decreased expression of NOS2 and ICAM-1 mRNA in whole lung. Bronchoalveolar lavage fluid levels of RT140, a marker of type I cell injury, were 2.5 times lower following IL-1Ra treatment (p<0.05). In isolated type II pneumocytes, IL-1 beta reduced electrical resistance and increased transepithelial permeability. Conclusions: IL-1 contributes to alveolar barrier dysfunction in VILI by promoting lung neutrophil recruitment and by increasing epithelial injury and permeability. Because preserved alveolar barrier function is associated with better outcomes in patients with acute lung injury, these data support further testing of IL-1Ra for the treatment of acute lung injury. C1 [Frank, J. A.; Pittet, J-F; Matthay, M. A.] Univ Calif San Francisco, San Francisco VA Med Ctr, No Calif Inst Res & Educ, Cardiovasc Res Inst, San Francisco, CA 94121 USA. [Frank, J. A.; Matthay, M. A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Pittet, J-F; Matthay, M. A.] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. [Pittet, J-F] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. RP Frank, JA (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, No Calif Inst Res & Educ, Cardiovasc Res Inst, 4150 Clement St,Box 111D, San Francisco, CA 94121 USA. EM james.frank@ucsf.edu FU NHLBI NIH HHS [HL69900, R01 HL088440, HL51854, R01 HL088440-01A1, R56 HL088440] NR 44 TC 71 Z9 73 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 J9 THORAX JI Thorax PD FEB PY 2008 VL 63 IS 2 BP 147 EP 153 DI 10.1136/thx.2007.079608 PG 7 WC Respiratory System SC Respiratory System GA 256HH UT WOS:000252718500012 PM 17901159 ER PT J AU Bergmeier, W Chauhan, AK Wagner, DD AF Bergmeier, Wolfgang Chauhan, Anil K. Wagner, Denisa D. TI Glycoprotein Ib alpha and von Willebrand factor in primary platelet adhesion and thrombus formation: Lessons from mutant mice SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE thrombosis; glycoprotein; von Willebrand factor; mutant; mice ID IX-V COMPLEX; BERNARD-SOULIER-SYNDROME; VIII-VONWILLEBRAND FACTOR; THROMBOCYTOPENIC PURPURA; SHEAR-STRESS; VENOUS THROMBOSIS; MOUSE MODEL; ARTERIAL THROMBOSIS; INJURED ARTERIOLES; FACTOR MULTIMERS AB The von Willebrand factor (VWF) receptor complex, glycoprotein (GP)Ib-V-IX, and its main ligand VWF play a key role in the adhesion process of platelets to sites of vascular injury. Recent studies in mutant mice have shed new light on the importance of either molecule for the development of arterial and venous thrombosis. In this review, we summarize the most important aspects from these studies. C1 [Bergmeier, Wolfgang] Thomas Jefferson Univ, Cardeza Fdn Hematol Res, Philadelphia, PA 19007 USA. [Bergmeier, Wolfgang] Thomas Jefferson Univ, Dept Med, Philadelphia, PA 19007 USA. [Chauhan, Anil K.; Wagner, Denisa D.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Chauhan, Anil K.; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Bergmeier, W (reprint author), Thomas Jefferson Univ, Cardeza Fdn Hematol Res, 803 Curtis,1015 Walnut St, Philadelphia, PA 19007 USA. EM wolfgang.bergmeier@jefferson.edu FU NHLBI NIH HHS [P01 HL 066105, R37 HL 41002, R37 HL041002] NR 74 TC 44 Z9 46 U1 0 U2 4 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD FEB PY 2008 VL 99 IS 2 BP 264 EP 270 DI 10.1160/TH07-10-0638 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 265DP UT WOS:000253339600005 PM 18278173 ER PT J AU Crunkhorn, S Patti, ME AF Crunkhorn, Sarah Patti, Mary-Elizabeth TI Links between thyroid hormone action, oxidative metabolism, and diabetes risk? SO THYROID LA English DT Review ID HUMAN SKELETAL-MUSCLE; SEVERE INSULIN-RESISTANCE; GENE-EXPRESSION PATTERNS; GLUCOSE-TOLERANCE; MITOCHONDRIAL BIOGENESIS; ADIPOSE-TISSUE; ERR-ALPHA; TRANSCRIPTIONAL ACTIVATION; ADAPTIVE THERMOGENESIS; THR92ALA POLYMORPHISM AB A key phenotype associated with type 2 diabetes in humans is impaired mitochondrial oxidative metabolism in skeletal muscle, a pattern potentially contributing to increased lipid accumulation and impaired metabolic flexibility-in turn, central features of both insulin resistance and diabetes. Since thyroid hormone regulates mitochondrial gene expression and function in skeletal muscle, reductions in T3-mediated transcription may contribute to diabetes-related impairments in oxidative metabolism. We review the evidence for relationships between thyroid hormone action and diabetes risk, and discuss potential mechanisms linking intracellular thyroid hormone availability, thyroid receptor action, and the transcriptional coactivator PGC1 in regulating oxidative metabolism. C1 [Crunkhorn, Sarah; Patti, Mary-Elizabeth] Joslin Diabet Ctr, Div Res, Boston, MA USA. RP Patti, ME (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA USA. EM mary.elizabeth.patti@joslin.harvard.edu FU NIDDK NIH HHS [DK060837, DK062948, DK36836] NR 133 TC 51 Z9 56 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD FEB PY 2008 VL 18 IS 2 BP 227 EP 237 DI 10.1089/thy.2007.0249 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 270LR UT WOS:000253722800016 PM 18279023 ER PT J AU Wang, S Nagrath, D Chen, PC Berthiaume, F Yarmush, ML AF Wang, Sihong Nagrath, Deepak Chen, Pohun C. Berthiaume, Francois Yarmush, Martin L. TI Three-dimensional primary hepatocyte culture in synthetic self-assembling peptide hydrogel SO TISSUE ENGINEERING PART A LA English DT Article ID LONG-TERM CULTURE; SANDWICH CONFIGURATION; COMPLEMENTARY OLIGOPEPTIDE; IN-VITRO; TISSUE; CELLS; MAINTENANCE; SCAFFOLDS; DIFFERENTIATION; REORGANIZATION AB Drug metabolism studies and liver tissue engineering necessitate stable hepatocyte cultures that express liver functions for a minimum of 4 days to 3 weeks. Current techniques, using different biomaterials and geometries, that maintain hepatocellular function in vitro exhibit a low cell density and functional capacity per unit volume. Herein we investigated a well-defined synthetic peptide that can self-assemble into three-dimensional interweaving nanofiber scaffolds to form a hydrogel, PuraMatrix, as a substrate for hepatocyte culture. Freshly isolated primary rat hepatocytes attached, migrated, and formed spheroids within 3 days after seeding on PuraMatrix. Hepatocytes expressed the apical membrane marker dipeptidyl peptidase IV at cell - cell contacts. Compared to the collagen sandwich, albumin and urea secretion on PuraMatrix were higher for the first week, and cytochrome P450IA1 activity was higher throughout the culture period. Mitochondrial membrane potential 1 day after seeding was higher on PuraMatrix than in the collagen sandwich, suggesting better preservation of the metabolic machinery. PuraMatrix and Matrigel showed similar albumin and urea production. PuraMatrix is an attractive system for generating hepatocyte spheroids that quickly restore liver functions after seeding. This system is also amenable to scale-up, which makes it suitable for in vitro toxicity, hepatocyte transplantation, and bioartificial liver development studies. C1 [Wang, Sihong; Nagrath, Deepak; Chen, Pohun C.; Berthiaume, Francois; Yarmush, Martin L.] Harvard Univ, Sch Med, Ctr Engn Med, Boston, MA USA. [Wang, Sihong; Nagrath, Deepak; Chen, Pohun C.; Berthiaume, Francois; Yarmush, Martin L.] Massachusetts Gen Hosp, Shriners Burns Inst, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM ireis@sbi.org OI Nagrath, Deepak/0000-0002-8999-2282 FU NIBIB NIH HHS [P41 EB002503, P41EB002503]; NIDDK NIH HHS [R01DK43371] NR 27 TC 82 Z9 85 U1 5 U2 22 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 J9 TISSUE ENG PT A JI Tissue Eng. Part A PD FEB PY 2008 VL 14 IS 2 BP 227 EP 236 DI 10.1089/tea.2007.0143 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 273VY UT WOS:000253961200002 PM 18333775 ER PT J AU Stepleman, LM Trezza, GR Santos, M Silberbogen, AK AF Stepleman, Lara M. Trezza, Glenn R. Santos, Melissa Silberbogen, Amy K. TI The Integration of HIV Training Into Internship Curricula: An Exploration and Comparison of Two Models SO TRAINING AND EDUCATION IN PROFESSIONAL PSYCHOLOGY LA English DT Article DE HIV; internship training; health psychology; curricula; education AB Psychologists are becoming increasingly involved in HIV disease prevention and intervention. Developing the competencies to work effectively with this population requires dedicated educational commitment. It can be challenging to get HIV experience during graduate school, and few programs have faculty devoted to HIV endeavors. The authors propose the internship year as a reasonable time to develop HIV competencies within a broader internship curriculum. To explore this idea further, the authors examined two internships that offer specialized HIV training. To increase psychology's capacity to provide HIV training, recommendations are proposed for the application of these models to other internship sites. C1 [Stepleman, Lara M.] Med Coll Georgia, Dept Psychiat & Hlth Behav, Augusta, GA 30912 USA. [Trezza, Glenn R.] VA Boston Healthcare Syst, Program Infect Dis, Boston, MA USA. [Trezza, Glenn R.; Silberbogen, Amy K.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Santos, Melissa] Med Coll Georgia, Augusta, GA 30912 USA. [Silberbogen, Amy K.] VA Boston Healthcare Syst, Androl Clin, Boston, MA USA. RP Stepleman, LM (reprint author), Med Coll Georgia, 1515 Pope Ave, Augusta, GA 30912 USA. EM lsteplem@mcg.edu NR 19 TC 2 Z9 3 U1 0 U2 0 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1931-3918 J9 TRAIN EDUC PROF PSYC JI Train. Educ. Prof. Psychol. PD FEB PY 2008 VL 2 IS 1 BP 35 EP 41 DI 10.1037/1931-3918.2.1.35 PG 7 WC Psychology, Educational SC Psychology GA V29EB UT WOS:000208730600005 ER PT J AU Merlo, LJ Collins, A Bernstein, J AF Merlo, Lisa J. Collins, Allison Bernstein, Jessey TI CUDCP-Affiliated Clinical Psychology Student Views of Their Science Training SO TRAINING AND EDUCATION IN PROFESSIONAL PSYCHOLOGY LA English DT Article DE scientist practitioner; training; student views; Boulder model AB Scientist-practitioner models of clinical psychology training emphasize the quality of science training that students receive, but student views on this topic have not been adequately explored. The current study reports findings of a large-scale survey distributed to 163 clinical psychology doctoral programs affiliated with CUDCP. Student representatives from 55 programs (34%) returned responses from a total of 611 students. Although this response rate was not ideal, a number of important patterns in student perspectives emerged. The overwhelming majority indicated that science training was very important to them. Overall, students reported experiencing a fairly balanced emphasis on science and clinical work, and endorsed receiving a good amount of high-quality training in science. However, discrepancies were noted in the degree to which science training in some areas is emphasized versus desired. Implications for training experiences are discussed. C1 [Merlo, Lisa J.] Univ Florida, Dept Psychiat, Gainesville, FL 32610 USA. [Collins, Allison] VA Boston Healthcare Syst, Med Psychol Serv, Boston, MA USA. [Bernstein, Jessey] McGill Univ, Montreal, PQ, Canada. RP Merlo, LJ (reprint author), Univ Florida, Dept Psychiat, Box 100234, Gainesville, FL 32610 USA. EM lmerlo@psychiatry.ufl.edu NR 38 TC 12 Z9 12 U1 0 U2 1 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1931-3918 J9 TRAIN EDUC PROF PSYC JI Train. Educ. Prof. Psychol. PD FEB PY 2008 VL 2 IS 1 BP 58 EP 65 DI 10.1037/1931-3918.2.1.58 PG 8 WC Psychology, Educational SC Psychology GA V29EB UT WOS:000208730600008 ER PT J AU Horner, BM Randolph, MA Huang, CA Butler, PEM AF Horner, Benjamin M. Randolph, Mark A. Huang, Christene A. Butler, Peter E. M. TI Skin tolerance: in search of the Holy Grail SO TRANSPLANT INTERNATIONAL LA English DT Review DE animal; clinical; research; skin; tolerance; transplant ID REGULATORY T-CELLS; BONE-MARROW-TRANSPLANTATION; COMPOSITE TISSUE ALLOGRAFT; DONOR-SPECIFIC TOLERANCE; LONG-TERM ACCEPTANCE; NONHUMAN PRIMATE MODEL; DENDRITIC CELLS; HEMATOPOIETIC CHIMERISM; MONOCLONAL-ANTIBODY; MINIATURE SWINE AB In 1943, Gibson and Medawar opened the modern era of transplantation research with a paper on the problem of skin allograft rejection. Ten years later Billingham, Brent and Medawar demonstrated that it was possible to induce selective immune acceptance of skin grafts in mice, a state of tolerance. After over six decades, however, the precise mechanism of skin allograft rejection remains still ill-defined. Furthermore, it has not been possible to achieve reliably clinical tolerance allowing the widespread application of skin allotransplantation techniques. The first successful applications of skin allotransplantation have included the hand and face. However, complications from the chronic immunosuppression regimens limit the application of these techniques. Induction of tolerance to skin (and the other tissues in the allograft) would be the most effective way to overcome all these difficulties, but this is yet to be achieved reliably, stimulating some to look for other ways to surmount the current limitations. This paper summarizes alternatives to enlarge the scope of skin allotransplantation techniques, current understanding of mechanisms of skin rejection, and the utility and limitations of animal models used to study skin rejection and tolerance induction. Finally, manipulation strategies to achieve skin tolerance are outlined. C1 [Horner, Benjamin M.; Huang, Christene A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Horner, Benjamin M.; Butler, Peter E. M.] UCL, Royal Free Hosp, Dept Plast Surg, London WC1E 6BT, England. [Randolph, Mark A.] Massachusetts Gen Hosp, Dept Surg, Plast Surg Res Lab, Boston, MA 02114 USA. RP Huang, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Bldg 149-9019,13th St,Charlestown Navy Yard, Boston, MA 02129 USA. EM christene.huang@tbrc.mgh.harvard.edu OI Butler, Peter/0000-0001-7419-1493 NR 124 TC 14 Z9 14 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0934-0874 J9 TRANSPL INT JI Transpl. Int. PD FEB PY 2008 VL 21 IS 2 BP 101 EP 112 DI 10.1111/j.1432-2277.2007.00559.x PG 12 WC Surgery; Transplantation SC Surgery; Transplantation GA 249XB UT WOS:000252262500001 PM 17903184 ER PT J AU Smith, MR Lee, H Fallon, MA Nathan, DM AF Smith, Matthew R. Lee, Hang Fallon, Mary Anne Nathan, David M. TI Adipocytokines, obesity, and insulin resistance during combined androgen blockade for prostate cancer SO UROLOGY LA English DT Article ID CORONARY-HEART-DISEASE; PLASMA ADIPONECTIN LEVELS; LEAN BODY-MASS; DEPRIVATION THERAPY; ARTERIAL STIFFNESS; METABOLIC SYNDROME; HORMONE; MEN; FAT; RISK AB OBJECTIVES Gonadotropin-releasing hormone agonists increase fat mass, decrease insulin sensitivity, and increase serum triglycerides. To better characterize the metabolic effects of gonadotropin releasing hormone agonist treatment, we prospectively. evaluated the changes in body composition, insulin sensitivity, and levels of adiponectin, resistin, C-reactive protein (CRP), and plasminogen activator inhibitor type 1 (PAI-1). We also assessed the relationships among changes in adipocytokines, body composition, and insulin sensitivity. METHODS In this prospective, 12-week study, 25 nondiabetic men with locally advanced or recurrent prostate cancer and no radiographic evidence of metastases were treated with leuprolide depot and bicalutamide. The outcomes studied included changes from baseline to week 12 in body composition, insulin sensitivity, and levels of adiponectin, resistin, CRP, and PAI-1. RESULTS The mean +/- standard error percentage of fat body mass increased by 4.3% +/- 1.3% from baseline to week 12 (P = 0.002). The insulin sensitivity index decreased by 12.9% +/- 7.6% (P = 0.02). The serum adiponectin levels increased by 37.4% +/- 7.2% from baseline to week 12 (P <0.001). In contrast, the resistin, CRT, and PAI-1 levels did not change significantly. Changes in body composition tended to be associated with changes in adiponectin, but not insulin sensitivity. CONCLUSIONS Combined androgen blockade with leuprolide and bicalutamide significantly increased fat mass and adiponectin levels and decreased insulin sensitivity but did not alter the resistin, CRP, or PAI-1 levels. This pattern of metabolic changes appears distinct from the classic metabolic syndrome. C1 [Smith, Matthew R.] Massachusetts Gen Hosp, Div Hematol Oncol, Mallinckrodt Gen Clin Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Mallinckrodt Gen Clin Res Ctr, Yawkey 7038,55 Fruit St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu FU NCI NIH HHS [K24 CA121990, K24 CA121990-01A1]; NCRR NIH HHS [M01-RR-01066, M01 RR001066] NR 30 TC 58 Z9 59 U1 0 U2 1 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 FEB PY 2008 VL 71 IS 2 BP 318 EP 322 DI 10.1016/j.urology.2007.08.035 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 265CZ UT WOS:000253338000044 PM 18308111 ER PT J AU Mortimer, JT Vuolo, M Staff, J Wakefield, S Xie, WL AF Mortimer, Jeylan T. Vuolo, Mike Staff, Jeremy Wakefield, Sara Xie, Wanling TI Tracing the timing of "Career" acquisition in a contemporary youth cohort SO WORK AND OCCUPATIONS LA English DT Article DE career; transition to adulthood; adolescent work; socioeconomic attainment ID LABOR-MARKET; HIGH-SCHOOL; LIFE-COURSE; WORK; TRANSITION; ADULTHOOD; CONSEQUENCES; EMPLOYMENT; FAMILY; MOBILITY AB Contemporary youth typically experience considerable floundering and uncertainty in their transition from school to work. This article examines patterns of schooling and working during adolescence and the transition to adulthood that hasten or delay an important subjective marker of transition to adulthood: acquiring a job that is recognized as a "career." We use Youth Development Study data, obtained from a prospective longitudinal study of 9th graders. Estimation of discrete-time logit models shows that adolescent work patterns during high school, as well as the cumulative investments they make in work and schooling in the years following, significantly influence this milestone. Time-varying predictors, including job characteristics and parenthood, also affect the process of movement into "careers.". C1 [Mortimer, Jeylan T.] Univ Minnesota, Life Course Ctr, Minneapolis, MN 55455 USA. [Staff, Jeremy] Penn State Univ, Dept Sociol, University Pk, PA 16802 USA. [Wakefield, Sara] Univ Calif Irvine, Dept Criminol Law & Soc, Irvine, CA USA. [Vuolo, Mike] Univ Minnesota, Dept Sociol, Minneapolis, MN 55455 USA. [Xie, Wanling] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mortimer, JT (reprint author), Univ Minnesota, Life Course Ctr, 1014 Social Sci Bldg,267 19th Ave S, Minneapolis, MN 55455 USA. EM morti002@umn.edu FU NICHD NIH HHS [R01 HD044138, R01 HD044138-19]; NIMH NIH HHS [R01 MH042843] NR 84 TC 31 Z9 31 U1 4 U2 15 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0730-8884 J9 WORK OCCUPATION JI Work Occup. PD FEB PY 2008 VL 35 IS 1 BP 44 EP 84 DI 10.1177/0730888407309761 PG 41 WC Industrial Relations & Labor; Sociology SC Business & Economics; Sociology GA 253QZ UT WOS:000252534000002 PM 18542713 ER PT J AU Belkora, J Edlow, B Aviv, C Sepucha, K Esserman, L AF Belkora, Jeffrey Edlow, Brian Aviv, Caryn Sepucha, Karen Esserman, Laura TI Training community resource center and clinic personnel to prompt patients in listing questions for doctors: Follow-up interviews about barriers and facilitators to the implementation of consultation planning SO IMPLEMENTATION SCIENCE LA English DT Article ID DECISION-SUPPORT FRAMEWORK; RANDOMIZED CONTROLLED-TRIAL; CANCER-PATIENTS; BREAST-CANCER; ASKING QUESTIONS; CALL CENTER; HELP; PHYSICIANS; CARE; PARTICIPATION AB Background: Visit preparation interventions help patients prepare to meet with a medical provider. Systematic reviews have found some positive effects, but there are no reports describing implementation experiences. Consultation Planning (CP) is a visit preparation technique in which a trained coach or facilitator elicits and documents patient questions for an upcoming medical appointment. We integrated CP into a university breast cancer clinic beginning in 1998. Representatives of other organizations expressed interest in CP, so we invited them to training workshops in 2000, 2001, and 2002. Objectives: In order to learn from experience and generate hypotheses, we asked: 1) How many trainees implemented CP? 2) What facilitated implementation? 3) How have trainees, patients, physicians, and administrative leaders of implementing organizations reacted to CP? 4) What were the barriers to implementation? Methods: We attempted to contact 32 trainees and scheduled follow-up, semi-structured, audio-recorded telephone interviews with 18. We analyzed quantitative data by tabulating frequencies and qualitative data by coding transcripts and identifying themes. Results: Trainees came from two different types of organizations, clinics (which provide medical care) versus resource centers (which provide patient support services but not medical care). We found that: 1) Fourteen of 21 respondents, from five of eight resource centers, implemented CP. Four of the five implementing resource centers were rural. 2) Implementers identified the championing of CP by an internal staff member as a critical success factor. 3) Implementers reported that modified CP has been productive. 4) Four respondents, from two resource centers and two clinics, did not implement CP, reporting resource limitations or conflicting priorities as the critical barriers. Conclusion: CP training workshops have been associated with subsequent CP implementations at resource centers but not clinics. We hypothesize that CP workshops combined with an internal champion and adequate program resources may be sufficient for some patient support organizations to implement CP. C1 [Belkora, Jeffrey; Esserman, Laura] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Edlow, Brian] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Aviv, Caryn] Univ Denver, Ctr Juda Studies, Denver, CO USA. [Sepucha, Karen] Massachusetts Gen Hosp, Hlth Decis Res Unit, Boston, MA USA. RP Belkora, J (reprint author), Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. EM jeff.belkora@ucsfmedctr.org; edlow@mac.com; caviv@du.edu; ksepucha@partners.org; laura.esserman@ucsfmedctr.org FU United States Department of Defense [DAMD17-961-6260] FX This survey was conducted as part of a Center of Excellence project based at the University of California, San Francisco Breast Care Center, with funding from the United States Department of Defense grant DAMD17-961-6260 (Laura Esserman, PI). The authors wish to thank manuscript reviewers (Elizabeth Murray, Matthew Hudson, and Cathy Charles) for their helpful comments and Professors Elizabeth Boyd of UCSF and Carol D'Onofrio of the University of California, Berkeley for their guidance and coaching. NR 32 TC 16 Z9 16 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD JAN 31 PY 2008 VL 3 AR 6 DI 10.1186/1748-5908-3-6 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 432QJ UT WOS:000265148900001 PM 18237380 ER PT J AU Shulman, LN Hitt, RA Ferry, JA AF Shulman, Lawrence N. Hitt, Rachel A. Ferry, Judith A. TI A pregnant woman with swelling of the left breast and shortness of breath - Diffuse large-B-cell lymphoma, consistent with primary mediastinal large-B-cell lymphoma, with involvement of breast and ovary SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MALIGNANT-LYMPHOMA; HODGKIN-LYMPHOMA; FEMALE BREAST; CANCER; EXPERIENCE; CHEMOTHERAPY; EXPRESSION; MULTICENTER; MANAGEMENT; CARCINOMA C1 [Shulman, Lawrence N.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Shulman, Lawrence N.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Hitt, Rachel A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Ferry, Judith A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Shulman, Lawrence N.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Hitt, Rachel A.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Ferry, Judith A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Shulman, LN (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 43 TC 10 Z9 10 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 JAN 31 PY 2008 VL 358 IS 5 BP 513 EP 523 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 256IW UT WOS:000252722900011 PM 18234756 ER PT J AU Burstein, HJ Schwartz, RS AF Burstein, Harold J. Schwartz, Robert S. TI Molecular origins of cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Burstein, Harold J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Burstein, Harold J.] Harvard Univ, Sch Med, Boston, MA USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 20 Z9 21 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 JAN 31 PY 2008 VL 358 IS 5 BP 527 EP 527 DI 10.1056/NEJMe0800065 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 256IW UT WOS:000252722900013 PM 18234758 ER PT J AU Podar, K Gouill, SL Zhang, J Opferman, JT Zorn, E Tai, YT Hideshima, T Amiot, M Chauhan, D Harousseau, JL Anderson, KC AF Podar, K. Gouill, S. L. Zhang, J. Opferman, J. T. Zorn, E. Tai, Y-T Hideshima, T. Amiot, M. Chauhan, D. Harousseau, J-L Anderson, K. C. TI A pivotal role for Mcl-1 in Bortezomib-induced apoptosis SO ONCOGENE LA English DT Article DE Mcl-1; apoptosis; Bortezomib ID PROTEASOME INHIBITOR PS-341; MULTIPLE-MYELOMA CELLS; DOWN-REGULATION; IN-VIVO; SURVIVAL; ACTIVATION; GROWTH; BCL-2; PROTEIN; DIFFERENTIATION AB Bortezomib is a proteasome inhibitor for the treatment of relapsed/refractory multiple myeloma (MM). Mechanisms of resistance to Bortezomib are undefined. Myeloid cell leukemia-1 (Mcl-1) is an antiapoptotic protein, which protects tumor cells against spontaneous and chemotherapy-induced apoptosis. In MM, specific downregulation of Mcl-1 induces apoptosis. Here, we examined the role of Mcl-1 in Bortezomib- and doxorubicin-induced apoptosis. We demonstrate that Bortezomib, but not doxorubicin, triggers caspase-dependent generation of a 28 kDa Mcl-1 fragment, in several MM cell lines, including MM.1S cells. Conversely, transient transfection of MM.1S cells with a previously reported 28 kDa Mcl-1(128-350) fragment, but not with the Mcl-1(1-127) fragment, induces apoptosis. Therefore, both downregulation of full-length antiapoptotic Mcl-1, as well as Bortezomib- induced generation of Mcl-1(128-350) cleaved protein, contribute to MM cell apoptosis. To verify further these findings, we next compared effects triggered by Bortezomib, doxorubicin and melphalan in Mcl-1(wt/wt) and Mcl-1(Delta/null) murine embryonic fibroblasts (MEFs). Our results show that Bortezomib, but not doxorubicin or melphalan, triggers Mcl-1 cleavage in Mcl-1(wt/wt), but not Mcl-1(Delta/null) MEFs and induces sub-G(1) phase cells; caspase-3 and -9, and PARP cleavage as well as morphological signs of apoptosis. Taken together, these results support an important role of Mcl-1 and a Mcl-1 fragment in Bortezomib- induced cell death in general, and in MM in particular. To prevent relapse of MM in patients treated with Bortezomib, we therefore recommend the combination of Bortezomib with agents that induce MM cell death independent of Mcl-1. C1 [Podar, K.; Gouill, S. L.; Zhang, J.; Tai, Y-T; Hideshima, T.; Chauhan, D.; Anderson, K. C.] Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma CtrDept Med Oncol, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02215 USA. [Gouill, S. L.; Amiot, M.; Harousseau, J-L] CHU Nantes, Hotel Dieu, Serv Hematol Clin, F-44035 Nantes 01, France. [Gouill, S. L.; Amiot, M.] INSERM, U 0601, Inst Biol, Quai Moncousu 9, F-44035 Nantes 01, France. [Opferman, J. T.] St Jude Childrens Hosp, Dept Biochem, Memphis, TN 38105 USA. [Zorn, E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Ctr Hematol Oncol,Dept Med, Boston, MA 02215 USA. RP Podar, K (reprint author), Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma CtrDept Med Oncol, Dana Farber Canc Inst,Dept Med Oncol, 44 Binney St, Boston, MA 02215 USA. EM klaus_podar@dfci.harvard.edu; kenneth_anderson@dfci.harvard.edu FU NCI NIH HHS [R0 CA 50947, P0-1 CA 78378, P50 CA 10070] NR 46 TC 71 Z9 74 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 31 PY 2008 VL 27 IS 6 BP 721 EP 731 DI 10.1038/sj.onc.1210679 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 258QZ UT WOS:000252884500001 PM 17653083 ER PT J AU Nardi, V Raz, T Cao, X Wu, CJ Stone, RM Cortes, J Deininger, MWN Church, G Zhu, J Daley, GQ AF Nardi, V. Raz, T. Cao, X. Wu, C. J. Stone, R. M. Cortes, J. Deininger, M. W. N. Church, G. Zhu, J. Daley, G. Q. TI Quantitative monitoring by polymerase colony assay of known mutations resistant to ABL kinase inhibitors SO ONCOGENE LA English DT Article DE mutations detection; solid-phase PCR; drug resistance ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; PHILADELPHIA-CHROMOSOME; DOMAIN MUTATIONS; BCR-ABL; DASATINIB BMS-354825; CHAIN-REACTION; IMATINIB; RECOMMENDATIONS; MUTAGENESIS AB Resistance to molecularly targeted chemotherapy, and the development of novel agents that are active against resistant forms of target proteins create the need for a sensitive and quantitative assay to monitor drug-resistant mutations in patients to guide treatment and assess response. Here, we describe an application of the polymerase colony (polony) method to identify and quantify known point mutations in the BCR-ABL oncogene in patients with chronic myelogenous leukemia who evolve resistance to ABL kinase inhibitors. The assay can detect mutations with a sensitivity of 10(-4), quantify the burden of drug-resistant cells, and simultaneously monitor the dynamics of several coexisting mutations. As a proof of concept, we analysed blood samples from three patients undergoing therapy with ABL kinase inhibitors and found that the patients' response to therapy correlated with our molecular monitoring. We were also able to detect mutations emerging in patients long before clinical relapse. Therefore, the polony assay could be applied to a larger patient sample to assess the utility of early mutation detection in patient-specific treatment decisions. Finally, this methodology could be a valuable research tool to shed light on the natural behavior of mutations pre-existing kinase inhibitors therapy and either disappearing over time or slowly taking over. C1 [Cao, X.; Zhu, J.] Duke Univ, Inst Genome Sci & Policy, Dept Cell Biol, Durham, NC 27708 USA. [Nardi, V.; Raz, T.; Daley, G. Q.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Biol Chem & Mol Pharmacol,Div Hematol Oncol, Boston, MA 02115 USA. [Wu, C. J.; Stone, R. M.] Childrens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Deininger, M. W. N.] Oregon Hlth & Sci Univ, Inst Canc, Div Hematol Oncol, Portland, OR 97201 USA. [Cortes, J.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Church, G.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Zhu, J (reprint author), Duke Univ, Inst Genome Sci & Policy, Dept Cell Biol, 2353A CIEMAS,101 Sci Dr, Durham, NC 27708 USA. EM jun.zhu@duke.edu; george.daley@childrens.harvard.edu FU NCI NIH HHS [F32-CA101505, R01 CA86691]; NHLBI NIH HHS [T32 HL066987-06] NR 21 TC 18 Z9 18 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 31 PY 2008 VL 27 IS 6 BP 775 EP 782 DI 10.1038/sj.onc.1210698 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 258QZ UT WOS:000252884500006 PM 17684485 ER PT J AU Shortell, SM Singer, SJ AF Shortell, Stephen M. Singer, Sara J. TI Improving patient safety by taking systems seriously SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID HOSPITALS C1 [Shortell, Stephen M.] Univ Calif Berkeley, Sch Publ Hlth, Div Hlth Policy & Management, Berkeley, CA 94720 USA. [Singer, Sara J.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Singer, Sara J.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. RP Shortell, SM (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Div Hlth Policy & Management, 50 Univ Hall, Berkeley, CA 94720 USA. EM shortell@berkeley.edu NR 24 TC 54 Z9 56 U1 2 U2 7 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 JAN 30 PY 2008 VL 299 IS 4 BP 445 EP 447 DI 10.1001/jama.299.4.445 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 256JK UT WOS:000252724500022 PM 18230782 ER PT J AU Truccolo, W Friehs, GM Donoghue, JP Hochberg, LR AF Truccolo, Wilson Friehs, Gerhard M. Donoghue, John P. Hochberg, Leigh R. TI Primary motor cortex tuning to intended movement kinematics in humans with tetraplegia SO JOURNAL OF NEUROSCIENCE LA English DT Article DE motor cortex; neuromotor prostheses; paralysis; motor control; spinal cord injury; stroke; quadriplegia ID GOAL-DIRECTED MOVEMENTS; FALSE DISCOVERY RATE; CORTICAL REPRESENTATION; ARM MOVEMENTS; PROSTHETIC DEVICES; ACTIVATION; DISCHARGE; ENSEMBLE; VELOCITY; POSITION AB The relationship between spiking activities in motor cortex and movement kinematics has been well studied in neurologically intact nonhuman primates. We examined the relationship between spiking activities in primary motor cortex (M1) and intended movement kinematics (position and velocity) using 96-microelectrode arrays chronically implanted in two humans with tetraplegia. Study participants were asked to perform two different tasks: imagined pursuit tracking of a cursor moving on a computer screen and a "neural cursor center-out" task in which cursor position was controlled by the participant's neural activity. In the pursuit tracking task, the majority of neurons were significantly tuned: 90% were tuned to velocity and 86% were tuned to position in one participant; 95% and 84%, respectively, in the other. Additionally, velocity and position of the tracked cursor could be decoded from the ensemble of neurons. In the neural cursor center-out task, tuning to direction of the intended target was well captured by a log-linear cosine function. Neural spiking soon after target appearance could be used to classify the intended target with an accuracy of 95% in one participant, and 80% in the other. It was also possible to extract information about the direction of the difference vector between the target position and the instantaneous neural cursor position. Our results indicate that correlations between spiking activity and intended movement velocity and position are present in human M1 after the loss of descending motor pathways, and that M1 spiking activities share many kinematic tuning features whether movement is imagined by humans with tetraplegia, or is performed as shown previously in able-bodied nonhuman primates. C1 [Truccolo, Wilson; Donoghue, John P.; Hochberg, Leigh R.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Friehs, Gerhard M.] Brown Univ, Dept Clin Neurosci Neurosurg, Providence, RI 02912 USA. [Truccolo, Wilson; Donoghue, John P.; Hochberg, Leigh R.] Brown Univ, Brain Sci Program, Providence, RI 02912 USA. [Hochberg, Leigh R.] Vet Hlth Adm, Ctr Restorat & Regenerat Med, Rehabil Res & Dev Serv, Dept Vet Affairs, Providence, RI 02908 USA. [Hochberg, Leigh R.] Massachusetts Gen Hosp, Dept Neurol, Brigham & Womens Hosp, Boston, MA 02114 USA. [Hochberg, Leigh R.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Boston, MA 02114 USA. [Friehs, Gerhard M.] Rhode Isl Hosp, Dept Neurosurg, Providence, RI 02905 USA. [Donoghue, John P.] Foxborough, Cyberkinet Neurotechnol Syst, Foxboro, MA 02035 USA. RP Truccolo, W (reprint author), Brown Univ, Dept Neurosci, 60 Olive St, Providence, RI 02912 USA. EM Wilson_Truccolo@Brown.edu FU NINDS NIH HHS [1K01NS057389, K01 NS057389, NS-25074, R01NS369744] NR 39 TC 116 Z9 116 U1 0 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 30 PY 2008 VL 28 IS 5 BP 1163 EP 1178 DI 10.1523/JNEUROSCI.4415-07.2008 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 257CY UT WOS:000252778000016 PM 18234894 ER PT J AU Wang, H Chen, HL Gao, X McGrath, M Deer, D De Vivo, I Schwarzschild, MA Ascherio, A AF Wang, Hao Chen, Honglei Gao, Xiang McGrath, Monica Deer, Dwayne De Vivo, Immaculata Schwarzschild, Michael A. Ascherio, Alberto TI Telomere length and risk of Parkinson's disease SO MOVEMENT DISORDERS LA English DT Article DE nested case-control study; Parkinson's disease; telomere length; relative risk ID OXIDATIVE STRESS; CIGARETTE-SMOKING; MORTALITY; CONSUMPTION; DEMENTIA; CELLS; WOMEN; MEN AB We investigated whether telomere length was associated with the risk of Parkinson's disease (PD) in a case-control study (96 cases and 172 age-matched controls) nested within the Health Professionals Follow-up Study. Relative ratio of telomere repeat copy number to single-gene copy number in peripheral blood leukocytes was determined by quantitative real time PCR. Men with shorter telomeres had a lower PD risk (multivariate adjusted relative risk for the lowest vs. the highest quartile 0.33; 95% confidence interval: 0.12-0.90). Our results suggest that, contrary to telomere attrition observed in several aging-related diseases, shorter telomeres are not associated with an increased risk of PD. (C) 2007 Movement Disorder Society. C1 [Wang, Hao; Gao, Xiang; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [McGrath, Monica; De Vivo, Immaculata; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [McGrath, Monica; Deer, Dwayne; De Vivo, Immaculata] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [McGrath, Monica; Deer, Dwayne; De Vivo, Immaculata] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Deer, Dwayne] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [De Vivo, Immaculata] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Wang, H (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM hwangi@hsph.harvard.edu OI Chen, Honglei/0000-0003-3446-7779 FU Intramural NIH HHS [Z01 ES101986-02]; NINDS NIH HHS [R01 NS048517-01A2, R01 NS048517] NR 17 TC 38 Z9 39 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JAN 30 PY 2008 VL 23 IS 2 BP 302 EP 305 DI 10.1002/mds.21867 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 258ME UT WOS:000252871200028 PM 18044760 ER PT J AU Egawa, T Kreslavsky, T Littman, DR von Boehmer, H AF Egawa, Takeshi Kreslavsky, Taras Littman, Dan R. von Boehmer, Harald TI Lineage Diversion of T Cell Receptor Transgenic Thymocytes Revealed by Lineage Fate Mapping SO PLOS ONE LA English DT Article AB Background. The binding of the T cell receptor (TCR) to major histocompatibility complex (MHC) molecules in the thymus determines fates of lymphocytes that subsequently home to secondary lymphoid tissue. TCR transgenic models have been used to study thymic selection and lineage commitment. Most TCR transgenic mice express the rearranged TCR alpha beta prematurely at the double negative stage and abnormal TCR alpha beta populations of T cells that are not easily detected in non-transgenic mice have been found in secondary lymphoid tissue of TCR transgenic mice. Methodology and Principal Findings. To determine developmental pathways of TCR-transgenic thymocytes, we used Cre-LoxP-mediated fate mapping and show here that premature expression of a transgenic TCR alpha beta diverts some developing thymocytes to a developmental pathway which resembles that of gamma delta cells. We found that most peripheral T cells with the HY-TCR in male mice have bypassed the ROR gamma t-positive CD4(+)8(+) ( double positive, DP) stage to accumulate either as CD4(-)8(-) ( double negative, DN) or as CD8 alpha(+) T cells in lymph nodes or gut epithelium. Likewise, DN TCR alpha beta cells in lymphoid tissue of female mice were not derived from DP thymocytes. Conclusion. The results further support the hypothesis that the premature expression of the TCR alpha beta can divert DN thymocytes into gamma delta lineage cells. C1 [Egawa, Takeshi; Littman, Dan R.] NYU, Sch Med, Skirball Inst Biomol Med, Helen L & Martin S Kimmel Ctr Biol & Med,Mol Path, New York, NY 10003 USA. [Littman, Dan R.] NYU, Sch Med, Skirball Inst Biomol Med, Helen L & Martin S Kimmel Ctr Biol & Med, New York, NY USA. [Kreslavsky, Taras; von Boehmer, Harald] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. RP Littman, DR (reprint author), NYU, Sch Med, Skirball Inst Biomol Med, Helen L & Martin S Kimmel Ctr Biol & Med,Mol Path, New York, NY 10003 USA. EM littman@saturn.med.nyu.edu; harald_von_boehmer@dfci.harvard.edu FU Human Frontier Science Program [LT00278/202]; Leukemia and Lymphoma Society [3547-07]; National Institutes of Health [R01AI45846] FX This study was supported by postdoctoral fellowships from the Human Frontier Science Program (LT00278/202) and the Leukemia and Lymphoma Society (3547-07) to TE and by a grant from the National Institutes of Health (R01AI45846) to HvB. DRL is an investigator of the Howard Hughes Medical Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 26 TC 31 Z9 32 U1 1 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 30 PY 2008 VL 3 IS 1 AR e1512 DI 10.1371/journal.pone.0001512 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 366SR UT WOS:000260504200024 PM 18231598 ER PT J AU Zhou, XH Li, SM Gatsonis, CA AF Zhou, Xiao-Hua Li, Sierra M. Gatsonis, Constantine A. TI Wilcoxon-based group sequential designs for comparison of areas under two correlated ROC curves SO STATISTICS IN MEDICINE LA English DT Article DE group sequential design; ROC curve areas; non-parametric ID OPERATING CHARACTERISTIC CURVES; CLINICAL-TRIALS AB Clinical studies to evaluate the relative accuracies of two diagnostic modalities via their receiver operating characteristic (ROC) curves are currently conducted using fixed sample designs: cases are accrued until a predetermined sample size is achieved and, at that point, the areas under the ROC curves are computed and compared (Radiology 1982; 143:29-36; Radiology 1983; 148:839-843). In prospective ROC studies (Radiology 1990; 175:571-575), participants are recruited from a clinically defined cohort and diagnostic test information is obtained and interpreted in advance of ascertaining the definitive proof of diagnosis ('gold standard'). In retrospective studies, cases are selected from a set of patient records and their diagnostic tests are interpreted without knowledge of the 'gold standard'. The conduct of ROC studies requires considerable effort and resources, particularly for the collection of 'gold standard' information. Thus, it is highly desirable to search for designs which are more efficient than using a fixed sample. In this paper, we discuss the formulation and application of group sequential designs (GSDs) to comparative ROC studies based on non-parametric Wilcoxon estimators of the area under the ROC curves. The approach is applicable to comparisons of ROC curve areas of two tests measured on either continuous or ordinal scales on same cases ('paired' designs) with one reader. The adoption of GSDs may lead to substantial savings in the number of required cases, thus resulting in both time and resource use efficiency. Copyright (c) 2007 John Wiley & Sons, Ltd. C1 [Zhou, Xiao-Hua] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Zhou, Xiao-Hua; Li, Sierra M.] VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98108 USA. [Gatsonis, Constantine A.] Brown Univ, Ctr Stat Sci, Providence, RI USA. RP Zhou, XH (reprint author), Univ Washington, Dept Biostat, Seattle, WA 98195 USA. EM azhou@u.washington.edu FU NIBIB NIH HHS [R01 EB005829] NR 11 TC 5 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 30 PY 2008 VL 27 IS 2 BP 213 EP 223 DI 10.1002/sim.2856 PG 11 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 261RY UT WOS:000253098900010 PM 17357988 ER PT J AU Kawasaki, T Nosho, K Ohnishi, M Suemoto, Y Glickman, JN Chan, AT Kirkner, GJ Mino-Kenudson, M Fuchs, CS Ogino, S AF Kawasaki, Takako Nosho, Katsuhiko Ohnishi, Mutsuko Suemoto, Yuko Glickman, Jonathan N. Chan, Andrew T. Kirkner, Gregory J. Mino-Kenudson, Mari Fuchs, Charles S. Ogino, Shuji TI Cyclooxygenase-2 overexpression is common in serrated and non-serrated colorectal adenoma, but uncommon in hyperplastic polyp and sessile serrated polyp/adenoma SO BMC CANCER LA English DT Article ID CPG ISLAND; METHYLATOR PHENOTYPE; CANCER; EXPRESSION; CELECOXIB; COX-2; RISK; ASPIRIN; GROWTH; PREVENTION AB Background: Cyclooxygenase-2 (COX-2, PTGS2) plays an important role in colorectal carcinogenesis. COX-2 overexpression in colorectal cancer is inversely associated with microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP). Evidence suggests that MSI/CIMP+ colorectal cancer may arise through the serrated tumorigenic pathway through various forms of serrated neoplasias. Therefore, we hypothesized that COX-2 may play a less important role in the serrated pathway. Methods: By immunohistochemistry, we assessed COX-2 expression in 24 hyperplastic polyps, 7 sessile serrated polyp/adenomas (SSA), 5 mixed polyps with SSA and adenoma, 27 traditional serrated adenomas, 515 non-serrated adenomas (tubular adenoma, tubulovillous adenoma and villous adenoma), 33 adenomas with intramucosal carcinomas, 96 adenocarcinomas with serration (corkscrew gland) and 111 adenocarcinomas without serration. Results: Strong (2+) COX-2 overexpression was more common in non-serrated adenomas (28%=143/515) than in hyperplastic polyps (4.2%=1/24, p=0.008) and serrated polyps (7 SSAs and 5 mixed polyps) (0%=0/12, p=0.04). Furthermore, any (1+/2+) COX-2 overexpression was more frequent in non-serrated adenomas (60%=307/515) than in hyperplastic polyps (13%=3/24, p < 0.0001) and serrated polyps ( SSAs and mixed polyps) (25%=3/12, p=0.03). Traditional serrated adenomas and non-serrated adenomas showed similar frequencies of COX-2 overexpression. Regardless of serration, COX-2 overexpression was frequent (similar to 85%) in colorectal adenocarcinomas. Tumor location was not significantly correlated with COX-2 overexpression, although there was a trend towards higher frequencies of COX-2 overexpression in distal tumors (than proximal tumors) among hyperplastic polyps, SSAs, mixed polyps, traditional serrated adenomas and adenocarcinomas. Conclusion: COX-2 overexpression is infrequent in hyperplastic polyp, SSA and mixed polyp with SSA and adenoma, compared to non-serrated and serrated adenoma. COX-2 overexpression becomes more frequent as tumors progress to higher grade neoplasias. Our observations suggest that COX-2 may play a less significant role in the serrated pathway of tumorigenesis; however, COX-2 may still play a role in later stage of the serrated pathway. C1 [Kawasaki, Takako; Nosho, Katsuhiko; Ohnishi, Mutsuko; Suemoto, Yuko; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Glickman, Jonathan N.; Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Glickman, Jonathan N.; Chan, Andrew T.; Kirkner, Gregory J.; Mino-Kenudson, Mari; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Chan, Andrew T.; Kirkner, Gregory J.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Ogino, S (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM takako_kawasaki@dfci.harvard.edu; katsuhiko_nosho@dfci.harvard.edu; mutsuko_ohnishi@dfci.harvard.edu; yuyupon26@yahoo.co.jp; jglickman@partners.org; achan@partners.org; gregory.kirkner@channing.harvard.edu; mmino@partners.org; chales_fuchs@dfci.harvard.edu; shuji_ogino@dfci.harvard.edu FU NCI NIH HHS [P01 CA087969, P01 CA87969, P01 CA055075, P50 CA127003, K07 CA122826, P01 CA55075] NR 46 TC 12 Z9 12 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD JAN 29 PY 2008 VL 8 AR 33 DI 10.1186/1471-2407-8-33 PG 8 WC Oncology SC Oncology GA 268RO UT WOS:000253597300002 PM 18230181 ER PT J AU Wang, TJ Pencina, MJ Booth, SL Jacques, PF Ingelsson, E Lanier, K Benjamin, EJ D'Agostino, RB Wolf, M Vasan, RS AF Wang, Thomas J. Pencina, Michael J. Booth, Sarah L. Jacques, Paul F. Ingelsson, Erik Lanier, Katherine Benjamin, Emelia J. D'Agostino, Ralph B. Wolf, Myles Vasan, Ramachandran S. TI Vitamin D deficiency and risk of cardiovascular disease SO CIRCULATION LA English DT Article DE cardiovascular diseases; risk factors; vitamin D ID SMOOTH-MUSCLE-CELLS; CORONARY-HEART-DISEASE; NUTRITION EXAMINATION SURVEY; PLASMA-RENIN ACTIVITY; 3RD NATIONAL-HEALTH; BLOOD-PRESSURE; PARATHYROID-HORMONE; D SUPPLEMENTATION; PHYSICAL-ACTIVITY; D INSUFFICIENCY AB Background - Vitamin D receptors have a broad tissue distribution that includes vascular smooth muscle, endothelium, and cardiomyocytes. A growing body of evidence suggests that vitamin D deficiency may adversely affect the cardiovascular system, but data from longitudinal studies are lacking. Methods and Results - We studied 1739 Framingham Offspring Study participants (mean age 59 years; 55% women; all white) without prior cardiovascular disease. Vitamin D status was assessed by measuring 25-dihydroxyvitamin D (25-OH D) levels. Prespecified thresholds were used to characterize varying degrees of 25-OH D deficiency (< 15 ng/mL, < 10 ng/mL). Multivariable Cox regression models were adjusted for conventional risk factors. Overall, 28% of individuals had levels < 15 ng/mL, and 9% had levels < 10 ng/mL. During a mean follow-up of 5.4 years, 120 individuals developed a first cardiovascular event. Individuals with 25-OH D < 15 ng/mL had a multivariable-adjusted hazard ratio of 1.62 (95% confidence interval 1.11 to 2.36, P = 0.01) for incident cardiovascular events compared with those with 25-OH D >= 15 ng/mL. This effect was evident in participants with hypertension (hazard ratio 2.13, 95% confidence interval 1.30 to 3.48) but not in those without hypertension (hazard ratio 1.04, 95% confidence interval 0.55 to 1.96). There was a graded increase in cardiovascular risk across categories of 25-OH D, with multivariable-adjusted hazard ratios of 1.53 (95% confidence interval 1.00 to 2.36) for levels 10 to < 15 ng/mL and 1.80 (95% confidence interval 1.05 to 3.08) for levels < 10 ng/mL (P for linear trend = 0.01). Further adjustment for C-reactive protein, physical activity, or vitamin use did not affect the findings. Conclusions - Vitamin D deficiency is associated with incident cardiovascular disease. Further clinical and experimental studies may be warranted to determine whether correction of vitamin D deficiency could contribute to the prevention of cardiovascular disease. C1 [Wang, Thomas J.; Pencina, Michael J.; Ingelsson, Erik; Lanier, Katherine; Benjamin, Emelia J.; D'Agostino, Ralph B.; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Wolf, Myles] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Renal Div, Boston, MA USA. [Wang, Thomas J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Cardiol, Boston, MA USA. [Pencina, Michael J.; D'Agostino, Ralph B.] Boston Univ, Dept Math, Stat & Consulting Unit, Boston, MA 02215 USA. [Booth, Sarah L.; Jacques, Paul F.] Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Med Ctr, Sch Med, Sect Cardiol & Prevent Med, Boston, MA 02215 USA. RP Wang, TJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB-800,55 Fruit St, Boston, MA 02114 USA. EM tjwang@partners.org RI Osborne, Nicholas/N-4915-2015; OI Osborne, Nicholas/0000-0002-6700-2284; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NCRR NIH HHS [K23-RR-017376-04]; NHLBI NIH HHS [N01-HC-25195, K23-HL-074077, K24-HL-04334]; NIA NIH HHS [R01-AG14759]; NIAMS NIH HHS [K23 AR054334, K23 AR054334-03] NR 64 TC 1136 Z9 1189 U1 10 U2 115 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 29 PY 2008 VL 117 IS 4 BP 503 EP 511 DI 10.1161/CIRCULATIONAHA.107.706127 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 256FA UT WOS:000252711900008 PM 18180395 ER PT J AU Mukherjee, P Thomas, S Pasinetti, GM AF Mukherjee, Piali Thomas, Sunil Pasinetti, Giulio Maria TI Complement anaphylatoxin C5a neuroprotects through regulation of glutamate receptor subunit 2 in vitro and in vivo SO JOURNAL OF NEUROINFLAMMATION LA English DT Article ID ACTIVATED PROTEIN-KINASE; CEREBELLAR GRANULE CELLS; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; STATUS EPILEPTICUS; INDUCED APOPTOSIS; CORTICAL-NEURONS; MESSENGER-RNA; NEURODEGENERATION; KAINATE AB Background: The complement system is thought to be involved in the pathogenesis of numerous neurological diseases. We previously reported that pre-treatment of murine cortico-hippocampal neuronal cultures with the complement derived anaphylatoxin C5a, protects against glutamate mediated apoptosis. Our present study with C5a receptor knock out (C5aRKO) mice corroborates that the deficiency of C5a renders C5aRKO mouse more susceptible to apoptotic injury in vivo. In this study we explored potential upstream mechanisms involved in C5a mediated neuroprotection in vivo and in vitro. Methods: Based on evidence suggesting that reduced expression of glutamate receptor subunit 2 (GluR2) may influence apoptosis in neurons, we studied the effect of human recombinant C5a on GluR2 expression in response to glutamate neurotoxicity. Glutamate analogs were injected into C5aRKO mice or used to treat in vitro neuronal culture and GluR2 expression were assessed in respect with cell death. Results: In C5aRKO mice we found that the neurons are more susceptible to excitotoxicity resulting in apoptotic injury in the absence of the C5a receptor compared to WT control mice. Our results suggest that C5a protects against apoptotic pathways in neurons in vitro and in vivo through regulation of GluR2 receptor expression. Conclusion: Complement C5a neuroprotects through regulation of GluR2 receptor subunit. C1 [Mukherjee, Piali; Thomas, Sunil; Pasinetti, Giulio Maria] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Pasinetti, Giulio Maria] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. [Pasinetti, Giulio Maria] James J Peters Vet Affairs Med Ctr, Geriat Res & Clin Ctr, Bronx, NY 10468 USA. [Mukherjee, Piali] Cornell Univ, Weill Med Coll, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustav L,Levy Pl, New York, NY 10029 USA. EM pim2001@med.cornell.edu; sunil.thomas@mssm.edu; giulio.pasinetti@mssm.edu OI Mukherjee, Piali/0000-0003-2737-4849 FU NIA NIH HHS [AG13799, AG14239, AG14766, R01 AG013799, R01 AG014766] NR 35 TC 30 Z9 31 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PD JAN 29 PY 2008 VL 5 AR 5 DI 10.1186/1742-2094-5-5 PG 7 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 267UR UT WOS:000253535200001 PM 18230183 ER PT J AU Iakoubova, OA Sabatine, MS Rowland, CM Tong, CH Catanese, JJ Ranade, K Simonsen, KL Kirchgessner, TG Cannon, CP Devlin, JJ Braunwald, E AF Iakoubova, Olga A. Sabatine, Marc S. Rowland, Charles M. Tong, Carmen H. Catanese, Joseph J. Ranade, Koustubh Simonsen, Katy L. Kirchgessner, Todd G. Cannon, Christopher P. Devlin, James J. Braunwald, Eugene TI Polymorphism in KIF6 gene and benefit from statins after acute coronary syndromes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CHOLESTEROL-LOWERING THERAPY; CARDIOVASCULAR-DISEASE; SUPERFAMILY PROTEINS; KINESIN SUPERFAMILY; HEART-DISEASE; PHARMACOGENOMICS; PREVENTION; CARGO AB Objectives We explored whether the benefit of intensive versus moderate statin therapy would be greater in carriers of KIF6 719Arg than in noncarriers. Background The 719Arg variant of Trp719Arg (rs20455), a polymorphism in kinesin-like protein 6, is associated with greater risk of coronary events and greater benefit from pravastatin versus placebo. Methods We genotyped 1,778 acute coronary syndrome patients within the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy: Thrombolysis in Myocardial Infarction 22) trial and investigated different intensities of statin therapy in carriers of 719Arg and in noncarriers using Cox proportional hazards models that adjusted for traditional risk factors. Results Benefit from intensive, compared with moderate, statin therapy was significantly greater in the 59% of the cohort who were carriers (hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.45 to 0.77) than in those who were noncarriers (HR 0.94, 95% CI 0.70 to 1.27; p = 0.018 for interaction between 719Arg carrier status and treatment). Absolute risk reduction was 10.0% in carriers versus 0.8% in noncarriers. The benefit of intensive therapy in carriers was significant as early as day 30 of therapy. Carriers and noncarriers did not differ in on-treatment low-density lipoprotein cholesterol, triglyceride, or C-reactive protein (CRP) levels. Conclusions Carriers of 719Arg receive significantly greater benefit from intensive statin therapy than do noncarriers, a superior benefit that appears to be due to a mechanism distinct from lipid or CRP lowering. Functional studies of the KIF6 kinesin are warranted, given the consistent association of Trp719Arg with risk of coronary events and statin benefit. C1 [Iakoubova, Olga A.; Rowland, Charles M.; Tong, Carmen H.; Catanese, Joseph J.; Devlin, James J.] Celera Inc, Alameda, CA 94502 USA. [Sabatine, Marc S.; Cannon, Christopher P.; Braunwald, Eugene] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div, Boston, MA 02115 USA. [Ranade, Koustubh; Simonsen, Katy L.; Kirchgessner, Todd G.] Bristol Myers Squibb Co, Pharmaceut Res Inst, Princeton, NJ 08543 USA. RP Iakoubova, OA (reprint author), Celera Inc, 1401 Harbor Bay Pkwy, Alameda, CA 94502 USA. EM olga.iakoubova@celera.com RI Simonsen, Katy/A-4193-2012 NR 23 TC 97 Z9 100 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 29 PY 2008 VL 51 IS 4 BP 449 EP 455 DI 10.1016/j.jacc.2007.10.017 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 255CA UT WOS:000252633100005 PM 18222355 ER PT J AU Beeri, R Yosefy, C Guerrero, JL Nesta, F Abedat, S Chaput, M del Monte, F Handschumacher, MD Stroud, R Sullivan, S Pugatsch, T Gilon, D Vlahakes, GJ Spinale, FG Hajjar, RJ Levine, RA AF Beeri, Ronen Yosefy, Chaim Guerrero, J. Luis Nesta, Francesca Abedat, Suzan Chaput, Miguel del Monte, Federica Handschumacher, Mark D. Stroud, Robert Sullivan, Suzanne Pugatsch, Thea Gilon, Dan Vlahakes, Gus J. Spinale, Francis G. Hajjar, Roger J. Levine, Robert A. TI Mitral regurgitation augments post-myocardial infarction remodeling SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; LEFT-VENTRICULAR FUNCTION; MATRIX-METALLOPROTEINASE ACTIVITY; CONGESTIVE-HEART-FAILURE; VOLUME OVERLOAD; 3-DIMENSIONAL ECHOCARDIOGRAPHY; CONTRACTILE DYSFUNCTION; PROGNOSTIC IMPLICATIONS; VALVULAR REGURGITATION; CLINICAL-IMPLICATIONS AB Objectives We examined whether mitral regurgitation (MR) augments post-myocardial infarction (MI) remodeling. Background MR doubles mortality after MI, but its additive contribution to left ventricular (LV) remodeling is debated and has not been addressed in a controlled fashion. Methods Apical MIs were created in 12 sheep, and 6 had an LV-to-left atrial shunt implanted, consistently producing regurgitant fractions of similar to 30%. The groups were compared at baseline, 1, and 3 months. Results Left ventricular end-systolic volume progressively increased by 190% with MR versus 90% without MR (p < 0.02). Pre-load-recruitable stroke work declined by 82 +/- 13% versus 25 +/- 16% (p < 0.01) with MR, with decreased remote-zone sarcoplasmic reticulum Ca2+-ATPase levels (0.56 +/- 0.03 vs. 0.76 +/- 0.02, p < 0.001), and decreased isolated myocyte contractility. In remote zones, pro-hypertrophic Akt and gp130 were upregulated in both groups at 1 month, but significantly lower and below baseline in the MR group at 3 months. Pro-apoptotic caspase 3 remained high in both groups. Matrix metalloproteinase (MMP)-13 and membrane-type MMP-1 were increased in remote zones of MR versus infarct-only animals at I month, then fell below baseline. The MMP tissue inhibitors rose from baseline to 3 months in all animals, rising higher in the MI + MR-group border zone. Conclusions In this controlled model, moderate MR worsens post-MI remodeling, with reduced contractility. Pro-hypertrophic pathways are initially upregulated but subsequently fall below infarct-only levels and baseline; with sustained caspase 3 elevation, transformation to a failure phenotype occurs. Extracellular matrix turnover increases in MR animals. Therefore, MR can precipitate an earlier onset of dilated heart failure. C1 [Beeri, Ronen; Yosefy, Chaim; Guerrero, J. Luis; Nesta, Francesca; Chaput, Miguel; Handschumacher, Mark D.; Sullivan, Suzanne; Levine, Robert A.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [del Monte, Federica; Hajjar, Roger J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Vlahakes, Gus J.] Massachusetts Gen Hosp, Dept Cardiac Surg, Boston, MA 02114 USA. [Vlahakes, Gus J.] Harvard Univ, Sch Med, Boston, MA USA. [Abedat, Suzan; Pugatsch, Thea; Gilon, Dan] Hadassah Hebrew Univ, Med Ctr, Inst Heart, Jerusalem, Israel. [Abedat, Suzan; Pugatsch, Thea; Gilon, Dan] Hadassah Hebrew Univ, Med Ctr, Cardiovasc Res Lab, Jerusalem, Israel. [Stroud, Robert; Spinale, Francis G.] Med Univ S Carolina, Dept Cardiothorac Surg, Charleston, SC 29425 USA. RP Levine, RA (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab YAW5, 55 Fruit St, Boston, MA 02114 USA. EM rlevine@partners.org RI Beeri, Ronen/A-4035-2009 OI Beeri, Ronen/0000-0002-8014-0702 FU NHLBI NIH HHS [R01HL72265, K24HL67434, R01HL38176] NR 83 TC 34 Z9 37 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 29 PY 2008 VL 51 IS 4 BP 476 EP 486 DI 10.1016/j.jacc.2007.07.093 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 255CA UT WOS:000252633100010 PM 18222360 ER PT J AU Moll, NM Rietsch, AM Ransohoff, AJ Cossoy, MB Huang, D Eichler, FS Trapp, BD Ransohoff, RM AF Moll, N. M. Rietsch, A. M. Ransohoff, A. J. Cossoy, M. B. Huang, D. Eichler, F. S. Trapp, B. D. Ransohoff, R. M. TI Cortical demyelination in PML and MS - Similarities and differences SO NEUROLOGY LA English DT Article ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; MULTIPLE-SCLEROSIS; LESIONS; PATHOLOGY; DISEASE; PATHOGENESIS; NEURONS; INJURY; JCV AB Objective: To characterize pathologic changes in the cerebral cortex of patients with multiple sclerosis ( MS) and progressive multifocal leukoencephalopathy ( PML). Methods: Autopsy brain tissue was obtained from 13 patients with PML, 4 patients with MS, 2 patients with HIV encephalopathy, and 1 subject without neurologic pathology. Immunohistochemistry for myelin proteins, inflammatory cells, and neurofilaments was performed to evaluate the distribution of cortical lesions, their inflammatory activity, and neuritic pathology. Confocal microscopy was applied to examine pathologic changes in neurites in PML cortex. Results: Leukocortical, intracortical, and subpial patterns of cortical demyelination were represented in MS brain tissue. In PML brain tissue intracortical and leukocortical but not subpial lesions were observed. Cortical lesions in PML and MS contained fewer inflammatory cells than demyelinated areas in the white matter. Neuritic pathology in cortical PML lesions was represented by dystrophic and transected neurites. Pathologic modifications in neuritic processes in PML were more evident in highly inflamed white matter than in gray matter areas of demyelination, reminiscent of previous reports of neuritic pathology in MS. JC virus-infected cells were associated with PML white matter, leukocortical and intracortical lesions. Conclusions: Cortical pathology represents a distinct feature of progressive multifocal leukoencephalopathy. Similarities and differences with regard to multiple sclerosis cortical pathology were noted and may be informative regarding the pathogenesis of both disorders. C1 [Moll, N. M.; Rietsch, A. M.; Cossoy, M. B.; Trapp, B. D.; Ransohoff, R. M.] Cleveland Clin, Lerner Res Inst NC 30, Dept Neurosci, Cleveland, OH 44195 USA. [Moll, N. M.; Rietsch, A. M.; Ransohoff, A. J.; Cossoy, M. B.; Ransohoff, R. M.] Cleveland Clin, Neuroinflammat Res Ctr, Cleveland, OH 44106 USA. [Huang, D.; Ransohoff, R. M.] Cleveland Clin, Neurol Inst, Cleveland, OH 44106 USA. [Eichler, F. S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Ransohoff, RM (reprint author), Cleveland Clin, Lerner Res Inst NC 30, Dept Neurosci, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM ransohr@ccf.org FU NINDS NIH HHS [P01 NS38667] NR 24 TC 67 Z9 68 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JAN 29 PY 2008 VL 70 IS 5 BP 336 EP 343 DI 10.1212/01.wnl.0000284601.54436.e4 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 256HQ UT WOS:000252719500003 PM 17914063 ER PT J AU Gerstner, ER Carson, KA Grossman, SA Batchelor, TT AF Gerstner, Elizabeth R. Carson, Kathryn A. Grossman, Stuart A. Batchelor, Tracy T. TI Long-term outcome in pcnsl patients treated with high-dose methotrexate and deferred radiation SO NEUROLOGY LA English DT Editorial Material ID NERVOUS-SYSTEM LYMPHOMA; RADIOTHERAPY; TRIAL C1 [Gerstner, Elizabeth R.; Batchelor, Tracy T.] Massachusetts Gen Hosp, Cattherine Pappas Ctr Neuro Oncol, Dept Neurol, Boston, MA 02114 USA. [Gerstner, Elizabeth R.; Batchelor, Tracy T.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Carson, Kathryn A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Carson, Kathryn A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA. [Grossman, Stuart A.] Sidney Kimmel Comprehens Canc Ctr John Hopkins, Baltimore, MD USA. RP Batchelor, TT (reprint author), Massachusetts Gen Hosp, Cattherine Pappas Ctr Neuro Oncol, Dept Neurol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM tbatchelor@partners.org FU NCI NIH HHS [U01 CA062475] NR 4 TC 37 Z9 39 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JAN 29 PY 2008 VL 70 IS 5 BP 401 EP 402 DI 10.1212/01.wnl.0000300671.37279.0e PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 256HQ UT WOS:000252719500012 PM 18227422 ER PT J AU Jinushi, M Vanneman, M Munshi, NC Tai, YT Prabhala, RH Ritz, J Neuberg, D Anderson, KC Carrasco, DR Dranoff, G AF Jinushi, Masahisa Vanneman, Matthew Munshi, Nikhil C. Tai, Yu-Tzu Prabhala, Rao H. Ritz, Jerome Neuberg, Donna Anderson, Kenneth C. Carrasco, Daniel Ruben Dranoff, Glenn TI MHC class I chain-related protein A antibodies and shedding are associated with the progression of multiple myeloma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ERp5; MICA; NKG2D; plasma cell; tumor immunity ID PLASMA-CELL DIFFERENTIATION; TRANSCRIPTION FACTOR XBP-1; DELTA T-CELLS; MONOCLONAL GAMMOPATHY; DENDRITIC CELLS; UNDETERMINED SIGNIFICANCE; NKG2D RECEPTOR; TUMOR-IMMUNITY; NK CELLS; EXPRESSION AB Monoclonal gammopathy of undetermined significance (MGUS) is a common disorder of aging and a precursor lesion to full-blown multiple myeloma (MM). The mechanisms underlying the progression from MGUS to MM are incompletely understood but include the suppression of innate and adaptive antitumor immunity. Here, we demonstrate that NKG2D, an activating receptor on natural killer (NK) cells, CD8(+) T lymphocytes, and MHC class I chain-related protein A (MICA), an NKG2D ligand induced in malignant plasma cells through DNA damage, contribute to the pathogenesis of MGUS and MM. MICA expression is increased on plasma cells from MGUS patients compared with normal donors, whereas MM patients display intermediate MICA levels and a high expression of ERp5, a protein disulfide isomerase linked to MICA shedding (sMICA). MM, but not MGUS, patients harbor circulating sMICA, which triggers the down-regulation of NKG2D and impaired lymphocyte cytotoxicity. In contrast, MGUS, but not MM, patients generate high-titer anti-MICA antibodies that antagonize the suppressive effects of sMICA and stimulate dendritic cell cross-presentation of malignant plasma cells. Bortezomib, a proteasome inhibitor with anti-MM clinical efficacy, activates the DNA damage response to augment MICA expression in some MM cells, thereby enhancing their opsonization by anti-MICA antibodies. Together, these findings reveal that the alterations in the NKG2D pathway are associated with the progression from MGUS to MM and raise the possibility that anti-MICA monoclonal antibodies might prove therapeutic for these disorders. C1 [Jinushi, Masahisa; Vanneman, Matthew; Munshi, Nikhil C.; Tai, Yu-Tzu; Prabhala, Rao H.; Ritz, Jerome; Anderson, Kenneth C.; Carrasco, Daniel Ruben; Dranoff, Glenn] Dana Farber Canc Inst, Dept Med, Canc Vaccine Ctr, Dept Med Oncol, Boston, MA 02115 USA. [Carrasco, Daniel Ruben] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Neuberg, Donna] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Med, Canc Vaccine Ctr, Dept Med Oncol, Boston, MA 02115 USA. EM glenn_dranoff@dfci.harvard.edu RI Jinushi, Masahisa/A-4311-2012; OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [R01 CA111506, CA111506, CA78378, P01 CA078378]; NIAID NIH HHS [AI29530, P01 AI029530, U19 AI029530] NR 50 TC 111 Z9 121 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 JAN 29 PY 2008 VL 105 IS 4 BP 1285 EP 1290 DI 10.1073/pnas.0711293105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 258NF UT WOS:000252873900037 PM 18202175 ER PT J AU Wunderlich, FT Luedde, T Singer, S Schmidt-Supprian, M Baumgartl, J Schirmacher, P Pasparakis, M Bruening, JC AF Wunderlich, F. Thomas Luedde, Tom Singer, Stephan Schmidt-Supprian, Marc Baumgartl, Julia Schirmacher, Peter Pasparakis, Manolis Bruening, Jens C. TI Hepatic NF-kappa B essential modulator deficiency prevents obesity-induced insulin resistance but synergizes with high-fat feeding in tumorigenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE insulin sensitivity; spontaneous hepatic carcinoma; steatosis; hepatic NEMO deficiency ID NECROSIS-FACTOR-ALPHA; ACTIVATED RECEPTOR-ALPHA; IKK-BETA; HEPATOCELLULAR-CARCINOMA; LIPID-METABOLISM; PPAR-GAMMA; IN-VIVO; EXPRESSION; LIVER; CELLS AB Development of obesity-associated insulin resistance and diabetes mellitus type 2 has been linked to activation of proinflammatory pathways in the liver, leading to impaired insulin signal transduction. To further define the role of hepatic NF-kappa B activation in this process, we have analyzed glucose metabolism in mice with liver-specific inactivation of the NF-kappa B essential modulator gene (NEMOL-KO mice) exposed to a high-fat diet (HFD). These animals are protected from the development of obesity-associated insulin resistance, highlighting the importance of hepatic NF-kappa B activation in this context. However, hepatic NEMO deficiency synergizes with HFD in the development of liver steatosis as a consequence of decreased peroxisome proliferator-activated receptor (PPAR-alpha) and increased PPAR-gamma expression. Steatosis interacts with increased inflammation, causing elevated apoptosis in the livers of these mice under HFD. These changes result in liver tumorigenesis of NEMOL-KO mice under normal diet, a process that is largely aggravated when these mice are exposed to HFD. These data directly demonstrate the interaction of hepatic inflammation, dietary composition, and metabolism in the development of liver tumorigenesis. C1 [Wunderlich, F. Thomas; Baumgartl, Julia; Bruening, Jens C.] Univ Cologne, Ctr Mol Med, Inst Genet, Dept Mouse Genet & Metab, D-50674 Cologne, Germany. [Luedde, Tom; Pasparakis, Manolis] Univ Cologne, Inst Genet, Dept Mouse Genet & Inflammat, D-50674 Cologne, Germany. [Luedde, Tom; Pasparakis, Manolis] European Mol Biol Lab, Mouse Biol Unit, I-000016 Monterotondo, Italy. [Schirmacher, Peter] Univ Heidelberg, Inst Pathol, Heidelberg, Germany. [Schmidt-Supprian, Marc] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Bruening, JC (reprint author), Univ Cologne, Ctr Mol Med, Inst Genet, Dept Mouse Genet & Metab, D-50674 Cologne, Germany. EM jens.bruening@uni-koeln.de RI Schmidt-Supprian, Marc/F-5893-2011; OI Schmidt-Supprian, Marc/0000-0002-8543-6166; Pasparakis, Manolis/0000-0002-9870-0966 NR 29 TC 64 Z9 66 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 29 PY 2008 VL 105 IS 4 BP 1297 EP 1302 DI 10.1073/pnas.0707849104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 258NF UT WOS:000252873900039 PM 18216263 ER PT J AU Peterson, PN Magid, DJ Ross, C Ho, PM Rumsfield, JS Lauer, MS Lyons, EE Smith, SS Masoudi, FA AF Peterson, Pamela N. Magid, David J. Ross, Colleen Ho, P. Michael Rumsfield, John S. Lauer, Michael S. Lyons, Ella E. Smith, Scott S. Masoudi, Frederick A. TI Association of exercise capacity on treadmill with future cardiac events in patients referred for exercise testing SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CARDIOVASCULAR-DISEASE MORTALITY; HEART-RATE RECOVERY; PROGNOSTIC VALUE; CARDIORESPIRATORY FITNESS; ALL-CAUSE; METABOLIC EQUIVALENTS; FUNCTIONAL-CAPACITY; FOLLOW-UP; MEN; PREDICTOR AB Background: Little is known about the association between exercise capacity and nonfatal cardiac events in patients referred for exercise treadmill testing (ETT). Our objective was to determine the prognostic importance of exercise capacity for nonfatal cardiac events in a clinical population. Methods: A cohort study was performed of 9191 patients referred for ETT. Median follow-up was 2.7 years. Exercise capacity was quantified as the proportion of age- and sex-predicted metabolic equivalents achieved and categorized as less than 85%, 85% to 100%, and greater than 100%. Individual primary outcomes were myocardial infarction, unstable angina, and coronary revascularization. All-cause mortality was a secondary outcome. Results: Patients with lower exercise capacity were more likely to be female (55.38% vs 42.62%); to have comorbidities such as diabetes (23.16% vs 9.61%) and hypertension (59.43% vs 44.05%); and to have abnormal ETT findings such as chest pain on the treadmill (12.09% vs 7.63%), abnormal heart rate recovery (82.74% vs 64.13%), and abnormal chronotropic index (32.89% vs 12.20%). In multivariable analysis, including other ETT variables, lower exercise capacity (< 85% of predicted) was associated with increased risk of myocardial infarction (hazard ratio [HR], 2,36; 95% confidence interval [01, 1.55-3.60), unstable angina (HR, 2.39; 95% Cl, 1.78-3.21), coronary revascularization (HR, 1.75; 95% CI, 1.46-2.08), and all-cause mortality (HR, 2.90; 95% CI, 1.88-4.47) compared with exercise capacity greater than 100% of predicted. Conclusions: Adjusting for patient characteristics and other ETT variables, reduced exercise capacity was associated with both nonfatal cardiovascular events and mortality in patients referred for ETT. C1 [Peterson, Pamela N.; Masoudi, Frederick A.] Denver Hlth Med Ctr, Dept Med, Div Cardiol, Denver, CO 80204 USA. [Peterson, Pamela N.; Ho, P. Michael; Rumsfield, John S.; Masoudi, Frederick A.] Univ Colorado, Denver Hlth Sci Ctr, Dept Med, Div Cardiol, Denver, CO USA. [Peterson, Pamela N.; Magid, David J.; Ross, Colleen; Ho, P. Michael; Rumsfield, John S.; Lyons, Ella E.; Masoudi, Frederick A.] Kaiser Permanente, Clin Res Unit, Denver, CO USA. [Smith, Scott S.] Kaiser Permanente, Dept Internal Med, Denver, CO USA. [Ho, P. Michael; Rumsfield, John S.] Denver Vet Affairs Med Ctr, Dept Med, Div Cardiol, Denver, CO 80220 USA. [Lauer, Michael S.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Peterson, PN (reprint author), Denver Hlth Med Ctr, Dept Med, Div Cardiol, Mail Code 0960,777 Bannock St, Denver, CO 80204 USA. EM Pamela.Peterson@uchsc.edu RI Lauer, Michael/L-9656-2013 OI Lauer, Michael/0000-0002-9217-8177 NR 26 TC 35 Z9 36 U1 0 U2 3 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 JAN 28 PY 2008 VL 168 IS 2 BP 174 EP 179 DI 10.1001/archinternmed.2007.68 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 254NR UT WOS:000252593800010 PM 18227364 ER PT J AU Thorndike, AN Regan, S McKool, K Pasternak, RC Swartz, S Torres-Finnerty, N Rigotti, NA AF Thorndike, Anne N. Regan, Susan McKool, Kathleen Pasternak, Richard C. Swartz, Susan Torres-Finnerty, Nancy Rigotti, Nancy A. TI Depressive symptoms and smoking cessation after hospitalization for cardiovascular disease SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CORONARY-HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED CONTROLLED-TRIAL; HEALTH-CARE PROFESSIONALS; SECONDARY PREVENTION; NICOTINE DEPENDENCE; ARTERY DISEASE; RISK; MORTALITY; ASSOCIATION AB Background: Although smoking cessation is essential for prevention of secondary cardiovascular disease (CVD), many smokers do not stop smoking after hospitalization. Mild depressive symptoms are common during hospitalization for CVD. We hypothesized that depressive symptoms measured during hospitalization for acute CVD would predict return to smoking after discharge from the hospital. Methods: This was a planned secondary analysis of data from a placebo-controlled, double-blind, randomized trial of bupropion hydrochloride therapy in 245 smokers hospitalized for acute CVD. All subjects received smoking counseling in the hospital and for 12 weeks after discharge. Depressive symptoms were measured during hospitalization with the Beck Depression Inventory (BDI), and smoking cessation was biochemically validated at 2-week, 12-week, and 1-year follow-up. The effect of depressive symptoms on smoking cessation was assessed using multiple logistic regression and survival analyses. Results: Twenty-two percent of smokers had moderate to severe depressive symptoms (BDI >= 16) during hospitalization. These smokers were more likely to resume smoking by 4 weeks after discharge (P=.007 incidence rate ratio, 2.40; 95% confidence interval, 1.48-3.78) than were smokers with lower BDI scores. Smokers with low BDI scores were more likely to remain abstinent than were those with high BDI scores at 3-month follow-up (37% vs 15%; adjusted odds ratio, 3.02; 95% confidence interval, 1.28-7.09) and 1-year follow-up (27% vs 10%; adjusted odds ratio, 3.77; 95% confidence interval, 1.31-10.82). We estimate that 27% of the effect of the BDI score on smoking cessation was mediated by nicotine withdrawal symptoms. Conclusions:: Moderate to severe depressive symptoms during hospitalization for acute CVD are independently associated with rapid relapse to smoking after discharge and lower rates of smoking cessation at long-term follow-up. The relationship was mediated in part by the stronger nicotine withdrawal symptoms experienced by smokers with higher depressive symptoms. C1 [Thorndike, Anne N.; Regan, Susan; McKool, Kathleen; Pasternak, Richard C.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Div Gen Med, Boston, MA 02114 USA. [Thorndike, Anne N.; Regan, Susan; McKool, Kathleen; Pasternak, Richard C.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Div Cardiol, Boston, MA 02114 USA. [Torres-Finnerty, Nancy] Boston Univ, Med Ctr, Boston, MA USA. [Swartz, Susan] Maine Med Ctr, Portland, ME 04102 USA. RP Thorndike, AN (reprint author), Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM athorndike@partners.org FU NCRR NIH HHS [M01-RR-01066]; NHLBI NIH HHS [R01-HL-61779, K24-HL04440] NR 41 TC 50 Z9 51 U1 0 U2 4 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 JAN 28 PY 2008 VL 168 IS 2 BP 186 EP 191 DI 10.1001/archinternmed.2007.60 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 254NR UT WOS:000252593800012 PM 18227366 ER PT J AU Wright, JT Harris-Haywood, S Pressel, S Barzilay, J Bairnbridge, C Bareis, CJ Basile, JN Black, HR Dart, R Gupta, AK Hamilton, BP Einhorn, PT Haywood, LJ Jafri, SZA Louis, GT Whelton, PK Scott, CL Sinnnons, DL Stanford, C Davis, BR AF Wright, Jackson T. Harris-Haywood, Sonja Pressel, Sara Barzilay, Joshua Bairnbridge, Charles Bareis, Charles J. Basile, Jan N. Black, Henry R. Dart, Richard Gupta, Alok K. Hamilton, Bruce P. Einhorn, Paula T. Haywood, L. Julian Jafri, Syed Z. A. Louis, Gail T. Whelton, Paul K. Scott, Cranford L. Sinnnons, Debra L. Stanford, Carol Davis, Barry R. TI Clinical outcomes by race in hypertensive patients with and without the metabolic syndrome - Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the International-Society-for-Hypertension-in-Blacks CY JUN 23, 2006 CL Atlanta, GA ID CALCIUM-CHANNEL BLOCKER; PROSPECTIVELY-DESIGNED OVERVIEWS; ISOLATED SYSTOLIC HYPERTENSION; MAJOR CARDIOVASCULAR EVENTS; CONVERTING ENZYME-INHIBITOR; DIABETES-MELLITUS; RANDOMIZED-TRIALS; RISK; ASSOCIATION; GLUCOSE AB Background: Antihypertensive drugs with favorable metabolic effects are advocated for first-line therapy in hypertensive patients with metabolic/cardiometabolic syndrome (MetS). We compared outcornes by race in hypertensive individuals with and without MetS treated with a thiazide-type diuretic (chlorthalidone), a calcium channel blocker (amlodipine besylate), an a-blocker (doxazosin mesylate), or an angiotensin-converting enzyme inhibitor (lisinopril). Methods: A subgroup analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind hypertension treatment trial of 42 4.18 participants. We defined MetS as hypertension plus at least 2 of the following: fasting serum glucose level of at least 100 mg/dL, body mass index (calculated as weight in kilograms divided by height in meters squared) of at least 30, fasting triglyceride levels of at least 150 mg/dL, and high-density lipoprotein cholesterol levels of less than 40 mg/dL in men or less than 50 mg/dL in women. Results: Significantly higher rates of heart failure were consistent across all treatment comparisons those with MetS. Relative risks (RRs) were 1.50 (95% confidence interval, 1.1.8-1.90), 1.49 (1.17-1.90), and 1.88 (1.42-2.47) in black participants and 1.25 (1.06-1.47), 1.20 (1.01-1.41), and 1.82 (1.51-2.19) in nonblack participants for amlodipine, lisinopril, and doxazosin comparisons with chlorthalidone, respectively. Higher rates for combined cardiovascular disease were observed with lisinopril-chlorthalidone (RRs, 1.24 [1.09-1.40] and 1.10 [1.02-1.19], respectively) and doxazosin-chlorthalidone comparisons (RRs, 1.37 [1.19-1.58] and 1.18 [1.081.30], respectively) in black and nonblack participants with MetS. Higher rates of stroke were seen in black participants only (RR, 1.37 [1.07-1.76] for the lisinopril-chlorthalidone comparison, and RR, 1.49 [1.09-2.03] for the doxazosin-chlorthalidone comparison). Black patients with MetS a] so had higher rates of end-stage renal disease (RR, 1.70 [1.13-2.55]) with lisinopril compared with chlorthalidone. Conclusions: The ALLHAT findings fail to support the preference for calcium channel blockers, alpha-blockers, or angiotensin-converting enzyme inhibitors compared with thiazide-type diuretics in patients with the MetS, despite their more favorable metabolic profiles. This was particularly true for black participants. C1 [Pressel, Sara; Bairnbridge, Charles; Davis, Barry R.] Univ Texas Houston, Hlth Sci Ctr, Sch Publ Hlth, Coordnating Ctr Clin Trials, Houston, TX 77030 USA. [Wright, Jackson T.] Case Western Reserve Univ, Dept Med, Gen Clin Res Ctr, Cleveland, OH 44106 USA. [Harris-Haywood, Sonja] Case Western Reserve Univ, Dept Family Med, Cleveland, OH 44106 USA. [Barzilay, Joshua] Kaiser Permanente, Tucker, GA USA. [Bareis, Charles J.] MacNeal Ctr Clin Res, Dept Med, Berwyn, IL USA. [Basile, Jan N.] Med Univ S Carolina, Charleston, SC 29425 USA. [Basile, Jan N.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Black, Henry R.] NYU, Dept Internal Med, Cardiol Sect, New York, NY USA. [Dart, Richard] Marshfield Clin Fdn Med Res & Educ, Dept Nephrol, Marshfield, WI USA. [Gupta, Alok K.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Hamilton, Bruce P.] Vet Affairs Med Ctr, Endocrine Hypertens Unit, Baltimore, MD USA. [Einhorn, Paula T.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Haywood, L. Julian] Univ So Calif, Div Cardiovasc Med, Los Angeles, CA USA. [Jafri, Syed Z. A.] Vet Affairs Med Ctr, Dept Cardiol, Fargo, ND USA. [Louis, Gail T.] Tulane Univ, Hlth Sci Ctr, New Orleans, LA USA. [Whelton, Paul K.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Sinnnons, Debra L.] Univ Arkansas Med Sci, Dept Endocrinol, Little Rock, AR 72205 USA. [Stanford, Carol] Univ Missouri, Sch Med, Kansas City, MO USA. RP Pressel, S (reprint author), Univ Texas Houston, Hlth Sci Ctr, Sch Publ Hlth, Coordnating Ctr Clin Trials, 1200 Herman Pressel St,Ste E801, Houston, TX 77030 USA. EM Sara.L.Pressel@uth.tmc.edu FU NHLBI NIH HHS [N01 HC035130, N01HC35130, N01-HC-35130]; NIMHD NIH HHS [P60 MD002265] NR 35 TC 54 Z9 54 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JAN 28 PY 2008 VL 168 IS 2 BP 207 EP 217 DI 10.1001/archinternmed.2007.66 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 254NR UT WOS:000252593800016 PM 18227370 ER PT J AU Gluderer, S Oldham, S Rintelen, F Sulzer, A Schutt, C Wu, XD Raftery, LA Hafen, E Stocker, H AF Gluderer, Silvia Oldham, Sean Rintelen, Felix Sulzer, Andrea Schuett, Corina Wu, Xiaodong Raftery, Laurel A. Hafen, Ernst Stocker, Hugo TI Bunched, the Drosophila homolog of the mammalian tumor suppressor TSC-22, promotes cellular growth SO BMC DEVELOPMENTAL BIOLOGY LA English DT Article ID BETA-STIMULATED CLONE-22; GLAND CANCER-CELL; ACTIVATED-RECEPTOR-GAMMA; LEUCINE-ZIPPER PROTEIN; GENE-EXPRESSION; DIFFERENTIAL DISPLAY; TRANSCRIPTION FACTOR; ADULT DROSOPHILA; R7 PHOTORECEPTOR; PROSTATE-CANCER AB Background: Transforming Growth Factor-beta 1 stimulated clone-22 (TSC-22) is assumed to act as a negative growth regulator and tumor suppressor. TSC-22 belongs to a family of putative transcription factors encoded by four distinct loci in mammals. Possible redundancy among the members of the TSC-22/Dip/Bun protein family complicates a genetic analysis. In Drosophila, all proteins homologous to the TSC-22/Dip/Bun family members are derived from a single locus called bunched (bun). Results: We have identified bun in an unbiased genetic screen for growth regulators in Drosophila. Rather unexpectedly, bun mutations result in a growth deficit. Under standard conditions, only the long protein isoform BunA - but not the short isoforms BunB and BunC - is essential and affects growth. Whereas reducing bunA function diminishes cell number and cell size, overexpression of the short isoforms BunB and BunC antagonizes bunA function. Conclusion: Our findings establish a growth-promoting function of Drosophila BunA. Since the published studies on mammalian systems have largely neglected the long TSC-22 protein version, we hypothesize that the long TSC-22 protein is a functional homolog of BunA in growth regulation, and that it is antagonized by the short TSC-22 protein. C1 [Gluderer, Silvia; Hafen, Ernst; Stocker, Hugo] Swiss Fed Inst Technol, Inst Mol Syst Biol, CH-8093 Zurich, Switzerland. [Oldham, Sean; Rintelen, Felix; Sulzer, Andrea] Univ Zurich, Inst Zool, CH-8057 Zurich, Switzerland. [Schuett, Corina] Genet Co Inc, CH-8952 Schlieren, Switzerland. [Wu, Xiaodong; Raftery, Laurel A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. [Oldham, Sean] Burnham Inst Med Res, La Jolla, CA 92037 USA. [Rintelen, Felix] PFC Pharma Focus AG, CH-8604 Volketswil, Switzerland. RP Stocker, H (reprint author), Swiss Fed Inst Technol, Inst Mol Syst Biol, Wolfgang Pauli Str 16, CH-8093 Zurich, Switzerland. EM gluderer@imsb.biol.ethz.ch; soldham@burnham.org; felixrintelen@gmail.com; suan@irm.uzh.ch; corina.schuett@sl.ethz.ch; xwu3@partners.org; lraftery1@partners.org; hafen@imsb.biol.ethz.ch; stocker@imsb.biol.ethz.ch RI Raftery, Laurel/H-1406-2012 OI Raftery, Laurel/0000-0003-4797-4163 FU NIGMS NIH HHS [R01 GM060501] NR 66 TC 15 Z9 17 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-213X J9 BMC DEV BIOL JI BMC Dev. Biol. PD JAN 28 PY 2008 VL 8 AR 10 DI 10.1186/1471-213X-8-10 PG 12 WC Developmental Biology SC Developmental Biology GA 265XV UT WOS:000253396100001 PM 18226226 ER PT J AU Okumi, M Fishbein, JM Griesemer, AD Gianello, PR Hirakata, A Nobori, S Moran, S Samelson-Jones, E Shimizu, A Sachs, DH Yamada, K AF Okumi, Masayoshi Fishbein, Jonathan M. Griesemer, Adam D. Gianello, Pierre R. Hirakata, Atsushi Nobori, Shuji Moran, Shannon Samelson-Jones, Emma Shimizu, Akira Sachs, David H. Yamada, Kazuhiko TI Role of persistence of antigen and indirect recognition in the maintenance of tolerance to renal allografts SO TRANSPLANTATION LA English DT Article DE tolerance; kidney transplantation; miniature swine; indirect pathway ID MAJOR HISTOCOMPATIBILITY COMPLEX; MINIATURE SWINE; CLASS-I; TRANSPLANTATION TOLERANCE; STABLE INDUCTION; REGULATORY CELLS; T-CELLS; THYMUS; CYCLOSPORINE; LYMPHOCYTES AB Background. We have previously shown that a 12-day treatment with cyclosporine A (CyA) facilitates induction of tolerance to class-I disparate kidneys, as demonstrated by acceptance of second, donor-matched kidneys without immunosuppression. In the present study, we have examined 1) the duration of tolerance in the absence of donor antigen and 2) the pathway of antigen recognition determining maintenance or loss of tolerance. Methods. Seventeen miniature swine received class-I mismatched kidneys with 12 days of CyA, and received second donor-matched kidneys without immunosuppression at 0, 1, 3, or 4 months after nephrectomy of the primary graft. Five were sensitized 6 weeks after nephrectomy of the primary graft, three with donor-matched skin grafts, and two with donor class-I peptides to eliminate direct pathway involvement. In addition, two long-term tolerant animals received class-I-c peptides. Results. Rejection of second grafts required at least a 3 month absence of donor antigen. Although donor-matched skin grafts in animals tolerant to kidneys induced antidonor cytotoxic T lymphocyte responses, second renal transplants revealed no evidence of sensitization. In contrast, immunization of recipients with donor class-I peptides after nephrectomy of the primary graft led to loss of tolerance at both T-cell and B-cell levels, as evidenced by rejection of the second graft in 5 days and development of antidonor immunoglobulin G. Peptide immunization of long-term tolerant in recipients bearing long-term renal grafts did not break tolerance. Conclusions. These data indicate that the renal allograft is required for the indefinite maintenance of tolerance, that indirect antigen presentation is capable of breaking tolerance, and that in tolerant animals, direct antigen presentation may suppress rejection, allowing tolerance to persist. C1 [Yamada, Kazuhiko] Massachusetts Gen Hosp, Transplantat Biol Ctr, Organ Transplantat Tolerance & Xenotransplantat L, Boston, MA 02129 USA. [Okumi, Masayoshi; Fishbein, Jonathan M.; Griesemer, Adam D.; Gianello, Pierre R.; Hirakata, Atsushi; Nobori, Shuji; Moran, Shannon; Samelson-Jones, Emma; Shimizu, Akira; Sachs, David H.; Yamada, Kazuhiko] Massachusetts Gen Hosp, Harvard Med Sch, Transplanatat Biol Res Ctr, Boston, MA 02129 USA. RP Yamada, K (reprint author), Massachusetts Gen Hosp, Transplantat Biol Ctr, Organ Transplantat Tolerance & Xenotransplantat L, Bldg 149-9019,13th St, Boston, MA 02129 USA. EM kaz.yamada@tbrc.mgh.harvard.edu FU NIAID NIH HHS [R37 AI031046, R37 AI031046-16, R37 AI31046-16] NR 26 TC 19 Z9 19 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 JAN 27 PY 2008 VL 85 IS 2 BP 270 EP 280 DI 10.1097/TP.0b013e31815e8eed PG 11 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 255JK UT WOS:000252654100016 PM 18212633 ER PT J AU Koplan, KE David, SP Rigotti, NA AF Koplan, Kate E. David, Sean P. Rigotti, Nancy A. TI 10-minute consultation - Smoking cessation SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material C1 [Koplan, Kate E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 01225 USA. [David, Sean P.] Brown Univ, Ctr Primary Care & Prevent, Brown Med Sch, Providence, RI 02912 USA. [Rigotti, Nancy A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Koplan, KE (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 01225 USA. EM kkoplan@partners.org OI David, Sean/0000-0002-4922-2603 NR 0 TC 1 Z9 1 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8146 J9 BRIT MED J JI Br. Med. J. PD JAN 26 PY 2008 VL 336 IS 7637 BP 217 EP 217 DI 10.1136/bmj.39248.531748.47 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 259KT UT WOS:000252938900048 PM 18219045 ER PT J AU LaBresh, KA Reeves, MJ Frankel, MR Albright, D Schwamm, LH AF LaBresh, Kenneth A. Reeves, Mathew J. Frankel, Michael R. Albright, Dawn Schwamm, Lee H. TI Hospital treatment of patients with ischemic stroke or transient ischemic attack using the "get with the guidelines" program SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID OF-NEUROLOGY AFFIRMS; MEDICARE BENEFICIARIES; CARE; ASSOCIATION; PREVENTION; COUNCIL; QUALITY; MANAGEMENT; STATEMENT; OUTCOMES AB Background: Adherence to evidence-based interventions for hospitalized patients who have experienced a stroke is suboptimal. We examined the association of process improvement and Internet-based data collection and decision support with stroke care. Methods: A 1-year intervention study to assess performance measure adherence in hospitals using the "Get With The Guidelines-Stroke" program. The program included 18 410 patients with ischemic stroke or transient ischemic attack admitted to 99 volunteer community and teaching hospitals. Data from eligible patients in the preintervention baseline period were compared with data from 4 subsequent quarters for 12 acute care or secondary prevention measures and an all-or-none measure of care based on 7 prespecified measures. Results: Significant improvements from baseline to the fourth quarter were seen in 11 of 13 measures: use of thrombolytic medications for patients with ischemic stroke presenting within 2 hours,of onset, 23.5% vs 40.8% (P<.001); early use of antithrombotic medications, 88.2% vs 95.2% (P<.0011); antithrombotic medications prescribed at discharge, 91.0% vs 97.9% (P<.001); anticoagulation agents for atrial fibrillation, 81.4% vs 96.5% (P<.001); smoking cessation counseling, 38.3% vs 54.5% (P <.001); lipid treatment for low-density lipoprotein levels 100 mg/dL or greater, 58.7% vs 77.0% (P <.001); diabetes mellitus treatment, 48.5% vs 83.5% (P=.001); and weight reduction counseling 32.5% vs 43.4% (P<.001). The all-or-none measure increased from 50.2% to 58.0% (P<.001). Complications from thrombolytic medications and prophylaxis for deep venous thrombosis did not change. Conclusion: Statistically and clinically significant improvement in I I of 13 quality improvement measures for the treatment of patients hospitalized for cerebrovascular disease was seen in hospitals participating in the Get With The Guidelines program. C1 [LaBresh, Kenneth A.; Albright, Dawn] Masspro, Waltham, MA 02451 USA. [Reeves, Mathew J.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Frankel, Michael R.] Emory Univ, Sch Med, Atlanta, GA USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. RP LaBresh, KA (reprint author), Masspro, 245 Winter St, Waltham, MA 02451 USA. EM klabresh@masspro.org RI LaBresh, Kenneth/A-6995-2017; OI LaBresh, Kenneth/0000-0001-9040-1956; Schwamm, Lee/0000-0003-0592-9145 NR 26 TC 106 Z9 110 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 JAN 25 PY 2008 VL 168 IS 4 BP 411 EP 417 DI 10.1001/archinternmed.2007.101 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 265PY UT WOS:000253374600012 PM 18299497 ER PT J AU Sanders, MA Verhaak, RG Mc Geertsma-Kleinekoort, W Abbas, S Horsman, S van der Spek, PJ Lowenberg, B Valk, PJ AF Sanders, Mathijs A. Verhaak, Roel G. W. Mc Geertsma-Kleinekoort, Wendy Abbas, Saman Horsman, Sebastiaan van der Spek, Peter J. Lowenberg, Bob Valk, Peter J. M. TI SNPExpress: integrated visualization of genome-wide genotypes, copy numbers and gene expression levels SO BMC GENOMICS LA English DT Article ID ACUTE MYELOID-LEUKEMIA; LOSS-OF-HETEROZYGOSITY; NUCLEOTIDE POLYMORPHISM ANALYSIS; AFFYMETRIX SNP ARRAYS; UNIPARENTAL DISOMY; CANCER; PHENOTYPES; ALGORITHM; MODEL AB Background: Accurate analyses of comprehensive genome-wide SNP genotyping and gene expression data sets is challenging for many researchers. In fact, obtaining an integrated view of both large scale SNP genotyping and gene expression is currently complicated since only a limited number of appropriate software tools are available. Results: We present SNPExpress, a software tool to accurately analyze Affymetrix and Illumina SNP genotype calls, copy numbers, polymorphic copy number variations (CNVs) and Affymetrix gene expression in a combinatorial and efficient way. In addition, SNPExpress allows concurrent interpretation of these items with Hidden-Markov Model (HMM) inferred Loss-of-Heterozygosity (LOH)-and copy number regions. Conclusion: The combined analyses with the easily accessible software tool SNPExpress will not only facilitate the recognition of recurrent genetic lesions, but also the identification of critical pathogenic genes. C1 [Sanders, Mathijs A.; Verhaak, Roel G. W.; Mc Geertsma-Kleinekoort, Wendy; Abbas, Saman; Lowenberg, Bob; Valk, Peter J. M.] Erasmus Univ, Med Ctr, Dept Hematol, Rotterdam, Netherlands. [Verhaak, Roel G. W.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA USA. [Verhaak, Roel G. W.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Horsman, Sebastiaan; van der Spek, Peter J.] Erasmus Univ, Med Ctr, Dept Bioinformat, Rotterdam, Netherlands. RP Valk, PJ (reprint author), Erasmus Univ, Med Ctr, Dept Hematol, Rotterdam, Netherlands. EM m.sanders@erasmusmc.nl; verhaak@broad.mit.edu; w.geertsma-kleinekoort@erasmusmc.nl; s.abbas@erasmusmc.nl; s.horsman@erasmusmc.nl; p.vanderspek@erasmusmc.nl; b.lowenberg@erasmusmc.nl; p.valk@erasmusmc.nl RI Abbas, Saman/L-1981-2013 NR 34 TC 9 Z9 9 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD JAN 25 PY 2008 VL 9 AR 41 DI 10.1186/1471-2164-9-41 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 262KW UT WOS:000253148400001 PM 18221515 ER PT J AU Adams, EW Ratner, DM Seeberger, PH Hacohen, N AF Adams, Eddie W. Ratner, Daniel M. Seeberger, Peter H. Hacohen, Nir TI Carbohydrate-mediated targeting of antigen to dendritic cells leads to enhanced presentation of antigen to T cells SO CHEMBIOCHEM LA English DT Article DE carbohydrates; dendritic cells; glycoconjugates; targeting; tolerance ID C-TYPE LECTIN; MANNOSE RECEPTOR; CLASS-II; IN-VIVO; DC-SIGN; COMPLEX; OLIGOSACCHARIDES; RECOGNITION; MACROPHAGES; LIGANDS AB The unique therapeutic value of dendritic cells (DCs) for the treatment of allergy, autoimmunity and transplant rejection is predicated upon our ability to selectively deliver antigens, drugs or nucleic acids to DCs in vivo. Here we describe a method for delivering whole protein antigens to DCs based on carbohydrate-mediated targeting of DC-expressed lectins. A series of synthetic carbohydrates was chemically-coupled to a model antigen, I ovalbumin (OVA), and each conjugate was evaluated for its ability to increase the efficiency of antigen presentation by murine I DCs to OVA-specific T cells (CD4(+) and CD8(+)). In vitro data ore presented that demonstrate that carbohydrate modification of OVA leads to a 50-fold enhancement of presentation of antigenic peptide to CD4(+) T cells. A tenfold enhancement is observed for CD8(+) T cells; this indicates that the targeted lectin(s) can mediate cross-presentation of antigens on MHC class I. Our data indicate that the observed enhancements in antigen presentation are unique to OVA that is conjugated to complex oligosaccharides, such as a high-mannose nonasaccharide, but not to monosaccharides. Taken together, our data suggest that a DC targeting strategy that is based upon carbohydrate-lectin interactions is a promising approach for enhancing antigen presentation via class I and class II molecules. C1 [Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Adams, Eddie W.; Ratner, Daniel M.; Seeberger, Peter H.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Ratner, Daniel M.] Boston Med Ctr, Infect Dis Sect, Boston, MA 02118 USA. [Seeberger, Peter H.] ETH, Organ Chem Lab, CH-8093 Zurich, Switzerland. RP Hacohen, N (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NIAID NIH HHS [R21 AI063081, R21 AI063081-02, AI063 081, R21 AI063081-01] NR 30 TC 44 Z9 45 U1 0 U2 13 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 JAN 25 PY 2008 VL 9 IS 2 BP 294 EP 303 DI 10.1002/cbic.200700310 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 258PO UT WOS:000252880000017 PM 18186095 ER PT J AU Lee, MH El-Shewy, HM Luttrell, DK Luttrell, LM AF Lee, Mi-Hye El-Shewy, Hesham M. Luttrell, Deirdre K. Luttrell, Louis M. TI Role of beta-arrestin-mediated desensitization and signaling in the control of angiotensin AT1a receptor-stimulated transcription SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; NUCLEAR EXPORT SIGNAL; REGULATED KINASES; ERK1/2 ACTIVATION; EGF RECEPTOR; BETA-ARRESTIN-2; ENDOCYTOSIS; PATHWAYS; MAPK; PHOSPHORYLATION AB Heptahelical G protein-coupled receptors employ several mechanisms to activate the ERK1/2 cascade and control gene transcription. Previous work with the angiotensin AT1a receptor has shown that G(q/11) activation leads to a rapid and transient rise in ERK1/2 activity, whereas beta-arrestin binding supports sustained ERK1/2 activation by scaffolding a Raf center dot MEK center dot ERK complex associated with the internalized receptor. In this study, we compared the role of the two beta-arrestin isoforms in AT1a receptor desensitization, ERK1/2 activation and transcription using selective RNA interference. In HEK293 cells, both the native AT1a receptor and a G protein-coupling deficient DRY/AAY mutant recruited beta-arrestin1 and beta-arrestin2 upon angiotensin binding and internalized with the receptor. In contrast, only beta-arrestin2 supported protein kinase C-independent ERK1/2 activation by both the AT1a and DRY/AAY receptors. Using focused gene expression filter arrays to screen for endogenous transcriptional responses, we found that silencing beta-arrestin1 or beta-arrestin2 individually did not alter the response pattern but that silencing both caused a marked increase in the number of transcripts that were significantly up-regulated in response to AT1a receptor activation. The DRY/AAY receptor failed to elicit any detectable transcriptional response despite its ability to stimulate beta-arrestin2- dependent ERK1/2 activation. These results indicate that the transcriptional response to AT1a receptor activation primarily reflects heterotrimeric G protein activation. Although beta-arrestin1 and beta-arrestin2 are functionally specialized with respect to supporting G protein-independent ERK1/2 activation, their common effect is to dampen the transcriptional response by promoting receptor desensitization. C1 [Lee, Mi-Hye; El-Shewy, Hesham M.; Luttrell, Deirdre K.; Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. [Lee, Mi-Hye; El-Shewy, Hesham M.; Luttrell, Deirdre K.; Luttrell, Louis M.] Med Univ S Carolina, Dept Biochem, Charleston, SC 29425 USA. [Lee, Mi-Hye; El-Shewy, Hesham M.; Luttrell, Deirdre K.; Luttrell, Louis M.] Med Univ S Carolina, Dept Mol Biol, Charleston, SC 29425 USA. [Lee, Mi-Hye; El-Shewy, Hesham M.; Luttrell, Deirdre K.; Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29401 USA. RP Luttrell, LM (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, 96 Jonathan Lucas St, Charleston, SC 29425 USA. EM luttrell@musc.edu FU NIDDK NIH HHS [DK55524] NR 49 TC 43 Z9 47 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 JAN 25 PY 2008 VL 283 IS 4 BP 2088 EP 2097 DI 10.1074/jbc.M706892200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 253EH UT WOS:000252501000036 PM 18006496 ER PT J AU Vagin, O Tokhtaeva, E Yakubov, I Shevchenko, E Sachs, G AF Vagin, Olga Tokhtaeva, Elmira Yakubov, Iskandar Shevchenko, Eugenia Sachs, George TI Inverse correlation between the extent of N-glycan branching and intercellular adhesion in epithelia - Contribution of the Na,K-ATPase beta(1) subunit SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SEPTATE JUNCTION FUNCTION; TUBE-SIZE CONTROL; ACETYLGLUCOSAMINYLTRANSFERASE-V; CELL-ADHESION; PARACELLULAR TRANSPORT; ADHERENS JUNCTIONS; NA+/K+ ATPASE; EXPRESSION; CADHERIN; COMPLEX AB The majority of cell adhesion molecules are N-glycosylated, but the role of N-glycans in intercellular adhesion in epithelia remains ill-defined. Reducing N-glycan branching of cellular glycoproteins by swainsonine, the inhibitor of N-glycan processing, tightens and stabilizes cell-cell junctions as detected by a 3-fold decrease in the paracellular permeability and a 2-3-fold increase in the resistance of the adherens junction proteins to extraction by non-ionic detergent. In addition, exposure of cells to swainsonine inhibits motility of MDCK cells. Mutagenic removal of N-glycosylation sites from the Na,K-ATPase beta(1) subunit impairs cell-cell adhesion and decreases the effect of swainsonine on the paracellular permeability of the cell monolayer and also on detergent resistance of adherens junction proteins, indicating that the extent of N-glycan branching of this subunit is important for intercellular adhesion. The N-glycans of the Na,K-ATPase beta(1) subunit and E-cadherin are less complex in tight renal epithelia than in the leakier intestinal epithelium. The complexity of the N-glycans linked to these proteins gradually decreases upon the formation of a tight monolayer from dispersed MDCK cells. This correlates with a cell-cell adhesion-induced increase in expression of GnT-III (stops N-glycan branching) and a decrease in expression of GnTs IVC and V (promote N-glycan branching) as detected by real-time quantitative PCR. Consistent with these results, partial silencing of the gene encoding GnT-III increases branching of N-glycans linked to the Na,K-ATPase beta(1) subunit and other glycoproteins and results in a 2-fold increase in the paracellular permeability of MDCK cell monolayers. These results suggest epithelial cells can regulate tightness of cell junctions via remodeling of N-glycans, including those linked to the Na,K-ATPase beta(1)-subunit. C1 [Vagin, Olga; Tokhtaeva, Elmira; Yakubov, Iskandar; Shevchenko, Eugenia; Sachs, George] Vet Adm Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. [Vagin, Olga; Tokhtaeva, Elmira; Yakubov, Iskandar; Shevchenko, Eugenia; Sachs, George] Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90073 USA. RP Vagin, O (reprint author), VAGLAHS W LA, 11301 Wilshire Blvd,Rm 324,Bldg 113, Los Angeles, CA 90073 USA. EM olgav@ucla.edu FU NIDDK NIH HHS [R01 DK046917-09S2, DK077149, DK46917, DK58333, R01 DK046917, R01 DK053642, R01 DK053642-10, R01 DK058333, R01 DK058333-09, R01 DK077149, R01 DK077149-01A1, R01 DK077149-02, R56 DK058333]; PHS HHS [D53642] NR 42 TC 57 Z9 57 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 JAN 25 PY 2008 VL 283 IS 4 BP 2192 EP 2202 DI 10.1074/jbc.M704713200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 253EH UT WOS:000252501000047 PM 18025087 ER PT J AU Habib, SL Simone, S Barnes, JJ Abboud, HE AF Habib, Samy L. Simone, Simona Barnes, Jeff J. Abboud, Hanna E. TI Tuberin haploinsufficiency is associated with the loss of OGG1 in rat kidney tumors SO MOLECULAR CANCER LA English DT Article ID OXIDATIVE DNA-DAMAGE; RENAL-CELL CARCINOMA; FPG PROTEIN; EKER RAT; REPAIR; GENE; EXPRESSION; MUTATIONS; 8-HYDROXYGUANINE; GLYCOSYLASE AB Background: Tuberous sclerosis complex (TSC) is caused by defects in one of two tumor suppressor genes, TSC-1 or TSC-2. TSC-2 gene encodes tuberin, a protein involved in the pathogenesis of kidney tumors. Loss of heterozygosity (LOH) at the TSC2 locus has been detected in TSC-associated renal cell carcinoma (RCC) and in RCC in the Eker rat. Tuberin downregulates the DNA repair enzyme 8-oxoguanine DNA-glycosylase (OGG1) with important functional consequences, compromising the ability of cells to repair damaged DNA resulting in the accumulation of the mutagenic oxidized DNA, 8-oxo-dG. Loss of function mutations of OGG1 also occurs in human kidney clear cell carcinoma and may contribute to tumorgenesis. We investigated the distribution of protein expression and the activity of OGG1 and 8-oxo-dG and correlated it with the expression of tuberin in kidneys of wild type and Eker rats and tumor from Eker rat. Results: Tuberin expression, OGG1 protein expression and activity were higher in kidney cortex than in medulla or papilla in both wild type and Eker rats. On the other hand, 8-oxo-dG levels were highest in the medulla, which expressed the lowest levels of OGG1. The basal levels of 8-oxo-dG were also higher in both cortex and medulla of Eker rats compared to wild type rats. In kidney tumors from Eker rats, the loss of the second TSC2 allele is associated with loss of OGG1 expression. Immunostaining of kidney tissue shows localization of tuberin and OGG1 mainly in the cortex. Conclusion: These results demonstrate that OGG1 localizes with tuberin preferentially in kidney cortex. Loss of tuberin is accompanied by the loss of OGG1 contributing to tumorgenesis. In addition, the predominant expression of OGG1 in the cortex and its decreased expression and activity in the Eker rat may account for the predominant cortical localization of renal cell carcinoma. C1 [Habib, Samy L.; Simone, Simona] Univ Texas Hlth Sci Ctr San Antonio, OBrien Kidney Res Ctr, Dept Med, San Antonio, TX 78229 USA. [Habib, Samy L.; Barnes, Jeff J.; Abboud, Hanna E.] S Texas Vet Healthcare Syst, San Antonio, TX 78229 USA. [Simone, Simona] Univ Bari, Dept Emergency Transplantat, Bari, Italy. [Habib, Samy L.; Barnes, Jeff J.; Abboud, Hanna E.] Ctr Clin, San Antonio, TX 78229 USA. RP Habib, SL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, OBrien Kidney Res Ctr, Dept Med, San Antonio, TX 78229 USA. EM habib@uthscsa.edu; simones@uthscsa.edu; barnes@uthscsa.edu; abboud@uthscsa.edu FU NIDDK NIH HHS [P50 DK061597, R37 DK33665] NR 26 TC 12 Z9 12 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-4598 J9 MOL CANCER JI Mol. Cancer PD JAN 24 PY 2008 VL 7 AR 10 DI 10.1186/1476-4598-7-10 PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 272LX UT WOS:000253862000001 PM 18218111 ER PT J AU Fuerst, PG Koizumi, A Masland, RH Burgess, RW AF Fuerst, Peter G. Koizumi, Amane Masland, Richard H. Burgess, Robert W. TI Neurite arborization and mosaic spacing in the mouse retina require DSCAM SO NATURE LA English DT Article ID CELL-ADHESION MOLECULE; HOMOPHILIC INTERCELLULAR-ADHESION; AXON GUIDANCE; DROSOPHILA DSCAM; SELF-AVOIDANCE; DIVERSITY; NEURONS; SPECIFICITY; BINDING; SYSTEM AB To establish functional circuitry, retinal neurons occupy spatial domains by arborizing their processes, which requires the self-avoidance of neurites from an individual cell, and by spacing their cell bodies, which requires positioning the soma and establishing a zone within which other cells of the same type are excluded(1). The mosaic patterns of distinct cell types form independently and overlap. The cues that direct these processes in the vertebrate retina are not known(2,3). Here we show that some types of retinal amacrine cells from mice with a spontaneous mutation in Down syndrome cell adhesion molecule ( Dscam), a gene encoding an immunoglobulin- superfamily member adhesion molecule(4,5), have defects in the arborization of processes and in the spacing of cell bodies. In the mutant retina, cells that would normally express Dscam have hyperfasciculated processes, preventing them from creating an orderly arbor. Also, their cell bodies are randomly distributed or pulled into clumps rather than being regularly spaced mosaics. Our results indicate that mouse DSCAM mediates isoneuronal self- avoidance for arborization and heteroneuronal self- avoidance within specific cell types to prevent fasciculation and to preserve mosaic spacing. These functions are analogous to those of Drosophila DSCAM ( ref. 6) and DSCAM2 ( ref. 7). DSCAM may function similarly in other regions of the mammalian nervous system, and this role may extend to other members of the mammalian Dscam gene family. C1 [Fuerst, Peter G.; Burgess, Robert W.] Jackson Lab, Bar Harbor, ME 04609 USA. [Koizumi, Amane; Masland, Richard H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Burgess, RW (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. EM robert.burgess@jax.org RI Koizumi, Amane/E-7771-2011; OI Burgess, Robert/0000-0002-9229-3407 FU NEI NIH HHS [F32 EY015966, R03 EY016031, F32 EY015966-02, R03 EY016031-03] NR 28 TC 153 Z9 155 U1 0 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 24 PY 2008 VL 451 IS 7177 BP 470 EP U8 DI 10.1038/nature06514 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 253YS UT WOS:000252554100046 PM 18216855 ER PT J AU Lai, T Jabaudon, D Molyneaux, BJ Azim, E Arlotta, P Menezes, JRL Macklis, JD AF Lai, Tina Jabaudon, Denis Molyneaux, Bradley J. Azim, Eiman Arlotta, Paola Menezes, Joao R. L. Macklis, Jeffrey D. TI SOX5 controls the sequential generation of distinct corticofugal neuron subtypes SO NEURON LA English DT Article ID CEREBRAL CORTICAL DEVELOPMENT; CALRETININ-IMMUNOREACTIVITY; TRANSCRIPTION FACTORS; SUBCORTICAL TARGETS; AXONAL PROJECTIONS; LAYER NEURONS; CORTEX; NEOCORTEX; CELL; DIFFERENTIATION AB The molecular mechanisms controlling the development of distinct subtypes of neocortical projection neurons, and CNS neuronal diversity more broadly, are only now emerging. We report that the transcription factor SOX5 controls the sequential generation of distinct corticofugal neuron subtypes by preventing premature emergence of normally later-born corticofugal neurons. SOX5 loss-of-function causes striking overlap of the identities of the three principal sequentially born corticofugal neuron subtypes: subplate neurons, corticothalamic neurons, and subcerebral projection neurons. In Sox5(-/-) cortex, subplate neurons aberrantly develop molecular hallmarks and connectivity of subcerebral projection neurons; corticothalamic neurons are imprecisely differentiated, while differentiation of subcerebral projection neurons is accelerated. Gain-of-function analysis reinforces the critical role of SOX5 in controlling the sequential generation of corticofugal neurons-SOX5 overexpression at late stages of corticogenesis causes re-emergence of neurons with corticofugal features. These data indicate that SOX5 controls the timing of critical fate decisions during corticofugal neuron production and thus subtype-specific differentiation and neocortical neuron diversity. C1 [Lai, Tina; Jabaudon, Denis; Molyneaux, Bradley J.; Azim, Eiman; Arlotta, Paola; Menezes, Joao R. L.; Macklis, Jeffrey D.] Harvard Univ, Sch Med, MGH HMS Ctr Nervous Syst Repair, Dept Neurosurg,Program Neurosci, Cambridge, MA 02138 USA. [Lai, Tina; Jabaudon, Denis; Molyneaux, Bradley J.; Azim, Eiman; Arlotta, Paola; Menezes, Joao R. L.; Macklis, Jeffrey D.] Harvard Univ, Sch Med, MGH HMS Ctr Nervous Syst Repair, Dept Neurol,Program Neurosci, Boston, MA 02114 USA. [Lai, Tina; Jabaudon, Denis; Molyneaux, Bradley J.; Azim, Eiman; Arlotta, Paola; Menezes, Joao R. L.; Macklis, Jeffrey D.] Massachusetts Gen Hosp, Nayef Al Rodhan Labs, Boston, MA 02114 USA. [Lai, Tina; Jabaudon, Denis; Molyneaux, Bradley J.; Azim, Eiman; Arlotta, Paola; Menezes, Joao R. L.; Macklis, Jeffrey D.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Boston, MA 02114 USA. [Lai, Tina; Jabaudon, Denis; Molyneaux, Bradley J.; Azim, Eiman; Arlotta, Paola; Menezes, Joao R. L.; Macklis, Jeffrey D.] Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02114 USA. RP Macklis, JD (reprint author), Harvard Univ, Sch Med, MGH HMS Ctr Nervous Syst Repair, Dept Neurosurg,Program Neurosci, Cambridge, MA 02138 USA. EM jeffrey_macklis@hms.harvard.edu RI Menezes, Joao/D-5668-2012; PCM, PG/D-1034-2013; OI Azim, Eiman/0000-0002-1015-1772; Molyneaux, Bradley/0000-0002-3377-1229; Jabaudon, Denis/0000-0003-2438-4769 FU NINDS NIH HHS [T32 NS22215, NS49553, NS45523] NR 51 TC 149 Z9 151 U1 2 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD JAN 24 PY 2008 VL 57 IS 2 BP 232 EP 247 DI 10.1016/j.neuron.2007.12.023 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 256VQ UT WOS:000252758400008 PM 18215621 ER PT J AU Levine, JB Leeder, AD Parekkadan, B Berdichevsky, Y Rauch, SL Smoller, JW Konradi, C Berthialime, F Yarmush, ML AF Levine, J. B. Leeder, A. D. Parekkadan, B. Berdichevsky, Y. Rauch, S. L. Smoller, J. W. Konradi, C. Berthialime, F. Yarmush, M. L. TI Isolation rearing impairs wound healing and is associated with increased locomotion and decreased immediate early gene expression in the medial prefrontal cortex of juvenile rats SO NEUROSCIENCE LA English DT Article DE immediate early gene; isolation rearing; wound healing; burn injury; childhood adversity; gene expression ID LONG-TERM DEPRESSION; INDUCED SICKNESS BEHAVIOR; SYNAPTIC PLASTICITY; ANXIETY DISORDERS; PYRAMIDAL NEURONS; SOCIAL-ISOLATION; FEAR EXTINCTION; CEREBRAL-CORTEX; NEURAL ACTIVITY; REPEATED STRESS AB In addition to its maladaptive effects on psychiatric function, psychosocial deprivation impairs recovery from physical illness. Previously, we found that psychosocial deprivation, modeled by isolation rearing, depressed immediate early gene (IEG) expression in the medial prefrontal cortex (mPFC) and increased locomotion in the open field test [Levine JB, Youngs RM, et al. (2007) Isolation rearing and hyper-locomotion are associated with reduced immediate early gene expression levels in the medial prefrontal cortex. Neuroscience 145(1):42-55]. In the present study, we examined whether similar changes in behavior and gene expression are associated with the maladaptive effects of psychosocial deprivation on physical injury healing. After weaning, anesthetized rats were subjected to a 20% total body surface area third degree burn injury and were subsequently either group or isolation reared. After 4 weeks of either isolation or group rearing (a period that encompasses post-wearing and early adolescence), rats were killed, and their healing and gene expression in the mPFC were assessed. Locomotion in the open field test was examined at 3 weeks post-burn injury. We found that: 1) gross wound healing was significantly impaired in isolation-reared rats compared with group-reared rats, 2) locomotion was increased and IEG expression was suppressed for isolation-reared rats during burn injury healing, 3) the decreased activity in the open field and increased IEG expression was greater for burn injury healing group-reared rats than for uninjured group-reared rats, 4) the degree of hyperactivity and IEG suppression was relatively similar between isolation-reared rats during burn injury compared with uninjured isolation-reared rats. Thus, in the mPFC, behavioral hyperactivity to novelty (the open field test) along with IEG suppression may constitute a detectable biomarker of isolation rearing during traumatic physical injury. Implications of the findings for understanding, assessing, and treating the maladaptive effects of psychosocial deprivation on physical healing during childhood are discussed. C1 [Levine, J. B.; Leeder, A. D.; Berthialime, F.; Yarmush, M. L.] Shriners Burns Hosp Children, Boston, MA 02114 USA. [Levine, J. B.; Leeder, A. D.; Parekkadan, B.; Berdichevsky, Y.; Smoller, J. W.; Berthialime, F.; Yarmush, M. L.] Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. [Levine, J. B.; Leeder, A. D.; Parekkadan, B.; Berdichevsky, Y.; Berthialime, F.; Yarmush, M. L.] Massachusetts Gen Hosp, Ctr Engn & Med, Boston, MA 02114 USA. [Levine, J. B.; Rauch, S. L.; Smoller, J. W.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Berthialime, F.; Yarmush, M. L.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Rauch, S. L.] McLean Hosp, Belmont, MA 02478 USA. [Konradi, C.] Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37212 USA. RP Levine, JB (reprint author), Shriners Burns Hosp Children, Room 221,51 Blossom St, Boston, MA 02114 USA. EM jblevine@partners.org RI Levine, John/G-6221-2015 FU NIGMS NIH HHS [R01 GM065474]; NIMH NIH HHS [5T32MH016259, T32 MH016259] NR 80 TC 21 Z9 21 U1 1 U2 9 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 JAN 24 PY 2008 VL 151 IS 2 BP 589 EP 603 DI 10.1016/j.neuroscience.2007.10.014 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 255GB UT WOS:000252644600028 PM 18063315 ER PT J AU Kawai, T Cosimi, AB Spitzer, TR Tolkoff-Rubin, N Suthanthiran, M Saidman, SL Shaffer, J Preffer, FI Ding, RC Sharma, V Fishman, JA Dey, B Ko, DSC Hertl, M Goes, NB Wong, WC Williams, WW Colvin, RB Sykes, M Sachs, DH AF Kawai, Tatsuo Cosimi, A. Benedict Spitzer, Thomas R. Tolkoff-Rubin, Nina Suthanthiran, Manikkam Saidman, Susan L. Shaffer, Juanita Preffer, Frederic I. Ding, Ruchuang Sharma, Vijay Fishman, Jay A. Dey, Bimalangshu Ko, Dicken S. C. Hertl, Martin Goes, Nelson B. Wong, Waichi Williams, Winfred W., Jr. Colvin, Robert B. Sykes, Megan Sachs, David H. TI Brief report: HLA-mismatched renal transplantation without maintenance immunosuppression SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DONOR BONE-MARROW; ALLOGRAFT TOLERANCE; MIXED CHIMERISM; LYMPHOHEMATOPOIETIC CHIMERISM; CYNOMOLGUS MONKEYS; MULTIPLE-MYELOMA; BODY IRRADIATION; RECIPIENTS; INDUCTION; KIDNEY AB Five patients with end-stage renal disease received combined bone marrow and kidney transplants from HLA single-haplotype mismatched living related donors, with the use of a nonmyeloablative preparative regimen. Transient chimerism and reversible capillary leak syndrome developed in all recipients. Irreversible humoral rejection occurred in one patient. In the other four recipients, it was possible to discontinue all immunosuppressive therapy 9 to 14 months after the transplantation, and renal function has remained stable for 2.0 to 5.3 years since transplantation. The T cells from these four recipients, tested in vitro, showed donor-specific unresponsiveness and in specimens from allograft biopsies, obtained after withdrawal of immunosuppressive therapy, there were high levels of P3 (FOXP3) messenger RNA (mRNA) but not granzyme B mRNA. C1 [Kawai, Tatsuo; Cosimi, A. Benedict; Tolkoff-Rubin, Nina; Fishman, Jay A.; Ko, Dicken S. C.; Hertl, Martin; Goes, Nelson B.; Wong, Waichi; Williams, Winfred W., Jr.] Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. [Shaffer, Juanita; Sykes, Megan; Sachs, David H.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Spitzer, Thomas R.; Dey, Bimalangshu] Massachusetts Gen Hosp, Dept Med, Bone Marrow Transplantat Program, Boston, MA 02114 USA. [Saidman, Susan L.; Preffer, Frederic I.; Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kawai, Tatsuo; Cosimi, A. Benedict; Spitzer, Thomas R.; Tolkoff-Rubin, Nina; Saidman, Susan L.; Shaffer, Juanita; Preffer, Frederic I.; Fishman, Jay A.; Dey, Bimalangshu; Ko, Dicken S. C.; Hertl, Martin; Goes, Nelson B.; Wong, Waichi; Williams, Winfred W., Jr.; Colvin, Robert B.; Sykes, Megan; Sachs, David H.] Harvard Univ, Sch Med, Boston, MA USA. [Suthanthiran, Manikkam; Ding, Ruchuang; Sharma, Vijay] New York Presbyterian Hosp Weill Cornell Med Ctr, Dept Med & Transplant Med, Div Nephrol, New York, NY USA. RP Sachs, DH (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, 149 13th St, Charlestown, MA 02129 USA. FU NIAID NIH HHS [N01AI15416, N01 AI015416, R01 AI037692, R01 AI037692-09, R01 AI037692-10, R21 AI037692, R21 AI037692-06, U19 AI102405] NR 28 TC 585 Z9 614 U1 1 U2 25 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 24 PY 2008 VL 358 IS 4 BP 353 EP 361 DI 10.1056/NEJMoa071074 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 253GY UT WOS:000252507900005 PM 18216355 ER PT J AU Epstein, EH Shepard, JAO Flotte, TJ AF Epstein, Ervin H. Shepard, Jo-Anne O. Flotte, Thomas J. TI A woman with cutaneous basal-cell carcinomas and cysts of the jaws - The basal-cell nevus (Gorlin's) syndrome with multiple basal-cell carcinomas and odontogenic keratocysts. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PHOTODYNAMIC THERAPY; HUMAN HOMOLOG; MUTATIONS; CANCER; TAZAROTENE; GENE C1 [Epstein, Ervin H.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. [Shepard, Jo-Anne O.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Flotte, Thomas J.] Massachusetts Gen Hosp, Dept Dermatopathol, Boston, MA 02114 USA. [Shepard, Jo-Anne O.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Flotte, Thomas J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Epstein, EH (reprint author), Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. NR 22 TC 4 Z9 4 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 24 PY 2008 VL 358 IS 4 BP 393 EP 401 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 253GY UT WOS:000252507900012 PM 18216361 ER PT J AU D'Amico, AV Chen, MH Renshaw, AA Loffredo, M Kantoff, PW AF D'Amico, Anthony V. Chen, Ming-Hui Renshaw, Andrew A. Loffredo, Marian Kantoff, Philip W. TI Androgen suppression and radiation vs radiation alone for prostate cancer - A randomized trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RADICAL PROSTATECTOMY; DEPRIVATION THERAPY; COMPETING RISK; ONCOLOGY-GROUP; RADIOTHERAPY; COMORBIDITY; CANDIDATES; SURVIVAL; LIFE AB Context Comorbidities may increase the negative effects of specific anticancer treatments such as androgen suppression therapy ( AST). Objectives To compare 6 months of AST and radiation therapy ( RT) to RT alone and to assess the interaction between level of comorbidity and all- cause mortality. Design, Setting, and Patients At academic and community- based medical centers in Massachusetts, between December 1, 1995, and April 15, 2001, 206 men with localized but unfavorable- risk prostate cancer were randomized to receive RT alone or RT and AST combined. All- cause mortality estimates stratified by randomized treatment group and further stratified in a postrandomization analysis by the Adult Comorbidity Evaluation 27 comorbidity score were compared using a log- rank test. Main Outcome Measure Time to all- cause mortality. Results As of January 15, 2007, with a median follow- up of 7.6 ( range, 0.5- 11.0) years, 74 deaths have occurred. A significant increase in the risk of all- cause mortality ( 44 vs 30 deaths; hazard ratio [ HR], 1.8; 95% confidence interval [ CI], 1.1- 2.9; P=. 01) was observed in men randomized to RT compared with RT and AST. However, the increased risk in all- cause mortality appeared to apply only to men randomized to RT with no or minimal comorbidity ( 31 vs 11 deaths; HR, 4.2; 95% CI, 2.1- 8.5; P <. 001). Among men with moderate or severe comorbidity, those randomized to RT alone vs RT and AST did not have an increased risk of all- cause mortality ( 13 vs 19 deaths; HR, 0.54; 95% CI, 0.27- 1.10; P=. 08). Conclusions The addition of 6 months of AST to RT resulted in increased overall survival in men with localized but unfavorable- risk prostate cancer. This result may pertain only to men without moderate or severe comorbidity, but this requires further assessment in a clinical trial specifically designed to assess this interaction. Trial Registration clinicaltrials. gov Identifier: NCT00116220 C1 [D'Amico, Anthony V.; Loffredo, Marian] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Renshaw, Andrew A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kantoff, Philip W.] Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA. [D'Amico, Anthony V.; Renshaw, Andrew A.; Loffredo, Marian; Kantoff, Philip W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02115 USA. EM adamico@partners.org NR 27 TC 354 Z9 359 U1 1 U2 4 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 JAN 23 PY 2008 VL 299 IS 3 BP 289 EP 295 DI 10.1001/jama.299.3.289 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 253DB UT WOS:000252497800020 PM 18212313 ER PT J AU Iezzoni, LI Freedman, VA AF Iezzoni, Lisa I. Freedman, Vicki A. TI Turning the disability tide - The importance of definitions SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID OBESITY C1 [Iezzoni, Lisa I.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Freedman, Vicki A.] Univ Med & Dent New Jersey, Sch Publ Hlth, Dept Hlth Syst & Policy, Newark, NJ 07103 USA. RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St,Room 901B, Boston, MA 02114 USA. EM liezzoni@partners.org FU NIA NIH HHS [R01AG021516] NR 24 TC 47 Z9 47 U1 2 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 23 PY 2008 VL 299 IS 3 BP 332 EP 334 DI 10.1001/jama.299.3.332 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 253DB UT WOS:000252497800025 PM 18212318 ER PT J AU Cummings, DE Flum, DR AF Cummings, David E. Flum, David R. TI Gastrointestinal surgery as a treatment for diabetes SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID GASTRIC-BYPASS-SURGERY; BARIATRIC SURGERY; HYPERINSULINEMIC HYPOGLYCEMIA; NESIDIOBLASTOSIS; PREVALENCE; MORTALITY; MELLITUS; THERAPY; WEIGHT; HEALTH C1 [Cummings, David E.] Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. [Flum, David R.] Univ Washington, Dept Surg, 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 NR 23 TC 36 Z9 51 U1 1 U2 7 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 JAN 23 PY 2008 VL 299 IS 3 BP 341 EP 343 DI 10.1001/jama.299.3.341 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 253DB UT WOS:000252497800028 PM 18212321 ER PT J AU Spires-Jones, TL De Calignon, A Matsui, T Zehr, C Pitstick, R Wu, HY Osetek, JD Jones, PB Bacskai, BJ Feany, MB Carlson, GA Ashe, KH Lewis, J Hyman, BT AF Spires-Jones, Tara L. De Calignon, Alix Matsui, Toshifumi Zehr, Cindy Pitstick, Rose Wu, Hai-Yan Osetek, Jennifer D. Jones, Phillip B. Bacskai, Brian J. Feany, Mel B. Carlson, George A. Ashe, Karen H. Lewis, Jada Hyman, Bradley T. TI In vivo imaging reveals dissociation between caspase activation and acute neuronal death in tangle-bearing neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Alzheimer's; neurofibrillary tangle; caspase; apoptosis; multiphoton imaging; tauopathy ID NEUROFIBRILLARY TANGLES; ALZHEIMERS-DISEASE; TAU-PROTEIN; MOUSE MODEL; MICE; NEURODEGENERATION; APOPTOSIS; TAUOPATHY; CLEAVAGE; EXPRESSION AB Accumulation of neurofibrillary tangles (NFTs) in Alzheimer's disease correlates with neuronal loss and cognitive decline, but the precise relationship between NFTs and neuronal death and downstream mechanisms of cell death remain unclear. Caspase cleaved products accumulate in tangles, implying that tangles may contribute to apoptotic neuronal death. To test this hypothesis, we developed methods using multiphoton imaging to detect both neurofibrillary pathology and caspase activation in the living mouse brain. We examined rTg4510 mice, a reversible mouse model of tauopathy that develops tangles and neuronal loss. Only a small percentage of imaged neurons were caspase activity positive, but the vast majority of the cells with active caspases contained NFTs. We next tested the hypothesis that caspase activation led to acute, apoptotic neuronal death. Caspase positive cell bodies did not degenerate over hours of imaging, despite the presence of activated executioner caspases. Suppression of the transgene, which stops ongoing death, did not suppress caspase activity. Finally, histochemical assessments revealed evidence of caspase-cleaved tau, but no TUNEL (terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling) positive or apoptotic nuclei. With the novel technique of observing NFTs and caspase activation in the living brain, we demonstrate that aggregated tau in neurons can be associated with caspase activation, but that caspase activation is not sufficient to cause acute neuronal death in this model. C1 [Spires-Jones, Tara L.; De Calignon, Alix; Matsui, Toshifumi; Wu, Hai-Yan; Osetek, Jennifer D.; Jones, Phillip B.; Bacskai, Brian J.; Hyman, Bradley T.] Harvard Univ, Sch Med, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Jones, Phillip B.] Harvard Univ, Sch Med, Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Zehr, Cindy; Lewis, Jada] Mayo Clin, Neurogenet Neurotransgen & Neuropathol Labs, Jacksonville, FL 32224 USA. [Pitstick, Rose; Carlson, George A.] McLaughlin Res Inst, Great Falls, MT 59405 USA. [Feany, Mel B.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Feany, Mel B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ashe, Karen H.] Univ Minnesota, Sch Med, Dept Neurol, Minneapolis, MN 55455 USA. RP Hyman, BT (reprint author), Harvard Univ, Sch Med, MassGen Inst Neurodegenerat Dis, 114 16th St, Charlestown, MA 02129 USA. EM bhyman@partners.org OI Jones, Phillip/0000-0003-0525-6323; Spires-Jones, Tara/0000-0003-2530-0598 FU NIA NIH HHS [AG08487, AG26249, P50 AG005134, AG00277, R01 AG026249, R01-AG26252]; NIBIB NIH HHS [EB00768]; NINDS NIH HHS [R01-NS46355] NR 27 TC 90 Z9 92 U1 1 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 23 PY 2008 VL 28 IS 4 BP 862 EP 867 DI 10.1523/JNEUROSCI.3072-08.2008 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 257CX UT WOS:000252777900009 PM 18216194 ER PT J AU Morrow, EM Chen, CMA Cepko, CL AF Morrow, Eric M. Chen, C-M Amy Cepko, Constance L. TI Temporal order of bipolar cell genesis in the neural retina SO NEURAL DEVELOPMENT LA English DT Article ID MOUSE RETINA; RAT RETINA; PHOTORECEPTOR DIFFERENTIATION; VERTEBRATE RETINA; CONE; EXPRESSION; AMACRINE; CHX10; FATE AB Background: Retinal bipolar cells comprise a diverse group of neurons. Cone bipolar cells and rod bipolar cells are so named for their connections with cone and rod photoreceptors, respectively. Morphological criteria have been established that distinguish nine types of cone bipolar cells and one type of rod bipolar cell in mouse and rat. While anatomical and physiological aspects of bipolar types have been actively studied, little is known about the sequence of events that leads to bipolar cell type specification and the potential relationship this process may have with synapse formation in the outer plexiform layer. In this study, we have examined the birth order of rod and cone bipolar cells in the developing mouse and rat in vivo. Results: Using retroviral lineage analysis with the histochemical marker alkaline phosphatase, the percentage of cone and rod bipolar cells born on postnatal day 0 (P0), P4, and P6 were determined, based upon the well characterized morphology of these cells in the adult rat retina. In this in vivo experiment, we have demonstrated that cone bipolar genesis clearly precedes rod bipolar genesis. In addition, in the postnatal mouse retina, using a combination of tritiated-thymidine birthdating and immunohistochemistry to distinguish bipolar types, we have similarly found that cone bipolar genesis precedes rod bipolar genesis. The tritiated-thymidine birthdating studies also included quantification of the birth of all postnatally generated retinal cell types in the mouse. Conclusion: Using two independent in vivo methodologies in rat and mouse retina, we have demonstrated that there are distinct waves of genesis of the two major bipolar cell types, with cone bipolar genesis preceding rod bipolar genesis. These waves of bipolar genesis correspond to the order of genesis of the presynaptic photoreceptor cell types. C1 [Cepko, Constance L.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Morrow, Eric M.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Genet, Boston, MA 02115 USA. [Morrow, Eric M.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Chen, C-M Amy] Novartis Inst Biomed Res, Cambridge, MA 02139 USA. [Cepko, Constance L.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Cepko, CL (reprint author), Harvard Univ, Sch Med, Dept Genet, New Res Bldg,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM emorrow@partners.org; cmamychen@gmail.com; cepko@genetics.med.harvard.edu RI Morrow, Eric/J-2767-2013 FU NIH [EY09676]; HHMI; Burroughs Wellcome Fund; MGH; Charles H. Hood Foundation Child Health Research Award FX We thank Bob Molday for Rho4D2 antisera. This work was supported by NIH EY09676. AC and CLC were supported by HHMI. EMM holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund and is also grateful for support from the Rappaport Research Scholarship in Neuroscience at MGH and the Charles H. Hood Foundation Child Health Research Award. NR 35 TC 31 Z9 31 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1749-8104 J9 NEURAL DEV JI Neural Dev. PD JAN 23 PY 2008 VL 3 AR 2 DI 10.1186/1749-8104-3-2 PG 8 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 345PW UT WOS:000259009700001 PM 18215319 ER PT J AU Sidney, J Peters, B Frahm, N Brander, C Sette, A AF Sidney, John Peters, Bjoern Frahm, Nicole Brander, Christian Sette, Alessandro TI HLA class I supertypes: a revised and updated classification SO BMC IMMUNOLOGY LA English DT Review ID MHC CLASS-I; T-LYMPHOCYTE RESPONSES; PEPTIDE-BINDING REPERTOIRES; MAJOR HISTOCOMPATIBILITY COMPLEX; SARCOMA-ASSOCIATED HERPESVIRUS; TUMOR-ASSOCIATED ANTIGENS; PROSTATE-CANCER PATIENTS; PULSED DENDRITIC CELLS; VACCINE CANDIDATES; CTL EPITOPES AB Background: Class I major histocompatibility complex (MHC) molecules bind, and present to T cells, short peptides derived from intracellular processing of proteins. The peptide repertoire of a specific molecule is to a large extent determined by the molecular structure accommodating so-called main anchor positions of the presented peptide. These receptors are extremely polymorphic, and much of the polymorphism influences the peptide-binding repertoire. However, despite this polymorphism, class I molecules can be clustered into sets of molecules that bind largely overlapping peptide repertoires. Almost a decade ago we introduced this concept of clustering human leukocyte antigen (HLA) alleles and defined nine different groups, denominated as supertypes, on the basis of their main anchor specificity. The utility of this original supertype classification, as well several other subsequent arrangements derived by others, has been demonstrated in a large number of epitope identification studies. Results: Following our original approach, in the present report we provide an updated classification of HLA-A and -B class I alleles into supertypes. The present analysis incorporates the large amount of class I MHC binding data and sequence information that has become available in the last decade. As a result, over 80% of the 945 different HLA-A and -B alleles examined to date can be assigned to one of the original nine supertypes. A few alleles are expected to be associated with repertoires that overlap multiple supertypes. Interestingly, the current analysis did not identify any additional supertype specificities. Conclusion: As a result of this updated analysis, HLA supertype associations have been defined for over 750 different HLA-A and -B alleles. This information is expected to facilitate epitope identification and vaccine design studies, as well as investigations into disease association and correlates of immunity. In addition, the approach utilized has been made more transparent, allowing others to utilize the classification approach going forward. C1 [Sidney, John; Peters, Bjoern; Sette, Alessandro] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA. [Frahm, Nicole; Brander, Christian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Cambridge, MA 02139 USA. RP Sette, A (reprint author), La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, 9420 Athena Circle, La Jolla, CA 92037 USA. EM jsidney@liai.org; bpeters@liai.org; nfrahm@partners.org; brander@helix.mgh.harvard.edu; alex@liai.org OI Brander, Christian/0000-0002-0548-5778 FU NIAID NIH HHS [N01-AI-40024, N01AI40023, N01AI40024]; PHS HHS [HHSN266200400006C] NR 110 TC 216 Z9 221 U1 0 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2172 J9 BMC IMMUNOL JI BMC Immunol. PD JAN 22 PY 2008 VL 9 AR 1 DI 10.1186/1471-2172-9-1 PG 15 WC Immunology SC Immunology GA 274EP UT WOS:000253984900001 PM 18211710 ER PT J AU Sprenger, CC Plymate, SR Reed, MJ AF Sprenger, C. C. Plymate, S. R. Reed, M. J. TI Extracellular influences on tumour angiogenesis in the aged host SO BRITISH JOURNAL OF CANCER LA English DT Review DE prostate cancer; microenvironment; senescence; angiogenesis; growth factors; matrix metalloproteinases ID ENDOTHELIAL GROWTH-FACTOR; HUMAN PROSTATE-CANCER; GENE-EXPRESSION; DEPENDENT IMPAIRMENT; MMP-2 EXPRESSION; FACTOR RECEPTOR; BREAST-CANCER; FACTOR-I; INSULIN; CELLS AB Whether tumours are epithelial or non-epithelial in origin, it is generally accepted that once they reach a certain size all solid tumours are dependent upon a vascular supply to provide nutrients. Accordingly, there is great interest in how the extracellular environment enhances or inhibits vascular growth. In this minireview, we will examine key extracellular components, their changes with ageing, and discuss how these alterations may influence the subsequent development of tumour vasculature in the aged host. Because of the tight correlation between advanced age and development of prostate cancer, we will use prostate cancer as the model throughout this review. C1 [Sprenger, C. C.; Plymate, S. R.; Reed, M. J.] Univ Washington, Harborview Med Ctr, Dept Med, Div Gerontol, Seattle, WA 98104 USA. [Sprenger, C. C.] Univ Washington, Mol & Cellular Biol Program, Seattle, WA 98195 USA. [Plymate, S. R.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Reed, MJ (reprint author), Univ Washington, Harborview Med Ctr, Dept Med, Div Gerontol, 325 9th Ave,Box 359625, Seattle, WA 98104 USA. EM mjr@u.washington.edu FU NCI NIH HHS [U54CA126540-01, U54 CA126540]; NIA NIH HHS [R01AG15837, R01 AG015837] NR 52 TC 14 Z9 14 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JAN 22 PY 2008 VL 98 IS 2 BP 250 EP 255 DI 10.1038/sj.bjc.6604144 PG 6 WC Oncology SC Oncology GA 259IQ UT WOS:000252933400002 PM 18182993 ER PT J AU Curto, M McClatchey, AL AF Curto, M. McClatchey, A. L. TI Nf2/Merlin: a coordinator of receptor signalling and intercellular contact SO BRITISH JOURNAL OF CANCER LA English DT Review DE merlin; Ezrin; EGFR; contact-inhibition; adherens junctions; cytoskeleton ID NF2 TUMOR-SUPPRESSOR; HUMAN SCHWANNOMA CELLS; ERM PROTEINS; NEUROFIBROMATOSIS TYPE-2; CARCINOMA CELLS; GENE-PRODUCT; LINKER EZRIN; F-ACTIN; MERLIN; MEMBRANE AB This review explores possible mechanisms by which the neurofibromatosis type-2 tumour suppressor Merlin regulates contact-dependent inhibition of proliferation. Starting from an evolutionary perspective, the concurrent emergence of intercellular contacts and proliferation control in multicellular organisms is first considered. Following a brief survey of the molecular and subcellular milieus in which merlin performs its function, the importance of different cellular and biological contexts in defining the function of merlin is discussed. Finally, an integrated model for merlin and the Ezrin, Radixin, and Moesin (ERM) proteins functioning in the regulation of cellular interfaces is proposed. C1 [Curto, M.; McClatchey, A. L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [Curto, M.; McClatchey, A. L.] Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. RP McClatchey, AL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc Res, 149 13th St, Charlestown, MA 02129 USA. EM mcclatch@helix.mgh.harvard.edu NR 47 TC 59 Z9 59 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JAN 22 PY 2008 VL 98 IS 2 BP 256 EP 262 DI 10.1038/sj.bjc.6604002 PG 7 WC Oncology SC Oncology GA 259IQ UT WOS:000252933400003 PM 17971776 ER PT J AU Singh, M Gersh, BJ Li, S Rumsfeld, JS Spertus, JA O'Brien, SM Suri, RM Peterson, ED AF Singh, Mandeep Gersh, Bernard J. Li, Shuang Rumsfeld, John S. Spertus, John A. O'Brien, Sean M. Suri, Rakesh M. Peterson, Eric D. TI Mayo clinic risk score for percutaneous coronary intervention predicts in-hospital mortality in patients undergoing coronary artery bypass graft surgery SO CIRCULATION LA English DT Article DE angiography; angioplasty; mortality; revascularization; complications; risk factors ID EVALUATION EUROSCORE; EUROPEAN SYSTEM; STRATIFICATION; COMPLICATIONS; MORBIDITY; MODELS AB Background-Current risk models predict in-hospital mortality after either coronary artery bypass graft surgery or percutaneous coronary interventions separately, yet the overlap suggests that the same variables can define the risks of alternative coronary reperfusion therapies. Our goal was to seek a preprocedure risk model that can predict in-hospital mortality after either percutaneous coronary intervention or coronary artery bypass graft surgery. Methods and Results-We tested the ability of the recently validated, integer-based Mayo Clinic Risk Score (MCRS) for percutaneous coronary intervention, which is based solely on preprocedure variables (age, creatinine, ejection fraction, myocardial infarction <= 24 hours, shock, congestive heart failure, and peripheral vascular disease), to predict in-hospital mortality among 370 793 patients in the Society of Thoracic Surgeons database undergoing isolated coronary artery bypass graft surgery from 2004 to 2006. For the Society of Thoracic Surgeons coronary artery bypass graft surgery population studied, the median age was 66 years (quartiles 1 to 3, 57 to 74 years), with 37.2% of patients >= 70 years old. A high prevalence of comorbid conditions, including diabetes mellitus (37.1%), hypertension (80.5%), peripheral vascular disease (15.3%), and renal disease (creatinine >= 1.4 mg/dL; 11.8%), was present. A strong association existed between the MCRS and the observed mortality in the Society of Thoracic Surgeons database. The in-hospital mortality ranged between 0.3% (95% confidence interval 0.3% to 0.4%) with a score of 0 on the MCRS and 33.8% (95% confidence interval 27.3% to 40.3%) with an MCRS score of 20 to 24. The discriminatory ability of the MCRS was moderate, as measured by the area under the receiver operating characteristic curve (C-statistic = 0.715 to 0.784 among various subgroups); performance was inferior to the Society of Thoracic Surgeons model for most categories tested. Conclusions-This model, which is based on 7 preprocedure risk variables, may be useful for providing patients with individualized, evidence-based estimates of procedural risk as part of the informed consent process before percutaneous or surgical revascularization. C1 [Singh, Mandeep; Gersh, Bernard J.; Suri, Rakesh M.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN 55905 USA. [Li, Shuang; O'Brien, Sean M.; Peterson, Eric D.] Duke Univ, Clin Res Inst, Durham, NC USA. [Spertus, John A.] Mid Amer Heart Inst UMKC, Kansas City, MO USA. [Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. RP Singh, M (reprint author), Mayo Clin, Div Cardiovasc Dis, 200 1st St SW, Rochester, MN 55905 USA. RI O'Brien, Sean/H-6268-2013 NR 16 TC 27 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 22 PY 2008 VL 117 IS 3 BP 356 EP 362 DI 10.1161/CIRCULATIONAHA.107.711523 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 254QE UT WOS:000252601600013 PM 18172033 ER PT J AU Nahrendorf, M Zhang, HW Hembrador, S Panizzi, P Sosnovik, DE Aikawa, E Libby, P Swirski, FK Weissleder, R AF Nahrendorf, Matthias Zhang, Hanwen Hembrador, Sheena Panizzi, Peter Sosnovik, David E. Aikawa, Elena Libby, Peter Swirski, Filip K. Weissleder, Ralph TI Nanoparticle PET-CT imaging of macrophages in inflammatory atherosclerosis SO CIRCULATION LA English DT Article DE atherosclerosis; imaging; inflammation; nanoparticles; positron-emission tomography ID POSITRON-EMISSION-TOMOGRAPHY; ULTRASMALL SUPERPARAMAGNETIC PARTICLES; IRON-OXIDE; IN-VIVO; HYPERLIPIDEMIC RABBITS; F-18-FDG ACCUMULATION; PLAQUE INFLAMMATION; AORTIC-WALL; RESONANCE; RECRUITMENT AB Background-Macrophages participate centrally in atherosclerosis, and macrophage markers (eg, CD68, MAC-3) correlate well with lesion severity and therapeutic modulation. On the basis of the avidity of lesional macrophages for polysaccharide-containing supramolecular structures such as nanoparticles, we have developed a new positron emission tomography (PET) agent with optimized pharmacokinetics to allow in vivo imaging at tracer concentrations. Methods and Results-A dextranated and DTPA-modified magnetofluorescent 20-nm nanoparticle was labeled with the PET tracer Cu-64 (1 mCi/0.1 mg nanoparticles) to yield a PET, magnetic resonance, and optically detectable imaging agent. Peak PET activity 24 hours after intravenous injection into mice deficient in apolipoprotein E with experimental atherosclerosis mapped to areas of high plaque load identified by computed tomography such as the aortic root and arch and correlated with magnetic resonance and optical imaging. Accumulated dose in apolipoprotein E-deficient aortas determined by gamma counting was 260% and in carotids 392% of respective wild-type organs (P < 0.05 both). Autoradiography of aortas demonstrated uptake of the agent into macrophage-rich atheromata identified by Oil Red O staining of lipid deposits. The novel nanoagent accumulated predominantly in macrophages as determined by fluorescence microscopy and flow cytometry of cells dissociated from aortas. Conclusions-This report establishes the capability of a novel trimodality nanoparticle to directly detect macrophages in atherosclerotic plaques. Advantages include improved sensitivity; direct correlation of PET signal with an established biomarker (CD68); ability to readily quantify the PET signal, perform whole-body vascular surveys, and spatially localize and follow the trireporter by microscopy; and clinical translatability of the agent given similarities to magnetic resonance imaging probes in clinical trials. C1 [Nahrendorf, Matthias; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Nahrendorf, Matthias; Aikawa, Elena; Libby, Peter; Weissleder, Ralph] Harvard Univ, Sch Med, Boston, MA USA. [Nahrendorf, Matthias; Zhang, Hanwen; Hembrador, Sheena; Panizzi, Peter; Sosnovik, David E.; Aikawa, Elena; Swirski, Filip K.; Weissleder, Ralph] Harvard Univ, Sch Med, Charlestown, MA USA. [Nahrendorf, Matthias; Zhang, Hanwen; Hembrador, Sheena; Panizzi, Peter; Sosnovik, David E.; Aikawa, Elena; Swirski, Filip K.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. [Nahrendorf, Matthias; Aikawa, Elena; Libby, Peter; Weissleder, Ralph] Donald W Reynolds Cardiovasc Clin Res Ctr Atheros, Boston, MA USA. [Sosnovik, David E.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Libby, Peter] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Weissleder, Ralph] MGH CSB, Boston, MA 02114 USA. RP Weissleder, R (reprint author), MGH CSB, 185 Cambridge St, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu OI Panizzi, Peter/0000-0003-0141-8807 FU NCI NIH HHS [R24 CA092782, R24 CA092782-03, R24-CA92782]; NHLBI NIH HHS [R00 HL094533, R01 HL078641, R01 HL078641-03, R01-HL078641, U01 HL080731, U01 HL080731-03, U01-HL080731] NR 31 TC 291 Z9 303 U1 9 U2 92 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 22 PY 2008 VL 117 IS 3 BP 379 EP 387 DI 10.1161/CIRCULATIONAHA.107.741181 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 254QE UT WOS:000252601600016 PM 18158358 ER PT J AU Kircher, MF Grimm, J Swirski, FK Libby, P Gerszten, RE Allport, JR Weissleder, R AF Kircher, Moritz F. Grimm, Jan Swirski, Filip K. Libby, Peter Gerszten, Robert E. Allport, Jennifer R. Weissleder, Ralph TI Noninvasive in vivo imaging of monocyte trafficking to atherosclerotic lesions SO CIRCULATION LA English DT Article DE imaging; atherosclerosis; plaque; cells ID POSITRON-EMISSION-TOMOGRAPHY; ACUTE CORONARY SYNDROMES; C-REACTIVE PROTEIN; CIRCULATING MONOCYTES; MICE; INFLAMMATION; ATORVASTATIN; RECRUITMENT; MACROPHAGES; ATHEROGENESIS AB Background-Monocytes play a key role in atherogenesis, but their participation has been discerned largely via ex vivo analyses of atherosclerotic lesions. We sought to establish a noninvasive technique to determine monocyte trafficking to atherosclerotic lesions in live animals. Methods and Results-Using a micro-single-photon emission computed tomography small-animal imaging system and a Food and Drug Administration-approved radiotracer ([ indium 111] oxyquinoline, In-111-oxine), we demonstrate here that monocyte recruitment to atherosclerotic lesions can be visualized in a noninvasive, dynamic, and 3-dimensional fashion in live animals. We show in vivo that monocytes are recruited avidly to plaques within days of adoptive transfer. Using micro-single-photon emission computed tomography imaging as a screening tool, we were able to investigate modulatory effects on monocyte recruitment in live animals. We found that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors rapidly and substantially reduce monocyte recruitment to existing atherosclerotic lesions, as imaged here in vivo. Conclusions-This novel approach to track monocytes to atherosclerotic plaques in vivo should have broad applications and create new insights into the pathogenesis of atherosclerosis and other inflammatory diseases. C1 [Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Richard B Simches Res Ctr, Boston, MA 02114 USA. [Swirski, Filip K.; Libby, Peter; Gerszten, Robert E.; Weissleder, Ralph] Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr Atheros, Boston, MA USA. [Kircher, Moritz F.; Grimm, Jan; Swirski, Filip K.; Gerszten, Robert E.; Allport, Jennifer R.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. [Kircher, Moritz F.; Grimm, Jan; Swirski, Filip K.; Gerszten, Robert E.; Allport, Jennifer R.; Weissleder, Ralph] Harvard Univ, Sch Med, Charlestown, MA USA. [Swirski, Filip K.; Libby, Peter] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Gerszten, Robert E.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Richard B Simches Res Ctr, 185 Cambridge St,8th Floor, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu RI Grimm, Jan/B-1937-2008 FU NCI NIH HHS [R24 CA092782-05, R24 CA092782, R24 CA92782]; NHLBI NIH HHS [U01 HL080731, U01 HL080731-03] NR 33 TC 62 Z9 64 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 22 PY 2008 VL 117 IS 3 BP 388 EP 395 DI 10.1161/CIRCULATIONAHA.107.719765 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 254QE UT WOS:000252601600017 PM 18172031 ER PT J AU Fifer, MA Vlahakes, GJ AF Fifer, Michael A. Vlahakes, Gus J. TI Management of symptoms in hypertrophic cardiomyopathy SO CIRCULATION LA English DT Review ID VENTRICULAR DIASTOLIC FUNCTION; NONSURGICAL SEPTAL REDUCTION; OUTFLOW TRACT OBSTRUCTION; BLOOD-PRESSURE RESPONSE; TERM-FOLLOW-UP; SUBVALVULAR AORTIC STENOSIS; BETA-ADRENERGIC BLOCKADE; SUBAORTIC STENOSIS; DOUBLE-BLIND; PHARMACOLOGIC TREATMENT C1 [Fifer, Michael A.] Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA. [Vlahakes, Gus J.] Massachusetts Gen Hosp, Cardiac Surg Div, Dept Surg, Boston, MA 02114 USA. [Vlahakes, Gus J.] Harvard Univ, Sch Med, Boston, MA USA. RP Fifer, MA (reprint author), Massachusetts Gen Hosp, Div Cardiol, Dept Med, 55 Fruit St,Gray Bigelow Bldg,Suite 800,Mailstop, Boston, MA 02114 USA. EM mfifer@partners.org NR 120 TC 48 Z9 57 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 JAN 22 PY 2008 VL 117 IS 3 BP 429 EP 439 DI 10.1161/CIRCULATIONAHA.107.694158 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 254QE UT WOS:000252601600022 PM 18212300 ER PT J AU Levitzky, YS Pencina, MJ D'Agostino, RB Meigs, JB Murabito, JM Vasan, RS Fox, CS AF Levitzky, Yamini S. Pencina, Michael J. D'Agostino, Ralph B. Meigs, James B. Murabito, Joanne M. Vasan, Ramachandran S. Fox, Caroline S. TI Impact of impaired fasting glucose on cardiovascular disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; DIABETES-MELLITUS; RISK-FACTORS; FOLLOW-UP; DIAGNOSTIC-CRITERIA; OLDER-ADULTS; FRAMINGHAM; TOLERANCE; MORTALITY; POPULATION AB Objectives We sought to determine whether impaired fasting glucose (IFG) predicts cardiovascular disease (CVD) events. Background It is unclear which glucose threshold should define prediabetes. We compared the 1997 and 2003 American Diabetes Association (ADA) definitions of IFG to predict CVD. Methods Framingham offspring participants free of CVD, categorized by the 1997 ADA IFG definition (fasting plasma glucose 110 to 125 mg/dI; 6.1 to 6.9 mmol/l) or the 2003 definition (100 to 125 mg/dI; 5.6 to 6.9 mmol/1), were followed from 1983 to 2004. Pooled logistic regression was used to calculate multivariable-adjusted odds ratios (ORs) for incident coronary heart disease (CHD; 291 events) or CVD (423 events). Results Four-year CHD event rates among women were 1.3% (100 to 109 mg/dl), 2.3% (110 to 125 mg/dI), and 2.9% (diabetes); whereas corresponding rates in men were 2.9%, 3.0%, and 8.7%. For the 2003 IFG definition, the OR for CHD among women was 1.7 (95% confidence interval [CI] 1.0 to 3.0, p = 0.048), whereas for the 1997 IFG definition, the OR for CHD in women was 2.2 (95% Cl 1.1 to 4.4, p = 0.02), which was almost as high as for women with diabetes (OR 2.5, 95% Cl 1.2 to 5.2, p = 0.01). For CVD, only the 1997 IFG definition yielded significantly greater odds of CVD in women (OR 2.1, 95% Cl 1.2 to 3.6, p = 0.01). Men were not at increased odds of developing CVD or CHD by either definition. Conclusions In women, both IFG definitions were associated with increased CHD risk, whereas neither IFG definition identified men at increased short-term risk for CHD or CVD. The finding that: women with FPG 110 to 125 mg/dI had similar CHD risk compared with women with diabetes suggests that CHD risk in women may be elevated at a lower glucose level than for men. C1 [Levitzky, Yamini S.; Murabito, Joanne M.; Vasan, Ramachandran S.; Fox, Caroline S.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Fox, Caroline S.] NHLBI, Bethesda, MD 20892 USA. [Pencina, Michael J.; D'Agostino, Ralph B.] Boston Univ, Dept Mathemat, Stat & Consulting Unit, Boston, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02118 USA. [Murabito, Joanne M.] Boston Med Ctr, Dept Med, Sect Gen Internal Med, Boston, MA USA. [Fox, Caroline S.] Harvard Med Sch, Boston, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Diabet Endocrinol & Metab, Boston, MA 02115 USA. RP Fox, CS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite No 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [N01-HC-25195, 2K24 HL4334] NR 32 TC 122 Z9 135 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 22 PY 2008 VL 51 IS 3 BP 264 EP 270 DI 10.1016/j.jace.2007.09.039 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 254DD UT WOS:000252565700004 PM 18206734 ER PT J AU McCormick, AL Brown, RH Cudkowicz, ME Al-Chalabi, A Garson, JA AF McCormick, A. L. Brown, R. H., Jr. Cudkowicz, M. E. Al-Chalabi, A. Garson, J. A. TI Quantification of reverse transcriptase in ALS and elimination of a novel retroviral candidate SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DISEASE; HIV-1 INFECTION; CEREBROSPINAL-FLUID; SERUM; ASSAY; INDIVIDUALS; VIRUS; RNA AB Background: Retroviral involvement in amyotrophic lateral sclerosis (ALS) has been suspected for several years since the recognition that both murine and human retroviruses can cause ALS-like syndromes. Nonquantitative studies have demonstrated the retroviral enzyme reverse transcriptase (RT) in ALS patients' sera, but the amount and source of RT activity are unknown. We therefore developed a quantitative assay to study RT levels in ALS and examined the possibility that the recently discovered human gammaretrovirus XMRV (xenotropic MuLV - related virus) might be the source of the RT activity. Methods: A quantitative product-enhanced RT assay was used to measure RT activity levels in serum and CSF. XMRV sequences were sought by PCR analysis of DNA and RNA extracted from blood. Results: Fifty percent of ALS patients' sera contained > 6 x 10(-8) RT units/mL as opposed to 7% of control sera ( p = 0.008). The levels of RT activity in ALS patients were comparable to the levels observed in patients infected with HIV. RT activity was detected in only 1 of 25 CSF samples tested. XMRV sequences were not found in any of 25 nucleic acid extracts obtained from ALS patients' blood. Conclusions: These findings further support the concept of retroviral involvement in amyotrophic lateral sclerosis (ALS) and demonstrate that serum is more suitable than CSF for assay of reverse transcriptase (RT) activity in this disease. The levels of serum RT activity detected are comparable to those found in HIV infection. XMRV is not detectable in the blood of ALS patients, and the agent responsible for ALS-associated RT activity therefore remains unidentified. C1 [McCormick, A. L.; Garson, J. A.] UCL, Ctr Virol, Windeyer Inst, Dept Infect, London W1T 4JF, England. [Brown, R. H., Jr.; Cudkowicz, M. E.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Al-Chalabi, A.] Kings Coll London, Inst Psychiat, MRC, Ctr Neurodegenerat Res, London WC2R 2LS, England. [Garson, J. A.] UCL, Dept Virol, Hosp Natl Hlth Serv Fdn Trust, London, England. RP Garson, JA (reprint author), UCL, Ctr Virol, Windeyer Inst, Dept Infect, 46 Cleveland St, London W1T 4JF, England. EM j.garson@ucl.ac.uk RI Garson, Jeremy/C-5357-2008; Al-Chalabi, Ammar/E-5361-2010 OI Al-Chalabi, Ammar/0000-0002-4924-7712 NR 28 TC 38 Z9 39 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JAN 22 PY 2008 VL 70 IS 4 BP 278 EP 283 DI 10.1212/01.wnl.0000297552.13219.b4 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 253FW UT WOS:000252505100008 PM 18209202 ER PT J AU Greer, DM Varelas, PN Haque, S Wijdicks, EFM AF Greer, David M. Varelas, Panayiotis N. Haque, Shamael Wijdicks, Eelco F. M. TI Variability of brain death determination guidelines in leading US neurologic institutions SO NEUROLOGY LA English DT Article ID COMPUTED TOMOGRAPHIC ANGIOGRAPHY; DIAGNOSIS; CONSENSUS; ADULTS AB Background: In accordance with the Uniform Determination of Death Act, guidelines for brain death determination are developed at an institutional level, potentially leading to variability of practice. We evaluated the differences in brain death guidelines in major US hospitals with a strong presence of neurology and neurosurgery to determine whether there was evidence of variation from the guidelines as put forth by the American Academy of Neurology (AAN). Methods: We requested the guidelines for determination of death by brain criteria from the US News and World Report top 50 neurology/neurosurgery institutions in 2006. We evaluated the guidelines for five categories of data: guideline performance, preclinical testing, clinical examination, apnea testing, and ancillary tests. We compared the guidelines directly with the AAN guidelines for consistencies/differences. Results: There was an 82% response rate to requests. Major discrepancies were present among institutions for all five categories. Variability existed in the guidelines' requirements for performance of the evaluation, prerequisites prior to testing, specifics of the brainstem examination and apnea testing, and what types of ancillary tests could be performed, including what pitfalls or limitations might exist. Conclusions: Major differences exist in brain death guidelines among the leading neurologic hospitals in the Unites States. Adherence to the American Academy of Neurology guidelines is variable. If the guidelines reflect actual practice at each institution, there are substantial differences in practice which may have consequences for the determination of death and initiation of transplant procedures. C1 [Greer, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Varelas, Panayiotis N.; Haque, Shamael] Henry Ford Hosp, Detroit, MI 48202 USA. [Wijdicks, Eelco F. M.] Mayo Clin, Rochester, MN USA. RP Greer, DM (reprint author), Massachusetts Gen Hosp, ACC 835,55 Fruit St, Boston, MA 02114 USA. EM dgreer@partners.org NR 15 TC 109 Z9 113 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JAN 22 PY 2008 VL 70 IS 4 BP 284 EP 289 DI 10.1212/01.wnl.0000296278.59487.c2 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 253FW UT WOS:000252505100009 PM 18077794 ER PT J AU Weiss, AP Duff, M Roffman, JL Rauch, SL Strangman, GE AF Weiss, Anthony P. Duff, Margaret Roffman, Joshua L. Rauch, Scott L. Strangman, Gary E. TI Auditory stimulus repetition effects on cortical hemoglobin oxygenation: a near-infrared spectroscopy investigation SO NEUROREPORT LA English DT Article DE auditory cortex; near-infrared spectroscopy; neuroimaging ID CORTEX ACTIVATION; BRAIN ACTIVATION; BLOOD-FLOW; SOUND; FMRI; MODULATION; BOLD; ATTENTION; HUMANS; VOLUME AB The cortical response to repeated sensory stimuli plateaus (or declines) as repetition frequencies increase beyond 2-8 Hz. This study examined the underlying changes in cortical oxygenated and deoxygenated hemoglobin associated with this phenomenon using near-infrared spectroscopy. The optical signal was measured from II healthy volunteers listening to noise-burst trains presented at 2, 10, and 35 Hz. In a bilateral region consistent with the posterior superior temporal gyrus there was an inverse relationship between deoxyhemoglobin concentration change and stimulus frequency: greatest at 2 Hz, intermediate at 10 Hz, and smallest at 35 Hz. These findings provide preliminary support for a relationship between the perceptual characteristics of auditory stimuli and modulation of cortical oxygenation as measured via an emerging neuromonitoring technique. C1 Massachusetts Gen Hosp E, Dept Psychiat, Charlestown, MA 02129 USA. [Weiss, Anthony P.; Duff, Margaret; Roffman, Joshua L.; Rauch, Scott L.; Strangman, Gary E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Weiss, Anthony P.; Duff, Margaret; Roffman, Joshua L.; Rauch, Scott L.; Strangman, Gary E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Weiss, AP (reprint author), Massachusetts Gen Hosp E, Dept Psychiat, Bldg 149,Room 2606,13th St, Charlestown, MA 02129 USA. EM aweiss@partners.org FU NIMH NIH HHS [MH06019]; NINDS NIH HHS [NS46554] NR 26 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JAN 22 PY 2008 VL 19 IS 2 BP 161 EP 165 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 255GF UT WOS:000252645000006 PM 18185101 ER PT J AU Foland, LC Altshuler, LL Sugar, CA Lee, AD Leow, AD Townsend, J Narr, KL Asuncion, DM Toga, AW Thompson, PM AF Foland, Lara C. Altshuler, Lori L. Sugar, Catherine A. Lee, Agatha D. Leow, Alex D. Townsend, Jennifer Narr, Katherine L. Asuncion, Dina M. Toga, Arthur W. Thompson, Paul M. TI Increased volume of the amygdala and hippocampus in bipolar patients treated with lithium SO NEUROREPORT LA English DT Article DE amygdala; bipolar disorder; emotion; hippocampus; lithium; magnetic resonance imaging; mood disorder ID TEMPORAL-LOBE STRUCTURES; DISORDER; MATTER; MRI; SCHIZOPHRENIA; ABNORMALITIES; ADOLESCENTS; ADULTS AB Previous structural neuroimaging studies of bipolar disorder have reported conflicting findings in limbic structures. Medication heterogeneity of patient samples may have contributed to these inconsistencies. Using structural magnetic resonance imaging we assessed whether lithium treatment was associated with differences in amygdala and hippocampal volumes in a sample of bipolar adults. A total of 49 magnetic resonance imaging scans were collected from patients who were currently treated with or without lithium. Amygdala and hippocampal volumes were analyzed using tensor-based morphometry. Statistical between-group comparisons of deformation maps showed that patients treated with lithium exhibited significantly increased volumes of the amygdala and hippocampus compared with patients who were not taking lithium. Our findings may help to explain previous inconsistencies in the bipolar literature. C1 [Foland, Lara C.; Lee, Agatha D.; Leow, Alex D.; Narr, Katherine L.; Toga, Arthur W.; Thompson, Paul M.] Univ Calif Los Angeles, Lab Neuroimaging, Dept Neurol, Los Angeles, CA USA. [Altshuler, Lori L.; Asuncion, Dina M.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA USA. [Altshuler, Lori L.] Univ Calif Los Angeles, Sch Med, VA Greater Los Angeles Hlthcare Syst, Dept Psychiat, Los Angeles, CA USA. [Townsend, Jennifer] Univ Calif Los Angeles, Sch Med, Ahmanson Lovelace Brain Mappinng Ctr, Los Angeles, CA USA. RP Altshuler, LL (reprint author), Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, 300 Med Plaza,Suite 1544,Box 957057, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu RI Leow, Alex/K-3236-2014 OI Leow, Alex/0000-0002-5660-8651 FU NCRR NIH HHS [R21 RR019771, R21 RR019771-02, RR019771]; NIBIB NIH HHS [EB01651]; NICHD NIH HHS [HD050735, R01 HD050735, R01 HD050735-05]; NIEHS NIH HHS [U13 ES016515-01]; NIMH NIH HHS [F31 MH078556, F31 MH078556-03, K24 MH001848, K24 MH001848-08, K24 MH001848-10, MH01848, MH078556] NR 25 TC 82 Z9 84 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JAN 22 PY 2008 VL 19 IS 2 BP 221 EP 224 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 255GF UT WOS:000252645000017 PM 18185112 ER PT J AU Yagi, T Giallourakis, C Mohanty, S Scheidig, C Shen, J Zheng, H Xavier, RJ Shaw, AC AF Yagi, Tomohito Giallourakis, Cosmas Mohanty, Subhasis Scheidig, Christina Shen, Jie Zheng, Hui Xavier, Ramnik J. Shaw, Albert C. TI Defective signal transduction in B lymphocytes lacking presenilin proteins SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE B cell; computational biology; gene targeting; Toll-like receptor; B cell antigen receptor (BCR) ID ALZHEIMERS-DISEASE; MICE; EXPRESSION; CELLS; PROGRESSION; ACTIVATION; CASPASE-1; MUTATIONS; NOTCH2; GENES AB The mammalian presenilin (PS) proteins mediate the posttranslational cleavage of several protein substrates, including amyloid precursor protein, Notch family members, and CD44, but they have also been suggested to, function in diverse cellular processes, including calcium-dependent signaling and apoptosis. We carried out an integrative computational study of multiple genomic datasets, including RNA expression, protein interaction, and pathway analyses, which implicated PS proteins in Toll-like receptor signaling. To test these computational predictions, we analyzed mice carrying a conditional allele of PS1 and a germ line-inactivating allele of PS2, together with Cre site-specific recombinase expression under the influence of CD19 control sequences. Notably, B cells deficient in both PS1 and PS2 function have an unexpected and substantial deficit in both lipopolysaccharide and B cell antigen receptor-induced proliferation and signal transduction events, including a defect in anti-IgM-mediated calcium flux. Taken together, these results demonstrate a fundamental and unanticipated role for PS proteins in B cell function and emphasize the potency of (systems level) integrative analysis of whole-genome datasets in identifying novel biologic signal transduction relationships. Our findings also suggest that pharmacologic inhibition of PS for the treatment of conditions such as Alzheimer's disease may have potential consequences for immune system function. C1 [Yagi, Tomohito; Mohanty, Subhasis; Scheidig, Christina; Xavier, Ramnik J.; Shaw, Albert C.] Yale Univ, Sch Med, Infect Dis Sect, Dept Internal Med, New Haven, CT 06520 USA. [Giallourakis, Cosmas; Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02115 USA. [Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Shen, Jie] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. [Zheng, Hui] Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA. RP Shaw, AC (reprint author), Yale Univ, Sch Med, Infect Dis Sect, Dept Internal Med, 300 Cedar St,Box 208022, New Haven, CT 06520 USA. EM albert.shaw@yale.edu FU NIAID NIH HHS [AI062773, R01 AI062773, T32 AI007517]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-12]; NINDS NIH HHS [NS40039, NS41783, R01 NS040039, R01 NS041783] NR 32 TC 15 Z9 15 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 JAN 22 PY 2008 VL 105 IS 3 BP 979 EP 984 DI 10.1073/pnas.0707755105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255HE UT WOS:000252647900029 PM 18195359 ER PT J AU Panigrahy, D Kaipainen, A Huang, S Butterfield, CE Barnes, CM Fannon, M Laforme, AM Chaponis, DM Folkman, J Kieran, MW AF Panigrahy, Dipak Kaipainen, Arja Huang, Sui Butterfield, Catherine E. Barnes, Carmen M. Fannon, Michael Laforme, Andrea M. Chaponis, Deviney M. Folkman, Judah Kieran, Mark W. TI PPAR alpha agonist fenofibrate suppresses tumor growth through direct and indirect angiogenesis inhibition SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE stroma; inflammation; fibrates; microenvironment ID ACTIVATED RECEPTOR-ALPHA; ENDOTHELIAL-CELL PROLIFERATION; IN-VITRO; METRONOMIC CHEMOTHERAPY; DEFICIENT MICE; LIGANDS; CANCER; ATHEROSCLEROSIS; INFLAMMATION; HYPERLIPIDEMIA AB Angiogenesis and inflammation are central processes through which the tumor microenvironment influences tumor growth. We have demonstrated recently that peroxisome proliferator-activated receptor (PPAR)a deficiency in the host leads to overt inflammation that suppresses angiogenesis via excess production of thrombospondin (TSP)-1 and prevents tumor growth. Hence, we speculated that pharmacologic activation of PPAR alpha would promote tumor growth. Surprisingly, the PPAR alpha agonist fenofibrate potently suppressed primary tumor growth in mice. This effect was not mediated by cancer-cell-autonomous antiproliferative mechanisms but by the inhibition of angiogenesis and inflammation in the host tissue. Although PPAR alpha-deficient tumors were still susceptible to fenofibrate, absence of PPAR alpha in the host animal abrogated the potent antitumor effect of fenofibrate. In addition, fenofibrate suppressed endothelial cell proliferation and VEGF production, increased TSP-1 and endostatin, and inhibited corneal neovascularization. Thus, both genetic abrogation of PPAR alpha as well as its activation by ligands cause tumor suppression via overlapping antiangiogenic pathways. These findings reveal the potential utility of the well tolerated PPAR alpha agonists beyond their use as lipid-lowering drugs in anticancer therapy. Our results provide a mechanistic rationale for evaluating the clinical benefits of PPAR222 agonists in cancer treatment, alone and in combination with other therapies. C1 [Panigrahy, Dipak; Kaipainen, Arja; Huang, Sui; Butterfield, Catherine E.; Barnes, Carmen M.; Laforme, Andrea M.; Chaponis, Deviney M.; Folkman, Judah; Kieran, Mark W.] Harvard Univ, Sch Med, Dept Surg, Childrens Hosp,Vasc Biol Program, Boston, MA 02115 USA. [Laforme, Andrea M.; Chaponis, Deviney M.; Kieran, Mark W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. [Fannon, Michael] Univ Kentucky, Dept Ophthalmol & Visual Sci, Lexington, KY 40536 USA. RP Panigrahy, D (reprint author), Harvard Univ, Sch Med, Dept Surg, Childrens Hosp,Vasc Biol Program, Boston, MA 02115 USA. EM dipak.panigrahy@childrens.harvard.edu FU NCI NIH HHS [R01 CA064481, R01CA064481] NR 39 TC 131 Z9 145 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 22 PY 2008 VL 105 IS 3 BP 985 EP 990 DI 10.1073/pnas.0711281105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255HE UT WOS:000252647900030 PM 18199835 ER PT J AU Ip, WKE Takahashi, K Moore, KJ Stuart, LM Ezekowitz, RAB AF Ip, W. K. Eddie Takahashi, Kazue Moore, Kathryn J. Stuart, Lynda M. Ezekowitz, R. Alan B. TI Mannose-binding lectin enhances Toll-like receptors 2 and 6 signaling from the phagosome SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID COMPLEMENT ACTIVATION PATHWAY; SURFACTANT PROTEIN-A; STAPHYLOCOCCUS-AUREUS; INNATE IMMUNITY; ALVEOLAR MACROPHAGES; PATTERN-RECOGNITION; SERINE-PROTEASE; HOST-DEFENSE; INFECTION; RECEPTOR AB Innate immunity is the first-line defense against pathogens and relies on phagocytes, soluble components, and cell-surface and cytosolic pattern recognition receptors. Despite using hard-wired receptors and signaling pathways, the innate immune response demonstrates surprising specificity to different pathogens. We determined how combinatorial use of innate immune defense mechanisms defines the response. We describe a novel cooperation between a soluble component of the innate immune system, the mannose-binding lectin, and Toll-like receptor 2 that both specifies and amplifies the host response to Staphylococcus aureus. Furthermore, we demonstrate that this cooperation occurs within the phagosome, emphasizing the importance of engulfment in providing the appropriate cellular environment to facilitate the synergy between these defense pathways. C1 [Ip, W. K. Eddie; Takahashi, Kazue; Stuart, Lynda M.; Ezekowitz, R. Alan B.] Harvard Univ, Sch Med, Dept Pediat, Lab Dev Immunol, Boston, MA 02114 USA. [Moore, Kathryn J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metabolism Unit, Boston, MA 02114 USA. [Stuart, Lynda M.] Univ Edinburgh, Ctr Inflammat Res, Edinburgh EH8 9AG, Midlothian, Scotland. RP Ip, WKE (reprint author), Harvard Univ, Sch Med, Dept Pediat, Lab Dev Immunol, Boston, MA 02114 USA. EM eddie_ip@hms.harvard.edu; lstuart@partners.org RI Ip, Eddie/C-3042-2012; OI Moore, kathryn/0000-0003-2505-2547 FU Wellcome Trust [R36731] NR 47 TC 103 Z9 108 U1 0 U2 0 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 JAN 21 PY 2008 VL 205 IS 1 BP 169 EP 181 DI 10.1084/jem.20071164 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 253GQ UT WOS:000252507100017 PM 18180310 ER PT J AU Morin, NA Oakes, PW Hyun, YM Lee, DY Chin, EY King, MR Springer, TA Shimaoka, M Tang, JX Reichner, JS Kim, M AF Morin, Nicole A. Oakes, Patrick W. Hyun, Young-Min Lee, Dooyoung Chin, Eugene Y. King, Michael R. Springer, Timothy A. Shimaoka, Motomu Tang, Jay X. Reichner, Jonathan S. Kim, Minsoo TI Nonmuscle myosin heavy chain IIA mediates integrin LFA-1 de-adhesion during T lymphocyte migration SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CELL-MIGRATION; BLEBBISTATIN INHIBITION; AVIDITY REGULATION; STRUCTURAL BASIS; AFFINITY; ACTIVATION; DOMAIN; TALIN; MOTILITY; REVEALS AB Precise spatial and temporal regulation of cell adhesion and de-adhesion is critical for dynamic lymphocyte migration. Although a great deal of information has been learned about integrin lymphocyte function-associated antigen (LFA)-1 adhesion, the mechanism that regulates efficient LFA-1 de-adhesion from intercellular adhesion molecule (ICAM)-1 during T lymphocyte migration is unknown. Here, we show that nonmuscle myosin heavy chain IIA (MyH9) is recruited to LFA-1 at the uropod of migrating T lymphocytes, and inhibition of the association of MyH9 with LFA-1 results in extreme uropod elongation, defective tail detachment, and decreased lymphocyte migration on ICAM-1, without affecting LFA-1 activation by chemokine CXCL-12. This defect was reversed by a small molecule antagonist that inhibits both LFA-1 affinity and avidity regulation, but not by an antagonist that inhibits only affinity regulation. Total internal reflection fluorescence microscopy of the contact zone between migrating T lymphocytes and ICAM-1 substrate revealed that inactive LFA-1 is selectively localized to the posterior of polarized T lymphocytes, whereas active LFA-1 is localized to their anterior. Thus, during T lymphocyte migration, uropodal adhesion depends on LFA-1 avidity, where MyH9 serves as a key mechanical link between LFA-1 and the cytoskeleton that is critical for LFA-1 de-adhesion. C1 [Morin, Nicole A.; Chin, Eugene Y.; Reichner, Jonathan S.] Rhode Isl Hosp, Dept Surg, Providence, RI 02903 USA. [Morin, Nicole A.; Chin, Eugene Y.; Reichner, Jonathan S.] Brown Univ, Sch Med, Providence, RI 02903 USA. [Oakes, Patrick W.; Tang, Jay X.] Brown Univ, Dept Phys, Providence, RI 02912 USA. [Springer, Timothy A.; Shimaoka, Motomu] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. [Lee, Dooyoung] Univ Rochester, Aab Inst Biomed Sci, David H Smith Ctr Vaccine Biol & Immunol, Dept Chem Engn, Rochester, NY 14642 USA. [King, Michael R.] Univ Rochester, Aab Inst Biomed Sci, David H Smith Ctr Vaccine Biol & Immunol, Dept Biomed Engn, Rochester, NY 14642 USA. [Hyun, Young-Min; Kim, Minsoo] Univ Rochester, Aab Inst Biomed Sci, David H Smith Ctr Vaccine Biol & Immunol, Dept Microbiol & Immunol, Rochester, NY 14642 USA. RP Kim, M (reprint author), Rhode Isl Hosp, Dept Surg, Providence, RI 02903 USA. EM minsoo_kim@urmc.rochester.edu RI King, Michael/A-1138-2007; Lee, Dooyoung/B-9925-2008; OI Reichner, Jonathan/0000-0002-7349-6321 FU NCI NIH HHS [R37 CA031798, R37 CA031798-29]; NHLBI NIH HHS [HL087088, R01 HL087088-01A1, R01 HL087088]; NIGMS NIH HHS [R56 GM066194, R01 GM066194, GM066194] NR 57 TC 81 Z9 85 U1 0 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 JAN 21 PY 2008 VL 205 IS 1 BP 195 EP 205 DI 10.1084/jem.20071543 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 253GQ UT WOS:000252507100019 PM 18195072 ER PT J AU Oh, WY Yun, SH Vakoc, BJ Shishkov, M Desjardins, AE Park, BH de Boer, JF Tearney, GJ Bouma, E AF Oh, W. Y. Yun, S. H. Vakoc, B. J. Shishkov, M. Desjardins, A. E. Park, B. H. de Boer, J. F. Tearney, G. J. Bouma, E. TI High-speed polarization sensitive optical frequency domain imaging with frequency multiplexing SO OPTICS EXPRESS LA English DT Article ID SWEPT SEMICONDUCTOR-LASER; NERVE-FIBER LAYER; COHERENCE TOMOGRAPHY; IN-VIVO; BIREFRINGENCE CHARACTERIZATION; ATHEROSCLEROTIC PLAQUES; BIOLOGICAL TISSUE; LESIONS AB Polarization sensitive optical coherence tomography (PS-OCT) provides a cross-sectional image of birefringence in biological samples that is complementary in many applications to the standard reflectance-based image. Recent ex vivo studies have demonstrated that birefringence mapping enables the characterization of collagen and smooth muscle concentration and distribution in vascular tissues. Instruments capable of applying these measurements percutaneously in vivo may provide new insights into coronary atherosclerosis and acute myocardial infarction. We have developed a polarization sensitive optical frequency domain imaging (PS-OFDI) system that enables high-speed intravascular birefringence imaging through a fiber-optic catheter. The novel design of this system utilizes frequency multiplexing to simultaneously measure reflectance of two incident polarization states, overcoming concerns regarding temporal variations of the catheter fiber birefringence and spatial variations in the birefringence of the sample. We demonstrate circular cross-sectional birefringence imaging of a human coronary artery ex vivo through a flexible fiber-optic catheter with an A-line rate of 62 kHz and a ranging depth of 6.2 mm. (c) 2008 Optical Society of America. C1 [Oh, W. Y.; Yun, S. H.; Vakoc, B. J.; Shishkov, M.; Desjardins, A. E.; Park, B. H.; de Boer, J. F.; Tearney, G. J.; Bouma, E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Oh, W. Y.; Yun, S. H.; Vakoc, B. J.; Shishkov, M.; Desjardins, A. E.; Park, B. H.; de Boer, J. F.; Tearney, G. J.; Bouma, E.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Oh, WY (reprint author), Harvard Univ, Sch Med, 50 Blossom St,BAR 704, Boston, MA 02114 USA. EM woh1@partners.org RI Oh, Wang-Yuhl/C-2055-2011; de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU NCI NIH HHS [R33 CA110130, R33 CA110130-01]; NHLBI NIH HHS [R01 HL076398] NR 31 TC 78 Z9 79 U1 1 U2 16 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD JAN 21 PY 2008 VL 16 IS 2 BP 1096 EP 1103 DI 10.1364/OE.16.001096 PG 8 WC Optics SC Optics GA 252XB UT WOS:000252479700060 PM 18542183 ER PT J AU Kachnic, LA Hong, TS Ryan, DP AF Kachnic, Lisa A. Hong, Theodore S. Ryan, David P. TI Rectal cancer at the crossroads: The dilemma of clinically staged T3, N0,M0 disease SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID TOTAL MESORECTAL EXCISION; PREOPERATIVE RADIOTHERAPY; RANDOMIZED-TRIAL; RADIATION-THERAPY; ADJUVANT THERAPY; CHEMOTHERAPY; CARCINOMA; IMPACT C1 [Kachnic, Lisa A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kachnic, Lisa A.] Boston Univ, Med Ctr, Dept Radiat Oncol, Boston, MA USA. [Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Ryan, David P.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. RP Kachnic, LA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 18 TC 14 Z9 16 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2008 VL 26 IS 3 BP 350 EP 351 DI 10.1200/JCO.2007.14.6365 PG 2 WC Oncology SC Oncology GA 276XO UT WOS:000254177200004 PM 18202407 ER PT J AU Chiao, EY Giordano, TP Richardson, P El-Serag, HB AF Chiao, Elizabeth Y. Giordano, Thomas P. Richardson, Peter El-Serag, Hashem B. TI Human immunodeficiency virus-associated squamous cell cancer of the anus: Epidemiology and outcomes in the highly active Antiretroviral therapy era SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HIV-POSITIVE PATIENTS; ANAL CANCER; INTRAEPITHELIAL LESIONS; INFECTED PATIENTS; CARCINOMA; RISK; AIDS; MEN; CHEMORADIATION; TOLERANCE AB Purpose To evaluate and determine predictors of squamous cell carcinoma of the anus (SCCA) outcomes in the highly active antiretroviral therapy ( HAART) era for HIV-positive and -negative individuals using large national Veterans Affairs (VA) Administration databases. Patients and Methods We used the VA administrative databases to perform a retrospective cohort study in 1,184 veterans diagnosed with SCCA between 1998 and 2004. We calculated HIV infection rates and used logistic regression to identify epidemiologic factors that were associated with HIV infection. Kaplan-Meier curves and Cox proportional hazards models were calculated to compare survival between HIV-positive and HIV-negative veterans. Results In our cohort, 175 patients (15%) were HIV positive. The median age of the HIV-negative and -positive patients was 63 and 49 years, respectively ( P =.001). Individuals with HIV were eight times more likely to be male ( P =.01) and three times more likely to be African American ( P =.001). There were no differences between HIV-positive and HIV-negative individuals in the receipt of treatment. The 2-year observed survival rates were 77% and 75% among HIV-positive and HIV-negative individuals, respectively. In multivariate Cox analysis, significant predictors of survival were age, sex, metastasis at diagnosis, and comorbidity score. HIV infection did not affect survival. Conclusion A noteworthy proportion of individuals with SCCA in the VA system are HIV positive. HIV-associated SCCA seems mainly to be a disease among younger men. Survival of SCCA is equivalent between HIV-positive and HIV-negative individuals in the HAART era. Treatment should not be withheld or deintensified based on HIV status. C1 Michael E DeBakey Vet Affairs Med Ctr 152, Houston Ctr Quality Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Chiao, EY (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, Houston Ctr Quality Care & Utilizat Studies, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM echiao@bcm.edu FU NCI NIH HHS [K23CA124318]; NIMH NIH HHS [K23MH67505] NR 29 TC 64 Z9 64 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2008 VL 26 IS 3 BP 474 EP 479 DI 10.1200/JCO.2007.14.2810 PG 6 WC Oncology SC Oncology GA 276XO UT WOS:000254177200024 PM 18202423 ER PT J AU Ziegler, DS Kung, AL Kieran, MW AF Ziegler, David S. Kung, Andrew L. Kieran, Mark W. TI Anti-apoptosis mechanisms in malignant gliomas SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID GROWTH-FACTOR RECEPTOR; HUMAN GLIOBLASTOMA CELLS; HIGH-GRADE ASTROCYTOMA; BCL-2 FAMILY PROTEINS; BH3 MIMETIC ABT-737; PHASE-II TRIAL; IN-VIVO; IMATINIB MESYLATE; RECURRENT GLIOBLASTOMA; MAMMALIAN TARGET AB Malignant gliomas are characterized by an intrinsic resistance to apoptosis. Increasing evidence suggests that this is a fundamental mechanism by which gliomas evade elimination when treated with both conventional and targeted therapies. In this review, we describe the multiple antiapoptotic signals that have been demonstrated to be active in malignant gliomas. We describe the preclinical evidence that suggests that targeting those signaling anomalies can increase tumor responsiveness and enhance the elimination of gliomas in preclinical models. We discuss recent advances in translating pro-apoptotic compounds to clinical trial, and the potential for implementing agents that target the apoptotic pathway as a strategy for improving the outcomes for patients with high-grade gliomas. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Ziegler, David S.] Sydney Childrens Hosp, Ctr Childrens Canc & Blood Disorders, Randwick, NSW 2031, Australia. Harvard Univ, Sch Med, Boston, MA USA. RP Ziegler, DS (reprint author), Sydney Childrens Hosp, Ctr Childrens Canc & Blood Disorders, High St, Randwick, NSW 2031, Australia. EM d.ziegler@unsw.edu.au OI Kieran, Mark/0000-0003-2184-7692; Kung, Andrew/0000-0002-9091-488X NR 90 TC 63 Z9 63 U1 0 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2008 VL 26 IS 3 BP 493 EP 500 DI 10.1200/JCO.2007.13.9717 PG 8 WC Oncology SC Oncology GA 276XO UT WOS:000254177200026 PM 18202424 ER PT J AU Rivera, ML Donnelly, J Parry, BA Dinizio, A Johnson, CL Kline, JA Kabrhel, C AF Rivera, Morris L. Donnelly, Jason Parry, Blair A. Dinizio, Anthony Johnson, Charles L. Kline, Jeffrey A. Kabrhel, Christopher TI Prospective, randomized evaluation of a personal digital assistant-based research tool in the emergency department SO BMC MEDICAL INFORMATICS AND DECISION MAKING LA English DT Article ID CARE AB Background: Personal digital assistants (PDA) offer putative advantages over paper for collecting research data. However, there are no data prospectively comparing PDA and paper in the emergency department. The aim of this study was to prospectively compare the performance of PDA and paper enrollment instruments with respect to time required and errors generated. Methods: We randomized consecutive patients enrolled in an ongoing prospective study to having their data recorded either on a PDA or a paper data collection instrument. For each method, we recorded the total time required for enrollment, and the time required for manual transcription (paper) onto a computer database. We compared data error rates by examining missing data, nonsensical data, and errors made during the transcription of paper forms. Statistical comparisons were performed by Kruskal-Wallis and Poisson regression analyses for time and errors, respectively. Results: We enrolled 68 patients (37 PDA, 31 paper). Two of 31 paper forms were not available for analysis. Total data gathering times, inclusive of transcription, were significantly less for PDA (6: 13 min per patient) compared to paper (9: 12 min per patient; p < 0.001). There were a total of 0.9 missing and nonsense errors per paper form compared to 0.2 errors per PDA form (p < 0.001). An additional 0.7 errors per paper form were generated during transcription. In total, there were 1.6 errors per paper form and 0.2 errors per PDA form (p < 0.001). Conclusion: Using a PDA-based data collection instrument for clinical research reduces the time required for data gathering and significantly improves data integrity. C1 [Rivera, Morris L.] Hilo Med Ctr, Dept Emergency Med, Hilo, HI USA. [Rivera, Morris L.; Donnelly, Jason; Parry, Blair A.; Dinizio, Anthony; Kabrhel, Christopher] Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA. [Johnson, Charles L.] BreathQuant Med Syst Inc, Charlotte, NC USA. [Kline, Jeffrey A.] Carolinas Med Ctr, Dept Emergency Med, Charlotte, NC 28203 USA. RP Rivera, ML (reprint author), Hilo Med Ctr, Dept Emergency Med, Hilo, HI USA. EM moispo1@hotmail.com; jason_donnelly@nymc.edu; bparry@partners.org; dinizio@bc.edu; charlie@studymaker.com; jkline@carolina.rr.com; ckabrhel@partners.org OI Kabrhel, Christopher/0000-0002-8699-7176 NR 11 TC 9 Z9 9 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6947 J9 BMC MED INFORM DECIS JI BMC Med. Inform. Decis. Mak. PD JAN 18 PY 2008 VL 8 AR 3 DI 10.1186/1472-6947-8-3 PG 7 WC Medical Informatics SC Medical Informatics GA 273ZI UT WOS:000253970600001 PM 18205902 ER PT J AU Pakotiprapha, D Inuzuka, Y Bowman, BR Moolenaar, GF Goosen, N Jeruzalmi, D Verdinel, GL AF Pakotiprapha, Danaya Inuzuka, Yoshihiko Bowman, Brian R. Moolenaar, Geri F. Goosen, Nora Jeruzalmi, David Verdinel, Gregory L. TI Crystal structure of Bacillus stearothermophilus UvrA provides insight into ATP-modulated dimerization, UvrB interaction, and DNA binding SO MOLECULAR CELL LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; ESCHERICHIA-COLI UVRA; SITE-SPECIFIC MUTAGENESIS; TERMINAL ZINC-FINGER; GROUP-A PROTEIN; ABC-TRANSPORTER; MACROMOLECULAR STRUCTURES; THERMUS-THERMOPHILUS; HEMOLYSIN-B; ACTIVE-SITE AB The nucleotide excision repair pathway corrects many structurally unrelated DNA lesions. Damage recognition in bacteria is performed by UvrA, a member of the ABC ATPase superfamily whose functional form is a dimer with four nucleotide-binding domains (NBDs), two per protomer. In the 3.2 angstrom structure of UvrA from Bacillus stearothermophilus, we observe that the nucleotide-binding sites are formed in an intramolecular fashion and are not at the dimer interface as is typically found in other ABC ATPases. UvrA also harbors two unique domains; we show that one of these is required for interaction with UvrB, its partner in lesion recognition. In addition, UvrA contains three zinc modules, the number and ligand sphere of which differ from previously published models. Structural analysis, biochemical experiments, surface electrostatics, and sequence conservation form the basis for models of ATP-modulated dimerization, UvrA-UvrB interaction, and DNA binding during the search for lesions. C1 [Pakotiprapha, Danaya; Jeruzalmi, David; Verdinel, Gregory L.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Inuzuka, Yoshihiko; Bowman, Brian R.; Verdinel, Gregory L.] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. [Moolenaar, Geri F.; Goosen, Nora] Leiden Univ, Leiden Inst Chem, Mol Genet Lab, NL-2300 RA Leiden, Netherlands. [Verdinel, Gregory L.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. RP Jeruzalmi, D (reprint author), Harvard Univ, Dept Mol & Cellular Biol, 7 Divin Av, Cambridge, MA 02138 USA. EM dj@mcb.harvard.edu; gregory_verdine@harvard.edu RI Pakotiprapha, Danaya/B-1032-2013 OI Pakotiprapha, Danaya/0000-0002-1639-6105 FU NCI NIH HHS [CA100742, R01 CA100742, R01 CA100742-05]; NIGMS NIH HHS [F32 GM077935-01, F32 GM077935, F32 GM077935-02] NR 69 TC 46 Z9 47 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JAN 18 PY 2008 VL 29 IS 1 BP 122 EP 133 DI 10.1016/j.molcel.2007.10.026 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 253NN UT WOS:000252525000012 PM 18158267 ER PT J AU Flaherty, AW AF Flaherty, Alice W. TI Artscience: Creativity in the post-Google generation SO NATURE LA English DT Book Review C1 [Flaherty, Alice W.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Flaherty, Alice W.] Massachusetts Gen Hosp, Movement Disorders Fellowship, Boston, MA 02114 USA. RP Flaherty, AW (reprint author), Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 17 PY 2008 VL 451 IS 7176 BP 246 EP 246 DI 10.1038/451246a PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 252FJ UT WOS:000252432100018 ER PT J AU Ebert, BL Pretz, J Bosco, J Chang, CY Tamayo, P Galili, N Raza, A Root, DE Attar, E Ellis, SR Golub, TR AF Ebert, Benjamin L. Pretz, Jennifer Bosco, Jocelyn Chang, Cindy Y. Tamayo, Pablo Galili, Naomi Raza, Azra Root, David E. Attar, Eyal Ellis, Steven R. Golub, Todd R. TI Identification of RPS14 as a 5q(-) syndrome gene by RNA interference screen SO NATURE LA English DT Article ID DIAMOND-BLACKFAN ANEMIA; CHROMOSOME 5Q DELETION; MYELOID DISORDERS; EXPRESSION; CANCER AB Somatic chromosomal deletions in cancer are thought to indicate the location of tumour suppressor genes, by which a complete loss of gene function occurs through biallelic deletion, point mutation or epigenetic silencing, thus fulfilling Knudson's two- hit hypothesis(1). In many recurrent deletions, however, such biallelic inactivation has not been found. One prominent example is the 5q(-) syndrome, a subtype of myelodysplastic syndrome characterized by a defect in erythroid differentiation(2). Here we describe an RNA-mediated interference ( RNAi)- based approach to discovery of the 5q(-) disease gene. We found that partial loss of function of the ribosomal subunit protein RPS14 phenocopies the disease in normal haematopoietic progenitor cells, and also that forced expression of RPS14 rescues the disease phenotype in patient- derived bone marrow cells. In addition, we identified a block in the processing of pre- ribosomal RNA in RPS14- deficient cells that is functionally equivalent to the defect in Diamond- Blackfan anaemia, linking the molecular pathophysiology of the 5q(-) syndrome to a congenital syndrome causing bone marrow failure. These results indicate that the 5q(-) syndrome is caused by a defect in ribosomal protein function and suggest that RNAi screening is an effective strategy for identifying causal haploinsufficiency disease genes. C1 [Ebert, Benjamin L.; Pretz, Jennifer; Bosco, Jocelyn; Chang, Cindy Y.; Tamayo, Pablo; Root, David E.; Golub, Todd R.] MIT, Broad Inst, Cambridge, MA 02142 USA. [Ebert, Benjamin L.; Pretz, Jennifer; Bosco, Jocelyn; Chang, Cindy Y.; Tamayo, Pablo; Root, David E.; Golub, Todd R.] Harvard Univ, Cambridge, MA 02142 USA. [Ebert, Benjamin L.; Golub, Todd R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ebert, Benjamin L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Hematol, Boston, MA 02115 USA. [Galili, Naomi; Raza, Azra] Univ Massachusetts, Sch Med, Div Hematol Oncol, Worcester, MA 01655 USA. [Attar, Eyal] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. [Ellis, Steven R.] Univ Louisville, Dept Biochem & Mol Biol, Louisville, KY 40292 USA. [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Golub, TR (reprint author), MIT, Broad Inst, Cambridge, MA 02142 USA. EM golub@broad.mit.edu FU Howard Hughes Medical Institute; NCI NIH HHS [T32 CA009172]; NHLBI NIH HHS [K08 HL078818, R01 HL079583, R01 HL082945] NR 28 TC 479 Z9 496 U1 2 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 17 PY 2008 VL 451 IS 7176 BP 335 EP U7 DI 10.1038/nature06494 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 252FJ UT WOS:000252432100050 PM 18202658 ER PT J AU Schatton, T Murphy, GF Frank, NY Yamaura, K Waaga-Gasser, AM Gasser, M Zhan, Q Jordan, S Duncan, LM Weishaupt, C Fuhlbrigge, RC Kupper, TS Sayegh, MH Frank, MH AF Schatton, Tobias Murphy, George F. Frank, Natasha Y. Yamaura, Kazuhiro Waaga-Gasser, Ana Maria Gasser, Martin Zhan, Qian Jordan, Stefan Duncan, Lyn M. Weishaupt, Carsten Fuhlbrigge, Robert C. Kupper, Thomas S. Sayegh, Mohamed H. Frank, Markus H. TI Identification of cells initiating human melanomas SO NATURE LA English DT Article ID ACUTE MYELOID-LEUKEMIA; MALIGNANT-MELANOMA; STEM-CELLS; CANCER-CELLS; EXPRESSION; CHEMORESISTANCE; GENE AB Tumour- initiating cells capable of self- renewal and differentiation, which are responsible for tumour growth, have been identified in human haematological malignancies(1,2) and solid cancers(3-6). If such minority populations are associated with tumour progression in human patients, specific targeting of tumour- initiating cells could be a strategy to eradicate cancers currently resistant to systemic therapy. Here we identify a subpopulation enriched for human malignant- melanoma- initiating cells ( MMIC) defined by expression of the chemoresistance mediator ABCB5 ( refs 7, 8) and show that specific targeting of this tumorigenic minority population inhibits tumour growth. ABCB5(+) tumour cells detected in human melanoma patients show a primitive molecular phenotype and correlate with clinical melanoma progression. In serial human- to-mouse xenotransplantation experiments, ABCB5(+) melanoma cells possess greater tumorigenic capacity than ABCB5(-) bulk populations and re- establish clinical tumour heterogeneity. In vivo genetic lineage tracking demonstrates a specific capacity of ABCB5(+) sub-populations for self- renewal and differentiation, because ABCB5(+) cancer cells generate both ABCB5(+) and ABCB5(-) progeny, whereas ABCB5(-) tumour populations give rise, at lower rates, exclusively to ABCB5(-) cells. In an initial proof- of- principle analysis, designed to test the hypothesis that MMIC are also required for growth of established tumours, systemic administration of a monoclonal antibody directed at ABCB5, shown to be capable of inducing antibody- dependent cell- mediated cytotoxicity in ABCB5(+) MMIC, exerted tumour- inhibitory effects. Identification of tumour- initiating cells with enhanced abundance in more advanced disease but susceptibility to specific targeting through a defining chemoresistance determinant has important implications for cancer therapy. C1 [Schatton, Tobias; Frank, Natasha Y.; Yamaura, Kazuhiro; Jordan, Stefan; Sayegh, Mohamed H.; Frank, Markus H.] Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. [Schatton, Tobias; Murphy, George F.; Frank, Natasha Y.; Yamaura, Kazuhiro; Zhan, Qian; Jordan, Stefan; Sayegh, Mohamed H.; Frank, Markus H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Frank, Natasha Y.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Waaga-Gasser, Ana Maria; Gasser, Martin] Univ Wurzburg, Dept Surg, D-97080 Wurzburg, Germany. [Duncan, Lyn M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Weishaupt, Carsten; Fuhlbrigge, Robert C.; Kupper, Thomas S.] Brigham & Womens Hosp, Dept Dermatol, Harvard Skin Dis Res Ctr, Boston, MA 02115 USA. RP Frank, MH (reprint author), Childrens Hosp, Transplantat Res Ctr, 300 Longwood Ave, Boston, MA 02115 USA. EM mfrank@rics.bwh.harvard.edu RI Jordan, Stefan/G-6243-2011; Frank, Markus/O-1625-2014; OI Murphy, George/0000-0003-3464-793X; Frank, Markus/0000-0002-1312-0488; Jordan, Stefan/0000-0001-9330-1715 FU NCI NIH HHS [R01 CA113796-01A1, R01 CA113796]; NHLBI NIH HHS [R01 HL084815, R01 HL084815-17]; NIAMS NIH HHS [P30 AR042689, P30 AR042689-159006]; NINDS NIH HHS [K08 NS051349] NR 30 TC 772 Z9 813 U1 1 U2 35 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 17 PY 2008 VL 451 IS 7176 BP 345 EP U11 DI 10.1038/nature06489 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 252FJ UT WOS:000252432100052 PM 18202660 ER PT J AU Broom, WJ Johnson, DV Auwarter, KE Iafrate, AJ Russ, C Al-Chalabi, A Sapp, PC McKenna-Yasek, D Andersen, PM Brown, RH AF Broom, W. J. Johnson, D. V. Auwarter, K. E. Iafrate, A. J. Russ, C. Al-Chalabi, A. Sapp, P. C. McKenna-Yasek, D. Andersen, P. M. Brown, R. H., Jr. TI SOD1(A4V)-mediated ALS: Absence of a closely linked modifier gene and origination in Asia SO NEUROSCIENCE LETTERS LA English DT Article DE amyotrophic lateral sclerosis; heredity; founder effect; polymorphism; genetic; haplotypes ID AMYOTROPHIC-LATERAL-SCLEROSIS; CU/ZN SUPEROXIDE-DISMUTASE; MUTATIONS; HAPLOTYPE; SURVIVAL; MUTANTS AB Familial amyotrophic lateral sclerosis (ALS) accounts for 10% of all ALS. Approximately 20% of cases are due to mutations in the Cu/Zn superoxide dismutase gene (SOD1). In North America, SOD1(A4V) is the most common SOD1 mutation. Carriers of the SOD1(A4V) mutation share a common phenotype with rapid disease progression and death on average occurring at 1.4 years (versus 3-5 years with other dominant SOD1 mutations). Previous studies of SOD1(A4V) carriers identified a common haplotype around the SOD1 locus, suggesting a common founder for most SOD1(A4V) patients. In the current study we sequenced the entire common haplotypic region around SOD1 to test the hypothesis that polymorphisms in either previously undescribed coding regions or non-coding regions around SOD1 are responsible for the more aggressive phenotype in SOD1(A4V)-mediated ALS. We narrowed the conserved region around the SOD1 gene in SOD1(A4V) ALS to 2.8 Kb and identified five novel SNPs therein. None of these variants was specifically found in all SOD1(A4V) patients. It therefore appears likely that the aggressive nature of the SOD1(A4V) mutation is not a result of a modifying factor within the region around the SOD1 gene. Founder analysis estimates that the A4V mutation occurred 540 generations (similar to 12,000 years) ago (95% CI 480-700). The conserved minimal haplotype is statistically more similar to Asian than European population DNA sets, suggesting that the A4V mutation arose in native Asian-Americans who reached the Americas through the Bering Strait. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Broom, W. J.; Johnson, D. V.; Auwarter, K. E.; Russ, C.; Sapp, P. C.; McKenna-Yasek, D.; Brown, R. H., Jr.] Massachusetts Gen Hosp, Day Neuromuscular Res Lab, Charlestown, MA 02129 USA. [Iafrate, A. J.] Massachusetts Gen Hosp, Diagnost Mol Pathol Lab, Boston, MA 02114 USA. [Al-Chalabi, A.] Kings Coll London, MRC Ctr Neurodegenetat Res, Inst Psychiat, London SE5 8AF, England. [Sapp, P. C.] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. [Andersen, P. M.] Umea Univ, Dept Neurol, S-90187 Umea, Sweden. RP Broom, WJ (reprint author), Massachusetts Gen Hosp, Day Neuromuscular Res Lab, 114 16th St,Navy Yard, Charlestown, MA 02129 USA. EM wendy.broom@gmail.com RI Al-Chalabi, Ammar/E-5361-2010 OI Al-Chalabi, Ammar/0000-0002-4924-7712 FU Howard Hughes Medical Institute NR 21 TC 9 Z9 9 U1 0 U2 0 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 JAN 17 PY 2008 VL 430 IS 3 BP 241 EP 245 DI 10.1016/j.neulet.2007.11.004 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 261IH UT WOS:000253071800011 PM 18055113 ER PT J AU Loftis, JM Huckans, M Ruimy, S Hinrichs, DJ Hauser, P AF Loftis, Jennifer M. Huckans, Marilyn Ruimy, Samantha Hinrichs, David J. Hauser, Peter TI Depressive symptoms in patients with chronic hepatitis C are correlated with elevated plasma levels of interleukin-1 beta and tumor necrosis factor-alpha SO NEUROSCIENCE LETTERS LA English DT Article DE cytokines; inflammation; chronic infection; beck depression inventory; hypothalamic-pituitary-adrenal axis; serotonin ID OF-THE-LITERATURE; MAJOR DEPRESSION; MULTIPLE-SCLEROSIS; CYTOKINES; INFLAMMATION; ASSOCIATION; NEUROTOXICITY; HYPOTHESIS; DISORDER; THERAPY AB Studies suggest that cytokines have a role in the biology of depression. In this study, we evaluated depression and cytokine levels in patients with and without chronic hepatitis C (HCV) to better assess how chronic infection alters cytokines levels and may contribute to depressive symptomotology. Twenty-three adults with (n=16) and without (n=7) HCV were recruited through the Portland VA Medical Center. Research participants were excluded for current substance abuse, psychotic disorder, liver cirrhosis, or interferon (IFN) therapy. Participants completed the Beck Depression Inventory-II (BDI-II) and a blood draw to evaluate plasma cytokine levels [i.e., interleukin (IL)-1 beta, IL-10 and tumor necrosis factor (TNF)-alpha]. t-Tests were performed to compare cytokine levels in patients with or without HCV. HCV patients showed higher TNF-alpha values compared to patients without HCV (group means =7.94 vs. 3.41 pg/mL, respectively, p=0.047). There were no significant differences between the groups for the other cytokines assessed. In patients with HCV, TNF-alpha and IL-1 beta levels (but not IL-10) were correlated with BDI-II scores [r=0.594, p=0.020 and r=0.489, p=0.055 (trend), respectively]. Taken together, these results show an association between severity of depressive symptoms and expression of pro-inflammatory cytokines in patients with HCV. Future studies should investigate how inflammatory mediators play a role in the expression of specific depressive symptoms in patients with chronic infection. Patients with HCV represent an interesting model to examine this relationship. Published by Elsevier Ireland Ltd. C1 [Loftis, Jennifer M.; Huckans, Marilyn; Ruimy, Samantha; Hauser, Peter] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Psychiat, Behav Hlth & Clin Neurosci Div, Portland, OR 97239 USA. [Loftis, Jennifer M.; Huckans, Marilyn; Hauser, Peter] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. [Loftis, Jennifer M.; Huckans, Marilyn; Hauser, Peter] Oregon Hlth & Sci Univ, Portland VA Med Ctr, NW Hepatitis C Resource Ctr, Dept Psychiat,Behav Hlth & Clin Neurosci Div, Portland, OR 97239 USA. RP Loftis, JM (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Psychiat, Behav Hlth & Clin Neurosci Div, Portland, OR 97239 USA. EM loftisj@ohsu.edu FU NIMH NIH HHS [F32 MH071137-02, F32 MH071137] NR 30 TC 65 Z9 67 U1 0 U2 1 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 JAN 17 PY 2008 VL 430 IS 3 BP 264 EP 268 DI 10.1016/j.neulet.2007.11.001 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 261IH UT WOS:000253071800015 PM 18063307 ER PT J AU Magee, CC Coggins, MP Foster, CS Muse, VV Colvin, RB AF Magee, Colm C. Coggins, Matthew P. Foster, C. Stephen Muse, Victorine V. Colvin, Robert B. TI A woman with postpartum visual loss, shortness of breath, and renal failure - Postpartum renal failure due to thrombotic microangiopathy, associated with antiphospholipid antibodies SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID INTERNATIONAL CONSENSUS STATEMENT; CLASSIFICATION CRITERIA; NORMAL-PREGNANCY; POST-PARTUM; PREECLAMPSIA; MANIFESTATIONS; ENDOTHELIOSIS; EXPRESSION; DISEASE; UPDATE C1 [Magee, Colm C.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [Coggins, Matthew P.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Muse, Victorine V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Magee, Colm C.; Coggins, Matthew P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Muse, Victorine V.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Colvin, Robert B.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Foster, C. Stephen] Immunol & Uveitis Fdn, Cambridge, MA USA. [Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA. RP Magee, CC (reprint author), Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. NR 24 TC 2 Z9 3 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 JAN 17 PY 2008 VL 358 IS 3 BP 275 EP 289 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 251LS UT WOS:000252375600011 PM 18199867 ER PT J AU Arlotta, P Molyneaux, BJ Jabaudon, D Yoshida, Y Macklis, JD AF Arlotta, Paola Molyneaux, Bradley J. Jabaudon, Denis Yoshida, Yutaka Macklis, Jeffrey D. TI Ctip2 controls the differentiation of medium spiny neurons and the establishment of the cellular architecture of the striatum SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Ctip2; striatum; medium spiny neurons; striasomes; striatal patches; secretagogin ID LATERAL GANGLIONIC EMINENCE; CENTRAL-NERVOUS-SYSTEM; TRANSCRIPTION FACTOR; BASAL GANGLIA; RAT STRIATUM; MAMMALIAN FOREBRAIN; PROJECTION NEURONS; GABAERGIC NEURONS; PATTERN-FORMATION; GENE-EXPRESSION AB Striatal medium spiny neurons (MSN) are critically involved in motor control, and their degeneration is a principal component of Huntington's disease. We find that the transcription factor Ctip2 (also known as Bcl11b) is central to MSN differentiation and striatal development. Within the striatum, it is expressed by all MSN, although it is excluded from essentially all striatal interneurons. In the absence of Ctip2, MSN do not fully differentiate, as demonstrated by dramatically reduced expression of a large number of MSN markers, including DARPP-32, FOXP1, Chrm4, Reelin, MOR1 (mu-opioid receptor 1), glutamate receptor 1, and Plexin-D1. Furthermore, MSN fail to aggregate into patches, resulting in severely disrupted patch-matrix organization within the striatum. Finally, heterotopic cellular aggregates invade the Ctip2(-/-) striatum, suggesting a failure by MSN to repel these cells in the absence of Ctip2. This is associated with abnormal dopaminergic innervation of the mutant striatum and dramatic changes in gene expression, including dysregulation of molecules involved in cellular repulsion. Together, these data indicate that Ctip2 is a critical regulator of MSN differentiation, striatal patch development, and the establishment of the cellular architecture of the striatum. C1 [Arlotta, Paola; Molyneaux, Bradley J.; Jabaudon, Denis; Macklis, Jeffrey D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Neurosurg & Neurol,Program Neurosci, Ctr Nervous Syst Repair,Nayef Al Rodhan Labs, Boston, MA 02114 USA. [Arlotta, Paola; Molyneaux, Bradley J.; Jabaudon, Denis; Macklis, Jeffrey D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Stem Cell Inst, Boston, MA 02114 USA. [Yoshida, Yutaka] Columbia Univ, Howard Hughes Med Inst, Ctr Neurobiol & Behav, Dept Biochem & Mol Biophys, New York, NY 10032 USA. RP Macklis, JD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Neurosurg & Neurol,Program Neurosci, Ctr Nervous Syst Repair,Nayef Al Rodhan Labs, Boston, MA 02114 USA. EM jeffrey_macklis@hms.harvard.edu OI Molyneaux, Bradley/0000-0002-3377-1229; Jabaudon, Denis/0000-0003-2438-4769 FU NINDS NIH HHS [NS49553, NS45523] NR 60 TC 112 Z9 113 U1 1 U2 16 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 16 PY 2008 VL 28 IS 3 BP 622 EP 632 DI 10.1523/JNEUROSCI.2986-07.2008 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 252FP UT WOS:000252432700007 PM 18199763 ER PT J AU Francis, P Crown, J Di Leo, A Buyse, M Balil, A Andersson, M Nordenskjold, B Lang, I Jakesz, R Vorobiof, D Gutierrez, J van Hazel, G Dolci, S Jamin, S Bendahmane, B Gelber, RD Goldhirsch, A Castiglione-Gertsch, M Piccart-Gebhart, M AF Francis, Prudence Crown, John Di Leo, Angelo Buyse, Marc Balil, Ana Andersson, Michael Nordenskjold, Bo Lang, Istvan Jakesz, Raimund Vorobiof, Daniel Gutierrez, Jorge van Hazel, Guy Dolci, Stella Jamin, Sophie Bendahmane, Belguendouz Gelber, Richard D. Goldhirsch, Aron Castiglione-Gertsch, Monica Piccart-Gebhart, Martine CA BIG 02-98 Collaborat Grp TI Adjuvant chemotherapy with sequential or concurrent anthracycline and docetaxel: Breast International Group 02-98 randomized trial SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID DOXORUBICIN PLUS CYCLOPHOSPHAMIDE; PHASE-II TRIAL; COMBINATION CHEMOTHERAPY; 1ST-LINE TREATMENT; CANCER PATIENTS; THERAPY; FLUOROURACIL; METHOTREXATE; CMF; EPIRUBICIN AB Background Docetaxel is more effective than doxorubicin for patients with advanced breast cancer. The Breast International Group 02-98 randomized trial tested the effect of incorporating docetaxel into anthracycline-based adjuvant chemotherapy and compared sequential vs concurrent administration of doxorubicin and docetaxel. Methods Patients with lymph node - positive breast cancer ( n = 2887) were randomly assigned to one of four treatments: 1) sequential control ( four cycles of doxorubicin at 75 mg/ m(2), followed by three cycles of cyclophosphamide, methotrexate, and 5-fluorouracil [CMF]); 2) concurrent control (four cycles of doxorubicin at 60 mg/ m(2) plus cyclophosphamide at 600 mg/m(2), followed by three cycles of CMF); 3) sequential docetaxel ( three cycles of doxorubicin at 75 mg/m(2), followed by three cycles of docetaxel at 100 mg/ m(2), followed by three cycles of CMF); 4) concurrent docetaxel ( four cycles of doxorubicin at 50 mg/ m(2) plus docetaxel at 75 mg/ m(2), followed by three cycles of CMF). The primary comparison evaluated the efficacy of including docetaxel regardless of schedule and was planned after 1215 disease-free survival ( DFS) events ( ie, relapse, second primary cancer, or death from any cause). Docetaxel and control treatment groups were compared by log-rank tests, and hazard ratios ( HR) of DFS events were calculated by Cox modeling. All statistical tests were two-sided. Results Due to a lower-than-anticipated rate of relapse, this analysis was performed after 5 years with 732 events. Patients in control arms had a 5-year DFS of 73% ( 95% confidence interval [ CI] = 70% to 75%). Docetaxel treatment resulted in an improvement in DFS of borderline statistical significance compared with control treatment ( HR = 0.86, 95% CI = 0.74 to 1.00; P =.05). However, DFS in the sequential docetaxel arm was better than that in the concurrent docetaxel arm ( HR = 0.83, 95% CI = 0.69 to 1.00) and in the sequential control arm ( HR = 0.79, 95% CI = 0.64 to 0.98). Conclusions Incorporating docetaxel into anthracycline-based therapy resulted in an improvement in DFS that was of borderline statistical significance. However, important differences may be related to doxorubicin and docetaxel scheduling, with sequential but not concurrent administration, appearing to produce better DFS than anthracycline- based chemotherapy. C1 [Francis, Prudence] Peter MacCallum Canc Inst, Div Haematol & Med Oncol, Melbourne, Vic 8006, Australia. [Francis, Prudence] Australian New Zealand Breast Canc Trials Grp, Newcastle, NSW, Australia. [Francis, Prudence] Int Breast Canc Study Grp, Bern, Switzerland. [Crown, John] Irish Clin Oncol Res Grp, Dublin, Ireland. [Di Leo, Angelo] Hosp Prato, Prato, Italy. [Buyse, Marc] Int Inst Drug Dev, Louvain, Belgium. [Balil, Ana] Grp Espanol Invest & Canc Mama, Madrid, Spain. [Balil, Ana] Hosp Arnau Vilanova, Lleida, Spain. [Andersson, Michael] Danish Breast Canc Cooperat Grp, Copenhagen, Denmark. [Nordenskjold, Bo] Univ Sjukhuset, Swedish Breast Canc Grp, Linkoping, Sweden. [Lang, Istvan] Natl Inst Oncol, Budapest, Hungary. [Jakesz, Raimund] Vienna Med Sch, Austrian Breast & Colorectal Canc Study Grp, Vienna, Austria. [Vorobiof, Daniel] Sandton Oncol Ctr, Johannesburg, South Africa. [Gutierrez, Jorge] Grp Oncol Cooperat Chileno Invest, Clin Las Condes, Santiago, Chile. [van Hazel, Guy] Mt Hosp, Perth, WA, Australia. [Dolci, Stella; Jamin, Sophie; Piccart-Gebhart, Martine] Inst Jules Bordet, Breast European Adjuvant Studies Team, B-1000 Brussels, Belgium. [Bendahmane, Belguendouz] Sanofi Aventis, Paris, France. [Gelber, Richard D.] Ins Breast Canc Study Grp IBCSG, Ctr Stat, Boston, MA USA. [Gelber, Richard D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Goldhirsch, Aron] European Inst Oncol, IBCSG Sci Comm, Milan, Italy. [Castiglione-Gertsch, Monica] IBCSG Coordinating Ctr, Bern, Switzerland. [Castiglione-Gertsch, Monica] Inselspital Bern, Bern, Switzerland. RP Francis, P (reprint author), Peter MacCallum Canc Inst, Div Haematol & Med Oncol, Locked Bag 1,A Beckett St, Melbourne, Vic 8006, Australia. EM prue.francis@petermac.org RI Francis, Prudence/J-4003-2012 FU NCI NIH HHS [CA075362] NR 29 TC 100 Z9 100 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 16 PY 2008 VL 100 IS 2 BP 121 EP 133 DI 10.1093/jnci/djm287 PG 13 WC Oncology SC Oncology GA 258FO UT WOS:000252854000010 PM 18182617 ER PT J AU Kuo, B McCallum, RW Koch, KL Sitrin, MD Wo, JM Chey, WD Hasler, WL Lackner, JM Katzt, LA Semler, JR Wilding, GE Parkman, HP AF Kuo, B. McCallum, R. W. Koch, K. L. Sitrin, M. D. Wo, J. M. Chey, W. D. Hasler, W. L. Lackner, J. M. Katzt, L. A. Semler, J. R. Wilding, G. E. Parkman, H. P. TI Comparison of gastric emptying of a nondigestible capsule to a radio-labelled meal in healthy and gastroparetic subjects SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID HEIDELBERG CAPSULE; GASTROINTESTINAL PH; RADIOPAQUE MARKERS; SCINTIGRAPHY; TRANSIT; REPRODUCIBILITY; SOLIDS; HUMANS; TIME AB Background Gastric emptying scintigraphy (GES) using a radio-labelled meal is used to measure gastric emptying. A nondigestible capsule, SmartPill, records luminal pH, temperature, and pressure during gastrointestinal transit providing a measure of gastric emptying time (GET). Aims To compare gastric emptying time and GES by assessing their correlation, and to compare GET and GES for discriminating healthy subjects from gastroparetics. Methods Eighty-seven healthy subjects and 61 gastroparetics enrolled with Fasted subjects were ingested capsule simultaneous SmartPill and GES. and [Tc-99m]-SC radio-labelled meal. Images were obtained every 30 min for 6 h. Gastric emptying time and percentage of meal remaining at 2/4 h were determined for each subject. The sensitivity/specificity and receiver operating characteristic analysis of each measure were determined for each subject. Results Correlation between GET and GES-4 h was 0.73 and GES-2 h was 0.63. The diagnostic accuracy from the receiver operating characteristic curve between gastroparetics and healthy subjects was GET = 0.83, GES-4 h = 0.82 and GES-2 h = 0.79. The 300-min cut-off time for GET gives sensitivity of 0.65 and specificity of 0.87 for diagnosis of gastroparesis. The corresponding sensitivity/specificity for 2 and 4 h standard GES measures were 0.34/0.93 and 0.44/0.93, respectively. Conclusion SmartPill GET correlates with GES and discriminates between healthy and gastroparetic subjects offering a nonradioactive, standardized, ambulatory alternative to scintigraphy. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Kuo, B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastroenterol Unit, Boston, MA USA. [McCallum, R. W.] Univ Kansas, Ctr Med, Ctr Gastrointestinal Nerve & Muscle Func & GI Mot, Kansas City, KS USA. [Koch, K. L.] Wake Forest Univ, Baptist Med Ctr, Gastroenterol Sect, Winston Salem, NC 27109 USA. [Sitrin, M. D.] SUNY Buffalo, Western New York VA Med Ctr, Dept Med, Div Gastroenterol & Hepatol, Buffalo, NY 14260 USA. [Wo, J. M.] Univ Louisville, Div Gastroenterol & Hepatol, Louisville, KY 40292 USA. [Chey, W. D.; Hasler, W. L.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Lackner, J. M.] SUNY Buffalo, Sch Med, Dept Med Behav Med Clin, Div Gastroenterol Hepatol & Nutr, Buffalo, NY 14260 USA. [Katzt, L. A.] SUNY Buffalo, Sch Med, Dept Med, Buffalo, NY 14260 USA. [Semler, J. R.] SmartPill Corp, Buffalo, NY USA. [Wilding, G. E.] SUNY Buffalo, Dept Biostat, Buffalo, NY 14260 USA. [Parkman, H. P.] Temple Univ, Sch Med, Dept Med, Gastroenterol Sect, Philadelphia, PA 19122 USA. RP Kuo, B (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Blake 4,55 Fruit St, Boston, MA 02114 USA. EM bkuo@partners.org FU NIDDK NIH HHS [DK069614] NR 18 TC 130 Z9 133 U1 1 U2 13 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD JAN 15 PY 2008 VL 27 IS 2 BP 186 EP 196 DI 10.1111/j.1365-2036.2007.03564.x PG 11 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 266EI UT WOS:000253416900008 PM 17973643 ER PT J AU Patel, AM Singh, JP Ruskin, JN AF Patel, Anshul M. Singh, Jagmeet P. Ruskin, Jeremy N. TI Role of implantable cardioverter-defibrillators in patients with methadone-induced long QT syndrome SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID TORSADES-DE-POINTES; USERS; BUPRENORPHINE; PROLONGATION; MAINTENANCE; TRIAL AB Patients with methadone-induced long-QT syndrome may experience Torsades de Pointes (TDP) or aborted sudden death requiring the placement of implantable cardioverter-defibrillators (ICDs). Outcomes after ICD implantation in these patients are unknown. Eight patients presenting with methadone-induced long-QT syndrome and episodes of symptomatic TDP were followed after having undergone ICD implantation. The study group included 5 women and 3 men (mean age 48.5 +/- 5 years) receiving methadone doses of 204 +/- 173 mg. All but 1 subject had preserved ventricular function (mean left ventricular ejection fraction 61 +/- 1.1%). All of the patients had prolonged QTc intervals (mean 613 +/- 71 ms) while taking methadone. After ICD implantation, 6 of the 8 patients continued treatment with methadone as a result of intractable dependence. Over a mean follow-up period of 27 months, 1 patient expired from unknown causes. Three of those patients had interrogation-proved ICD shocks for TDP. In conclusion, patients with methadone-induced long-QT syndrome and TDP are at high risk for recurrent arrhythmic events if methadone is continued. This small cohort of patients suggests that ICDs may be lifesaving in those subjects who continue taking methadone after initial episodes of TDP. 2008 Elsevier Inc. All rights reserved. C1 [Patel, Anshul M.; Singh, Jagmeet P.; Ruskin, Jeremy N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiol Div,Cardiac Arrhythmia Serv, Boston, MA 02115 USA. RP Singh, JP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiol Div,Cardiac Arrhythmia Serv, Boston, MA 02115 USA. EM jsingh@partners.org NR 14 TC 20 Z9 20 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 15 PY 2008 VL 101 IS 2 BP 209 EP 211 DI 10.1016/j.amjcard.2007.07.068 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 251NF UT WOS:000252379600014 PM 18178408 ER PT J AU Shalaby, A Voigt, A El-Saed, A Saba, S AF Shalaby, Alaa Voigt, Andrew El-Saed, Aiman Saba, Samir TI Usefulness of pulmonary artery pressure by echocardiography to predict outcome in patients receiving cardiac resynchronization therapy heart failure SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID TRICUSPID REGURGITATION; DOPPLER ULTRASOUND; SYSTOLIC PRESSURE AB Secondary pulmonary hypertension is a marker of advanced heart failure (HF) that confers a poor prognosis. Consecutive patients from 2004 through 2005 who underwent echocardiographic assessments of systolic pulmonary arterial pressure (SPAP) before the implantation of cardiac resynchronization therapy defibrillators were included: Patients were divided into tertiles according to baseline SPAP. Patients in the lowest (group 1, 20 to 29 mm Hg) and highest (group III, 45 to 88 mm Hg) tertiles were compared for the end points or death or transplantation and for HF hospital admission. Two hundred seventy patients were evaluated, of whom 95% were Caucasians and 91% men. The mean age was 66.5 +/- 11.6 years, the mean QRS duration was 155 +/- 30 ms, the mean left ventricular ejection fraction was 22.6 +/- 9.7%, and the mean New York Heart Association functional class was 3.0 +/- 0.4. In a multivariate model, death or transplantation was significantly more likely in group III (hazard ratio 2.62, 95% confidence interval 1.1 to 6.4, p = 0.036), as was HF admission (hazard ratio 6.35, 95% confidence interval 2.6 to 15.8, p <0.001). In patients with follow-up echocardiographic assessments, a reduction in SPAP was a significant predictor of freedom from the combined end point (hazard ratio 0.29, 95% confidence interval 0.12 to 0.76, p = 0.011). In conclusion, elevated baseline SPAP in patients who underwent cardiac resynchronization therapy is an independent predictor of all-cause mortality or transplantation and HF admission. A decrease in SPAP on follow-up echocardiography is an independent positive prognostic marker. (C) 2008 Elsevier Inc. All rights reserved. C1 [Shalaby, Alaa; Voigt, Andrew; Saba, Samir] Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Pittsburgh, PA 15260 USA. [El-Saed, Aiman] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Shalaby, Alaa] VA Pittsburgh Healthcare Syst, Div Cardiol, Pittsburgh, PA USA. RP Shalaby, A (reprint author), Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Pittsburgh, PA 15260 USA. EM alaa.shalaby@med.va.gov OI El-Saed, Aiman/0000-0002-1781-2203 NR 6 TC 29 Z9 34 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 15 PY 2008 VL 101 IS 2 BP 238 EP 241 DI 10.1016/j.amjcard.2007.07.064 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 251NF UT WOS:000252379600019 PM 18178413 ER PT J AU Washko, GR Fan, VS Ramsey, SD Mohsenifar, Z Martinez, F Make, BJ Sciurba, FC Criner, GJ Minai, O DeCamp, MM Reilly, JJ AF Washko, George R. Fan, Vincent S. Ramsey, Scott D. Mohsenifar, Zab Martinez, Fernando Make, Barry J. Sciurba, Frank C. Criner, Gerald J. Minai, Omar DeCamp, Malcolm M. Reilly, John J. CA Natl Emphysema Treatment Trial Res TI The effect of lung volume reduction surgery on chronic obstructive pulmonary disease exacerbations SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE COPD; LVRS; exacerbation ID BRONCHIAL EPITHELIAL-CELLS; RANDOMIZED-TRIAL; EMPHYSEMA; FLUTICASONE; BUDESONIDE; PROPIONATE; SALMETEROL; FORMOTEROL AB Rationale: Lung volume reduction surgery (LVRS) has been demonstrated to provide a functional and mortality benefit to a select group of subjects with chronic obstructive pulmonary disease (COPD). The effect of LVRS on COPD exacerbations has not been as extensively studied, and whether improvement in postoperative lung function alters the risk of disease exacerbations is not known. Objectives: To examine the effect, and mechanism of potential benefit, of LVRS on COPD exacerbations by comparing the medical and surgical cohorts of the National Emphysema Treatment Trial (NETT). Methods A COPD exacerbation was defined using Centers for Medicare and Medicaid Services data and International Classification of Diseases, Ninth Revision, discharge diagnosis. Measurements and Main Results: There was no difference in exacerbation rate or time to first exacerbation between the medical and surgical cohorts during the year before study randomization (P = 0.58 and 0.85, respectively). Postrandomization, the surgical cohort experienced an approximate 30% reduction in exacerbation frequency (P = 0.0005). This effect was greatest in those subjects with the largest postoperative improvement in FEV1 (P = 0.04) when controlling for changes in other spirometric measures of lung function, lung capacities, and room air arterial blood gas tensions. Finally, LVRS increased the time to first exacerbation in both those subjects with and those without a prior history of exacerbations (P = 0.0002 and P < 0.0001, respectively). Conclusions: LVRS reduces the frequency of COPD exacerbations and increases the time to first exacerbation. One explanation for this benefit may be the postoperative improvement in lung function. Clinical trial registered with www.clinicaltrials.gov (NCT 00000606). C1 [Washko, George R.; Reilly, John J.] Brigham & Womens Hosp, Div Pulm & Crit Care, Boston, MA 02115 USA. [Fan, Vincent S.; Ramsey, Scott D.] Univ Washington, Seattle, WA 98195 USA. [Fan, Vincent S.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Ramsey, Scott D.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Mohsenifar, Zab] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Martinez, Fernando] Univ Michigan, Ann Arbor, MI 48109 USA. [Make, Barry J.] Natl Jewish Med & Res Ctr, Denver, CO USA. [Sciurba, Frank C.] Univ Pittsburgh, Pittsburgh, PA USA. [Criner, Gerald J.] Temple Univ, Philadelphia, PA 19122 USA. [Minai, Omar] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [DeCamp, Malcolm M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Washko, GR (reprint author), Brigham & Womens Hosp, Div Pulm & Crit Care, 75 Francis St, Boston, MA 02115 USA. EM gwashko@partners.org FU NHLBI NIH HHS [N01HR76103, HL 007633, HL 074428, HL 082541, N01HR76101, N01HR76102, N01HR76104, N01HR76105, N01HR76106, N01HR76107, N01HR76108, N01HR76109, N01HR76110, N01HR76111, N01HR76112, N01HR76113, N01HR76114, N01HR76115, N01HR76116, N01HR76118, N01HR76119] NR 25 TC 39 Z9 39 U1 0 U2 5 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 15 PY 2008 VL 177 IS 2 BP 164 EP 169 DI 10.1164/rccm.200708-1194OC PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 251BJ UT WOS:000252345300007 PM 17962632 ER PT J AU Esteban, A Ferguson, ND Meade, MO Frutos-Vivar, F Apezteguia, C Brochard, L Raymondos, K Nin, N Hurtado, J Tomicic, V Gonzalez, M Elizalde, J Nightingale, P Abroug, F Pelosi, P Arabi, Y Moreno, R Jibaja, M D'Empaire, G Sandi, F Matamis, D Montanez, AM Anzueto, A AF Esteban, Andres Ferguson, Niall D. Meade, Maureen O. Frutos-Vivar, Fernando Apezteguia, Carlos Brochard, Laurent Raymondos, Konstantinos Nin, Nicolas Hurtado, Javier Tomicic, Vinko Gonzalez, Marco Elizalde, Jose Nightingale, Peter Abroug, Fekri Pelosi, Paolo Arabi, Yaseen Moreno, Rui Jibaja, Manuel D'Empaire, Gabriel Sandi, Fredi Matamis, Dimitros Montanez, Ana Maria Anzueto, Antonio CA VENTILA Grp TI Evolution of mechanical ventilation in response to clinical research SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE mechanical ventilation; mortality; acute respiratory distress syndrome; noninvasive positive-pressure ventilation; weaning ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; CARDIOGENIC PULMONARY-EDEMA; TIDAL VOLUMES; HEALTH-CARE; METAANALYSIS; STRATEGIES; PRESSURES; MORTALITY; MEDICINE AB Rationale: Recent literature in mechanical ventilation includes strong evidence from randomized trials. Little information is available regarding the influence of these trials on usual clinical practice. Objectives: To describe current mechanical ventilation practices and to assess the influence of interval randomized trials when compared with findings from a 1998 cohort. Methods: A prospective international observational cohort study, with a nested comparative study performed in 349 intensive care units in 23 countries. We enrolled 4,968 consecutive patients receiving mechanical ventilation over a 1-month period. We recorded demographics and daily data related to mechanical ventilation for the duration of ventilation. We systematically reviewed the literature and developed 11 practice-change hypotheses for the comparative cohort study before seeing these results. In assessing practice changes, we only compared data from the 107 intensive care units (1,675 patients) that also participated in the 1998 cohort (1,383 patients). Measurements and Main Results: In 2004 compared with 1998, the use of noninvasive ventilation increased (11.1 vs. 4.4%, P < 0.001). Among patients with acute respiratory distress syndrome, tidal volumes decreased (7.4 vs. 9.1 ml/kg, P < 0.001) and positive end-expiratory pressure levels increased slightly (8.7 vs. 7.7 cm H2O, P = 0.02). More patients were successfully extubated after their first attempt of spontaneous breathing (77 vs. 62%, P < 0.001). Use of synchronized intermittent mandatory ventilation fell dramatically (1.6 vs. 11%, P < 0.001). Observations confirmed 10 of our 11 practice-change hypotheses. Conclusions: The strong concordance of predicted and observed practice changes suggests that randomized trial results have advanced mechanical ventilation practices internationally. C1 [Esteban, Andres; Frutos-Vivar, Fernando; Nin, Nicolas] Univ Hosp, Intens Care Unit, CIBER Enfermedades Respiratorias, Madrid 28905, Spain. [Ferguson, Niall D.] Univ Toronto, Univ Hlth Network, Dept Med, Div Respirol, Toronto, ON, Canada. [Ferguson, Niall D.] Univ Toronto, Interdepartmental Div Crit Care, Toronto, ON, Canada. [Meade, Maureen O.] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Apezteguia, Carlos] Hosp Profesor A Posadas, Buenos Aires, DF, Argentina. [Brochard, Laurent] Univ Paris 12, INSERM U 841, AP HP, Ctr Hosp Albert Chenvier Henri Mondor, Paris, France. [Raymondos, Konstantinos] Med Hsch, Hannover, Germany. [Hurtado, Javier] Hosp Clin Montevideo, Montevideo, Uruguay. [Tomicic, Vinko] Clin Alemana Santiago, Santiago, Chile. [Gonzalez, Marco] Clin Medellin & Univ Pontificia Bolivariana, Medellin, Colombia. [Elizalde, Jose] Hosp ABC, Mexico City, DF, Mexico. [Nightingale, Peter] Wythenshawe Hosp, Manchester M23 9LT, Lancs, England. [Abroug, Fekri] Fattouma Bourguiba Monastir, Monastir, Tunisia. [Pelosi, Paolo] Univ Insubria, Osp Circolo, Varese, Italy. [Arabi, Yaseen] King Fahad Natl Guard Hosp, Riyadh, Saudi Arabia. [Moreno, Rui] Hosp Santo Antonio Capuchos, Lisbon, Portugal. [Jibaja, Manuel] Hosp Militar Quito, Quito, Ecuador. [D'Empaire, Gabriel] Hosp Clin, Caracas, Venezuela. [Sandi, Fredi] Hosp Obrero Numero 1, La Paz, Bolivia. [Matamis, Dimitros] Papageorgiou Gen Hosp, Thessaloniki, Greece. [Montanez, Ana Maria] Sociedad Peruana Med Intens, Lima, Peru. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Anzueto, Antonio] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Esteban, A (reprint author), Univ Hosp, Intens Care Unit, CIBER Enfermedades Respiratorias, Carretera Toledo Km 12500, Madrid 28905, Spain. EM aesteban@ucigetafe.com RI Lapinsky, Stephen/C-4624-2015; koca, ugur/F-1265-2016; OI Lapinsky, Stephen/0000-0002-6930-0306; koca, ugur/0000-0002-2949-4265; Frutos-Vivar, Fernando/0000-0002-4648-9636; Ferguson, Niall/0000-0002-6213-5264 NR 27 TC 319 Z9 336 U1 0 U2 16 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 15 PY 2008 VL 177 IS 2 BP 170 EP 177 DI 10.1164/rccm.200706-893OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 251BJ UT WOS:000252345300008 PM 17962636 ER PT J AU Lorenz, KA Lynn, J Dy, SM Shugarman, LR Wilkinson, A Mularski, RA Morton, SC Hughes, RG Hilton, LK Maglione, M Rhodes, SL Rolon, C Sun, VC Shekelle, PG AF Lorenz, Karl A. Lynn, Joanne Dy, Sydney M. Shugarman, Lisa R. Wilkinson, Anne Mularski, Richard A. Morton, Sally C. Hughes, Ronda G. Hilton, Lara K. Maglione, Margaret Rhodes, Shannon L. Rolon, Cony Sun, Virginia C. Shekelle, Paul G. TI Evidence for improving palliative care at the end of life: A systematic review SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; OBSTRUCTIVE PULMONARY-DISEASE; QUALITY-OF-LIFE; CONGESTIVE-HEART-FAILURE; PLACEBO-CONTROLLED CROSSOVER; ILL HOSPITALIZED ADULTS; NURSING-HOME RESIDENTS; CANCER-PATIENTS; DOUBLE-BLIND; AROMATHERAPY MASSAGE AB Background: Many persons and their families are burdened by serious chronic illness in late life. How to best support quality of life is an important consideration for care. Purpose: To assess evidence about interventions to improve palliative and end-of-life care. Data Sources: English-language citations (January 1990 to November 2005) from MEDLINE, the Database of Abstracts of Reviews of Effects, the National Consensus Project for Quality Palliative Care bibliography, and November 2005 to January 2007 updates from expert reviews and literature surveillance. Study Selection: Systematic reviews that addressed "end of life," including terminal illness (for example, advanced cancer) and chronic, eventually fatal illness with ambiguous prognosis (for example, advanced dementia), and intervention studies (randomized and nonrandomized designs) that addressed pain, dyspnea, depression, advance care planning, continuity, and caregiving. Data Extraction: Single reviewers screened 24423 titles to find 6381 relevant abstracts and reviewed 1274 articles in detail to identify 33 high-quality systematic reviews and 89 relevant intervention studies. They synthesized the evidence by using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) classification. Data Synthesis: Strong evidence supports treating cancer pain with opioids, nonsteroidals, radionuclides, and radiotherapy; dyspnea from chronic lung disease with short-term opioids; and cancer-associated depression with psychotherapy, tricyclics, and selective serotonin reuptake inhibitors. Strong evidence supports multicomponent interventions to improve continuity in heart failure. Moderate evidence supports advance care planning led by skilled facilitators who engage key decision makers and interventions to alleviate caregiver burden. Weak evidence addresses cancer-related dyspnea management, and no evidence addresses noncancer pain, symptomatic dyspnea management in advanced heart failure, or short-acting antidepressants in terminal illness. No direct evidence addresses improving continuity for patients with dementia. Evidence was weak for improving caregiver burdens in cancer and was absent for heart failure. Limitations: Variable literature indexing for advanced chronic illness and end of life limited the comprehensiveness of searches, and heterogeneity was too great to do meta-analysis. Conclusion: Strong to moderate evidence supports interventions to improve important aspects of end-of-life care. Future research should quantify these effects and address the generalizability of insights across the conditions and settings of the last part of life. Many critical issues lack high-quality evidence. C1 [Lorenz, Karl A.] Vet Affairs Greater Los Angeles Hlthcare Syst, Vet Integrated Palliat Program, Div Gen Internal Med, Los Angeles, CA 90073 USA. RP Lorenz, KA (reprint author), Vet Affairs Greater Los Angeles Hlthcare Syst, Vet Integrated Palliat Program, Div Gen Internal Med, 11031 Wilshire Blvd,Code 111-G, Los Angeles, CA 90073 USA. EM karl.lorenz@med.va.gov FU NCI NIH HHS [K07-CA096 783]; PHS HHS [290-02-0003] NR 152 TC 263 Z9 267 U1 33 U2 130 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 JAN 15 PY 2008 VL 148 IS 2 BP 147 EP 159 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 254NZ UT WOS:000252594600008 PM 18195339 ER PT J AU Muller, FL Liu, YH Abdul-Ghani, MA Lustgarten, MS Bhattacharya, A Jang, YC Van Remmen, H AF Muller, Florian L. Liu, Yuhong Abdul-Ghani, Muhammad A. Lustgarten, Michael S. Bhattacharya, Arunabh Jang, Youngmok C. Van Remmen, Holly TI High rates of superoxide production in skeletal-muscle mitochondria respiring on both complex I- and complex II-linked substrates SO BIOCHEMICAL JOURNAL LA English DT Article DE complex I; electron transport chain; H(2)O(2); mitochondria; oxaloacetate; superoxide ID HYDROGEN-PEROXIDE PRODUCTION; ELECTRON-TRANSPORT CHAIN; NADH-UBIQUINONE REDUCTASE; BRAIN MITOCHONDRIA; HEART-MITOCHONDRIA; SUCCINATE-DEHYDROGENASE; H2O2 PRODUCTION; BC(1) COMPLEX; SERUM ALBUMIN; FATTY-ACIDS AB Despite the considerable interest in superoxide as a potential cause of pathology, the mechanisms of its deleterious production by mitochondria remain poorly understood. Previous studies in purified mitochondria have found that the highest rates of superoxide production are observed with succinate-driven reverse-electron transfer through complex I, although the physiological importance of this pathway is disputed because it necessitates high concentrations of succinate and is thought not to occur when NAD is in the reduced state. However, very few studies have examined the rates of superoxide production with mitochondria respiring on both NADH-linked (e.g. glutamate) and complex II-linked substrates. In the present study, we find that the rates of superoxide production (measured indirectly as H,02) with glutamate + succinate (similar to 1100 pmol of H(2)O(2) center dot min(-1) mg(-1)) were unexpectedly much higher than with succinate (similar to 400 pmol of H(2)O(2) center dot min(-1) . mg(-1)) or glutamate (similar to 80 pmol of H(2)O(2) center dot min(-1) . mg(-1)) alone. Superoxide production with glutamate + succinate remained high even at low substrate concentrations (< 1 mM), was decreased by rotenone and was completely eliminated by FCCP (carbonyl cyanide p-trifluoromethoxyphenylhydrazone), indicating that it must in large part originate from reverse-electron transfer through complex I. Similar results were obtained when glutamate was replaced with pyruvate, a-ketoglutarate or palmitoyl carnitine. In contrast, superoxide production was consistently lowered by the addition of malate (malate + succinate - 30 pmol of H(2)O(2) - min(-1) - mg(-1)). We propose that the inhibitory action of malate on superoxide production can be explained by oxaloacetate inhibition of complex II. In summary, the present results indicate that reverse-electron transfer-mediated superoxide production can occur under physiologically realistic substrate conditions and suggest that oxaloacetate inhibition of complex 11 may be an adaptive mechanism to minimize this. C1 [Muller, Florian L.; Bhattacharya, Arunabh; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Liu, Yuhong; Bhattacharya, Arunabh; Jang, Youngmok C.; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Abdul-Ghani, Muhammad A.; Van Remmen, Holly] S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. [Lustgarten, Michael S.; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. RP Muller, FL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, Texas Res Pk Campus,15355 Lambda Dr, San Antonio, TX 78229 USA. EM aettius@aol.com FU NIA NIH HHS [P01AG020591, P01AG19316, 1P30-AG13319, 5T3-AG021890-02] NR 57 TC 89 Z9 90 U1 0 U2 4 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JAN 15 PY 2008 VL 409 BP 491 EP 499 DI 10.1042/BJ20071162 PN 2 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 259BV UT WOS:000252915000017 PM 17916065 ER PT J AU Raffetto, JD Khalil, RA AF Raffetto, Joseph D. Khalil, Raouf A. TI Matrix metalloproteinases and their inhibitors in vascular remodeling and vascular disease SO BIOCHEMICAL PHARMACOLOGY LA English DT Review DE MMP; TIMP; blood vessels; extracellular matrix; aneurysm; varicose veins ID ABDOMINAL AORTIC-ANEURYSMS; ATHEROSCLEROTIC PLAQUE STABILITY; SALT HYPERTENSIVE-RATS; TISSUE INHIBITOR; VARICOSE-VEINS; EFFICIENT ACTIVATION; RESISTANCE ARTERIES; VENOUS DISORDERS; MESSENGER-RNA; PLASMA-LEVELS AB Matrix metalloprotemases (MMPs) are a family of proteolytic enzymes that degrade various components of the extracellular matrix (ECM). Members of the MMP family include collagenases, gelatinases, stromelysins, matrilysins and membrane-type MMPs. ProMMPs are cleaved into active forms that promote degradation of ECM proteins. Also, recent evidence suggests direct or indirect effects of MMPs on ion channels in the endothelium and vascular smooth muscle, and on other mechanisms of vascular relaxation/contraction. Endogenous tissue inhibitors of metalloproteinases (TIMPs) reduce excessive proteolytic ECM degradation by MMPs. The balance between MMPs and TIMPs plays a major role in vascular remodeling, angiogenesis, and the uterine and systemic vasodilation during normal pregnancy. An imbalance in the MMPs/TIMPs activity ratio may underlie the pathogenesis of vascular diseases such as abdominal aortic aneurysm, varicose veins, hypertension and preeclampsia. Downregulation of MMPs using genetic manipulations of endogenous TIMPs, or synthetic pharmacological inhibitors such as BB-94 (Batimastat) and doxycycline, and Ro28-2653, a more specific inhibitor of gelatinases and membrane type 1-MMP, could be beneficial in reducing the MMP-mediated vascular dysfunction and the progressive vessel wall damage associated with vascular disease. (c) 2007 Elsevier Inc. All rights reserved. C1 [Khalil, Raouf A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Vasc Surg, Boston, MA 02115 USA. [Raffetto, Joseph D.] VA Boston Healthcare Syst, Dept Surg, W Roxbury, MA USA. RP Khalil, RA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Vasc Surg, 75 Francis st, Boston, MA 02115 USA. EM raouf_khalil@hms.harvard.edu RI 龙, 安雄/H-5775-2011 FU NHLBI NIH HHS [HL-70659, R01 HL065998, HL-65998, R01 HL065998-07A1, R01 HL070659, R01 HL070659-05] NR 113 TC 349 Z9 398 U1 5 U2 57 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JAN 15 PY 2008 VL 75 IS 2 BP 346 EP 359 DI 10.1016/j.bcp.2007.07.004 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 258BB UT WOS:000252842300002 PM 17678629 ER PT J AU Malanga, CJ Riday, TT Carlezon, WA Kosofsky, BE AF Malanga, C. J. Riday, Thorfinn T. Carlezon, William A., Jr. Kosofsky, Barry E. TI Prenatal exposure to cocaine increases the rewarding potency of cocaine and selective dopaminergic agonists in adult mice SO BIOLOGICAL PSYCHIATRY LA English DT Article DE brain stimulation-reward; BSR; gestation; ICSS; in utero; intracranial self-stimulation; psychostimulant ID BRAIN-STIMULATION REWARD; RECEPTOR AGONISTS; SELF-STIMULATION; IN-UTERO; NUCLEUS-ACCUMBENS; MATERNAL SMOKING; ALCOHOL EXPOSURE; D-2 AGONISTS; BIRTH COHORT; RAT AB Background: Substance abuse during pregnancy results in persistent affective and behavioral deficits in drug-exposed children, and increased rates of substance abuse have been observed in young adults prenatally exposed to drugs of abuse. Animal models of prenatal cocaine exposure have yielded differing results depending on the behavioral method used to assess drug potency. Methods: The effects of cocaine, the dopamine D1 agonists SKF-81297 and SKF-82958, and the D2 agonist quinpirole on intracranial self-stimulation were measured in adult Swiss-Webster mice exposed to cocaine in utero (40 mg/kg/day) and vehicle controls with the curve-shift method of brain stimulation-reward (BSR) threshold determination. Results: The reward-potentiating effects of cocaine (0.3-30 mg/kg IP) and SKF-82958 but not SKF-81297 on BSR were increased in adult male but not female mice after prenatal cocaine exposure. Quinpirole exerted biphasic effects on BSR, both elevating (0.1-0.3 mg/kg IP) and lowering (1.0-10 mg/kg IP) reward thresholds. Both effects of quinpirole were also enhanced in adult male mice after prenatal cocaine exposure. Conclusions: Prenatal cocaine exposure results in increased reward-potentiating potency of cocaine on BSR in adult mice in a sexually-dimorphic manner. This augmented rewarding effect of cocaine is also associated with increased sensitivity to both D1- and D2-selective agonists. C1 [Malanga, C. J.; Riday, Thorfinn T.; Kosofsky, Barry E.] Massachusetts Gen Hosp, Dept Neurol, Lab Mol & Dev Neurosci, Boston, MA 02114 USA. [Carlezon, William A., Jr.] McLean Hosp, Mailman Res Ctr, Behav Genet Lab, New York Presbyterian Hosp, Belmont, MA 02178 USA. [Kosofsky, Barry E.] Cornell Univ, Weil Med Coll, New York Presbyterian Hosp, Dept Pediat, New York, NY USA. RP Malanga, CJ (reprint author), Univ N Carolina, Dept Neurol, 3114 Bioinformat Bldg,CB 7025, Chapel Hill, NC 27599 USA. EM malangacj@neurology.unc.edu OI Malanga, C.J./0000-0003-4808-3995 FU NIDA NIH HHS [R29 DA008648, DA000354, DA015429, K02 DA000354-06A2, K08 DA015429, K08 DA015429-04, R01 DA008648-08, R01 DA012736-02, DA012736, K02 DA000354, K02 DA000354-07, R01 DA012736, R01 DA012736-01A2, K02 DA000354-05, R01 DA008648-07, R01 DA012736-03, R01 DA008648, DA008648] NR 60 TC 24 Z9 25 U1 1 U2 5 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 JAN 15 PY 2008 VL 63 IS 2 BP 214 EP 221 DI 10.1016/j.biopsych.2007.01.014 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 250MO UT WOS:000252304400013 PM 17568568 ER PT J AU Woodland, RT Fox, CJ Schmidt, MR Hammerman, PS Opferman, JT Korsmeyer, SJ Hilbert, DM Thompson, CB AF Woodland, Robert T. Fox, Casey J. Schmidt, Madelyn R. Hammerman, Peter S. Opferman, Joseph T. Korsmeyer, Stanley J. Hilbert, David M. Thompson, Craig B. TI Multiple signaling pathways promote B lymphocyte stimulator-dependent B-cell growth and survival SO BLOOD LA English DT Review ID HUMAN LEUKEMIA-CELLS; RICTOR-MTOR COMPLEX; LUPUS-LIKE DISEASE; FAMILY-MEMBER; ACTIVATING FACTOR; CUTTING EDGE; HEMATOPOIETIC-CELLS; AUTOIMMUNE-DISEASE; CYCLE PROGRESSION; RECEPTOR SIGNALS AB We investigated the mechanism by which B lymphocyte stimulator (BLyS)/BAFF, a tumor necrosis factor superfamily ligand, promotes B-cell survival and resistance to atrophy. BLyS stimulation activates 2 independent signaling pathways, Akt/ mTOR and Pim 2, associated with cell growth and survival. BLyS blocks the cell volume loss (atrophy) that freshly isolated B cells normally undergo when maintained in vitro while concurrently increasing glycolytic activity and overall metabolism. This atrophy resistance requires Akt/mTOR. We used a genetic approach to resolve the contributions of Akt/mTOR and Pim kinase pathways to BLyS-mediated survival. Pim 2-deficient B cells are readily protected from death by BLyS stimulation, but this protection is completely abrogated by treatment with the mTOR inhibitor rapamycin. Furthermore, rapamycin treatment in vivo significantly reduces both follicular and marginal zone B cells in Pim-deficient but not healthy hosts. BLyS-dependent survival requires the antiapoptotic protein Mcl-1. Mcl-1 protein levels rise and fall in response to BLyS addition and withdrawal, respectively, and conditional deletion of the Mcl-1 gene renders B cells refractory to BLyS-mediated protection. Because BlyS is required for the normal homeostasis of all B cells, these data suggest a therapeutic strategy simultaneously inhibiting mTOR and Pim 2 could target pathogenic B cells. C1 [Woodland, Robert T.; Schmidt, Madelyn R.] Univ Massachusetts, Sch Med, Dept Mol Genet & Microbiol, Worcester, MA 01655 USA. [Woodland, Robert T.; Schmidt, Madelyn R.] Univ Massachusetts, Sch Med, Immunol & Virol Program, Worcester, MA 01655 USA. [Fox, Casey J.; Hammerman, Peter S.; Thompson, Craig B.] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Opferman, Joseph T.; Korsmeyer, Stanley J.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Ctr, Boston, MA 02115 USA. [Hilbert, David M.] Human Genome Sci, Rockville, MD USA. RP Woodland, RT (reprint author), Univ Massachusetts, Sch Med, Dept Mol Genet & Microbiol, Worcester, MA 01655 USA. FU NIAID NIH HHS [AI041054, AI057463, R01 AI041054, R21 AI041054, R21 AI057463]; NIDDK NIH HHS [P30 DK032520, DK32520] NR 92 TC 96 Z9 98 U1 0 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 2008 VL 111 IS 2 BP 750 EP 760 DI 10.1182/blood-2007-03-077222 PG 11 WC Hematology SC Hematology GA 252PP UT WOS:000252458700048 PM 17942753 ER PT J AU Boyd, LB Atmar, RL Randall, GL Hamill, RJ Steffen, D Zechiedrich, L AF Boyd, Lauren Becnel Atmar, Robert L. Randall, Graham L. Hamill, Richard J. Steffen, David Zechiedrich, Lynn TI Increased fluoroquinolone resistance with time in Escherichia coli from > 17,000 patients at a large county hospital as a function of culture site, age, sex, and location SO BMC INFECTIOUS DISEASES LA English DT Article ID GRAM-NEGATIVE BACILLI; URINARY-TRACT-INFECTIONS; UNITED-STATES; ANTIBIOTIC-RESISTANCE; ANTIMICROBIAL RESISTANCE; QUINOLONE RESISTANCE; SUSCEPTIBILITY; CIPROFLOXACIN; SURVEILLANCE; PATHOGENS AB Background: Escherichia coli infections are common and often treated with fluoroquinolones. Fluoroquinolone resistance is of worldwide importance and is monitored by national and international surveillance networks. In this study, we analyzed the effects of time, culture site, and patient age, sex, and location on fluoroquinolone resistance in E. coli clinical isolates. Methods: To understand how patient factors and time influenced fluoroquinolone resistance and to determine how well data from surveillance networks predict trends at Ben Taub General Hospital in Houston, TX, we used Perl to parse and MySQL to house data from antibiograms (n congruent to 21,000) for E. coli isolated between 1999 to 2004 using Chi Square, Bonferroni, and Multiple Linear Regression methods. Results: Fluoroquinolone resistance (i) increased with time; (ii) exceeded national averages by 2- to 4- fold; (iii) was higher in males than females, largely because of urinary isolates from male outpatients; (iv) increased with patient age; (v) was 3% in pediatric patients; (vi) was higher in hospitalized patients than outpatients; (vii) was higher in sputum samples, particularly from inpatients, than all other culture sites, including blood and urine, regardless of patient location; and (viii) was lowest in genital isolates than all other culture sites. Additionally, the data suggest that, with regard to susceptibility or resistance by the Dade Behring MicroScan system, a single fluoroquinolone suffices as a "surrogate marker" for all of the fluoroquinolone tested. Conclusion: Large surveillance programs often did not predict E. coli fluoroquinolone resistance trends at a large, urban hospital with a largely indigent, ethnically diverse patient population or its affiliated community clinics. C1 [Boyd, Lauren Becnel; Atmar, Robert L.; Hamill, Richard J.; Zechiedrich, Lynn] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Atmar, Robert L.; Hamill, Richard J.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Randall, Graham L.; Zechiedrich, Lynn] Baylor Coll Med, Interinstitut Program Struct & Computat Biol & Mo, Houston, TX 77030 USA. [Steffen, David] Baylor Coll Med, Bioinformat Resource Ctr, Houston, TX 77030 USA. [Hamill, Richard J.] Michael E Debakey Vet Adm Med Ctr, Houston, TX 77030 USA. RP Zechiedrich, L (reprint author), Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. EM lb144335@bcm.edu; ratmar@bcm.edu; grandall@bcm.edu; richard.hamill@med.va.gov; steffen@bcm.edu; elz@bcm.edu FU NIAID NIH HHS [R01 AI054830]; NIDDK NIH HHS [T90 DK070109, T90DK070109]; NLM NIH HHS [T15 LM007093, T15 LM07093] NR 32 TC 43 Z9 44 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD JAN 15 PY 2008 VL 8 AR 4 DI 10.1186/1471-2334-8-4 PG 7 WC Infectious Diseases SC Infectious Diseases GA 274EJ UT WOS:000253984300001 PM 18197977 ER PT J AU Zuckerman, DS Ryan, DR AF Zuckerman, Dan S. Ryan, David R. TI Adjuvant therapy for pancreatic cancer - A review SO CANCER LA English DT Review DE pancreatic cancer; adjuvant therapy; gastrointestinal tumor study group; European study group for pancreatic cancer-1; chemoradiation; gemcitabine ID INTRAOPERATIVE RADIATION-THERAPY; RANDOMIZED CONTROLLED-TRIAL; PHASE-II TRIAL; CURATIVE RESECTION; PREOPERATIVE CHEMORADIATION; OPERATIVE MORTALITY; ADENOCARCINOMA; CARCINOMA; CHEMOTHERAPY; PANCREATICODUODENECTOMY AB Pancreatic cancer is uniformly fatal unless it can be surgically resected. Survival rates for the 15% to 20% of patients who have resectable disease, however, are a disappointing 10% to 30%, depending on the status of margins and surrounding lymph nodes. In the mid-1980s, a landmark study by the Gastrointestinal Tumor Study Group was the first to demonstrate a survival benefit from adjuvant therapy in the form of chemoradiation. Since then, several studies in both North America and Europe have tested the role of adjuvant chemotherapy or chemoradiation in pancreatic cancer, and the results have stirred great controversy. For this review, the evidence for adjuvant therapy in pancreatic cancer was examined, and the significant practice differences that exist between North American and European oncologists were highlighted. The authors investigated the results from the European Study Group for Pancreatic Cancer-1 trial and the reasons why that study has served to reinforce rather than resolve these trans-Atlantic differences. They also reviewed preliminary data from more recent adjuvant trials and explored the possible benefits of a neoadjuvant approach. C1 [Zuckerman, Dan S.; Ryan, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA USA. RP Ryan, DR (reprint author), Massachusetts Gen Hosp, Div Med Oncol, 55 Fruit St,Yawkey 7, Boston, MA 02114 USA. EM dpryan@partners.org RI qiao, zhixin/I-3408-2012 NR 51 TC 33 Z9 37 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 15 PY 2008 VL 112 IS 2 BP 243 EP 249 DI 10.1002/cncr.23174 PG 7 WC Oncology SC Oncology GA 249YH UT WOS:000252266200003 PM 18050292 ER PT J AU Zhu, AX AF Zhu, Andrew X. TI Development of sorafenib and other molecularly targeted agents in hepatocellular carcinoma SO CANCER LA English DT Review DE hepatocellular carcinoma; targeted therapy; sorafenib; antiangiogenesis ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; FACTOR-RECEPTOR; FACTOR-ALPHA; PHASE-II; PROGNOSTIC-SIGNIFICANCE; RAF/MEK/ERK PATHWAY; ANTITUMOR-ACTIVITY; TUMOR VASCULATURE; CANCER-THERAPY AB It is well appreciated that hepatocellular carcinoma (HCC) represents one of the most challenging malignancies of worldwide importance. In fact, HCC is the fifth most common cancer and the third most common cause of cancer-related death globally. The incidence rates for HCC in the U.S. and Western Europe have been rising. Unresectable or metastatic HCC carries a poor prognosis, and systemic therapy with cytotoxic agents provides marginal benefit. Because of the poor track record of systemic therapy in HCC, there has been a sense of nihilism for this disease in the oncology community for decades. However, with the arrival of newly developed, molecularly targeted agents and the success of some of these agents in other traditionally challenging cancers, such as renal cell carcinoma, there has been renewed interest in developing novel systemic therapy in HCC. At the recent Annual Meeting of the American Society of Clinical Oncology, results of a phase 3, randomized, placebo-controlled trial were presented in which sorafenib demonstrated improved survival in patients with advanced HCC. This landmark study represents the first agent that has demonstrated an improved overall survival benefit in this disease and sets the new standard for first-line treatment of advanced HCC. For this review, the author concisely summarized the current status of molecularly targeted agents that are under clinical development in advanced HCC. C1 [Zhu, Andrew X.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc,Tucker Gosnell Ctr Gastrointestinal Canc, Boston, MA 02114 USA. RP Zhu, AX (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc,Tucker Gosnell Ctr Gastrointestinal Canc, Lawrence House POB 232,55 Fruit St, Boston, MA 02114 USA. EM azhu@partners.org NR 59 TC 92 Z9 102 U1 0 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 15 PY 2008 VL 112 IS 2 BP 250 EP 259 DI 10.1002/cncr23175 PG 10 WC Oncology SC Oncology GA 249YH UT WOS:000252266200004 PM 18041064 ER PT J AU Aprile, G Ramoni, M Keefe, D Sonis, S AF Aprile, Giuseppe Ramoni, Marco Keefe, Dorothy Sonis, Stephen TI Application of distance matrices to define associations between acute toxicities in colorectal cancer patients receiving chemotherapy SO CANCER LA English DT Article DE toxicity; chemotherapy; colorectal cancer; distance matrix ID QUALITY-OF-LIFE; SYMPTOM CLUSTER; BREAST-CANCER; FATIGUE; POPULATION; ONCOLOGY; IMPACT AB BACKGROUND. Colorectal cancer patients undergoing chemotherapy (CT) are likely to experience multiple concurrent toxicities that, rather than appearing singularly, may be associated with one another. Graphic and tabular representations of distance matrices were used to identify associations between toxicities and to define the strengths of these relations. METHODS. Using a standardized data collection tool, electronic medical charts of 300 consecutive patients receiving either the combination of leucovorin, 5-fluorouracil (5-FU), and oxaliplatin (FOLFOX); the combination of leucovorin, 5-FU, and irinotecan (FOLFIRI); or 5-FU) were retrospectively reviewed to record baseline demographic and clinical information. Treatment-related toxicities were recorded using National Cancer Institute Common Toxicity Criteria during the first cycle of CT. Using a distance matrix approach, an analysis of CT-induced toxicity associations was elaborated. RESULTS. The graphic analysis, in which associations between toxicities were represented as links, identified 6 major hubs (fever, dehydration, fatigue, anorexia, pain, and weight loss), defined as central nodes with more connections than expected by chance. These were highly linked with minor nodes and provided evidence suggesting the existence of symptom clusters associated with CT-induced toxicities. CONCLUSIONS. The application of distance matrix analyses to define CT-induced toxicity associations is new. The technique was effective in defining the global landscape of the binary relations among toxicities associated with Cycle 1 therapy. The coherent clinical picture emerging from the network provides a strong suggestion that the toxicities in each cluster share a common pathobiologic basis, which may provide an opportunity for intervention. These findings could become useful for the early prediction of co-occurring toxicities and, in the future, as a phenotyping framework for the pharmacogenomic analysis of individual responses to chemotherapy. C1 [Aprile, Giuseppe; Sonis, Stephen] Brigham & Womens Hosp, Div Oral Med, Boston, MA 02115 USA. [Aprile, Giuseppe; Sonis, Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ramoni, Marco] Harvard Univ, Sch Med, Div Hlth Sci & Technol, Boston, MA USA. [Ramoni, Marco] MIT, Boston, MA USA. [Keefe, Dorothy] Univ Adelaide, Fac Hlth Sci, Royal Adelaide Hosp, Dept Med Oncol, Adelaide, SA, Australia. [Keefe, Dorothy] Univ Adelaide, Fac Hlth Sci, Discipline Med, Adelaide, SA, Australia. RP Sonis, S (reprint author), Brigham & Womens Hosp, Div Oral Med, 75 Francis St, Boston, MA 02115 USA. EM ssonis@partners.org NR 28 TC 27 Z9 28 U1 8 U2 9 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 15 PY 2008 VL 112 IS 2 BP 284 EP 292 DI 10.1002/cncr.23182 PG 9 WC Oncology SC Oncology GA 249YH UT WOS:000252266200008 PM 18041060 ER PT J AU Franco, AT Johnston, E Krishna, U Yamaoka, Y Israel, DA Nagy, TA Wroblewski, LE Piazuelo, MB Correa, P Peek, RM AF Franco, Aime T. Johnston, Elizabeth Krishna, Uma Yamaoka, Yoshio Israel, Dawn A. Nagy, Toni A. Wroblewski, Lydia E. Piazuelo, Maria Blanca Correa, Pelayo Peek, Richard M., Jr. TI Regulation of gastric carcinogenesis by helicobacter pylori virulence factors SO CANCER RESEARCH LA English DT Article ID OUTER-MEMBRANE PROTEINS; EPITHELIAL-CELLS; BETA-CATENIN; GENE POLYMORPHISMS; MONGOLIAN GERBIL; INCREASED RISK; IV SECRETION; TRANSCRIPTIONAL ACTIVITY; GASTRODUODENAL DISEASE; VACUOLATING CYTOTOXIN AB Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, and strains that possess the cag secretion system, which translocates the bacterial effector CagA into host cells, augment cancer risk. H. pylori strains that express the vacuolating cytotoxin or the outer membrane protein OipA are similarly associated with severe pathologic outcomes. We previously reported that an in vivo adapted H. pylori strain, 7.13, induces gastric adenocarcinoma in rodent models of gastritis. In the current study, we used carcinogenic strain 7.13 as a prototype to define the role of virulence constituents in H. pylori-mediated carcinogenesis. Mongolian gerbils were infected with wild-type strain 7.13 or cagA(-), vacA(-), or oipA(-) mutants for 12 to 52 weeks. All infected gerbils developed gastritis; however, inflammation was significantly attenuated in animals infected with the cagA(-) hut not the vacA(-) or oipA(-) strains. Gastric dysplasia and cancer developed in >50% of gerbils infected with either the wild-type or vacA- strain but in none of the animals infected with the cagA(-) strain. Inactivation of oipA decreased beta-catenin nuclear localization in vitro and reduced the incidence of cancer in gerbils. OipA expression was detected significantly more frequently among H. pylori strains isolated from human subjects with gastric cancer precursor lesions versus persons with gastritis alone. These results indicate that loss of CagA prevents the development of cancer in this model. Inactivation of oipA attenuates P-catenin nuclear translocation and also decreases the incidence of carcinoma. In addition to defining factors that mediate H. pylori-induced cancer, these results provide insight into mechanisms that may regulate the development of other malignancies arising within the context of inflammatory states. C1 [Franco, Aime T.; Krishna, Uma; Israel, Dawn A.; Nagy, Toni A.; Wroblewski, Lydia E.; Piazuelo, Maria Blanca; Correa, Pelayo; Peek, Richard M., Jr.] Vanderbilt Univ, Sch Med, Div Gastroenterol, Dept Med, Nashville, TN 37232 USA. [Franco, Aime T.; Krishna, Uma; Israel, Dawn A.; Nagy, Toni A.; Wroblewski, Lydia E.; Piazuelo, Maria Blanca; Correa, Pelayo; Peek, Richard M., Jr.] Vanderbilt Univ, Dept Canc Biol, Nashville, TN 37232 USA. [Johnston, Elizabeth] Vanderbilt Univ, Dept Pathol, Nashville, TN 37232 USA. [Peek, Richard M., Jr.] Dept Vet Affairs Med Ctr, Nashville, TN 37212 USA. [Yamaoka, Yoshio] Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX USA. [Yamaoka, Yoshio] Baylor Coll Med, Houston, TX 77030 USA. RP Peek, RM (reprint author), Vanderbilt Univ, Sch Med, Div Gastroenterol, Dept Med, 1030C MRB IV 2215B Garland Ave, Nashville, TN 37232 USA. EM richard.peek@vanderbilt.edu FU NCI NIH HHS [CA-028842, P01 CA028842, P01 CA028842-16, R01 CA077955, R01 CA077955-06]; NIDDK NIH HHS [DK-58587, DK-62813, DK-73902, DK-77955, K01 DK077955, R01 DK058587, R01 DK058587-01A1, R01 DK062813, R01 DK062813-01A2, R01 DK062813-04, R01 DK073902, R01 DK073902-01] NR 50 TC 123 Z9 127 U1 1 U2 5 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 JAN 15 PY 2008 VL 68 IS 2 BP 379 EP 387 DI 10.1158/0008-5472.CAN-07-0824 PG 9 WC Oncology SC Oncology GA 253FJ UT WOS:000252503800008 PM 18199531 ER PT J AU Zhao, XS Goswami, M Pokhriyal, N Ma, H Du, HY Yao, J Victor, TA Polyak, K Sturgis, CD Band, H Band, V AF Zhao, Xiangshan Goswami, Monica Pokhriyal, Nidhi Ma, Hui Du, Hongyan Yao, Jun Victor, Thomas A. Polyak, Kornelia Sturgis, Charles D. Band, Hamid Band, Vimla TI Cyclooxygenase-2 expression during immortalization and breast cancer progression SO CANCER RESEARCH LA English DT Article ID MAMMARY EPITHELIAL-CELLS; CARCINOMA IN-SITU; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; TRANSFORMATION; METHYLATION; MODELS; COX-2; OVEREXPRESSION; PREVENTION; SENESCENCE AB Identification of molecular aberrations in premalignant human mammary epithelial cells (hMEC), the precursors for breast cancers, is a central goal in breast cancer biology. Recent studies implicated expression of cyclooxygenase 2 (COX-2) as a marker to identify precursor cells for breast cancer. In this study, we analyzed COX-2 expression in preselection and postselection hMEC cells and observed similar COX-2 levels in both cells. Interestingly, immortalization of postselection cells using various methods leads to a dramatic decrease in COX-2 expression. Similar to immortal cells, the majority of breast cancer cell lines expressed low levels of COX-2 protein. Finally, analyses of COX-2 expression in a series of specimens from reduction mammoplasty, adenosis, ductal carcinoma in situ, and infiltrating ductal carcinoma showed down-regulation of COX-2 expression during tumor progression. Importantly, down-regulation of COX-2 using small interfering RNA in cells showed no effect on cell proliferation, anchorage-independent growth, migration, or invasion. These results show that (a) COX-2 overexpression does not seem to predict a breast cancer precursor cell and does not provide advantage for the cell to be transformed; (b) inhibition of COX-2 does not affect hMEC growth and oncogenic behavior in the conditions analyzed; and (c) COX-2 expression is decreased in breast cancer cell lines and cancer specimens as compared with normal mammary epithelial cells. C1 [Zhao, Xiangshan; Goswami, Monica; Pokhriyal, Nidhi; Ma, Hui; Band, Vimla] Evanston Northwestern Healthcare Res Inst, Div Canc Biol, Evanston, IL USA. [Band, Hamid] Evanston Northwestern Healthcare Res Inst, Div Mol Oncol, Dept Med, Evanston, IL USA. [Goswami, Monica; Victor, Thomas A.; Sturgis, Charles D.] Evanston Northwestern Healthcare Res Inst, Dept Pathol, Evanston, IL USA. [Du, Hongyan] Evanston Northwestern Healthcare Res Inst, Ctr Outcome Res & Educ, Evanston, IL USA. Feinberg Sch Med, Evanston, IL USA. [Band, Hamid; Band, Vimla] Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL USA. [Yao, Jun; Polyak, Kornelia] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Band, V (reprint author), Univ Nebraska, Med Ctr, Dept Genet Cell Biol & Anat, DRC 6th Floor,985805 Nebraska Med Ctr, Omaha, NE 68198 USA. EM vband@unmc.edu FU NCI NIH HHS [CA99900, CA94143, P50 CA089393-080014, R01 CA094074, CA76118, P50 CA089393-070014, CA87986, P50 CA089393-060014, R01 CA094074-05, CA81076, P50 CA089393, CA99163, CA96844] NR 49 TC 27 Z9 27 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 JAN 15 PY 2008 VL 68 IS 2 BP 467 EP 475 DI 10.1158/0008-5472.CAN-07-0782 PG 9 WC Oncology SC Oncology GA 253FJ UT WOS:000252503800018 PM 18199541 ER PT J AU Sawai, A Chandarlapaty, S Greulich, H Gonen, M Ye, Q Arteaga, CL Sellers, W Rosen, N Solit, DB AF Sawai, Ayana Chandarlapaty, Sarat Greulich, Heidi Gonen, Mithat Ye, Qing Arteaga, Carlos L. Sellers, William Rosen, Neal Solit, David B. TI Inhibition of Hsp90 down-regulates mutant epidermal growth factor receptor (EGFR) expression and sensitizes EGFR mutant tumors to paclitaxel SO CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; TYROSINE KINASE INHIBITOR; SHOCK-PROTEIN 90; ONCOGENIC TRANSFORMATION; DOMAIN MUTATIONS; HERBIMYCIN-A; IN-VITRO; B-RAF; GEFITINIB; HEAT-SHOCK-PROTEIN-90 AB Mutations in the kinase domain of the epidermal growth factor receptor (EGFR) are found in a subset of patients with lung cancer and correlate with response to EGFR tyrosine kinase inhibitors (TKI). Resistance to these agents invariably develops, and current treatment strategies have limited efficacy in this setting. Hsp90 inhibitors, such as 17-allylamino-17-demethoxygeldanamycin (17-AAG), induce the degradation of EGFR and other Hsp90 interacting proteins and may thus have utility in tumors dependent upon sensitive Hsp90 clients. We find that the EGFR mutations found most commonly in patients with lung adenocarcinoma who respond to EGFR TKIs are potently degraded by 17-AAG. Although the expression of wild-type EGFR was also down-regulated by 17-AAG, its degradation required higher concentrations of drug and a longer duration of drug exposure. In animal models, a single dose of 17-AAG was sufficient to induce degradation of mutant EGFR and inhibit downstream signaling. 17-AAG treatment, at its maximal tolerated dose, caused a significant delay in H3255 (1,85811 EGFR) xenograft growth but was less effective than the EGFR TKI gefitinib. 17-AAG alone delayed, but did not completely inhibit, the growth of H1650 and H1975 xenografts, two EGFR mutant models which show intermediate and high levels of gefitinib resistance. 17-AAG could be safely coadministered with paclitaxel, and the combination was significantly more effective than either drug alone. These data suggest that Hsp90 inhibition in combination with chemotherapy may represent an effective treatment strategy for patients whose tumors express EGFR kinase domain mutations, including those with de novo and acquired resistance to EGFR TKIs. C1 [Chandarlapaty, Sarat; Rosen, Neal; Solit, David B.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA. [Sawai, Ayana; Chandarlapaty, Sarat; Ye, Qing; Rosen, Neal; Solit, David B.] Mem Sloan Kettering Canc Ctr, Dept Mol Pharmacol, New York, NY 10021 USA. [Gonen, Mithat] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Greulich, Heidi; Sellers, William] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Greulich, Heidi; Sellers, William] Broad Inst MIT & Harvard, Cambridge, MA USA. [Arteaga, Carlos L.] Vanderbilt Univ, Dept Med, Breast Canc Res Program, Nashville, TN USA. [Arteaga, Carlos L.] Vanderbilt Univ, Dept Canc Biol, Breast Canc Res Program, Nashville, TN USA. RP Solit, DB (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10065 USA. EM solitd@mskcc.org RI Gonen, Mithat/E-4826-2012 FU NCI NIH HHS [P01 CA094060, P01 CA94060, P50 CA092629, P50-CA92629] NR 45 TC 107 Z9 112 U1 1 U2 4 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 JAN 15 PY 2008 VL 68 IS 2 BP 589 EP 596 DI 10.1158/0008-5472.CAN-07-1570 PG 8 WC Oncology SC Oncology GA 253FJ UT WOS:000252503800033 PM 18199556 ER PT J AU Das, S Boswell, SA Aaronson, SA Lee, SW AF Das, Sanjeev Boswell, Sarah A. Aaronson, Stuart A. Lee, Sam W. TI P53 promoter selection - Choosing between life and death SO CELL CYCLE LA English DT Article DE p53; cell fate decision; Hzf; apoptosis; cell cycle arrest ID FAMILY TRANSCRIPTION FACTOR; PROLYL ISOMERASE PIN1; BOX-BINDING-PROTEIN; ZINC-FINGER PROTEIN; CELL-CYCLE ARREST; DNA-DAMAGE; APOPTOTIC FUNCTION; P53-DEPENDENT APOPTOSIS; SER46 PHOSPHORYLATION; TUMOR-SUPPRESSOR AB A crucial unresolved issue about the genotoxic stress response is how the activation of the p53 tumor suppressor can lead either to cell cycle arrest and DNA repair or to apoptosis. p53 is one of the most important tumor suppressor proteins in the cell to prevent to heritable transfer of damaged DNA. In response to different stress conditions p53 rapidly accumulates and functions as a sequence specific DNA-binding transcription factor to regulate a large number of target genes. Activation of p53 has two major outcomes: cell cycle arrest or apoptosis. In this review we attempt to enumerate the different modifications and co-factors that influence p53 promoter selection and demonstrate how p53 chooses life or death for the cell. C1 [Das, Sanjeev; Boswell, Sarah A.; Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Hillsborough, MA 02129 USA. [Das, Sanjeev; Boswell, Sarah A.; Lee, Sam W.] Harvard Univ, Sch Med, Charlestown, MA USA. [Aaronson, Stuart A.] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY USA. RP Lee, SW (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Hillsborough, MA 02129 USA. EM sam.lee@cbrc2.mgh.harvard.edu FU NCI NIH HHS [CA80058, CA097216, CA078356, CA85214, CA85681] NR 41 TC 48 Z9 49 U1 1 U2 6 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JAN 15 PY 2008 VL 7 IS 2 BP 154 EP 157 PG 4 WC Cell Biology SC Cell Biology GA 266OS UT WOS:000253446300006 PM 18212532 ER PT J AU Friel, AM Sergent, PA Patnaude, C Szotek, PP Oliva, E Scadden, DT Seiden, MV Foster, R Rueda, BR AF Friel, Anne M. Sergent, Petra A. Patnaude, Christine Szotek, Paul P. Oliva, Esther Scadden, David T. Seiden, Michael V. Foster, Rosemary Rueda, Bo R. TI Functional analyses of the cancer stem cell-like properties of human endometrial tumor initiating cells SO CELL CYCLE LA English DT Article DE endometrial cancer; tumor initiating cells; side population cells; stem cells ID SIDE-POPULATION; PROSPECTIVE IDENTIFICATION; MOUSE ENDOMETRIUM; MYELOID-LEUKEMIA; OVARIAN-CANCER; EFFLUX; HOECHST-33342; TRANSPORTER; EXPRESSION; RESISTANCE AB Recent data suggest that rare stem cell populations with the capacity to self renew and drive tumor formation are a feature of solid tumors. Several investigators have identified putative stem cells from solid tumors and cancer cell lines following isolation of a side population (SP) defined by dye exclusion. We investigated this parameter in our efforts to identify an endometrial cancer (EnCa) stem cell population. Multiple EnCa cell lines were assessed and verapamil sensitive SP and non-SP cells were isolated from two human EnCa cell lines. The functional significance of the SP and non-SP derived from AN3CA was evaluated in vitro and in vivo. SP cells proliferated at a significantly slower rate than the non-SP fraction, and a larger proportion of the SP cells were in the G(1) phase of the cell cycle as compared to the non-SP fraction. The SP fraction was more resistant to the chemotherapeutic agent paclitaxel. The SP comprised similar to 0.02% of the initial AN3CA cell population and this proportion of SP cells was maintained within the larger heterogeneous population following repeated passages of purified SP cells. These findings suggest that SP cells derived from the AN3CA cell line have the stem cell properties of low proliferative activity, chemoresistance and self-renewal. We also tested relative tumor formation activity of the SP and non-SP fractions. Only the SP fraction was tumorigenic. Additionally, we identified SP fractions in primary EnCa. Together these results are consistent with the hypothesis that EnCa contain a subpopulation of tumor initiating cells with stem like properties. C1 [Friel, Anne M.; Sergent, Petra A.; Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. [Szotek, Paul P.; Foster, Rosemary] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Szotek, Paul P.] Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. [Patnaude, Christine; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regnerat Med, Boston, MA 02114 USA. [Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Rueda, BR (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Obstet & Gynecol Serv, THR 901A,55 Fruit St, Boston, MA 02114 USA. EM brueda@partners.org FU NCI NIH HHS [5T32CA071345-10] NR 43 TC 52 Z9 62 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JAN 15 PY 2008 VL 7 IS 2 BP 242 EP 249 PG 8 WC Cell Biology SC Cell Biology GA 266OS UT WOS:000253446300018 PM 18256549 ER PT J AU Nishimura, M Izumiya, Y Higuchi, A Shibata, R Qiu, J Kudo, C Shin, HK Moskowitz, MA Ouchi, N AF Nishimura, Masaki Izumiya, Yasuhiro Higuchi, Akiko Shibata, Rei Qiu, Jianhua Kudo, Chiho Shin, Hwa Kyoung Moskowitz, Michael A. Ouchi, Noriyuki TI Adiponectin prevents cerebral ischemic injury through endothelial nitric oxide synthase-dependent mechanisms SO CIRCULATION LA English DT Article DE adiponectin; stroke; cerebral ischemia; reperfusion; nitric oxide synthase ID ACTIVATED PROTEIN-KINASE; PLASMA-PROTEIN; STIMULATES ANGIOGENESIS; INSULIN-RESISTANCE; REPERFUSION INJURY; BLOOD-FLOW; MICE; DISEASE; STROKE; HYPOADIPONECTINEMIA AB Background-Adiponectin is a fat-derived plasma protein that has beneficial actions on cardiovascular disorders. A low level of plasma adiponectin is associated with increased mortality after ischemic stroke; however, the causal role of adiponectin in ischemic stroke is unknown. Methods and Results-To explore the role of adiponectin in the development of acute cerebral injury, we subjected adiponectin-deficient (APN-KO) and wild-type (WT) mice to 1 hour of middle cerebral artery occlusion followed by 23 hours of reperfusion. APN-KO mice exhibited enlarged brain infarction and increased neurological deficits after ischemia-reperfusion compared with WT mice. Conversely, adenovirus-mediated supplementation of adiponectin significantly reduced cerebral infarct size in WT and APN-KO mice. APN-KO mice showed decreased cerebral blood flow during ischemia by laser speckle flowmetry methods. Adiponectin colocalized within the cerebral vascular endothelium under transient ischemic conditions by immunohistochemical analysis. Phosphorylation of endothelial nitric oxide synthase in ischemic brain tissues and the production of nitric oxide metabolites in plasma were attenuated in APN-KO mice compared with WT mice. Adenovirus-mediated administration of adiponectin stimulated endothelial nitric oxide synthase phosphorylation and nitric oxide metabolites during cerebral ischemia in both WT and APN-KO mice. Neuronal nitric oxide synthase expression during ischemia did not differ between WT and APN-KO mice. Adenovirus-mediated delivery of adiponectin did not affect brain infarction in mice deficient in endothelial nitric oxide synthase. Conclusions-These data provide causal evidence that adiponectin exerts a cerebroprotective action through an endothelial nitric oxide synthase-dependent mechanism. Adiponectin could represent a molecular target for the prevention of ischemic stroke. C1 [Izumiya, Yasuhiro; Higuchi, Akiko; Shibata, Rei; Ouchi, Noriyuki] Boston Univ, Sch Med, Mol Cardiol Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Nishimura, Masaki; Qiu, Jianhua; Kudo, Chiho; Shin, Hwa Kyoung; Moskowitz, Michael A.] Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurol & Radiol, Charlestown, MA USA. Harvard Med Sch, Charlestown, MA USA. RP Ouchi, N (reprint author), Boston Univ, Sch Med, Mol Cardiol Whitaker Cardiovasc Inst, 715 Albany St, Boston, MA 02118 USA. EM nouchi@bu.edu RI OUCHI, Noriyuki/I-7306-2014 FU NINDS NIH HHS [P50 NS10828] NR 35 TC 113 Z9 123 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 15 PY 2008 VL 117 IS 2 BP 216 EP 223 DI 10.1161/CIRCULATIONAHA.107.725044 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 254QC UT WOS:000252601400019 PM 18158361 ER PT J AU Polyak, K AF Polyak, Kornelia TI Is breast tumor progression really linear? SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID CARCINOMA IN-SITU; DUCTAL CARCINOMA; STEM-CELLS; CANCER; POPULATIONS; EVOLUTION; PATTERNS; LESIONS; RISK C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM kornelia-polyak@dfci.harvard.edu FU NCI NIH HHS [CA116235, CA89393, CA94074] NR 20 TC 22 Z9 23 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 JAN 15 PY 2008 VL 14 IS 2 BP 339 EP 341 DI 10.1158/1078-0432.CCR-07-2188 PG 3 WC Oncology SC Oncology GA 256JQ UT WOS:000252725200002 PM 18223205 ER PT J AU Yoshimoto, K Dang, J Zhu, S Nathanson, D Huang, T Dumont, R Seligson, DB Yong, WH Xiong, Z Rao, N Winther, H Chakravarti, A Bigner, DD Mellinghoff, IK Horvath, S Cavenee, WK Cloughesy, TF Mischel, PS AF Yoshimoto, Koji Dang, Julie Zhu, Shaojun Nathanson, David Huang, Tiffany Dumont, Rebecca Seligson, David B. Yong, William H. Xiong, Zhenggang Rao, Nagesh Winther, Henrik Chakravarti, Arnab Bigner, Darell D. Mellinghoff, Ingo K. Horvath, Steve Cavenee, Webster K. Cloughesy, Timothy F. Mischel, Paul S. TI Development of a real-time RT-PCR assay for detecting EGFRvIII in glioblastoma samples SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-RECEPTOR; KINASE INHIBITORS; LUNG CARCINOMAS; CANCER; MUTANT; GLIOMAS; VARIANT; TUMORIGENICITY; SENSITIVITY; EXPRESSION AB Purpose: Epidermal growth factor receptor variant III (EGFRvIII) is an oncogenic, constitutively active mutant form of the EGFR that is commonly expressed in glioblastoma and is also detected in a number of epithelial cancers. EGFRvIII presents a unique antigenic target for anti-EGFRvIII vaccines and it has been shown to modulate response to EGFR kinase inhibitor therapy. Thus, detection in clinical samples may be warranted. Existing patents preclude the use of anti-EGFRvIII antibodies for clinical detection. Further, frozen tissue is not routinely available, particularly for patients treated in the community. Thus, detection of EGFRvIII in formalin-fixed paraffin-embedded (FFPE) clinical samples is a major challenge. Experimental Design: We developed a real-time reverse transcription-PCR (RT-PCR) assay for detecting EGFRvIII in FFPE samples and analyzed 59 FFPE glioblastoma clinical samples with paired frozen tissue from the same surgical resection. We assessed EGFRvIII protein expression by immunohistochemistry using two distinct specific anti-EGFRvIII antibodies and examined EGFR gene amplification by fluorescence in situ hybridization. Results: The FFPE RT-PCR assay detected EGFRvIII in 16 of 59 (27%) samples, exclusively in cases with EGFR amplification, consistent with the expected frequency of this alteration. The FFPE RT-PCR assay was more sensitive and specific for detecting EGFRvIII than either of the two antibodies alone, or in combination, with a sensitivity of 93% (95% confidence interval, 0.78-1.00) and a specificity of 98% (95% confidence interval, 0.93-1.00). Conclusion: This assay will facilitate accurate assessment of EGFRvIII in clinical samples and may aid in the development of strategies for stratifying patients for EGFRvIII-directed therapies. C1 [Yoshimoto, Koji; Dang, Julie; Zhu, Shaojun; Nathanson, David; Huang, Tiffany; Dumont, Rebecca; Seligson, David B.; Yong, William H.; Xiong, Zhenggang; Mischel, Paul S.] Univ Calif Los Angeles, David Greffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. [Yoshimoto, Koji; Dang, Julie; Zhu, Shaojun; Nathanson, David; Huang, Tiffany; Dumont, Rebecca; Seligson, David B.; Yong, William H.; Xiong, Zhenggang; Mischel, Paul S.] Univ Calif Los Angeles, David Greffen Sch Med, Lab Med, Los Angeles, CA USA. [Seligson, David B.; Mellinghoff, Ingo K.; Mischel, Paul S.] Univ Calif Los Angeles, David Greffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA USA. [Horvath, Steve] Univ Calif Los Angeles, David Greffen Sch Med, Dept Human Genet, Los Angeles, CA USA. [Horvath, Steve] Univ Calif Los Angeles, David Greffen Sch Med, Dept Biostat, Los Angeles, CA USA. [Cloughesy, Timothy F.; Mischel, Paul S.] Univ Calif Los Angeles, David Greffen Sch Med, Dept Neurol, Los Angeles, CA USA. [Mellinghoff, Ingo K.; Cloughesy, Timothy F.; Mischel, Paul S.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, David Greffen Sch Med, Los Angeles, CA 90024 USA. [Mellinghoff, Ingo K.; Cloughesy, Timothy F.; Mischel, Paul S.] Univ Calif Los Angeles, David Greffen Sch Med, Henry E Singleton Brain Tumor Program, Los Angeles, CA 90024 USA. [Winther, Henrik] DAKO A S, Glostrup, Denmark. [Chakravarti, Arnab] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Bigner, Darell D.] Preston Robert Tisch Brain Tumor Ctr Duke, Dept Pathol, Durham, NC USA. [Cavenee, Webster K.] Univ Calif San Diego, Ludwig Inst Canc Res, San Diego, CA 92103 USA. RP Mischel, PS (reprint author), Univ Calif Los Angeles, David Greffen Sch Med, Dept Pathol, 10833 Le Cone, Los Angeles, CA 90095 USA. EM pmischel@mednet.ucla.edu FU NCI NIH HHS [CA108633, CA119347, CA95616]; NINDS NIH HHS [NS050151] NR 23 TC 48 Z9 48 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2008 VL 14 IS 2 BP 488 EP 493 DI 10.1158/1078-0432.CCR-07-1966 PG 6 WC Oncology SC Oncology GA 256JQ UT WOS:000252725200022 PM 18223223 ER PT J AU Zhai, RH Liu, GF Zhou, W Su, L Heist, RS Lynch, TJ Wain, JC Asomaning, K Lin, XH Christiani, DC AF Zhai, Rihong Liu, Geoffrey Zhou, Wei Su, Li Heist, Rebecca Suk Lynch, Thomas J. Wain, John C. Asomaning, Kofi Lin, Xihong Christiani, David C. TI Vascular endothelial growth factor genotypes, haplotypes, gender, and the risk of non - Small cell lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID VEGF GENE; TUMOR ANGIOGENESIS; PROSTATE CARCINOMA; FACTOR EXPRESSION; HISTOLOGIC TYPE; MESSENGER-RNA; PLASMA-LEVELS; POLYMORPHISMS; PROGNOSIS; ANDROGENS AB Purpose: The vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis involving tumor growth and metastasis. Polymorphisms in the VEGF gene may regulate VEGF production. In this large case-control study, we investigated whether functional polymorphisms (-460C/T, +405C/G, +936C/T) in the VEGF gene are associated with the risk of non -small cell lung cancer (NSCLC). Experimental Design: VEGF genotypes and haplotypes were determined in 1,900 Caucasian patients with NSCLC and 1,458 healthy controls. The results were analyzed using logistic regression models, adjusting for age, gender, smoking status, pack-years of smoking, and years since smoking cessation (for ex-smokers). The false-positive report probability was estimated for the observed odds ratios (OR). Results: There were no overall associations between individual VEGF genotypes and the risk of NSCLC. Stratified analysis suggested that the combined +405CC+CG genotype was significantly associated with increased risk of lung adenocarcinoma in males (adjusted OR, 1.40; 95% confidence interval, 1.03-1.87). In haplotype analysis, haplotypes were globally associated with differences between cases and controls in males (P = 0.03). Specifically, the -460T/ +405G/+936C haplotype was significantly (P = 0.02) associated with decreased risk of adenocarcinoma in males when compared with the most common CGC haplotype (adjusted OR, 0.76; 95% confidence interval, 0.50-0.98). None of the VEGF genotypes and haplotypes studied significantly influenced the susceptibility to NSCLC in females. Conclusions: Polymorphisms of -460C/T, +405C/G, and +936C/T in the VEGF gene do not play a major role in NSCLC risk. However, we could not exclude a minor role for the +405CC+CG genotypes and the 460T/+405G/+936C haplotype in lung adenocarcinogenesis in male Caucasians. C1 [Zhai, Rihong; Liu, Geoffrey; Zhou, Wei; Su, Li; Heist, Rebecca Suk; Asomaning, Kofi; Christiani, David C.] Univ Toronto, Princess Margaret Hosp, Dept Environm Hlth, Toronto, ON, Canada. [Heist, Rebecca Suk; Lynch, Thomas J.] Univ Toronto, Princess Margaret Hosp, Dept Hematol Oncol, Toronto, ON, Canada. [Liu, Geoffrey] Univ Toronto, Princess Margaret Hosp, Dept Med & Med Biophys, Toronto, ON, Canada. [Wain, John C.] Harvard Univ, Sch Publ Hlth, Dept Surg, Boston, MA 02115 USA. [Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu FU NCI NIH HHS [CA90578, CA119650, CA74386, CA92824, ES/CA 06409] NR 40 TC 48 Z9 50 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2008 VL 14 IS 2 BP 612 EP 617 DI 10.1158/1078-0432.CCR-07-1655 PG 6 WC Oncology SC Oncology GA 256JQ UT WOS:000252725200037 PM 18223238 ER PT J AU Gerding, DN Muto, CA Owens, RC AF Gerding, Dale N. Muto, Carlene A. Owens, Robert C., Jr. TI Treatment of Clostridium difficile infection SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID ANTIBIOTIC-ASSOCIATED COLITIS; INTRAVENOUS IMMUNE GLOBULIN; IN-VITRO ACTIVITY; PSEUDOMEMBRANOUS COLITIS; SACCHAROMYCES-BOULARDII; TOXIN-A; MULTIPLE RELAPSES; ANTIBODY-RESPONSE; DOUBLE-BLIND; HYPERVIRULENT STRAIN AB Recent outbreaks of Clostridium difficile infection (CDI) in North America have been due to a more virulent, possibly more resistant strain that causes more-severe disease, making prompt recognition of cases and optimal management of infection essential for a successful therapeutic outcome. Treatment algorithms are presented to help guide the management of patients with CDI. Metronidazole has been recommended as initial therapy since the late 1990s and continues to be the first choice for all but seriously ill patients and those with complicated or fulminant infections or multiple recurrences of CDI, for whom vancomycin is recommended. Other options for recurrent CDI, such as probiotics and currently available anion-exchange resins, have limited efficacy and are potentially harmful. Intravenous immunoglobulin may benefit patients with refractory, recurrent, or severe disease, but no controlled data are available. Two antimicrobials available in the United States for other indications, nitazoxanide and rifaximin, have been used successfully for CDI treatment but, like metronidazole, lack United States Food and Drug Administration approval for this indication. Experimental treatments currently in clinical development include a toxin-binding polymer, tolevamer; 2 poorly absorbed antimicrobials, OPT-80 (formerly known as Difimicin) and ramoplanin; monoclonal antibodies; and a C. difficile vaccine. C1 [Gerding, Dale N.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Gerding, Dale N.] Loyola Univ, Stritch Sch Med, Chicago, IL 60611 USA. [Muto, Carlene A.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Owens, Robert C., Jr.] Maine Med Ctr, Portland, ME 04102 USA. [Owens, Robert C., Jr.] Univ Vermont, Coll Med, Burlington, VT USA. RP Gerding, DN (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, 5th Ave & Roosevelt Rd,POB 5000, Hines, IL 60141 USA. EM dale.gerding2@va.gov NR 114 TC 170 Z9 174 U1 1 U2 22 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 JAN 15 PY 2008 VL 46 SU 1 BP S32 EP S42 DI 10.1086/521860 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 249YU UT WOS:000252268000005 PM 18177219 ER PT J AU Gerding, DN Muto, CA Owens, RC AF Gerding, Dale N. Muto, Carlene A. Owens, Robert C., Jr. TI Measures to control and prevent Clostridium difficile infection SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PROTON PUMP INHIBITORS; HOSPITALIZED-PATIENTS; REDUCE TRANSMISSION; CARE FACILITIES; DIARRHEA; DISEASE; RISK; COLITIS; EPIDEMIOLOGY; ACQUISITION AB Control of Clostridium difficile infection (CDI) outbreaks in health care facilities presents significant challenges to infection control specialists and other health care workers. C. difficile spores survive routine environmental cleaning with detergents and hand hygiene with alcohol-based gels. Enhanced cleaning of all potentially contaminated surfaces with 10% sodium hypochlorite reduces the environmental burden of C. difficile, and use of barrier precautions reduces C. difficile transmission. Thorough handwashing with chlorhexidine or with soap and water has been shown to be effective in removing C. difficile spores from hands. Achieving high-level compliance with these measures is a major challenge for infection control programs. Good antimicrobial stewardship complements infection control efforts and environmental interventions to provide a comprehensive strategy to prevent and control outbreaks of CDI. The efficacy of metronidazole or vancomycin prophylaxis to prevent CDI in patients who are receiving other antimicrobials is unproven, and treatment with these agents is ineffective against C. difficile in asymptomatic carriers. C1 [Gerding, Dale N.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Gerding, Dale N.] Loyola Univ, Stritch Sch Med, Chicago, IL 60611 USA. [Muto, Carlene A.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Owens, Robert C., Jr.] Maine Med Ctr, Portland, ME 04102 USA. [Owens, Robert C., Jr.] Univ Vermont, Coll Med, Burlington, VT USA. RP Gerding, DN (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, 5th Ave & Roosevelt Rd,POB 5000, Hines, IL 60141 USA. EM dale.gerding2@va.gov NR 50 TC 140 Z9 145 U1 1 U2 20 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 JAN 15 PY 2008 VL 46 SU 1 BP S43 EP S49 DI 10.1086/521861 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 249YU UT WOS:000252268000006 PM 18177221 ER PT J AU Laugwitz, KL Moretti, A Caron, L Nakano, A Chien, KR AF Laugwitz, Karl-Ludwig Moretti, Alessandra Caron, Leslie Nakano, Atsushi Chien, Kenneth R. TI Islet1 cardiovascular progenitors: a single source for heart lineages? SO DEVELOPMENT LA English DT Review ID FORKHEAD TRANSCRIPTION FACTORS; STEM-CELL DIFFERENTIATION; VASCULAR SMOOTH-MUSCLE; CARDIAC OUTFLOW TRACT; ATRIAL SEPTAL-DEFECT; HOMEOBOX GENE NKX2-5; NEURAL CREST; ENDOTHELIAL-CELLS; EXPRESSION DOMAIN; MYOCARDIAL-CELLS AB The creation of regenerative stem cell therapies for heart disease requires that we understand the molecular mechanisms that govern the fates and differentiation of the diverse muscle and non-muscle cell lineages of the heart. Recently, different cardiac cell types have been reported to arise from a common, multipotent Islet1 (Isl1)-positive progenitor, suggesting that a clonal model of heart lineage diversification might occur that is analogous to hematopoiesis. The ability to isolate, renew and differentiate Isl1(+) precursors from postnatal and embryonic hearts and from embryonic stem cells provides a powerful cell-based system for characterizing the signaling pathways that control cardiovascular progenitor formation, renewal, lineage specification and conversion to specific differentiated progeny. C1 [Laugwitz, Karl-Ludwig; Moretti, Alessandra; Caron, Leslie; Nakano, Atsushi; Chien, Kenneth R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Laugwitz, Karl-Ludwig; Moretti, Alessandra] Tech Univ Munich, Klinikum Rechts Isar, D-81675 Munich, Germany. [Laugwitz, Karl-Ludwig; Moretti, Alessandra] Tech Univ Munich, Deutsch Herzzentrum, D-81675 Munich, Germany. [Chien, Kenneth R.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Chien, Kenneth R.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Laugwitz, KL (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charles River Plaza CPZN 3208,185 Cambridge St, Boston, MA 02114 USA. EM klaugwitz@med1.med.tum.de; amoretti@med1.med.tum.de RI Moretti, Alessandra/O-9271-2015 NR 109 TC 138 Z9 153 U1 0 U2 14 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 JAN 15 PY 2008 VL 135 IS 2 BP 193 EP 205 DI 10.1242/dev.001883 PG 13 WC Developmental Biology SC Developmental Biology GA 249UF UT WOS:000252254700001 PM 18156162 ER PT J AU Enshell-Seijffers, D Lindon, C Morgan, BA AF Enshell-Seijffers, David Lindon, Catherine Morgan, Bruce A. TI The serine protease Corin is a novel modifier of the agouti pathway SO DEVELOPMENT LA English DT Article DE corin; dermal papilla; agouti; pigmentation ID PROATRIAL NATRIURETIC PEPTIDE; STEM-CELLS; DERMAL PAPILLA; MICE LACKING; HAIR-GROWTH; IN-VITRO; MELANOCORTIN; PIGMENTATION; FOLLICLE; EXPRESSION AB The hair follicle is a model system for studying epithelial-mesenchymal interactions during organogenesis. Although analysis of the epithelial contribution to these interactions has progressed rapidly, the lack of tools to manipulate gene expression in the mesenchymal component, the dermal papilla, has hampered progress towards understanding the contribution of these cells. In this work, Corin was identified in a screen to detect genes specifically expressed in the dermal papilla. It is expressed in the dermal papilla of all pelage hair follicle types from the earliest stages of their formation, but is not expressed elsewhere in the skin. Mutation of the Corin gene reveals that it is not required for morphogenesis of the hair follicle. However, analysis of the 'dirty blonde' phenotype of these mice reveals that the transmembrane protease encoded by Corin plays a critical role in specifying coat color and acts downstream of agouti gene expression as a suppressor of the agouti pathway. C1 [Enshell-Seijffers, David; Lindon, Catherine; Morgan, Bruce A.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Enshell-Seijffers, David; Lindon, Catherine; Morgan, Bruce A.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Morgan, BA (reprint author), Harvard Univ, Sch Med, 149 13th St, Charlestown, MA 02129 USA. EM bruce.morgan@cbrc2.mgh.harvard.edu OI Enshell-Seijffers, David/0000-0002-8228-2659 FU NIAMS NIH HHS [R01 AR055256, R01 AR055256-01, R01AR055256-01] NR 42 TC 53 Z9 54 U1 0 U2 2 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 JAN 15 PY 2008 VL 135 IS 2 BP 217 EP 225 DI 10.1242/dev.011031 PG 9 WC Developmental Biology SC Developmental Biology GA 249UF UT WOS:000252254700003 PM 18057101 ER PT J AU Yeh, JRJ Munson, KM Chao, YL Peterson, QP MacRae, CA Peterson, RT AF Yeh, Jing-Ruey J. Munson, Kathleen M. Chao, Yvonne L. Peterson, Quinn P. MacRae, Calum A. Peterson, Randall T. TI AML1-ETO reprograms hematopoietic cell fate by downregulating scl expression SO DEVELOPMENT LA English DT Article DE hematopoiesis; myeloid; leukemia; zebrafish ID ACUTE MYELOID-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; BINDING PROTEIN-ALPHA; TRANSCRIPTION-FACTOR; GENE-EXPRESSION; FUSION PROTEIN; DEFINITIVE HEMATOPOIESIS; GRANULOCYTIC SARCOMA; TRANSGENIC ZEBRAFISH; 21 TRANSLOCATION AB AML1-ETO is one of the most common chromosomal translocation products associated with acute myelogenous leukemia ( AML). Patients carrying the AML1-ETO fusion gene exhibit an accumulation of granulocyte precursors in the bone marrow and the blood. Here, we describe a transgenic zebrafish line that enables inducible expression of the human AML1-ETO oncogene. Induced AML1-ETO expression in embryonic zebrafish causes a phenotype that recapitulates some aspects of human AML. Using this highly tractable model, we show that AML1-ETO redirects myeloerythroid progenitor cells that are developmentally programmed to adopt the erythroid cell fate into the granulocytic cell fate. This fate change is characterized by a loss of gata1 expression and an increase in pu.1 expression in myeloerythroid progenitor cells. Moreover, we identify scl as an early and essential mediator of the effect of AML1-ETO on hematopoietic cell fate. AML1-ETO quickly shuts off scl expression, and restoration of scl expression rescues the effects of AML1-ETO on myeloerythroid progenitor cell fate. These results demonstrate that scl is an important mediator of the ability of AML1-ETO to reprogram hematopoietic cell fate decisions, suggesting that scl may be an important contributor to AML1-ETO- associated leukemia. In addition, treatment of AML1-ETO transgenic zebrafish embryos with a histone deacetylase inhibitor, Trichostatin A, restores scl and gata1 expression, and ameliorates the accumulation of granulocytic cells caused by AML1-ETO. Thus, this zebrafish model facilitates in vivo dissection of AML1-ETO-mediated signaling, and will enable large-scale chemical screens to identify suppressors of the in vivo effects of AML1-ETO. C1 [Yeh, Jing-Ruey J.; Munson, Kathleen M.; Chao, Yvonne L.; Peterson, Quinn P.; MacRae, Calum A.; Peterson, Randall T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dev Biol Lab, Charlestown, MA 02129 USA. [Yeh, Jing-Ruey J.; Munson, Kathleen M.; Chao, Yvonne L.; Peterson, Quinn P.; MacRae, Calum A.; Peterson, Randall T.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Yeh, Jing-Ruey J.; Munson, Kathleen M.; Peterson, Randall T.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. RP Yeh, JRJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dev Biol Lab, Charlestown, MA 02129 USA. EM jyeh1@partners.org; peterson@cvrc.mgh.harvard.edu NR 57 TC 56 Z9 59 U1 2 U2 6 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 JAN 15 PY 2008 VL 135 IS 2 BP 401 EP 410 DI 10.1242/dev.008904 PG 10 WC Developmental Biology SC Developmental Biology GA 249UF UT WOS:000252254700020 PM 18156164 ER PT J AU DeYoung, MP Horak, P Sofer, A Sgroi, D Ellisen, LW AF DeYoung, Maurice Phillip Horak, Peter Sofer, Avi Sgroi, Dennis Ellisen, Leif W. TI Hypoxia regulates TSC1/2-mTOR signaling and tumor suppression through REDD1-mediated 14-3-3 shuttling SO GENES & DEVELOPMENT LA English DT Article DE hypoxia; tuberous sclerosis; mTOR; REDD1; tumor suppressor ID TUBEROUS SCLEROSIS COMPLEX; MESSENGER-RNA TRANSLATION; CELL-GROWTH; ENERGY STRESS; MAMMALIAN TARGET; GENE-PRODUCT; S6 KINASE; MTOR; TSC2; PHOSPHORYLATION AB Hypoxia induces rapid and dramatic changes in cellular metabolism, in part through inhibition of target of rapamycin ( TOR) kinase complex 1 (TORC1) activity. Genetic studies have shown the tuberous sclerosis tumor suppressors TSC1/2 and the REDD1 protein to be essential for hypoxia regulation of TORC1 activity in Drosophila and in mammalian cells. The molecular mechanism and physiologic significance of this effect of hypoxia remain unknown. Here, we demonstrate that hypoxia and REDD1 suppress mammalian TORC1 (mTORC1) activity by releasing TSC2 from its growth factor-induced association with inhibitory 14-3-3 proteins. Endogenous REDD1 is required for both dissociation of endogenous TSC2/14-3-3 and inhibition of mTORC1 in response to hypoxia. REDD1 mutants that fail to bind 14-3-3 are defective in eliciting TSC2/14-3-3 dissociation and mTORC1 inhibition, while TSC2 mutants that do not bind 14-3-3 are inactive in hypoxia signaling to mTORC1. In vitro, loss of REDD1 signaling promotes proliferation and anchorage-independent growth under hypoxia through mTORC1 dysregulation. In vivo, REDD1 loss elicits tumorigenesis in a mouse model, and down-regulation of REDD1 is observed in a subset of human cancers. Together, these findings define a molecular mechanism of signal integration by TSC1/2 that provides insight into the ability of REDD1 to function in a hypoxia-dependent tumor suppressor pathway. C1 [DeYoung, Maurice Phillip; Horak, Peter; Sofer, Avi; Sgroi, Dennis; Ellisen, Leif W.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [DeYoung, Maurice Phillip; Horak, Peter; Sofer, Avi; Sgroi, Dennis; Ellisen, Leif W.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Sgroi, Dennis] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Ellisen, LW (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM ellisen@helix.mgh.harvard.edu FU Austrian Science Fund FWF [J 2575]; NCI NIH HHS [R01 CA122589] NR 40 TC 313 Z9 321 U1 4 U2 20 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 JAN 15 PY 2008 VL 22 IS 2 BP 239 EP 251 DI 10.1101/gad.1617608 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 251TJ UT WOS:000252397700010 PM 18198340 ER PT J AU Mujat, C Greiner, C Baldwin, A Levitt, JM Tian, F Stucenski, LA Hunter, M Kim, YL Backman, V Feld, M Muenger, K Georgakoudi, I AF Mujat, Claudia Greiner, Cherry Baldwin, Amy Levitt, Jonathan M. Tian, Fenghua Stucenski, Lee A. Hunter, Martin Kim, Young L. Backman, Vadim Feld, Michael Muenger, Karl Georgakoudi, Irene TI Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE cancer biomarkers; noninvasive imaging; cancer diagnosis; spectroscopy; fluorescence; light scattering; HPV; cervical cancer ID CERVICAL INTRAEPITHELIAL NEOPLASIA; LIGHT-SCATTERING SPECTROSCOPY; LASER-INDUCED FLUORESCENCE; IN-VIVO DETECTION; BREAST-CANCER; HUMAN KERATINOCYTES; NUCLEAR MORPHOLOGY; BARRETTS-ESOPHAGUS; E7 ONCOPROTEIN; TRANSFORMATION AB Cellular transformation is associated with a number of phenotypic, cell biological, biochemical and metabolic alterations. The detection and classification of morphological cellular abnormalities represents the foundation of classical histopathology and remains an important mainstay in the clinic. More recently, significant effort is being expended towards the development of noninvasive modalities for the detection of cancer at an early stage, when therapeutic interventions are highly successful. Methods that rely on the detection of optical signatures represent one class of such approaches that have yielded promising results. In our study, we have applied two spectroscopic imaging approaches to systematically identify in a quantitative manner the fluorescence and light scattering signatures of subcellular abnormalities that are associated with cellular transformation. Notably, we find that tryptophan images reveal not only intensity but also localization differences between normal and human papillomavirus immortalized cells, possibly originating from changes in the expression, 3D packing and organization of proteins and protein-rich subcellular organelles. Additionally, we detect alterations in cellular metabolism through quantitative evaluation of the NADH, FAD fluorescence and the corresponding redox ratio. Finally, we use light scattering spectroscopy to identify differences in nuclear morphology and subcellular organization that occur from the nanometer to the micrometer scale. Thus, these optical approaches provide complementary biomarkers based on endogenous fluorescence and scattering cellular changes that occur at the molecular, biochemical and morphological level. Since they obviate the need for staining and tissue removal and can be easily combined, they provide desirable options for further clinical development and assessment. (C) 2007 Wiley-Liss, Inc. C1 [Mujat, Claudia; Greiner, Cherry; Levitt, Jonathan M.; Tian, Fenghua; Stucenski, Lee A.; Hunter, Martin; Georgakoudi, Irene] Tufts Univ, Dept Biomed Engn, Medford, MA 02155 USA. [Baldwin, Amy; Muenger, Karl] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. [Hunter, Martin] MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. [Kim, Young L.; Backman, Vadim] Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA. [Georgakoudi, Irene] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Georgakoudi, I (reprint author), Tufts Univ, Dept Biomed Engn, 4 Colby St,Rm 153, Medford, MA 02155 USA. EM irene.georgakoudi@tufts.edu RI Backman, Vadim/B-6689-2009; OI Munger, Karl/0000-0003-3288-9935 FU NCI NIH HHS [R01 CA097966] NR 45 TC 34 Z9 34 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 15 PY 2008 VL 122 IS 2 BP 363 EP 371 DI 10.1002/ijc.23120 PG 9 WC Oncology SC Oncology GA 242DJ UT WOS:000251704400014 PM 17935126 ER PT J AU Pai, SY Kang, BY Sabadini, AM Parisini, E Truitt, ML Ho, IC AF Pai, Sung-Yun Kang, Bok Yun Sabadini, Amelia M. Parisini, Emilio Truitt, Morgan L. Ho, I-Cheng TI Distinct structural requirements of GATA-3 for the regulation of thymocyte and Th2 cell differentiation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TRANSCRIPTION FACTOR GATA-3; DNA-BINDING; HISTONE ACETYLATION; GENE; EXPRESSION; SPECIFICITY; LOCUS; COMMITMENT; MECHANISM; RESPONSES AB GATA-3, the only T cell-specific member of the GATA family of transcription factors, is essential for the intrathymic development of CD4(+) T cells and for the differentiation of Th2 cells. However, whether distinct biochemical features, unique to GATA-3 compared with other GATA family members, are required to drive T cell transcriptional programs or whether the T cell-specific functions of GATA-3 can simply be ascribed to its expression pattern is unclear. Nor do we understand the protein structural requirements for each individual function of GATA-3. In this study, we report that a heterologous GATA factor, GATA-4, was competent in supporting the development of CD4(+) T cells but could not fully compensate for GATA-3 in regulating the expression of Th cytokines. Specifically, GATA-3 was more potent than GATA-4 in driving the production of IL-13 due to a mechanism independent of DNA binding or chromatin remodeling of the IL-13 locus. The difference was mapped to a partially conserved region C-terminal to the second zinc finger. Converting a single proline residue located in this region of GATA-4 to its counterpart, a methionine of GATA-3, was sufficient to enhance the IL-13-promoting function of GATA-4 but had no effect on other cytokines. Taken together, our data demonstrate that the unique function of GATA-3 is conferred by both its cell type-specific expression and distinct protein structure. C1 [Pai, Sung-Yun; Sabadini, Amelia M.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Pai, Sung-Yun] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Parisini, Emilio] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Pai, Sung-Yun; Parisini, Emilio; Ho, I-Cheng] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Kang, Bok Yun; Truitt, Morgan L.; Ho, I-Cheng] Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. RP Ho, IC (reprint author), Smith Bldg,1 Jimmy Fund Way, Boston, MA 02115 USA. EM iho@partners.org FU NIAID NIH HHS [R01 AI054451, K08 AI050601] NR 29 TC 9 Z9 10 U1 2 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2008 VL 180 IS 2 BP 1050 EP 1059 PG 10 WC Immunology SC Immunology GA 250HG UT WOS:000252290000042 PM 18178845 ER PT J AU Yamauchi, K Choi, IJ Lu, H Ogiwara, H Graham, DY Yamaoka, Y AF Yamauchi, Kazuyoshi Choi, Il-Ju Lu, Hong Ogiwara, Hiroaki Graham, David Y. Yamaoka, Yoshio TI Regulation of IL-18 in Helicobacter pylori infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GAMMA-INDUCING FACTOR; HUMAN GASTRIC-MUCOSA; IFN-GAMMA; INTERFERON-GAMMA; EPITHELIAL-CELLS; GENE-EXPRESSION; T-CELLS; PROMOTER ACTIVATION; DEFICIENT MICE; MYELOID CELLS AB The gastric mucosal immune response is thought to be comprised predominantly of the Th1 type; however, there are limited data regarding the role of IL-18 in Helicobacter pylori-induced inflammation. We investigated IL-18 levels in gastric mucosal biopsy specimens as well as in isolated gastric epithelial cells and lamina propria mononuclear cells. We also investigated IL-18 levels in gastric epithelial cells and the monocyte cell line THP-1 cocultured with H. pylori. In both systems, IL-18 levels were markedly enhanced in H. pylori-infected epithelial cells and monocytes. IL-18 levels in H. pylori-infected gastric mucosa were well correlated with the severity of gastric inflammation, confirming that H. pylori-induced IL-18 plays an important role in gastric injury. Virulence factors of H. pylori; the cap pathogenicity island and OipA affected IL-18 induction in different manners. Up-regulation of IL-18 mRNA/protein in epithelial cells was dependent on both virulence factors. Interestingly, up-regulation of IL-18 mRNA in monocytes was independent of both factors, whereas IL-18 protein was OipA dependent -cag pathogenicity island independent, indicating that OipA regulates IL-18 induction in monocytes at the posttranscriptional level. IL-18 levels in the gastric biopsy specimens showed similar patterns to those in lamina propria mononuclear cells with respect to virulence factors, suggesting that submucosal monocytes/macrophages are the main source of IL-18 induced by H. pylori infection. H. pylori appeared to regulate the ERK/JNK -> AP-1 pathway in both cell types. In addition, OipA and its related p38 pathway may be closely involved in IL-18 induction in H. pylori-infected gastric mucosa and may contribute to gastric injury. C1 [Yamauchi, Kazuyoshi; Choi, Il-Ju; Lu, Hong; Ogiwara, Hiroaki; Graham, David Y.; Yamaoka, Yoshio] Michael E DeBakey Vet Affairs Med Ctr, Dept Med Gastroenterol, Houston, TX 77030 USA. [Yamauchi, Kazuyoshi; Choi, Il-Ju; Lu, Hong; Ogiwara, Hiroaki; Graham, David Y.; Yamaoka, Yoshio] Baylor Coll Med, Houston, TX 77030 USA. [Choi, Il-Ju] Natl Canc Ctr, Res Inst & Hosp, Gyeonggi, South Korea. [Lu, Hong] Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Digest Dis, Renji Hosp,Dept Gastroenterol, Shanghai 200030, Peoples R China. RP Yamaoka, Y (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Med, 2002 Holcombe Blvd,111D Room,3A-320, Houston, TX 77030 USA. EM yyamaoka@bcm.tmc.edu FU NIDDK NIH HHS [DK 62813, P30 DK056338, DK56338, R01 DK062813-04, R01 DK062813-05, R01 DK062813] NR 46 TC 31 Z9 33 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2008 VL 180 IS 2 BP 1207 EP 1216 PG 10 WC Immunology SC Immunology GA 250HG UT WOS:000252290000058 PM 18178861 ER PT J AU Atkinson, C Qiao, F Song, H Gilkeson, GS Tomlinson, S AF Atkinson, Carl Qiao, Fei Song, Hongbin Gilkeson, Gary S. Tomlinson, Stephen TI Low-dose targeted complement inhibition protects against renal disease and other manifestations of autoimmune disease in MRL/lpr mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PULMONARY INFLAMMATION; CARDIAC ALLOGRAFTS; MURINE LUPUS; EXPRESSION; RECEPTOR; GLOMERULONEPHRITIS; DEFICIENCY; SURVIVAL; SUSCEPTIBILITY AB Complement appears to play a dual role in the progression of systemic lupus erythematosus, serving a beneficial role in enhancing immune complex clearance, while serving a pathogenic role in inducing local inflammation. To investigate these different roles of complement in a therapeutic setting, MRL/lpr mice were treated with the targeted murine C3 complement inhibitor, CR2-Crry, from 16 to 24 wk of age (after the development of proteinuria). The targeting moiety, CR2, binds to C3 breakdown products deposited at sites of complement activation and has the potential to provide complement inhibition locally without causing systemic inhibition. Administration of CR2-Crry i.v., at a dose of 0.25 mg once a week, was associated with a significant survival benefit, improved kidney function, and a significant reduction in glomerulonephritis and renal vasculitis. The presence of skin lesions and lung bronchiolar and vascular inflammation was also dramatically reduced by CR2-Crry treatment. CR2-Crry treatment also resulted in a significant reduction in autoantibody production, as measured by anti-dsDNA Ab levels, and did not cause an increase in circulating immune complex levels. These effects on autoimmunity and circulating immune complexes represent significant potential advantages over the use of Crry-Ig in MRL/lpr mice, a systemic counterpart of CR2-Crry. CR2-Crry localized preferentially to the kidneys in 16-wk MRL/lpr mice with a kidney-localized half-life of similar to 24 h. Thus, targeted complement inhibition at the C3 level is an effective treatment in murine lupus, even beginning after onset of disease. C1 [Atkinson, Carl; Qiao, Fei; Song, Hongbin; Tomlinson, Stephen] Med Univ S Carolina, Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Gilkeson, Gary S.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Gilkeson, Gary S.] Ralph H Johnson Vet Affairs Med Ctr, Med Res Serv, Charleston, SC 29425 USA. RP Tomlinson, S (reprint author), Med Univ S Carolina, Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA. EM tomlinss@musc.edu RI Song, Hongbin/C-1963-2013 FU NCRR NIH HHS [C06 RR015455] NR 28 TC 41 Z9 41 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2008 VL 180 IS 2 BP 1231 EP 1238 PG 8 WC Immunology SC Immunology GA 250HG UT WOS:000252290000060 PM 18178863 ER PT J AU Huan, J Kaler, LJ Mooney, JL Subramanian, S Hopke, C Vandenbark, AA Rosloniec, EF Burrows, GG Offner, H AF Huan, Jianya Kaler, Laurie J. Mooney, Jeffery L. Subramanian, Sandhya Hopke, Corwyn Vandenbark, Arthur A. Rosloniec, Edward F. Burrows, Gregory G. Offner, Halina TI MHC class II derived recombinant T cell receptor ligands protect DBA/1LacJ mice from collagen-induced arthritis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MAJOR HISTOCOMPATIBILITY COMPLEX; SHARED EPITOPE HYPOTHESIS; RHEUMATOID-ARTHRITIS; SELF-TOLERANCE; PASSIVE TRANSFER; PEPTIDE; INDUCTION; ACTIVATION; MOLECULES AB We previously demonstrated the therapeutic effects of MHC class II derived recombinant T cell receptor ligands (RTL), single-chain two domain complexes of the alpha 1 and beta 1 domains of MHC class II molecules genetically linked with an immunodominant peptide, in experimental autoimmune encephalomyelitis. In the current study, we produced a monomeric murine I-A(q)-derived RTL construct covalently linked with bovine collagen type II peptide (bCII257-270) suitable for use in DBA/1LacJ mice that develop collagen-induced arthritis (CIA), an animal model of human rheumatoid arthritis, after immunization with bCII protein in CFA. In this study, we demonstrate that the I-A(q)-derived RTLs reduced the incidence of the disease, suppressed the clinical and histological signs of CIA and induced long-term modulation of T cells specific for arthritogenic Ags. Our results showed that the I-A(q)/bCII257-270 molecule could systemically reduce proinflammatory IL-17 and IFN-gamma production and significantly increase anti-inflammatory IL-10, IL-13, and FoxP3 gene expression in splenocytes. Moreover, I-A(q)/bCII257-270 molecule could also selectively inhibit IL-1 beta, IL-6, and IL-23 expression in local joint tissue. This is the first report demonstrating effective prevention of joint inflammation and clinical signs of CIA with an I-A(q)-derived RTL, thus supporting the possible clinical use of this approach for treating rheumatoid arthritis in humans. C1 [Huan, Jianya; Kaler, Laurie J.; Subramanian, Sandhya; Hopke, Corwyn; Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Portland, OR 97201 USA. [Huan, Jianya; Mooney, Jeffery L.; Vandenbark, Arthur A.; Burrows, Gregory G.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. [Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. [Rosloniec, Edward F.] Vet Affairs Med Ctr, Memphis, TN 38104 USA. RP Offner, H (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu FU NIAID NIH HHS [R01 AI043960, AI43960]; NIDDK NIH HHS [R41 DK068881, DK068881, R42 DK068881]; NIMHD NIH HHS [MD001833, R41 MD001833]; NINDS NIH HHS [NS41965, R01 NS041965] NR 70 TC 18 Z9 20 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2008 VL 180 IS 2 BP 1249 EP 1257 PG 9 WC Immunology SC Immunology GA 250HG UT WOS:000252290000062 PM 18178865 ER PT J AU John, JF Lindsay, JA AF John, Joseph F., Jr. Lindsay, Jodi A. TI Clones and drones: Do variants of Panton-Valentine leukocidin extend the reach of community-associated methicillin-resistant Staphylococcus aureus? SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID SOFT-TISSUE INFECTIONS; PNEUMONIA; GENES; SKIN; EVOLUTION; LINEAGES; STRAINS; GENOME C1 [John, Joseph F., Jr.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. [John, Joseph F., Jr.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [John, Joseph F., Jr.] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Lindsay, Jodi A.] St Georges Univ London, Dept Cellular & Mol Med, Ctr Infect, London, ON, Canada. RP John, JF (reprint author), Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. EM joseph.john2@va.gov RI Lindsay, Jodi/B-9565-2008 OI Lindsay, Jodi/0000-0002-5219-1625 NR 30 TC 6 Z9 6 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 15 PY 2008 VL 197 IS 2 BP 175 EP 178 DI 10.1086/524693 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 251TX UT WOS:000252399200001 PM 18177251 ER PT J AU Thacker, EL Chen, H Patel, AV McCullough, ML Calle, EE Thun, MJ Schwarzschild, MA Ascherio, A AF Thacker, Evan L. Chen, Honglei Patel, Alpa V. McCullough, Marjorie L. Calle, Eugenia E. Thun, Michael J. Schwarzschild, Michael A. Ascherio, Alberto TI Recreational physical activity and risk of Parkinson's disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; epidemiology; cohort study; behavioral risk factors; physical activity ID II NUTRITION COHORT; URIC-ACID LEVELS; CANCER PREVENTION; EXERCISE; DIAGNOSIS; ACCURACY AB The purpose of this study was to investigate associations between recreational physical activity and Parkinson's disease (PD) risk. We prospectively followed 143,325 participants in the Cancer Prevention Study 11 Nutrition Cohort from 1992 to 2001 (mean age at baseline = 63). Recreational physical activity was estimated at baseline from the reported number of hours per week on average spent performing light intensity activities (walking, dancing) and moderate to vigorous intensity activities (jogging/running, lap swimming, tennis/racquetball, bicycling/stationary bike, aerobics/calisthenics). Incident cases of PD (n = 413) were confirmed by treating physicians and medical record review. Relative risks (RR) were estimated using proportional hazards models, adjusting for age, gender, smoking, and other risk factors. Risk of PD declined in the highest categories of baseline recreational activity. The RR comparing the highest category of total recreational activity (men >= 23 metabolic equivalent task-hours/week [MET-h/wk], women >= 18.5 MET-h/wk) to no activity was 0.8 (95% CI: 0.6, 1.2; P trend = 0.07). When light activity and moderate to vigorous activity were examined separately, only the latter was found to be associated with PD risk. The RR comparing the highest category of moderate to vigorous activity (men >= 16 MET-h/wk, women >= 11.5 MET-h/wk) to the lowest (0 MET-h/wk) was 0.6 (95% CI: 0.4, 1.0; P trend = 0.02). These results did not differ significantly by gender. The results were similar when we excluded cases with symptom onset in the first 4 years of follow-up. Our results may be explained either by a reduction in PD risk through moderate to vigorous activity, or by decreased baseline recreational activity due to preclinical PD. (D 2007 Movement Disorder Society. C1 [Thacker, Evan L.; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Patel, Alpa V.; McCullough, Marjorie L.; Calle, Eugenia E.; Thun, Michael J.] Amer Canc Soc, Epidemiol & Surveillance Res Dept, Atlanta, GA 30329 USA. [Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ascherio, Alberto] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Thacker, EL (reprint author), Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. EM ethacker@post.harvard.edu OI Thacker, Evan/0000-0002-3813-0885; Chen, Honglei/0000-0003-3446-7779 FU Intramural NIH HHS [Z01 ES101986-02]; NINDS NIH HHS [NS048517, R01 NS048517, R01 NS048517-01A2] NR 22 TC 64 Z9 67 U1 1 U2 14 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 JAN 15 PY 2008 VL 23 IS 1 BP 69 EP 74 DI 10.1002/mds.21772 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 258WS UT WOS:000252901400010 PM 17960818 ER PT J AU Mamikonyan, E Siderowf, AD Duda, JE Potenza, MN Horn, S Stem, MB Weintraub, D AF Mamikonyan, Eugenia Siderowf, Andrew D. Duda, John E. Potenza, Marc N. Horn, Stacy Stem, Matthew B. Weintraub, Daniel TI Long-term follow-up of impulse control disorders in Parkinson's disease SO MOVEMENT DISORDERS LA English DT Article DE dopamine agonist; gambling; impulse control disorders; Parkinson's disease ID SUBTHALAMIC NUCLEUS STIMULATION; DOPAMINE AGONIST THERAPY; PREVALENCE; ASSOCIATION AB Recent studies have linked dopamine agonist (DA) usage with the development of impulse control disorders (ICDs) in Parkinson's disease (PD). Little is known about optimal management strategies or the long-term outcomes of affected patients. To report on the clinical interventions and long-term outcomes of PD patients who developed an ICD after DA initiation. Subjects contacted by telephone for a follow-up interview after a mean time period of 29.2 months. They were administered a modified Minnesota Impulse Disorder Interview for compulsive buying, gambling, and sexuality, and also self-rated changes in their ICD symptomatology. Baseline and follow-up dopamine replacement therapy use was recorded and verified by chart review. Of 18 subjects, 15 (83.3%) participated in the follow-up interview. At follow-up, patients were receiving a significantly lower DA levodopa equivalent daily dosage (LEDD) (Z = -3. 1, P = 0.002) and a higher daily levodopa dosage (Z = -1.9, P = 0.05), but a similar total LEDD dosage (Z = -0.47, P = 0.64) with no changes in Unified Parkinson's Disease Rating Scale motor score (Z = -1.3, P = 0.19). As part of ICD management, 12 (80.0%) patients discontinued or significantly decreased DA treatment, all of whom experienced full or partial remission of ICD symptoms by self-report, and 10 (83.3%) of whom no longer met diagnostic criteria for an ICD. For PD patients who develop an ICD in the context of DA treatment, discontinuing or significantly decreasing DA exposure, even when offset by an increase in levodopa treatment, is associated with remission of or significant reduction in ICD behaviors without worsening in motor symptoms. (c) 2007 Movement Disorder Society. C1 [Mamikonyan, Eugenia; Weintraub, Daniel] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Siderowf, Andrew D.; Duda, John E.; Horn, Stacy; Stem, Matthew B.; Weintraub, Daniel] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Siderowf, Andrew D.; Duda, John E.; Stem, Matthew B.; Weintraub, Daniel] Vet Affairs Med Ctr, PADRECC, Philadelphia, PA USA. [Potenza, Marc N.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Potenza, Marc N.] Vet Affairs Med Ctr, MIRECC, West Haven, CT USA. [Weintraub, Daniel] Vet Affairs Med Ctr, MIRECC, Philadelphia, PA USA. RP Weintraub, D (reprint author), Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. EM weintrau@upenn.edu FU NIDA NIH HHS [R01 DA019039, R01 DA019039-05]; NIMH NIH HHS [K23 MH067894, K23 MH067894-05]; PHS HHS [NIMH 067894] NR 21 TC 115 Z9 119 U1 1 U2 6 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 JAN 15 PY 2008 VL 23 IS 1 BP 75 EP 80 DI 10.1002/mds.21770 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 258WS UT WOS:000252901400011 PM 17960796 ER PT J AU Powers, KM Kay, DM Factor, SA Zabetian, CP Higgins, DS Samii, A Nutt, JG Griffith, A Leis, B Roberts, JW Martinez, ED Montimurro, JS Checkoway, H Payami, H AF Powers, Karen M. Kay, Denise M. Factor, Stewart A. Zabetian, Cyrus P. Higgins, Donald S. Samii, All Nutt, John G. Griffith, Alida Leis, Berta Roberts, John W. Martinez, Erica D. Montimurro, Jennifer S. Checkoway, Harvey Payami, Haydeh TI Combined effects of smoking, coffee, and NSAIDs on Parkinson's disease risk SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; smoking; coffee; NSAIDs; nonsteroidal anti-inflammatory drugs ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CAFFEINE INTAKE; DOPAMINERGIC-NEURONS; CIGARETTE-SMOKING; NICOTINE; CONSUMPTION; RELIABILITY; PROTECTS; ALCOHOL; TRAITS AB Inverse associations of Parkinson's disease (PD) with cigarette smoking, coffee drinking, and nonsteroidal anti-inflammatory drug (NSAID) use have been reported individually. but their joint effects have not been examined. To quantify associations with PD for the individual, two-way and three-way combinations of these factors, a case-control association study with 1,186 PD patients and 928 controls was conducted. The study setting was the NeuroGenetics Research Consortium. Subjects completed a structured questionnaire regarding smoking. coffee, and NSAID consumption. Odds ratios were calculated using unconditional logistic regression. Smoking, coffee, and over the counter NSAID use as individual factors exhibited significantly reduced risks of 20% to 30%. The two-way and three-way combinations were associated with risk reduction of 37% to 49%, and 62%, respectively. Smoking and coffee exhibited significant inverse risk trends with increasing cumulative exposures, suggesting dose-response relations. With respect to the combination of all three exposures, persons who were at the highest exposure strata for smoking and coffee and used NSAIDs had an estimated 87% reduction in risk (OR 0.13, 95% CI = 0.06-0.29). Whether this finding reflects true biologic protection needs to be investigated. (c) 2007 Movement Disorder Society. C1 [Kay, Denise M.; Montimurro, Jennifer S.; Payami, Haydeh] New York State Dept Hlth, Genom Inst, Wadsworth Ctr, Albany, NY 12201 USA. [Powers, Karen M.; Checkoway, Harvey] Univ Washington, Sch Publ Hlth & Community Med, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. [Factor, Stewart A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Factor, Stewart A.; Higgins, Donald S.] Albany Med Ctr, Parkinsons Dis & Movement Disorder Ctr, Albany, NY USA. [Zabetian, Cyrus P.; Martinez, Erica D.] VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. [Zabetian, Cyrus P.; Samii, All; Martinez, Erica D.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. [Samii, All] VA Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. [Nutt, John G.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Griffith, Alida; Leis, Berta] Evergreen Hosp Med Ctr, Booth Gardner Parkinsons Care Ctr, Washington, DC USA. [Roberts, John W.] Virginia Mason Med Ctr, Seattle, WA 98101 USA. RP Payami, H (reprint author), New York State Dept Hlth, Genom Inst, Wadsworth Ctr, POB 22002, Albany, NY 12201 USA. EM hpayami@wadsworth.org OI Zabetian, Cyrus/0000-0002-7739-4306; Kay, Denise/0000-0002-9928-2698 FU NIA NIH HHS [AG 08017]; NINDS NIH HHS [K08-NS044138, R01NS036960] NR 27 TC 75 Z9 78 U1 0 U2 4 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 JAN 15 PY 2008 VL 23 IS 1 BP 88 EP 95 DI 10.1002/mds.21782 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 258WS UT WOS:000252901400013 PM 17987647 ER PT J AU Schon, K Tinaz, S Somers, DC Stern, CE AF Schon, Karin Tinaz, Sule Somers, David C. Stern, Chantal E. TI Delayed match to object or place: An event-related fMRI study of short-term stimulus maintenance and the role of stimulus pre-exposure SO NEUROIMAGE LA English DT Review DE orbitofrontal cortex; frontal eye fields; dorsolateral prefrontal cortex; superior frontal sulcus; match-to-sample; working memory ID SPATIAL WORKING-MEMORY; FRONTAL EYE-FIELD; PRIMATE PREFRONTAL CORTEX; POSITRON EMISSION TOMOGRAPHY; DISTRIBUTED NEURAL SYSTEM; POSTERIOR PARIETAL CORTEX; TO-SAMPLE TASK; ORBITOFRONTAL CORTEX; PROACTIVE-INTERFERENCE; FUNCTIONAL-ORGANIZATION AB Recent delayed matching studies have demonstrated that maintaining trial-unique stimuli in working memory modulates activity in temporal lobe structures. In contrast, most previous studies that focused on the role of the prefrontal cortex (PFC) used familiar stimuli. We combined fMRI with a delayed-match-to-sample (DMS) task in humans that allowed us to manipulate stimulus pre-exposure (trial-unique vs. familiar objects) and stimulus domain (object vs. location). A visually guided saccade task was used to localize the frontal eye fields (FEF). We addressed two questions: First, we examined whether delay-period activity within PFC regions was more strongly engaged when stimuli were familiar (pre-exposed) than when they were not seen previously (trial-unique). Second, we examined the role of regions within the PFC in object vs. location working memory. Subjects were instructed to remember one stimulus domain while ignoring the other over an 8-s delay period. Object-specific delay-period activity was greatest in the posterior orbitofrontal cortex (OFC) bilaterally, and was stronger for familiar than trial-unique objects. In addition, consistent with previous findings, right posterior superior frontal sulcus, and the FEF were specifically active during the delay period of the location DMS task. These activations outside FEF were not related to saccadic eye movements. In contrast to previous reports, object-specific delay activity was more prominent in the posterior OFC than in the ventrolateral PFC, and was found to be greater for familiar than for trial-unique objects. These results suggest a critical role for the orbitofrontal cortex for maintaining object information in working memory. (C) 2007 Elsevier Inc. All rights reserved. C1 [Schon, Karin; Tinaz, Sule; Somers, David C.; Stern, Chantal E.] Boston Univ, Ctr Memory & Brain, Boston, MA 02215 USA. [Schon, Karin; Somers, David C.; Stern, Chantal E.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Tinaz, Sule; Somers, David C.; Stern, Chantal E.] Boston Univ, Program Neurosci, Boston, MA 02215 USA. [Somers, David C.; Stern, Chantal E.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Schon, K (reprint author), Boston Univ, Ctr Memory & Brain, 2 Cummington St, Boston, MA 02215 USA. EM kschon@bu.edu RI Somers, David/G-5802-2010; OI Somers, David/0000-0002-4169-5895; Schon, Karin/0000-0003-2963-8449 FU NCRR NIH HHS [P41 RR014075, P41 RR014075-01A1, P41RR14075]; NIMH NIH HHS [P50 MH071702, P50 MH071702-01A2, P50 MH071702-A2] NR 119 TC 20 Z9 20 U1 2 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 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JAN 15 PY 2008 VL 39 IS 2 BP 857 EP 872 DI 10.1016/j.neuroimage.2007.09.023 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 241CL UT WOS:000251634400029 PM 17950623 ER PT J AU Choi, WS Fang-Yen, C Badizadegan, K Dasari, RR Feld, MS AF Choi, Wonshik Fang-Yen, Christopher Badizadegan, Kamran Dasari, Ramachandra R. Feld, Michael S. TI Extended depth of focus in tomographic phase microscopy using a propagation algorithm SO OPTICS LETTERS LA English DT Article AB Tomographic phase microscopy is a laser interferometry technique in which a 3D refractive index map of a biological sample is constructed from quantitative phase images collected at a set of illumination angles. Although the resulting tomographic images provide valuable information, their resolution declines at axial distances beyond about 1 mu m from the focal plane. We describe an improved 3D reconstruction algorithm in which the field at the focal plane is numerically propagated to depths throughout the sample. Diffraction is thus incorporated, extending the depth of focus to more than 10 mu m. Tomograms with improved focal depth are demonstrated for single HT29 cells. (c) 2008 Optical Society of America. C1 [Choi, Wonshik; Fang-Yen, Christopher; Badizadegan, Kamran; Dasari, Ramachandra R.; Feld, Michael S.] MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. [Badizadegan, Kamran] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Choi, WS (reprint author), MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. EM wonshik@mit.edu OI Fang-Yen, Christopher/0000-0002-4568-3218 FU NCRR NIH HHS [P41 RR002594-24, P41-RR02594-18, P41 RR002594] NR 8 TC 34 Z9 34 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 JAN 15 PY 2008 VL 33 IS 2 BP 171 EP 173 DI 10.1364/OL.33.000171 PG 3 WC Optics SC Optics GA 262ZJ UT WOS:000253187100028 PM 18197229 ER PT J AU Krzywkowski, K Davies, PA Feinberg-Zadek, PL Brauner-Osborne, H Jensen, AA AF Krzywkowski, Karen Davies, Paul A. Feinberg-Zadek, Paula L. Brauner-Osborne, Hans Jensen, Anders A. TI High-frequency HTR3B variant associated with major depression dramatically augments the signaling of the human 5-HT3AB receptor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE 5-HT3; ligand-gated ion channel; polymorphism; serotonin; receptor kinetics ID 3B RECEPTOR; SEROTONIN; 5-HYDROXYTRYPTAMINE; GENES; EXPRESSION; SUBUNIT; CHANNEL; HIPPOCAMPUS; MODULATION; PAROXETINE AB The 5-hydroxytryptamine-3 (5-HT3) receptor mediates the fast excitatory neurotransmission of serotonin and is known to mediate the nausea/emesis induced by radio/chemotherapy and anesthetics. A polymorphism encoding the variation Y129S in the 5-HT3B subunit exists in high frequency in the general population and has been shown to be inversely correlated to the incidence of major depression in women. We show that 5-HT3AB(Y129S) receptors exhibit a substantially increased maximal response to serotonin compared with WT receptors in two fluorescence-based cellular assays. In electrophysiological recordings, the deactivation and desensitization kinetics of the 5-HT3AB(Y129S) receptor are 20- and 10-fold slower, respectively, than those of the WT receptor. Single-channel measurements reveal a 7-fold-increased mean open time of 5-HT3AB(Y129S) receptors compared with WT receptors. The augmented signaling displayed by 5-HT3AB(Y129S) receptors may confer protection against the development of depression. The variant also may influence the development and/or treatment of nausea and other disorders involving 5-HT3 receptors. Thus, the impact of the high-frequency variant 5-HT3B(Y129S) on 5-HT3AB receptor signaling calls for a search for additional phenotypes, and the variant may thus aid in establishing the role of the 5-HT3AB receptor in pathophysiology. C1 [Krzywkowski, Karen; Jensen, Anders A.] Univ Copenhagen, Fac Pharmaceut Sci, Dept Med Chem, DK-2100 Copenhagen, Denmark. [Davies, Paul A.; Feinberg-Zadek, Paula L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02115 USA. RP Jensen, AA (reprint author), Univ Copenhagen, Fac Pharmaceut Sci, Dept Med Chem, Univ Pk 2, DK-2100 Copenhagen, Denmark. EM aaj@farma.ku.dk RI Brauner-Osborne, Hans/D-7260-2011; OI Brauner-Osborne, Hans/0000-0001-9495-7388; Jensen, Anders/0000-0002-7927-5052; Davies, Paul/0000-0002-3973-3143 NR 34 TC 44 Z9 45 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 JAN 15 PY 2008 VL 105 IS 2 BP 722 EP 727 DI 10.1073/pnas.0708454105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 253XO UT WOS:000252551100059 PM 18184810 ER PT J AU Foland, LC Altshuler, LL Bookheimer, SY Eisenberger, N Townsend, J Thompson, PM AF Foland, Lara C. Altshuler, Lori L. Bookheimer, Susan Y. Eisenberger, Naomi Townsend, Jennifer Thompson, Paul M. TI Evidence for deficient modulation of amygdala response by prefrontal cortex in bipolar mania SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE bipolar disorder; fMRI; functional connectivity; emotion regulation ID FACIAL AFFECT RECOGNITION; FUNCTIONAL CONNECTIVITY; ORBITOFRONTAL CORTEX; NEGATIVE AFFECT; RATING-SCALE; BLOOD-FLOW; DISORDER; BRAIN; FMRI; ACTIVATION AB Several studies have implicated the involvement of two major components of emotion regulatory networks, the ventrolateral prefrontal cortex (VLPFC) and amygdala, in the pathophysiology of bipolar disorder. In healthy subjects, the VLPFC has been shown to negatively modulate amygdala response when subjects cognitively evaluate an emotional face by identifying and labeling the emotion it expresses. The current study used such a paradigm to assess whether the strength of this modulation was altered in bipolar subjects when manic. During functional magnetic resonance imaging (fMRI), nine manic subjects with bipolar I disorder and nine healthy subjects either named the emotion shown in a face by identifying one of two words that correctly expressed the emotion (emotion labeling task) or matched the emotion shown in a face to one of two other faces (emotion perception task). The degree to which the VLPFC regulated amygdala response during these tasks was assessed using a psychophysiological interaction (PPI) analysis. Compared with healthy subjects, manic patients had a significantly reduced VLPFC regulation of amygdala response during the emotion labeling task. These findings, taken in context with previous fMRI studies of bipolar mania, suggest that reductions in inhibitory frontal activity in these patients may lead to an increased reactivity of the amygdala. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Foland, Lara C.; Thompson, Paul M.] Univ Calif Los Angeles, Dept Neurol, Lab NeuroImaging, Los Angeles, CA USA. [Altshuler, Lori L.; Bookheimer, Susan Y.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA USA. [Altshuler, Lori L.] W Los Angeles Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. [Bookheimer, Susan Y.; Townsend, Jennifer] Univ Calif Los Angeles, Ahmanson Lovelace Brain Mapping Ctr, Sch Med, Los Angeles, CA USA. [Eisenberger, Naomi] Univ Calif Los Angeles, Cousins Ctr Psychoneuroimmunol, Los Angeles, CA USA. RP Altshuler, LL (reprint author), Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, 300 Med Plaza,Suite 1544, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu FU NCRR NIH HHS [R21 RR019771, U54 RR021813-020001, U54 RR021813, RR019771]; NIBIB NIH HHS [R01 EB008281-11A1, R01 EB007813, R01 EB008281, EB01651, R01 EB007813-01A2]; NICHD NIH HHS [HD050735, R01 HD050735]; NIMH NIH HHS [MH01848, F31 MH078556-01A1, K24 MH001848-01A1, K24 MH001848, F31 MH078556] NR 62 TC 133 Z9 133 U1 3 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD JAN 15 PY 2008 VL 162 IS 1 BP 27 EP 37 DI 10.1016/j.pscychresns.2007.04.007 PG 11 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 266NM UT WOS:000253442900003 PM 18063349 ER PT J AU Tzermiadianos, MN Mekhail, A Voronov, LI Zook, J Havey, RM Renner, SM Carandang, G Abjornson, C Patwardhan, AG AF Tzermiadianos, Michael N. Mekhail, Anis Voronov, Leonard I. Zook, Jason Havey, Robert M. Renner, Susan M. Carandang, Gerard Abjornson, Celeste Patwardhan, Avinash G. TI Enhancing the stability of anterior lumbar interbody fusion SO SPINE LA English DT Article DE anterior lumbar interbody fusion (ALIF); femoral ring allograft (FRA); anterior tension band plate; transpedicular instrumentation ID DONOR SITE PAIN; BIOMECHANICAL ANALYSIS; LUMBOSACRAL FIXATION; PEDICLE SCREWS; IN-VITRO; SPINE; CAGES; INSTRUMENTATION; STABILIZATION; PRELOAD AB Study Design. Biomechanical study using human cadaver spines. Objective. To assess the stabilizing effect of a supplemental anterior tension band (ATB, Synthes) plate on L5-S1 anterior lumbar interbody fusion (ALIF) using a femoral ring allograft (FRA) under physiologic compressive preloads, and to compare the results with the stability achieved using FRA with supplemental transpedicular instrumentation. Summary of Background Data. Posterior instrumentation can improve the stability of ALIF cages. Anterior plates have been proposed as an alternative to avoid the additional posterior approach. Methods. Eight human specimens (L3 to sacrum) were tested in the following sequence: (i) intact, (ii) after anterior insertion of an FRA at L5-S1, (iii) after instrumentation with the ATB plate, and (iv) after removal of the plate and adding transpedicular instrumentation at the same level. Specimens were tested in flexion-extension, lateral bending, and axial rotation. Flexion-extension was tested under 0 N, 400 N, and 800 N compressive follower preload to simulate physiologic compressive preloads on the lumbar spine. Results. Stand-alone FRAs significantly decreased the range of motion (ROM) in all tested directions (P < 0.05); however, the resultant ROM was large in flexion-extension ranging between 6.1 +/- 3.1 and 5.1 +/- 2.2 under 0 N to 800 N preloads. The ATB plate resulted in a significant additional decrease in flexion-extension ROM under 400 N and 800 N preloads (P < 0.05). The flexion-extension ROM with the ATB plate was 4.1 +/- 2.3 under 0 N preload and ranged from 3.1 +/- 1.8 to 2.4 +/- 1.3 under 400 N to 800 N preloads. The plate did not significantly decrease lateral bending or axial rotation ROM compared with stand-alone FRA (P > 0.05), but the resultant ROM was 2.7 +/- 1.9 degrees and 0.9 +/- 0.6 degrees, respectively. Compared with the ATB plate, the transpedicular instrumentation resulted in significantly less ROM in flexion-extension and lateral bending (P < 0.05), but not in axial rotation (P > 0.05). Conclusion. The ATB plate can significantly increase the stability of the anterior FRA at L5-S1 level. Although supplemental transpedicular instrumentation results in a more stable biomechanical environment, the resultant ROM with the addition of a plate is small, especially under physiologic preload, suggesting that the plate can sufficiently resist motion. Therefore, clinical assessment of the ATB plate as an alternative to transpedicular instrumentation to enhance ALIF cage stability is considered reasonable. C1 [Tzermiadianos, Michael N.; Voronov, Leonard I.; Havey, Robert M.; Patwardhan, Avinash G.] Loyola Univ, Med Ctr, Dept Orthopaed Surg & Rehabil, Maywood, IL 60153 USA. [Tzermiadianos, Michael N.; Voronov, Leonard I.; Havey, Robert M.; Renner, Susan M.; Carandang, Gerard; Patwardhan, Avinash G.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Mekhail, Anis; Zook, Jason; Renner, Susan M.] Univ Illinois, Chicago, IL USA. [Abjornson, Celeste] Synthes Spine, W Chester, PA USA. RP Patwardhan, AG (reprint author), Loyola Univ, Med Ctr, Dept Orthopaed Surg & Rehabil, 2160 S 1st Ave, Maywood, IL 60153 USA. EM apatwar@lumc.edu NR 29 TC 12 Z9 12 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD JAN 15 PY 2008 VL 33 IS 2 BP E38 EP E43 PG 6 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 267XM UT WOS:000253542500023 PM 18197089 ER PT J AU Garcia, DA Regan, S Henault, LE Upadhyay, A Baker, J Othman, M Hylek, EM AF Garcia, David A. Regan, Susan Henault, Lori E. Upadhyay, Ashish Baker, Jaclyn Othman, Mohamed Hylek, Elaine M. TI Risk of thromboembolism with short-term interruption of warfarin therapy SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID MOLECULAR-WEIGHT HEPARIN; PROSTHETIC HEART-VALVES; ELECTIVE SURGERY; ANTICOAGULATION; MANAGEMENT; OPERATIONS; HEMORRHAGE; ENOXAPARIN AB Background: Significant uncertainty surrounds the treatment of patients who must discontinue warfarin sodium therapy before an invasive procedure. In part, the uncertainty results from the lack of published information about the risk of thromboembolism associated with short-term warfarin therapy interruption. We aimed to assess the frequency of thromboembolism and bleeding within a large cohort of patients whose warfarin therapy was temporarily withheld for an outpatient invasive procedure. Methods: This prospective, observational cohort study was performed at 101 sites (primarily community-based physician office practices) in the United States. Enrollment was conducted from April 4, 2000, to March 6, 2002. The main outcome measures were thromboembolism or clinically significant hemorrhage within 30 days of warfarin therapy interruption. Results: A total of 1293 episodes of warfarin therapy interruption in 1024 individuals were included. The mean (SD) patient age was 71.9 (10.6) years; 438 (42.8%) were female. The most common indications for anticoagulant therapy were atrial fibrillation (n = 550), venous thromboembolism (n = 144), and mechanical heart valve (n = 13 2). The most common procedures were colonoscopy and oral and ophthalmic surgery. Perioperative heparin or low-molecular-weight heparin was used in only 8.3% of cases overall. Seven patients (0.7%; 95% confidence interval [CI], 0.3%-1.4%) experienced postprocedure thromboembolism within 30 days. None of the 7 patients who experienced thromboembolism received periprocedural bridging therapy. Six patients (0.6%; 95% CI, 0.2%-1.3%) experienced major bleeding, whereas an additional 17 patients (1.7%; 95% CI, 1.0%-2.6%) experienced a clinically significant, nonmajor bleeding episode. Of these 23 patients who had bleeding episodes, 14 received periprocedural heparin or low-molecular-weight heparin. The duration of warfarin therapy interruption was variable; however, more than 80% of patients had warfarin therapy withheld for 5 days or fewer. Conclusions: For many patients receiving long-term anticoagulation who need to undergo a minor outpatient intervention, a brief (<= 5 days) periprocedural interruption of warfarin therapy is associated with a low risk of thromboembolism. The risk of clinically significant bleeding, even among outpatients undergoing minor procedures, should be weighed against the thromboembolic risk of an individual patient before the administration of bridging anticoagulant therapy. C1 [Garcia, David A.; Othman, Mohamed] Univ New Mexico, Hlth Sci Ctr, Dept Internal Med, Albuquerque, NM 87131 USA. [Regan, Susan] Massachusetts Gen Hosp, Gen Med Unit, Dept Med, Boston, MA 02114 USA. [Henault, Lori E.; Baker, Jaclyn; Hylek, Elaine M.] Boston Univ, Sch Med, Dept Med, Res Unit,Sect Gen Internal Med, Boston, MA 02215 USA. [Upadhyay, Ashish] Tufts Univ, Sch Med, Caritas St Elizabeths Med Ctr, Dept Med, Boston, MA 02111 USA. RP Garcia, DA (reprint author), 1 Univ New Mexico, Dept Internal Med, MSC105550, Albuquerque, NM 87131 USA. NR 17 TC 172 Z9 177 U1 0 U2 4 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 JAN 14 PY 2008 VL 168 IS 1 BP 63 EP 69 DI 10.1001/archinternmed.2007.23 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 249RX UT WOS:000252248500010 PM 18195197 ER PT J AU Sebastiani, P Zhao, Z Abad-Grau, MM Riva, A Hartley, SW Sedgewick, AE Doria, A Montano, M Melista, E Terry, D Perls, TT Steinberg, MH Baldwin, CT AF Sebastiani, Paola Zhao, Zhenming Abad-Grau, Maria M. Riva, Alberto Hartley, Stephen W. Sedgewick, Amanda E. Doria, Alessandro Montano, Monty Melista, Efthymia Terry, Dellara Perls, Thomas T. Steinberg, Martin H. Baldwin, Clinton T. TI A hierarchical and modular approach to the discovery of robust associations in genome-wide association studies from pooled DNA samples SO BMC GENETICS LA English DT Article ID SICKLE-CELL-ANEMIA; G-CSF; MYOCARDIAL-INFARCTION; EXCEPTIONAL LONGEVITY; FETAL-HEMOGLOBIN; KSNP MICROARRAYS; IDENTIFICATION; DISEASE; DETERMINANTS; MOBILIZATION AB Background: One of the challenges of the analysis of pooling-based genome wide association studies is to identify authentic associations among potentially thousands of false positive associations. Results: We present a hierarchical and modular approach to the analysis of genome wide genotype data that incorporates quality control, linkage disequilibrium, physical distance and gene ontology to identify authentic associations among those found by statistical association tests. The method is developed for the allelic association analysis of pooled DNA samples, but it can be easily generalized to the analysis of individually genotyped samples. We evaluate the approach using data sets from diverse genome wide association studies including fetal hemoglobin levels in sickle cell anemia and a sample of centenarians and show that the approach is highly reproducible and allows for discovery at different levels of synthesis. Conclusion: Results from the integration of Bayesian tests and other machine learning techniques with linkage disequilibrium data suggest that we do not need to use too stringent thresholds to reduce the number of false positive associations. This method yields increased power even with relatively small samples. In fact, our evaluation shows that the method can reach almost 70% sensitivity with samples of only 100 subjects. C1 [Sebastiani, Paola; Zhao, Zhenming; Hartley, Stephen W.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Abad-Grau, Maria M.] Univ Granada, Dept Software Engn, E-18071 Granada, Spain. [Riva, Alberto] Univ Florida, Dept Mol Genet, Gainesville, FL 32611 USA. [Sedgewick, Amanda E.] Boston Univ, Sch Engn, Bioinformat Program, Boston, MA 02116 USA. [Doria, Alessandro] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. [Montano, Monty; Melista, Efthymia; Steinberg, Martin H.; Baldwin, Clinton T.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Terry, Dellara; Perls, Thomas T.] Boston Univ, Med Ctr, Geriatr Sect, Boston, MA 02118 USA. RP Sebastiani, P (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. EM sebas@bu.edu; zmzhao@bu.edu; mabad@ugr.es; ariva@ufl.edu; shartley@bu.edu; asedge@bu.edu; Alessandro.Doria@joslin.harvard.edu; mmontano@bu.edu; emelista@bu.edu; laterry@bu.edu; thperls@bu.edu; mhsteinb@bu.edu; cbaldwin@bu.edu RI Abad Grau, Maria del Mar/B-2172-2012; OI Abad Grau, Maria del Mar/0000-0001-8470-9719; Perls, Thomas/0000-0002-2492-4334; Steinberg, Martin/0000-0001-8800-8020; sebastiani, paola/0000-0001-6419-1545; Riva, Alberto/0000-0001-9150-8333 FU NHLBI NIH HHS [R01 HL068970, R01 HL68970, R21 HL080463]; NIA NIH HHS [K23 AG026754, K24 AG025727, K24 AG025727-02] NR 55 TC 14 Z9 17 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD JAN 14 PY 2008 VL 9 AR 6 DI 10.1186/1471-2156-9-6 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 265YI UT WOS:000253397400001 PM 18194558 ER PT J AU Kuntzen, T Tural, C Li, B Feldmann, G Kupfer, B Nischalke, HD Clotet, B Sauerbruch, T Rockstroh, JK Spengler, U AF Kuntzen, Thomas Tural, Cristina Li, Bin Feldmann, Georg Kupfer, Bernd Nischalke, Hans Dieter Clotet, Bonaventura Sauerbruch, Tilman Rockstroh, Juergen K. Spengler, Ulrich TI Intrahepatic rnRNA expression in hepatitis C virus and HIV/hepatitis C virus co-infection: infiltrating cells, cytokines, and influence of HAART SO AIDS LA English DT Article DE interferon gamma; interferon-inducible protein 10; macrophage chemoattractant protein 1; macrophage inflammatory protein 1 alpha; regulated upon activation : normal T-cell expressed and secreted; stroma-derived factor 1; secondary lymphochemokine ID CD8(+) T-CELLS; ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; LIVER-DISEASE; INDUCIBLE PROTEIN-10; HCV/HIV COINFECTION; HIV COINFECTION; LYMPHOCYTES; RESPONSES; FIBROSIS AB Objective: Liver disease is more progressive in HIV/hepatitis C virus (HCV) co-infection than in HCV infection alone. This accelerated pathogenesis is probably influenced by differences in the composition of infiltrating inflammatory cells and the local release of inflammatory and profibrogenic cytokines. Methods: Using quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) we studied intrahepatic messenger RNA levels of cytokines and cellular markers defining distinct subsets of inflammatory cells in liver biopsies from 33 HCV-mono-infected and 40 HIV/HCV-co-infected patients. Results: Despite their well preserved peripheral blood CD4 cell counts (median 598 cells/mu l), HIV/HCV-co-infected patients displayed significantly lower CD4 mRNA levels than HCV-mono-infected patients, whereas increased mRNA levels of CD3 epsilon, TCR alpha, CD8 alpha and CD8 beta suggested intrahepatic enrichment of CD8 T cells in HIV co-infection. Intrahepatic mRNA levels of the inflammatory cytokines interferon gamma (IFN-gamma), regulated upon activation, normal T-cell expressed and secreted (RANTES, CCL5), macrophage inflammatory protein 1 alpha (CCL3) and interferon-inducible protein 10 (CXCL10) were significantly higher in HIV-positive than in HIV-negative patients, whereas mRNA levels of the profibrogenic cytokines macrophage chemoattractant protein 1 (CCL2), secondary lymphochemokine (CCL21) and stroma-derived factor 1 (CXCL12) did not differ between the two groups. All changes were less pronounced in the subgroup of HIV-positive patients receiving antiretroviral treatment (HAART) than in untreated HIV-positive patients. Conclusion: The accelerated liver disease observed in HIV/HCV-co-infected patients might reflect enhanced intrahepatic inflammatory responses rather than increased local transcription of directly profibrogenic cytokines. (c) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Kuntzen, Thomas; Li, Bin] Massachusetts Gen Hosp, Harvard Med Sch, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. [Kuntzen, Thomas; Feldmann, Georg; Nischalke, Hans Dieter; Sauerbruch, Tilman; Rockstroh, Juergen K.; Spengler, Ulrich] Univ Hosp Bonn, Dept Internal Med 1, Bonn, Germany. [Kupfer, Bernd] Univ Hosp Bonn, Inst Med Microbiol Immunol & Parasitol, Bonn, Germany. [Tural, Cristina; Clotet, Bonaventura] Univ Autonoma Barcelona, Hosp Univ German Trias Pujol, HIV Unit, E-08193 Barcelona, Spain. [Tural, Cristina; Clotet, Bonaventura] Univ Autonoma Barcelona, Hosp Univ German Trias Pujol, Irsicaixa Fdn, E-08193 Barcelona, Spain. RP Kuntzen, T (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. EM tkuntzen@partners.org NR 43 TC 24 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 11 PY 2008 VL 22 IS 2 BP 203 EP 210 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 251LX UT WOS:000252376100005 PM 18097222 ER PT J AU Currie, SL Ryan, JC Tracy, D Wright, TL George, S McQuaid, R Kim, M Shen, H Monto, A AF Currie, Sue L. Ryan, James C. Tracy, Daniel Wright, Teresa L. George, Sally McQuaid, Rosemary Kim, Michael Shen, Hui Monto, Alexander TI A prospective study to examine persistent HCV reinfection in injection drug users who have previously cleared the virus SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE hepatitis; hepatitis C virus; IDUs; HCV reinfection; HCV resolution ID HEPATITIS-C VIRUS; UNITED-STATES; IMMUNE-RESPONSE; INFECTION; MANAGEMENT; PREVALENCE AB Background: Many HCV-infected persons with recent or ongoing injection drug use (IDU) do not receive HCV treatment due to the perceived risk of HCV reinfection. There are few prospective studies investigating HCV reinfection among IDUs. Methods: Two hundred and twenty-four persons with past or ongoing IDU were followed from 1997 to 2007. Baseline and every 6-month follow-up data were collected including demographics, IDU, and sexual behaviors. Serum was tested for the presence of HCV antibody and serially for HCV RNA. Resolvers were defined as HCV antibody and RIBA positive and RNA negative at two consecutive time points or as becoming HCV RNA negative after HCV antiviral treatment. Reinfection was defined by the presence of HCV RNA at >= 2 visits. Results: One hundred and eighty-six persons had chronic HCV and 38 had resolved HCV The resolvers were followed for a total of 214 person-years. Forty-two percent of resolvers reported ongoing IDU, representing 58 person-years of IDU. Only one reinfection occurred in the resolvers, for a reinfection rate of 0.47 cases/100 person-years of follow-up. The single reinfection, which occurred in a person who continued to inject drugs, represents a reinfection rate of 1.75 cases/100 person-years of IDU. Conclusion: These data suggest that despite ongoing IDU, persistent HCV reinfection is lower than previously published. This can be attributed to a more clinically relevant definition of reinfection. This information will better help clinicians make informed decisions regarding HCV treatment options for patients who may continue to inject illicit drugs. Published by Elsevier Ireland Ltd. C1 [Currie, Sue L.; Ryan, James C.; Tracy, Daniel; Kim, Michael; Shen, Hui; Monto, Alexander] Univ Calif San Francisco, Dept Med, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Ryan, James C.; Wright, Teresa L.; George, Sally; McQuaid, Rosemary; Kim, Michael; Monto, Alexander] San Francisco VA Med Ctr, Div Gastroenterol, San Francisco, CA USA. RP Currie, SL (reprint author), Univ Calif San Francisco, Dept Med, San Francisco VA Med Ctr, 111,4150 Clement st, San Francisco, CA 94121 USA. EM sue.currie@va.gov FU NIDA NIH HHS [R01 DA13737-01] NR 19 TC 40 Z9 40 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 11 PY 2008 VL 93 IS 1-2 BP 148 EP 154 DI 10.1016/j.drugalcdep.2007.09.011 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 260SW UT WOS:000253031700017 PM 17977668 ER PT J AU Kuraoka, I Ito, S Wada, T Hayashida, M Lee, L Saijo, M Nakatsu, Y Matsumoto, M Matsunaga, T Handa, H Qin, J Nakatani, Y Tanaka, K AF Kuraoka, Isao Ito, Shinsuke Wada, Tadashi Hayashida, Mika Lee, Lily Saijo, Masafumi Nakatsu, Yoshimichi Matsumoto, Megumi Matsunaga, Tsukasa Handa, Hiroshi Qin, Jun Nakatani, Yoshihiro Tanaka, Kiyoji TI Isolation of XAB2 complex involved in pre-mRNA splicing, transcription, and transcription-coupled repair SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; CYCLOBUTANE PYRIMIDINE DIMER; DNA-REPAIR; COCKAYNE-SYNDROME; POLYMERASE-II; SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; XERODERMA-PIGMENTOSUM; NUCLEAR-MATRIX; CANCER-CELLS AB Nucleotide excision repair is a versatile repair pathway that counteracts the deleterious effects of various DNA lesions. In nucleotide excision repair, there is a transcription-coupled repair (TCR) pathway that focuses on DNA damage that blocks RNA polymerase IIo in transcription elongation. XAB2 (XPA-binding protein 2), containing tetratricopeptide repeats, has been isolated by virtue of its ability to interact with xeroderma pigmentosum group A protein (XPA). Moreover, XAB2 has been shown to interact with Cockayne syndrome group A and B proteins (CSA and CSB) and RNA polymerase II, as well as XPA, and is involved in TCR and transcription. Here we purified XAB2 as a multimeric protein complex consisting of hAquarius, XAB2, hPRP19, CCDC16, hISY1, and PPIE, which are involved in pre-mRNA splicing. Knockdown of XAB2 with small interfering RNA in HeLa cells resulted in a hypersensitivity to killing by UV light and a decreased recovery of RNA synthesis after UV irradiation and regular RNA synthesis. Enhanced interaction of XAB2 with RNA polymerase IIo or XPA was observed in cells treated with DNA-damaging agents, indicating DNA damage-responsive activity of the XAB2 complex. These results indicated that the XAB2 complex is a multifunctional factor involved in pre-mRNA splicing, transcription, and TCR. C1 [Kuraoka, Isao; Ito, Shinsuke; Hayashida, Mika; Lee, Lily; Saijo, Masafumi; Nakatsu, Yoshimichi; Tanaka, Kiyoji] Osaka Univ, Grad Sch Frontier Biosci, Labs Organismal Biosyst, Suita, Osaka 5650871, Japan. [Kuraoka, Isao; Saijo, Masafumi; Tanaka, Kiyoji] Japan Sci & Technol Agcy, Solut Oriented Res Sci & Technol, Suita, Osaka 5650871, Japan. [Matsumoto, Megumi; Matsunaga, Tsukasa] Kanazawa Univ, Grad Sch Nat Sci & Technol, Lab Human Mol Genet, Kakuma, Kanazawa 9201192, Japan. [Wada, Tadashi; Handa, Hiroshi] Tokyo Inst Technol, Fac Biosci & Biotechnol, Yokohama, Kanagawa 2268501, Japan. [Wada, Tadashi; Handa, Hiroshi] Tokyo Inst Technol, Frontier Collaborat Res Ctr, Yokohama, Kanagawa 2268501, Japan. [Qin, Jun] Baylor Coll Med, Dept Biochem, Houston, TX 77030 USA. [Nakatani, Yoshihiro] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nakatani, Yoshihiro] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kuraoka, I (reprint author), Osaka Univ, Grad Sch Frontier Biosci, Labs Organismal Biosyst, 1-3 Yamadaoka, Suita, Osaka 5650871, Japan. EM ikuraoka@nk-cc.go.jp; ktanaka@fbs.osaka-u.ac.jp NR 54 TC 38 Z9 44 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 JAN 11 PY 2008 VL 283 IS 2 BP 940 EP 950 DI 10.1074/jbc.M706647200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 248CE UT WOS:000252128100034 PM 17981804 ER PT J AU Yeung, T Gilbert, GE Shi, J Silvius, J Kapus, A Grinstein, S AF Yeung, Tony Gilbert, Gary E. Shi, Jialan Silvius, John Kapus, Andras Grinstein, Sergio TI Membrane phosphatidylserine regulates surface charge and protein localization SO SCIENCE LA English DT Article ID PLASMA-MEMBRANE; ELECTROSTATIC SWITCH; BINDING; LACTADHERIN; ASSOCIATION; APOPTOSIS; K-RAS4B; DOMAIN AB Electrostatic interactions with negatively charged membranes contribute to the subcellular targeting of proteins with polybasic clusters or cationic domains. Although the anionic phospholipid phosphatidylserine is comparatively abundant, its contribution to the surface charge of individual cellular membranes is unknown, partly because of the lack of reagents to analyze its distribution in intact cells. We developed a biosensor to study the subcellular distribution of phosphatidylserine and found that it binds the cytosolic leaflets of the plasma membrane, as well as endosomes and lysosomes. The negative charge associated with the presence of phosphatidylserine directed proteins with moderately positive charge to the endocytic pathway. More strongly cationic proteins, normally associated with the plasma membrane, relocalized to endocytic compartments when the plasma membrane surface charge decreased on calcium influx. C1 [Yeung, Tony; Grinstein, Sergio] Hosp Sick Children, Div Cell Biol, Toronto, ON M5G 1X8, Canada. [Gilbert, Gary E.; Shi, Jialan] Harvard Univ, Dept Vet Affairs, Brigham & Womens Hosp, Dept Med,VA Boston Healthcare Syst,Sch Med, Boston, MA 02115 USA. [Silvius, John] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada. [Kapus, Andras] Univ Toronto, St Michaels Hosp, Keenan Res Ctr, Li Ka Sheng Knowledge Inst, Toronto, ON M5B 1W8, Canada. [Kapus, Andras] Univ Toronto, Dept Surg, Toronto, ON M5B 1W8, Canada. RP Grinstein, S (reprint author), Hosp Sick Children, Div Cell Biol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM sga@sickkids.ca NR 17 TC 417 Z9 428 U1 9 U2 81 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 11 PY 2008 VL 319 IS 5860 BP 210 EP 213 DI 10.1126/science.1152066 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 249RC UT WOS:000252246400043 PM 18187657 ER PT J AU Li, YQ Wang, XY Zhai, HF Zhang, XY Kosten, T Lu, L AF Li, Yan-Qin Wang, Xiao-yi Zhai, Hai-feng Zhang, Xiang Yang Kosten, Therese Lu, Lin TI Sex- and age-dependent effects of early postnatal sibling deprivation on spatial learning and memory in adult rats SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE early postnatal sibling deprivation; development; spatial learning and memory; sex; age ID PYRAMIDAL NEURON MORPHOLOGY; FACTOR MESSENGER-RNA; GUINEA-PIG; ENVIRONMENTAL ENRICHMENT; SOCIAL-ISOLATION; COGNITIVE-DEVELOPMENT; ENTORHINAL CORTEX; ISOLATION STRESS; DENTATE GYRUS; MATERNAL-CARE AB In this study. we investigated the effects of early postnatal sibling deprivation (EPSD) on spatial learning and memory in adult rats. Litters were culled to one pup with its mother on postnatal day (PN) 1 or 7 and their spatial learning and memory ability were examined with Morris water maze in adult. EPSD on PN1 improved, but on PN7 impaired performance of the spatial learning task in adult female rats. However, EPSD did not have any effect on the spatial learning ability in adult male rats. (c) 2007 Elsevier B.V. All rights reserved. C1 [Li, Yan-Qin; Wang, Xiao-yi; Zhai, Hai-feng; Lu, Lin] Peking Univ, Natl Inst Drug Dependence, Beijing 100083, Peoples R China. [Zhang, Xiang Yang; Kosten, Therese] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, VA Med Ctr, Houston, TX 77030 USA. RP Lu, L (reprint author), Peking Univ, Natl Inst Drug Dependence, 38 Xue Yuan Rd,Haidian Dist, Beijing 100083, Peoples R China. EM linlu@bjmu.edu.cn NR 30 TC 3 Z9 4 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD JAN 10 PY 2008 VL 186 IS 1 BP 138 EP 142 DI 10.1016/j.bbr.2007.07.028 PG 5 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 244MG UT WOS:000251869400018 PM 17765982 ER PT J AU Tsimberidou, AM Wierda, WG Plunkett, W Kurzrock, R O'Brien, S Wen, S Ferrajoli, A Ravandi-Kashani, F Garcia-Manero, G Estrov, Z Kipps, TJ Brown, JR Fiorentino, A Lerner, S Kantarjian, HM Keating, MJ AF Tsimberidou, Apostolia M. Wierda, William G. Plunkett, William Kurzrock, Razelle O'Brien, Susan Wen, Sijin Ferrajoli, Alessandra Ravandi-Kashani, Farhad Garcia-Manero, Guillermo Estrov, Zeev Kipps, Thomas J. Brown, Jennifer R. Fiorentino, Albert Lerner, Susan Kantarjian, Hagop M. Keating, Michael J. TI Phase I-II study of oxaliplatin, fludarabine, cytarabine, and rituximab combination therapy in patients with Richter's syndrome or fludarabine-refractory chronic lymphocytic leukemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol ID NON-HODGKINS-LYMPHOMA; HIGH-DOSE CYTARABINE; ARA-C; INITIAL THERAPY; SALVAGE THERAPY; PLUS RITUXIMAB; GM-CSF; CISPLATIN; CYCLOPHOSPHAMIDE; CANCER AB Purpose Richter's syndrome (RS) and fludarabine-refractory chronic lymphocytic leukemia (CLL) are associated with poor clinical outcomes. We conducted a phase I-II trial of oxaliplatin, fludarabine, cytarabine, and rituximab (OFAR) in these diseases. Patients and Methods The OFAR regimen consisted of increasing doses of oxaliplatin (17.5, 20, or 25 mg/m(2)/d) on days 1 to 4 (phase I), fludarabine 30 mg/m(2) on days 2 to 3, cytarabine 1 g/m(2) on days 2 to 3, rituximab 375 mg/m(2) on day 3 of cycle 1 and day 1 of subsequent cycles, and pegfilgrastim 6 mg on day 6, every 4 weeks for a maximum of six courses. Dose-limiting toxicity (DLT) was defined as any nonhematologic, treatment-related toxicity >= grade 3. Results Fifty patients were treated (20 patients had RS, and 30 had CLL). The highest tolerated oxaliplatin dose was 25 mg/m(2), which was the highest dose tested. DLT was not observed. Pharmacodynamic analyses demonstrated enhanced leukemia cell killing by oxaliplatin in the presence of fludarabine and cytarabine. The overall response rates were 50% in RS and 33% in fludarabine-refractory CLL. The overall response rate in 14 patients with age >= 70 years was 50%. Responses were achieved in seven (35%) of 20 patients with 17p deletion, two (29%) of seven patients with 11q deletion, all four patients with trisomy 12, and two (40%) of five patients with 13q deletion. The median response duration was 10 months. Toxicities were mainly hematologic; prolonged myelosuppression was not observed. Conclusion The OFAR regimen is highly active in RS and has activity in fludarabine-refractory patients with CLL. This regimen warrants further investigation in the treatment of these disorders. C1 Univ Texas MD Anderson Canc Ctr, Unit 455, Dept Leukemia, Houston, TX 77030 USA. Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Phase Program 1, Houston, TX 77030 USA. Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. Univ Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92103 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Tsimberidou, AM (reprint author), Univ Texas MD Anderson Canc Ctr, Unit 455, Dept Leukemia, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM atsimber@mdanderson.org NR 45 TC 78 Z9 79 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2008 VL 26 IS 2 BP 196 EP 203 DI 10.1200/JCO.2007.11.8513 PG 8 WC Oncology SC Oncology GA 276XN UT WOS:000254177100008 PM 18182662 ER PT J AU Friedberg, JW Cohen, P Chen, L Robinson, KS Forero-Torres, A La Casce, AS Fayad, LE Bessudo, A Camacho, ES Williams, ME Van der Jagt, RH Oliver, JW Cheson, BD AF Friedberg, Jonathan W. Cohen, Philip Chen, Ling Robinson, K. Sue Forero-Torres, Andres La Casce, Ann S. Fayad, Luis E. Bessudo, Alberto Camacho, Elber S. Williams, Michael E. Van der Jagt, Richard H. Oliver, Jennifer W. Cheson, Bruce D. TI Bendamustine in patients with rituximab-refractory indolent and transformed non-Hodgkin's lymphoma: Results from a phase II multicenter, single-agent study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol ID IODINE I-131 TOSITUMOMAB; CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; FOLLICULAR LYMPHOMA; PLUS RITUXIMAB; MANTLE-CELL; IBRITUMOMAB TIUXETAN; MONOCLONAL-ANTIBODY; B-CELL; THERAPY AB Purpose Bendamustine hydrochloride is an alkylating agent with novel mechanisms of action. This phase II multicenter study evaluated the efficacy and toxicity of bendamustine in patients with B-cell non-Hodgkin's lymphoma (NHL) refractory to rituximab. Patients and Methods Patients received bendamustine 120 mg/m(2) intravenously on days 1 and 2 of each 21-day cycle. Outcomes included response, duration of response, progression-free survival, and safety. Results Seventy-six patients, ages 38 to 84 years, with predominantly stage III/IV indolent (80%) or transformed (20%) disease were treated; 74 were assessable for response. Twenty-four (32%) were refractory to chemotherapy. Patients received a median of two prior unique regimens. An overall response rate of 77% (15% complete response, 19% unconfirmed complete response, and 43% partial) was observed. The median duration of response was 6.7 months (95% CI, 5.1 to 9.9 months), 9.0 months (95% CI, 5.8 to 16.7) for patients with indolent disease, and 2.3 months (95% CI, 1.7 to 5.1) for those with transformed disease. Thirty-six percent of these responses exceeded 1 year. The most frequent nonhematologic adverse events included nausea and vomiting, fatigue, constipation, anorexia, fever, cough, and diarrhea. Grade 3 or 4 reversible hematologic toxicities included neutropenia (54%), thrombocytopenia (25%), and anemia (12%). Conclusion Single-agent bendamustine produced durable objective responses with acceptable toxicity in heavily pretreated patients with rituximab-refractory, indolent NHL. These findings are promising and will serve as a benchmark for future clinical trials in this novel patient population. C1 Univ Rochester, Wilmot Canc Ctr, Rochester, NY 14642 USA. Georgetown Univ Hosp, Washington, DC 20007 USA. Cephalon Inc, Frazer, PA USA. QE II Hlth Sci Ctr, Halifax, NS, Canada. Ottawa Hosp, Ottawa, ON, Canada. Univ Alabama, Birmingham, AL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX USA. San Diego Canc Ctr, San Diego, CA USA. Desert Reg Med Ctr, Palm Springs, CA USA. Univ Virginia, Charlottesville, VA USA. RP Friedberg, JW (reprint author), Univ Rochester, Ctr Canc, 601 Elmwood Ave,Box 704, Rochester, NY 14642 USA. EM Jonathan_Friedberg@URMC.Rochester.edu FU NCI NIH HHS [CA-102216] NR 39 TC 172 Z9 177 U1 0 U2 6 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 JAN 10 PY 2008 VL 26 IS 2 BP 204 EP 210 DI 10.1200/JCO.2007.12.5070 PG 7 WC Oncology SC Oncology GA 276XN UT WOS:000254177100009 PM 18182663 ER PT J AU Park, IH Zhao, R West, JA Yabuuchi, A Huo, HG Ince, TA Lerou, PH Lensch, MW Daley, GQ AF Park, In-Hyun Zhao, Rui West, Jason A. Yabuuchi, Akiko Huo, Hongguang Ince, Tan A. Lerou, Paul H. Lensch, M. William Daley, George Q. TI Reprogramming of human somatic cells to pluripotency with defined factors SO NATURE LA English DT Article ID EMBRYONIC STEM-CELLS; FIBROBLASTS; GENERATION; DIFFERENTIATION; INDUCTION; SELECTION; SURVIVAL; REGIONS; NANOG; LINES AB Pluripotency pertains to the cells of early embryos that can generate all of the tissues in the organism. Embryonic stem cells are embryo- derived cell lines that retain pluripotency and represent invaluable tools for research into the mechanisms of tissue formation. Recently, murine fibroblasts have been reprogrammed directly to pluripotency by ectopic expression of four transcription factors ( Oct4, Sox2, Klf4 and Myc) to yield induced pluripotent stem ( iPS) cells. Using these same factors, we have derived iPS cells from fetal, neonatal and adult human primary cells, including dermal fibroblasts isolated from a skin biopsy of a healthy research subject. Human iPS cells resemble embryonic stem cells in morphology and gene expression and in the capacity to form teratomas in immune- deficient mice. These data demonstrate that defined factors can reprogramme human cells to pluripotency, and establish a method whereby patient- specific cells might be established in culture. C1 [Park, In-Hyun; Zhao, Rui; West, Jason A.; Yabuuchi, Akiko; Huo, Hongguang; Lerou, Paul H.; Lensch, M. William; Daley, George Q.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Park, In-Hyun; Zhao, Rui; West, Jason A.; Yabuuchi, Akiko; Huo, Hongguang; Lensch, M. William; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Park, In-Hyun; Zhao, Rui; West, Jason A.; Yabuuchi, Akiko; Huo, Hongguang; Lensch, M. William; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Park, In-Hyun; Zhao, Rui; West, Jason A.; Yabuuchi, Akiko; Huo, Hongguang; Lensch, M. William; Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Park, In-Hyun; Zhao, Rui; West, Jason A.; Yabuuchi, Akiko; Huo, Hongguang; Lensch, M. William; Daley, George Q.] Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA. [Ince, Tan A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Lerou, Paul H.] Brigham & Womens Hosp, Div Newborn Med, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Childrens Hosp, Div Pediat Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu RI West, Jason/I-4445-2014 OI West, Jason/0000-0002-7252-8651 NR 24 TC 1745 Z9 1860 U1 41 U2 460 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 10 PY 2008 VL 451 IS 7175 BP 141 EP U1 DI 10.1038/nature06534 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 249GA UT WOS:000252214400032 PM 18157115 ER PT J AU de Moya, MA Reisner, AT LaMuraglia, GM Kalva, SP AF de Moya, Marc A. Reisner, Andrew T. LaMuraglia, Glenn M. Kalva, Sanjeeva P. TI A man with sudden onset of abdominal pain and hypotension - Celiac-artery stenosis and multiple aneurysms of the pancreaticoduodenal arcade, with rupture SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID IRREVERSIBLE HEMORRHAGIC SHOCK; DAMAGE CONTROL RESUSCITATION; FLUID RESUSCITATION; VOLUME REPLACEMENT; CARDIAC MECHANISM; FLOW-RATE; COAGULOPATHY; MANAGEMENT; PRESSURE; TRAUMA C1 [de Moya, Marc A.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [LaMuraglia, Glenn M.] Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. [Reisner, Andrew T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Kalva, Sanjeeva P.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [de Moya, Marc A.; LaMuraglia, Glenn M.] Harvard Univ, Sch Med, Gen Surg Serv, Cambridge, MA 02138 USA. [Reisner, Andrew T.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Kalva, Sanjeeva P.] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. RP de Moya, MA (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. NR 29 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 JAN 10 PY 2008 VL 358 IS 2 BP 178 EP 186 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 249CJ UT WOS:000252204200011 PM 18184964 ER PT J AU Paul, E Thiele, E AF Paul, Elahna Thiele, Elizabeth TI Efficacy of sirolimus in treating tuberous sclerosis and lymphangioleiomyomatosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MAMMALIAN TARGET; COMPLEX; RAPAMYCIN; PATHWAY; TUMORS; MTOR C1 [Paul, Elahna] Massachusetts Gen Hosp, Div Pediat Nephrol, Boston, MA 02114 USA. [Thiele, Elizabeth] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Thiele, Elizabeth] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Paul, E (reprint author), Massachusetts Gen Hosp, Div Pediat Nephrol, Boston, MA 02114 USA. NR 12 TC 35 Z9 36 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 JAN 10 PY 2008 VL 358 IS 2 BP 190 EP 192 DI 10.1056/NEJMe0707153 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 249CJ UT WOS:000252204200013 PM 18184966 ER PT J AU Takeyama, K Monti, S Manis, JP Dal Cin, P Getz, G Beroukhim, R Dutt, S Aster, JC Alt, FW Golub, TR Shipp, MA AF Takeyama, K. Monti, S. Manis, J. P. Dal Cin, P. Getz, G. Beroukhim, R. Dutt, S. Aster, J. C. Alt, F. W. Golub, T. R. Shipp, M. A. TI Integrative analysis reveals 53BP1 copy loss and decreased expression in a subset of human diffuse large B-cell lymphomas SO ONCOGENE LA English DT Article DE DNA damage; 53BP1; lymphoma; genetic abnormalities; high-density single nucleotide polymorphism array ID CLASS-SWITCH RECOMBINATION; DNA-DAMAGE; HUMAN GENOME; PROTEIN 53BP1; BCL6; P53; SUPPRESS; BREAKS; TRANSLOCATIONS; TRANSCRIPTION AB p53-Binding protein 1 (53BP1) encodes a critical checkpoint protein that localizes to sites of DNA double-strand breaks (DSBs) and participates in DSB repair. Mice that are 53bp1 deficient or hemizygous have an increased incidence of lymphoid malignancies. However, 53BP1 abnormalities in primary human tumors have not been described. By combining high-density single nucleotide polymorphism (HD SNP) array data and gene expression profiles, we found 9 of 63 newly diagnosed human diffuse large B-cell lymphomas (DLBCLs) with single copy loss of the chromosome 15q15 region including the 53BP1 locus; these nine tumors also had significantly lower levels of 53BP1 transcripts. 53BP1 single copy loss found with the HD SNP array platform was subsequently confirmed by fluorescence in situ hybridization. These studies highlight the role of 53BP1 copy loss in primary human DLBCLs and the value of integrative analyses in detecting this genetic lesion in human tumors. C1 [Takeyama, K.; Beroukhim, R.; Shipp, M. A.] Dana Fraber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Monti, S.; Getz, G.; Beroukhim, R.; Golub, T. R.] Broad Inst Massachusetts Inst Technol, Cambridge, MA USA. [Monti, S.; Getz, G.; Beroukhim, R.; Golub, T. R.] Harvard Univ, Cambridge, MA 02138 USA. [Manis, J. P.; Dutt, S.] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Dal Cin, P.; Aster, J. C.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Alt, F. W.] Childrens Hosp, Howard Hughes Med Inst, CBR Inst Biomed Res, Boston, MA 02115 USA. [Alt, F. W.] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA. [Golub, T. R.] Dana Fraber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Shipp, MA (reprint author), Dana Fraber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM margaret_shipp@dfci.harvard.edu FU NCI NIH HHS [P01 CA092625, K08 CA122833-01A1, P01 CA92625, K08 CA122833] NR 30 TC 17 Z9 17 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 10 PY 2008 VL 27 IS 3 BP 318 EP 322 DI 10.1038/sj.onc.1210650 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 249UR UT WOS:000252256000007 PM 17637749 ER PT J AU Rodgers, JT Lerin, C Gerhart-Hines, Z Puigserver, P AF Rodgers, Joseph T. Lerin, Carles Gerhart-Hines, Zachary Puigserver, Pere TI Metabolic adaptations through the PGC-1 alpha and SIRT1 pathways SO FEBS LETTERS LA English DT Review DE PGC-1 alpha; SIRT1; mitochondrial oxidation; glucose metabolism; lipid metabolism; aging ID TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; CALORIE RESTRICTION; WHITE ADIPOCYTES; SKELETAL-MUSCLE; PPAR-GAMMA; MITOCHONDRIAL BIOGENESIS; ENERGY-METABOLISM; ACTIVATION; COMPLEX; PROTEIN AB Energy homeostasis in mammals is achieved through tight regulation of tissue-specific metabolic pathways that become dysregulated in metabolic diseases including diabetes and obesity. At the molecular level, main nutrient and hormonal signaling pathways impinge on expression of genes encoding for metabolic enzymes. Among the major components of this transcriptional circuitry are the PGC-1 alpha transcriptional complexes. An important regulatory mechanism of this complex is through acetylation and SIRT1-mediated lysine de-acetylation under low nutrient conditions. Activation of SIRT1 can mimic several metabolic aspects of calorie restriction that target selective nutrient utilization and mitochondrial oxidative function to regulate energy balance. Thus, understanding the PGC-1 alpha and SIRT1 pathways might have important implications for comprehending metabolic and age-associated diseases. (C) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. RP Puigserver, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 1 Jimmy Fund Way,Smith 936C, Boston, MA 02215 USA. EM pere_puigserver@dfci.harvard.edu FU NIDDK NIH HHS [R01 DK069966, R01 DK069966-01A1] NR 53 TC 294 Z9 308 U1 7 U2 34 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JAN 9 PY 2008 VL 582 IS 1 BP 46 EP 53 DI 10.1016/j.febslet.2007.11.034 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 317MA UT WOS:000257023100008 PM 18036349 ER PT J AU Berman, SM Naliboff, BD Suyenobu, B Labus, JS Stains, J Ohning, G Kilpatrick, L Bueller, JA Ruby, K Jarcho, J Mayer, EA AF Berman, Steven M. Naliboff, Bruce D. Suyenobu, Brandall Labus, Jennifer S. Stains, Jean Ohning, Gordon Kilpatrick, Lisa Bueller, Joshua A. Ruby, Kim Jarcho, Johanna Mayer, Emeran A. TI Reduced brainstem inhibition during anticipated pelvic visceral pain correlates with enhanced brain response to the visceral stimulus in women with irritable bowel syndrome SO JOURNAL OF NEUROSCIENCE LA English DT Article DE fMRI; brainstem; irritable bowel syndrome; anticipation; pain; corticolimbic inhibition ID ANTERIOR CINGULATE CORTEX; RECTAL PAIN; CEREBRAL ACTIVATION; PREFRONTAL CORTEX; HEALTHY CONTROLS; ANXIETY; PLACEBO; DISORDERS; DEACTIVATION; STIMULATION AB Cognitive factors such as fear of pain and symptom-related anxiety play an important role in chronic pain states. The current study sought to characterize abnormalities in preparatory brain response before aversive pelvic visceral distention in irritable bowel syndrome (IBS) patients and their possible relationship to the consequences of distention. The brain functional magnetic resonance imaging ( fMRI) blood oxygen level-dependent ( BOLD) response to anticipated and delivered mild and moderate rectal distention was recorded from 14 female IBS patients and 12 healthy controls. During cued anticipation of distention, activity decreased in the insula, supragenual anterior cingulate cortex (sACC), amygdala, and dorsal brainstem (DBS) of controls. IBS patients showed less anticipatory inactivation. Group differences were significant in the right posterior insula and bilateral DBS. Self-rated measures of negative affect during scanning were higher in patients than controls (p < 0.001), and the anticipatory BOLD decreases in DBS were inversely correlated with these ratings. During subsequent distention, both groups showed activity increases in insula, dorsal ACC, and DBS and decreases in the infragenual ACC. The increases were more extensive in patients, producing significant group differences in dorsal ACC and DBS. The amplitude of the anticipatory decrease in the pontine portion of DBS was associated with greater activation during distention in right orbitofrontal cortex and bilateral sACC. Both regions have been associated previously with corticolimbic inhibition and cognitive coping. Deficits in preparatory inhibition of DBS, including the locus ceruleus complex and parabrachial nuclei, may interfere with descending corticolimbic inhibition and contribute to enhanced brain responsiveness and perceptual sensitivity to visceral stimuli in IBS. C1 [Berman, Steven M.; Naliboff, Bruce D.; Suyenobu, Brandall; Labus, Jennifer S.; Stains, Jean; Ohning, Gordon; Kilpatrick, Lisa; Bueller, Joshua A.; Ruby, Kim; Jarcho, Johanna; Mayer, Emeran A.] Univ Calif Los Angeles, Los Angeles Ctr Neurovisceral Sci & Womens Hlth, Vet Affairs Greater Los Angeles Healthcare Syst, David Geffen Sch Med,Dept Med, Los Angeles, CA 90073 USA. [Berman, Steven M.; Naliboff, Bruce D.; Suyenobu, Brandall; Labus, Jennifer S.; Stains, Jean; Ohning, Gordon; Kilpatrick, Lisa; Bueller, Joshua A.; Ruby, Kim; Jarcho, Johanna; Mayer, Emeran A.] Univ Calif Los Angeles, Los Angeles Ctr Neurovisceral Sci & Womens Hlth, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90073 USA. [Berman, Steven M.; Naliboff, Bruce D.; Suyenobu, Brandall; Labus, Jennifer S.; Stains, Jean; Ohning, Gordon; Kilpatrick, Lisa; Bueller, Joshua A.; Ruby, Kim; Jarcho, Johanna; Mayer, Emeran A.] Univ Calif Los Angeles, Los Angeles Ctr Neurovisceral Sci & Womens Hlth, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90073 USA. [Berman, Steven M.; Naliboff, Bruce D.; Suyenobu, Brandall; Labus, Jennifer S.; Stains, Jean; Ohning, Gordon; Kilpatrick, Lisa; Bueller, Joshua A.; Ruby, Kim; Jarcho, Johanna; Mayer, Emeran A.] Univ Calif Los Angeles, Los Angeles Ctr Neurovisceral Sci & Womens Hlth, David Geffen Sch Med, Dept Behav Sci, Los Angeles, CA 90073 USA. RP Mayer, EA (reprint author), Univ Calif Los Angeles, Los Angeles Ctr Neurovisceral Sci & Womens Hlth, Vet Affairs Greater Los Angeles Healthcare Syst, David Geffen Sch Med,Dept Med, Bldg 115,Room 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM emayer@ucla.edu RI Kilpatrick, Lisa/E-6995-2015; OI Jarcho, Johanna/0000-0001-9075-6968 FU NCCIH NIH HHS [R24 AT002681]; NIDDK NIH HHS [P50DK64539, DK48351]; NINR NIH HHS [NR04881] NR 59 TC 134 Z9 138 U1 6 U2 17 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 9 PY 2008 VL 28 IS 2 BP 349 EP 359 DI 10.1523/JNEUROSCI.2500-07.2008 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 249QE UT WOS:000252243100004 PM 18184777 ER PT J AU Nieland, TJF Shaw, JT Jaipuri, FA Duffner, JL Koehler, AN Banakos, S Zannis, VI Kirchhausen, T Krieger, M AF Nieland, Thomas J. F. Shaw, Jared T. Jaipuri, Firoz A. Duffner, Jay L. Koehler, Angela N. Banakos, Sotirios Zannis, Vassilis I. Kirchhausen, Tomas Krieger, Monty TI Identification of the molecular target of small molecule inhibitors of HDL receptor SR-BI activity SO BIOCHEMISTRY LA English DT Article ID HIGH-DENSITY-LIPOPROTEIN; HEPATITIS-C-VIRUS; SELECTIVE LIPID UPTAKE; SERUM-AMYLOID-A; CELLULAR CHOLESTEROL EFFLUX; HIGH-LEVEL EXPRESSION; SCAVENGER RECEPTOR; NEUTRALIZING ANTIBODIES; BIDIRECTIONAL FLUX; PLASMA-MEMBRANE AB Scavenger receptor, class B, type I (SR-131), controls high-density lipoprotein (HDC) metabolism by mediating cellular selective uptake of lipids from HDL without the concomitant degradation of the lipoprotein particle. We previously identified in a high-throughput chemical screen of intact cells five compounds (BLT-1-5) that inhibit SR-BI-dependent lipid transport from HDL, but do not block HDL binding to SR-131 on the cell surface. Although these BLTs are widely used to examine the diverse functions of SR-131, their direct target(s), SR-131 itself or some other component of the SR-131 pathway, has not been identified. Here we show that SR-BI in the context of a membrane lipid environment is the target of BLT- 1, -3, -4, and -5. The analysis using intact cells and an in vitro system of purified SR-131 reconstituted into liposomes was aided by information derived from structure-activity relationship (SAR) analysis of the most potent of these BLTs, the thiosemicarbazone BLT-1. We found that the sulfur atom of BLT-1 was crucially important for its inhibitory activity, because changing it to an oxygen atom resulted in the isostructural, but essentially inactive, semicarbazone derivative BLT-1sc. SAR analysis also established the importance of BLT-I's hydrophobic tail. BLTs and their corresponding inactive compounds can be used to explore the mechanism and function of SR-BI-mediated selective lipid uptake in diverse mammalian experimental models. Consequently, BUS may help determine the therapeutic potential of SR-BI-targeted pharmaceutical drugs. C1 [Nieland, Thomas J. F.; Banakos, Sotirios; Krieger, Monty] MIT, Dept Biol, Cambridge, MA 02139 USA. [Nieland, Thomas J. F.] MIT, Cambridge Ctr, Broad Inst Harvard, Cambridge, MA 02139 USA. Univ Calif Davis, Dept Chem, Davis, CA 95616 USA. [Zannis, Vassilis I.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Dept Biochem,Sect Mol Genet, Boston, MA 02215 USA. Harvard Univ, Harvard Med Sch, Immune Dis Inst, Dept Cell Biol, Boston, MA 02115 USA. RP Krieger, M (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM krieger@mit.edu OI Shaw, Jared/0000-0001-5190-493X FU NCI NIH HHS [N01-CO-12400, N01CO12400]; NHLBI NIH HHS [HL48739, R01 HL048739-11, R01 HL048739, R01 HL052212, R01 HL052212-09, HL52212]; NIAID NIH HHS [R01 AI063430, R01 AI063430-02]; PHS HHS [AIO63430] NR 81 TC 24 Z9 24 U1 2 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 8 PY 2008 VL 47 IS 1 BP 460 EP 472 DI 10.1021/bi701277x PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 246RG UT WOS:000252024100044 PM 18067275 ER PT J AU Bernhard, J Zahrieh, D Zhang, JJ Martinelli, G Basser, R Hurny, C Forbes, JF Aebi, S Yeo, W Thurlimann, B Green, MD Colleoni, M Gelber, RD Castiglione-Gertsch, M Price, KN Goldhirsch, A Coates, AS AF Bernhard, J. Zahrieh, D. Zhang, J. J. Martinelli, G. Basser, R. Huerny, C. Forbes, J. F. Aebi, S. Yeo, W. Thuerlimann, B. Green, M. D. Colleoni, M. Gelber, R. D. Castiglione-Gertsch, M. Price, K. N. Goldhirsch, A. Coates, A. S. CA Int Breast Canc Study Grp TI Quality of life and quality-adjusted survival (Q-TWiST) in patients receiving dose-intensive or standard dose chemotherapy for high-risk primary breast cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE breast cancer; adjuvant chemotherapy; quality of life; adaptation; quality-adjusted survival ID ADJUVANT CHEMOTHERAPY; CLINICAL-TRIALS; COGNITIVE FUNCTION; RANDOMIZED-TRIAL; FOLLOW-UP; WOMEN; THERAPY; IMPACT; CYCLOPHOSPHAMIDE; PREMENOPAUSAL AB Quality of life ( QL) is an important consideration when comparing adjuvant therapies for early breast cancer, especially if they differ substantially in toxicity. We evaluated QL and Q-TWiST among patients randomised to adjuvant dose-intensive epirubicin and cyclophosphamide administered with filgrastim and progenitor cell support ( DI-EC) or standard-dose anthracycline-based chemotherapy ( SD-CT). We estimated the duration of chemotherapy toxicity ( TOX), time without disease symptoms and toxicity ( TWiST), and time following relapse ( REL). Patients scored QL indicators. Mean durations for the three transition times were weighted with patient reported utilities to obtain mean Q-TWiST. Patients receiving DI-EC reported worse QL during TOX, especially treatment burden ( month 3: P < 0.01), but a faster recovery 3 months following chemotherapy than patients receiving SD-CT, for example, less coping effort ( P < 0.01). Average Q-TWiST was 1.8 months longer for patients receiving DI-EC ( 95% CI, -2.5 to 6.1). Q-TWiST favoured DI-EC for most values of utilities attached to TOX and REL. Despite greater initial toxicity, quality-adjusted survival was similar or better with dose-intensive treatment as compared to standard treatment. Thus, QL considerations should not be prohibitive if future intensive therapies show superior efficacy. C1 [Bernhard, J.; Castiglione-Gertsch, M.] IBCSG Coordinating Ctr, CH-3008 Bern, Switzerland. [Bernhard, J.] Univ Bern, Inselspital, Dept Med Oncol, CH-3010 Bern, Switzerland. [Zahrieh, D.; Gelber, R. D.; Price, K. N.] Dana Farber Canc Inst, IBCSG Stat Ctr, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Zhang, J. J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Martinelli, G.] European Inst Oncol, Div Haematol, Dept Med, I-20141 Milan, Italy. [Basser, R.] Royal Melbourne Hosp, Dept Med Oncol, Melbourne, Vic, Australia. [Huerny, C.] Burgerspital, CH-9000 St Gallen, Switzerland. [Forbes, J. F.] Univ Newcastle, Newcastle Mater Hosp, Hunter Reg Mail Ctr,Dept Surg Oncol, New Zealand Breast Canc Trials Grp, Newcastle, NSW 2310, Australia. [Aebi, S.] Inselspital Bern, Dept Med Oncol, CH-3010 Bern, Switzerland. [Basser, R.] CSL, Melbourne, Vic, Australia. [Aebi, S.; Thuerlimann, B.] Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. [Yeo, W.] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Clin Oncol, Hong Kong, Peoples R China. [Thuerlimann, B.] Kantonsspital, Senol Ctr Eastern Switzerland, CH-9007 St Gallen, Switzerland. [Green, M. D.] Royal Melbourne & Western Hosp, Private Med Ctr, Dept Med Oncol, Parkville, Vic 3052, Australia. [Gelber, R. D.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Frontier Sci Technol & Res Fdn, Boston, MA 02115 USA. [Price, K. N.] Frontier Sci Technol & Res Fdn, Boston, MA USA. [Goldhirsch, A.] Oncol Inst So Switzerland, CH-6962 Viganello Lugano, Bellinzona, Switzerland. [Coates, A. S.] Int Breast Canc Study Grp, Bern, Switzerland. [Coates, A. S.] Univ Sydney, Sch Publ Hlth, Centennial Pk, NSW 2021, Australia. RP Bernhard, J (reprint author), IBCSG Coordinating Ctr, Effingerstr 40, CH-3008 Bern, Switzerland. EM juerg.bernhard@ibcsg.org RI Aebi, Stefan/F-2004-2010 OI Aebi, Stefan/0000-0002-3383-9449 FU NCI NIH HHS [T32 CA009337, U24 CA075362] NR 28 TC 8 Z9 8 U1 0 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD JAN 8 PY 2008 VL 98 IS 1 BP 25 EP 33 DI 10.1038/sj.bjc.6604092 PG 9 WC Oncology SC Oncology GA 249RL UT WOS:000252247300007 PM 18043579 ER PT J AU Johannessen, CM Johnson, BW Williams, SMG Chan, AW Reczek, EE Lynch, RC Rioth, MJ McClatchey, A Ryeom, S Cichowski, K AF Johannessen, Cory M. Johnson, Bryan W. Williams, Sybil M. Genther Chan, Annie W. Reczek, Elizabeth E. Lynch, Ryan C. Rioth, Matthew J. McClatchey, Andrea Ryeom, Sandra Cichowski, Karen TI TORC1 is essential for NF1-associated malignancies SO CURRENT BIOLOGY LA English DT Article ID RENAL-CELL CARCINOMA; NEUROFIBROMATOSIS TYPE-1; MAMMALIAN TARGET; MTOR INHIBITORS; RAPAMYCIN; CANCER; AKT; GROWTH; NF1 AB Inactivating mutations in NF1 underlie the prevalent familial cancer syndrome neurofibromatosis type 1 [1]. The NF1-encoded protein is a Ras GTPase-activating protein (RasGAP) [2]. Accordingly, Ras is aberrantly activated in NF1-deficient tumors; however, it is unknown which effector pathways critically function in tumor development. Here we provide in vivo evidence that TORC1/mTOR activity is essential for tumorigenesis. Specifically, we show that the mTOR inhibitor rapamycin potently suppresses the growth of aggressive NF1-associated malignancies in a genetically engineered murine model. However, in these tumors rapamycin does not function via mechanisms generally assumed to mediate tumor suppression, including inhibition of HIF-1 alpha and indirect suppression of AKT, but does suppress the mTOR target Cyclin D1 [3]. These results demonstrate that mTOR inhibitors may be an effective targeted therapy for this commonly untreatable malignancy. Moreover, they indicate that mTOR inhibitors do not suppress all tumor types via the same mechanism, suggesting that current biomarkers that rely on HIF-1 alpha suppression may not be informative for all cancers. Finally, our results reveal important differences between the effects of mTOR inhibition on the microvasculature in genetically engineered versus xenograft models and indicate that the former may be required for effective preclinical screening with this class of inhibitors. C1 [Johannessen, Cory M.; Johnson, Bryan W.; Williams, Sybil M. Genther; Reczek, Elizabeth E.; Cichowski, Karen] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Johannessen, Cory M.; Johnson, Bryan W.; Cichowski, Karen] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA 02115 USA. [Johannessen, Cory M.; Johnson, Bryan W.; Williams, Sybil M. Genther; Reczek, Elizabeth E.; Lynch, Ryan C.; Rioth, Matthew J.; Ryeom, Sandra; Cichowski, Karen] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chan, Annie W.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Lynch, Ryan C.; Rioth, Matthew J.; Ryeom, Sandra] Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. [Chan, Annie W.; McClatchey, Andrea] Harvard Univ, Sch Med, MGH Ctr Canc Res, Charlestown, MA 02129 USA. [McClatchey, Andrea] Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. RP Cichowski, K (reprint author), Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA. EM keichowski@rics.bwh.harvard.edu FU NCI NIH HHS [R01 CA111754-01] NR 26 TC 111 Z9 111 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JAN 8 PY 2008 VL 18 IS 1 BP 56 EP 62 DI 10.1016/j.cub.2007.11.066 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 250IE UT WOS:000252292400029 PM 18164202 ER PT J AU Arevalo, E Shanmugasundararaj, S Wilkerneyer, MF Dou, X Chen, S Charness, ME Miller, KW AF Arevalo, Enrique Shanmugasundararaj, Sivananthaperurnal Wilkerneyer, Michael F. Dou, Xiaowei Chen, Suzhen Charness, Michael E. Miller, Keith W. TI An alcohol binding site on the neural cell adhesion molecule L1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ethyl alcohol; fetal alcohol spectrum disorders; photolabel ID NEURITE OUTGROWTH; CRYSTAL-STRUCTURE; MUTATIONS; PROTEIN; GENE; IDENTIFICATION; ANTAGONISTS; INHIBITION; PREVENTION; DISORDERS AB Prenatal ethanol exposure causes fetal alcohol spectrum disorders (FASD) in part by disrupting the neural cell adhesion molecule L1. L1 gene mutations cause neuropathological abnormalities similar to those of FASD. Ethanol and 1-butanol inhibit L1-mediated cell-cell adhesion (L1 adhesion), whereas 1-octanol antagonizes this action. To test the hypothesis that there are alcohol binding sites on L1, we used 3-azibutanol and 3-azioctanol, the photoactivatable analogs of 1-butanol and 1-octanol, to photolabel the purified Ig-4 domain of human L1 (hL1 Ig-4). 3-Azibutanol (11 mM), like ethanol, inhibited L1adhesion in NIH/3T3 cells stably transfected with hL1, whereas subanesthetic concentrations of 3-azioctanol (14 mu M) antagonized ethanol inhibition of L1 adhesion. 3-Azibutanol (100-1,000 mu M) and 3-azioctanol (10-100 mu M) photoincorporated into Tyr-418 on Ig4 and into two adjacent regions in the N terminus, Glu-33 and Glu-24 to Glu-27. A homology model of hL1 Ig1-4 (residues 33-422), based on the structure of the Ig1-4 domains of axonin-1, suggests that Glu-33 and Tyr-418 hydrogen-bond at the interface of Ig1 and Ig4 to stabilize a horseshoe conformation of L1 that favors homophilic binding. Furthermore, this alcohol binding pocket lies within 7 A of Leu-120 and Gly-121, residues in which missense mutations cause neurological disorders similar to FASD. These data suggest that ethanol or selected mutations produce neuropathological abnormalities by disrupting the domain interface between Ig1 and Ig4. Characterization of alcohol agonist and antagonist binding sites on L1 will aid in understanding the molecular basis for FASD and might accelerate the development of ethanol antagonists. C1 [Wilkerneyer, Michael F.; Dou, Xiaowei; Chen, Suzhen; Charness, Michael E.] Harvard Univ, Sch Med, Vet Affairs Boston Healthcare Syst, Boston, MA 02132 USA. [Arevalo, Enrique; Shanmugasundararaj, Sivananthaperurnal; Miller, Keith W.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Arevalo, Enrique; Shanmugasundararaj, Sivananthaperurnal; Miller, Keith W.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Wilkerneyer, Michael F.; Dou, Xiaowei; Chen, Suzhen; Charness, Michael E.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02132 USA. RP Charness, ME (reprint author), Harvard Univ, Sch Med, Vet Affairs Boston Healthcare Syst, Boston, MA 02132 USA. EM mcharness@hms.harvard.edu OI Charness, Michael/0000-0002-3301-8966 FU NIAAA NIH HHS [AA12974, R37 AA012974, R01 AA012974, U01 AA014812] NR 37 TC 36 Z9 38 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 JAN 8 PY 2008 VL 105 IS 1 BP 371 EP 375 DI 10.1073/pnas.0707815105 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 252GP UT WOS:000252435300068 PM 18165316 ER PT J AU Faraone, SV Smoller, JW AF Faraone, S. V. Smoller, J. W. TI The New Neuropsychiatric Genetics SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Editorial Material C1 [Faraone, S. V.] SUNY Upstate Med Univ, Genet Res Program, Syracuse, NY USA. [Faraone, S. V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, S. V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA. [Smoller, J. W.] Harvard Univ, Sch Med, Ctr Human Genet Res, Massachusetts Gen Hosp, Boston, MA USA. [Smoller, J. W.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Faraone, SV (reprint author), SUNY Upstate Med Univ, Genet Res Program, Syracuse, NY USA. OI Faraone, Stephen/0000-0002-9217-3982 NR 0 TC 2 Z9 2 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 JAN 5 PY 2008 VL 147B IS 1 BP 1 EP 2 DI 10.1002/ajmg.b.30691 PG 2 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 246BB UT WOS:000251981400001 ER PT J AU Lasky-Su, J Lange, C Biederman, J Tsuang, M Doyle, AE Smoller, JW Laird, N Faraone, S AF Lasky-Su, Jessica Lange, Christoph Biederman, Joseph Tsuang, Ming Doyle, Alysa E. Smoller, Jordan W. Laird, Nan Faraone, Stephen TI Family-Based Association Analysis of a Statistically Derived Quantitative Traits for ADHD Reveal an Association in DRD4 With Inattentive Symptoms in ADHD Individuals SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE ADHD; DRD4; family-based association ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DOPAMINE-D4 RECEPTOR GENE; 7-REPEAT ALLELE; LATENT CLASS; MOUSE MODEL; CHILDREN; SUBTYPES; RELIABILITY; PERFORMANCE AB The objective of this study was to determine whether single nucleotide polymorphisms (SNPs) within candidate genes for ADHD are associated with quantitative phenotypes generated from inattentive and hyperactive-impulsive symptoms. One hundred forty-three SNPs were genotyped in and around five ADHD candidate genes. A highly heritable quantitative phenotype was generated at each SNP by weighting inattentive and hyperactive-impulsive symptoms. Once these phenotypes were generated, a screening procedure was used to select and test the five SNP/phenotype combinations with the greatest power to detect an association for each candidate gene. Adjacent SNPs in the promoter region of DRD4, hCV26775267 and hCV26775266, were associated with the quantitative phenotypes generated from the ADHD symptoms (corrected P-values = 0.012 for both SNPs). The correlations between the ADHD symptoms and quantitative phenotype revealed that inattentive symptoms had a strong influence on the generated phenotype. Subsequent family-based association test-principal components (FBAT-PC) analyses using inattentive symptoms only also had significant associations. SNPs in the promoter region of DRD4 are associated with the phenotypes generated from ADHD symptoms. The strong correlation of the inattentive symptoms with these quantitative phenotypes and the subsequent FBAT-PC analyses suggest this region is primarily associated with inattentive symptoms. This analysis adds to previous findings by suggesting that variants at these loci may be specifically associated with inattentive symptoms. (C) 2007 Wiley-Liss, Inc. C1 [Faraone, Stephen] SUNY Upstate Med Univ, Dept Psychiat, Genet Res Program, Syracuse, NY 13210 USA. [Lasky-Su, Jessica; Faraone, Stephen] SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY 13210 USA. [Lange, Christoph; Laird, Nan] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Biederman, Joseph; Doyle, Alysa E.] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. [Tsuang, Ming] Univ Calif San Diego, Dept Psychiat, Inst Behav Genom, San Diego, CA 92103 USA. [Smoller, Jordan W.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Charlestown, MA USA. RP Faraone, S (reprint author), SUNY Upstate Med Univ, Dept Psychiat, Genet Res Program, 750 E Adams St, Syracuse, NY 13210 USA. EM faraones@upstate.edu OI Faraone, Stephen/0000-0002-9217-3982 FU National Institute of Mental Health [T32-MH017119]; National Institut of Health [R01HD37694, R01HD37999, R01MH66877] FX Grant sponsor: National Institute of Mental Health through the Psychiatric Epidemiology and Biostatistics Training Grant; Grant number: T32-MH017119; Grant sponsor: National Institut of Health; Grant numbers: R01HD37694, R01HD37999, R01MH66877. NR 43 TC 26 Z9 26 U1 4 U2 10 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 JAN 5 PY 2008 VL 147B IS 1 BP 100 EP 106 DI 10.1002/ajmg.b.30567 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 246BB UT WOS:000251981400017 PM 17579349 ER PT J AU Supekova, L Supek, F Lee, J Chen, S Gray, N Pezacki, JP Schlapbach, A Schultz, PG AF Supekova, Lubica Supek, Frantisek Lee, Jongkook Chen, Shawn Gray, Nathanael Pezacki, John P. Schlapbach, Achim Schultz, Peter G. TI Identification of human kinases involved in hepatitis C virus replication by small interference RNA library screening SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VACCINIA-RELATED KINASE-1; SRC FAMILY KINASES; TYROSINE KINASES; B-VIRUS; PROTEIN; CELLS; DISRUPTION; ACTIVATION; REPLICONS; GENE AB The propagation of the hepatitis C virus (HCV) is a complex process that requires both host and viral proteins. To facilitate identification of host cell factors that are required for HCV replication, we screened a panel of small interference RNAs that preferentially target human protein kinases using an HCV replicon expressing the firefly luciferase gene as a genetic reporter. Small interference RNAs specific for three human kinases, Csk, Jak1, and Vrk1, were identified that reproducibly reduce viral RNA and viral protein levels in HCV replicon-bearing cells. Treatment of replicon cells with a small molecule inhibitor of Csk also resulted in a significant reduction in HCV RNA and proteins, further supporting a role for Csk in HCV replication. The effects of siRNAs targeting eight kinases known to be negatively regulated by Csk were then examined; knock down of one of these kinases, Fyn, resulted in up-regulation of the HCV replicon, suggesting that Csk mediates its effect on HCV replication through Fyn. This conclusion was further corroborated by demonstration that replicon cells treated with Csk inhibitor contained lower levels of the phosphorylated form of Fyn than control cells. C1 [Supekova, Lubica; Lee, Jongkook; Schultz, Peter G.] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. [Supek, Frantisek; Schultz, Peter G.] Genom Inst Novartis Res Fdn, Dept Drug Discovery, San Diego, CA 92121 USA. [Gray, Nathanael] Harvard Med Sch, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Pezacki, John P.] Steacie Inst Mol Sci, Ottawa, ON K1A 0R6, Canada. [Schlapbach, Achim] Novartis Inst Biomed Res, CH-4002 Basel, Switzerland. RP Schultz, PG (reprint author), 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM schultz@scripps.edu RI Chen, Shawn/K-3585-2012 NR 38 TC 71 Z9 75 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 JAN 4 PY 2008 VL 283 IS 1 BP 29 EP 36 DI 10.1074/jbc.M703988200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 245MV UT WOS:000251940300005 PM 17951261 ER PT J AU Bouffard, J Kim, Y Swager, TM Weissleder, R Hilderbrand, SA AF Bouffard, Jean Kim, Youngmi Swager, Timothy M. Weissleder, Ralph Hilderbrand, Scott A. TI A highly selective fluorescent probe for thiol bioimaging SO ORGANIC LETTERS LA English DT Article ID CARDIOVASCULAR-DISEASE; OXIDATIVE STRESS; HOMOCYSTEINE; CYSTEINE; DESIGN AB A new fluorescent turn-on probe (3) for the selective sensing and bioimaging of thiols is reported. In aqueous buffer solutions at physiological pH, thiols cleave the 2,4-dinitrobenzenesulfonyl group to release the red-emissive donor-acceptor fluorophore (4). The probe displays excellent immunity to interference from nitrogen and oxygen nucleophiles and the imaging of thiols in living cells is demonstrated. C1 [Bouffard, Jean; Kim, Youngmi; Swager, Timothy M.; Weissleder, Ralph; Hilderbrand, Scott A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [Bouffard, Jean; Kim, Youngmi; Swager, Timothy M.; Weissleder, Ralph; Hilderbrand, Scott A.] MIT, Dept Chem, Cambridge, MA 02139 USA. RP Hilderbrand, SA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. EM scott_hilderbrand@hms.harvard.edu RI Swager, Timothy/H-7459-2012 OI Swager, Timothy/0000-0002-3577-0510 FU NHLBI NIH HHS [1-U01-HL080731] NR 30 TC 196 Z9 197 U1 5 U2 57 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 JAN 3 PY 2008 VL 10 IS 1 BP 37 EP 40 DI 10.1021/ol702539v PG 4 WC Chemistry, Organic SC Chemistry GA 245IT UT WOS:000251929000010 PM 18062694 ER PT J AU Tanabe, KK Lemoine, A Finkelstein, DM Kawasaki, H Fujii, T Chung, RT Lauwers, GY Kulu, Y Muzikansky, A Kuruppu, D Lanuti, M Goodwin, JM Azoulay, D Fuchs, BC AF Tanabe, Kenneth K. Lemoine, Antoinette Finkelstein, Dianne M. Kawasaki, Hiroshi Fujii, Tsutomu Chung, Raymond T. Lauwers, Gregory Y. Kulu, Yakup Muzikansky, Alona Kuruppu, Darshini Lanuti, Michael Goodwin, Jonathan M. Azoulay, Daniel Fuchs, Bryan C. TI Epidermal growth factor gene functional polymorphism and the risk of hepatocellular carcinoma in patients with cirrhosis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID EGF GENE; EXPRESSION; CANCER; LIVER; RESPONSIVENESS; HEPATOCYTES; ASSOCIATION; INHIBITOR; GEFITINIB; MELANOMA AB Context Overexpression of epidermal growth factor (EGF) in the liver induces transformation to hepatocellular carcinoma in animal models. Polymorphisms in the EGF gene modulate EGF levels. Objective To assess the relationship among human EGF gene single-nucleotide polymorphism, EGF expression, and risk of hepatocellular carcinoma. Design, Setting, and Participants Molecular mechanisms linking the 61*G allele polymorphism to EGF expression were examined in human hepatocellular carcinoma cell lines and human liver tissue. A case-control study involving 207 patients with cirrhosis was conducted at the Massachusetts General Hospital (1999-2006) and a validation case-control study involving 121 patients with cirrhosis was conducted at Hopital Paul Brousse (1993-2006). Restriction fragment-length polymorphism was used to determine the EGF gene polymorphism genotype. Logistic regression analysis was used to assess the association between the EGF polymorphism and hepatocellular carcinoma risk. Main Outcome Measures Mechanisms by which the EGF gene polymorphism modulates EGF levels and associations among EGF gene polymorphism, EGF levels, and hepatocellular carcinoma. Results Transcripts from the EGF 61*G allele exhibited more than a 2-fold longer half-life than those from the 61*A allele, and EGF secretion was 2.3-fold higher in G/G hepatocellular carcinoma cell lines than A/A cell lines. Serum EGF levels were 1.8-fold higher in G/G patients than A/A patients, and liver EGF levels were 2.4-fold higher in G/G patients than A/A patients. Among the 207 patients with cirrhosis in the Massachusetts study population, 59 also had hepatocellular carcinoma. Analysis of the distribution of allelic frequencies revealed that there was a 4-fold odds of hepatocellular carcinoma in G/G patients compared with A/A patients in the Massachusetts study population (odds ratio, 4.0; 95% confidence interval [0], 1.6-9.6; P=.002). Logistic regression analysis demonstrated that the number of copies of G was significantly associated with hepatocellular carcinoma after adjusting for age, sex, race, etiology, and severity of cirrhosis (G/G or A/G vs A/A; hazard ratio, 3.49; 95% Cl, 1.29-9.44; P=.01). The significant association was validated in the French patients with alcoholic cirrhosis and hepatocellular carcinoma. Conclusion The EGF gene polymorphism genotype is associated with risk for development of hepatocellular carcinoma in liver cirrhosis through modulation of EGF levels. C1 [Tanabe, Kenneth K.; Kawasaki, Hiroshi; Fujii, Tsutomu; Kulu, Yakup; Kuruppu, Darshini; Fuchs, Bryan C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Finkelstein, Dianne M.; Muzikansky, Alona] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Chung, Raymond T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Gastrointestinal Unit, Boston, MA 02114 USA. [Lauwers, Gregory Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lanuti, Michael; Goodwin, Jonathan M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. [Lemoine, Antoinette; Azoulay, Daniel] Hop Paul Brousse, Assistance Publ Hop Paris, Ctr Chirurg Hepatobiliaire, Villejuif, France. Univ Paris 11, Fac Pharm, F-92290 Chatenay Malabry, France. INSERM, U602, Villejuif, France. RP Tanabe, KK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Surg Oncol, Yawkey 7-924,55 Fruit St, Boston, MA 02114 USA. EM ktanabe@partners.org RI Fujii, Tsutomu/M-4838-2014 FU NCI NIH HHS [2P30 CA06516-43, P30 CA006516, 2R01CA76183, 5P01CA111519]; NIAID NIH HHS [AI06993]; NIDDK NIH HHS [DK078772] NR 33 TC 125 Z9 126 U1 2 U2 6 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 JAN 2 PY 2008 VL 299 IS 1 BP 53 EP 60 DI 10.1001/jama.2007.65 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 247BL UT WOS:000252052000016 PM 18167406 ER PT J AU Sharma, V Simpson, RC LoPresti, EF Mostowy, C Olson, J Puhlman, J Hayashi, S Cooper, RA Konarski, E Kerley, B AF Sharma, Vinod Simpson, Richard C. LoPresti, Edmund F. Mostowy, Casimir Olson, Joseph Puhlman, Jeremy Hayashi, Steve Cooper, Rory A. Konarski, Ed Kerley, Barry TI Participatory design in the development of the wheelchair convoy system SO JOURNAL OF NEUROENGINEERING AND REHABILITATION LA English DT Article ID POWER-ASSISTED WHEELCHAIR; SMART WHEELCHAIRS; NAVIGATION AB Background: In long-term care environments, residents who have severe mobility deficits are typically transported by having another person push the individual in a manual wheelchair. This practice is inefficient and encourages staff to hurry to complete the process, thereby setting the stage for unsafe practices. Furthermore, the time involved in assembling multiple individuals with disabilities often deters their participation in group activities. Methods: The Wheelchair Convoy System (WCS) is being developed to allow a single caregiver to move multiple individuals without removing them from their wheelchairs. The WCS will consist of a processor, and a flexible cord linking each wheelchair to the wheelchair in front of it. A Participatory Design approach - in which several iterations of design, fabrication and evaluation are used to elicit feedback from users - was used. Results: An iterative cycle of development and evaluation was followed through five prototypes of the device. The third and fourth prototypes were evaluated in unmanned field trials at J. Iverson Riddle Development Center. The prototypes were used to form a convoy of three wheelchairs that successfully completed a series of navigation tasks. Conclusion: A Participatory Design approach to the project allowed the design of the WCS to quickly evolve towards a viable solution. The design that emerged by the end of the fifth development cycle bore little resemblance to the initial design, but successfully met the project's design criteria. Additional development and testing is planned to further refine the system. C1 [Sharma, Vinod; Simpson, Richard C.; Cooper, Rory A.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA. [Simpson, Richard C.; Olson, Joseph; Cooper, Rory A.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Simpson, Richard C.; Olson, Joseph; Puhlman, Jeremy; Hayashi, Steve; Cooper, Rory A.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [LoPresti, Edmund F.; Mostowy, Casimir] AT Sci, Pittsburgh, PA USA. [Konarski, Ed; Kerley, Barry] J Iverson Riddle Dev Ctr, Morganton, NC USA. RP Simpson, RC (reprint author), Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA. EM vks3@pitt.edu; ris20@pitt.edu; edlopresti@at-sciences.com; caz@ieee.org; olsonj@herlpitt.org; puhlmanj@herlpitt.org; hayashis@herlpitt.org; rcooper@pitt.edu; Ed.Konarski@ncmail.net; Barry.Kerley@ncmail.net NR 21 TC 11 Z9 11 U1 2 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-0003 J9 J NEUROENG REHABIL JI J. NeuroEng. Rehabil. PD JAN 2 PY 2008 VL 5 AR 1 DI 10.1186/1743-0003-5-1 PG 10 WC Engineering, Biomedical; Neurosciences; Rehabilitation SC Engineering; Neurosciences & Neurology; Rehabilitation GA 278US UT WOS:000254312400001 PM 18171465 ER PT J AU Liu, Y Yang, FC Okuda, T Dong, XZ Zylka, MJ Chen, CL Anderson, DJ Kuner, R Ma, QF AF Liu, Yang Yang, Fu-Chia Okuda, Tsukasa Dong, Xinzhong Zylka, Mark J. Chen, Chih-Li Anderson, David J. Kuner, Rohini Ma, Qiufu TI Mechanisms of compartmentalized expression of Mrg class G-protein-coupled sensory receptors SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Runx1; nociceptors; Mrg class G-protein-coupled receptors; nociceptive ion channels and receptors; cell type specification; dorsal root ganglia ID DORSAL-ROOT GANGLIA; TRANSCRIPTION FACTOR; REGULATES DEVELOPMENT; GENE FAMILY; DRG NEURONS; CELLS; RUNX1; NGF; DIFFERENTIATION; REPRESSION AB Mrg class G-protein-coupled receptors (GPCRs) are expressed exclusively in sensory neurons in the trigeminal and dorsal root ganglia. Pharmacological activation of Mrg proteins is capable of modulating sensory neuron activities and elicits nociceptive effects. In this study, we illustrate a control mechanism that allows the Runx1 runt domain transcription factor to generate compartmentalized expression of these sensory GPCRs. Expression of MrgA, MrgB, and MrgC subclasses is confined to an "A/B/C" neuronal compartment that expresses Runx1 transiently ( or does not express Runx1), whereas MrgD expression is restricted to a "D" compartment with persistent Runx1 expression. Runx1 is initially required for the expression of all Mrg genes. However, during late development Runx1 becomes a repressor for MrgA/B/C genes. As a result, MrgA/B/C expression persists only in the Runx1(-) "A/B/C" compartment. In Delta 446 mice, in which Runx1 lacks the C-terminal repression domain, expression of MrgA/B/C genes is dramatically expanded into the Runx1 (+) "D" compartment. MrgD expression, however, is resistant to Runx1-mediated repression in the "D" compartment. Therefore, the creation of Runx1(+) and Runx1 (-) compartments, in conjunction with different responses of Mrg genes to Runx1-mediated repression, results in the compartmentalized expression of MrgA/B/C versus MrgD genes. Within the MrgA/B/C compartment, MrgB4-expressing neurons innervate exclusively the hairy skin. Here we found that Smad4, a downstream component of bone morphological protein-mediated signaling, is required selectively for the expression of MrgB4. Our study suggests a new line of evidence that specification of sensory subtypes is established progressively during perinatal and postnatal development. C1 [Ma, Qiufu] Dana Farber Canc Inst, Boston, MA 02115 USA. [Okuda, Tsukasa; Zylka, Mark J.] Kyoto Prefectural Univ Med, Dept Biochem & Mol Biol, Kamigyo Ku, Kyoto 6028566, Japan. [Dong, Xinzhong] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. [Zylka, Mark J.] Univ N Carolina, Sch Med, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA. [Chen, Chih-Li] Fu Jen Catholic Univ, Sch Med, Taipei 24205, Taiwan. [Anderson, David J.] CALTECH, Div Biol, Pasadena, CA 91125 USA. [Anderson, David J.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA. [Kuner, Rohini] Univ Heidelberg, Inst Pharmacol, Dept Mol Pharmacol, D-69120 Heidelberg, Germany. RP Ma, QF (reprint author), Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM qiufu_ma@dfci.harvard.edu FU NIDCR NIH HHS [1R01DE018025, R01 DE013843, R01 DE018025]; NINDS NIH HHS [5P01NS047572, 5T32NS007473-09] NR 34 TC 33 Z9 33 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 2 PY 2008 VL 28 IS 1 BP 125 EP 132 DI 10.1523/JNEUROSCI.4472-07.2008 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 249QC UT WOS:000252242900015 PM 18171930 ER PT S AU Hahn, JO Asada, HH Reisner, AT Jaffer, FA AF Hahn, Jin-Oh Asada, H. Harry Reisner, Andrew T. Jaffer, Farouc A. GP IEEE TI A New Approach to Reconstruction of Central Aortic Blood Pressure Using "Adaptive" Transfer Function SO 2008 30TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-8 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 30th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 20-24, 2008 CL Vancouver, CANADA SP DEVICIX, Green Coll, Natl Inst Hlth, NIBIB, NSF, PLEXON Inc, UBC Engn Biomed Engn, Univ Washington, Coll Engn, Bentham Sci Publ Ltd, Recent Patents Biomed Engn, Recent Patents Engn ID BLIND SYSTEM-IDENTIFICATION; CARDIAC-OUTPUT; WAVE-FORM; DERIVATION AB This paper presents a new system identification approach to the reconstruction of central aortic blood pressure signal by exploiting a non-invasive peripheral blood pressure measurement This technique, which Is called the "adaptive" transfer function, is able to reconstruct the aortic blood pressure signal by characterizing the aortic-to-peripheral cardiovascular dynamics solely based on the peripheral measurement. In contrast to the previous related efforts, it does not require any a prior! knowledge on the empirical and/or population-based relationship, e.g. the predetermined or generalized transfer function, as well as multiple peripheral measurements. The initial proof-of-principle on the efficacy of the adaptive transfer function is demonstrated by the experimental results from human and animal subjects. C1 [Hahn, Jin-Oh; Asada, H. Harry] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Reisner, Andrew T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Jaffer, Farouc A.] Massachusetts Gen Hosp, Dept Cardiovasc Med, Boston, MA 02114 USA. RP Hahn, JO (reprint author), MIT, Dept Mech Engn, Cambridge, MA 02139 USA. EM stardust@mit.edu; asada@mit.edu; areisner@partners.org; fjaffer@mgh.harvard.edu OI Jaffer, Farouc/0000-0001-7980-384X FU Sharp Corporation FX This work was supported in part by the Sharp Corporation. NR 9 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-1814-5 J9 IEEE ENG MED BIO PY 2008 BP 813 EP + PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BIS22 UT WOS:000262404500205 ER PT S AU Wichakool, W Pierquet, B Durand, K Hsu, B Sheridan, R Ma, HS AF Wichakool, Warit Pierquet, Brandon Durand, Keith Hsu, Byron Sheridan, Rob Ma, Hongshen GP IEEE TI Magnetic Endotracheal Tube Imaging Device SO 2008 30TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-8 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 30th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 20-24, 2008 CL Vancouver, CANADA SP DEVICIX, Green Coll, Natl Inst Hlth, NIBIB, NSF, PLEXON Inc, UBC Engn Biomed Engn, Univ Washington, Coll Engn, Bentham Sci Publ Ltd, Recent Patents Biomed Engn, Recent Patents Engn AB This paper describes an accurate, economical, and portable device that helps to locate the position of an endotracheal tube (ETT) in situ. The device uses an array of magnetic field sensors to detect an anomaly in magnetic field caused by magnet embedded near the cuff of an ETT, and displays an intuitive map of relative magnetic field intensity under the sensor area. The device provides real-time feedback of the position to a clinician, so that corrective measures can be taken if the ETT is determined to be outside of normal positioning with respect to the patient's airway. Variations of the proposed design are suitable for continuous monitoring. C1 [Wichakool, Warit; Pierquet, Brandon; Durand, Keith; Hsu, Byron; Ma, Hongshen] MIT, Grad Program Elect Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Sheridan, Rob] Shriners Hosp Children, Boston, MA 02114 USA. [Sheridan, Rob] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ma, Hongshen] MIT, Dept Elect Engn, Cambridge, MA 02139 USA. RP Wichakool, W (reprint author), MIT, Grad Program Elect Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM hongma@mit.edu FU Center for Integration of Medicine and Innovative Technology (CIMIT) FX This work was supported by the Center for Integration of Medicine and Innovative Technology (CIMIT). NR 10 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-1814-5 J9 IEEE ENG MED BIO PY 2008 BP 985 EP + DI 10.1109/IEMBS.2008.4649320 PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BIS22 UT WOS:000262404500247 ER PT S AU McCombie, DB Reisner, AT Asada, HH AF McCombie, Devin B. Reisner, Andrew T. Asada, H. Harry GP IEEE TI Motion Based Adaptive Calibration of Pulse Transit Time Measurements to Arterial Blood Pressure for an Autonomous, Wearable Blood Pressure Monitor SO 2008 30TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-8 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 30th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 20-24, 2008 CL Vancouver, CANADA SP DEVICIX, Green Coll, Natl Inst Hlth, NIBIB, NSF, PLEXON Inc, UBC Engn Biomed Engn, Univ Washington, Coll Engn, Bentham Sci Publ Ltd, Recent Patents Biomed Engn, Recent Patents Engn ID SENSOR CONTACT FORCE; CLINICAL-APPLICATIONS AB This paper presents a novel adaptive algorithm for calibrating non-invasive pulse transit time (PTT) measurements to arterial blood pressure (BP). This new algorithm allows complete calibration of PTT to BP without the use of an oscillometric blood pressure cuff or external pressure sensor. Further, the algorithm can be used to continually update the identified parameters in the calibration equation while the patient is wearing the device. The technique utilizes natural patient motion to generate a known change in the transmural pressure (input) acting on the arteries monitored by our device to produce a measurable change in pulse transit time (output). The natural motion includes varying the height of the sensor relative to the heart to alter hydrostatic pressure at the measurement site and adjusting proximal joint posture to vary the external arterial pressure at the measurement site. This new algorithm is applied to a unique wearable sensor architecture that combines two in-line PPG sensors, one located at the ulnar artery of the wrist and one located at the digital artery of the little finger along with a multi-axis accelerometer for height measurement. Initial human subject tests results using the new algorithm and device will be presented. C1 [McCombie, Devin B.; Asada, H. Harry] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Reisner, Andrew T.] Massachusetts Gen Hosp, Boston, MA USA. RP McCombie, DB (reprint author), MIT, Dept Mech Engn, Cambridge, MA 02139 USA. EM mccombie@mit.edu; areisner@partners.org; asada@mit.edu FU Sharp Electronics Corporation FX This work was supported in part by the Sharp Electronics Corporation NR 13 TC 7 Z9 7 U1 0 U2 5 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-1814-5 J9 IEEE ENG MED BIO PY 2008 BP 989 EP + DI 10.1109/IEMBS.2008.4649321 PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BIS22 UT WOS:000262404500248 ER PT S AU Chen, F Wu, H Hsu, PL Stronger, B Sheridan, R Ma, HS AF Chen, Fred Wu, Henry Hsu, Pei-Lan Stronger, Brad Sheridan, Robert Ma, Hongshen GP IEEE TI SmartPad: A Wireless, Adhesive-Electrode-Free, Autonomous ECG Acquisition System SO 2008 30TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-8 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 30th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 20-24, 2008 CL Vancouver, CANADA SP DEVICIX, Green Coll, Natl Inst Hlth, NIBIB, NSF, PLEXON Inc, UBC Engn Biomed Engn, Univ Washington, Coll Engn, Bentham Sci Publ Ltd, Recent Patents Biomed Engn, Recent Patents Engn AB During medical procedures, such as surgery, a patient's vital signs are typically monitored using a web of wires connected to adhesive electrodes. The large number of wires inhibits the medical team's access to the patient while the adhesive electrodes can detach, fail, or be out-of-stock, causing delays in the procedure. In order to combat these problems, we have developed the SmartPad: a system that displays a patient's electrocardiogram (ECG) signal without adhesive pads, wires, or active intervention from a clinician. The system automatically selects three electrodes from an array of Cu/Ni-fabric based electrodes patterned on a thin pad on which the patient lies. The selected electrodes are used to provide a differential 3-lead measurement of the patient's ECG, which is then transmitted wirelessly and displayed on a laptop computer. C1 [Chen, Fred; Wu, Henry; Hsu, Pei-Lan] MIT, Program Elect Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Stronger, Brad] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Sheridan, Robert] Shriners Hosp Children Boston, Boston, MA 02114 USA. [Sheridan, Robert] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ma, Hongshen] MIT, Dept Elect Engn, Cambridge, MA 02139 USA. RP Chen, F (reprint author), MIT, Program Elect Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM fredchen@mit.edu; hongma@mit.edu FU Center for Integration of Medicine and Innovative Technology FX Manuscript received April 6, 2008. This work was supported in by the Center for Integration of Medicine and Innovative Technology. NR 10 TC 1 Z9 1 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-1814-5 J9 IEEE ENG MED BIO PY 2008 BP 2345 EP + DI 10.1109/IEMBS.2008.4649669 PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BIS22 UT WOS:000262404501189 ER PT S AU Chen, Z Brown, EN Barbieri, R AF Chen, Zhe Brown, Emery N. Barbieri, Riccardo GP IEEE TI Characterizing Nonlinear Heartbeat Dynamics within a Point Process Framework SO 2008 30TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-8 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 30th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 20-24, 2008 CL Vancouver, CANADA SP DEVICIX, Green Coll, Natl Inst Hlth, NIBIB, NSF, PLEXON Inc, UBC Engn Biomed Engn, Univ Washington, Coll Engn, Bentham Sci Publ Ltd, Recent Patents Biomed Engn, Recent Patents Engn ID TIME-SERIES AB Heartbeat intervals are known to have nonlinear and non-stationary dynamics. In this paper, we propose a nonlinear Volterra-Wiener expansion modeling of human heartbeat dynamics within a point process framework. Inclusion of second-order nonlinearity allows us to estimate dynamic bispectrum. The proposed probabilistic model was examined with two recorded heartbeat interval data sets. Preliminary results show that our model is beneficial to characterize the inherent nonlinearity of the heartbeat dynamics. C1 [Chen, Zhe; Brown, Emery N.; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. RP Chen, Z (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM zhechen@neurostat.mgh.harvard.edu; brown@neurostat.mgh.harvard.edu; barbieri@neurostat.mgh.harvard.edu OI Barbieri, Riccardo/0000-0001-9381-3833; Chen, Zhe/0000-0002-6483-6056 NR 16 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-1814-5 J9 IEEE ENG MED BIO PY 2008 BP 2781 EP 2784 DI 10.1109/IEMBS.2008.4649779 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BIS22 UT WOS:000262404501299 ER PT S AU Barbieri, R Chen, Z Brown, EN AF Barbieri, Riccardo Chen, Zhe Brown, Emery N. GP IEEE TI Assessment of Hippocampal and Autonomic Neural Activity by Point Process Models SO 2008 30TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-8 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 30th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 20-24, 2008 CL Vancouver, CANADA SP DEVICIX, Green Coll, Natl Inst Hlth, NIBIB, NSF, PLEXON Inc, UBC Engn Biomed Engn, Univ Washington, Coll Engn, Bentham Sci Publ Ltd, Recent Patents Biomed Engn, Recent Patents Engn C1 [Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Neurosci Stat Res Lab, Boston, MA 02115 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA USA. RP Barbieri, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Neurosci Stat Res Lab, Boston, MA 02115 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-1814-5 J9 IEEE ENG MED BIO PY 2008 BP 3679 EP 3679 DI 10.1109/IEMBS.2008.4650006 PG 1 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BIS22 UT WOS:000262404502115 ER PT S AU Patel, S Hughes, R Huggins, N Standaert, D Growdon, J Dy, J Bonato, P AF Patel, Shyamal Hughes, Richard Huggins, Nancy Standaert, David Growdon, John Dy, Jennifer Bonato, Paolo GP IEEE TI Using Wearable Sensors to Predict the Severity of Symptoms and Motor Complications in Late Stage Parkinson's Disease SO 2008 30TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-8 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 30th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 20-24, 2008 CL Vancouver, CANADA SP DEVICIX, Green Coll, Natl Inst Hlth, NIBIB, NSF, PLEXON Inc, UBC Engn Biomed Engn, Univ Washington, Coll Engn, Bentham Sci Publ Ltd, Recent Patents Biomed Engn, Recent Patents Engn AB This paper is focused on the analysis of data obtained from wearable sensors in patients with Parkinson's Disease. We implemented Support Vector Machines (SVM's) to predict clinical scores of the severity of Parkinsonian symptoms and motor complications. We determined the optimal window length to extract features from the sensor data. Furthermore, we performed tests to determine optimal parameters for the SVM's. Finally, we analyzed how well individual tasks performed by patients captured the severity of various symptoms and motor complications. C1 [Patel, Shyamal; Hughes, Richard; Bonato, Paolo] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA 02114 USA. [Huggins, Nancy; Growdon, John] Massachusetts Gen Hosp, Dept Neurol Harvard Med Sch, Boston, MA 02114 USA. RP Bonato, P (reprint author), Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA 02114 USA. EM spatel19@partners.org; rhughes1@partners.org; nhuggins@partners.org; jgrowdon@partners.org; pbonato@partners.org OI Standaert, David/0000-0003-2921-8348 FU National Institute of Neurological Disorders and Stroke; National Institutes of Health [R21NS045401-02] FX This work was supported in part by the National Institute of Neurological Disorders and Stroke, National Institutes of Health under the grant #R21NS045401-02. NR 8 TC 8 Z9 8 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-1814-5 J9 IEEE ENG MED BIO PY 2008 BP 3686 EP + DI 10.1109/IEMBS.2008.4650009 PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BIS22 UT WOS:000262404502118 ER PT S AU Hahn, JO Reisner, A Asada, HH AF Hahn, Jin-Oh Reisner, Andrew Asada, H. Harry GP IEEE TI Physiologic-state-adaptive recovery of aortic blood pressure and flow using blind 2-channel IIR cardiovascular system identification SO 2008 AMERICAN CONTROL CONFERENCE, VOLS 1-12 SE Proceedings of the American Control Conference LA English DT Proceedings Paper CT American Control Conference 2008 CY JUN 11-13, 2008 CL Seattle, WA SP IEEE ID SIGNALS; WAVE AB This paper presents the development and analysis of a method to identify a two-channel cardiovascular system using two distinct peripheral blood pressure signals. The method is able to characterize the upper- and lower-limb arterial path dynamics as well as the aortic root impedance, and recover the aortic blood pressure and flow signals fed to it. The blind system identification and input de-convolution algorithms for a class of two-channel infinite impulse response systems are developed and applied to a gray-box model of a two-channel cardiovascular system. Persistent excitation condition, model identifiability and asymptotic variance are analyzed to quantify the method's validity and reliability. Experimental results based on 83 data segments obtained from a swine subject show that the cardiovascular dynamics can be identified very accurately and reliably, and the aortic blood pressure and flow signals are stably recovered from two distinct peripheral blood pressure signals under diverse physiologic conditions. The benefit of the proposed method is demonstrated by comparing it to a predetermined transfer function describing the cardiovascular dynamics at nominal physiologic conditions. C1 [Hahn, Jin-Oh; Asada, H. Harry] MIT, Arbeloff Lab Informat Syst & Technol, Cambridge, MA 02139 USA. [Reisner, Andrew] Massachusetts Gen Hosp, Dept Emergency, Boston, MA USA. RP Hahn, JO (reprint author), MIT, Arbeloff Lab Informat Syst & Technol, Cambridge, MA 02139 USA. EM stardust@mit.edu; areisner@partners.org; asada@mit.edu NR 12 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0743-1619 BN 978-1-4244-2078-0 J9 P AMER CONTR CONF PY 2008 BP 838 EP + PG 2 WC Automation & Control Systems; Engineering, Electrical & Electronic SC Automation & Control Systems; Engineering GA BIG00 UT WOS:000259261500142 ER PT B AU Dogan, M Goldberg, BB Jain, S Goldberg, MB Swan, AK Unlu, MS AF Dogan, Mehmet Goldberg, Bennett B. Jain, Sumita Goldberg, Marcia B. Swan, Anna K. Uenlue, M. Selim GP IEEE TI Probing Bacterial Surfaces Using 4Pi Spectral Self-interference Fluorescence Microscopy SO 2008 CONFERENCE ON LASERS AND ELECTRO-OPTICS & QUANTUM ELECTRONICS AND LASER SCIENCE CONFERENCE, VOLS 1-9 LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics/Quantum Electronics and Laser Science Conference (CLEO/QELS 2008) CY MAY 04-09, 2008 CL San Jose, CA ID RESOLUTION; LIMIT AB We present nanometer scale axial localization of fluorescent markers to probe subcellular structures using self-interference based fluorescence microscopy. We show probing the membrane topography of a gram-negative bacterium, Shigella flexneri, and discuss further applications. (C) 2008 Optical Society of America C1 [Dogan, Mehmet; Goldberg, Bennett B.] Boston Univ, Dept Phys, 590 Commonwealth Ave, Boston, MA 02215 USA. [Jain, Sumita; Goldberg, Marcia B.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Cambridge, MA 02139 USA. [Jain, Sumita; Goldberg, Marcia B.] Harvard Univ, Sch Med, Cambridge, MA 02139 USA. [Swan, Anna K.; Uenlue, M. Selim] Boston Univ, Dept Elect & Comp Engn, Boston, MA 02215 USA. RP Dogan, M (reprint author), Boston Univ, Dept Phys, 590 Commonwealth Ave, Boston, MA 02215 USA. EM mdozan@bu.edu; goldberg@bu.edu; sumita@u.washington.edu; mgoldberg1@partnes.org; swan@bu.edu; selim@bu.edu RI Unlu, Selim/B-4244-2013 NR 10 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-55752-859-9 PY 2008 BP 254 EP + PG 2 WC Engineering, Electrical & Electronic; Optics SC Engineering; Optics GA BIL52 UT WOS:000260498400128 ER PT S AU Chen, Z Brown, EN Barbieri, R AF Chen, Zhe Brown, Emery N. Barbieri, Riccardo GP IEEE TI A study of probabilistic models for characterizing human heart beat dynamics in autonomic blockade control SO 2008 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH AND SIGNAL PROCESSING, VOLS 1-12 SE International Conference on Acoustics Speech and Signal Processing ICASSP LA English DT Proceedings Paper CT 33rd IEEE International Conference on Acoustics, Speech and Signal Processing CY MAR 30-APR 04, 2008 CL Las Vegas, NV DE heart rate variability; point processes; adaptive filters; autoregressive processes ID TIME-SERIES AB In this paper, we compare and validate different probabilistic models of human heart beat intervals for assessment of the electrocardiogram data recorded with varying conditions in posture and pharmacological autonomic blockade. The models are validated using the adaptive point process filtering paradigm and Kolmogorov-Smirnov test. The inverse Gaussian model was found to achieve the overall best performance in the analysis of autonomic control. We further improve the model by incorporating the respiratory covariate measurements and present dynamic respiratory sinus arrhythmia (RSA) analysis. Our results suggest the instantaneous RSA gain computed from our proposed model as a potential index of vagal control dynamics. C1 [Chen, Zhe; Brown, Emery N.; Barbieri, Riccardo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Stat Res Lab, Boston, MA 02114 USA. RP Chen, Z (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM zhechen@neurostat.mgh.harvard.edu; brown@neurostat.mgh.harvard.edu; barbieri@neurostat.mgh.harvard.edu OI Barbieri, Riccardo/0000-0001-9381-3833; Chen, Zhe/0000-0002-6483-6056 FU NHLBI NIH HHS [R01 HL084502, R01 HL084502-02]; NIDA NIH HHS [R01 DA015644] NR 9 TC 6 Z9 6 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1520-6149 BN 978-1-4244-1483-3 J9 INT CONF ACOUST SPEE PY 2008 BP 481 EP 484 PG 4 WC Acoustics; Computer Science, Artificial Intelligence; Computer Science, Cybernetics; Engineering, Biomedical; Engineering, Electrical & Electronic; Mathematical & Computational Biology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging; Telecommunications SC Acoustics; Computer Science; Engineering; Mathematical & Computational Biology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging; Telecommunications GA BHY47 UT WOS:000257456700121 PM 19593392 ER PT S AU Maddah, M Zollei, L Grimson, WEL Westin, CF Wells, WM AF Maddah, Mahnaz Zollei, Lilla Grimson, W. Eric L. Westin, Carl-Fredrik Wells, William M. GP IEEE TI A mathematical framework for incorporating anatomical knowledge in DT-MRI analysis SO 2008 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1-4 SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 5th IEEE International Symposium on Biomedical Imaging CY MAY 14-17, 2008 CL Paris, FRANCE SP IEEE DE diffusion tensor MRI; clustering; anatomical information; tract-oriented quantitative analysis ID DIFFUSION TENSOR MRI; WHITE-MATTER ANATOMY AB We propose a Bayesian approach to incorporate anatomical information in the clustering of fiber trajectories. An expectation-maximization (EM) algorithm is used to cluster the trajectories, in which an atlas serves as the prior on the labels. The atlas guides the clustering algorithm and makes the resulting bundles anatomically meaningful. In addition, it provides the seed points for the tractography and initial settings of the EM algorithm. The proposed approach provides a robust and automated tool for tract-oriented analysis both in a single subject and over a population. C1 [Maddah, Mahnaz; Grimson, W. Eric L.] MIT, Comp Sci & Artificial Intelligence Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Zollei, Lilla] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Westin, Carl-Fredrik; Wells, William M.] Brigham & Womens Hosp, Surg Planning Lab, Boston, MA 02115 USA. RP Maddah, M (reprint author), MIT, Comp Sci & Artificial Intelligence Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. FU NIH [P41 RR013218, U54 EB005149, U41 RR019703, P30 HD018655, R01 RR021885, R03 CA126466, P41-RR14075, BIRN002,, U24 RR021382, R21 MH067054, R01 MH074794]; NMSS [RG 3478A2/2] FX This work is supported in part by NIH grants P41 RR013218,U54 EB005149, U41 RR019703, P30 HD018655, R01 RR021885, R03 CA126466, P41-RR14075, BIRN002, U24 RR021382, and R21 MH067054 and NIH R01 MH074794, and grant RG 3478A2/2 from the NMSS. NR 14 TC 6 Z9 6 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4244-2002-5 J9 I S BIOMED IMAGING PY 2008 BP 105 EP + DI 10.1109/ISBI.2008.4540943 PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Nanoscience & Nanotechnology; Imaging Science & Photographic Technology SC Engineering; Science & Technology - Other Topics; Imaging Science & Photographic Technology GA BIB70 UT WOS:000258259800027 ER PT S AU Sun, W Cetin, M Chan, R Willsky, AS AF Sun, Walter Cetin, Muejdat Chan, Ray Willsky, Alan S. GP IEEE TI Segmentation of the evolving left ventricle by learning the dynamics SO 2008 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1-4 SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 5th IEEE International Symposium on Biomedical Imaging CY MAY 14-17, 2008 CL Paris, FRANCE SP IEEE DE magnetic resonance imaging; cardiac imaging; left ventricle; image segmentation; recursive estimation; curve evolution; graphical models; particle filtering; learning ID TRACKING AB We propose a method for recursive segmentation of the left ventricle (LV) across a temporal sequence of magnetic resonance (MR) images. The approach involves a technique for learning the LV boundary dynamics together with a particle-based inference algorithm on a loopy graphical model capturing the temporal periodicity of the heart. The dynamic system state is a low-dimensional representation of the boundary, and boundary estimation involves incorporating curve evolution into state estimation. By formulating the problem as one of state estimation, the segmentation at each particular time is based not only on the data observed at that instant, but also on predictions based on past and future boundary estimates. We assess and demonstrate the effectiveness of the proposed framework on a large data set of breath-hold cardiac MR image sequences. C1 [Sun, Walter] Microsoft Corp, Redmond, WA 98052 USA. [Cetin, Muejdat] Sabanci Univ, Fac Engn & Nat, Istanbul, Turkey. [Cetin, Muejdat; Willsky, Alan S.] MIT, Informat & Decis Syst Lab, Cambridge, MA 02139 USA. [Chan, Ray] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sun, W (reprint author), Microsoft Corp, Redmond, WA 98052 USA. FU MURI through AFOSR [FA9550-06-1-0324]; Shell International Exploration and Production, Inc.; European Commission [MIRG-CT-2006-041919] FX This work was supported in part by a MURI funded through AFOSR Grant FA9550-06-1-0324, in part by Shell International Exploration and Production, Inc., and in part by the European Commission under Grant MIRG-CT-2006-041919. NR 14 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4244-2002-5 J9 I S BIOMED IMAGING PY 2008 BP 229 EP + DI 10.1109/ISBI.2008.4540974 PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Nanoscience & Nanotechnology; Imaging Science & Photographic Technology SC Engineering; Science & Technology - Other Topics; Imaging Science & Photographic Technology GA BIB70 UT WOS:000258259800058 ER PT S AU Liang, ZL Karl, WC Do, S Brady, T Pien, H AF Liang, Zhuangli Karl, W. Clem Do, Synho Brady, Thomas Pien, Homer GP IEEE TI Analysis and mitigation of calcium artifacts in cardiac multidetector CT SO 2008 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1-4 SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 5th IEEE International Symposium on Biomedical Imaging CY MAY 14-17, 2008 CL Paris, FRANCE SP IEEE DE cardiac CT; MDCT; calcium blooming ID STATISTICAL IMAGE-RECONSTRUCTION AB Multi-detector Computed Tomography offers the promise of a non-invasive alternative to invasive coronary angiography for the evaluation of coronary artery disease. An impediment preventing its widespread adoption is the presence of image "blooming" artifacts due to the presence vascular calcium. This blooming has been linked to cardiac motion, beam hardening, and resolution effects. In this paper we study the contribution of these elements to blooming in a controlled way and conclude that the strongest effect for current systems is due to resolution. We then present a multicomponent algebraic-type reconstruction approach to mitigate such blooming artifacts, motivated by recent results in image inpainting. The reconstruction approach decomposes the image into a collection of spatially localized components, each with a set of homogeneous properties. The local nature of the decomposition and constraints prevents artifacts from contaminating other image regions. C1 [Liang, Zhuangli; Karl, W. Clem] Boston Univ, Dept Elect & Comp Engn, Boston, MA 02215 USA. [Do, Synho; Brady, Thomas; Pien, Homer] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Liang, ZL (reprint author), Boston Univ, Dept Elect & Comp Engn, Boston, MA 02215 USA. FU Center for Integration of Medicine and Innovative Technology (CIMIT); NSF funded Engineering Research Center for Subsurface Sensing and Imaging Systems; Siemens Medical provided the DRASIM simulation package and made details of the Sensation-64MDC Tavailabletous FX This work was supported in part by the Center for Integration of Medicine and Innovative Technology (CIMIT), and by the NSF funded Engineering Research Center for Subsurface Sensing and Imaging Systems. Siemens Medical provided the DRASIM simulation package and made details of the Sensation-64MDC Tavailabletous. NR 8 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4244-2002-5 J9 I S BIOMED IMAGING PY 2008 BP 1477 EP + DI 10.1109/ISBI.2008.4541287 PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Nanoscience & Nanotechnology; Imaging Science & Photographic Technology SC Engineering; Science & Technology - Other Topics; Imaging Science & Photographic Technology GA BIB70 UT WOS:000258259800371 ER PT B AU Sharma, G Rege, K Budil, D Yarmush, M Mavroidis, C AF Sharma, Gaurav Rege, Kaushal Budil, David Yarmush, Martin Mavroidis, Constantinos BE Chatila, R Kelly, A Merlet, JP TI Design and Modeling of a Protein Based NanoGripper SO 2008 IEEE/RSJ INTERNATIONAL CONFERENCE ON ROBOTS AND INTELLIGENT SYSTEMS, VOLS 1-3, CONFERENCE PROCEEDINGS LA English DT Proceedings Paper CT IEEE/RSJ International Conference on Intelligent Robots and Systems CY SEP 22-26, 2008 CL Nice, FRANCE SP IEEE, Robot Soc Japan, IEEE Robot & Automat Soc, IEEE Ind Elect Soc, Soc Instrument & Control Engineers, Inst Natl Rech Informat & Automat, CNRS, Inst Control, Robot & Syst ID GCN4 LEUCINE-ZIPPER; X-RAY-STRUCTURE; MOLECULAR-DYNAMICS; COILED-COILS; ELECTROSTATIC INTERACTIONS; SIMULATIONS; PREDICTION; ALGORITHMS; BINDING AB The design hypothesis, architectures, and computational modeling of a novel peptide based nanoGripper are presented in this paper. We engineered the a-helical coiled coil portion of the yeast transcriptional activator peptide called GCN4 to obtain an environmentally-responsive nanoGripper. The dimeric coiled-coil peptide consists of two identical similar to 4.5 nm long and similar to 3 nm wide polypeptide chains. The actuation mechanism depends on the modification of electrostatic charges along the peptide by varying the pH of the solution resulting in the reversible movement of helices and therefore, creating the motion of a gripper. Using molecular dynamics simulations we showed that pH changes led to a reversible opening of up-to 1.5 nm which is approximately 150% of the initial separation of the nanoGripper. We also investigated the forces generated by the nanoGripper upon pH actuation. Using a new method based on a modified steered molecular dynamics technique we were able to show that the force output of the nanoGripper is comparable to that generated by ATP-based molecular motors such as myosin and kinesin even though our molecular tweezer is smaller in size to these molecular motors. C1 [Sharma, Gaurav] Burnham Inst Med Res, La Jolla, CA USA. [Sharma, Gaurav] NE Univ, Boston, MA USA. [Rege, Kaushal] Massachusetts Gen Hosp, Boston, MA USA. [Rege, Kaushal] Arizona State Univ, Dept Chem Engn, Tempe, AZ USA. [Budil, David] NE Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. [Yarmush, Martin] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. [Mavroidis, Constantinos] NE Univ, Dept Mech Engn, Boston, MA 02115 USA. RP Sharma, G (reprint author), Burnham Inst Med Res, La Jolla, CA USA. EM gsharma@burnham.org; kaushal.rege@asu.edu; d.budil@neu.edu; ireis@sbi.org; mavro@coe.neu.edu RI Budil, David/A-9931-2012 OI Budil, David/0000-0003-2384-7928 FU NASA Institute for Advanced Concepts (NIAC); National Science Foundation [DMI-0422724] FX This work was supported in part by the NASA Institute for Advanced Concepts (NIAC) Phase II grant and the National Science Foundation (grant DMI-0422724). NR 20 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-2057-5 PY 2008 BP 476 EP 481 DI 10.1109/IROS.2008.4651051 PG 6 WC Computer Science, Artificial Intelligence; Computer Science, Cybernetics; Computer Science, Theory & Methods; Engineering, Electrical & Electronic; Robotics SC Computer Science; Engineering; Robotics GA BIJ26 UT WOS:000259998200075 ER PT J AU Sebastian, S Lee, SI Horowitz, NS Scott, JA Fischman, AJ Simeone, JF Fuller, AF Hahn, PF AF Sebastian, Sunit Lee, Susanna I. Horowitz, Neil S. Scott, James A. Fischman, Alan J. Simeone, Joseph F. Fuller, Arlan F. Hahn, Peter F. TI PET-CT vs. CT alone in ovarian cancer recurrence SO ABDOMINAL IMAGING LA English DT Article ID FOLLOW-UP; CYTOREDUCTIVE SURGERY; PERITONEAL METASTASES; CARCINOMA; CA-125; SCANS AB Background: To compare fusion, positron emission tomography-computed tomography (PET-CT) with CT alone in detecting ovarian carcinoma recurrence. Methods: Fifty-one consecutive patients underwent 53 restaging PET-CT scans with a concurrent diagnostic quality CT scan. Two body imaging radiologists independently assessed the CT's; each then teamed with a nuclear medicine specialist to review the PET-CT's. Two teams conferred for consensus on the presence of disease in the chest, abdomen, and body overall with CT alone and with PET-CT, using a six-point reader confidence metric to determine accuracy and receiver operating characteristic (ROC) curves. Reader agreement was compared using kappa. Recurrence was determined by two gynecologic oncologists reviewing clinical records from time of presentation to at least 13 months (mean 22.7) after imaging. Results: Recurrence was based on histopathology in 17% (9/53). Seventy-two percent (38/53) cases had recurrence, with two cases showing isolated chest recurrence. PET-CT accuracy exceeded CT for body 92% (49/53) vs. 83% (44/53), chest 96% (51/53) vs. 89% (47/53), and abdomen 91% (48/53) vs. 79% (42/53). ROC curves for PET-CT dominated that for CT alone; this difference was statistically significant for abdomen and for body overall (P < 0.01). Interobserver agreement was better for PET-CT than for CT alone. Conclusions: PET-CT demonstrates greater accuracy and less interobserver variability than CT alone. C1 [Sebastian, Sunit; Lee, Susanna I.; Scott, James A.; Fischman, Alan J.; Simeone, Joseph F.; Hahn, Peter F.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Sebastian, Sunit] Emory Sch Med, Dept Radiol, Atlanta, GA USA. [Horowitz, Neil S.; Fuller, Arlan F.] Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Boston, MA 02114 USA. RP Lee, SI (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM slee0@partners.org NR 24 TC 54 Z9 55 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD JAN PY 2008 VL 33 IS 1 BP 112 EP 118 DI 10.1007/s00261-007-9218-0 PG 7 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 243TV UT WOS:000251821100025 PM 17404789 ER PT J AU Pujol, S Kikinis, R Gollub, R AF Pujol, Sonia Kikinis, Ron Gollub, Randy TI Lowering the barriers inherent in translating advances in neuroimage analysis to clinical research applications SO ACADEMIC RADIOLOGY LA English DT Article DE technology transfer; biomedical image processing; diffusion tensor Imaging ID RESEARCH OPPORTUNITIES WORKSHOP; RECOMMENDATIONS; SCHIZOPHRENIA AB Rationale and Objectives. This article presents an initiative for the translation of advances in neuroimage analysis techniques to clinical research scientists. Our objective is to bridge the gap between scientific advances made by the biomedical imaging community and their widespread use in the clinical research community. Through national collaborative effort supported by the National Institutes of Health Roadmap, the integration of the most sophisticated algorithms into usable working open-source systems enables clinical researchers to have access to a broad spectrum of cutting edge analysis techniques. A critical step to maximize the long-term positive impact of this collaborative effort is to translate these techniques into new skills of clinical researchers. To address this challenge, we developed a methodology based on three criteria: a multidisciplinary approach, a balance between theory and common practice, and an immersive collaborative environment. The article illustrates our initiative through the exemplar case of diffusion tensor imaging tractography, and reports on our experience over the past two years of designing and delivering training workshops to more than 300 clinicians and scientists using the developed methodology. C1 [Gollub, Randy] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Athinoula A Martinos Ctr Biomed Imaging, Dept Psychiat, Charlestown, MA 02129 USA. [Pujol, Sonia; Kikinis, Ron] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol,Surg Planning Lab, Boston, MA 02115 USA. RP Pujol, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol,Surg Planning Lab, L1-050,75 Francis St, Boston, MA 02115 USA. EM spujol@bwh.harvard.edu OI Gollub, Randy L./0000-0002-9434-4044 FU NIBIB NIH HHS [P41 EB015902, U54 EB005149, U54 EB005149-04] NR 13 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JAN PY 2008 VL 15 IS 1 BP 114 EP 118 DI 10.1016/j.acra.2007.08.002 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 246CH UT WOS:000251984600014 PM 18078914 ER PT J AU Gurubhagavatula, I Nkwuo, JE Maislin, G Pack, AI AF Gurubhagavatula, Indira Nkwuo, Jonathan E. Maislin, Greg Pack, Allan I. TI Estimated cost of crashes in commercial drivers supports screening and treatment of obstructive sleep apnea SO ACCIDENT ANALYSIS AND PREVENTION LA English DT Article DE polysomnography; nocturnal pulse oximetry; questionnaire; economics; cost analysis ID QUALITY-OF-LIFE; POSITIVE AIRWAY PRESSURE; MOTOR-VEHICLE COLLISIONS; HEALTH-CARE UTILIZATION; HAUL TRUCK DRIVERS; APNOEA/HYPOPNOEA SYNDROME; TRAFFIC ACCIDENTS; NASAL CPAP; RISK-FACTORS; DIAGNOSIS AB Sleep apnea among commercial drivers may increase the risk of fall-asleep crashes, which incur large expenses. Drivers of passenger cars whose apnea is treated experience lower crash risk. Among community-based holders of commercial driver's licenses, we considered three methods for identifying sleep apnea syndrome: (1) in-lab polysomnography; (2) selective in-lab polysomnography for high-risk drivers, where high risk is first identified by body mass index, age and gender, followed by oximetry in a subset of drivers; (3) not screening. The costs for each of these three programs equaled the sum of the costs of testing, treatment of identified cases, and crashes. Assuming that treatment prevents apnea-related crashes, polysomnography is not cost-effective, because it was more expensive than the cost of crashes when no screening is done. Screening with BMI, age and gender, however, with confirmatory in-lab polysomnography only on high-risk drivers was cost-effective, as long as a high proportion (73.8%) of screened drivers accepts treatment. These findings indicate that strategies that reduce reliance on in-laboratory polysomnography may be more cost-effective than not screening, and that treatment acceptance may need to be a condition of employment for affected drivers. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Gurubhagavatula, Indira; Nkwuo, Jonathan E.; Maislin, Greg; Pack, Allan I.] Univ Penn, Med Ctr, Dept Med,Div Sleep Med, Ctr Sleep & Resp Neurobiol, Philadelphia, PA 19104 USA. [Gurubhagavatula, Indira] Philadelphia VA Med Ctr, Pulm Crit Care & Sleep Sect, Philadelphia, PA USA. RP Gurubhagavatula, I (reprint author), Univ Penn, Med Ctr, Dept Med,Div Sleep Med, Ctr Sleep & Resp Neurobiol, 3624 Market St,Suite 205, Philadelphia, PA 19104 USA. EM gurubhag@mail.med.upenn.edu FU NCRR NIH HHS [K23 RR016068, 3-M01-RR00040-39S2, K23 RR016068-05, K23RR16068-03, M01 RR000040, M01 RR000040-440871]; NHLBI NIH HHS [P01-HL-60287, P50 HL060287] NR 50 TC 20 Z9 20 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0001-4575 J9 ACCIDENT ANAL PREV JI Accid. Anal. Prev. PD JAN PY 2008 VL 40 IS 1 BP 104 EP 115 DI 10.1016/j.aap.2007.04.011 PG 12 WC Ergonomics; Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary; Transportation SC Engineering; Public, Environmental & Occupational Health; Social Sciences - Other Topics; Transportation GA 265GG UT WOS:000253346500013 PM 18215538 ER PT J AU Eikermann, M Malhotra, A AF Eikermann, M. Malhotra, A. TI Predictive value of stimulated muscle force assessment in critically ill patients SO ACTA ANAESTHESIOLOGICA SCANDINAVICA LA English DT Editorial Material ID FATIGUE C1 [Eikermann, M.] Massachusetts Gen Hosp, Dept Anesthesia & CCM, Boston, MA 02114 USA. [Eikermann, M.] Harvard Med Sch, Div Pulm & Crit Care, Boston, MA USA. [Malhotra, A.] Brigham & Womens Hosp, Div Pulm & Crit Care, Boston, MA 02115 USA. RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & CCM, 55 Fruit St, Boston, MA 02114 USA. EM meikermann@partners.org FU NHLBI NIH HHS [K24 HL093218, R01 HL090897, R01 HL085188] NR 8 TC 2 Z9 2 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-5172 J9 ACTA ANAESTH SCAND JI Acta Anaesthesiol. Scand. PD JAN PY 2008 VL 52 IS 1 BP 1 EP 2 DI 10.1111/j.1399-6576.2007.01536.x PG 2 WC Anesthesiology SC Anesthesiology GA 242ZD UT WOS:000251763800001 PM 18173429 ER PT J AU Wang, XL Wang, HW Hillemanns, P Hamblin, MR AF Wang, Xiu L. Wang, Hong W. Hillemanns, Peter Hamblin, Michael R. TI Distinctive Features of Foreskin Condylomata Acuminata Associated with Diabetes Mellitus SO ACTA DERMATO-VENEREOLOGICA LA English DT Article DE condylomata acuminata; diabetes mellitus; clinical features ID POPULATIONS; INFECTIONS AB The aim of this study was to test the hypothesis that particular clinical features of foreskin condylomata acuminata in Chinese male patients are associated with diabetes. A prospective study enrolled 126 men presenting with foreskin condylomata acuminata from 2001 to 2006. Mean age was 46 years (age range 25-74 years) and mean duration of disease was 4.8 months (range 1-18 months). Patients were divided into two groups according to clinical features. In group 1, 42 men had distinctive signs such as redundant prepuce, crown warts circling the entire preputial ring, maceration, fissures, phimosis and balanitis, and 37 of 42 (88%) patients were found to have concurrent type 2 diabetes, furthermore 32 of these 37 patients had an insidious onset and were previously undiagnosed. In group 2, 84 male patients did not have those distinctive clinical features and type 2 diabetes was found in only 10 cases (11.9%, p < 0.0001, Fisher's exact test). These clinical features strongly suggest the presence of diabetes. Therapy should address diabetes and condylomata concurrently. C1 [Wang, Xiu L.; Wang, Hong W.] Shanghai Skin Dis & STD Hosp, Dept Dermatol & Venereol, Shanghai 200050, Peoples R China. [Hillemanns, Peter] Hannover Med Sch, Dept Obstet & Gynecol, D-3000 Hannover, Germany. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Wang, XL (reprint author), Shanghai Skin Dis & STD Hosp, Dept Dermatol & Venereol, Wuyi Rood 196, Shanghai 200050, Peoples R China. EM xiuliwang2001@yahoo.com.cn OI Hamblin, Michael/0000-0001-6431-4605 FU NCI NIH HHS [R01 CA083882-02, R01 CA083882] NR 16 TC 2 Z9 2 U1 0 U2 2 PU ACTA DERMATO-VENEREOLOGICA PI UPPSALA PA TRADGARDSGATAN 14, UPPSALA, SE-753 09, SWEDEN SN 0001-5555 J9 ACTA DERM-VENEREOL JI Acta Derm.-Venereol. PY 2008 VL 88 IS 6 BP 578 EP 583 DI 10.2340/00015555-0537 PG 6 WC Dermatology SC Dermatology GA 375FA UT WOS:000261098300006 PM 19002342 ER PT J AU Abdel-Wahab, OI Rosovsky, RP Warth, JA AF Abdel-Wahab, Omar I. Rosovsky, Rachel P. Warth, James A. TI Warfarin-Induced Skin Necrosis in a Patient with Heparin-Induced Thrombocytopenia: Two Diseases or One? SO ACTA HAEMATOLOGICA LA English DT Article DE Anticoagulation-induced skin necrosis; Heparin-induced thrombocytopenia; Heparin skin necrosis; Warfarin-induced skin necrosis ID VENOUS LIMB GANGRENE; PARTIAL THROMBOPLASTIN TIME; PROTEIN-S; FONDAPARINUX; ANTICOAGULATION; DEFICIENCY; COUMARIN; PROPHYLAXIS; ENOXAPARIN; HIT AB A 64-year-old woman with colon carcinoma presented with subsegmental pulmonary emboli. Platelet count on presentation was 598 X 10(9)/l. The patient was anticoagulated with intravenous heparin. By hospital day 3, heparin was replaced with enoxaparin and warfarin. On hospital day 6, the patient developed a 20 X 15 cm area of necrotic skin on her left hip and a 1 X 3 cm area of necrosis on her right hip. By that time, her platelet count had fallen to 433 X 10(9)/l. Three days later (hospital day 9), anticoagulation was switched from the combination of enoxaparin and warfarin to argatroban. Her platelet count reached a nadir of 82 X 10(9)/l by the 12th hospital day. The areas of skin necrosis had never been sites of heparin injection. Heparin/platelet factor 4 antibody, sent on hospital day 9, returned positive and (14)C-serotonin release assay was also positive. This case illustrates that processes underlying heparin-induced thrombocytopenia (HIT) may also underlie warfarin-induced skin necrosis. Skin necrosis may be the earliest manifestation of HIT and need not be accompanied by thrombocytopenia. This patient's course illustrates that HIT should be considered in all patients presenting with skin necrosis while receiving anticoagulation with heparin or a combination of heparin and warfarin. Copyright (C) 2008 S. Karger AG, Basel C1 [Abdel-Wahab, Omar I.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Warth, James A.] Brigham & Womens Hosp Faulkner, Dept Hematol & Oncol, Boston, MA USA. [Rosovsky, Rachel P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Warth, James A.] Harvard Univ, Sch Med, Boston, MA USA. [Warth, James A.] Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Abdel-Wahab, OI (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. EM oabdel@gmail.com OI Abdel-Wahab, Omar/0000-0002-3907-6171 NR 29 TC 3 Z9 5 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5792 J9 ACTA HAEMATOL-BASEL JI Acta Haematol. PY 2008 VL 120 IS 2 BP 117 EP 122 DI 10.1159/000174756 PG 6 WC Hematology SC Hematology GA 375RS UT WOS:000261131600011 PM 19018128 ER PT J AU Eskild, A Jeansson, S Jenum, PA Staff, AC Thadhani, R Karumanchi, A Vatten, LJ AF Eskild, Anne Jeansson, Stig Jenum, Pal A. Staff, Anne C. Thadhani, Ravi Karumanchi, Ananth Vatten, Lars J. TI Levels of angiogenic factors in pregnancy and post-partum bleeding SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE Post-partum; bleeding; angiogenic factors; soluble fms-like tyrosine kinase-1 (sFlt-1); pregnancy ID PREECLAMPSIA AB We have studied if serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placenta growth factor (PlGF) in pregnancy could predict excess post-partum bleeding. In 392 normotensive singleton pregnancies, concentrations of sFlt-1 and PlGF in the first, second, and third trimester were compared between women with and without excess post-partum bleeding, defined as blood loss volume of at least 500 mL. Mean concentrations of sFlt-1 were consistently higher in all three trimesters among women who had excess post-partum bleeding compared to women without this, but significantly higher only in the second trimester. For PlGF, there were no significant differences between the groups. High concentrations of the anti-angiogenic factor sFlt-1 in maternal circulation during pregnancy may be associated with an increased risk of excess post-partum bleeding. C1 [Eskild, Anne] Akershus Univ Hosp, Dept Obstet & Gynecol, N-1478 Lorenskog, Norway. [Eskild, Anne; Jeansson, Stig; Staff, Anne C.] Univ Oslo, Fac Med, N-0316 Oslo, Norway. [Eskild, Anne] Norwegian Inst Publ Hlth, Div Mental Hlth, Oslo, Norway. [Jeansson, Stig] Ullevaal Univ Hosp, Dept Microbiol, Oslo, Norway. [Jenum, Pal A.] Asker & Baerum Hosp, Dept Microbiol, Baerum, Norway. [Staff, Anne C.] Ullevaal Univ Hosp, Dept Obstet & Gynecol, Oslo, Norway. [Thadhani, Ravi; Karumanchi, Ananth] Harvard Univ, Sch Med, Boston, MA USA. [Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. [Karumanchi, Ananth] Beth Israel Deaconess Med Ctr, Dept Med Obstet & Gynecol, Boston, MA 02215 USA. [Vatten, Lars J.] Norwegian Univ Sci & Technol, Dept Publ Hlth, N-7034 Trondheim, Norway. RP Eskild, A (reprint author), Akershus Univ Hosp, Dept Obstet & Gynecol, N-1478 Lorenskog, Norway. EM anne.eskild@medisin.uio.no FU Health Authority of Eastern Norway ('Helse Ost'); Norwegian Research Council FX This study was supported financially by the Health Authority of Eastern Norway ('Helse Ost'), and the Norwegian Research Council. NR 6 TC 3 Z9 3 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PY 2008 VL 87 IS 10 BP 1081 EP 1083 DI 10.1080/00016340802415622 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 374BF UT WOS:000261016500016 PM 18792843 ER PT J AU Graham, DP Cardon, AL AF Graham, David P. Cardon, Aaron L. TI An Update on Substance Use and Treatment following Traumatic Brain Injury SO ADDICTION REVIEWS 2008 SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article DE traumatic brain injury; substance abuse; prevalence; treatment outcome; review ID ALCOHOL-USE PATTERNS; ABUSE TREATMENT; HEAD-INJURY; DRUG-USE; REHABILITATION; PREVALENCE; OUTCOMES; PROGRAM; INDIVIDUALS; POPULATION AB Traumatic brain injury (TBI) is a leading cause of mortality and morbidity among young adults. Substance abusers constitute a disproportionate percentage of these patients. A history of substance abuse predicts increased disability, poorer prognosis, and delayed recovery. While consensus in the literature indicates that substance-abuse rates decline following injury, conflicting literature shows a significant history of brain injury in addicts. We reviewed the literature on substance abuse after TBI to explore the state of knowledge on TBI as a risk factor for substance abuse. While recent reviews regarding substance abuse in TBI patients concur that substance-abuse rates decline even after mild TBI, an emerging literature suggests mild TBI may cause subtle impairments in cognitive, executive, and decision-making functions that are often poorly recognized in early diagnosis and treatment. When combined with difficulties in psychosocial adjustment and coping skills, these impairments may increase the risk for chronic substance abuse in a subset of TBI patients. Preliminary results from veterans indicate these patterns hold in a combat-related post-traumatic stress disorder population with TBI. This increasingly prevalent combination presents a specific challenge in rehabilitation. While this comorbidity presents a challenge for the successful treatment and rehabilitation of both disorders, there is sparse evidence to recommend any specific treatment strategy for these individuals. Mild TBI and substance abuse are bidirectionally related both for risks and treatment. Further understanding the neuropsychiatric pathology and different effects of different types of injuries will likely improve the implementation of effective treatments for each of these two conditions. C1 [Graham, David P.] Michael E DeBakey VAMC 152, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res, Houston, TX 77030 USA. [Graham, David P.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Graham, David P.] Menninger Dept Psychiat & Behav Sci, Houston, TX USA. [Graham, David P.] Vet Affairs S Cent Mental Illness Res Educ & Clin, Houston, TX USA. [Cardon, Aaron L.] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. RP Graham, DP (reprint author), Michael E DeBakey VAMC 152, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res, 2002 Holcombe, Houston, TX 77030 USA. EM david.graham@med.va.gov RI Graham, David /J-1158-2014 NR 54 TC 47 Z9 48 U1 4 U2 15 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1141 BP 148 EP 162 DI 10.1196/annals.1441.029 PG 15 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BIM56 UT WOS:000260859100008 PM 18991956 ER PT J AU Berman, S O'Neill, J Fears, S Bartzokis, G London, ED AF Berman, Steven O'Neill, Joseph Fears, Scott Bartzokis, George London, Edythe D. TI Abuse of Amphetamines and Structural Abnormalities in the Brain SO ADDICTION REVIEWS 2008 SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article DE brain structure; drug abuse; amphetamine; methamphetamine; ecstasy ID VOXEL-BASED MORPHOMETRY; ABSTINENT METHAMPHETAMINE ABUSERS; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; VESICULAR MONOAMINE TRANSPORTERS; WHITE-MATTER HYPERINTENSITIES; DOPAMINERGIC DRUG TREATMENTS; TEMPORAL-LOBE EPILEPSY; GRAY-MATTER; DECISION-MAKING; LONG-TERM AB We review evidence that structural brain abnormalities are associated with abuse of amphetamines. A brief history of amphetamine use/abuse and evidence for toxicity is followed by a summary of findings from structural magnetic resonance imaging (MRI) studies of human subjects who had abused amphetamines and children who were exposed to amphetamines in utero. Evidence comes from studies that used a variety of techniques including manual tracing, pattern matching, voxel-based, tensor-based, or cortical thickness mapping, quantification of white matter signal hyperintensities, and diffusion tensor imaging. Ten studies compared controls to individuals who were exposed to methamphetamine. Three studies assessed individuals exposed to 3-4-methylenedioxymethamphetamine (MDMA). Brain structural abnormalities were consistently reported in amphetamine abusers, as compared to control subjects. These included lower cortical gray matter volume and higher striatal volume than control subjects. These differences might reflect brain features that could predispose to substance dependence. High striatal volumes might also reflect compensation for toxicity in the dopamine-rich basal ganglia. Prenatal exposure was associated with striatal volume that was below control values, suggesting that such compensation might not occur in utero. Several forms of white matter abnormality are also common and may involve gliosis. Many of the limitations and inconsistencies in the literature relate to techniques and cross-sectional designs, which cannot infer causality. Potential confounding influences include effects of pre existing risk/protective factors, development, gender, severity of amphetamine abuse, abuse of other drugs, abstinence, and differences in lifestyle. Longitudinal designs in which multimodal datasets are acquired and are subjected to multivariate analyses would enhance our ability to provide general conclusions regarding the associations between amphetamine abuse and brain structure. C1 [London, Edythe D.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. [London, Edythe D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90024 USA. [Berman, Steven; Bartzokis, George; London, Edythe D.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90024 USA. [Berman, Steven; Bartzokis, George] Greater Los Angeles VA Med Ctr, Los Angeles, CA USA. RP London, ED (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza,Box 175919, Los Angeles, CA 90024 USA. EM elondon@mednet.ucla.edu RI Bartzokis, George/K-2409-2013 FU National Institute on Drug Abuse [R01DA015179, R01DA020726, P20DA022539, R03DA20512, R21DA023192, M01RR00865] FX This work was supported in part by grants from the National Institute on Drug Abuse: R01DA015179, R01DA020726, and P20DA022539 (EDL); R03DA20512 and R21DA023192 JON); and M01RR00865 (UCLA GCRC). NR 133 TC 88 Z9 90 U1 5 U2 28 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1141 BP 195 EP 220 DI 10.1196/annals.1441.031 PG 26 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BIM56 UT WOS:000260859100011 PM 18991959 ER PT J AU Rotunda, RJ O'Farrell, TJ Murphy, M Babey, SH AF Rotunda, Robert J. O'Farrell, Timothy J. Murphy, Marie Babey, Susan H. TI Behavioral couples therapy for comorbid substance use disorders and combat-related posttraumatic stress disorder among male veterans: An initial evaluation SO ADDICTIVE BEHAVIORS LA English DT Article DE PTSD; couples therapy; alcohol dependence; dual-diagnosis; treatment outcome ID SCALES AB Outcomes after behavioral couples therapy (BCT) were compared for 19 dually diagnosed veterans with combat-related PTSD and a substance use disorder (SUD, primarily alcohol dependence) and 19 veterans with SUD only. Clients with and without comorbid PTSD had very similar pre-treatment clinical profiles on dimensions of substance misuse, relationship functioning, and psychological symptoms. Further, both PTSD and non-PTSD clients showed good compliance with BCT, attending a high number of BCT sessions, taking Antabuse, and going to AA. Finally, both PTSD and non-PTSD groups improved from before BCT to immediately after and 12 months after BCT. Specific improvements noted were increased relationship satisfaction and reductions in drinking, negative consequences of drinking, male-to-female violence, and psychological distress symptoms. Extent and pattern of improvement over time were similar whether the client had PTSD or not. The present results suggest that BCT may have promise in treating clients with comorbid SUD and combat-related PTSD. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Rotunda, Robert J.] Univ W Florida, Dept Psychol, Pensacola, FL 32514 USA. [Rotunda, Robert J.; O'Farrell, Timothy J.; Murphy, Marie] Harvard Univ, Sch Med, Dept Psychiat, Families & Addiction Program,VA Boston Healthcare, Brockton, MA 02401 USA. [Babey, Susan H.] Univ Calif Los Angeles, Sch Publ Hlth, Ctr Hlth Policy Res, Los Angeles, CA 90024 USA. RP Rotunda, RJ (reprint author), Univ W Florida, Dept Psychol, Pensacola, FL 32514 USA. EM rrotunda@uwf.edu; timothy_ofarrell@hms.harvard.edu FU NIAAA NIH HHS [R01 AA010356, K02 AA000234-04, K02 AA000234, K02AA0234, R01 AA008637] NR 16 TC 17 Z9 17 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD JAN PY 2008 VL 33 IS 1 BP 180 EP 187 DI 10.1016/j.addbeh.2007.06.001 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 265WD UT WOS:000253391600018 PM 17628345 ER PT J AU Wilens, TE AF Wilens, Timothy E. BE Kaminer, Y Bukstein, OG TI Attention-Deficit/Hyperactivity Disorder and Adolescent Substance Use Disorders SO ADOLESCENT SUBSTANCE ABUSE: PSYCHIATRIC COMORBIDITY AND HIGH-RISK BEHAVIORS LA English DT Article; Book Chapter ID DEFICIT HYPERACTIVITY DISORDER; NATIONAL-COMORBIDITY-SURVEY; 15-YEAR FOLLOW-UP; ILLICIT DRUG-USE; PSYCHIATRIC STATUS; ORAL METHYLPHENIDATE; COCAINE ABUSERS; YOUNG-ADULTS; HUMAN BRAIN; EXTRACELLULAR DOPAMINE C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Boston, MA 02115 USA. RP Wilens, TE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Boston, MA 02115 USA. NR 123 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-7890-3172-3 PY 2008 BP 195 EP 220 DI 10.1300/5785_09 PG 26 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA BUQ18 UT WOS:000290025800009 ER PT S AU McLaughlin, KA Wucherpfennig, KW AF McLaughlin, Katherine A. Wucherpfennig, Kai W. BE Alt, FW TI B cells and autoantibodies in the pathogenesis of multiple sclerosis and related inflammatory demyelinating diseases SO ADVANCES IN IMMUNOLOGY, VOL 98 SE Advances in Immunology LA English DT Review; Book Chapter ID MYELIN OLIGODENDROCYTE GLYCOPROTEIN; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CLINICALLY ISOLATED SYNDROMES; LYMPHOTOXIN BETA-RECEPTOR; TUMOR-NECROSIS-FACTOR; CEREBROSPINAL-FLUID; T-CELLS; NEUROMYELITIS-OPTICA AB Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). The mainstream view is that MS is caused by an autoimmune attack of the CNS myelin by myelin-specific CD4 T cells, and this perspective is supported by extensive work in the experimental autoimmune encephalomyelitis (EAE) model of MS as welt as immunological and genetic studies in humans. However, it is important to keep in mind that other cell populations of the immune system are also essential in the complex series of events leading to MS, as exemplified by the profound clinical efficacy of B cell depletion with Rituximab, This review discusses the mechanisms by which B cells contribute to the pathogenesis of MS and dissects their role as antigen-presenting cells (APCs) to T cells with matching antigen specificity. the production of proinflammatory cytokines and chemokines, as well as the secretion of autoantibodies that target structures on the myelin sheath and the axon. Mechanistic dissection of the interplay between T cells and B cells in MS may permit the development of B cell based therapies that do not require depletion of this important cell population. C1 [McLaughlin, Katherine A.; Wucherpfennig, Kai W.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [McLaughlin, Katherine A.; Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA. [Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP McLaughlin, KA (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. FU NIAID NIH HHS [P01 AI045757] NR 168 TC 48 Z9 48 U1 3 U2 10 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 BN 978-0-12-374331-2 J9 ADV IMMUNOL JI Adv.Immunol. PY 2008 VL 98 BP 121 EP 149 DI 10.1016/S0065-2776(08)00404-5 PG 29 WC Immunology SC Immunology GA BIH29 UT WOS:000259482100004 PM 18772005 ER PT S AU Perlot, T Alt, FW AF Perlot, Thomas Alt, Frederick W. BE Alt, FW Austen, KF Honjo, T Melchers, F Uhr, JW Unanue, ER TI Cis-Regulatory Elements and Epigenetic Changes Control Genomic Rearrangements of the IgH Locus SO ADVANCES IN IMMUNOLOGY, VOL 99 SE Advances in Immunology LA English DT Review; Book Chapter ID HEAVY-CHAIN LOCUS; B-CELL-DEVELOPMENT; CLASS-SWITCH RECOMBINATION; ANTISENSE INTERGENIC TRANSCRIPTION; MATRIX-ATTACHMENT REGIONS; VH GENE SEGMENTS; TCR-BETA LOCUS; V(D)J RECOMBINATION; ALLELIC EXCLUSION; INTRONIC ENHANCER AB Immunoglobulin variable region exons are assembled from discontinuous variable (V), diversity (D), and joining (J) segments by the process of V(D recombination. V(D)J rearrangements of the immunoglobulin heavy chain (IgH) locus are tightly controlled in a tissue-specific, ordered and allele-specific manner by regulating accessibility of V, D, and J segments to the recombination activating gene proteins which are the specific components of the V(D recombinase. in this review we discuss recent advances and established models brought forward to explain the mechanisms underlying accessibility control of V(D)J recombination, including research on germline transcripts, spatial organization, and chromatin modifications of the immunoglobulin heavy chain (IgH) locus. Furthermore, we review the functions of well-described and potential new cis-regulatory elements with regard to processes such as V(D recombination, allelic exclusion, and IgH class switch recombination. C1 [Perlot, Thomas; Alt, Frederick W.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,Immune Dis Inst, Boston, MA 02115 USA. [Perlot, Thomas; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Perlot, Thomas] Univ Vienna, Vienna, Austria. RP Perlot, T (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,Immune Dis Inst, Boston, MA 02115 USA. FU Howard Hughes Medical Institute; NCI NIH HHS [P01 CA092625, P01CA092625-05]; NIAID NIH HHS [2P01AI031541-15, P01 AI031541, R01 AI020047, R37 AI020047, R37 AI020047-17] NR 156 TC 38 Z9 38 U1 1 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 BN 978-0-12-374325-1 J9 ADV IMMUNOL JI Adv.Immunol. PY 2008 VL 99 BP 1 EP 32 DI 10.1016/S0065-2776(08)00601-9 PG 32 WC Immunology SC Immunology GA BIR24 UT WOS:000262126600001 PM 19117530 ER PT S AU Goldmann, WH Bechinger, B Lele, T AF Goldmann, Wolfgang H. Bechinger, Burkhard Lele, Tanmay BE Liu, AL TI CYTOSKELETAL PROTEINS AT THE LIPID MEMBRANE SO ADVANCES IN PLANAR LIPID BILAYERS AND LIPOSOMES, VOL 6 SE Advances in Planar Lipid Bilayers and Liposomes LA English DT Article; Book Chapter ID SOLID-STATE NMR; CHEMICAL-SHIFT TENSORS; DIFFERENTIAL SCANNING CALORIMETRY; ORIENTED PHOSPHOLIPID-BILAYERS; MAGAININ ANTIBIOTIC PEPTIDES; NUCLEAR-MAGNETIC-RESONANCE; ANGLE-SPINNING NMR; FOCAL ADHESIONS; ALPHA-ACTININ; PHOSPHATIDYLCHOLINE MEMBRANES AB The interface at the cell membrane and cytosol offers a wealth of possibilities for intermolecular interactions. Molecular anchors, -bridges, -transmembrane connectors as well as cascades of proteins inside the cell regulate the bidirectional exchange of information between the cell and extracellular environment. Previously, little attention has been given to lipids that are essential for the membrane architecture and for the regulation and function of membrane-associated cytoskeletal proteins. The emergence of new biophysical techniques has spurred rapid acceleration in the ability of researchers to investigate and understand protein-lipid membrane interactions in artificial systems as well as in cells. Stopped-flow kinetics, differential scanning calorimetry (DSC), solid-state nuclear magnetic resonance (NMR) spectroscopy as well as fluorescence recovery after photobleaching (FRAP) will be described and their application will be discussed. C1 [Goldmann, Wolfgang H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. [Goldmann, Wolfgang H.] Univ Erlangen Nurnberg, Ctr Med Phys & Technol, Biophys Grp, D-91052 Erlangen, Germany. [Bechinger, Burkhard] Univ Strasbourg 1, CNRS, Inst Chim, UMR LC3 7177, F-67070 Strasbourg, France. [Lele, Tanmay] Univ Florida, Dept Chem Engn, Gainesville, FL 32611 USA. RP Goldmann, WH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. EM wgoldmann@biomed.uni-erlangen.de NR 102 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1554-4516 BN 978-0-08-055453-2 J9 ADV PLANAR LIP BILAY PY 2008 VL 6 BP 227 EP 255 DI 10.1016/S1554-4516(07)06008-5 PG 29 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BCQ60 UT WOS:000311033100009 ER PT J AU Lu, M Safren, SA Skolnik, PR Rogers, WH Coady, W Hardy, H Wilson, IB AF Lu, Minyi Safren, Steven A. Skolnik, Paul R. Rogers, William H. Coady, William Hardy, Helene Wilson, Ira B. TI Optimal recall period and response task for self-reported HIV medication adherence SO AIDS AND BEHAVIOR LA English DT Article DE patient compliance; HIV infection; HIV infection; drug therapy; questionnaires ID ANTIRETROVIRAL THERAPY ADHERENCE; HEALTH LITERACY; PROTEASE INHIBITORS; DECISION-MAKING; NUMERACY; POPULATION; INFECTION; CARE; INSTRUMENTS; RELIABILITY AB Self-reported measures of antiretroviral adherence vary greatly in recall time periods and response tasks. To determine which time frame is most accurate, we compared 3-, 7-day, and 1-month self-reports with data from medication event monitoring system (MEMS). To determine which response task is most accurate we compared three different 1-month self-report tasks (frequency, percent, and rating) to MEMS. We analyzed 643 study visits made by 156 participants. Over-reporting (self-report minus MEMS) was significantly less for the 1-month recall period (9%) than for the 3 (17%) or 7-day (14%) periods. Over-reporting was significantly less for the 1-month rating task (3%) than for the 1-month frequency and percent tasks (both 12%). We conclude that 1-month recall periods may be more accurate than 3- or 7-day periods, and that items that ask respondents to rate their adherence may be more accurate than those that ask about frequencies or percents. C1 [Lu, Minyi; Rogers, William H.; Coady, William; Wilson, Ira B.] Tufts Univ New England Med Ctr, Dept Med, Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 USA. [Safren, Steven A.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp,Fenway Community Hlth Ctr, Boston, MA 02115 USA. [Skolnik, Paul R.; Hardy, Helene] Boston Univ, Ctr HIV AIDS Care & Res, Med Ctr, Boston, MA 02215 USA. RP Wilson, IB (reprint author), Tufts Univ New England Med Ctr, Dept Med, Inst Clin Res & Hlth Policy Studies, 345,750 Washington St, Boston, MA 02111 USA. EM iwilson@tufts-nemc.org RI Wilson, Ira/F-9190-2016 OI Wilson, Ira/0000-0002-0246-738X FU NCRR NIH HHS [K24 RR020300, M01-RR00054]; NIAID NIH HHS [P30 AI42853]; NIDA NIH HHS [R01 DA015679, R01DA015679] NR 40 TC 133 Z9 133 U1 3 U2 5 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 JAN PY 2008 VL 12 IS 1 BP 86 EP 94 DI 10.1007/s10461-007-9261-4 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 254BZ UT WOS:000252562700009 PM 17577653 ER PT J AU Mimiaga, MJ Skeer, M Mayer, KH Safren, SA AF Mimiaga, M. J. Skeer, M. Mayer, K. H. Safren, S. A. TI Study participation as a social group influencing sexual behaviours in an HIV-prevention trial for men who have sex with men SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; BASE-LINE DATA; RISK BEHAVIORS; SAFER-SEX; DRUG-USE; EXPLORE; ACCEPTABILITY; INTERVENTION; UTILITY; GAY AB Perceived group membership, perceptions about accompanying group norms and the degree to which a person identifies with a social group are predictive of a wide range of human behaviours. Behavioural clinical trials in general, and HIV-prevention intervention trials in particular, however, have not examined the degree to which individuals who join a large behavioural study (and hence, a group) may, in an unanticipated way, develop a sense of social identity related to the study, and how this identity or associated group norms may influence participants' behaviours and, potentially, study outcomes. Project EXPLORE was a large-scale behavioural intervention trial in six US cities to prevent HIV seroconversion among men who have sex with men (MSM) (EXPLORE Study Team, 2004). We previously found that participants (examined at one study site) were more likely to engage in high-risk sexual activities with other MSM who were EXPLORE participants than other partners. The present ancillary study (n=271) sought to examine the degree to which perceived group membership, group identity and group norms among EXPLORE study participants was associated with sexual behaviour with other EXPLORE participants, high-risk sexual behaviours with other EXPLORE participants and intentions to engage in high-risk sex with other EXPLORE participants. A principal components analysis of a 14-item scale assessing perceived group membership and norms regarding being part of EXPLORE yielded six principal components (PCs): PC1: perception that EXPLORE participants engage in safer sex; PC2: social comfort with EXPLORE participants; PC3: perceived group identity with EXPLORE; PC4: trust of other EXPLORE participants; PC5: perception that EXPLORE participants are cunning; and PC6: feeling detached from EXPLORE. Social comfort with other EXPLORE participants (OR = 1.24; p = 0.013) and trust of other EXPLORE participants (OR = 1.44; p=0.003) was significantly associated with a higher odds of having sex with another EXPLORE participant. Feeling detached from EXPLORE (OR = 0.56; p=0.020) was significantly associated with a lower odds of engaging in high-risk sexual behaviour with other EXPLORE participants. Regarding intentions to engage in high-risk sexual behaviour with other EXPLORE participants, social comfort with EXPLORE participants (OR = 1.39; p < 0.001) and trust of other EXPLORE participants (OR = 1.30; p0.027) were significantly associated with higher odds of this outcome and the perception that EXPLORE participants are cunning (OR = 0.66; p < 0.004) and feeling detached from EXPLORE (OR = 0.68; p < 0.007) were significantly associated with lower odds of this outcome. Final models controlled for potential confounders found to be statistically significant in the bivariate analyses. These findings suggest that large-scale studies such as EXPLORE may result in participant's perceptions about group membership, identity and norms, and that these perceptions can influence study outcomes. C1 [Mimiaga, M. J.; Skeer, M.; Mayer, K. H.; Safren, S. A.] Fenway Inst, Res & Evaluat Dept, Fenway Community Hlth, Boston, MA 02199 USA. [Mimiaga, M. J.; Safren, S. A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Skeer, M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Mayer, K. H.] Brown Univ, Sch Med, Miriam Hosp, Providence, RI 02912 USA. RP Mimiaga, MJ (reprint author), Fenway Inst, Res & Evaluat Dept, Fenway Community Hlth, Prundential Tower,4th Floor,800 Boylston St, Boston, MA 02199 USA. EM mmimiaga@fenwayhealth.org FU NIAID NIH HHS [5 U01 AI46749, N01 AI35176, U01 AI48040, N01 AI45200] NR 37 TC 4 Z9 4 U1 2 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2008 VL 20 IS 3 BP 346 EP 355 DI 10.1080/09540120701562070 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 277LJ UT WOS:000254213800012 PM 18351483 ER PT J AU Jean-Jacques, M Walensky, RP Aaronson, WH Chang, Y Freedberg, KA AF Jean-Jacques, M. Walensky, R. P. Aaronson, W. H. Chang, Y. Freedberg, K. A. TI Late diagnosis of HIV infection at two academic medical centers: 1994-2004 SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE HIV infections/testing; HIV infections/epidemiology; HIV infections/diagnosis ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; UNITED-STATES; COST-EFFECTIVENESS; CARE; SETTINGS; ROUTINE; DELAY; MORTALITY; HAART AB Over the last decade, there has been increased attention to the role of earlier HIV testing in the United States. Our objective was to determine if this has translated into changes in the proportion of inpatients with advanced disease at the time of initial HIV diagnosis. We identified inpatients discharged with a new diagnosis of HIV infection or AIDS between 1994 and 2004 at two academic medical centers. We examined trends in initial CD4 count at diagnosis over three time periods: 1994-1996, 1997-2000 and 2001-2004. Between 1994 and 2004, 235 inpatients were newly diagnosed with HIV infection or AIDS in the two centers. For the 217 patients with available CD4 count data, the median initial CD4 count was 41/mu l (interquartile range 19-138/mu l). Of the 217 patients, 184(85%) had CD4 <= 200/mu l and 119/217 (55%) had CD4 <= 50/mu l. There were no significant differences in median CD4 count by time period. A large majority of inpatients with newly diagnosed HIV infection at two academic medical centers between 1994 and 2004 had signs of advanced immunodeficiency. Over this recent 11-year period there was no evidence that inpatients with a new HIV diagnosis were identified at earlier stages of disease. C1 [Jean-Jacques, M.] Univ Chicago Hosp, Dept Med, Sect Gen Med, Chicago, IL 60637 USA. [Walensky, R. P.; Aaronson, W. H.; Chang, Y.; Freedberg, K. A.] Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. [Walensky, R. P.; Freedberg, K. A.] Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA. [Walensky, R. P.] Brigham & Womens Hosp, Div Infect Dis, Dept Med, Boston, MA 02115 USA. [Walensky, R. P.; Freedberg, K. A.] Harvard Univ, Sch Med, Harvard Ctr AIDS Res CFAR, Boston, MA USA. RP Jean-Jacques, M (reprint author), Univ Chicago Hosp, Dept Med, Sect Gen Med, Chicago, IL 60637 USA. EM Muriel.Jean-Jacques@uchospitals.edu OI Walensky, Rochelle P./0000-0002-8795-379X FU NIAID NIH HHS [R37AI42006, K23 AI001794, K23 AI01794, P30 AI060354, R37 AI042006, P30 AI060345, K24 AI062476] NR 31 TC 6 Z9 7 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2008 VL 20 IS 8 BP 977 EP 983 DI 10.1080/09540120701767257 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 345DZ UT WOS:000258977600012 PM 18608072 ER PT J AU Ngumbela, KC Day, CL Mncube, Z Nair, K Ramduth, D Thobakgale, C Moodley, E Reddy, S de Pierres, C Mkhwanazi, N Bishop, K van der Stok, M Ismail, N Honeyborne, I Crawford, H Kavanagh, DG Rousseau, C Nickle, D Mullins, J Heckerman, D Korber, B Coovadia, H Kiepiela, P Goulder, PJR Walker, BD AF Ngumbela, K. C. Day, C. L. Mncube, Z. Nair, K. Ramduth, D. Thobakgale, C. Moodley, E. Reddy, S. de Pierres, C. Mkhwanazi, N. Bishop, K. van der Stok, M. Ismail, N. Honeyborne, I. Crawford, H. Kavanagh, D. G. Rousseau, C. Nickle, D. Mullins, J. Heckerman, D. Korber, B. Coovadia, H. Kiepiela, P. Goulder, P. J. R. Walker, B. D. TI Targeting of a CD8 T cell Env epitope presented by HLA-B*5802 is associated with markers of HIV disease progression and lack of selection pressure SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; VIRAL LOAD; CLASS-I; HLA-B; LYMPHOCYTE RESPONSES; ANTIRETROVIRAL THERAPY; IMMUNE-RESPONSES; ESCAPE VARIANTS; INFECTION; VIREMIA AB In HIV-infected persons, certain HLA class I alleles are associated with effective control of viremia, while others are associated with rapid disease progression. Among the most divergent clinical outcomes are the relatively good prognosis in HLA-B*5801 expressing persons and poor prognosis with HLA-B*5802. These two alleles differ by only three amino acids in regions involved in HLA-peptide recognition. This study evaluated a cohort of over 1000 persons with chronic HIV clade C virus infection to determine whether clinical outcome differences associated with B*5801 (n = 93) and B*5802 (n = 259) expression are associated with differences in HIV-1-specific CD8(+) T cell responses. The overall breadth and magnitude of HIV-1-specific CD8(+) T cell responses were lower in persons expressing B*5802, and epitope presentation by B*5802 contributed significantly less to the overall response as compared to B*5801-restricted CD8(+) T cells. Moreover, viral load in B*5802-positive persons was higher and CD4 cell counts lower when this allele contributed to the overall CD8(+) T cell response, which was detected exclusively through a single epitope in Env. In addition, persons heterozygous for B*5802 compared to persons homozygous for other HLA-B alleles had significantly higher viral loads. Viral sequencing revealed strong selection pressure mediated through B*5801-restricted responses but not through B*5802. These data indicate that minor differences in HLA sequence can have a major impact on epitope recognition, and that selective targeting of Env through HLA-B*5802 is at least ineffectual if not actively adverse in the containment of viremia. These results provide experimental evidence that not all epitope-specific responses contribute to immune containment, a better understanding of which is essential to shed light on mechanisms involved in HIV disease progression. C1 [Ngumbela, K. C.; Day, C. L.; Mncube, Z.; Nair, K.; Ramduth, D.; Thobakgale, C.; Moodley, E.; Reddy, S.; de Pierres, C.; Mkhwanazi, N.; Bishop, K.; van der Stok, M.; Ismail, N.; Honeyborne, I.; Coovadia, H.; Kiepiela, P.; Goulder, P. J. R.; Walker, B. D.] Univ Kwazulu Natal, Nelson Mandela Sch Med, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4013 Congella, Durban, South Africa. [Day, C. L.; Kavanagh, D. G.; Goulder, P. J. R.; Walker, B. D.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. [Honeyborne, I.; Crawford, H.; Goulder, P. J. R.] Nuffield Dept Med, Dept Paediat, Oxford OX1 3SY, England. [Rousseau, C.; Nickle, D.; Mullins, J.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Heckerman, D.] Microsoft Res, Machine Learning & Appl Stat Grp, Redmond, WA 98052 USA. [Korber, B.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA. [Korber, B.] Santa Fe Inst, Santa Fe, NM 87501 USA. [Walker, B. D.] Howard Hughes Med Inst, Chevy Chase, MD 20185 USA. RP Walker, BD (reprint author), Univ Kwazulu Natal, Nelson Mandela Sch Med, Doris Duke Med Res Inst, HIV Pathogenesis Programme, 719 Umbilo Rd, ZA-4013 Congella, Durban, South Africa. EM bwalker@partners.org RI Day, Cheryl/J-9844-2012; OI Bishop, Karen/0000-0003-4935-7708; Korber, Bette/0000-0002-2026-5757 FU NIAID NIH HHS [AI067072, AI28568, AI46995, F32 AI058457, N-01-AI-15442, P30 AI027757] NR 62 TC 42 Z9 42 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN PY 2008 VL 24 IS 1 BP 72 EP 82 DI 10.1089/aid.2007.0124 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 254PH UT WOS:000252598000010 PM 18275350 ER PT J AU Pasinetti, GM Hiller-Sturmhofel, S AF Pasinetti, Giulio M. Hiller-Sturmhoefel, Susanne TI Systems biology in the study of neurological disorders: Focus on Alzheimer's disease SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE Alzheimer's disease (AD); cognitive impairment; dementia; genetic risk factors; biomarkers; complementary DNA (cDNA) microarray analysis; protein array analysis; systems biology; proteomics; alcohol and other drug effects (AODEs) ID MOUSE MODEL; EXPRESSION; BRAIN; RISK; NEUROPATHOLOGY; DEPOSITION; MICROARRAY; ARRAYS AB Systems biology approaches may be useful for studying the mechanisms underlying alcohol's harmful effects on the brain. Such approaches already are used in the study of Alzheimer's disease (AD), a progressive neurodegenerative disorder that, with the overall increase in life expectancy, will affect an increasing proportion of the population and become an increasingly serious public health concern. Systems biology approaches such as complementary DNA (cDNA) microarray analyses have helped identify several genes whose expression is altered in patients exhibiting the earliest stages of AD. Several of these genes are involved in the release of messenger molecules from the ends of nerve cells (Le, in synaptic vesicle functioning), and their particular role in AD must be investigated further using conventional molecular biological approaches. Similarly, protein array analyses have identified candidate proteins that may play a role in the development of AD. Finally, proteomic approaches, such as certain mass spectrometry techniques, have been used to search for biomarkers of the progression from normal cognitive functioning to mild cognitive impairment and AD, which eventually may allow early and reliable diagnosis of the disease. These approaches already have yielded some candidate molecules whose validity and reliability as biomarkers of AD, however, still need to be confirmed. C1 [Pasinetti, Giulio M.] Mt Sinai Sch Med, Ctr Excellence Res Complementary & Alternat Med A, Dept Psychiat, New York, NY USA. [Pasinetti, Giulio M.] James J Peters Vet Affairs Med Ctr, Basic & Biomed Res & Training Program, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Ctr Excellence Res Complementary & Alternat Med A, Dept Psychiat, New York, NY USA. NR 19 TC 4 Z9 4 U1 0 U2 0 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2008 VL 31 IS 1 BP 60 EP 65 PG 6 WC Substance Abuse SC Substance Abuse GA 326LH UT WOS:000257660100007 PM 23584752 ER PT J AU Hitzemann, R Oberbeck, D AF Hitzemann, Robert Oberbeck, Denesa TI STRATEGIES TO STUDY THE NEUROSCIENCE OF ALCOHOLISM: INTRODUCTION SO ALCOHOL RESEARCH & HEALTH LA English DT Editorial Material C1 [Hitzemann, Robert; Oberbeck, Denesa] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Hitzemann, Robert; Oberbeck, Denesa] Portland VA Med Ctr, Res Serv, Portland, OR USA. RP Hitzemann, R (reprint author), Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. FU NIAAA NIH HHS [P60 AA010760] NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2008 VL 31 IS 3 BP 231 EP 232 PG 2 WC Substance Abuse SC Substance Abuse GA 374TL UT WOS:000261066500004 PM 23584864 ER PT J AU Oberbeck, D AF Oberbeck, Denesa TI LASER-ASSISTED MICRODISSECTION SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE Alcohol-related research; alcohol and other drug effects and consequences; brain; brain cells; brain function; brain structure; laser-assisted microdissection (LMD); laser capture; laser microbeam; reverse-transcription polymerase chain reaction (RT-PCR); expression profiling ID CONSUMPTION; AMYGDALA; C57BL/6J; ETHANOL C1 [Oberbeck, Denesa] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Oberbeck, Denesa] Portland VA Med Ctr, Res Serv, Portland, OR 97201 USA. RP Oberbeck, D (reprint author), Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2008 VL 31 IS 3 BP 249 EP 250 PG 2 WC Substance Abuse SC Substance Abuse GA 374TL UT WOS:000261066500009 PM 23584869 ER PT J AU Hitzemann, R Belknap, JK McWeeney, SK AF Hitzemann, Robert Belknap, John K. McWeeney, Shannon K. TI QUANTITATIVE TRAIT LOCUS ANALYSIS: MULTIPLE CROSS AND HETEROGENEOUS STOCK MAPPING SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE Genetic theory of alcohol and other drug use; genetic factors; environmental factors; behavioral phenotype; behavioral trait; quantitative trait gene (QTG); inbred animal strains; recombinant inbred (RI) mouse strains; quantitative traits; quantitative trait locus (QTL) mapping; multiple cross mapping (MCM); heterogeneous stock (HS) mapping; microsatellite mapping; animal models ID RECOMBINANT INBRED STRAINS; LABORATORY MICE; COMPLEX TRAITS; MOUSE GENOME; GENETIC-MAP; RESOLUTION; IDENTIFICATION; INTERCROSS; BEHAVIOR; ALCOHOL C1 [Hitzemann, Robert; Belknap, John K.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Hitzemann, Robert; Belknap, John K.] Portland VA Med Ctr, Res Serv, Portland, OR USA. [McWeeney, Shannon K.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Preventat Med, Div Biostat, Portland, OR 97201 USA. [McWeeney, Shannon K.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. RP Hitzemann, R (reprint author), Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. NR 35 TC 3 Z9 3 U1 0 U2 1 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2008 VL 31 IS 3 BP 261 EP 265 PG 5 WC Substance Abuse SC Substance Abuse GA 374TL UT WOS:000261066500013 PM 23584873 ER PT J AU Denmark, DL Milner, LC Buck, KJ AF Denmark, Deaunne L. Milner, Lauren C. Buck, Karl J. TI INTERVAL-SPECIFIC CONGENIC ANIMALS FOR HIGH-RESOLUTION QUANTITATIVE TRAIT LOCI MAPPING SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE Genetic theory of alcohol and other drug use; genetics and heredity; behavioral phenotypes, genetic trait, quantitative traits; quantitative trait locus (QTL); QTL mapping; congenics; interval-specific congenics (ISCs); congenic strains; animal models ID ALCOHOL PHYSICAL-DEPENDENCE; RECOMBINANT INBRED MICE; COMPLEX TRAITS; WITHDRAWAL; GENES; IDENTIFICATION; CONFIRMATION; SENSITIVITY C1 [Denmark, Deaunne L.] Portland VA Med Ctr, Grad Program Neurosci, Portland, OR USA. [Buck, Karl J.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Milner, Lauren C.] Portland VA Med Ctr, Behav Neurosci Program, Portland, OR USA. RP Denmark, DL (reprint author), Portland VA Med Ctr, Grad Program Neurosci, Portland, OR USA. FU NIAAA NIH HHS [P60 AA010760-16, R01 AA011114-12, R01 AA011114, P60 AA010760]; NIDA NIH HHS [R01 DA005228, R01 DA005228-17] NR 14 TC 1 Z9 1 U1 0 U2 1 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2008 VL 31 IS 3 BP 266 EP 269 PG 4 WC Substance Abuse SC Substance Abuse GA 374TL UT WOS:000261066500014 PM 23584874 ER PT J AU Walter, NAR McWeeney, SK Peters, ST Belknap, JK Hitzemann, R Buck, KJ AF Walter, Nicole A. R. McWeeney, Shannon K. Peters, Sandra T. Belknap, John K. Hitzemann, Robert Buck, Kari J. TI SINGLE-NUCLEOTIDE POLYMORPHISM MASKING SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE expression; genome; genetic analysis; microarray analysis; singular nucleotide polymorphism (SNP); SNP masking; mouse genome; laboratory mice; animal models C1 [Walter, Nicole A. R.] Oregon Hlth & Sci Univ, Dept Behav Sci, Portland, OR 97201 USA. [McWeeney, Shannon K.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Preventat Med, Div Biostat, Portland, OR 97201 USA. [McWeeney, Shannon K.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. [Peters, Sandra T.] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97201 USA. [Belknap, John K.; Hitzemann, Robert; Buck, Kari J.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Belknap, John K.; Hitzemann, Robert] Portland VA Med Ctr, Res Serv, Portland, OR USA. RP Walter, NAR (reprint author), Oregon Hlth & Sci Univ, Dept Behav Sci, Portland, OR 97201 USA. FU NIAAA NIH HHS [P60 AA010760]; NIDA NIH HHS [R01 DA005228] NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2008 VL 31 IS 3 BP 270 EP 271 PG 2 WC Substance Abuse SC Substance Abuse GA 374TL UT WOS:000261066500015 PM 23584875 ER PT J AU Singal, AK Rosman, AS Post, JB Bauman, WA Spungen, AM Korsten, MA AF Singal, A. K. Rosman, A. S. Post, J. B. Bauman, W. A. Spungen, A. M. Korsten, M. A. TI The renal safety of bowel preparations for colonoscopy: a comparative study of oral sodium phosphate solution and polyethylene glycol SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID PROSPECTIVE TRIAL; LAVAGE SOLUTION; FAILURE; NEPHROCALCINOSIS; COLON; MULTICENTER; EFFICACY; IMPACT; PEG AB Background Rare cases of nephrotoxicity have been reported with oral sodium phosphate solution (OSPS). Aim To evaluate whether OSPS is associated with changes in renal function. Methods A chart review performed on 311 patients who had colonoscopy at the James J. Peters VA Medical Centre prepared with either OSPS (n = 157) or polyethylene glycol (PEG) (n = 154). Patients had a baseline serum creatinine <= 1.5 mg/dL. Effect of bowel preparation on the renal function was evaluated by measuring the absolute change in levels of serum creatinine and the proportion of patients who developed a 50% or more increase above their baseline serum creatinine value. Results Oral sodium phosphate solution resulted in a slight increase in serum creatinine from 1.0 +/- 0.02 to 1.1 +/- 0.02 mg/dL (P = 0.07) and PEG resulted in a small decrease in serum creatinine from 1.1 +/- 0.02 to 1.0 +/- 0.03 mg/dL (P = 0.03). The absolute change in serum creatinine was slightly higher with OSPS than with PEG (0.04 +/- 0.02 vs. -0.05 +/- 0.02 mg/dL; P = 0.005). However, the proportion of patients who had a >= 50% increase above their baseline creatinine was similar (OSPS vs. PEG, 5% vs. 3%, P = 0.77). Conclusions Oral sodium phosphate solution was associated with a slight increase in serum creatinine, which was not clinically significant. Renal toxicity from OSPS appears to be minimal when used in patients with serum creatinine value <1.5 mg/dL. C1 [Singal, A. K.; Rosman, A. S.; Post, J. B.; Bauman, W. A.; Korsten, M. A.] James J Peters Vet Affairs Med Ctr, Dept Med, Bronx, NY USA. [Rosman, A. S.; Korsten, M. A.] James J Peters Vet Affairs Med Ctr, Div Gastroenterol, Bronx, NY USA. [Post, J. B.] Mt Sinai Sch Med, Div Nephrol, New York, NY USA. [Bauman, W. A.; Korsten, M. A.] James J Peters VA Med Ctr, Dev Ctr Excellence Med Consequences Spinal Cord, Dept Vet Affairs Rehabilitat Res, Bronx, NY USA. RP Korsten, MA (reprint author), James J Peters Vet Affairs Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM mark.korsten@va.gov NR 22 TC 30 Z9 30 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD JAN 1 PY 2008 VL 27 IS 1 BP 41 EP 47 DI 10.1111/j.1365-2036.2007.03558.x PG 7 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 265UB UT WOS:000253385300005 PM 17956596 ER PT J AU Banerji, A Oren, E Hesterberg, P Hsu, Y Camargo, CA Wong, JT AF Banerji, Aleena Oren, Eyal Hesterberg, Paul Hsu, Yulan Camargo, Carlos A., Jr. Wong, Johnson T. TI Ten-year study of causes of moderate to severe angioedema seen by an inpatient allergy/immunology consult service SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article DE allergy; angioedema; angiotensin-converting enzyme inhibitors; aspirin; drug allergy; immunology; intubation; mast cell; NSAID ID CONVERTING ENZYME-INHIBITORS; HISTAMINE-RELEASE; PERIOPERATIVE ANGIOEDEMA; ACE-INHIBITORS; MAST-CELLS; LATE-ONSET; ANGIOTENSIN; THERAPY AB The causes of angioedema are not well described, especially in the inpatient setting. The purpose of this study was to examine the causes of moderate to severe angioedema in patients requiring inpatient treatment. We performed a retrospective review in patients requiring inpatient consultation by the Division of Allergy and Immunology at our institution between 1995 and 2004. We focused on potential interactions among medications that elicited life-threatening angioedema requiring intubation. The allergy/immunology service was consulted on 69 patients with moderate to severe angioedema. Medications were the most common cause of angioedema (n = 64, 93%). In most cases (n = 46, 67%), the angioedema was attributed to two or more medications. Patients previously stable on ACE inhibitors (ACEI), aspirin (ASA), or non-steroidal anti-inflammatory drugs (NSAIDs) appeared more likely to develop angioedema soon after the addition of another drug (i.e., ACEI, ASAINSAIDs, direct mast cell degranulators, and antibiotics). ACEL ASA/NSAID, and direct mast cell degranulators were contributing causes in 36 patients (56%), 45 patients (70%), and 23 patients (36%), respectively. Twenty patients required intubation, 14 (70%) patients were on ACEI, 12 (60%) patients were on ASA/NSAID, and 7 (35%) patients were on direct mast cell degranulators. ACEL ASA/NSAID, or direct mast cell degranulators were a cause in 95% (n = 19) of patients requiring intubation. The combination of ACEI and ASA/NSAID was the most frequent cause of angioedema among all patients (n = 17, 25%) and those requiring intubation (n = 8, 40%). Moderate to severe angioedema often is a result of interactions between two or more medications involved in different pathways causing angioedema. In particular, combinations of ACEI, ASA/NSAID, or direct mast cell degranulators may lead to life-threatening angioedema requiring intubation. C1 [Banerji, Aleena; Oren, Eyal; Hesterberg, Paul; Hsu, Yulan; Wong, Johnson T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Dept Emergency Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Banerji, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Rheumatol Allergy & Immunol, Cox 201,100 Blossom St, Boston, MA 02114 USA. EM abanerji@partners.org NR 20 TC 18 Z9 18 U1 1 U2 2 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD JAN-FEB PY 2008 VL 29 IS 1 BP 88 EP 92 DI 10.2500/aap2008.29.3085 PG 5 WC Allergy SC Allergy GA 264XJ UT WOS:000253323400015 PM 18302843 ER PT J AU Jarvik, L Larue, A Blacker, D Gatz, M Kawas, C McArdle, JJ Morris, JC Mortimer, JA Ringman, JM Ercoli, L Freimer, N Gokhman, I Manly, JJ Plassman, BL Rasgon, N Roberts, JS Sunderland, T Swan, GE Wolf, PA Zonderman, AB AF Jarvik, Lissy LaRue, Asenath Blacker, Deborah Gatz, Margaret Kawas, Claudia McArdle, John J. Morris, John C. Mortimer, James A. Ringman, John M. Ercoli, Linda Freimer, Nelson Gokhman, Izabella Manly, Jennifer J. Plassman, Brenda L. Rasgon, Natalie Roberts, Jeffrey Scott Sunderland, Trey Swan, Gary E. Wolf, Phillip A. Zonderman, Alan B. TI Children of persons with Alzheimer disease - What does the future hold? SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Review DE Alzheimer disease offspring; risk factors ID APOLIPOPROTEIN-E GENOTYPE; MILD COGNITIVE IMPAIRMENT; ELDERLY AFRICAN-AMERICANS; OLDER MEXICAN-AMERICANS; POPULATION-BASED COHORT; APOE EPSILON-4 ALLELE; MIDDLE-AGED CHILDREN; CEREBROSPINAL-FLUID; GENETIC RISK; DIABETES-MELLITUS AB Children of persons with Alzheimer disease (AD), as a group, face an increased risk of developing AD. Many of them, throughout their adult lives, seek input on how to reduce their chances of one day suffering their parent's fate. We examine the state of knowledge with respect to risk and protective factors for AD and recommend a research agenda with special emphasis on AD offspring. C1 [Jarvik, Lissy; Ercoli, Linda; Freimer, Nelson] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. [Ringman, John M.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Ringman, John M.] Univ Calif Los Angeles, Alzheimers Dis Res Ctr, Los Angeles, CA 90024 USA. [LaRue, Asenath] VA Greater Los Angeles Hlth Care Syst, Dept Vet Affairs, Los Angeles, CA USA. [Jarvik, Lissy; Ercoli, Linda; Freimer, Nelson] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Gatz, Margaret; McArdle, John J.] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. [Kawas, Claudia] Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA. [Kawas, Claudia] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA 92717 USA. [Gokhman, Izabella] S Bay Mental Hlth Ctr, Dept Mental Hlth, Hawthorne, CA USA. [Rasgon, Natalie] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Swan, Gary E.] SRI Int, Hlth Sci Ctr, Menlo Pk, CA 94025 USA. [LaRue, Asenath] Univ Wisconsin, Wisconsin Alzheimers Inst, Dept Med, Madison, WI USA. [Blacker, Deborah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Wolf, Phillip A.] Boston Univ, Sch Med, Framingham Heart Study, Boston, MA 02118 USA. [Morris, John C.] Washington Univ, Sch Med, St Louis, MO USA. [Mortimer, James A.] Univ S Florida, Coll Publ Hlth, Dept Epidemiol & Biostat, MDC, Tampa, FL USA. [Manly, Jennifer J.] Columbia Univ, GH Sergievsky Ctr, New York, NY USA. [Manly, Jennifer J.] Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Ctr, New York, NY USA. [Plassman, Brenda L.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Roberts, Jeffrey Scott] Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. [Zonderman, Alan B.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. RP Jarvik, L (reprint author), Univ Calif Los Angeles, Dept Psychiat & Behav Sci, 760 Westwood Plaza, Los Angeles, CA 90095 USA. EM ljarvik@ucla.edu RI Morris, John/A-1686-2012; OI Zonderman, Alan B/0000-0002-6523-4778 FU Intramural NIH HHS; NHGRI NIH HHS [R01 HG002213]; NHLBI NIH HHS [HL51429]; NIA NIH HHS [5R01 AG08122, 5R01 AG16495, AG08549, K08 AG022228, K08AG-22228, P01 AG-1657, P01 AG026276, P50 AG005134, P50 AG016573, P50 AG16573, R01 AG008122, R01 AG008549, R01 AG016495, R01 AG021055, R01 AG08724, R01 HG/AG 02213]; PHS HHS [5 P50 AGO5134, G09341] NR 202 TC 15 Z9 15 U1 7 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD JAN-MAR PY 2008 VL 22 IS 1 BP 6 EP 20 PG 15 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 270DK UT WOS:000253700000003 PM 18317242 ER PT J AU Meinert, CL Breitner, JCS AF Meinert, Curtis L. Breitner, John C. S. TI Chronic disease long-term drug prevention trials: Lessons from the Alzheimer's disease anti-inflammatory prevention trial (ADAPT) SO ALZHEIMERS & DEMENTIA LA English DT Article; Proceedings Paper CT Leon Thal Symposium on the Prevention of Dementia CY DEC 02-04, 2007 CL Las Vegas, NV SP Lou Ruvo Brain Inst DE clinical trials ID MILD COGNITIVE IMPAIRMENT; RANDOMIZED CONTROLLED-TRIAL; POSTMENOPAUSAL WOMEN; CLINICAL-TRIALS; CACHE COUNTY; VITAMIN-E; HEALTH; RISK; CELECOXIB; DEMENTIA AB A randomized trial is a randomized trial. The basic ingredients do not change with different purposes whether for treatment or prevention of disease. Likewise, the problems and difficulties are mostly the same. But there are differences in approach and philosophy. Here we discuss problems in trials focused on healthy people to determine whether drugs can delay or prevent adverse health events, with the Alzheimer's Disease Anti -inflammatory Prevention Trial (ADAPT) as an example. An important difference separating treatment trials from prevention trials is the length of time needed to demonstrate a difference with treatment. Related to this is the risk-benefit calculus of the trial. Treatment trials are aimed at "curing" or ameliorating disease, for example, as with trials involving people with Alzheimer's disease (AD) dementia to determine whether treatment is useful in dealing with the AD-induced dementia. Like other treatment trials, those targeting AD dementia balance these benefits against the risks of treatment. But by contrast, benefit in prevention trials, if any, will be found only in the absence or delay in disease onset, often after years of continuous treatment. As in ADAPT, the separation in timing of risk versus benefit often brings difficult decisions about how long to continue the trial in the absence of any apparent benefit to treatment. Other difficulties similarly relate to the length of prevention trials. In hopes that some lessons teamed from ADAPT will assist future prevention trials, especially in the elderly, we describe several conundrums and problems experienced in this trial and attempt when possible to extend our observations to the larger class of long-term drug prevention trials. 0 2008 The Alzheimer's Association. All rights reserved. C1 [Meinert, Curtis L.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Breitner, John C. S.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Div Geriatr Psychiat, Seattle, WA 98195 USA. [Breitner, John C. S.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Meinert, CL (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. EM cmeinert@jhsph.edu FU NIA NIH HHS [U01 AG15477] NR 40 TC 15 Z9 15 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JAN PY 2008 VL 4 IS 1 SU 1 BP S7 EP S14 DI 10.1016/j.jalz.2007.10.007 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 256AI UT WOS:000252699700003 PM 18632005 ER PT J AU Jellinek, MS AF Jellinek, Michael S. TI Commentary: caring for the psychosocial needs of children: From advocacy to structural change SO AMBULATORY PEDIATRICS LA English DT Editorial Material ID PEDIATRIC PRIMARY-CARE; PSYCHOPATHOLOGY C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Jellinek, MS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bulfinch 351, Boston, MA 02114 USA. EM mjellinek@partners.org NR 12 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 1530-1567 J9 AMBUL PEDIATR JI Ambul. Pediatr. PD JAN-FEB PY 2008 VL 8 IS 1 BP 8 EP 10 DI 10.1016/j.ambp.2007.11.003 PG 3 WC Pediatrics SC Pediatrics GA 254PI UT WOS:000252598100003 PM 18191775 ER PT J AU Morrow, DA Wang, Y Croce, K Sakuma, M Sabatine, MS Gao, H Pradhan, AD Healy, AM Buros, J McCabe, CH Libby, P Cannon, CP Braunwald, E Simon, DI AF Morrow, David A. Wang, Yunmei Croce, Kevin Sakuma, Masashi Sabatine, Marc S. Gao, Huiyun Pradhan, Aruna D. Healy, Aileen M. Buros, Jacki McCabe, Carolyn H. Libby, Peter Cannon, Christopher P. Braunwald, Eugene Simon, Daniel I. TI Myeloid-related protein 8/14 and the risk of cardiovascular death or myocardial infarction after an acute coronary syndrome in the Pravastatin or Atorvastatin Evaluation and Infection Theraphy: Thrombolysis in Myocardial Infarction (PROVE IT-TIMI 22) trial SO AMERICAN HEART JOURNAL LA English DT Article ID SERUM-LEVELS; INFLAMMATION; EXPRESSION; BIOMARKERS; MONOCYTES; STATINS; DISEASE; ANGINA AB Background Using a transcriptional profiling approach, we recently identified myeloid-related protein 8/14 (MRP-8/14) to be expressed by platelets during acute myocardial infarction (MI). Elevated concentrations of MRP-8/14 are associated with a higher risk for future cardiovascular events in apparently healthy individuals but have not been assessed with respect to prognosis in patients with acute coronary syndrome. Methods We performed a nested case-control study (n = 237 case-control pairs) among patients enrolled in the Pravastatin or Atorvastatin Evaluation and Infection Theraphy: Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial (mean follow-up 24 months) to investigate the risk of cardiovascular death or MI associated with MRP-8/14 measured at 30 days after an acute coronary syndrome. Results Patients with cardiovascular death or MI after 30 days (cases) had higher median [25th, 75th percentile] MRP-8/14 levels than patients who remained free of recurrent events (5.6 [2.8, 13.5] mg/L vs 4.0 [1.9, 10.1] mg/L, P =.020). The risk of a recurrent cardiovascular event increased with each increasing quartile of MRP-8/1 4 (P-trend = 0.007) such that patients with the highest levels had a 2.0-fold increased odds (95% CI 1.1-3.6, P =.029) of a. recurrent event after adjusting for standard risk indicators, randomized treatment, and C-reactive protein. Patients with elevated levels of MRP-8/14 and high-sensitivity C-reactive protein showed significantly increased risk of cardiovascular death or MI compared with patients with the lowest levels of both markers (adjusted odds ratio 2.1, 95% CI 1.2-3.8). Conclusions Myeloid-related protein 8/14 may be a useful biomarker of platelet and inflammatory disease activity in atherothrombosis and may serve as a novel target for therapeutic intervention. C1 [Morrow, David A.; Croce, Kevin; Sabatine, Marc S.; Buros, Jacki; McCabe, Carolyn H.; Libby, Peter; Cannon, Christopher P.; Braunwald, Eugene] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Wang, Yunmei; Sakuma, Masashi; Gao, Huiyun; Healy, Aileen M.; Simon, Daniel I.] Case Western Reserve Univ, Sch Med, Univ Hosp Case Med Ctr, Div Cardiovasc Med, Cleveland, OH 44106 USA. [Morrow, David A.; Sabatine, Marc S.; Libby, Peter; Cannon, Christopher P.; Braunwald, Eugene] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Sabatine, Marc S.; Pradhan, Aruna D.] Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA. [Sabatine, Marc S.; Libby, Peter] Womens Hosp Med Ctr, Brigham & Womens Hosp, Donald W Reynolds Ctr Clin Cardiovasc Res, Boston, MA USA. RP Morrow, DA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM dmorrow@rics.bwh.harvard.edu; daniel.simon@uhhospitals.org FU NHLBI NIH HHS [HL57506, HL082740, HL60942, K08 HL082740, K08 HL086672, R01 HL057506, R01 HL057506-06, R01 HL060942, R37 HL057506, U01 HL083-1341] NR 22 TC 77 Z9 79 U1 0 U2 2 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 JAN PY 2008 VL 155 IS 1 BP 49 EP 55 DI 10.1016/j.ahj.2007.08.018 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 242NO UT WOS:000251732400008 PM 18082488 ER PT J AU Deo, R Fyr, CLW Fried, LF Newman, AB Harris, TB Angleman, S Green, C Kritchevsky, SB Chertow, GM Cummings, SR Shlipak, MG AF Deo, Rajat Fyr, Christina L. Wassel Fried, Linda F. Newman, Anne B. Harris, Tamara B. Angleman, Sara Green, Christie Kritchevsky, Stephen B. Chertow, Glenn M. Cummings, Steven R. Shlipak, Michael G. CA Hlth ABC Study TI Kidney dysfunction and fatal cardiovascular disease - an association independent of atherosclerotic events: Results from the Health, Aging, and Body Composition (Health ABC) study SO AMERICAN HEART JOURNAL LA English DT Article ID GLOMERULAR-FILTRATION-RATE; SERUM CYSTATIN-C; RENAL-INSUFFICIENCY; CLINICAL EVALUATION; ELDERLY PERSONS; MORTALITY RISK; MARKER; CREATININE; PREDICTOR; PLASMA AB Background Impaired kidney function has been associated with increased risk for death, myocardial infarction, stroke, and heart failure in high-risk populations. We evaluated whether impaired kidney function predicted risk of fatal cardiovascular disease independent of prevalent and incident cardiovascular events. Methods The Health, Aging, and Body Composition study is a cohort of well-functioning, elderly participants aged 70 to 79 years at entry. We measured serum cystatin C and creatinine from baseline plasma samples of 3044 participants and followed them over 6 years, examining the associations among kidney function, cardiovascular death,. and incident cardiovascular events. Cystatin C was categorized as low (< 0.84 mg/L), medium (0.84-1.18 mg/L), or high (>= 1.19 mg/L); serum creatinine (cutoff value of >= 1.3 in women and >= 1.5 in men) and estimated glomerular filtration rate (eGFR; greater and less than 60 mL/min per 1.73 m(2)) were dichotomized. Results During follow-up, 242 cardiovascular deaths occurred, of which 69 were in participants without prior cardiovascular events; 294 incident cardiovascular events occurred including 135 myocardial infarctions and 163 strokes. Higher cystatin C concentrations were significantly associated with cardiovascular death (adjusted hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.05-2.76 for the medium cystatin C group; and HR 2.24, 95% CI 1.30-3.86 for the high cystatin C group, relative to the low cystatin C group). The point estimate was of greater magnitude in the analysis that excluded prevalent cardiovascular disease (adjusted HR 2.68, 95% CI 0.94-7.70 for the medium cystatin C group; and HR 4.91, 95% CI, 1.55-15.54 for the high cystatin C group). Elevated creatinine levels (adjusted HR 1.54, 95% CI 1.02-2.33, and HR 2.28, 95% CI 1.10-4.73 among participants without a history of cardiovascular disease) were also associated with cardiovascular death. No significant association was found between low eGFR and cardiovascular death. In addition, cystatin C, low eGFR, or elevated creatinine levels were not associated with other cardiovascular events. Conclusion Impaired kidney function is a strong predictor of cardiovascular death, particularly among participants without prior history of cardiovascular disease. C1 [Shlipak, Michael G.] Univ Calif San Francisco, Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. [Cummings, Steven R.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, J Paul Sticht Ctr Aging & Rehabil, Winston Salem, NC USA. [Green, Christie] Univ Tennessee, Dept Med, Div Nephrol, Memphis, TN 38104 USA. [Harris, Tamara B.; Angleman, Sara] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Newman, Anne B.] Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA USA. [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Fried, Linda F.] VA Pittsburgh Hlth Care Syst, Renal Sect, Pittsburgh, PA USA. [Fried, Linda F.] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA. [Fyr, Christina L. Wassel; Chertow, Glenn M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Fyr, Christina L. Wassel; Chertow, Glenn M.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Deo, Rajat] Johns Hopkins Univ Hosp, Div Cardiol, Baltimore, MD 21287 USA. RP Shlipak, MG (reprint author), Univ Calif San Francisco, VA Med Ctr 111A1, Gen Internal Med Sect, 4150 Clement St, San Francisco, CA 94121 USA. EM Michael.Shlipak@ucsf.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Angleman, Sara/0000-0002-9520-5716; Kritchevsky, Stephen/0000-0003-3336-6781 FU Intramural NIH HHS; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 17 TC 59 Z9 66 U1 1 U2 6 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 JAN PY 2008 VL 155 IS 1 BP 62 EP 68 DI 10.1016/j.ahj.2007.08.012 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 242NO UT WOS:000251732400010 PM 18082491 ER PT J AU Gibson, CM Murphy, SA Pride, YB Kirtane, AJ Aroesty, JM Stein, EB Ciaglo, LN Southard, MC Sabatine, MS Cannon, CP Braunwald, E AF Gibson, C. Michael Murphy, Sabina A. Pride, Yuri B. Kirtane, Ajay J. Aroesty, Julian M. Stein, Erica B. Ciaglo, Lauren N. Southard, Matthew C. Sabatine, Marc S. Cannon, Christopher P. Braunwald, Eugene CA TIMI Study Grp TI Effects of pretreatment with clopidogrel on nonemergent percutaneous coronary intervention after fibrinolytic administration for ST-segment elevation myocardial infarction: A Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction (CLARITY-TIMI) 28 study SO AMERICAN HEART JOURNAL LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; FRAME COUNT; ANGIOPLASTY; EXPRESSION; ALTEPLASE; TENECTEPLASE; IMMEDIATE; RETEPLASE; OUTCOMES; ASPIRIN AB Background The use of routine nonemergent percutaneous coronary intervention (PCI) among patients with ST-segment elevation myocardial infarction (STEMI) after fibrinolytic therapy is unknown. We sought to evaluate the effect of nonemergent PCI on mortality among patients with STEMI treated with fibrinolytic administration and the consequence of clopidogrel pretreatment on this effect. Methods CLARITY-TIMI 28 randomized 3491 patients with STEMI treated with fibrinolytic administration and aspirin to clopidogrel or placebo. All patients were to undergo angiography 48 to 192 hours after randomization. Percutaneous coronary intervention was performed at the discretion of the treating physician. Nonemergent PCI, which was defined as PCI that was not precipitated by recurrent myocardial infarction, was performed in 178 1 patients (55.7%). Results Nonemergent PCI did not affect 30-day mortality (2.0% vs 2.3% among patients who did not undergo PCI). However, nonemergent PCI was associated with lower mortality among patients randomized to clopidogrel (1.3% vs 2.8%, P = .04) but not among those randomized to placebo (2.6% vs 1.7%, P = .25; interaction P = .025). In multivariate modeling, PCI remained associated with lower mortality among patients randomized to clopidogrel (OR 0.34, 95% CI 0.13-0.92, P = .034) but not placebo (OR 1.41, 95% CI 0.63-3.19, P = .40, interaction P = .028). Conclusion Among patients with STEMI treated with fibrinolytic administration and aspirin, nonemergent PCI was associated with lower mortality among patients pretreated with clopidogrel. These results suggest that routine nonemergent PCI is beneficial among such patients, although further confirmatory randomized studies are needed. C1 [Gibson, C. Michael; Murphy, Sabina A.; Stein, Erica B.; Ciaglo, Lauren N.; Southard, Matthew C.; Sabatine, Marc S.; Cannon, Christopher P.; Braunwald, Eugene] Harvard Univ, Sch Med, TIMI Study Grp, Boston, MA 02115 USA. [Gibson, C. Michael; Kirtane, Ajay J.; Aroesty, Julian M.] Harvard Univ, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. [Pride, Yuri B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02115 USA. [Sabatine, Marc S.; Cannon, Christopher P.; Braunwald, Eugene] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. RP Gibson, CM (reprint author), Harvard Univ, Sch Med, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM mgibson@timi.org RI bashzar, salman/R-5748-2016 NR 29 TC 9 Z9 9 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 JAN PY 2008 VL 155 IS 1 BP 133 EP 139 DI 10.1016/j.ahj.2007.08.034 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 242NO UT WOS:000251732400021 PM 18082504 ER PT J AU Kesselheim, JC Joffe, S AF Kesselheim, Jennifer C. Joffe, Steven TI The challenge of research on ethics education SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID MEDICAL HOUSE OFFICERS C1 [Kesselheim, Jennifer C.; Joffe, Steven] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Joffe, S (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM steven_joffe@dfci.harvard.edu OI Joffe, Steven/0000-0002-0667-7384 FU NCI NIH HHS [T32 CA009172, T32CA009172-32] NR 9 TC 2 Z9 2 U1 1 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2008 VL 8 IS 4 BP 12 EP 13 DI 10.1080/15265160802147132 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 318SU UT WOS:000257113900005 PM 18576242 ER PT J AU Hamburg, NM Larson, MG Vita, JA Vasan, RS Keyes, MJ Widlansky, ME Fox, CS Mitchell, GF Levy, D Meigs, JB Benjamin, EJ AF Hamburg, Naomi M. Larson, Martin G. Vita, Joseph A. Vasan, Ramachandran S. Keyes, Michelle J. Widlansky, Michael E. Fox, Caroline S. Mitchell, Gary F. Levy, Daniel Meigs, James B. Benjamin, Emelia J. TI Metabolic syndrome, insulin resistance, and brachial artery vasodilator function in Framingham Offspring participants without clinical evidence of cardiovascular disease SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID VASCULAR ENDOTHELIAL FUNCTION; FLOW-MEDIATED DILATION; DIABETES-MELLITUS; PLASMA-GLUCOSE; DYSFUNCTION; RISK; OBESITY; ADULTS; ASSOCIATION; CHOLESTEROL AB The metabolic syndrome (MS), a clustering of metabolic disturbances, is associated with increased cardiovascular risk. Limited information is available about the relations between MS, insulin resistance, and vascular function. We measured brachial artery flow-mediated dilation (n = 2,123) and reactive hyperemia (n = 1,521) in Framingham Offspring participants without diabetes or clinical cardiovascular disease (mean age 59 +/- 9 years, 57% women). MS, determined by National Cholesterol Education Program criteria, was present in 36% of participants. Insulin resistance was determined using Homeostatic Model Assessment. In age- and gender-adjusted models, MS was associated with lower flow-mediated dilation and reactive hyperemia. There was progressively lower vasodilator function with increasing number of MS components (p for trend <0.0001). In multivariable models adjusting for the 5 MS components as continuous variables, MS (presence vs absence) remained associated with lower flow-mediated dilation (2.84 +/- 0.12% vs 3.17 +/- 0.08%, p = 0.0496) and reactive hyperemia (50.8 +/- 1.0 vs 54.4 +/- 0.7 cm/s, p = 0.009). Insulin resistance was inversely associated with flow-mediated dilation and reactive hyperemia in age- and gender-adjusted models, but these relations were not significant in models adjusting for the MS components. In conclusion, our observations are consistent with the hypothesis that MS and insulin resistance impair vascular function predominantly through the influence of the component metabolic abnormalities that comprise MS. (c) 2008 Elsevier Inc. All rights reserved. C1 [Hamburg, Naomi M.; Vita, Joseph A.; Vasan, Ramachandran S.; Widlansky, Michael E.; Benjamin, Emelia J.] Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA. [Larson, Martin G.; Vasan, Ramachandran S.; Keyes, Michelle J.; Fox, Caroline S.; Levy, Daniel; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Larson, Martin G.; Keyes, Michelle J.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Mitchell, Gary F.] Cardiovasc Engn Inc, Waltham, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Div Gen Med, Boston, MA USA. RP Benjamin, EJ (reprint author), Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA. EM emelia@bu.edu OI Vita, Joseph/0000-0001-5607-1797; Hamburg, Naomi/0000-0001-5504-5589; 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, HL 060040, HL 70100, K24 HL004334, N01 HC 25195, N01 HC025195, N01HC25195, R01 HL060040, R01 HL060040-01A1, R01 HL060040-02, R01 HL060040-03, R01 HL060040-04, R01 HL070100, R01 HL070100-01, R01 HL070100-02, R01 HL070100-03, R01 HL070100-04, R01 HL076784, R01 HL076784-01, R01 HL076784-02, R01 HL076784-03, R01 HL076784-04] NR 30 TC 53 Z9 55 U1 0 U2 5 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 1 PY 2008 VL 101 IS 1 BP 82 EP 88 DI 10.1016/j.amjcard.2007.07.053 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 248FC UT WOS:000252136400015 PM 18157970 ER PT J AU Kashani, A Giugliano, RP AF Kashani, Amir Giugliano, Robert P. TI Management of ST-elevation myocardial infarction - An update on pharmacoinvasive recanalization SO AMERICAN JOURNAL OF CARDIOVASCULAR DRUGS LA English DT Review ID PERCUTANEOUS CORONARY INTERVENTION; GLYCOPROTEIN IIB/IIIA INHIBITION; RANDOMIZED CONTROLLED-TRIAL; PRIMARY ANGIOPLASTY; SEGMENT ELEVATION; FIBRINOLYTIC THERAPY; FACILITATED ANGIOPLASTY; THROMBOLYTIC THERAPY; RECEPTOR BLOCKADE; PILOT TRIAL AB The immediate goal of reperfusion in acute ST-elevation myocardial infarction (STEMI) is the prompt restoration of myocardial blood flow. Over the past 50 years, numerous advances have been made in achieving this goal by combining pharmacologic regimens with primary percutaneous coronary intervention (PCI) [i.e. pharmacoinvasive recanalizaton]. Fibrinolytics and glycoprotein (GP) IIb/IIIa inhibitors remain the most promising and widely used pharmacologic agents used to date. Early GP IIb/IIIa inhibition in patients undergoing PCI for STEMI results in early reperfusion and can result in improved clinical outcomes. Combination therapy with fibrinolytics and GP IIb/IIIa inhibitors is currently under investigation. The importance of time in the administration of these agents, especially in patients with expected delays to mechanical reperfusion, cannot be overemphasized. Benefits of revascularization are dependent on establishing reperfusion early enough to salvage the myocardium and preserve the left ventricular ejection fraction. As time passes, the effectiveness of treatments decline and patient outcomes are worse. This dependence upon time applies to both fibrinolytic therapy as well as primary PCI. In the current era, primary PCI is the preferred modality for treating patients with STEMI with a goal door-to-balloon time of < 90 minutes. However, this modality is not available to all patients presenting with STEMI. Given the importance of time to reperfusion, a pharmacoinvasive approach may be ideal for this patient population. In this paper, we review the literature on pharmacoinvasive recanalization and discuss the optimal combination and timing of these agents. We have linked current American College of Cardiology/American Heart Association Clinical Practice Guidelines to clinical data available in the literature. C1 [Kashani, Amir] Yale Univ, Sch Med, Cardiol Sect, New Haven, CT USA. [Giugliano, Robert P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA USA. RP Giugliano, RP (reprint author), 350 Longwood Ave,1st Floor Off, Boston, MA USA. EM rgiugliano@partners.org NR 54 TC 2 Z9 4 U1 0 U2 2 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1175-3277 J9 AM J CARDIOVASC DRUG JI Am. J. Cardiovasc. Drugs PY 2008 VL 8 IS 3 BP 187 EP 197 DI 10.2165/00129784-200808030-00005 PG 11 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 320XK UT WOS:000257268300005 PM 18533739 ER PT J AU Wang, TF Zhang, QH Xue, XL Yeungt, A AF Wang, Tianfang Zhang, Qunhao Xue, Xiaolin Yeungt, Albert TI A systematic review of acupuncture and moxibustion treatment for chronic fatigue syndrome in China SO AMERICAN JOURNAL OF CHINESE MEDICINE LA English DT Review DE acupuncture and moxbiustion treatment; chronic fatigue syndrome; China; systematic review ID DEFINITION AB Studies on the treatment of chronic fatigue syndrome (CFS) with acupuncture and moxibustion in China were reviewed. All studies concluded the treatments were effective, with response rates ranging from 78.95% to 100%. However, the qualities of the studies were generally poor, and none of them used a RCT design. The common acupoints/sites used in the treatment of CFS, which may reflect the collective experience of acupuncturists in China based on Traditional Chinese Medicine theories can be used to evaluate the effectiveness of acupuncture for the treatment of CFS in future studies using more scientifically rigorous study designs. C1 [Wang, Tianfang; Xue, Xiaolin] Beijing Univ Chinese Med, Preclin Coll, Dept TCM Diagnost, Beijing 100029, Peoples R China. [Zhang, Qunhao; Yeungt, Albert] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wang, TF (reprint author), Beijing Univ Chinese Med, Preclin Coll, Dept TCM Diagnost, Beijing 100029, Peoples R China. EM tianfangwang@hotmail.com NR 47 TC 25 Z9 28 U1 0 U2 10 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 0192-415X J9 AM J CHINESE MED JI Am. J. Chin. Med. PY 2008 VL 36 IS 1 BP 1 EP 24 DI 10.1142/S0192415X08005540 PG 24 WC Integrative & Complementary Medicine; Medicine, General & Internal SC Integrative & Complementary Medicine; General & Internal Medicine GA 274HE UT WOS:000253991600001 PM 18306446 ER PT J AU Haile, CN Kosten, TA Kosten, TR AF Haile, Colin N. Kosten, Therese A. Kosten, Thomas R. TI Pharmacogenetic treatments for drug addiction: Alcohol and opiates SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Review DE genetics; mutations; drug dependence; drug abuse; pharmaceuticals; drug reinforcement ID MU-OPIOID-RECEPTOR; SINGLE-NUCLEOTIDE POLYMORPHISM; STEVENS-JOHNSON-SYNDROME; PITUITARY-ADRENAL AXIS; GENE OPRM1; FUNCTIONAL POLYMORPHISM; SUBSTANCE DEPENDENCE; A118G POLYMORPHISM; HEROIN-ADDICTS; BETA-ENDORPHIN AB Aims: Psychiatric pharmacogenetics involves the use of genetic tests that can predict the effectiveness of treatments for individual patients with mental illness such as drug dependence. This review aims to cover these developments in the pharmacotherapy of alcohol and opiates, two addictive drugs for which we have the majority of our FDA approved pharmacotherapies. Methods: We conducted a literature review using Medline searching terms related to these two drugs and their pharmacotherapies crossed with related genetic studies. Results: Alcohol's physiological and subjective effects are associated with enhanced beta-endorphin release. Naltrexone increases baseline beta-endorphin release blocking further release by alcohol. Naltrexone's action as an alcohol pharmacotherapy is facilitated by a putative functional single nucleotide polymorphism (SNP) in the opioid mu receptor gene (Al18G) which alters receptor function. Patients with this SNP have significantly lower relapse rates to alcoholism when treated with naltrexone. Caucasians with various forms of the CYP2D6 enzyme results in a 'poor metabolizer' phenotype and appear to be protected from developing opioid dependence. Others with a "ultra-rapid metabolizer" phenotype do poorly on methadone maintenance and have frequent withdrawal symptoms. These patients can do well using buprenorphine because it is not significantly metabolized by CYP2D6. Conclusions: Pharmacogenetics has great potential for improving treatment outcome as we identify gene variants that affect pharmacodynamic C1 [Kosten, Thomas R.] Baylor Coll Med, VA Med Ctr, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP Kosten, TR (reprint author), Baylor Coll Med, VA Med Ctr, Menninger Dept Psychiat & Behav Sci, Res Bldg 110,Room 229,2002 Holcombe Blvd, Houston, TX 77030 USA. EM Kosten@bcm.edu OI Haile, Colin/0000-0001-8293-7291 FU NIDA NIH HHS [K05-DA0454, P50-DA18827] NR 175 TC 40 Z9 41 U1 0 U2 11 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0095-2990 EI 1097-9891 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PY 2008 VL 34 IS 4 BP 355 EP 381 DI 10.1080/00952990802122564 PG 27 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 318XA UT WOS:000257124900001 PM 18584566 ER PT J AU Yu, E Miotto, K Akerele, E O'Brien, CP Ling, W Kleber, H Fischman, MW Elkashef, A Herman, BH Al-Ghananeem, AM AF Yu, Elmer Miotto, Karen Akerele, Evaristo O'Brien, Charles P. Ling, Walter Kleber, Herbert Fischman, Marian W. Elkashef, Ahmed Herman, Barbara H. Al-Ghananeem, Abeer M. TI Clinical pharmacokinetics of lofexidine, the alpha 2-adrenergic receptor agonist, in opiate addicts plasma using a highly sensitive liquid chromatography tandem mass spectrometric analysis SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE clinical trial; LC-MS/MS; lofexidine; pharmacokinetic; substance abuse ID WITHDRAWAL; CLONIDINE AB Objectives: The objective of this investigation was to characterize the pharmacokinetic profile of lofexidine. Lofexidine is an orally bioavailable alpha 2- adrenergic receptor agonist analogue of clonidine that acts centrally to suppress opiate withdrawal symptoms. Methods: During the detoxification period of a phase 3 placebo-controlled, randomized, double-blind trial, six subjects were entered in this preliminary pharmacokinetic study. Results: Pharmacokinetic analysis of plasma samples collected during study day 7 indicated that Cmax was 3242 +/- 917 ng/L. The mean trough levels between the study days were not significantly different (p > .05), suggesting that the subjects were at steady-state. Conclusions: Although preliminary due to the limited number of subjects, these findings are the first to document lofexidine clinical pharmacokinetics in opiate addicts using a highly sensitive liquid chromatography tandem mass spectrometric analysis. C1 [Al-Ghananeem, Abeer M.] Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, Lexington, KY 40536 USA. [Yu, Elmer; O'Brien, Charles P.] Univ Penn, Philadelphia, PA 19104 USA. [Yu, Elmer; O'Brien, Charles P.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Miotto, Karen; Ling, Walter] Univ Calif Los Angeles, Los Angeles, CA USA. [Akerele, Evaristo; Kleber, Herbert; Fischman, Marian W.] Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, New York, NY 10032 USA. [Miotto, Karen; Ling, Walter] Long Beach Vet Affairs Med Ctr, Los Angeles, CA USA. [Elkashef, Ahmed; Herman, Barbara H.] NIDA, Div Pharmacotherapeut & Med Consequences Drug Abu, PMC, NIH, Bethesda, MD 20892 USA. RP Al-Ghananeem, AM (reprint author), Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, Lexington, KY 40536 USA. EM amalg0@email.uky.edu FU NIDA NIH HHS [Y1-DA1001] NR 7 TC 4 Z9 4 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PY 2008 VL 34 IS 5 BP 611 EP 616 DI 10.1080/00952990802308122 PG 6 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 353XV UT WOS:000259603400011 PM 18821454 ER PT J AU Baumann, BM McCans, K Stahmer, SA Leonard, MB Shults, J Holmes, WC AF Baumann, Brigitte M. McCans, Kathryn Stahmer, Sarah A. Leonard, Mary B. Shults, Justine Holmes, William C. TI Volumetric bladder ultrasound performed by trained nurses increases catheterization success in pediatric patients SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-Academic-Emergency-Medicine CY MAY 16-19, 2007 CL Chicago, IL SP Soc Acad Emergency Med ID URINARY-TRACT-INFECTIONS; CLEAN INTERMITTENT CATHETERIZATION; SPINAL-CORD INJURY; FEBRILE INFANTS; YOUNG-CHILDREN; SUPRAPUBIC ASPIRATION; URETHRAL CATHETERIZATION; LOW-RISK; BACTERIURIA; VALIDATION AB Objective: The objective of the study was to determine whether the use of volumetric ultrasound by trained pediatric emergency department (ED) nurses improves first-attempt urine collection success rates. Methods: This randomized controlled trial was conducted in children aged <= 36 months requiring diagnostic urine samples. Children were randomized to either the conventional (nonimaged) or the ultrasound arm. Demographics, number of catheterizations required for success, postponements, and collection times were recorded. Results: Forty-five children were assigned to the conventional and 48 to the ultrasound arm (n = 93). First-attempt success rates were higher in the ultrasound arm: 67% (conventional) vs 92% (ultrasound) (P = .003). Both urinalysis and culture were less likely to be completed on conventional group specimens (91% vs 100%; P =.04). However, mean conventional group urine collection time was less than the ultrasound group's collection time (12 vs 28 minutes; P <.001). Conclusions: Although there is a time delay, urine collection in the ultrasound arm generated a significant improvement over conventional catheterization in obtaining an adequate urine sample. (c) 2008 Elsevier Inc. All rights reserved. C1 [Baumann, Brigitte M.; McCans, Kathryn; Stahmer, Sarah A.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Emergency Med, Camden, NJ 08103 USA. [Baumann, Brigitte M.; Leonard, Mary B.; Shults, Justine; Holmes, William C.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Leonard, Mary B.] Childrens Hosp Philadelphia, Div Nephrol, Dept Pediat, Philadelphia, PA 19104 USA. [Holmes, William C.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Holmes, William C.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Baumann, BM (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Emergency Med, Camden, NJ 08103 USA. EM baumann-b@cooperhealth.edu NR 34 TC 12 Z9 12 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD JAN PY 2008 VL 26 IS 1 BP 18 EP 23 DI 10.1016/j.ajem.2007.03.020 PG 6 WC Emergency Medicine SC Emergency Medicine GA 248NZ UT WOS:000252161800004 PM 18082776 ER PT J AU Chen, H O'Reilly, EJ Schwarzschild, MA Ascherio, A AF Chen, Honglei O'Reilly, Eilis J. Schwarzschild, Michael A. Ascherio, Alberto TI Peripheral inflammatory biomarkers and risk of Parkinson's disease SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE biological markers; C-reactive protein; inflammation; interleukin-6; odds ratio; Parkinson disease; tumor necrosis factor-alpha ID C-REACTIVE PROTEIN; URIC-ACID LEVELS; SUBSTANTIA-NIGRA; TNF-ALPHA; MEN; PLASMA; WOMEN; MICE; IL-6; MICROGLIA AB Experimental and postmortem evidence indicates a role of neuroinflammation in the pathogenesis of Parkinson's disease. The authors prospectively examined whether plasma concentrations of inflammatory biomarkers assessed before Parkinson's disease diagnosis were predictive of future risk of the disease in a nested case-control study in the United States (1993-2002), including 84 incident cases and 165 matched controls. Blood was collected from patients on average 4.3 years before the diagnosis. After adjustment for potential confounders, higher level of interleukin-6 was associated with a greater risk of Parkinson's disease. Compared with the lowest quintile, the odds ratios were 1.5 for the second, 1.6 for the third, 2.7 for the fourth, and 3.4 for the fifth quintiles (p for trend = 0.03). In contrast, concentrations of other inflammatory biomarkers including C-reactive protein, fibrinogen, and tumor necrosis factor-alpha receptors were not related to the risk. These data suggest that men with high plasma concentrations of interleukin-6 have an increased risk of developing Parkinson's disease. However, this finding should be interpreted with caution because of the small sample size and the lack of associations with other biomarkers of inflammation. C1 [O'Reilly, Eilis J.; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Chen, Honglei] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. [Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Ascherio, Alberto] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA USA. RP Ascherio, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM aascheri@hsph.harvard.edu OI Chen, Honglei/0000-0003-3446-7779 FU Intramural NIH HHS; NINDS NIH HHS [R01 NS048517] NR 29 TC 119 Z9 126 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 1 PY 2008 VL 167 IS 1 BP 90 EP 95 DI 10.1093/aje/kwm260 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 244KF UT WOS:000251864100014 PM 17890755 ER PT J AU Hornick, JL Mino-Kenudson, M Lauwers, GY Liu, WT Goyal, R Odze, RD AF Hornick, Jason L. Mino-Kenudson, Mari Lauwers, Gregory Y. Liu, Weitian Goyal, Raj Odze, Robert D. TI Buried Barrett's epithelium following photodynamic therapy shows reduced crypt proliferation and absence of DNA content abnormalities SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol ID ARGON PLASMA COAGULATION; HIGH-GRADE DYSPLASIA; RANDOMIZED-CONTROLLED-TRIAL; ESOPHAGEAL ADENOCARCINOMA; ENDOSCOPIC SURVEILLANCE; NEOPLASTIC PROGRESSION; 5-AMINOLEVULINIC ACID; COLUMNAR METAPLASIA; CLONAL EXPANSION; ABLATION AB OBJECTIVES: Photodynamic therapy (PDT) is increasingly used for the treatment of patients with Barrett's esophagus (BE) with dysplasia or early carcinoma. Post-PDT, some patients show residual BE either exposed to the luminal surface (nonburied) or buried underneath reepithelialized squamous mucosa (buried BE). Buried BE may be a serious clinical problem since it can go unnoticed during surveillance endoscopies. The neoplastic potential of buried BE is poorly understood. The aim of this study was to evaluate the biological characteristics of nonburied and buried BE in patients treated with PDT. METHODS: Twelve patients selected from a cohort of 52 BE patients who received PDT for high-grade dysplasia or intramucosal adenocarcinoma were used for this study because they all had both pre- and post-PDT (nonburied), and post-PDT buried, BE biopsies, without dysplasia, available for analysis. The biopsies were immunostained for Ki-67, p53, cyclin D1, bcl-2, TGF-alpha, EGFR, and AMACR. High fidelity DNA histograms were obtained by image cytometry analysis of Feulgen stained slides, and used to determine peak DNA index (DI), DNA heterogeneity, and 5N exceeding rate (5NER). Comparisons were made between pre-PDT nonburied BE and post-PDT nonburied and buried BE. RESULTS: Pre-PDT BE showed an elevated Ki-67 crypt proliferation rate (43.3%) and p53, bcl-2, TGF-alpha, and EGFR positivity in 8%, 25%, 75%, and 25% of cases, respectively. Cyclin D1 and AMACR were negative in all cases. High fidelity DNA histograms showed mild aneuploidy in 73% of cases. Post-PDT buried BE showed a significantly lower Ki-67 crypt proliferation rate (29.9%) in comparison to nonburied BE, in both pre- PDT (43.3%) and post-PDT (44.4%) biopsies (P < 0.05), but similar rates of positivity for the other peptide markers. In contrast to pre-PDT nonburied BE biopsies, high fidelity DNA histograms revealed that none of the buried BE (0%), and only 2/9 (11%) nonburied BE post-PDT, showed aneuploidy. CONCLUSIONS: Pre-PDT nonburied BE, without dysplasia, shows elevated crypt proliferation and mild, but frequent, DNA content abnormalities. Post-PDT, nonburied BE shows persistently elevated crypt proliferation, but significantly less frequent DNA content abnormalities, whereas buried BE shows decreased crypt proliferation and normal DNA content profile. These results suggest that post-PDT buried BE may have a lower neoplastic potential than pre-PDT BE. C1 [Hornick, Jason L.; Odze, Robert D.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Mino-Kenudson, Mari; Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Liu, Weitian] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Goyal, Raj] Boston Healthcare Syst, Dept Med, Boston, MA USA. RP Hornick, JL (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK62867] NR 44 TC 44 Z9 45 U1 0 U2 2 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 JAN PY 2008 VL 103 IS 1 BP 38 EP 47 DI 10.1111/j.1572-0241.2007.01560.x PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 247UP UT WOS:000252108400007 PM 18076737 ER PT J AU Siegel, AB McBride, RB El-Serag, HB Hershman, DL Brown, RS Renz, JF Emond, J Neugut, AI AF Siegel, Abby B. McBride, Russell B. El-Serag, Hashem B. Hershman, Dawn L. Brown, Robert S. Renz, John F. Emond, Jean, Jr. Neugut, Alfred I. TI Racial disparities in utilization of liver transplantation for hepatocellular carcinoma in the United States, 1998-2002 SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID RENAL-TRANSPLANTATION; LUNG-CANCER; ACCESS; POPULATION; SURGERY; RACE AB BACKGROUND AND AIMS: The extent of use of liver transplantation on a population scale to treat hepatocellular carcinoma (HCC) in the United States is unknown. We assessed recent predictors of use of liver transplantation and its effect on survival for those with nonmetastatic HCC. METHODS: The Surveillance, Epidemiology, and End Results (SEER) program is a collection of population-based cancer registries. We identified adults registered in SEER with HCC between 1998 and 2002. We examined determinants for receipt of a liver transplant in univariate and multivariable analyses. Kaplan-Meier survival curves were constructed for those who received and did not receive a transplant for HCC. RESULTS: We identified 1,156 adults with small (5 cm or less) nonmetastatic HCC. Approximately 45% were white, 29% Asian, 17% Hispanic, and 9% African American. Only 21% received a transplant. More recent year of diagnosis, younger age, being married, white race, and smaller tumor size each predicted receipt of transplant. African Americans and Asians were about half as likely to receive a transplant as compared with white patients (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.21-0.90 for African Americans, and 0.57, 95% CI 0.36-0.89 for Asians). Hispanics trended in the same direction, but this was not statistically significant (OR 0.66, 95% CI 0.39-1.12). Those who underwent liver transplantation for localized HCC had 3- and 5-yr survivals of 81% and 75%, respectively. CONCLUSIONS: Only one-fifth of those with small, nonmetastatic HCC received liver transplantation. Transplanted patients have long-term survival similar to that of the best single-institution studies. However, marked racial variations were seen, with African Americans and Asians significantly less likely to receive a transplant after controlling for other variables. C1 [Siegel, Abby B.; Hershman, Dawn L.; Brown, Robert S.; Renz, John F.; Emond, Jean, Jr.; Neugut, Alfred I.] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. [Siegel, Abby B.; Hershman, Dawn L.; Brown, Robert S.; Renz, John F.; Emond, Jean, Jr.; Neugut, Alfred I.] Columbia Univ, Coll Phys & Surg, Dept Surg, New York, NY USA. [McBride, Russell B.; Hershman, Dawn L.; Neugut, Alfred I.] Columbia Univ, Coll Phys & Surg, Herbert Irving Comprehens Canc Ctr, New York, NY USA. [McBride, Russell B.; Hershman, Dawn L.; Neugut, Alfred I.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [El-Serag, Hashem B.] Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX USA. [El-Serag, Hashem B.] Houston Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX USA. [El-Serag, Hashem B.] Baylor Coll Med, Houston, TX 77030 USA. RP Siegel, AB (reprint author), 622 W 168th St,PH 14, New York, NY 10032 USA. FU NCI NIH HHS [CA94061, CA89155, CA95597]; NCRR NIH HHS [ULI RR024156]; NIDDK NIH HHS [DK58369] NR 22 TC 47 Z9 47 U1 2 U2 4 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 JAN PY 2008 VL 103 IS 1 BP 120 EP 127 DI 10.1111/j.1572-0241.2007.01634.x PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 247UP UT WOS:000252108400019 PM 18005365 ER PT J AU Kozel, FA Trivedi, MH Wisniewski, SR Miyahara, S Husain, MM Fava, M Lebowitz, B Zisook, S Rush, AJ AF Kozel, F. Andrew Trivedi, Madhukar H. Wisniewski, Stephen R. Miyahara, Sachiko Husain, Mustafa M. Fava, Maurizio Lebowitz, Barry Zisook, Sidney Rush, A. John TI Treatment outcomes for older depressed patients with earlier versus late onset of first depressive episode - A sequenced treatment alternatives to relieve depression (STAR*D) report SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE depression; Sequenced Treatment Alternatives to Relieve Depression (STAR*D); citalopram; late onset ID LATE-LIFE DEPRESSION; DEFINED VASCULAR DEPRESSION; TREATMENT-RESPONSE; MAJOR DEPRESSION; GERIATRIC DEPRESSION; QUICK INVENTORY; RATING-SCALE; AGE; MRI; HYPERINTENSITIES AB Objective: Controversy exists whether age at onset of the first depressive episode predicts chance of response and remission or the timing of such outcome. In this study of older depressed outpatients, the authors evaluated whether the age at onset of the first major depressive episode (MDE) was related to clinical outcomes. Design: Post-hoc dataset analysis for older par pants treated with citalopram in the Sequenced Treatment Alternatives to Relieve Depression trial was performed. Side effects, remission rates, and baseline characteristics were compared for participants whose first MDE began at or before age 55 (earlier onset) versus those with their first MDE after age 55 (late onset) Setting: Participants were enrolled from 23 psychiatric and 18 primary care settings. Participants: There were 574 treatment-seeking outpatients (age range: 55-75 years) with nonpsychotic major depressive disorder who bad a baseline 17-item Hamilton Rating Scale for Depression score of >= 14. Intervention: Participants received citalopram treatment for up to 14 weeks. Measurements: Remission was defined by a 16-item Quick Inventory of Depressive Symptomatology-Self-Rated score of <= 5 at study exit. Side effects were measured by the Frequency, Intensity, and Burden of Side Effects Rating. Results: Of 574 participants, 72.1% had earlier-onset depression and 27.9% had late-onset depression. Remission rates were not statistically different between earlier-onset (30.8%) and late-onset (31.9%) participants. Time to remission did not differ as well. Conclusion: The self-reported age at onset of the first MDE being after age 55 was not related to clinical outcomes for participants 55 to 75 years of age. C1 [Kozel, F. Andrew; Trivedi, Madhukar H.; Husain, Mustafa M.; Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Wisniewski, Stephen R.; Miyahara, Sachiko] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. [Fava, Maurizio] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02138 USA. [Lebowitz, Barry; Zisook, Sidney] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Zisook, Sidney] San Diego VA Med Ctr, La Jolla, CA USA. [Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. RP Kozel, FA (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM Andrew.Kozel@utsouthwestern.edu RI Kozel, Frank/I-5366-2012; OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [5K23 MH 070897-01, N01 MH 90003] NR 29 TC 22 Z9 22 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JAN PY 2008 VL 16 IS 1 BP 58 EP 64 DI 10.1097/JGP.0b013e31815a43d7 PG 7 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 251VQ UT WOS:000252404200007 PM 18165462 ER PT J AU Lloyd-Richardson, EE Stanton, CA Papandonatos, GD Betancourt, RM Stein, M Tashima, K Morrow, K Niaura, R AF Lloyd-Richardson, Elizabeth E. Stanton, Cassandra A. Papandonatos, George D. Betancourt, Rene M. Stein, Michael Tashima, Karen Morrow, Kathleen Niaura, Raymond TI HIV-positive smokers considering quitting: Differences by race/ethnicity SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article DE nicotine dependence predictors; HIV; smoking ID QUALITY-OF-LIFE; SMOKING-CESSATION; ETHNIC-DIFFERENCES; CIGARETTE-SMOKING; UNITED-STATES; HEALTH; BEHAVIOR; TOBACCO; WOMEN; DEPRESSION AB Objective: To better characterize smoking in HIV-positive individuals and to identify critical components of a targeted smoking cessation intervention for multiethnic HIV-positive smokers. Methods: Differences in baseline characteristics of 444 HIV-positive smokers were examined by race, and a multivariate linear regression model evaluated factors associated with nicotine dependence in an HIV-positive population, with a particular emphasis on race/ethnic differences. Results: Low smoking self-efficacy and higher contemplation of quitting were predictive of greater nicotine dependence. An interaction between age and race was noted, with older Hispanic Americans less likely to be nicotine dependent. Conclusions: Efforts should be made to tailor smoking cessation intervention content to HIV-positive racial/ethnic minority groups. C1 [Lloyd-Richardson, Elizabeth E.] Brown Univ, Miriam Hosp, Sch Med, Weight Control & Diabet Res Ctr, Providence, RI 02903 USA. [Stanton, Cassandra A.; Niaura, Raymond] Transdisciplinary Res Grp, Providence, RI USA. [Papandonatos, George D.] Brown Univ, Ctr Stat Sci, Providence, RI USA. [Betancourt, Rene M.] Massachusetts Gen Hosp, Inst Hlth Policy, Partners Healthcare Syst, Boston, MA 02114 USA. [Stein, Michael] Brown Univ, Rhode Isl Hosp, Providence, RI 02903 USA. [Morrow, Kathleen] Ctr Behav & Prevent Med, Providence, RI USA. RP Lloyd-Richardson, EE (reprint author), Brown Univ, Miriam Hosp, Sch Med, Weight Control & Diabet Res Ctr, 196 Richmond St, Providence, RI 02903 USA. EM erichardson@lifespan.org RI Papandonatos, George/J-2328-2014; OI Papandonatos, George/0000-0001-6770-932X FU NIDA NIH HHS [R01 DA012344, R01 DA012344-05] NR 57 TC 19 Z9 20 U1 1 U2 1 PU PNG PUBLICATIONS PI STAR CITY PA PO BOX 4593, STAR CITY, WV 26504-4593 USA SN 1087-3244 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD JAN-FEB PY 2008 VL 32 IS 1 BP 3 EP 15 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 251MT UT WOS:000252378400001 PM 18021029 ER PT J AU Kim, HG Kishikawa, S Higgins, AW Seong, IS Donovan, DJ Shen, Y Lally, E Weiss, LA Najm, J Kutsche, K Descartes, M Holt, L Braddock, S Troxell, R Kaplan, L Volkmar, F Klin, A Tsatsanis, K Harris, DJ Noens, I Pauls, DL Daly, MJ MacDonald, ME Morton, CC Quade, BJ Gusella, JE AF Kim, Hyung-Goo Kishikawa, Shotaro Higgins, Anne W. Seong, Ihn-Sik Donovan, Diana J. Shen, Yiping Lally, Eric Weiss, Lauren A. Najm, Juliane Kutsche, Kerstin Descartes, Maria Holt, Lynn Braddock, Stephen Troxell, Robin Kaplan, Lee Volkmar, Fred Klin, Ami Tsatsanis, Katherine Harris, David J. Noens, Ilse Pauls, David L. Daly, Mark J. MacDonald, Marcy E. Morton, Cynthia C. Quade, Bradley J. Gusella, James E. TI Disruption of neurexin 1 associated with autism spectrum disorder SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID ALPHA-NEUREXINS; CHROMOSOMAL REARRANGEMENTS; HIGH-FREQUENCY; CELL-ADHESION; CLEFT-LIP; GENES; NEUROLIGINS; SYNAPSE; MUTATION; HAPLOINSUFFICIENCY AB Autism is a neurodevelopmental disorder of complex etiology in which genetic factors play a major role. We have implicated the neurexin 1 (NRXN1) gene in two independent subjects who display an autism spectrum disorder (ASD) in association with a balanced chromosomal abnormality involving 2p16.3. In the first, with karyotype 46,XX,ins(16;2)(q22.1;p16.1p16.3)pat, NRXN1 is directly disrupted within intron 5. Importantly, the father possesses the same chromosomal abnormality in the absence of ASD, indicating that the interruption of alpha-NRXN1 is not fully penetrant and must interact with other factors to produce ASD. The breakpoint in the second subject, with 46,XY,t(1;2)(q31.3;p16.3)dn, occurs similar to 750 kb 5' to NRXN1 within a 2.6 Mb genomic segment that harbors no currently annotated genes. A scan of the NRXN1 coding sequence in a cohort of ASD subjects, relative to non-ASD controls, revealed that amino acid alterations in neurexin 1 are not present at high frequency in ASD. However, a number of rare sequence variants in the coding region, including two missense changes in conserved residues of the alpha-neurexin 1 leader sequence and of an epidermal growth factor (EGF)-like domain, respectively, suggest that even subtle changes in NRXN1 might contribute to susceptibility to ASD. C1 [Kim, Hyung-Goo; Kishikawa, Shotaro; Seong, Ihn-Sik; Shen, Yiping; Kaplan, Lee; MacDonald, Marcy E.; Gusella, James E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Mol Neurogenet Unit, Boston, MA 02114 USA. [Kim, Hyung-Goo; Kishikawa, Shotaro; Seong, Ihn-Sik; Shen, Yiping; Kaplan, Lee; MacDonald, Marcy E.; Gusella, James E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Higgins, Anne W.; Donovan, Diana J.; Lally, Eric; Morton, Cynthia C.; Quade, Bradley J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Weiss, Lauren A.; Pauls, David L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Psychiat & Neurodev Genet Uni, Boston, MA 02114 USA. [Weiss, Lauren A.; Pauls, David L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Weiss, Lauren A.; Daly, Mark J.; MacDonald, Marcy E.; Morton, Cynthia C.; Gusella, James E.] Broad Inst Harvard, Cambridge, MA 02142 USA. [Weiss, Lauren A.; Daly, Mark J.; MacDonald, Marcy E.; Morton, Cynthia C.; Gusella, James E.] MIT, Cambridge, MA 02142 USA. [Najm, Juliane; Kutsche, Kerstin] Univ Klinikum Hamburg Eppendorf, Inst Humangenet, Hamburg, Germany. [Descartes, Maria; Holt, Lynn] Univ Alabama, Dept Genet, Birmingham, AL 35294 USA. [Braddock, Stephen] Univ Virginia Hlth Syst, Dept Pediat, Div Med Genet, Charlottesville, VA 22908 USA. [Troxell, Robin] Univ Missouri, Dept Child Hlth, Div Med Genet, Columbia, MO 65212 USA. [Volkmar, Fred; Klin, Ami; Tsatsanis, Katherine] Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT 06520 USA. [Harris, David J.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Genet, Boston, MA 02115 USA. [Noens, Ilse] Leiden Univ, NL-2300 RA Leiden, Netherlands. [Pauls, David L.; Daly, Mark J.; Gusella, James E.] Autism Consortium, Boston, MA 02115 USA. [Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Morton, Cynthia C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Gusella, James E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Gusella, JE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Mol Neurogenet Unit, Boston, MA 02114 USA. EM gusella@helix.mgh.harvard.edu RI Donovan, Diana/A-1256-2010 FU NICHD NIH HHS [U19-HD35482, P01-HD00300838, U19 HD035482]; NIGMS NIH HHS [P01 GM061354, P01-GM061354]; NIMH NIH HHS [MH64547, R01 MH064547]; NINDS NIH HHS [R01 NS016648, R01-NS16648] NR 41 TC 312 Z9 330 U1 2 U2 34 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN PY 2008 VL 82 IS 1 BP 199 EP 207 DI 10.1016/j.ajhg.2007.09.011 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 263NM UT WOS:000253223800022 PM 18179900 ER PT J AU Ingelfinger, JR AF Ingelfinger, Julie R. TI Weight for gestational age as a baseline predictor of kidney function in adulthood SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material ID SOUTHEASTERN UNITED-STATES; LOW-BIRTH-WEIGHT; NEPHRON NUMBER; RENAL-DISEASE; GLOMERULAR NUMBER; HYPERTENSION; GROWTH; MICROALBUMINURIA; SIZE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, MassGen Hosp Children, Boston, MA 02115 USA. RP Ingelfinger, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MassGen Hosp Children, Yawkey 6C,25 Shattuck St, Boston, MA 02115 USA. EM jingelfinger@partners.org NR 18 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JAN PY 2008 VL 51 IS 1 BP 1 EP 4 DI 10.1053/j.ajkd.2007.11.004 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 285TQ UT WOS:000254799500002 PM 18155526 ER PT J AU Young, BA Lin, E Von Korff, M Simon, G Ciechanowski, P Ludman, EJ Everson-Stewart, S Kinder, L Oliver, M Boyko, EJ Katon, WJ AF Young, Bessie Ann Lin, Elizabeth Von Korff, Michael Simon, Greg Ciechanowski, Paul Ludman, Evette J. Everson-Stewart, Siobhan Kinder, Leslie Oliver, Malia Boyko, Edward J. Katon, Wayne J. TI Diabetes complications severity index and risk of mortality, hospitalization, and healthcare utilization SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID CORONARY-HEART-DISEASE; LOWER-EXTREMITY AMPUTATION; MYOCARDIAL-INFARCTION; MANAGED-CARE; CARDIOVASCULAR MORTALITY; ALL-CAUSE; POPULATION; MELLITUS; DEPRESSION; SURVIVAL AB Objective:To determine whether the number and severity of diabetes complications are associated with increased risk of mortality and hospitalizations. Study Design: Validation sample. Methods:The Diabetes Complications Severity Index (DCSI) was developed from automated clinical baseline data of a primary care diabetes cohort and compared with a simple count of complications to predict mortality and hospitalizations. Cox proportional hazard and Poisson regression models were used to predict mortality and hospitalizations, respectively. Results: Of 4229 respondents, 356 deaths occurred during 4 years of follow-up. Those with 1 complication did not have an increased risk of mortality, whereas those with 2 complications (hazard ratio [HR) = 1.90, 95% confidence interval [CI] = 1.27,2.83), 3 complications (HR = 2.66, 95% CI = 1.77, 4.01), 4 complications (HR = 3.41, 95% CI = 2.18, 5.33), and >= 5 complications (HR = 7.18, 95% CI = 4.39, 11.74) had greater risk of death. Replacing the complications count with the DCSI showed a similar mortality risk. Each level of the continuous DCSI was associated with a 1.34-fold (95% CI = 1.28, 1.41) greater risk of death. Similar results were obtained for the association of the DCSI with risk of hospitalization. Comparison of receiver operating characteristic curves verified that the DCSI was a slightly better predictor of mortality than a count of complications (P<.0001). Conclusion: Compared with the complications count, the DCSI performed slightly better and appears to be a useful too] for prediction of mortality and risk of hospitalization. C1 [Young, Bessie Ann; Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. [Young, Bessie Ann; Kinder, Leslie] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA. [Young, Bessie Ann; Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Primary & Special Med Care Serv, Seattle, WA 98108 USA. [Lin, Elizabeth; Von Korff, Michael; Simon, Greg; Ludman, Evette J.; Oliver, Malia] Ctr Hlth Studies Grp Hlth Cooperat, Seattle, WA USA. [Ciechanowski, Paul; Katon, Wayne J.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Everson-Stewart, Siobhan] Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA. [Young, Bessie Ann; Boyko, Edward J.] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA. [Young, Bessie Ann] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. RP Young, BA (reprint author), Vet Affairs Puget Sound Hlth Care Syst 152 E, Epidemiol Res & Informat Ctr, 1660 S Columbian Way, Seattle, WA 98108 USA. EM youngb@u.washington.edu FU NIMH NIH HHS [K02 MH001643, MH0-1643, MH4-1739, R01 MH041739] NR 43 TC 145 Z9 146 U1 3 U2 15 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JAN PY 2008 VL 14 IS 1 BP 15 EP 24 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 253HZ UT WOS:000252510600002 PM 18197741 ER PT J AU Leaf, DA AF Leaf, David Alexander TI Chylomicronemia and the chylomicronemia syndrome: A practical approach to management SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE chylomicronemia; lipids; pancreatitis ID FATTY-ACIDS; HYPERTRIGLYCERIDEMIA; PERSPECTIVES; CHOLESTEROL; METABOLISM; METFORMIN; OBESITY; INSULIN; ADULTS AB Chylomicronemia is present when triglyceride levels exceed 1000 mg/dL. Chylomicronemia, when accompanied by eruptive xanthoma, lipemia retinalis, or abdominal symptoms, is referred to as the "chylomicronemia syndrome" and can cause acute pancreatitis. Treatment aimed at reducing triglyceride levels includes lifestyle modifications to promote weight loss with diet and physical activity coupled with medications, including fibrates, n-3 polyunsaturated fatty acids, and nicotinic acid. Chylomicronemic patients with acute pancreatitis require insulinization in an inpatient setting to abolish chylomicronemia. (C) 2008 Elsevier Inc. All rights reserved. C1 [Leaf, David Alexander] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. RP Leaf, DA (reprint author), Div Gen Internal Med, Greater Los Angeles VA Healthcare Syst, 111G,Wilshire & Sawtelle Blvds, Los Angeles, CA 90073 USA. EM davidleaf@med.va.gov NR 21 TC 30 Z9 32 U1 0 U2 3 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 JAN PY 2008 VL 121 IS 1 BP 10 EP 12 DI 10.1016/j.amjmed.2007.10.004 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 249XC UT WOS:000252262600004 PM 18187065 ER PT J AU Stein, PD Beemath, A Matta, F Goodman, LR Weg, JG Hales, CA Hull, RD Leeper, KV Sostman, HD Woodard, PK AF Stein, Paul D. Beemath, Afzal Matta, Fadi Goodman, Lawrence R. Weg, John G. Hales, Charles A. Hull, Russell D. Leeper, Kenneth V., Jr. Sostman, H. Dirk Woodard, Pamela K. TI Enlarged right ventricle without shock in acute pulmonary embolism: Prognosis SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE pulmonary embolism; right ventricular dysfunction; venous thromboembolism ID CHEST COMPUTED-TOMOGRAPHY; HELICAL CT; DYSFUNCTION SECONDARY; RISK STRATIFICATION; MORTALITY; ECHOCARDIOGRAPHY; ASSOCIATION; ANGIOGRAPHY; PREDICTORS; ALTEPLASE AB OBJECTIVE: An unsettled issue is the use of thrombolytic agents in patients with acute pulmonary embolism (PE) who are hemodynamically stable but have right ventricular (RV) enlargement. We assessed the in-hospital mortality of hemodynamically stable patients with PE and RV enlargement. METHODS: Patients were enrolled in the Prospective Investigation of Pulmonary Embolism Diagnosis II. Exclusions included shock, critical illness, ventilatory support, or myocardial infarction within 1 month, and ventricular tachycardia or ventricular fibrillation within 24 hours. We evaluated the ratio of the RV minor axis to the left ventricular minor axis measured on transverse images during computed tomographic angiography. RESULTS: Among 76 patients with RV enlargement treated with anticoagulants and/or inferior vena cava filters, in-hospital deaths from PE were 0 of 76 (0%) and all-cause mortality was 2 of 76 (2.6%). No septal motion abnormality was observed in 49 patients (64%), septal flattening was observed in 25 patients (33%), and septal deviation was observed in 2 patients (3%). No patients required ventilatory support, vasopressor therapy, rescue thrombolytic therapy, or catheter embolectomy. There were no in-hospital deaths caused by PE. There was no difference in all-cause mortality between patients with and without RV enlargement (relative risk = 1.04). CONCLUSION: In-hospital prognosis is good in patients with PE and RV enlargement if they are not in shock, acutely ill, or on ventilatory support, or had a recent myocardial infarction or life-threatening arrhythmia. RV enlargement alone in patients with PE, therefore, does not seem to indicate a poor prognosis or the need for thrombolytic therapy. (C) 2008 Elsevier Inc. All rights reserved. C1 [Stein, Paul D.] Wayne State Univ, Sch Med, Dept Med, Detroit, MI 48201 USA. [Goodman, Lawrence R.] Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA. [Stein, Paul D.; Beemath, Afzal; Matta, Fadi] St Joseph Mercy Oakland Hosp, Dept Res, Pontiac, MI 48341 USA. [Weg, John G.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Hales, Charles A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Hales, Charles A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hull, Russell D.] Univ Calgary, Dept Med, Calgary, AB, Canada. [Leeper, Kenneth V., Jr.] Emory Univ, Dept Med, Atlanta, GA 30322 USA. [Sostman, H. Dirk] Well Cornell Med Coll, Off Dean, Houston, TX USA. [Sostman, H. Dirk] Methodist Hosp, Houston, TX 77030 USA. [Woodard, Pamela K.] Washington Univ, Dept Radiol, St Louis, MO USA. RP Stein, PD (reprint author), St Joseph Mercy Oakland, 44405 Woodwaard Ave, Pontiac, MI 48341 USA. EM Steinp@trinity-health.org FU NHLBI NIH HHS [U01 HL063899-04, HL63899, HL63928, HL63931, HL63940, HL63981, HL63982, HL67453, U01 HL063899, U01 HL063928, U01 HL063928-04, U01 HL063931, U01 HL063931-04, U01 HL063940, U01 HL063940-04, U01 HL063981, U01 HL063981-04, U01 HL063982, U01 HL063982-04, U01 HL067453, U01 HL067453-04] NR 32 TC 54 Z9 57 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 JAN PY 2008 VL 121 IS 1 BP 34 EP 42 DI 10.1016/j.amjmed.2007.06.032 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 249XC UT WOS:000252262600010 PM 18187071 ER PT J AU Shlipak, MG Ix, JH Bibbins-Domingo, K Lin, F Whooley, MA AF Shlipak, Michael G. Ix, Joachim H. Bibbins-Domingo, Kirsten Lin, Feng Whooley, Mary A. TI Biomarkers to predict recurrent cardiovascular disease: The heart and soul study SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE albuminuria; biomarkers; cardiovascular events; coronary artery disease; C-reactive protein; cystatin C; fibrinogen; interleukin-6; N-terminal prohormone brain natriuretic peptide ID C-REACTIVE PROTEIN; ACUTE CORONARY SYNDROMES; NATRIURETIC PEPTIDE; CYSTATIN-C; ARTERY-DISEASE; RISK-FACTORS; FETUIN-A; ASSOCIATION; PREVENTION; EVENTS AB PURPOSE: The study purpose was to evaluate the ability of 6 biomarkers to improve the prediction of cardiovascular events among persons with established coronary artery disease. BACKGROUND: Cardiovascular risk algorithms are designed to predict the initial onset of coronary artery disease but are less effective in persons with preexisting coronary artery disease. METHODS: We examined the association of N-terminal prohormone brain natriuretic peptide (Nt-proBNP), cystatin C, albuminuria, C-reactive protein (CRP), interleukin-6, and fibrinogen with cardiovascular events in 979 Heart and Soul Study participants with coronary artery disease after adjusting for demographic, lifestyle, and behavior variables; cardiovascular risk factors; cardiovascular disease severity; medication use; and left ventricular ejection fraction. The outcome was a composite of stroke, myocardial infarction, and coronary heart disease death during an average of 3.5 years of follow-up. RESULTS: During follow-up, 142 participants (15%) developed cardiovascular events. The highest quartiles ( vs lower 3 quartiles) of 5 biomarkers were individually associated with cardiovascular risk after multivariate analysis: Nt-proBNP hazard ratio (HR) = 2.13 (95% confidence interval [CI], 1.43-3.18); cystatin C HR = 1.72 (95% CI, 1.10-2.70); albuminuria HR = 1.71 (95% CI, 1.15-2.54); CRP HR = 2.00 ( 95% CI, 1.40-2.85); and interleukin-6 HR = 1.76 (95% CI, 1.22-2.53). When all biomarkers were included in the multivariable analysis, only Nt-proBNP, albuminuria, and CRP remained significant predictors of events: HR = 1.88 (95% CI, 1.23-2.85), HR = 1.63 (95% CI, 1.09-2.43), and HR = 1.82 (95% CI, 1.24-2.67), respectively. The area under the receiver operator curve for clinical predictors alone was 0.73 (95% CI, 0.68-0.78); adding Nt-proBNP, albuminuria, and CRP significantly increased the area under the receiver operator curve to 0.77 ( 95% CI, 0.73-0.82, P <. 005). CONCLUSION: Among persons with prevalent coronary artery disease, biomarkers reflecting hemodynamic stress, kidney damage, and inflammation added significant risk discrimination for cardiovascular events. (C) 2008 Elsevier Inc. All rights reserved. C1 [Shlipak, Michael G.; Whooley, Mary A.] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. [Shlipak, Michael G.; Whooley, Mary A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Shlipak, Michael G.; Lin, Feng; Whooley, Mary A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Ix, Joachim H.] Univ Calif San Diego, Div Nephrol, San Diego, CA 92103 USA. [Bibbins-Domingo, Kirsten] San Francisco Gen Hosp, Div Gen Internal Med, San Francisco, CA 94110 USA. RP Shlipak, MG (reprint author), 4150 Clement St,111A1, San Francisco, CA 94121 USA. EM Michael.shlipak@ucsf.edu FU NHLBI NIH HHS [R03 HL068099-01, R01 HL073208, R01 HL073208-01, R01 HL073208-02, R03 HL068099]; NIDDK NIH HHS [R01 DK066488, R01 DK066488-01, R01 DK066488-02, R01 DK066488-03, R01 DK066488-04] NR 17 TC 81 Z9 86 U1 1 U2 7 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 JAN PY 2008 VL 121 IS 1 BP 50 EP 57 DI 10.1016/j.amjmed.2007.06.030 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 249XC UT WOS:000252262600012 PM 18187073 ER PT J AU Chonchol, M Whittle, J Desbien, A Orner, MB Petersen, LA Kressin, NR AF Chonchol, Michel Whittle, Jeff Desbien, Angela Orner, Michelle B. Petersen, Laura A. Kressin, Nancy R. TI Chronic kidney disease is associated with angiographic coronary artery disease SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE chronic kidney disease; coronary artery disease; coronary angiography ID ISCHEMIC-HEART-DISEASE; CHRONIC-RENAL-FAILURE; PRACTICE GUIDELINES; RACIAL-DIFFERENCES; UNITED-STATES; RISK-FACTORS; TASK-FORCE; PREVALENCE; INSUFFICIENCY; HEMODIALYSIS AB Background/Aims: Patients with chronic kidney disease (CKD) have a dramatically increased risk for cardiovascular mortality. Few prior studies have examined the independent association of CKD with coronary anatomy. Methods: We evaluated the relationship between CKD and severe coronary artery disease (CAD) in 261 male veterans with nuclear perfusion imaging tests suggesting coronary ischemia. We used chart review and patient and provider interviews to collect demographics, clinical characteristics, and coronary anatomy results. We defined CKD as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m 2, based on the creatinine obtained prior to angiography. We defined significant coronary obstruction as at least one 70% or greater stenosis. We used logistic regression to determine whether CKD was independently associated with significant coronary obstruction. Results: The likelihood of CAD increased monotonically with decreasing eGFR, from 51% among patients with eGFR >= 90 ml/min/1.73 m 2 to 84% in those with eGFR <30 ml/min/1.73 m(2) (p = 0.0046). Patients with CKD were more likely than those without CKD to have at least one significant coronary obstruction (75.9 vs. 60.7%, p = 0.016). Patients with CKD also had more significant CAD, that is, were more likely to have three-vessel and/or left main disease than those without CKD (34.9 vs. 16.9%, p = 0.0035). In logistic regression analysis, controlling for demographics and comorbidity, CKD continued to be independently associated with the presence of significant CAD (p = 0.0071). Conclusion: CKD patients have a high prevalence of obstructive coronary disease, which may contribute to their high cardiovascular mortality. Copyright (C) 2007 S. Karger AG, Basel. C1 Univ Colorado, Hlth Sci Ctr, Div Renal Dis & Hypertens, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Clement J Zablocki VA Med Ctr, Primary Care Div, Milwaukee, WI USA. Bedford VA Med Ctr, Ctr Hlth Quality Outcomes & Econ Res, Bedford, MA USA. Baylor Coll Med, Houston VA Med Ctr, Dev Ctr Excellence, Houston Ctr Quality Care & Utilizat Studies, Houston, TX USA. Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA USA. RP Chonchol, M (reprint author), Univ Colorado, Hlth Sci Ctr, Div Renal Dis & Hypertens, Box C 281, Denver, CO 80262 USA. EM Michel.Chonchol@uchsc.edu OI Kressin, Nancy/0000-0003-2767-4286 NR 28 TC 39 Z9 43 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2008 VL 28 IS 2 BP 354 EP 360 DI 10.1159/000111829 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 238GS UT WOS:000251436000023 PM 18046083 ER PT J AU Fischer, MJ Brimhall, BB Parikh, CR AF Fischer, Michael J. Brimhall, Bradley B. Parikh, Chirag R. TI Uncomplicated acute renal failure and post-hospital care: A not so uncomplicated illness SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE acute renal failure, outcomes; extended facility care; home health care; nephrology clinical ID CRITICALLY ILL PATIENTS; RISK-FACTORS; RESOURCE UTILIZATION; MEDICAL ILLNESS; SERIOUSLY ILL; NURSING-HOME; MORTALITY; MULTICENTER; OUTCOMES; AGE AB Background: Although uncomplicated acute renal failure (ARF) is associated with significant hospital resource utilization, its health care requirements following hospital discharge are not well understood. The goal of this study was to characterize the post-hospital care requirements incurred by patients with uncomplicated ARF and to determine its important influencing factors. Methods: We obtained hospital case mix data sets for a 2-year period (1999-2000) from the Massachusetts Division of Health Care Finance and Policy. Utilizing DRG and ICD-9-CM codes from 23 Massachusetts hospitals, we identified 2,128 adult patients whose primary reason for hospitalization was uncomplicated ARF. Post-hospital care was defined as the receipt of extended facility care or home health care following hospital discharge. Results: Nearly 50% of patients hospitalized with uncomplicated ARF required some type of post-hospital care, of whom 27% underwent extended facility care while 22% received home health care. The post-hospital care requirements for uncomplicated ARF were similar to those for serious medical conditions (e.g. heart failure) and exceeded those of many common illnesses (e.g., bronchitis). Advancing age, worsening severity of illness, female gender, and emergency room admission were independently associated with receipt of post-hospital care (p < 0.05). A trend existed between less frequent post-hospital care requirements and hospitalization at academic medical centers compared with non-academic hospitals. Conclusions: Uncomplicated ARF is frequently associated with prolonged care following hospitalization. As the health care utilization for ARF becomes better characterized, these post-hospital care resources should not be overlooked. Copyright (C) 2008 S. Karger AG, Basel. C1 [Fischer, Michael J.] Univ Illinois, Dept Med, Nephrol Sect, Med Ctr, Chicago, IL 60612 USA. [Fischer, Michael J.] Jesse Brown VA Med Ctr, Nephrol Sect, Dept Internal Med, Chicago, IL USA. [Fischer, Michael J.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA. [Brimhall, Bradley B.] Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA. [Brimhall, Bradley B.] Univ New Mexico, Sch Med, Tricore Reference Labs, Albuquerque, NM 87131 USA. [Parikh, Chirag R.] Yale Univ, Sch Med, Dept Internal Med, Nephrol Sect, New Haven, CT 06510 USA. [Parikh, Chirag R.] Vet Affairs Med Ctr, New Haven, CT USA. RP Fischer, MJ (reprint author), Univ Illinois, Dept Med, Nephrol Sect, Med Ctr, MC 793,820 S Wood St, Chicago, IL 60612 USA. EM fischerm@uic.edu FU NIDDK NIH HHS [K23-DK064689-01, K23 DK064689] NR 37 TC 9 Z9 14 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2008 VL 28 IS 3 BP 523 EP 530 DI 10.1159/000114005 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 271GU UT WOS:000253777700020 PM 18223306 ER PT J AU Ozgen, B Cunnane, ME Caruso, PA Curtin, HD AF Ozgen, B. Cunnane, M. E. Caruso, P. A. Curtin, H. D. TI Comparison of 45 degrees oblique reformats with axial reformats in CT evaluation of the vestibular aqueduct SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID SENSORINEURAL HEARING-LOSS; COMPUTED-TOMOGRAPHY; MENIERES-DISEASE; CHILDREN; BONE AB BACKGROUND AND PURPOSE: Measurement of the vestibular aqueduct on CT scans of the temporal bone is important for the detection of large vestibular aqueduct syndrome; typically this is done in the axial plane. We sought to determine the usefulness of reformats performed in the 45 degrees oblique plane for evaluating the vestibular aqueduct. In addition, we provide reference measurements for the vestibular aqueduct in the 45 degrees oblique plane. MATERIALS AD METHODS: We selected 15 subjects referred for reasons other than sensorineural hearing loss, and without radiographic evidence of abnormality of the inner ear. Two neuroradiologists independently evaluated both axial and 45 degrees oblique images for ease in visualizing the vestibular aqueduct. Then, one of the readers (B.O.) performed reference measurements of the diameter at the mouth and midpoint of the aqueduct. RESULTS: Combining the results of both observers, we judged 82% of vestibular aqueducts as well-defined or easily traced on 45 degrees oblique views, whereas we judged only 55% as well-defined or easily traced on axial views. The difference in the degrees of visualization between the 45 degrees oblique and axial reformats was significant for observer 1 (P =.022) and observer 2 (P =.001). Intraobserver agreement about the visibility of the aqueduct was higher on the 45 degrees oblique than the axial views: (kappa = 0.682, SE = 0.171) for 45 degrees oblique reformats; (kappa= 0.480, SE = 0.145) for axial reformats. On the 45 degrees oblique reformats, the mean external aperture dimension of the vestibular aqueduct was measured as 0.616 +/- 0.133 mm, and the postisthmic segment had a mean width of 0.482 +/- 0.099 mm. CONCLUSIONS: The 45 degrees oblique plane gives a more reliable depiction of the vestibular aqueduct than the axial plane in CT evaluation of the temporal bone. This technique can be useful in cases of borderline enlargement of the vestibular aqueduct. C1 [Cunnane, M. E.; Caruso, P. A.; Curtin, H. D.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Ozgen, B.] Hacettepe Univ, Fac Med, Dept Radiol, TR-06100 Ankara, Turkey. RP Cunnane, ME (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM mary_beth_cunnane@meei.harvard.edu RI Ozgen Mocan, Burce/I-9403-2013 OI Ozgen Mocan, Burce/0000-0003-0758-2712 NR 23 TC 11 Z9 12 U1 0 U2 1 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 JAN PY 2008 VL 29 IS 1 BP 30 EP 34 DI 10.3174/ajnr.A0735 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 252VT UT WOS:000252475600012 PM 17947373 ER PT J AU Nogueira, RG Dabus, G Rabinov, JD Eskey, CJ Ogilvy, CS Hirsch, JA Pryor, JC AF Nogueira, R. G. Dabus, G. Rabinov, J. D. Eskey, C. J. Ogilvy, C. S. Hirsch, J. A. Pryor, J. C. TI Preliminary experience with Onyx embolization for the treatment of intracranial dural arteriovenous fistulas SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the American-Society-of-Neuroradiology CY JUN 09-11, 2007 CL Chicago, IL SP Amer Soc Neuroradiol ID MALFORMATIONS; SINUS; SWINE AB BACKGROUND AND PURPOSE: Onyx was recently approved for the treatment of pial arteriovenous malformations, but its use to treat dural arteriovenous fistulas (DAVFs) is not yet well established. We now report on the treatment of intracranial DAVFs using this nonadhesive liquid embolic agent. MATERIALS AND METHODS: We performed a retrospective analysis of 12 consecutive patients with intracranial DAVFs who were treated with Onyx as the single treatment technique at our institution between March 2006 and February 2007. RESULTS: A total of 17 procedures were performed in 12 patients. In all of the cases, transarterial microcatheterization was performed, and Onyx-18 or a combination of Onyx-18/Onyx-34 was used. Eight patients were men. The mean age was 56 +/- 12 years. Nine patients were symptomatic. There was an average of 5 feeders per DAVF (range, 1-9). Cortical venous reflux was present in all of the cases except for 1 of the symptomatic patients. Complete resolution of the DAVF on immediate posttreatment angiography was achieved in 10 patients. The remaining 2 patients had only minimal residual shunting postembolization, 1 of whom appeared cured on a follow-up angiogram 8 weeks later. The other patient has not yet had angiographic follow-up. Follow-up angiography (mean, 4.4 months) is currently available in 9 patients. There was I angiographic recurrence (asymptomatic), which was subsequently re-embolized with complete occlusion of the fistula and its draining vein. There was no significant morbidity or mortality. CONCLUSION: In our experience, the endovascular treatment of intracranial DAVFs with Onyx is feasible, safe, and highly effective with a small recurrence rate in the short-term follow-up. C1 [Nogueira, R. G.; Dabus, G.; Rabinov, J. D.; Eskey, C. J.; Hirsch, J. A.; Pryor, J. C.] Massachusetts Gen Hosp, Dept Intervent Neuroradiol & Endovasc Neurosurg, Div Intervent Neuroradiol & Endovasc Neurosurg, Boston, MA 02114 USA. [Nogueira, R. G.] Massachusetts Gen Hosp, Div Vasc & Crit Care Neurol, Boston, MA 02114 USA. [Ogilvy, C. S.] Massachusetts Gen Hosp, Div Vasc Neurosurg, Boston, MA 02114 USA. RP Nogueira, RG (reprint author), Massachusetts Gen Hosp, Dept Intervent Neuroradiol & Endovasc Neurosurg, Div Intervent Neuroradiol & Endovasc Neurosurg, 55 Fruit St,GRB 2-241, Boston, MA 02114 USA. EM rnogueira@partners.org NR 16 TC 96 Z9 103 U1 0 U2 1 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 JAN PY 2008 VL 29 IS 1 BP 91 EP 97 DI 10.3174/ajnr.A0768 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 252VT UT WOS:000252475600025 PM 17974618 ER PT J AU Bouskila, M Hirshman, MF Jensen, J Goodyear, LJ Sakamoto, K AF Bouskila, Michale Hirshman, Michael F. Jensen, Jorgen Goodyear, Laurie J. Sakamoto, Kei TI Insulin promotes glycogen synthesis in the absence of GSK3 phosphorylation in skeletal muscle SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Editorial Material DE glycogen synthase kinase 3; phosphorylase; muscle metabolism; insulin signaling; type 2 diabetes ID GLUT4 GLUCOSE-TRANSPORTER; TRANSGENIC MICE; SYNTHASE; METABOLISM; ADRENALINE; ACTIVATION; MECHANISM; RAT; IDENTIFICATION; ACCUMULATION AB Insulin promotes dephosphorylation and activation of glycogen synthase (GS) by inactivating glycogen synthase kinase (GSK) 3 through phosphorylation. Insulin also promotes glucose uptake and glucose 6-phosphate (G-6-P) production, which allosterically activates GS. The relative importance of these two regulatory mechanisms in the activation of GS in vivo is unknown. The aim of this study was to investigate if dephosphorylation of GS mediated via GSK3 is required for normal glycogen synthesis in skeletal muscle with insulin. We employed GSK3 knockin mice in which wild-type GSK3 alpha and -beta genes are replaced with mutant forms (GSK3 alpha/beta(S21A/S21A/S9A/S9A)), which are nonresponsive to insulin. Although insulin failed to promote dephosphorylation and activation of GS in GSK3 alpha/beta(S21A/S21A/S9A/S9A) mice, glycogen content in different muscles from these mice was similar compared with wild-type mice. Basal and epinephrine-stimulated activity of muscle glycogen phosphorylase was comparable between wild-type and GSK3 knockin mice. Incubation of isolated soleus muscle in Krebs buffer containing 5.5 mM glucose in the presence or absence of insulin revealed that the levels of G-6-P, the rate of [C-14] glucose incorporation into glycogen, and an increase in total glycogen content were similar between wild-type and GSK3 knockin mice. Injection of glucose containing 2-deoxy-[H-3] glucose and [C-14] glucose also resulted in similar rates of muscle glucose uptake and glycogen synthesis in vivo between wild-type and GSK3 knockin mice. These results suggest that insulin-mediated inhibition of GSK3 is not a rate-limiting step in muscle glycogen synthesis in mice. This suggests that allosteric regulation of GS by G-6-P may play a key role in insulin-stimulated muscle glycogen synthesis in vivo. C1 [Bouskila, Michale; Sakamoto, Kei] Univ Dundee, Coll Life Sci, MRC, Prot Phosphorylat Unit, Dundee DD1 5EH, Scotland. [Hirshman, Michael F.; Goodyear, Laurie J.] Brigham & Womens Hosp, Joslin Diabet Ctr, Div Res, Dept Med, Boston, MA 02115 USA. [Hirshman, Michael F.; Goodyear, Laurie J.] Harvard Univ, Sch Med, Boston, MA USA. [Jensen, Jorgen] Natl Inst Occupat Hlth, Dept Physiol, Oslo, Norway. RP Sakamoto, K (reprint author), Univ Dundee, Coll Life Sci, MRC, Prot Phosphorylat Unit, Dow St, Dundee DD1 5EH, Scotland. EM k.sakamoto@dundee.ac.uk RI Jensen, Jorgen/O-2245-2013 FU Diabetes UK [07/0003529]; Medical Research Council [MC_U127088492]; NIAMS NIH HHS [AR-045670]; NIDDK NIH HHS [DK-068626] NR 29 TC 55 Z9 57 U1 1 U2 7 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 JAN PY 2008 VL 294 IS 1 BP E28 EP E35 DI 10.1152/ajpendo.00481.2007 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 250LZ UT WOS:000252302900005 PM 18003720 ER PT J AU Gukovsky, I Lugea, A Shahsahebi, M Cheng, JH Hong, PP Jung, YJ Deng, QG French, BA Lungo, W French, SW Tsukamoto, H Pandol, SJ AF Gukovsky, Ilya Lugea, Aurelia Shahsahebi, Mohammad Cheng, Jason H. Hong, Peggy P. Jung, Yoon J. Deng, Quing-gao French, Barbara A. Lungo, William French, Samuel W. Tsukamoto, Hidekazu Pandol, Stephen J. TI A rat model reproducing key pathological responses of alcoholic chronic pancreatitis SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE ethanol; inflammatory response; pancreatic stellate cells; cerulein; cyclosporin A ID CERULEIN-INDUCED PANCREATITIS; NF-KAPPA-B; ACINAR-CELLS; DIBUTYLTIN DICHLORIDE; CYCLOSPORINE-A; LONG-TERM; TUBULAR COMPLEXES; OXIDATIVE STRESS; STELLATE CELLS; ANIMAL-MODELS AB Although alcohol abuse is the major cause of chronic pancreatitis, the pathogenesis of alcoholic chronic pancreatitis (ACP) remains obscure. A critical obstacle to understanding the mechanism of ACP is lack of animal models. Our objective was to develop one such model. Rats were pair-fed for 8 wk ethanol or control Lieber-DeCarli liquid diet. For the last 2 wk, they received cyclosporin A (CsA; 20 mg/kg once daily) or vehicle. After 1 wk on CsA, one episode of acute pancreatitis was induced by four 20 mu g/kg injections of cerulein (Cer); controls received saline. Pancreas was analyzed 1 wk after the acute pancreatitis. CsA or Cer treatments alone did not result in pancreatic injury in either control (C)- or ethanol (E)- fed rats. We found, however, that alcohol dramatically aggravated pathological effect of the combined CsA+Cer treatment on pancreas, resulting in massive loss of acinar cells, persistent inflammatory infiltration, and fibrosis. Macrophages were prominent in the inflammatory infiltrate. Compared with control-fed C+CsA+Cer rats, their ethanol-fed E + CsA + Cer counterparts showed marked increases in pancreatic NF-kappa B activation and cytokine/ chemokine mRNA expression, collagen and fibronectin, the expression and activities of matrix metalloproteinase-2 and - 9, and activation of pancreatic stellate cells. Thus we have developed a model of alcohol-mediated postacute pancreatitis that reproduces three key responses of human ACP: loss of parenchyma, sustained inflammation, and fibrosis. The results indicate that alcohol impairs recovery from acute pancreatitis, suggesting a mechanism by which alcohol sensitizes pancreas to chronic injury. C1 [Gukovsky, Ilya; Lugea, Aurelia; Shahsahebi, Mohammad; Cheng, Jason H.; Hong, Peggy P.; Jung, Yoon J.; Pandol, Stephen J.] Vet Affairs Greater Los Angels Healthcare Syst, Torrance, CA USA. [Gukovsky, Ilya; Lugea, Aurelia; Shahsahebi, Mohammad; Cheng, Jason H.; Hong, Peggy P.; Jung, Yoon J.; Deng, Quing-gao; French, Barbara A.; Lungo, William; French, Samuel W.; Tsukamoto, Hidekazu; Pandol, Stephen J.] USC UCLA, Res Ctr Alcohol Liver & Pancreat Dis, Torrance, CA USA. [Gukovsky, Ilya; Lugea, Aurelia; Shahsahebi, Mohammad; Cheng, Jason H.; Hong, Peggy P.; Jung, Yoon J.; Pandol, Stephen J.] Univ Calif Los Angeles, Torrance, CA USA. [French, Barbara A.; Lungo, William; French, Samuel W.] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. RP Gukovsky, I (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, W Los Angeles VA Healthcare Ctr, Bldg 258,Rm 340,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM igukovsk@ucla.edu FU PHS HHS [P50-A11999] NR 74 TC 35 Z9 37 U1 1 U2 4 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 JAN PY 2008 VL 294 IS 1 BP G68 EP G79 DI 10.1152/ajpgi.00006.2007 PG 12 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 252RP UT WOS:000252464600009 PM 17884979 ER PT J AU Parrish, DC Gritman, K Van Winkle, DM Woodward, WR Bader, M Habecker, BA AF Parrish, Diana C. Gritman, Kurt Van Winkle, Donna M. Woodward, William R. Bader, Michael Habecker, Beth A. TI Postinfarct sympathetic hyperactivity differentially stimulates expression of tyrosine hydroxylase and norepinephrine transporter SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE ischemia-reperfusion; sympathetic hyperactivity; autonomic ID ACUTE MYOCARDIAL-INFARCTION; LOW BRAIN ANGIOTENSINOGEN; NERVE GROWTH-FACTOR; TRANSGENIC RATS; TIME-COURSE; HEART-RATE; NEURONS; ISCHEMIA; DEPOLARIZATION; CATECHOLAMINES AB The balance between norepinephrine (NE) synthesis, release, and reuptake is disrupted after acute myocardial infarction, resulting in elevated extracellular NE. Stimulation of sympathetic neurons in vitro increases NE synthesis and the synthetic enzyme tyrosine hydroxylase (TH) to a greater extent than it increases NE reuptake and the NE transporter (NET), which removes NE from the extracellular space. We used TGR(ASrAOGEN) transgenic rats, which lack postinfarct sympathetic hyperactivity, to test the hypothesis that increased cardiac sympathetic nerve activity accounts for the imbalance in TH and NET expression in these neurons after myocardial infarction. TH and NET mRNA levels were identical in the stellate ganglia of unoperated TGR( ASrAOGEN) rats compared with Sprague Dawley (SD) controls, but the threefold increase in TH and twofold increase in NET mRNA seen in the stellate ganglia of SD rats 1 wk after ischemia-reperfusion was absent in TGR( ASrAOGEN) rats. Similarly, the increase in TH and NET protein observed in the base of the SD ventricle was absent in the base of the TGR ( ASrAOGEN) ventricle. Neuronal TH content was depleted in the left ventricle of both genotypes, whereas NET was unchanged. Basal heart rate and cardiac function were similar in both genotypes, but TGR( ASrAOGEN) hearts were more sensitive to the beta-agonist dobutamine. Tyramine-induced release of endogenous NE generated similar changes in ventricular pressure and contractility in both genotypes, but postinfarct relaxation was enhanced in TGR( ASrAOGEN) hearts. These data support the hypothesis that postinfarct sympathetic hyperactivity is the major stimulus increasing TH and NET expression in cardiac neurons. C1 [Parrish, Diana C.; Gritman, Kurt; Habecker, Beth A.] Oregon Hlth & Sci Univ, Sch Med, Dept Physiol & Pharmacol, Portland, OR 97239 USA. [Van Winkle, Donna M.] Oregon Hlth & Sci Univ, Sch Med, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA. [Woodward, William R.] Oregon Hlth & Sci Univ, Sch Med, Dept Neurol, Portland, OR 97239 USA. [Van Winkle, Donna M.] Portland VA Med Ctr, Portland, OR USA. [Bader, Michael] Max Delbruck Ctr Mol Med, Berlin, Germany. RP Habecker, BA (reprint author), Oregon Hlth & Sci Univ, Sch Med, Dept Physiol & Pharmacol, L334,3181 SW Sam Jackson Pk,Rd, Portland, OR 97239 USA. EM habecker@ohsu.edu OI Habecker, Beth/0000-0002-4658-8730; Bader, Michael/0000-0003-4780-4164 FU NHLBI NIH HHS [R01 HL 68231, R01 HL068231] NR 35 TC 28 Z9 30 U1 0 U2 0 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 JAN PY 2008 VL 294 IS 1 BP H99 EP H106 DI 10.1152/ajpheart.00533.2007 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 249WO UT WOS:000252261200014 PM 17951370 ER PT J AU Rumbaut, RE Mirkovic, D AF Rumbaut, Rolando E. Mirkovic, Dragan TI Magnetic therapy for edema in inflammation: a physiological assessment SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Editorial Material ID FIELD THERAPY; DOUBLE-BLIND; COMPLEMENTARY; PAIN C1 [Rumbaut, Rolando E.] Baylor Coll Med, Childrens Nutr Res Ctr, Dept Med, Houston, TX 77030 USA. [Rumbaut, Rolando E.] Baylor Coll Med, Childrens Nutr Res Ctr, Dept Pediat, Houston, TX 77030 USA. [Rumbaut, Rolando E.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Mirkovic, Dragan] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX USA. RP Rumbaut, RE (reprint author), Baylor Coll Med, Childrens Nutr Res Ctr, Dept Med, 1100 Bates Ave,Rm 6014441, Houston, TX 77030 USA. EM rrumbaut@bcm.tmc.edu NR 20 TC 3 Z9 3 U1 0 U2 1 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 JAN PY 2008 VL 294 IS 1 BP H19 EP H20 DI 10.1152/ajpheart.01342.2007 PG 2 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 249WO UT WOS:000252261200005 PM 18032520 ER PT J AU Wecht, JM Weir, JP Goldstein, DS Krothe-Petroff, A Spungen, AM Holmes, C Bauman, WA AF Wecht, Jill M. Weir, Joseph P. Goldstein, David S. Krothe-Petroff, Annmarie Spungen, Ann M. Holmes, Courtney Bauman, William A. TI Direct and reflexive effects of nitric oxide synthase inhibition on blood pressure SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE spinal cord injury; nitro-L-arginine methyl ester; norepinephrine; sympathetic nervous system ID SYMPATHETIC NERVOUS-SYSTEM; CONSCIOUS RATS; L-ARGININE; HUMANS; TONE; HYPERTENSION; TETRAPLEGIA; HYPOTENSION; MUSCLE AB Direct effects of vasoactive substances on blood pressure can be examined in individuals with tetraplegia due to disruption of descending spinal pathways to sympathetic preganglionic neurons, as cervical lesions interfere with baroreceptor reflex buffering of sympathetic outflow. In this study, we assessed effects of the nitric oxide synthase inhibitor nitro-L-arginine methyl ester (L- NAME) on mean arterial pressure, heart rate, and plasma norepinephrine concentrations in individuals with tetraplegia vs. effects shown in a neurologically intact control group. Seven individuals with tetraplegia and seven age-matched controls received, on separate visits and in the following order, placebo (30 ml normal saline) and 0.5, 1, 2, and 4 mg/ kg L- NAME intravenously over 60 min. Supine hemodynamic data were collected, and blood was sampled at the end of each infusion and at 120, 180, and 240 min thereafter. L- NAME increased mean arterial pressure, and the relative increase was greater in the tetraplegia group than in the control group. Heart rate was reduced after L- NAME administration in both groups. L- NAME decreased plasma norepinephrine in the control group but not in the group with tetraplegia. These findings suggest that reflexive sympathoinhibition normally buffers the pressor response to nitric oxide synthase inhibition, an effect that is not evident in individuals with tetraplegia as a result of decentralized sympathetic vasomotor control. C1 [Wecht, Jill M.] James J Peters Vet Affairs Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA. [Wecht, Jill M.; Spungen, Ann M.; Bauman, William A.] Mt Sinai Hosp, Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Wecht, Jill M.; Spungen, Ann M.; Bauman, William A.] Mt Sinai Hosp, Mt Sinai Sch Med, Dept Rehabil Med, New York, NY 10029 USA. [Weir, Joseph P.] Des Moines Univ Osteopath Med Ctr, Des Moines, IA USA. [Goldstein, David S.; Holmes, Courtney] Natl Inst Neurol Disorders & Stroke, NIH, Div Intramural Res, Clin Neurosci Program,Clin Neurocardiol Sect, Bethesda, MD USA. RP Wecht, JM (reprint author), James J Peters Vet Affairs Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Rm 1E-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM jm.wecht@va.gov FU Intramural NIH HHS NR 30 TC 12 Z9 13 U1 0 U2 0 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 JAN PY 2008 VL 294 IS 1 BP H190 EP H197 DI 10.1152/ajpheart.00366.2007 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 249WO UT WOS:000252261200023 PM 17965289 ER PT J AU Habib, SL Riley, DJ Mahimainathan, L Bhandari, B Choudhury, GG Abboud, HE AF Habib, Samy L. Riley, Daniel J. Mahimainathan, Lenin Bhandari, Basant Choudhury, Goutam Ghosh Abboud, Hanna E. TI Tuberin regulates the DNA repair enzyme OGG1 SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article ID RENAL-CELL CARCINOMA; EKER RAT MODEL; SACCHAROMYCES-CEREVISIAE; SCLEROSIS COMPLEX; BASE DAMAGE; GENE; TUMORS; TSC2; EXPRESSION; KIDNEY AB The tuberous sclerosis complex (TSC) is caused by defects in one of two tumor suppressor genes, TSC-1 or TSC-2. The TSC-2 gene encodes tuberin, a protein involved in the pathogenesis of kidney tumors, both angiomyolipomas and renal cell carcinomas. We investigated a potential role for tuberin in regulating a key DNA repair pathway. Downregulation of tuberin in human renal epithelial cells using siRNA resulted in a marked decrease in the abundance of the 8-oxoG-DNA glycosylase (OGG1). Mouse embryonic fibroblasts deficient in tuberin (TSC2(-/-) and TSC2(+/-)) also had markedly decreased OGG1 mRNA and protein expression, as well as undetectable OGG1 activity accompanied by accumulation of 8-oxodG. Gel shift analyses and chromatin immunoprecipatation identified the transcription factor NF-YA as a regulator of OGG1 activity. The binding of NF-YA to the OGG1 promoter was significantly reduced in TSC2(-/-) compared with TSC2(+/+) cells. Introduction of TSC2 cDNA into the tuberin-deficient cells restored NF-YA and OGG1 expression. Transcriptional activity of the OGG1 promoter was also decreased in tuberin-null cells. In addition, mutation of both CAAT boxes, the sites to which NF-YA binds, completely inhibits OGG1 promoter activity. These data provide the first evidence that tuberin regulates a specific DNA repair enzyme, OGG1. This regulation may be important in the pathogenesis of kidney tumors in patients with TSC. C1 [Habib, Samy L.; Riley, Daniel J.; Mahimainathan, Lenin; Bhandari, Basant; Choudhury, Goutam Ghosh; Abboud, Hanna E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, George Obrien Kidney Res Ctr, San Antonio, TX 78229 USA. [Habib, Samy L.; Riley, Daniel J.; Choudhury, Goutam Ghosh; Abboud, Hanna E.] S Texas Vet Healthcare Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. RP Habib, SL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med MSC 7882, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM habib@uthscsa.edu OI /0000-0001-5077-3552 NR 35 TC 21 Z9 21 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 2008 VL 294 IS 1 BP F281 EP F290 DI 10.1152/ajprenal.00370.2007 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 249OF UT WOS:000252237500032 PM 17989114 ER PT J AU Paunescu, TG Da Silva, N Russo, LM Mckee, M Lu, HAJ Breton, S Brown, D AF Paunescu, Teodor G. Da Silva, Nicolas Russo, Leileata M. McKee, Mary Lu, Hua A. J. Breton, Sylvie Brown, Dennis TI Association of soluble adenylyl cyclase with the V-ATPase in renal epithelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE proton pump; kidney; intercalated cells; acid-base homeostasis ID VACUOLAR H+-ATPASE; MEDULLARY COLLECTING DUCT; MALE REPRODUCTIVE-TRACT; B2 SUBUNIT ISOFORM; INTERCALATED CELLS; RAT-KIDNEY; METABOLIC-ACIDOSIS; PROXIMAL TUBULES; APICAL MEMBRANE; B1 SUBUNIT AB Activation of soluble adenylyl cyclase (sAC) by bicarbonate causes local cAMP generation, indicating that sAC might act as a pH and/or bicarbonate sensor in kidney cells involved in acid-base homeostasis. Therefore, we examined the expression of sAC in renal acid-base transporting intercalated cells (IC) and compared its distribution to that of the vacuolar proton pumping ATPase (V-ATPase) under different conditions. In all IC, sAC and V-ATPase showed considerable overlap under basal conditions, but sAC staining was also found in other cellular locations in the absence of V-ATPase. In type A-IC, both sAC and V-ATPase were apically and subapically located, whereas in type B-IC, significant basolateral colocalization of sAC and the V-ATPase was seen. When apical membrane insertion of the V-ATPase was stimulated by treatment of rats with acetazolamide, sAC was also concentrated in the apical membrane of A-IC. In mice that lack a functional B1 subunit of the V-ATPase, sAC was colocalized apically in A-IC along with V-ATPase containing the alternative B2 subunit isoform. The close association between these two enzymes was confirmed by coimmuno-precipitation of sAC from kidney homogenates using anti-V-ATPase antibodies. Our data show that sAC and the V-ATPase colocalize in IC, that they are concentrated in the IC plasma membrane under conditions that "activate" these proton secretory cells, and that they are both present in an immunoprecipitated complex. This suggests that these enzymes have a close association and could be part of a protein complex that is involved in regulating renal distal proton secretion. C1 [Paunescu, Teodor G.; Da Silva, Nicolas; Russo, Leileata M.; McKee, Mary; Lu, Hua A. J.; Breton, Sylvie; Brown, Dennis] Massachusetts Gen Hosp, Program Membrane Biol, Div Nephrol, Simches Res Ctr, Boston, MA 02114 USA. [Paunescu, Teodor G.; Da Silva, Nicolas; Russo, Leileata M.; McKee, Mary; Lu, Hua A. J.; Breton, Sylvie; Brown, Dennis] Massachusetts Gen Hosp, Program Membrane Biol, Ctr Syst Biol, Boston, MA 02114 USA. [Paunescu, Teodor G.; Da Silva, Nicolas; Russo, Leileata M.; McKee, Mary; Lu, Hua A. J.; Breton, Sylvie; Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. RP Brown, D (reprint author), Massachusetts Gen Hosp, Program Membrane Biol, Div Nephrol, Simches Res Ctr, Rm 8202,185 Cambridge St, Boston, MA 02114 USA. EM brown@receptor.mgh.harvard.edu FU NICHD NIH HHS [HD-40793]; NIDDK NIH HHS [DK-57521, DK-38452, DK-42956, DK-43341, KO1 DK-73266, KO8 DK-75940] NR 53 TC 46 Z9 48 U1 0 U2 1 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 JAN PY 2008 VL 294 IS 1 BP F130 EP F138 DI 10.1152/ajprenal.00406.2007 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 249OF UT WOS:000252237500015 PM 17959750 ER PT J AU Biederman, J Petty, CR Wilens, TE Fraire, MG Purcell, CA Mick, E Monuteaux, MC Faraone, SV AF Biederman, Joseph Petty, Carter R. Wilens, Timothy E. Fraire, Maria G. Purcell, Caitlin A. Mick, Eric Monuteaux, Michael C. Faraone, Stephen V. TI Familial risk analyses of attention deficit hyperactivity disorder and substance use disorders SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID NATIONAL-COMORBIDITY-SURVEY; DSM-III-R; DEFICIT/HYPERACTIVITY DISORDER; UNITED-STATES; FOLLOW-UP; PSYCHIATRIC COMORBIDITY; ALCOHOL; DEPENDENCE; CHILDREN; ADULTS AB Objective: A robust and bidirectional comorbidity between attention deficit hyperactivity disorder (ADHD) and psychoactive substance use disorder (alcohol or drug abuse or dependence) has been consistently reported in the extant literature. Method: First-degree relatives from a large group of pediatrically and psychiatrically referred boys with (112 probands, 385 relatives) and without (105 probands, 358 relatives) ADHD were comprehensively assessed by blind raters with structured diagnostic interviews, Familial risk analysis examined the risks in first-degree relatives for ADHD, psychoactive substance use disorder, alcohol dependence, and drug dependence after stratifying probands by the presence and absence of these disorders. Results: ADHD in the proband was consistently associated with a significant risk for ADHD in relatives. Drug dependence in probands increased the risk for drug dependence in relatives irrespective of ADHD status, whereas alcohol dependence in relatives was predicted only by ADHD probands with comorbid alcohol dependence. in addition, ADHD in the proband predicted drug dependence in relatives, and drug dependence in comparison probands increased the risk for ADHD in relatives. Both alcohol dependence and drug dependence bred true in families without evidence for a common risk between these disorders. Conclusions: Patterns of familial risk analysis suggest that the association between ADHD and drug dependence is most consistent with the hypothesis of variable expressivity of a common risk between these disorders, whereas the association between ADHD and alcohol dependence is most consistent with the hypothesis of independent transmission of these disorders. Findings also suggest specificity for the transmission of alcohol and drug dependence. C1 [Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Pschopharmacol, Dept Psychiat, Boston, MA 02114 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Pschopharmacol, Dept Psychiat, 55 Fruit St,Warren 705, Boston, MA 02114 USA. EM jbiederman@partners.org OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [5R01 HD-36317-07]; NIDA NIH HHS [R01 DA14419, 5RK24 DA01664] NR 37 TC 56 Z9 58 U1 2 U2 5 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 JAN PY 2008 VL 165 IS 1 BP 107 EP 115 PG 9 WC Psychiatry SC Psychiatry GA 248VU UT WOS:000252186000020 PM 18006872 ER PT J AU Yan, E Ko, E Luong, V Wang, HJ Romanova, M Li, ZP AF Yan, Eric Ko, Elizabeth Luong, Vincent Wang, He-Jing Romanova, Maria Li, Zhaoping TI Long-term changes in weight loss and obesity-related comorbidities after Roux-en-Y gastric bypass: a primary care experience SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Roux-en-Y gastric bypass; comorbidities; obesity; veterans affairs ID BARIATRIC SURGERY; VETERANS-AFFAIRS; MORBID-OBESITY; RISK-FACTORS; OUTCOMES; FACILITIES; MORTALITY; OLDER AB Background: Long-term results of Roux-en-Y gastric bypass (RYGB) are nonexistent in the veterans affairs (VA) population. We compare excess weight loss (EWL) success and medical comorbidity changes between the VA and non-VA population after RYGB. Methods: Retrospective review of consecutive subjects undergoing RYGB from 1997 to 2002 at the Los Angeles VA. Weight and comorbidity data were collected every 6 and 12 months, respectively. Results: Fifty-nine subjects were included; 54%, 58%,46.8%, and 44.1% Of Subjects achieved EWL > 50% at years 1 to 4. Hypertension resolved in 23%, 30%, and 32% at months 12 to 36. Obstructive sleep apnea resolved in 37%, 48%, 48%, 44%, and 60% at months 12 to 60. Diabetes mellitus resolved in 86%, 84%, 79%, and 80% at months 12 to 48. Improvements in the lipid panel were observed by month 12 and maintained thereafter. Conclusions: EWL and proportion of subjects with resolved hypertension and obstructive sleep apnea are inferior to the non-VA population. Nevertheless, improvements in measures of success are maintained in the VA population. (c) 2008 Excerpta Medica Inc. All rights reserved. C1 [Yan, Eric; Ko, Elizabeth; Luong, Vincent; Li, Zhaoping] Univ Calif Los Angeles, Ctr Human Nutr, David Geffen Sch Med, Los Angeles, CA USA. [Wang, He-Jing] Univ Calif Los Angeles, Med Ctr, Dept Biomath, Los Angeles, CA 90024 USA. [Romanova, Maria] Greater Los Angeles VA Hlth Care Syst, Los Angeles, CA USA. RP Yan, E (reprint author), Univ Calif Los Angeles, Ctr Human Nutr, David Geffen Sch Med, Los Angeles, CA USA. EM eyan@mednet.ucla.edu NR 20 TC 19 Z9 21 U1 1 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD JAN PY 2008 VL 195 IS 1 BP 94 EP 98 DI 10.1016/j.amjsurg.2007.01.036 PG 5 WC Surgery SC Surgery GA 245WA UT WOS:000251968300018 PM 18082548 ER PT J AU Bakaeen, FG Huh, J Fagan, SP Bellows, CF AF Bakaeen, Faisal G. Huh, Joseph Fagan, Shawn P. Bellows, Charles F. TI Surgical treatment of sternoclavicular joint infections in cirrhotic patients SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE sternoclavicular joint; infection; cirrhosis; surgery ID SEPTIC ARTHRITIS; MANAGEMENT AB Background: Cirrhotic patients with sternoclavicular joint (SCJ) infection pose a unique challenge for which there are no management guidelines. We reviewed our experience with this unusual infection in this high-risk patient population. Methods: We performed a retrospective analysis of all patients with cirrhosis (n = 5) treated surgically for SCJ infection from January 1998 to July 2006. Results: All infections were locally advanced with bone necrosis, complex abscess formation, or mediastinal involvement. En bloc SCJ resection was performed in 3 patients. A more conservative approach of incision and drainage with debridement was performed in 2 patients. Sepsis and/or pulmonary compromise occurred in all patients postoperatively and the surgical mortality rate was 40%. All deaths occurred after en bloc SCJ resection. Conclusions: Sternoclavicular joint infections in cirrhotic patients tend to be extensive in nature and pose a high surgical risk. Adequate surgical drainage and debridement may be better tolerated than a radical en block resection. (c) 2008 Excerpta Medica Inc. All rights reserved. C1 [Bakaeen, Faisal G.; Huh, Joseph; Fagan, Shawn P.; Bellows, Charles F.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. RP Bakaeen, FG (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. EM fbakaeen@bcm.edu NR 10 TC 2 Z9 5 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD JAN PY 2008 VL 195 IS 1 BP 130 EP 133 DI 10.1016/j.amjsurg.2007.04.009 PG 4 WC Surgery SC Surgery GA 245WA UT WOS:000251968300026 PM 18070732 ER PT J AU Farris, AB Misdraji, J Srivastava, A Muzikansky, A Deshpande, V Lauwers, GY Mino-Kenudson, M AF Farris, Alton B. Misdraji, Joseph Srivastava, Amitabh Muzikansky, Alona Deshpande, Vikram Lauwers, Gregory Y. Mino-Kenudson, Mari TI Sessile serrated adenorna - Challenging discrimination from other serrated colonic polyps SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE sessile serrated adenoma; hyperplastic polyp; serrated adenoma; interobserver agreement ID SPORADIC COLORECTAL CARCINOMAS; MICROSATELLITE INSTABILITY; HYPERPLASTIC POLYPS; MISMATCH REPAIR; MUTATOR PATHWAYS; CANCER; MUTATIONS; BRAF; METHYLATION; HMLH1 AB Sessile serrated adenoma (SSA) is the proposed precursor for microsatellite unstable colorectal carcinomas and some authorities recommend that SSAs should be managed similar to adenomas. The aim of our study was to determine whether serrated polyps can be classified with sufficient consistency to support current treatment recommendations. One hundred eighty-five serrated polyps were classified as hyperplastic polyp (HP), SSA, or traditional serrated adenoma (TSA) by 5 pathologists blinded to clinical data. The observers documented which histologic features they considered most helpful in reaching their diagnosis in each case. In a second round, the observers were provided with polyp site and size. After reaching a consensus on minimum criteria for SSA and TSA, the pathologists classified another set of 50 polyps. The interobserver concordance was calculated using K statistics. In the first round, the overall interobserver agreement was moderate (kappa = 0.55). Concordance for HP and SSA was moderate whereas it was nearly perfect for TSA. In the second round, there was no improvement in the concordance. All observers relied more often on architectural features than on cytologic ones to distinguish SSA from HP and agreement was reached that architectural features should provide the basis for the diagnosis of SSA. Subsequently, interobserver concordance was slightly improved but remained moderate (kappa = 0.58). Interobserver agreement for the diagnosis of serrated polyps is moderate. However, this level of variability is acceptable because the presence of SSA indicates increased risk of developing additional serrated polyps and carcinoma, and surveillance is appropriate. C1 [Farris, Alton B.; Misdraji, Joseph; Deshpande, Vikram; Lauwers, Gregory Y.; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Srivastava, Amitabh] Dartmouth Hitchcock Med Ctr, Dept Pathol, Lebanon, NH 03766 USA. [Srivastava, Amitabh] Dartmouth Med Sch, Lebanon, NH USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Mino-Kenudson, M (reprint author), Massachusetts Gen Hosp, Dept Pathol WRN 122, Gastrointestinal Pathol Serv, 55 Fruit St, Boston, MA 02114 USA. EM mminokenudson@partners.org RI Srivastava, Amitabh/A-9386-2009 NR 34 TC 97 Z9 109 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 JAN PY 2008 VL 32 IS 1 BP 30 EP 35 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 248ES UT WOS:000252135300005 PM 18162767 ER PT J AU Gleason, BC Hirsch, MS Nucci, MR Schmidt, BA Zembowicz, A Mihm, MC Mckee, PH Brenn, T AF Gleason, Briana C. Hirsch, Michelle S. Nucci, Marisa R. Schmidt, Birgitta A. Zembowicz, Artur Mihm, Martin C., Jr. Mckee, Phillip H. Brenn, Thomas TI Atypical genital Nevi - A clinicopothologic analysis of 56 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE atypical genital nevi; vulva; melanoma ID MELANOCYTIC NEVI; HISTOLOGIC CHARACTERISTICS; HISTOPATHOLOGIC FEATURES; DIAGNOSTIC DIFFICULTIES; PAGETOID MELANOCYTOSIS; MALIGNANT-MELANOMA; VULVAR NEVI; LESIONS; BENIGN; RISK AB Atypical genital nevi are rare melanocytic lesions that most commonly arise on the vulva of young women. They are currently regarded as nevi of special sites, in that despite histologically worrisome features, their clinical behavior is reportedly benign. However, only few studies with limited follow-up data are available. To better characterize the clinical presentation and behavior of these lesions and to further delineate their histologic features, we retrieved 56 atypical genital nevi arising in the lower female genital tract from our departmental and consultation files. The 56 lesions arose in 55 female patients with a median age of 26 years (range, 6 to 54y). The dominant histologic feature was a lentiginous and nested junctional component composed of prominent round or fusiform nests, which often showed retraction artifact and/or cellular dyscohesion. Cytologic atypia was mild in I I cases (20%), moderate in 34 (60%), and severe in 11 (20%). Ten cases, (18%) showed focal pagetoid spread, with extension to the granular layer and stratum corneum in I case. The atypical junctional melanocytic proliferation was associated with a large common dermal nevus component that dominated the lesion in 26 cases (46%). Adnexal spread (46%) and nuclear atypia of melanocytes situated in the superficial dermis (39%) were relatively common, but dermal mitoses (7%) were uncommon and maturation was present in all cases. A broad zone of dense cosinophilic fibrosis within the superficial dermis was a frequent finding (41%). Clinical follow-up was available in 45 cases (80%) with a median follow-up period of 3.5 years (range, I to 16y). Only I lesion recurred, 1.5 years after the initial excision. The original nevus in this patient had only mild cytologic atypia and was present at the margins of excision. The recurrent/persistent nevus was reexcised, and there was no further clinical recurrence in 11.5 additional years of follow-up. Our data support the hypothesis that atypical genital nevi have a benign clinical course despite their occasionally striking cytologic and architectural atypia. Awareness and recognition of this group of melanocytic lesions is important to avoid over diagnosis as melanoma with subsequent wide excision and possibly sentinel lymph node biopsy. C1 [Gleason, Briana C.; Hirsch, Michelle S.; Nucci, Marisa R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Gleason, Briana C.; Hirsch, Michelle S.; Nucci, Marisa R.] Harvard Univ, Sch Med, Boston, MA USA. [Schmidt, Birgitta A.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Zembowicz, Artur; Mihm, Martin C., Jr.] Massachusetts Gen Hosp, Dermatopathol Unit, Boston, MA 02114 USA. [Brenn, Thomas] Western Gen Hosp, Dept Pathol, Edinburgh EH4 2XU, Midlothian, Scotland. [Brenn, Thomas] Univ Edinburgh, Edinburgh, Midlothian, Scotland. RP Brenn, T (reprint author), Western Gen Hosp, Dept Pathol, Alexander Donald Bldg,1st Floor Crewe Rd, Edinburgh EH4 2XU, Midlothian, Scotland. EM t_brenn@yahoo.com NR 27 TC 37 Z9 37 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 JAN PY 2008 VL 32 IS 1 BP 51 EP 57 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 248ES UT WOS:000252135300008 PM 18162770 ER PT J AU Yantiss, RK Panczykowski, A Misdraji, J Hahn, HP Odze, RD Rennert, H Chen, YT AF Yantiss, Rhonda K. Panczykowski, Andrea Misdraji, Joseph Hahn, Hejin P. Odze, Robert D. Rennert, Hanna Chen, Yao-Tseng TI A comprehensive study of nondysplastic and dysplastic serrated polyps of the vermiform appendix (vol 31, pg 1742, 2007) SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Correction C1 [Yantiss, Rhonda K.; Panczykowski, Andrea; Rennert, Hanna] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10021 USA. [Misdraji, Joseph; Hahn, Hejin P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hahn, Hejin P.; Odze, Robert D.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Yantiss, RK (reprint author), Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10021 USA. NR 1 TC 0 Z9 0 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 JAN PY 2008 VL 32 IS 1 BP 175 EP 175 PG 1 WC Pathology; Surgery SC Pathology; Surgery GA 248ES UT WOS:000252135300027 ER PT J AU Merrill, WW AF Merrill, William W. TI From the match to the torch: New progress against an old adversary SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE COPD; oxygen; therapy; lung function ID OBSTRUCTIVE PULMONARY-DISEASE; LUNG-VOLUME-REDUCTION; SEVERE EMPHYSEMA; RANDOMIZED-TRIAL; MEDICAL THERAPY; EXACERBATIONS; COPD; SALMETEROL; SURGERY; SMOKERS AB Chronic obstructive pulmonary disease is a medical problem of significant worldwide importance. Millions of patients are severely affected worldwide, and healthcare costs range in the billions of dollars per year. The importance of this illness and its effect on the world population have recently been emphasized in the report of the international consortium called the Gold Initiative. This group has now published several updates to their original report. The following monograph summarizes this important disease process and review recent research in this significant area of clinical medicine. C1 [Merrill, William W.] Med Univ S Carolina, Dept Med, Charleston, SC 29401 USA. [Merrill, William W.] Med Univ S Carolina, Med Serv, Ralph H Johnson VAMC, Charleston, SC 29401 USA. RP Merrill, WW (reprint author), Med Univ S Carolina, Med Serv, Ralph H Johnson VAMC 111, 109 Bee St, Charleston, SC 29401 USA. EM William.merrill2@va.gov NR 26 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD JAN PY 2008 VL 335 IS 1 BP 2 EP 6 DI 10.1097/MAJ.0b013e31815f1e24 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 251NJ UT WOS:000252380000002 PM 18195576 ER PT J AU Gordon, AJ Liberto, J Granda, S Salmon-Cox, S Andree, T McNicholas, L AF Gordon, Adam J. Liberto, Joseph Granda, Stephanie Salmon-Cox, Sara Andree, Tykia McNicholas, Laura TI Outcomes of DATA 2000 Certification Trainings for the Provision of Buprenorphine Treatment in the Veterans Health Administration SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article AB Despite the high numbers of veterans with opioid dependence, few receive pharmacologic treatment for this disorder. The adoption of buprenorphine treatment within the Veterans Health Administration (VHA) has been slow. To expand capacity for buprenorphine treatment, the VHA sponsored two eight-hour credentialing courses for the Drug Addiction Treatment Act of 2000. We sought to describe the outcomes of such training. Following the training sessions, 29 participants (18 physicians) were highly satisfied with course content and affirmed their intention to prescribe buprenorphine; after nine-month follow-up, two physicians were prescribing. We conclude that providing credentialing courses, while popular, did not markedly promote the prescription of buprenorphine. C1 [Gordon, Adam J.; Salmon-Cox, Sara; Andree, Tykia] VA Pittsburgh Healthcare Syst, VISN 4, Ctr Hlth Equ Res & Promot, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA 15206 USA. [Gordon, Adam J.] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Liberto, Joseph] VA Maryland Healthcare Syst, Baltimore, MD USA. [Liberto, Joseph] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Granda, Stephanie] St Louis Univ, Dept Psychol, St Louis, MO 63103 USA. [McNicholas, Laura] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Gordon, AJ (reprint author), VA Pittsburgh Healthcare Syst, VISN 4, Ctr Hlth Equ Res & Promot, Mental Illness Res Educ & Clin Ctr, Mailcode 151 C-H,7180 Highland Dr, Pittsburgh, PA 15206 USA. EM adam.gordon@va.gov NR 12 TC 14 Z9 14 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PY 2008 VL 17 IS 6 BP 459 EP 462 AR PII 905998268 DI 10.1080/10550490802408613 PG 4 WC Substance Abuse SC Substance Abuse GA 376MQ UT WOS:000261188100001 PM 19034736 ER PT J AU Suh, JJ Pettinati, HM Kampman, KM O'Brien, CP AF Suh, Jesse J. Pettinati, Helen M. Kampman, Kyle M. O'Brien, Charles P. TI Gender Differences in Predictors of Treatment Attrition with High Dose Naltrexone in Cocaine and Alcohol Dependence SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; ADDICTION SEVERITY INDEX; OPIOID RECEPTOR GENE; FUNCTIONAL POLYMORPHISM; DRINKING BEHAVIOR; SUBSTANCE-ABUSE; SELF-REPORTS; RELIABILITY; DISORDERS; VALIDITY AB Recently, we reported that naltrexone at 150 mg/day significantly decreased cocaine and alcohol use for men but not women with co-occurring cocaine and alcohol dependence. The present study is an exploratory investigation of predictors that explain the different gender responses to naltrexone, with a particular focus on differential predictors of treatment attrition. No significant predictors were associated with treatment discontinuation in men. Women, however, were more likely to discontinue treatment when reporting severe pre-treatment psychiatric problems or nausea while in treatment. Further research on the impact of pre-treatment and in-treatment gender differences with naltrexone is warranted. C1 [Suh, Jesse J.; Pettinati, Helen M.; Kampman, Kyle M.; O'Brien, Charles P.] Univ Penn, Dept Psychiat, Ctr Studies Addict, Sch Med, Philadelphia, PA 19104 USA. [Suh, Jesse J.; Kampman, Kyle M.; O'Brien, Charles P.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Suh, JJ (reprint author), Univ Penn, Dept Psychiat, Ctr Studies Addict, Sch Med, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM Suh_J@mail.TRC.Upenn.edu FU NIAAA NIH HHS [R01 AA014657, R01 AA009544]; NIDA NIH HHS [P60 DA005186, P50 DA012756, T32 DA007241, P60-DA-05186-17, T32-DA-07241-13, P50 DA012756-04, P50-DA-012756-04, P60 DA005186-17] NR 44 TC 14 Z9 14 U1 4 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PY 2008 VL 17 IS 6 BP 463 EP 468 AR PII 906011123 DI 10.1080/10550490802409074 PG 6 WC Substance Abuse SC Substance Abuse GA 376MQ UT WOS:000261188100002 PM 19034737 ER PT J AU Wilens, TE Vitulano, M Upadhyaya, H Adamson, J Parcell, T Westerberg, D Biederman, J AF Wilens, Timothy E. Vitulano, Michael Upadhyaya, Himanshu Adamson, Joel Parcell, Tiffany Westerberg, Diana Biederman, Joseph TI Concordance between Cigarette Smoking and the Modified Fagerstrom Tolerance Questionnaire in Controlled Studies of ADHD SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; NICOTINE DEPENDENCE; TOBACCO DEPENDENCE; DRUG-USE; ADOLESCENCE; INITIATION; SCHEDULE; PATTERNS; CHILDREN; SMOKERS AB Our objective was to compare scores on a smoking questionnaire to a diagnosis of cigarette smoking. As part of follow-ups in studies of ADHD, we assessed for cigarette smoking using structured interviews and the modified Fagerstrom Tolerance Questionnaire (mFTQ). Data were obtained from 162 subjects (mean = 19.2 yrs). ROC analysis and kappa coefficients revealed that a cutoff score of 3 on the mFTQ showed the strongest agreement with a full diagnosis of cigarette smoking (kappa = 0.68). Clinicians and researchers using the mFTQ in adolescents and young adults should consider a cutoff score of 3 to be indicative of cigarette smoking. C1 [Wilens, Timothy E.] Harvard Univ, Massachusetts Gen Hosp, Pediat Psychopharmacol Program, Pediat Psychopharmacol Unit,Sch Med, Boston, MA 02114 USA. [Upadhyaya, Himanshu] Eli Lilly & Co, ADAP Team, Indianapolis, IN 46285 USA. RP Wilens, TE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Pediat Psychopharmacol Program, Pediat Psychopharmacol Unit,Sch Med, 55 Fruit St,YAW 6A, Boston, MA 02114 USA. EM twilens@partners.org OI Adamson, Joel/0000-0002-1399-5786 FU NIDA NIH HHS [5U10DA015831-0, DA016264, R01 DA014419, R01 DA014419-05, R01 DA14419, U10 DA015831, K24 DA016264, U10 DA015831-07S1, K24 DA016264-05] NR 26 TC 5 Z9 5 U1 2 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PY 2008 VL 17 IS 6 BP 491 EP 496 AR PII 905995097 DI 10.1080/10550490802409082 PG 6 WC Substance Abuse SC Substance Abuse GA 376MQ UT WOS:000261188100006 PM 19034741 ER PT J AU Schoenfeld, DA Cudkowicz, M AF Schoenfeld, David A. Cudkowicz, Merit TI Design of phase II ALS clinical trials SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Article DE clinical trials; amyotrophic lateral sclerosis; motor neuron disease; futility; lead in period; group sequential trials; endpoints; survival ID AMYOTROPHIC-LATERAL-SCLEROSIS; FUNCTIONAL RATING-SCALE; FUTILITY DESIGN; MICE; RILUZOLE; CREATINE; STOP AB Several important design issues for clinical trials in ALS were presented at the World Federation of Neurology conference at the International Motor Neuron Disease meeting in Yokahama, Japan. We present a discussion, and critique, of the important ideas that were presented with regard to phase II trials. In particular we critique the use of 'Futility Designs' because, as presented at the meeting they will too often lead to the testing of ineffective drugs. We show that except under a highly restrictive model, the use of a 'Lead In' period has only a minor effect on trial efficiency. We show the advantage of using multi-drug phase II trials to select drugs for further study and the advantage of studies that combine phase II and III. We also describe how group sequential trials can be used to stop trials early. C1 [Schoenfeld, David A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02115 USA. [Cudkowicz, Merit] Neurol Clin, Trials Unit, Charlestown, MA USA. RP Schoenfeld, DA (reprint author), Massachusetts Gen Hosp, Ctr Biostat, 50 Staniford St, Boston, MA 02115 USA. EM dschoenfeld@partners.org NR 29 TC 25 Z9 25 U1 2 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PY 2008 VL 9 IS 1 BP 16 EP 23 DI 10.1080/17482960701875896 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 262AW UT WOS:000253122400003 PM 18273715 ER PT J AU Lanka, V Cudkowicz, M AF Lanka, Veena Cudkowicz, Merit TI Therapy development for ALS: Lessons learned and path forward SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Review DE amyotrophic lateral sclerosis; clinical trials; study design ID AMYOTROPHIC-LATERAL-SCLEROSIS; PLACEBO-CONTROLLED TRIAL; MOTOR-NEURON DEGENERATION; THYROTROPIN-RELEASING-HORMONE; RANDOMIZED CONTROLLED-TRIAL; CU/ZN SUPEROXIDE-DISMUTASE; TRANSGENIC MOUSE MODEL; DOUBLE-BLIND; CLINICAL-TRIAL; CEREBROSPINAL-FLUID AB Several therapies have shown promise in preclinical models of motor neuron disease. Several of these treatment approaches, however, failed in human studies. In moving forward with new promising therapies, it is important to first identify whether the past trials were unsuccessful due to wrong therapy and biological target or because of flaws in trial design and conduct. We review treatment development in ALS and discuss the strengths and limitations of past clinical trials. Better biomarkers of disease and markers of biological activity of the therapies under development are urgently needed. Obtaining information regarding dosage, pharmacokinetics, short-term safety and biological activity in well designed phase I and II studies is critical to the design of phase III trials that will yield meaningful results. C1 [Lanka, Veena; Cudkowicz, Merit] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurol Clin Trials Unit, Charlestown, MA 02129 USA. RP Cudkowicz, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurol Clin Trials Unit, 149 13th St,Room 2274, Charlestown, MA 02129 USA. EM mcudkowicz@partners.org NR 109 TC 23 Z9 24 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PY 2008 VL 9 IS 3 BP 131 EP 140 DI 10.1080/17482960802112819 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 317NP UT WOS:000257027200001 PM 18574756 ER PT J AU Broom, WJ Greenway, M Sadri-Vakili, G Russ, C Auwarter, KE Glajch, KE Dupre, N Swingler, RJ Purcell, S Hayward, C Sapp, PC Mckenna-Yasek, D Valdmanis, PN Bouchard, JP Meininger, V Hosler, BA Glass, JD Polack, M Rouleau, GA Cha, JHJ Hardiman, O Brown, RH AF Broom, Wendy J. Greenway, Matthew Sadri-Vakili, Ghazaleh Russ, Carsten Auwarter, Kristen E. Glajch, Kelly E. Dupre, Nicolas Swingler, Robert J. Purcell, Shaun Hayward, Caroline Sapp, Peter C. Mckenna-Yasek, Diane Valdmanis, Paul N. Bouchard, Jean-Pierre Meininger, Vincent Hosler, Betsy A. Glass, Jonathan D. Polack, Meraida Rouleau, Guy A. Cha, Jang-Ho J. Hardiman, Orla Brown, Robert H., Jr. TI 50bp deletion in the promoter for superoxide dismutase 1 (SOD1) reduces SOD1 expression in vitro and may correlate with increased age of onset of sporadic amyotrophic lateral sclerosis SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Article DE amyotrophic lateral sclerosis; heredity; polymorphism; genetic; gene expression; regulatory sequences; nucleic acid ID ZINC SUPEROXIDE-DISMUTASE; APOLIPOPROTEIN-E; ASSOCIATION; MUTATIONS; DISEASE; ALS; SUSCEPTIBILITY; EPIDEMIOLOGY; BRAIN; GENE AB The objective was to test the hypothesis that a described association between homozygosity for a 50bp deletion in the SOD1 promoter 1684bp upstream of the SOD1 ATG and an increased age of onset in SALS can be replicated in additional SALS and control sample sets from other populations. Our second objective was to examine whether this deletion attenuates expression of the SOD1 gene. Genomic DNA from more than 1200 SALS cases from Ireland, Scotland, Quebec and the USA was genotyped for the 50bp SOD1 promoter deletion. Reporter gene expression analysis, electrophoretic mobility shift assays and chromatin immunoprecipitation studies were utilized to examine the functional effects of the deletion. The genetic association for homozygosity for the promoter deletion with an increased age of symptom onset was confirmed overall in this further study (p = 0.032), although it was only statistically significant in the Irish subset, and remained highly significant in the combined set of all cohorts (p = 0.001). Functional studies demonstrated that this polymorphism reduces the activity of the SOD1 promoter by approximately 50%. In addition we revealed that the transcription factor SP1 binds within the 50bp deletion region in vitro and in vivo. Our findings suggest the hypothesis that this deletion reduces expression of the SOD1 gene and that levels of the SOD1 protein may modify the phenotype of SALS within selected populations. C1 [Broom, Wendy J.; Russ, Carsten; Auwarter, Kristen E.; Sapp, Peter C.; Mckenna-Yasek, Diane; Hosler, Betsy A.; Brown, Robert H., Jr.] Massachusetts Gen Hosp, Day Neuromuscular Res Lab, Charlestown, MA 02129 USA. [Greenway, Matthew; Hardiman, Orla] Royal Coll Surgeons Ireland, Dept Clin Neurol Sci, Dublin 2, Ireland. [Greenway, Matthew] Our Ladys Hosp Sick Children, Natl Ctr Med Genet, Dublin, Ireland. [Sadri-Vakili, Ghazaleh; Glajch, Kelly E.; Cha, Jang-Ho J.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Dupre, Nicolas; Valdmanis, Paul N.; Rouleau, Guy A.] Univ Montreal, Notre Dame Hosp, Ctr Study Brain Dis, CHUM Res Ctr, Montreal, PQ H3C 3J7, Canada. [Dupre, Nicolas; Valdmanis, Paul N.; Rouleau, Guy A.] Univ Montreal, St Jusine Hosp, Res Ctr, Montreal, PQ, Canada. [Dupre, Nicolas; Bouchard, Jean-Pierre] Univ Laval, Dept Neurol Sci, CHAUQ Enfant Jesus, Quebec City, PQ, Canada. [Swingler, Robert J.] Ninewells Hosp, Dundee DD1 9SY, Scotland. [Swingler, Robert J.] Sch Med, Dundee, Scotland. [Purcell, Shaun] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Hayward, Caroline] MRC, Human Genet Unit, Med Genet Sect, Edinburgh, Midlothian, Scotland. [Sapp, Peter C.] MIT, Dept Biol, Cambridge, MA USA. [Meininger, Vincent] Unite Rech Sclerose Laterale Amyotroph, Paris, France. [Glass, Jonathan D.; Polack, Meraida] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Hardiman, Orla] Beaumont Hosp, Dept Neurol, Dublin 9, Ireland. RP Broom, WJ (reprint author), Massachusetts Gen Hosp, Day Neuromuscular Res Lab, 114 16th St, Charlestown, MA 02129 USA. EM wendy.broom@gmail.com RI Hayward, Caroline/M-8818-2016; OI Hayward, Caroline/0000-0002-9405-9550; Hardiman, Orla/0000-0003-2610-1291 FU NINDS NIH HHS [NS045242, NS038106] NR 27 TC 14 Z9 14 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PY 2008 VL 9 IS 4 BP 229 EP 237 DI 10.1080/17482960802103107 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 327TY UT WOS:000257752600004 PM 18608091 ER PT J AU Bedlack, RS Pastula, D Welsh, E Pulley, D Cudkowicz, ME AF Bedlack, Richard S. Pastula, Daniel Welsh, Emily Pulley, Darlene Cudkowicz, Merit E. TI Scrutinizing enrollment in ALS clinical trials: Room for improvement? SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Article DE ALS; clinical trials; enrollment ID AMYOTROPHIC-LATERAL-SCLEROSIS; INFORMED CONSENT; CANCER; DIAGNOSIS; THERAPIES; SURVIVAL; CRITERIA AB Enrollment in ALS trials has not been systematically studied. We surveyed the ALS Research Group (ALSRG) to learn their impressions of enrollment at ALS clinics across North America. We also reviewed completed ALS trials to determine an enrollment rate (subjects per site per month), its variability across trials, whether it is changing over time, and whether it is influenced by 'trial factors'. ALSRG members were polled via an online survey. ALS trials were identified by literature review and investigator contact. Enrollment rate versus publication year was plotted for each trial. Models were created to examine how 'trial factors' were associated with enrollment rate. By survey, percent enrollment is 25% and highly variable (range 0-75%). By literature review, enrollment rate is 2.2 participants/site/month and highly variable (range 0.1-7.5). Enrollment is not improving over time; no 'trial factor' explains the variability in enrollment across trials. Behaviors among clinic directors and patients were identified that may influence enrollment. In conclusion, ALS trial enrollment rate is low, highly variable and not influenced by trial design factors. 'Patient factors' and 'physician factors' may play more important roles in influencing enrollment, as in oncology trials. Our survey data support this idea, and provide potential mechanisms for improving enrollment. C1 [Bedlack, Richard S.; Pastula, Daniel] Duke Univ, Med Ctr, Durham, NC 27702 USA. [Welsh, Emily; Pulley, Darlene; Cudkowicz, Merit E.] Massachusetts Gen Hosp, Neurol Clin Trial Unit, Charlestown, MA USA. RP Bedlack, RS (reprint author), Duke Univ, Med Ctr, Box 3333,932 Morreene Rd, Durham, NC 27702 USA. EM Bedla001@mc.duke.edu FU UCB Pharma FX The authors thank David Schoenfeld for checking the statistical analyses. Richard Bedlack is a speaker for Pfizer and Lilly, a consultant for Metabolon Inc., and has a research grant from UCB Pharma. NR 27 TC 15 Z9 16 U1 1 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PY 2008 VL 9 IS 5 BP 257 EP 265 DI 10.1080/17482960802195913 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 349YF UT WOS:000259318500001 PM 18608092 ER PT J AU Badayan, I Cudkowicz, ME AF Badayan, Irina Cudkowicz, Merit E. TI Is it too soon for Mesenchymal Stem Cell trials in people with ALS? SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Article DE Amyotrophic Lateral Sclerosis; SOD1; Clinical Trials; Therapy ID AMYOTROPHIC-LATERAL-SCLEROSIS; PARKINSONS-DISEASE; SHAM SURGERY; TRANSPLANTATION AB Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting primarily the motor neurons. Stem cell therapy is under development as a possible treatment approach. A pilot study of intraspinal injections of mesenchymal stem cells (MSC) was conducted in 9 participants. We review this paper, the rationale, preclinical data and study design. C1 [Badayan, Irina; Cudkowicz, Merit E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurol Clin Trials Unit, Charlestown, MA 02129 USA. RP Badayan, I (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurol Clin Trials Unit, 149 13th St,Room 2274, Charlestown, MA 02129 USA. EM ibadayan@partners.org NR 11 TC 13 Z9 13 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PY 2008 VL 9 IS 6 BP 321 EP 322 DI 10.1080/17482960802425559 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 399FU UT WOS:000262786600001 PM 18819027 ER PT J AU Caraganis, A Benn, S Cudkowicz, M Brown, RH AF Caraganis, Andrew Benn, Susanna Cudkowicz, Merit Brown, Robert H., Jr. TI Thrombopoietin is ineffective in a mouse model of motor neuron disease SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Article DE Thrombopoietin; ALS; mouse model; platelets; growth factors ID AMYOTROPHIC-LATERAL-SCLEROSIS; ENDOTHELIAL GROWTH-FACTOR; MICE; TRIAL; ALS; DEGENERATION; RILUZOLE; GABAPENTIN; VEGF AB This study assessed the therapeutic efficacy of thrombopoietin (TPO) in the mouse model of ALS using two treatment paradigms. TPO was administered either daily or in 13-day treatment cycles to SOD1-G93A mice. Quantitative analysis of platelet levels, VEGF and TGF-beta 1 trophic factors were assessed. The effect of TPO on disease progression was analyzed by behavioral analysis and clinical examination. TPO treatment increased levels of platelets and TGF-beta 1 but not VEGF. This treatment did not affect onset or survival in these mice. Although biologically active, demonstrated by increased platelet and TGF-beta 1 levels, rmTPO did not attenuate disease progression in ALS mice. C1 Massachusetts Gen Hosp, Dept Neurol, Day Neuromuscular Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Cudkowicz, M (reprint author), 13th St,Bldg 149,Room 2274, Charlestown, MA 02129 USA. EM mcudkowicz@partners.org FU A1-Athel ALS Research Foundation; Angel Fund; Project ALS; National Institute of Health (NINDS); Pierre L. de Bourgknecht ALS Research Foundation FX We thank Saniya Fayzullina and Sarah Stern for their help with this project. We also thank the Department of Pathology at Massachusetts General Hospital for assistance in developing initial protocols for platelets counts. Our ALS investigations are generously supported by the A1-Athel ALS Research Foundation, the Angel Fund, Project ALS, the ALS Therapy Alliance, the National Institute of Health (NINDS), and the Pierre L. de Bourgknecht ALS Research Foundation. NR 27 TC 1 Z9 1 U1 5 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PY 2008 VL 9 IS 6 BP 354 EP 358 DI 10.1080/17482960802103040 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 399FU UT WOS:000262786600005 PM 18608089 ER PT J AU Qureshi, M Shui, A Dibernardo, AB Brown, RH Schoenfeld, DA Cudkowicz, ME AF Qureshi, Muddasir Shui, Amy Dibernardo, Allitia B. Brown, Robert H., Jr. Schoenfeld, David A. Cudkowicz, Merit E. TI Medications and laboratory parameters as prognostic factors in amyotrophic lateral sclerosis SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Article DE Amyotrophic lateral sclerosis; neuromuscular disease; motor neuron disease; inflammation; epidemiology ID PARKINSONISM-DEMENTIA COMPLEX; MAGNESIUM-DEFICIENCY; CONTROLLED TRIAL; CLINICAL-TRIAL; DISEASE; ALS; RILUZOLE; MODEL; GUAM AB We sought to examine the influence of medication usage and laboratory measurements on disease progression in amyotrophic lateral sclerosis (ALS). A database of 596 volunteers with ALS was generated from three clinical trials and one observational study. Disease course was measured by survival and three functional measures: the ALS Functional Rating Scale (ALSFRS), Vital Capacity (VC) and Maximum Voluntary Isometric Contraction (MVIC). Survival modeling was performed using Cox proportional hazards regression. The association of medication or laboratory measurements with disease progression was determined using a random effects model. In the multivariate analysis, survival was shorter in participants who took aspirin (HR = 1.93, p = 0.046); NSAIDs (HR = 1.51, p = 0.054); had low blood chloride (HR = 0.76, p = 0.020) or high bicarbonate levels (HR = 1.37, p = 0.006). Individuals who took calcium had better survival (HR = 0.37, p = 0.008) and a slower rate of decline of MVIC arm megascore (p = 0.033). Vital capacity declined faster in individuals with lower serum chloride (p<0.0001), or higher bicarbonate (p = 0.002) levels and those taking paracetamol (acetaminophen) (p = 0.035). We conclude that aspirin or NSAID use may shorten survival in ALS, while calcium use may prolong survival. Our results support a need to further explore the role of neuroinflammation in the pathogenesis of ALS. C1 [Qureshi, Muddasir; Dibernardo, Allitia B.; Cudkowicz, Merit E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurol Clin Trials Unit, Charlestown, MA 02129 USA. [Qureshi, Muddasir; Dibernardo, Allitia B.; Brown, Robert H., Jr.; Cudkowicz, Merit E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Shui, Amy; Schoenfeld, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Biostat Ctr,Dept Med, Charlestown, MA 02129 USA. [Brown, Robert H., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Day Neuromuscular Res Lab, Charlestown, MA 02129 USA. RP Qureshi, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurol Clin Trials Unit, Bldg 149,13th St,Room 2274, Charlestown, MA 02129 USA. EM mqureshi@partners.org FU Northeast ALS (NEALS) Consortium; Digiovanni Fund; Angel Fund; ALS Research Foundation; NINDS [5R01NS050557-02, 5R01NS05050641-04] FX We thank the study participants and the members of the Northeast ALS (NEALS) Consortium. MEC receives support from the Digiovanni Fund. RHB receives support from the Angel Fund, ALS Therapy Alliance, Project ALS, the A1-Athel ALS Research Foundation, the Pierre L. de Bourgknecht ALS Research Foundation and the NINDS (5R01NS050557-02 and 5R01NS05050641-04). NR 31 TC 7 Z9 7 U1 5 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PY 2008 VL 9 IS 6 BP 369 EP 374 DI 10.1080/17482960802163614 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 399FU UT WOS:000262786600007 PM 18608098 ER PT J AU Sandberg, WS Sandberg, EH Seim, AR Anupama, S Ehrenfeld, JM Spring, SF Walsh, JL AF Sandberg, Warren S. Sandberg, Elisabeth H. Seim, Andreas R. Anupama, Shaji Ehrenfeld, Jesse M. Spring, Stephen F. Walsh, John L. TI Real-time checking of electronic anesthesia records for documentation errors and automatically text messaging clinicians improves quality of documentation SO ANESTHESIA AND ANALGESIA LA English DT Article ID STATISTICAL PROCESS-CONTROL; INFORMATION-MANAGEMENT-SYSTEM; CARE; TOOL; TIMELINESS; FEEDBACK AB INTRODUCTION: The quality of electronic anesthesia documentation is important for downstream communication and to demonstrate appropriate diligence to care. Documentation quality will also impact the success of reimbursement contracts that require timely and complete documentation of specific interventions. We implemented a system to improve completeness of clinical documentation and evaluated the results over time. METHODS: We used custom software to continuously scan for missing clinical documentation during anesthesia. We used patient allergies as a test case, taking advantage of a unique requirement in our system that allergies be manually entered into the electronic record. If no allergy information was entered within 15 min of the "start of anesthesia care" event, a one-time prompt was sent via pager to the person performing the anesthetic. We tabulated the daily fraction of cases missing allergy data for the 6 mo before activating the alert system. We then obtained the same data for the subsequent 9 mo. We tested for -systematic performance changes using statistical process control methodologies. RESULTS: Before initiating the alert system, the fraction of charts without an allergy comment was slightly more than 30%. This decreased to about 8% after initiating the alerts, and was significantly different from baseline within 5 days. Improvement lasted for the duration of the trial. Paging was suspended on nights, weekends, and holidays, yet weekend documentation performance also improved, indicating that weekday reminders had far-reaching effects. DISCUSSION: Electronic anesthesia documentation performance can be rapidly managed and improved by using an automatic process monitoring and alerting system. C1 [Sandberg, Warren S.; Anupama, Shaji; Ehrenfeld, Jesse M.; Spring, Stephen F.; Walsh, John L.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Sandberg, Elisabeth H.] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. [Seim, Andreas R.] Norwegian Univ Sci & Technol, Dept Prod & Qual Engn, N-7034 Trondheim, Norway. [Sandberg, Warren S.; Ehrenfeld, Jesse M.; Walsh, John L.] Harvard Univ, Sch Med, Boston, MA USA. RP Sandberg, WS (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Jackson 4, Boston, MA 02114 USA. EM wsandberg@partners.org OI Ehrenfeld, Jesse/0000-0003-3427-0140; Sandberg, Warren/0000-0002-9246-777X NR 22 TC 53 Z9 53 U1 0 U2 2 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 JAN PY 2008 VL 106 IS 1 BP 192 EP 201 DI 10.1213/01.ane.0000289640.38523.bc PG 10 WC Anesthesiology SC Anesthesiology GA 243VB UT WOS:000251824300036 PM 18165578 ER PT J AU Zhong, HJ Rusch, D Forman, SA AF Zhong, Huijun Ruesch, Dirk Forman, Stuart A. TI Photo-activated azi-etomidate, a general anesthetic photolabel, irreversibly enhances gating and desensitization of gamma-aminobutyric acid type A receptors SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT 7th International Conference on Basic and Systemic Mechanisms of Anesthesia CY FEB 25-27, 2005 CL Nara, JAPAN ID GABA(A) RECEPTOR; BETA-3 SUBUNIT; MODULATION; CHANNEL; ANALOG; SITES; POTENTIATION; MECHANISMS; ISOMERS; AGONIST AB Background: The general anesthetic etomidate acts via gamma-aminobutyric acid type A (GABA(A)) receptors, enhancing activation at low GABA and prolonging deactivation. Azi-etomidate is a photo-reactive etomidate derivative with similar pharmacological actions, which has been used to identify putative binding sites. The authors examine the irreversible effects of azi-etomidate photo-modification on functional GABA(A) receptors in cell membranes. Methods: GABAA receptors (alpha(1)beta(2)gamma(21)) were expressed in both Xenopus oocytes; and human embryonic kidney cells exposed to 365 nm light-activated azi-etomidate with or without GABA, then extensively washed. Receptor-mediated chloride currents were measured using voltage clamp electrophysiology to assess the ratio of peak responses at 10 mu M and 1 mM GABA (I-10/I-1000) and deactivation time course. Results: After azi-etomidate photo-modification, I-10/I-1000 ratios were persistently enhanced and deactivation was prolonged, mimicking reversible azi-etomidate actions. Azi-etomidate and ultraviolet light were required to produce irreversible receptor modulation. Adding GABA during photo-modification greatly enhanced irreversible modulation. Azi-etomidate modification also dose-dependently reduced maximal GABA-activated currents, consistent with accumulation of permanently desensitized receptors. Excess etomidate during azi-etomidate photo-modification competitively reduced permanent desensitization. Persistent channel modulation was blocked by 320-fold excess etomidate but enhanced when 32-fold excess etomidate was present. Conclusions: Azi-etomidate efficiently photo-modifies etomidate sites on GABA(A) receptors in intact cells, producing persistent functional changes that mimic its reversible effects. The results demonstrate sequential modification at more than one etomidate site per receptor. The sites display reciprocal positive cooperativity. In combination with focal photo-activation, azi-etomidate may prove useful for studies of anesthetic actions in neural circuits. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Beecher Mallincrodt Labs, Boston, MA 02114 USA. RP Forman, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Beecher Mallincrodt Labs, Gray Jackson 4,55 Fruit St, Boston, MA 02114 USA. EM saforman@partners.org FU NIGMS NIH HHS [R01 GM066724, P01 GM058448-09, R01 GM066724-06, P01 GM058448, P01GM58448, R01GM66724] NR 36 TC 12 Z9 12 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 2008 VL 108 IS 1 BP 103 EP 112 PG 10 WC Anesthesiology SC Anesthesiology GA 245AA UT WOS:000251905400016 PM 18156888 ER PT J AU Gu, XP Yang, LF Wang, SX Sung, B Lim, G Mao, J Zeng, Q Yang, C Mao, JM AF Gu, Xiaoping Yang, Lifing Wang, Shuxing Sung, Backil Lim, Grewo Mao, Ji Zeng, Qing Yang, Chang Mao, Jianren TI A rat model of radicular pain induced by chronic compression of lumbar dorsal root ganglion with SURGIFLO (TM) SO ANESTHESIOLOGY LA English DT Article ID NF-KAPPA-B; PROTEIN-KINASE-C; PROINFLAMMATORY CYTOKINES; PERIPHERAL MONONEUROPATHY; MATRIX METALLOPROTEINASES; TRANSCRIPTION FACTOR; NEUROPATHIC PAIN; DISK HERNIATION; SCIATIC-NERVE; NITRIC-OXIDE AB Background: Radicular pain is a common and debilitating clinical pain condition. To date, the mechanisms of radicular pain remain unclear, partly because of the lack of suitable preclinical models. The authors report a modified rat model of radicular pain that could mimic a subset of clinical radicular pain conditions induced by the soft tissue compression on dorsal root ganglion. Methods: A rat model of radicular pain was produced by infiltrating the L5 intervertebral foramen with 60 mu 1 of a hemostatic matrix (SURGIFLO (TM); Johnson & Johnson, Somerville, NJ) resulting in chronic compression of lumbar dorsal root ganglion. Thermal hyperalgesia and mechanical allodynia were measured with or without epidural treatment with triamcinolone. Western blot was used to assess the expression of the NR1 subunit of the N-methyl-D-aspartate receptor and inhibitory factor kappa beta-alpha, an inflammatory marker, within the affected L5 dorsal root ganglion and spinal cord dorsal horn. Results: Chronic compression of lumbar dorsal root ganglion resulted in: (1) persistent mechanical allodynia and thermal hyperalgesia up to 4 or 5 postoperative weeks and (2) upregulation of the N-methyl-D-aspartate receptor and inhibitory factor kappa beta-alpha within the ipsilateral L5 dorsal root ganglion and spinal cord dorsal horn. Epidural administration of triamcinolone (6.25-100 mu g) on postoperative day 3 dose-dependently attenuated both thermal hyperalgesia and mechanical allodynia in rats with chronic compression of lumbar dorsal root ganglion. Conclusion: The data suggest that this modified rat model of chronic compression of lumbar dorsal root ganglion may be a useful tool to explore the mechanisms as well as new therapeutic options of radicular pain. C1 [Gu, Xiaoping; Yang, Lifing; Wang, Shuxing; Sung, Backil; Lim, Grewo; Mao, Ji; Zeng, Qing; Yang, Chang; Mao, Jianren] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,MGH Ctr Translat Pain, Boston, MA 02114 USA. RP Mao, JM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,MGH Ctr Translat Pain, WACC 324,15 Parkman St, Boston, MA 02114 USA. EM jmao@partners.org FU NIDCR NIH HHS [R01 DE18538]; NINDS NIH HHS [R01 NS42661, R01 NS45681] NR 30 TC 14 Z9 24 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 2008 VL 108 IS 1 BP 113 EP 121 PG 9 WC Anesthesiology SC Anesthesiology GA 245AA UT WOS:000251905400017 PM 18156889 ER PT J AU Koh, I Hong, R Weissleder, R Josephson, L AF Koh, Isaac Hong, Rid Weissleder, Ralph Josephson, Lee TI Sensitive NMR sensors detect antibodies to influenza SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE antibodies; biosensors; magnetic properties; peptides; viruses ID MAGNETIC-RELAXATION; TRANSVERSE RELAXATION; NANOPARTICLES; PRECIPITATION; AGGLUTINATION; AGGREGATION; SPHERES C1 [Koh, Isaac; Hong, Rid; Weissleder, Ralph; Josephson, Lee] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02129 USA. [Koh, Isaac; Hong, Rid; Weissleder, Ralph; Josephson, Lee] Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Josephson, L (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St, Boston, MA 02129 USA. EM josephso@helix.mgh.harvard.edu FU NCI NIH HHS [U54 CA119349, U54 CA119349-040003]; NIBIB NIH HHS [R01 EB004626, R01 EB004626-03, R01EB0004626]; PHS HHS [U54A119349] NR 22 TC 57 Z9 59 U1 0 U2 17 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2008 VL 47 IS 22 BP 4119 EP 4121 DI 10.1002/anie.200800069 PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 306QC UT WOS:000256261900012 PM 18428168 ER PT J AU Nair, SA Kolodziej, AE Bhole, G Greenfield, MT McMurry, TJ Caravan, P AF Nair, Shrikumar A. Kolodziej, Andrew E. Bhole, Gandhali Greenfield, Matthew T. McMurry, Thomas J. Caravan, Peter TI Monovalent and bivalent fibrin-specific MRI contrast agents for detection of thrombus SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE contrast agent; fibrin; gadolinium; magnetic resonance imaging; thrombus ID IN-VIVO; MAGNETIC-FIELD; SWINE MODEL; BINDING; RELAXIVITY; MS-325 C1 [Caravan, Peter] Massachusetts Gen Hosp, Athinoula A Martinos Biomed Imaging, Charlestown, MA 02129 USA. [Nair, Shrikumar A.] Affinergy Inc, Durham, NC 27713 USA. [Kolodziej, Andrew E.; Bhole, Gandhali; Greenfield, Matthew T.; McMurry, Thomas J.; Caravan, Peter] EPIX Pharmaceut Inc, Lexington, MA 02421 USA. RP Caravan, P (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM caravan@nmr.mgh.harvard.edu NR 19 TC 34 Z9 34 U1 0 U2 5 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2008 VL 47 IS 26 BP 4918 EP 4921 DI 10.1002/anie.200800563 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 317SS UT WOS:000257040800027 PM 18496805 ER PT S AU Martins-Green, M Petreaca, M Yao, M AF Martins-Green, Manuela Petreaca, Melissa Yao, Min BE Cheresh, DA TI An assay system for in vitro detection of permeability in human "endothelium" SO ANGIOGENESIS: IN VITRO SYSTEMS SE Methods in Enzymology LA English DT Review; Book Chapter ID NITRIC-OXIDE SYNTHASE; GROWTH-FACTOR; VASCULAR-PERMEABILITY; CELLS; ANGIOGENESIS; RECEPTOR; TRANSACTIVATION; HYPERPERMEABILITY; KDR/FLK-1; PATHWAYS AB The molecular mechanisms by which encdothelial permeability occurs are often studied more readily in vitro, underscoring the importance of the use of systems that mimic human endothelium in vivo. We present an assay that accurately models human endothelium by use of primary human microvascular endothelial cells (hMVEC), because permeability primarily occurs at the microvascular level, and transwell filter units coated with Matrigel, extracellular matrix that mimics basal lamina, the matrix that is tightly associated with endothelium and is critical for its proper function. As a tracer molecule, we used 3-kDa dextran-FITC to detect leakage through the small gaps present in the early stages of permeability induction. The permeability-inducing agents IL-8 and VEGF were added to the lower chamber of the transwell units to mimic inflammatory conditions in vivo. After optimization, we were able to minimize basal permeability and to detect rapid changes in permeability stimulated by IL-8 and VEGF, similar to that observed in vivo. Furthermore, we have used this system to delineate the importance of the transactivation of VEGFR2 in IL-8-induced permeability and have confirmed the relevance of this signaling in vivo, suggesting that our permeability assay system adequately mimics the in vivo situation. Therefore, this system can be used to better understand the molecular mechanisms of human vascular permeability in a more in vivo-like setting and, thus, may be used to test effective therapeutics to prevent and treat diseases involving persistent permeability. C1 [Martins-Green, Manuela] Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA. [Petreaca, Melissa] Univ Calif Riverside, Grad Program Cell Mol & Dev Biol, Riverside, CA USA. [Yao, Min] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Martins-Green, M (reprint author), Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA. FU American Hea Association. FX We thank Qjjing Li and Lina Wong, for their work in establishing the in vitro penueability assay systern, and the colleagues in our laboratory for helpful discussions. This work was Supported in part by the American Hea Association. NR 31 TC 12 Z9 14 U1 1 U2 11 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-374315-2 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2008 VL 443 BP 137 EP 153 DI 10.1016/S0076-6879(08)20008-9 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BIH31 UT WOS:000259483400008 PM 18772015 ER PT J AU Davis, AE AF Davis, Alvin E., III TI Hereditary angioedema: a current state-of-the-art review. III: mechanisms of hereditary angioedema SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID MOLECULAR-WEIGHT KININOGEN; ANGIONEUROTIC EDEMA PLASMA; TISSUE-PLASMINOGEN-ACTIVATOR; C1 INHIBITOR DYSFUNCTION; VASCULAR-PERMEABILITY; HAGEMAN-FACTOR; C'1 ESTERASE; 1ST COMPONENT; ACUTE ATTACKS; CL-INHIBITOR AB Objective: To review the available evidence on the pathophysiologic mechanism of episodes of edema in hereditary angioedema (HAE). Data Sources: MEDLINE and PubMed were searched using the following keywords: hereditary angioedema, C1 inhibitor, complement system, contact system, and bradykinin. Study Selection: Studies were selected based on their relevance to the pathophysiologic features of HAE. Results: Early studies from the 1970s and 1980s disagreed as to whether the symptoms in HAE were mediated via complement or contact system activation. Studies have demonstrated that, in vitro, in C1 inhibitor (C1-INH)-deficient plasma, only contact system activation results in generation of a vascular permeability enhancing factor. Furthermore, individuals who express a variant C1-INH that is a normal inhibitor of contact system proteases but is deficient in the ability to inactivate complement system proteases do not develop angioedema. The blood of patients with HAE, during attacks, contains elevated levels of cleaved high-molecular-weight kininogen and bradykinin. Last, C1-INH-deficient mice develop increased vascular permeability that is mediated via contact system activation. Conclusions: Hereditary angioedema attacks are mediated by bradykinin generated via contact system activation. The specific factors that trigger attacks remain unclear. C1 [Davis, Alvin E., III] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Davis, AE (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM aldavis@cbr.med.harvard.edu FU NIAID NIH HHS [AI057366]; NICHD NIH HHS [HD22082] NR 49 TC 38 Z9 39 U1 0 U2 0 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD JAN PY 2008 VL 100 IS 1 SU 2 BP S7 EP S12 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 250WJ UT WOS:000252331700003 PM 18220146 ER PT J AU McDonald, AJ Pelletier, AJ Ellinor, PT Carnargo, CA AF McDonald, Alden J. Pelletier, Andrea J. Ellinor, Patrick T. Carnargo, Carlos A., Jr. TI Increasing US emergency department visit rates and subsequent hospital admissions for atrial fibrillation from 1993 to 2004 SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID STROKE PREVENTION; DOSE WARFARIN; RISK-FACTORS; ASPIRIN; TRIAL; ANTICOAGULATION; MANAGEMENT; TRENDS; IMPACT; CARE AB Study objective: Atrial fibrillation is a significant public health problem that is becoming increasingly prevalent. The clinical epidemiology of US emergency department (ED) visits for atrial fibrillation is uncertain. This study seeks to describe recent trends in ED visits for atrial fibrillation. Methods: ED visits with a primary diagnosis of atrial fibrillation were analyzed using data from the US National Hospital Ambulatory Medical Care Survey, 1993 to 2004. Results: During the 12-year period, there were approximately 2.7 million (95% confidence interval [CI] 2.4 to 3.0 million) ED visits for atrial fibrillation in the United States, and the population-adjusted visit rate increased from 0.6 to 1.2 per 1,000 US population (P for trend=.02). Similarly, the absolute number of visits increased 88%, from 300,000 (95% CI 209,000 to 392,000) in 1993 to 1994 to 564,000 (95% Cl 423,000 to 705,000) in 2003 to 2004. Approximately 64% (95% CI 59% to 69%) of these patients were admitted to the hospital, a rate that remained constant throughout the 12-year period (P for trend =.73). Admission rates were significantly lower in the western region of the United States (48%; 95% CI 36% to 60% versus 76%; in the Northeast, 95% CI 68% to 84%). Patient characteristics and ED management did not materially differ by admission status. In a multivariate model, congestive heart failure was the only predictor of admission but accounted for only 14% of admissions. Conclusion: From 1993 to 2004, the population-adjusted rate of ED visits for atrial fibrillation increased, whereas the proportion admitted to the hospital remained stable. Patient characteristics and ED management were similar regardless of admission status, and there were relatively few predictors of admission. C1 [McDonald, Alden J.; Pelletier, Andrea J.; Ellinor, Patrick T.; Carnargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Pelletier, Andrea J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. [McDonald, Alden J.; Ellinor, Patrick T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Carnargo, CA (reprint author), Massachusetts Gen Hosp, EMNet Coordinating Ctr, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org FU NHLBI NIH HHS [HL-71632] NR 25 TC 83 Z9 84 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 JAN PY 2008 VL 51 IS 1 BP 58 EP 65 DI 10.1016/j.annemergmed.2007.03.007 PG 8 WC Emergency Medicine SC Emergency Medicine GA 251OJ UT WOS:000252382700011 PM 17466409 ER PT J AU Bernheim, SM Ross, JS Krumholz, HM Bradley, EH AF Bernheim, Susannah M. Ross, Joseph S. Krumholz, Harlan M. Bradley, Elizabeth H. TI Influence of patients' socioeconomic status on clinical management decisions: A qualitative study SO ANNALS OF FAMILY MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; PAY-FOR-PERFORMANCE; HEALTH-CARE; DISPARITIES; INCOME; ASSOCIATION; SERVICES; OUTCOMES; COMMUNICATION; MORTALITY AB PURPOSE Little is known about how patients' socioeconomic status (SES) influences physicians' clinical management decisions, although this information may have important implications for understanding inequities in health care quality. We investigated physician perspectives on how patients' SES influences care. METHODS The study consisted of in-depth semistructured interviews with primary care physicians in Connecticut. Investigators coded interviews line by line and refined the coding structure and interview guide based on successive interviews. Recurrent themes emerged through iterative analysis of codes and tagged quotations. RESULTS We interviewed 18 physicians from varied practice settings, 6 female, 9 from minority racial backgrounds, and 3 of Hispanic ethnicity. Four themes emerged from our interviews: (1) physicians held conflicting views about the effect of patient SES on clinical management, (2) physicians believed that changes in clinical management based on the patient's SES were made in the patient's interest, (3) physicians varied in the degree to which they thought changes in clinical management influenced patient outcomes, and (4) physicians faced personal and financial strains when caring for patients of low SES. CONCLUSIONS Physicians indicated that patient SES did affect their clinical management decisions. As a result, physicians commonly undertook changes to their management plan in an effort to enhance patient outcomes, but they experienced numerous strains when trying to balance what they believed was feasible for the patient with what they perceived as established standards of care. C1 [Bernheim, Susannah M.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT USA. [Bernheim, Susannah M.] Yale New Haven Hlth Syst, New Haven, CT USA. [Bernheim, Susannah M.; Krumholz, Harlan M.; Bradley, Elizabeth H.] Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT USA. [Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA. [Ross, Joseph S.] James J Peter Vet Adm, Div Hlth Policy & Adm, Dept Epidemiol & Publ Hlth, Bronx, NY USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, Dept Med, Sect Cardiovasc Med, New Haven, CT USA. [Krumholz, Harlan M.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. RP Bernheim, SM (reprint author), Yale Univ, Sch Med, Dept Internal Med, 333 Cedar St, New Haven, CT USA. EM Susannah.bernheim@yale.edu FU NIA NIH HHS [T32AG1934] NR 39 TC 48 Z9 48 U1 0 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 JAN-FEB PY 2008 VL 6 IS 1 BP 53 EP 59 DI 10.1370/afm.749 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 258BV UT WOS:000252844300009 PM 18195315 ER PT J AU Hazin, R Ibrahimi, OA Hazin, MI Kimyai-Asadi, A AF Hazin, Ribhi Ibrahimi, Omar A. Hazin, Moustafa I. Kimyai-Asadi, Arash TI Stevens-Johnson syndrome: Pathogenesis, diagnosis, and management SO ANNALS OF MEDICINE LA English DT Review DE Stevens-Johnson syndrome; toxic epidermal necrolysis; erythema multiforme; intravenous immunoglobulins; adverse drug reaction; drug hypersensitivity; dermatological emergencies; mucocutaneous lesions; HLA B1501/HLA B1502; keratinocyte apoptosis ID TOXIC EPIDERMAL NECROLYSIS; HERPES-SIMPLEX-VIRUS; INTRAVENOUS IMMUNOGLOBULIN THERAPY; CUTANEOUS ADVERSE-REACTIONS; SELECTIVE COX-2 INHIBITORS; VERSUS-HOST DISEASE; OF-THE-LITERATURE; ERYTHEMA MULTIFORME; HYPERSENSITIVITY REACTIONS; MYCOPLASMA-PNEUMONIAE AB Cutaneous drug reactions are the most common type of adverse drug reaction. These reactions, ranging from simple pruritic eruptions to potentially life-threatening events, are a significant cause of iatrogenic morbidity and mortality. Stevens-Johnson syndrome (SJS) is a serious and potentially life-threatening cutaneous drug reaction. Although progress has been made in the management of SJS through early detection, prompt hospitalization, and immediate cessation of offending agents, the prevalence of permanent disabilities associated with SJS remains unchanged. Nevertheless, despite being a problem that is global in scope, government and health care agencies worldwide have yet to find a consensus on either diagnostic criteria or therapy for this disorder. Here, we provide the internist and emergency room physician with a brief review the SJS literature and summarize the latest recommended interventions with the hope of improving early recognition of this disease and prevention of permanent sequelae and mortality that frequently complicate SJS. C1 [Kimyai-Asadi, Arash] DermSurg Assoc, Houston, TX 77030 USA. [Hazin, Moustafa I.] St Josephs Hosp, Dept Internal Med, Phoenix, AZ USA. [Ibrahimi, Omar A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. [Hazin, Ribhi] Harvard Univ, Fac Arts & Sci, Cambridge, MA 02138 USA. RP Kimyai-Asadi, A (reprint author), DermSurg Assoc, 7515 Main ,Suite 210, Houston, TX 77030 USA. EM akimyai@yahoo.com NR 135 TC 27 Z9 30 U1 1 U2 9 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0785-3890 J9 ANN MED JI Ann. Med. PY 2008 VL 40 IS 2 BP 129 EP 138 DI 10.1080/07853890701753664 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 267JN UT WOS:000253505400005 PM 18293143 ER PT J AU Weintraub, D AF Weintraub, Daniel TI Dopamine and Impulse Control Disorders in Parkinson's Disease SO ANNALS OF NEUROLOGY LA English DT Article ID HEDONISTIC HOMEOSTATIC DYSREGULATION; SUBTHALAMIC NUCLEUS STIMULATION; VENTROMEDIAL PREFRONTAL CORTEX; DECISION-MAKING; PATHOLOGICAL GAMBLERS; AGONIST THERAPY; DRUG-USE; PREVALENCE; MEDICATION; BEHAVIORS AB There is an increasing awareness that impulse control disorders (ICDs), including compulsive gambling, buying, sexual behavior, and eating, can occur as a complication of Parkinson's disease (PD). In addition, other impulsive or compulsive disorders have been reported to occur, including dopamine dysregulation syndrome (DDS) and punding. Case reporting and prospective studies have reported an association between ICDs and the use of dopamine agonists (DAs), particularly at greater dosages, whereas dopamine dysregulation syndrome has been associated with greater dosages of levodopa or short-acting DAs. Data suggest that risk factors for an ICD may include male sex, younger age or younger age at PD onset, a pre-PD history of ICD symptoms, personal or family history of substance abuse or bipolar disorder, and a personality style characterized by impulsiveness. Although psychiatric medications are used clinically in the treatment of ICDs, there is no empiric evidence supporting their use in PD. Therefore, management for clinically significant ICD symptoms should consist of modifications to dopamine replacement therapy, particularly DAs, and there is emerging evidence that Such management is associated with all overall improvement in ICD symptomatology. It is important that PD patients be aware that DA use may lead to the development of an ICD, and that clinicians monitor patients as part of routine clinical care. As empirically validated treatments for ICDs are emerging, it will be important to examine their efficacy and tolerability in individuals with cooccurring PD and ICDs. C1 [Weintraub, Daniel] Univ Penn, Sch Med, Dept Psychiat, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. RP Weintraub, D (reprint author), Univ Penn, Sch Med, Dept Psychiat, Parkinsons Dis Res Educ & Clin Ctr, 3615 Chestnut St 330, Philadelphia, PA 19104 USA. EM weintrau@mail.med.upenn.edu FU NIH (National Institute of Mental Health) [K23MH067894] FX This work was supported by the NIH (National Institute of Mental Health, K23MH067894). NR 71 TC 80 Z9 80 U1 0 U2 13 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. PY 2008 VL 64 IS 6 BP S93 EP S100 DI 10.1002/ana.21454 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 389RN UT WOS:000262112300009 PM 19127573 ER PT J AU Wyller, VB Barbieri, R Thaulow, E Saul, JP AF Wyller, Vegard Bruun Barbieri, Riccardo Thaulow, Erik Saul, J. Philip TI Enhanced vagal withdrawal during mild orthostatic stress in adolescents with chronic fatigue SO ANNALS OF NONINVASIVE ELECTROCARDIOLOGY LA English DT Article DE heart rate variability; chronic fatigue syndrome; autonomic nervous system; cardiovascular regulation ID NEURALLY-MEDIATED HYPOTENSION; HEART-RATE-VARIABILITY; AUTONOMIC NERVOUS-SYSTEM; BODY NEGATIVE-PRESSURE; UP TILT; CARDIOVASCULAR REGULATION; BLOOD-PRESSURE; INTOLERANCE; PATHOGENESIS; TACHYCARDIA AB Background: Hemodynamic abnormalities have been documented in the chronic fatigue syndrome (CFS), indicating functional disturbances of the autonomic nervous system responsible for cardiovascular regulation. The aim of this study was to investigate autonomic heart rate control during mild orthostatic stress in adolescents with CFS. Methods: A total of 14 CFS patients and 56 healthy controls having equal distribution of age and gender underwent lower body negative pressure (LBNP) of 20 mmHg. The RR interval (RRI) was recorded continuously, and spectral power densities were computed in the low-frequency (LF) band (0.04-0.15 Hz) and the high-frequency (HF) band (0.15-0.50 Hz) from segments of 120-second length, using an autoregressive algorithm. In addition, the time-domain indices SDNN, pNN50, and r-MSSD were computed. Results: At rest, CFS had lower RRI than controls (P < 0.05), but indices of variability were similar in the two groups. During LBNP, compared to controls, CFS patients had lower normalized and absolute HF power and r-MSSD (P < 0.05), and higher RRI (P < 0.001), normalized LF power and LF/HF (P < 0.05). Conclusions: During mild orthostatic stress, adolescents with CFS appear to have enhanced vagal withdrawal, leading to a sympathetic predominance of heart rate control compared to controls. Possible underlying mechanisms include hypovolemia and abnormalities of reflex mechanisms. C1 [Wyller, Vegard Bruun; Thaulow, Erik] Natl Hosp Norway, Radiumhosp, Med Ctr, Dept Pediat, N-0027 Oslo, Norway. [Wyller, Vegard Bruun] Univ Oslo, Dept Physiol, Oslo, Norway. [Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. [Saul, J. Philip] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. RP Wyller, VB (reprint author), Natl Hosp Norway, Radiumhosp, Med Ctr, Dept Pediat, N-0027 Oslo, Norway. EM brwylle@online.no OI Barbieri, Riccardo/0000-0001-9381-3833 NR 45 TC 25 Z9 25 U1 2 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1082-720X J9 ANN NONINVAS ELECTRO JI Ann. Noninvasive Electrocardiol. PD JAN PY 2008 VL 13 IS 1 BP 67 EP 73 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 281QQ UT WOS:000254514000010 PM 18234008 ER PT J AU Houk, B Bello, C Cohen, D Casali, P Shirao, K Demetri, G AF Houk, B. Bello, C. Cohen, D. Casali, P. Shirao, K. Demetri, G. TI An exposure-response-based meta-analysis of the efficacy of sunitinib in patients with gastrointestinal stromal tumor SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th World Congress on Gastrointestinal Cancer CY JUN 25-28, 2008 CL Barcelona, SPAIN SP ESMO C1 [Houk, B.; Bello, C.; Cohen, D.] Pfizer Global, Res & Dev, La Jolla, CA USA. [Casali, P.] Ist Nazl Tumori, I-20133 Milan, Italy. [Shirao, K.] Natl Canc Ctr, Tokyo, Japan. [Demetri, G.] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 6 BP 11 EP 12 PG 2 WC Oncology SC Oncology GA 330OD UT WOS:000257951800013 ER PT J AU Blay, J George, S Casall, P Le, CA Deprimo, S Harmon, G Law, C Tassel, V Baum, C Demetri, G AF Blay, J. George, S. Casall, P. Le Cesne, A. Deprimo, S. Harmon, G. Law, C. Tassel, V Baum, C. Demetri, G. TI Efficacy, safety, pharmacokinetic and pharmacodynamic analysis of sunitinib adminstered on a continuous daily dosing schedule in patients with advanced gastrointestinal stromal tumor SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th World Congress on Gastrointestinal Cancer CY JUN 25-28, 2008 CL Barcelona, SPAIN SP ESMO C1 [Blay, J.] Ctr Leon Berard, F-69373 Lyon, France. [George, S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Casall, P.] Ist Nazl Tumori, I-20133 Milan, Italy. [Le Cesne, A.] Inst Gustave Roussy, Villejuif, France. [Deprimo, S.; Harmon, G.; Law, C.; Tassel, V; Baum, C.] Pfizer Global, Res & Dev, La Jolla, CA USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 6 BP 12 EP 13 PG 2 WC Oncology SC Oncology GA 330OD UT WOS:000257951800016 ER PT J AU Garrett, C Huang, X Casali, P Schoffski, P Blackstein, M Shah, M Verweij, J Tassel, V Baum, C Demetri, G AF Garrett, C. Huang, X. Casali, P. Schoffski, P. Blackstein, M. Shah, M. Verweij, J. Tassel, V Baum, C. Demetri, G. TI Long-term survival INA phase III trial of sunitinib in imatinib-resistant/intolerant gastrointestinal stromal tumor with novel statistical analysis to account for crossover SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th World Congress on Gastrointestinal Cancer CY JUN 25-28, 2008 CL Barcelona, SPAIN SP ESMO C1 [Garrett, C.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Huang, X.; Tassel, V; Baum, C.] Pfizer Global, Res & Dev, La Jolla, CA USA. [Casali, P.] Ist Nazl Tumori, I-20133 Milan, Italy. [Schoffski, P.] Univ Hosp Gasthuisberg, B-3000 Leuven, Belgium. [Blackstein, M.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Blackstein, M.] Univ Toronto, Toronto, ON, Canada. [Shah, M.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Verweij, J.] Erasmus Univ, Med Ctr, Rotterdam, Netherlands. [Demetri, G.] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 6 BP 12 EP 12 PG 1 WC Oncology SC Oncology GA 330OD UT WOS:000257951800014 ER PT J AU Rutkowski, P Reichardt, P Kang, Y Ruka, W Seddon, B Guerriero, A Breazna, A Lowry, S Demetri, G AF Rutkowski, P. Reichardt, P. Kang, Y. Ruka, W. Seddon, B. Guerriero, A. Breazna, A. Lowry, S. Demetri, G. TI Sunitinib in a worldwide treatment-use trial of patients with imatinib, resistant/intolerant gastrointestinal stromal tumor: Detailed analysis of survival and safety SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th World Congress on Gastrointestinal Cancer CY JUN 25-28, 2008 CL Barcelona, SPAIN SP ESMO C1 [Rutkowski, P.; Ruka, W.] Marie Sklodowska Curie Mem Canc Ctr, Warsaw, 02115, Poland. [Reichardt, P.] HELIOS Klinikurn Bad Saarow, Bad Saarow Pieskow, Germany. [Kang, Y.] Asan Med Ctr, Dept Oncol, Seoul, South Korea. [Seddon, B.] Univ Coll Hosp NHS Trust, London, England. [Guerriero, A.; Breazna, A.; Lowry, S.] Pfizer Inc, New York, NY USA. [Demetri, G.] Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 6 BP 12 EP 12 PG 1 WC Oncology SC Oncology GA 330OD UT WOS:000257951800015 ER PT J AU Anderson, KC AF Anderson, K. C. TI Oncogenomics to target the myeloma cell in its bone marrow microenvironment SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Anderson, K. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 18 EP 18 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300016 ER PT J AU DeCillis, A Baselga, J Edelman, G LoRusso, P Markman, B Papadopoulous, K Shapiro, G Aggarwal, S Nguyen, L Laird, D AF DeCillis, A. Baselga, J. Edelman, G. LoRusso, P. Markman, B. Papadopoulous, K. Shapiro, G. Aggarwal, S. Nguyen, L. Laird, D. TI PI3 kinase targeting agents: XL147 and XL765 SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Baselga, J.] Vall Dhebron Univ Hosp, Barcelona, Spain. [Edelman, G.] Mary Crowley Med Res Ctr, Dallas, TX USA. [LoRusso, P.] Karmanos Canc Inst, Detroit, MI USA. [Papadopoulous, K.] S Texas Accelerated Res Therapeut, San Antonio, TX USA. [Shapiro, G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Aggarwal, S.; Nguyen, L.; Laird, D.] Exelixis, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 21 EP 21 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300030 ER PT J AU Engelman, J AF Engelman, J. TI C-Met, a marker of resistance to EGFR inhibitors in NSCLC SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Engelman, J.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 22 EP 22 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300036 ER PT J AU Driscoll, JJ Lefkimmiatis, K Fulciniti, M Prabhala, RH Pelluru, D Li, C Hu, J Greipp, PR Barlogie, B Anderson, KC Shaughnessy, JD Munshi, NC AF Driscoll, J. J. Lefkimmiatis, K. Fulciniti, M. Prabhala, R. H. Pelluru, D. Li, C. Hu, J. Greipp, P. R. Barlogie, B. Anderson, K. C. Shaughnessy, J. D., Jr. Munshi, N. C. TI The sumoylation pathway is dysfunctional in multiple myeloma and predicts patient survival SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Driscoll, J. J.; Lefkimmiatis, K.; Prabhala, R. H.; Pelluru, D.; Munshi, N. C.] VA Boston Healthcare, W Roxbury, MA USA. [Driscoll, J. J.; Fulciniti, M.; Prabhala, R. H.; Pelluru, D.; Li, C.; Hu, J.; Anderson, K. C.; Munshi, N. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Driscoll, J. J.; Lefkimmiatis, K.; Fulciniti, M.; Prabhala, R. H.; Pelluru, D.; Li, C.; Hu, J.; Anderson, K. C.; Munshi, N. C.] Harvard Univ, Sch Med, Boston, MA USA. [Lefkimmiatis, K.; Greipp, P. R.] Mayo Clin, Rochester, MN USA. [Barlogie, B.; Shaughnessy, J. D., Jr.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 26 EP 27 PG 2 WC Oncology SC Oncology GA 318EL UT WOS:000257074300054 ER PT J AU Lee, L Pintilie, M Hodgson, DC Goss, PE Crump, M AF Lee, L. Pintilie, M. Hodgson, D. C. Goss, P. E. Crump, M. TI Screening mammography for young women treated with supradiaphragmatic radiation for Hodgkin's lymphoma SO ANNALS OF ONCOLOGY LA English DT Article DE breast cancer; Hodgkin's lymphoma; late complications; screening ID BREAST-CANCER RISK; 2ND MALIGNANCY; FOLLOW-UP; DISEASE; SURVIVORS; MRI; CHEMOTHERAPY; IRRADIATION; NEOPLASMS; DENSITY AB Background: Female survivors of Hodgkin's lymphoma (HQ treated with supradiaphragmatic radiation therapy (SRT) are at increased risk of breast cancer (BC) but there is little data on the optimal screening strategy. Patient and methods: We report a prospective surveillance study of women treated for HL with SRT before age 30 participating in a high-risk screening clinic. Starting 8 years after treatment, women received annual mammography and clinical follow-up from 1997 to 2006. Method of detection and characteristics of BCs were identified. Results: In all, 115 female HL survivors attended at least one clinic; 100 participated in annual surveillance. The majority had mammography alone; adjunctive magnetic resonance imaging (MRI) was used more frequently in women with high breast density (P = 0.025). Median age at first mammogram was 36 years and decreased with more recent year of diagnosis. Twelve of the 100 participating women (12%) were diagnosed with BC after a median of 5 years of surveillance (range, 1-9). Seven BCs presented as palpable masses [six invasive, one ductal carcinoma in situ (DCIS)], five were detected by mammography (one invasive, four DCIS). Conclusions: Despite earlier initiation of mammographic screening, most BCs were detected clinically and had unfavorable pathologic characteristics. Evaluation of more intensive screening and the contribution of MRI for earlier detection is warranted. C1 [Lee, L.; Crump, M.] Princess Margaret Hosp, Div Hematol & Med Oncol, Toronto, ON M5G 2M9, Canada. [Pintilie, M.] Princess Margaret Hosp, Dept Biostat, Toronto, ON M5G 2M9, Canada. [Hodgson, D. C.] Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON M5G 2M9, Canada. [Goss, P. E.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Med Oncol, Boston, MA 02114 USA. RP Crump, M (reprint author), Princess Margaret Hosp, Div Hematol & Med Oncol, Room 5-108,610 Univ Ave, Toronto, ON M5G 2M9, Canada. EM michael.crump@uhn.on.ca NR 33 TC 32 Z9 32 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 2008 VL 19 IS 1 BP 62 EP 67 DI 10.1093/annonc/mdm440 PG 6 WC Oncology SC Oncology GA 262VP UT WOS:000253176400009 PM 17878177 ER PT J AU Casali, P Furnagalli, E Bello, A George, S AF Casali, P. Furnagalli, E. Bello, A. George, S. TI Initiation of sunitinis treatment 24 hours following a final dose of imatinib in patients with advanced gastrointestinal stromal tumor: Safety and tolerability SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th World Congress on Gastrointestinal Cancer CY JUN 25-28, 2008 CL Barcelona, SPAIN SP ESMO C1 [Casali, P.; Furnagalli, E.] Ist Nazl Tumori, I-20133 Milan, Italy. [Bello, A.] Pfizer Global, Res & Dev, New York, NY USA. [George, S.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 6 BP 74 EP 74 PG 1 WC Oncology SC Oncology GA 330OD UT WOS:000257951800244 ER PT J AU Smith, MR AF Smith, M. R. TI Treatment-related diabetes and cardiovascular disease in prostate cancer survivors SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol ID ANDROGEN-DEPRIVATION THERAPY; BONE-MINERAL DENSITY; HORMONE AGONIST TREATMENT; LEAN BODY-MASS; BREAST-CANCER; METABOLIC SYNDROME; POSTMENOPAUSAL WOMEN; SUPPRESSION THERAPY; ARTERIAL STIFFNESS; HEART-DISEASE C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 39 TC 6 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 7 BP 86 EP 90 DI 10.1093/annonc/mdn458 PG 5 WC Oncology SC Oncology GA 354CH UT WOS:000259616000012 ER PT J AU Finocchiaro, G Cappuzz, F Toschi, L Rossj, E Janne, PA Roncalli, M Ligorio, C Rimassa, L Santoro, A Varella-Garcia, M AF Finocchiaro, G. Cappuzz, F. Toschi, L. Rossj, E. Janne, P. A. Roncalli, M. Ligorio, C. Rimassa, L. Santoro, A. Varella-Garcia, M. TI Molecular predictors of cetuximab resistance in colorectal cancer patients SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Joint Annual Conference of the European-Society-of-Medical-Oncology/Japanese-Society-of-Medical-Oncolog y CY JUL 03-06, 2008 CL Lugano, SWITZERLAND SP European Soc Med Oncol, Japanese Soc Med Oncol C1 [Finocchiaro, G.; Cappuzz, F.; Ligorio, C.] Ist Humanitas, Milan, Italy. [Toschi, L.] Dana Farber Canc Inst, Ist Humanitas, Boston, MA 02115 USA. [Rossj, E.] CINECA, Interhuniv Censorium, Bologna, Italy. [Janne, P. A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Rimassa, L.; Santoro, A.] Ist Clin Humanitas, Milan, Italy. [Varella-Garcia, M.] Colorado Canc Ctr, Dept Med Med Oncol, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 5 BP 141 EP 141 PG 1 WC Oncology SC Oncology GA 330OC UT WOS:000257951700064 ER PT J AU Perry, CD Hutter, MM Smith, DB Newhouse, JP McNeil, BJ AF Perry, Cynthia D. Hutter, Matthew M. Smith, Daniel B. Newhouse, Joseph P. McNeil, Barbara J. TI Survival and changes in comorbidities after bariatric surgery SO ANNALS OF SURGERY LA English DT Article ID GASTRIC BYPASS; RISK-FACTORS; OPERATION; MORTALITY; OUTCOMES; OBESITY; LIFE AB Objective: To evaluate survival rates and changes in weight-related comorbid conditions after bariatric surgery in a high-risk patient population as compared with a similar cohort of morbidly obese patients who did not undergo surgery. Summary Background Data: Morbid obesity is increasingly becoming a major public health issue. Existing studies are limited in their ability to assess the risks and benefits of bariatric surgery because few studies compare surgical patients to a similar, morbidly obese, nonsurgical cohort, especially in high-risk populations like the elderly and disabled. Methods: A retrospective cohort analysis using Medicare fee-for-service patients from 2001 to 2004. Survival rates and diagnosed presence of 5 conditions commonly comorbid with morbid obesity were examined for morbidly obese patients who did and did not undergo bariatric surgery, with up to 2 years follow-up. Results: Morbidly obese Medicare patients who underwent bariatric surgery had increased survival rates over the 2 years of this study when compared with a similar morbidly obese nonsurgical group (P < 0.001). For patients under the age of 65, this survival advantage started at 6 months postoperatively and for patients over age 65, at 11 months. The surgical group also experienced significant improvements in the diagnosed prevalence of 5 weight-related comorbid conditions (diabetes, sleep apnea, hypertension, hyperlipidemia, and coronary artery disease) relative to the nonsurgical cohort after 1 year postsurgery (P < 0.001). Conclusions: Bariatric surgery appears to increase survival even in the high-risk, Medicare population, both for individuals aged 65 and older and those disabled and under 65. In addition, the diagnosed prevalence of weight-related comorbid conditions declined after bariatric surgery relative to a control cohort of morbidly obese patients who did not undergo surgery. C1 [Perry, Cynthia D.] Urban Inst, Washington, DC 20037 USA. [Hutter, Matthew M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Smith, Daniel B.; Newhouse, Joseph P.; McNeil, Barbara J.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02138 USA. [Newhouse, Joseph P.] Harvard Univ, John F Kennedy Sch Govt, Cambridge, MA 02138 USA. [Newhouse, Joseph P.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [McNeil, Barbara J.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Perry, CD (reprint author), Urban Inst, 2100 M Str,NW, Washington, DC 20037 USA. EM cperry@ui.urban.org NR 25 TC 61 Z9 67 U1 1 U2 5 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 JAN PY 2008 VL 247 IS 1 BP 21 EP 27 DI 10.1097/SLA.0b013e318142cb4b PG 7 WC Surgery SC Surgery GA 246BL UT WOS:000251982400005 PM 18156918 ER PT J AU Nikfarjam, M Warshaw, AL Axelrod, L Deshpande, V Thayer, SP Ferrone, CR Castillo, CFD AF Nikfarjam, Mehrdad Warshaw, Andrew L. Axelrod, Lloyd Deshpande, Vikram Thayer, Sarah P. Ferrone, Cristina R. Castillo, Carlos Fernandez-del TI Improved contemporary surgical management of insulinomas - A 25-year experience at the Massachusetts General Hospital SO ANNALS OF SURGERY LA English DT Article ID ISLET CELL TUMORS; NEOPLASIA TYPE-I; PREOPERATIVE LOCALIZATION; PANCREATIC INSULINOMAS; NEUROENDOCRINE TUMORS; DISTAL PANCREATECTOMY; ENDOSCOPIC ULTRASOUND; SURGERY; HYPOGLYCEMIA; CARCINOMA AB Objective: To determine changes in the management strategy of patients with insulinomas and identify critical factors in patient outcome. Background: Pancreatic insulinomas are rare neoplasms that are present in various ways. The optimal approach to localization, operative management, and follow-up of insulinomas is undetermined. Methods: Sixty-one patients with a diagnosis of insulinoma requiring surgery at a tertiary care center between 1983 and 2007 were reviewed. Demographic details, mode of presentation, preoperative localization, operative procedures, and pathology data were assessed. The effect of different factors on survival was determined. Results: Seven of 61 (11%) patients had a diagnosis of multiple endocrine neoplasia-type 1 (MEN-1). Multiple insulinomas were noted in 8% of cases and were more common in MEN-1 patients. The overall rate of malignancy was 8%. Confusion (67%), visual disturbances (42%), and diaphoresis (30%) were the most common presenting symptoms. Weight gain was noted in 44% of patients. The median duration of symptoms before diagnosis was 18 (1-240) months. The sensitivity of preoperative imaging of tumors before 1994 was 75%, compared with 98% after this period, which included use of endoscopic ultrasound scanning (P = 0.012). A combination of palpation and intraoperative ultrasound detected 92% of tumors. Distal pancreatectomy (40%), enucleation (34%), and pancreaticoduodenectomy (16%) were the most common procedures and pancreatic fistula occurred in 18% of patients. Three patients underwent noncurative distal pancreatectomy in the early period. The 10-year disease-specific and disease-free survival was 100% and 90% respectively. There were 5 patients with disease recurrence. Lymph node metastases (P < 0.001), lymphovascular invasion (P < 0.001), and the presence of MEN-1 (P = 0.035) were prognostically significant adverse factors in disease-free survival. Lymphovascular invasion was the only significant factor on multivariate analysis (P = 0.002). Conclusion: Pancreatic insulinomas can be readily localized preoperatively with modem imaging to avoid unsuccessful blind pancreatic resection. Surgical resection is associated with low morbidity and mortality and achieves long-term disease-free survival in the absence of lymphovascular invasion. C1 [Nikfarjam, Mehrdad; Warshaw, Andrew L.; Thayer, Sarah P.; Ferrone, Cristina R.; Castillo, Carlos Fernandez-del] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Axelrod, Lloyd] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Deshpande, Vikram; Castillo, Carlos Fernandez-del] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Castillo, CFD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,WAC 460, Boston, MA 02114 USA. EM cfernandez@partners.org OI Nikfarjam, Mehrdad/0000-0003-4866-276X FU NCI NIH HHS [P01 CA117969] NR 40 TC 76 Z9 87 U1 0 U2 5 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 JAN PY 2008 VL 247 IS 1 BP 165 EP 172 DI 10.1097/SLA.0b013e31815792ed PG 8 WC Surgery SC Surgery GA 246BL UT WOS:000251982400024 PM 18156937 ER PT J AU Schnelldorfer, T David, BA Warshaw, AL Lillemoe, KD Sarr, MG AF Schnelldorfer, Thomas David, B. Adams Warshaw, Andrew L. Lillemoe, Keith D. Sarr, Michael G. TI Forgotten pioneers of pancreatic surgery - Beyond the favorite few SO ANNALS OF SURGERY LA English DT Review ID CHRONIC RELAPSING PANCREATITIS; SURGICAL-MANAGEMENT; AMPULLARY REGION; RADICAL SURGERY; CARCINOMA; OPERATION; RESECTION; DUODENUM; PANCREATICODUODENECTOMY; EXPERIENCE AB Who would associate a small-town German physician by the name of Friedrich Wilhelm Wandesleben with the performance of the first reported operation on the human pancreas or the German surgeon Oskar Ehrhardt with the first successful partial pancreatoduodenectomy? Along with other pioneers of pancreatic surgery, they have been essentially forgotten and, to the best of our knowledge, have not been cited or credited by others in modem literature. The intent of this review is to shine light on a piece of lost history in our profession. Creation of operative pancreatic fistulae, as well as more complex partial pancreatic resections, was performed on animals as early as the 1660s.(1,2) Yet the pancreas remained for the longest time a mysterious and misunderstood organ, off limits to therapeutic interventions. Until the 1880s, only pathologists showed any practical interest in pancreatic diseases because of the lack of safe methods of diagnosis and treatment by clinicians.(3) Laboratory tests to diagnose pancreatic dysfunction were not available until introduction of the Cammidge reaction (Cammidge reaction is a somewhat unscientific laboratory test assessing crystal formation in chemically treated urine, most likely assessing glycosuria) from urine in 1900 and the detection of serum amylase activity in 1908.(4,5) The first radiographic visualization of the pancreas (or more precisely of pancreatic calcifications) was not described until 1911.(6) The development of pancreatic surgery eventually paralleled the diagnostic understanding of pancreatic disease and the improvements in intra-abdominal operative techniques and postoperative patient care. Major resections of the pancreas were for the longest time considered futile because of limited techniques of hemostasis, the absence of adequate resuscitation, and the lack of postoperative nutritional support. The use of thermocautery for hemostasis and postoperative resuscitation with saline solutions in pancreatic surgery was first mentioned by Franke(7) in 1900. With the development of blood typing and the introduction of anticoagulants for blood storage, blood transfusion became available in the late 1920s.(8,9) The recognition of the role of vitamin K in 1929 and the ability to give exogenous vitamin K preoperatively added another key piece.(10) The accumulation of those and many other small steps eventually opened the doors to the growth of modem pancreatic surgery. C1 [Schnelldorfer, Thomas; Sarr, Michael G.] Mayo Clin, Div Gastroenterol & Gen Surg, Rochester, MN 55905 USA. [David, B. Adams] Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. [Warshaw, Andrew L.] Harvard Univ, Sch Med, Boston, MA USA. [Warshaw, Andrew L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Lillemoe, Keith D.] Indiana Univ, Sch Med, Dept Surg, Indianapolis, IN USA. RP Schnelldorfer, T (reprint author), Mayo Clin, Div Gastroenterol & Gen Surg, 200 1st St SW, Rochester, MN 55905 USA. EM schnelidorfer.thomas@mayo.edu NR 120 TC 18 Z9 19 U1 0 U2 2 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 JAN PY 2008 VL 247 IS 1 BP 191 EP 202 DI 10.1097/SLA.0b013e3181559a97 PG 12 WC Surgery SC Surgery GA 246BL UT WOS:000251982400027 PM 18156940 ER PT J AU Raut, CP DeMatteo, RP AF Raut, Chandrajit P. DeMatteo, Ronald P. TI Prognostic factors for primary GIST: Prime time for personalized therapy? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID GASTROINTESTINAL STROMAL TUMORS; SURGICAL RESECTION; IMATINIB MESYLATE; PHASE-I; MUTATIONS; SURGERY C1 [Raut, Chandrajit P.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA. [Raut, Chandrajit P.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [DeMatteo, Ronald P.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10024 USA. RP Raut, CP (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM craut@partners.org NR 18 TC 9 Z9 16 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 2008 VL 15 IS 1 BP 4 EP 6 DI 10.1245/s10434-007-9634-y PG 3 WC Oncology; Surgery SC Oncology; Surgery GA 249TD UT WOS:000252251800002 PM 17932720 ER PT J AU Posner, MC Niedzwiecki, D Venook, AP Hollis, DR Kindler, HL Martin, EW Schilsky, RL Goldberg, RM AF Posner, Mitchell C. Niedzwiecki, Donna Venook, Alan P. Hollis, Donna R. Kindler, Hedy L. Martin, Edward W. Schilsky, Richard L. Goldberg, Richard M. CA Cancer Leukemia Grp B TI A phase II prospective multi-institutional trial of adjuvant active specific immunotherapy following curative resection of colorectal cancer hepatic metastases: Cancer and leukemia group b study 89903 SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 60th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 15-18, 2007 CL Washington, DC SP Soc Surg Oncol DE immunotherapy; colorectal cancer; liver metastases ID MULTICENTER RANDOMIZED-TRIAL; MONOCLONAL-ANTIBODY VACCINE; LONG-TERM SURVIVAL; COLON-CANCER; CARCINOEMBRYONIC ANTIGEN; LIVER METASTASES; IMMUNE-RESPONSES; STAGE-II; FLUOROURACIL; SURGERY AB Background: Patients with curatively resected colorectal cancer hepatic metastases often harbor occult metastatic disease and are at high risk of experiencing recurrence. This patient cohort is ideally suited to test novel therapies such as immunotherapy. We treated patients-post-hepatic resection-with anti-idiotype monoclonal antibody vaccines to the tumor-associated antigens carcinoembryonic antigen (CeaVac) and human milk fat globule (TriAb), both of which are co-expressed in more than 90% of colorectal cancer patients. Methods: Vaccinations commenced 6-12 weeks post-hepatic resection and consisted of four biweekly treatments of 2 mg CeaVac and TriAb, then monthly treatments for 2 years, then on every other month for 3 years. The primary endpoint was to investigate the proportion of patients recurrence-free at 2 years, and the objective of the study was to demonstrate that at least 58% would be recurrence-free at this time to consider the regimen worthy of further study. Results: Between July 2001 and October 2004, 56 patients were accrued; 52 patients with margin-negative resection were eligible for analysis. Hepatic lobectomy was performed in 56% of patients with a median of one metastasis (range 1-3). Of the 52 eligible patients, 49 were evaluable for the primary end point. Median follow-up was 3.1 years. The proportion of patients recurrence-free at 2 years was 39%, with a lower confidence bound (LCB) of 0.29. Median recurrence-free survival was 16 months. The 2-year overall survival was 94% (95% CI, 0.81, 0.98). Only 10% of patients had documented grade-3 adverse events. Conclusions: Anti-idiotype monoclonal antibody vaccine therapy with CeaVac and TriAb as an adjuvant to curative resection of colorectal cancer hepatic metastases is well tolerated but did not improve 2-year recurrence-free survival when compared with the expected value of 40% reported for hepatic resection alone. C1 [Posner, Mitchell C.; Kindler, Hedy L.; Schilsky, Richard L.] Univ Chicago, Chicago, IL 60637 USA. [Niedzwiecki, Donna; Hollis, Donna R.] Duke Univ, Med Ctr, CALGB Stat Ctr, Durham, NC USA. [Venook, Alan P.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Goldberg, Richard M.] Univ N Carolina, Chapel Hill, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. [Martin, Edward W.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. RP Posner, MC (reprint author), Univ Chicago, 5841 S Maryland Ave MC5031, Chicago, IL 60637 USA. EM mposner@surgery.bsd.uchicago.edu RI Goldberg , Richard/M-1311-2013 FU NCI NIH HHS [CA33601, CA31946, CA32291, CA41287, CA47559, CA60138, CA77658] NR 20 TC 16 Z9 18 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 2008 VL 15 IS 1 BP 158 EP 164 DI 10.1245/s10434-007-9654-7 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 249TD UT WOS:000252251800023 PM 18008108 ER PT J AU Dominguez, FJ Golshan, M Black, DM Hughes, KS Gadd, MA Christian, R Lesnikoski, BA Specht, M Michaelson, J Smith, BL AF Dominguez, Francisco J. Golshan, Mehra Black, Dalliah M. Hughes, Kevin S. Gadd, Michele A. Christian, Roger Lesnikoski, Beth-Ann Specht, Michelle Michaelson, James Smith, Barbara L. TI Sentinel node biopsy is important in mastectomy for ductal carcinoma in situ SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE breast neoplasm; carcinoma intraductal; sentinel lymph node biopsy; mastectomy ID BREAST-CANCER; AXILLARY DISSECTION; LYMPH-NODES; METASTASES; DIAGNOSIS; WOMEN AB Background: There is uncertainty about the utility of sentinel node biopsy (SNB) for ductal carcinoma in situ (DCIS) and its potential to avoid axillary lymph node dissection (ALND) in patients undergoing mastectomy for DCIS. Methods: A review was conducted of 179 patients who underwent mastectomy with sentinel node biopsy for DCIS without invasion or microinvasion on premastectomy pathology review. Results: The sentinel node identification rate was 98.9% (177/179). Twenty (11.3%) of 177 mastectomies for DCIS had a positive SNB: two micrometastasis (pN1mi) and 18 isolated tumor cells [pN0(i+)]. Unsuspected invasive cancer was found in 20 (11.2%) of 179 mastectomies, eight T1mic, five T1a, three T1b, and four T1c tumors. Sentinel nodes were identified in 19 of 20 patients with invasive cancer and four were positive: one pN1mi and three pN0( i+). Eighteen of 19 patients with unsuspected invasive cancer were able to avoid axillary dissection on the basis of SNB results. Of the 159 patients whose final pathology revealed DCIS without invasion, a sentinel node was identified in 158 (99.4%). The SNB was positive in 16 patients (10.1%): one pN1mi and 15 pN0(i+). Three patients underwent ALND on the basis of positive SNBs and in each the SNB was the only positive node. Conclusions: 11% of patients undergoing mastectomy for DCIS were found to have invasive cancer on final pathology. The use of SNB during mastectomy for DCIS allowed nearly all such patients to avoid axillary dissection. These results support routine use of SNB during mastectomy for DCIS. C1 [Dominguez, Francisco J.; Black, Dalliah M.; Hughes, Kevin S.; Gadd, Michele A.; Specht, Michelle; Michaelson, James; Smith, Barbara L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Boston, MA 02115 USA. [Golshan, Mehra; Christian, Roger; Lesnikoski, Beth-Ann] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Surg Oncol, Boston, MA 02115 USA. RP Smith, BL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Boston, MA 02115 USA. EM blsmith1@partners.org OI Hughes, Kevin/0000-0003-4084-6484 NR 28 TC 26 Z9 33 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 2008 VL 15 IS 1 BP 268 EP 273 DI 10.1245/s10434-007-9610-6 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA 249TD UT WOS:000252251800039 PM 17891441 ER PT S AU Tontonoz, P Spiegelman, BM AF Tontonoz, Peter Spiegelman, Bruce M. TI Fat and beyond: The diverse biology of PPAR gamma SO ANNUAL REVIEW OF BIOCHEMISTRY SE Annual Review of Biochemistry LA English DT Review; Book Chapter DE adipocyte; inflammation; insulin sensitivity; metabolism; macrophage; nuclear receptor; thiazolidindione ID ACTIVATED-RECEPTOR-GAMMA; HEPATIC INSULIN SENSITIVITY; SMOOTH-MUSCLE-CELLS; RETINOID-X-RECEPTOR; MACROPHAGE-GENE-EXPRESSION; TYPE-2 DIABETES-MELLITUS; HUMAN DENDRITIC CELLS; ACID-BINDING PROTEIN; B SIGNALING PATHWAY; BODY-MASS INDEX AB The nuclear receptor PPAR gamma is a ligand-activated transcription factor that plays an important role in the control of gene expression linked to a variety of physiological processes. PPAR gamma was initially characterized as the master regulator for the development of adipose cells. Ligands for PPAR gamma include naturally occurring fatty acids and the thiazolidinedione (TZD) class of antidiabetic drugs. Activation of PPAR gamma improves insulin sensitivity in rodents and humans through a combination of metabolic actions, including partitioning of lipid stores and the regulation of metabolic and inflammatory mediators termed adipokines. PPAR gamma signaling has also been implicated in the control of cell proliferation, atherosclerosis, macrophage function, and immunity. Here, we review recent advances in our understanding of the diverse biological actions of PPAR gamma with an eye toward the expanding therapeutic potential of PPAR gamma agonist drugs. C1 [Tontonoz, Peter] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA. [Tontonoz, Peter] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Tontonoz, P (reprint author), Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA. EM ptontonoz@mednet.ucla.edu; bruce_spiegelman@dfci.harvard.edu FU Howard Hughes Medical Institute; NHLBI NIH HHS [HL 66088]; NIDDK NIH HHS [R37 DK 3140] NR 171 TC 899 Z9 937 U1 11 U2 138 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4154 BN 978-0-8243-0877-3 J9 ANNU REV BIOCHEM JI Annu. Rev. Biochem. PY 2008 VL 77 BP 289 EP 312 DI 10.1146/annurev.biochem.77.061307.091829 PG 24 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 325NY UT WOS:000257596800013 PM 18518822 ER PT S AU Payer, B Lee, JT AF Payer, Bernhard Lee, Jeannie T. TI X Chromosome Dosage Compensation: How Mammals Keep the Balance SO ANNUAL REVIEW OF GENETICS SE Annual Review of Genetics LA English DT Review; Book Chapter DE X chromosome inactivation; epigenetics; imprinting; evolution; chromatin; noncoding RNA ID EMBRYONIC STEM-CELLS; EARLY MOUSE DEVELOPMENT; PRIMORDIAL GERM-CELLS; CHICKEN Z-CHROMOSOME; REPRESSIVE HISTONE METHYLATION; NOVO DNA METHYLTRANSFERASES; IMPRINTED XIST EXPRESSION; POLYCOMB GROUP-COMPLEXES; LINKED GENE-EXPRESSION; GROUP PROTEIN EED AB The development of genetic sex determination and cytologically distinct sex chromosomes leads to the potential problem of gene dosage imbalances between autosomes and sex chromosomes and also between males and females. To circumvent these imbalances, mammals have developed an elaborate system of dosage compensation that includes both upregulation and repression of the X chromosome. Recent advances have provided insights into the evolutionary history of how both the imprinted and random forms of X chromosome inactivation have come about. Furthermore, our understanding of the epigenetic switch at the X-inactivation center and the molecular aspects of chromosome-wide silencing has greatly improved recently. Here, we review various facets of the ever-expanding field of mammalian dosage compensation and discuss its evolutionary, developmental, and mechanistic components. C1 [Payer, Bernhard] Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Payer, B (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. EM payer@molbio.mgh.harvard.edu; lee@molbio.mgh.harvard.edu RI Payer, Bernhard/F-7353-2010 OI Payer, Bernhard/0000-0002-4694-2082 FU International Human Frontier Science Program Organization (HFSP); NIH RO1 [GM58839]; Howard Hughes Medical Institute FX The authors would like to thank the entire Lee laboratory for insightful discussions and suggestions and in particular J. Erwin, S. Namekawa, L. Nolen and Y. Ogawa for critical reading of the manuscript. We also would like to thank S. Namekawa for sharing unpublished results. B.P. is supported by a fellowship of the International Human Frontier Science Program Organization (HFSP) and J.T.L. by an NIH RO1 grant (GM58839). J.T.L. is an investigator of the Howard Hughes Medical Institute. NR 268 TC 265 Z9 270 U1 5 U2 35 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4197 BN 978-0-8243-1242-8 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 2008 VL 42 BP 733 EP 772 DI 10.1146/annurev.genet.42.110807.091711 PG 40 WC Genetics & Heredity SC Genetics & Heredity GA 384TL UT WOS:000261767000030 PM 18729722 ER PT S AU Medoff, BD Thomas, SY Luster, AD AF Medoff, Benjamin D. Thomas, Seddon Y. Luster, Andrew D. TI T cell trafficking in allergic asthma: The ins and outs SO ANNUAL REVIEW OF IMMUNOLOGY SE Annual Review of Immunology LA English DT Review; Book Chapter DE asthma; T lymphocytes; chemotaxis; chemokines ID BRONCHOALVEOLAR LAVAGE FLUID; INFLAMMATORY PROTEIN 3-ALPHA; AIRWAY EPITHELIAL-CELLS; ACTIVATION-REGULATED CHEMOKINE; THYMUS-EXPRESSED CHEMOKINE; HUMAN TH17 CELLS; TH2 CELLS; DENDRITIC CELLS; EOTAXIN EXPRESSION; LUNG INFLAMMATION AB T cells are critical mediators of the allergic airway inflammation seen in asthma. Pathogenic allergen-specific T cells ire generated in regional lymph nodes and are then recruited into the airway by chemoattractants produced by the asthmatic lung. These recruited effector T cells and their products then mediate the cardinal features of asthma: airway eosinophilia, mucus hypersecretion, and airway hyperreactivity. There has been considerable progress in delineating the molecular mechanisms that control T cell trafficking into peripheral tissue, including the asthmatic lung. In this review, we summarize these advances and formulate them into a working model that proposes that T cell trafficking into and out of the allergic lung is controlled by several discrete regulatory pathways that involve the collaboration of innate and acquired immune cells. C1 [Medoff, Benjamin D.; Thomas, Seddon Y.; Luster, Andrew D.] Massachusetts Gen Hosp East, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. [Medoff, Benjamin D.] Massachusetts Gen Hosp East, Pulm & Crit Care Unit, Charlestown, MA 02129 USA. [Medoff, Benjamin D.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Medoff, BD (reprint author), Massachusetts Gen Hosp East, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. EM aluster@mgh.harvard.edu OI Thomas, Seddon/0000-0003-0075-0744 FU NHLBI NIH HHS [KO8 HL072775]; NIAID NIH HHS [R01 AI40618, T32 AI060548] NR 176 TC 115 Z9 118 U1 0 U2 6 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 BN 978-0-8243-3026-2 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2008 VL 26 BP 205 EP 232 DI 10.1146/annurev.immunol.26.021607.090312 PG 28 WC Immunology SC Immunology GA 293QH UT WOS:000255349300007 PM 18304002 ER PT S AU Chowdhury, D Lieberman, J AF Chowdhury, Dipanjan Lieberman, Judy TI Death by a thousand cuts: Granzyme pathways of programmed cell death SO ANNUAL REVIEW OF IMMUNOLOGY SE Annual Review of Immunology LA English DT Review; Book Chapter DE cytotoxic T lymphocyte; cytotoxic granule; natural killer cell; serine protease; granule exocytosis; serpin ID SERINE-PROTEASE GRANZYME; CYTOTOXIC T-LYMPHOCYTES; NATURAL-KILLER-CELLS; SECRETORY TRYPSIN-INHIBITOR; CYTOCHROME-C RELEASE; HUMAN POLYMORPHONUCLEAR NEUTROPHILS; GLUCOCORTICOID-INDUCED APOPTOSIS; CYTOKINE RESPONSE MODIFIER; GRANULE-MEDIATED APOPTOSIS; PAPILLON-LEFEVRE-SYNDROME AB The granzymes ire cell death-inducing enzymes, stored in the cytotoxic granules of cytotoxic T lymphocytes and natural killer cells, that are released during granule exocytosis when a specific virus-infected or transformed target cell is marked for elimination. Recent work suggests that this homologous family of serine esterases can activate at least three distinct pathways of cell death. This redundancy likely evolved to provide protection against pathogens and tumors with diverse strategies for evading cell death. This review discusses what is known about granzyme-mediated pathways of cell death as well as recent studies that implicate granzymes in immune regulation and extracellular proteolytic functions in inflammation. C1 [Chowdhury, Dipanjan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Chowdhury, Dipanjan] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. [Lieberman, Judy] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Chowdhury, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM Dipanjan_Chowdhury@dfci.harvard.edu; lieberman@cbr.med.harvard.edu RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI45587, AI63430, R01 AI045587, R01 AI045587-10, R01 AI063430, R01 AI063430-04, R56 AI045587] NR 206 TC 235 Z9 241 U1 0 U2 9 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 BN 978-0-8243-3026-2 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2008 VL 26 BP 389 EP 420 DI 10.1146/annurev.immunol.26.021607.090404 PG 32 WC Immunology SC Immunology GA 293QH UT WOS:000255349300013 PM 18304003 ER PT S AU Keir, ME Butte, MJ Freeman, GJ Sharpel, AH AF Keir, Mary E. Butte, Manish J. Freeman, Gordon J. Sharpel, Arlene H. TI PD-1 and its ligands in tolerance and immunity SO ANNUAL REVIEW OF IMMUNOLOGY SE Annual Review of Immunology LA English DT Review; Book Chapter DE costimulation; T cell; autoimmunity; infectious disease; tumor ID T-CELL-ACTIVATION; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; PROGRAMMED DEATH-1 PATHWAY; GAMMA-DEPENDENT MECHANISM; GASTRIC EPITHELIAL-CELLS; CROSS-LINKING ANTIBODY; CHRONIC HEPATITIS-B; RESPONSES IN-VIVO; DENDRITIC CELLS AB Programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, deliver inhibitory signals that regulate the balance between T cell activation, tolerance, and immunopathology. Immune responses to foreign and self-antigens require specific and balanced responses to clear pathogens and tumors and yet maintain tolerance. Induction and maintenance of T cell tolerance requires PD-1, and its ligand PD-L1 on nonhematopoietic cells can limit effector T cell responses and protect tissues from immune-mediated tissue damage. The PD-1:PD-L pathway also has been usurped by microorganisms and tumors to attenuate antimicrobial or tumor immunity and facilitate chronic infection and tumor survival. The identification of B7-1 as an additional binding partner for PD-L1, together with the discovery of an inhibitory bidirectional interaction between PD-L1 and B7-1, reveals new ways the B7:CD28 family regulates T cell activation and tolerance. In this review, we discuss current understanding of the immunoregulatory functions of PD-1 and its ligands and their therapeutic potential. C1 [Keir, Mary E.; Butte, Manish J.; Sharpel, Arlene H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Keir, Mary E.; Butte, Manish J.; Sharpel, Arlene H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. RP Keir, ME (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM arlene_sharpe@hms.harvard.edu OI Butte, Manish/0000-0002-4490-5595 NR 152 TC 1372 Z9 1457 U1 58 U2 236 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 BN 978-0-8243-3026-2 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2008 VL 26 BP 677 EP 704 DI 10.1146/annurev.immunol.26.021607.090331 PG 28 WC Immunology SC Immunology GA 293QH UT WOS:000255349300022 PM 18173375 ER PT S AU Kaye, DM Hoshijima, M Chien, KR AF Kaye, David M. Hoshijima, Masahiko Chien, Kenneth R. TI Reversing advanced heart failure by targeting Ca(2+) cycling SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE sarcoplasmic reticulum ATPase; phospholamban; excitation contraction coupling; gene therapy ID LEFT-VENTRICULAR DYSFUNCTION; FAILING HUMAN HEARTS; SARCOPLASMIC-RETICULUM CA2+-ATPASE; ADENOVIRAL GENE-TRANSFER; INTACT HUMAN HEART; CARDIAC-HYPERTROPHY; IN-VIVO; CONTRACTILE DYSFUNCTION; INTRACORONARY DELIVERY; CARDIOVASCULAR-DISEASE AB Heart failure is a major cardiovascular disease, characterized by considerable morbidity and mortality. Despite major advances in the pharmacotherapy of heart failure, the options for patients with severe end-stage symptoms remain limited. However, recent developments in the identification of the molecular basis for the progressive nature of heart failure have identified a number of potentially important new therapeutic targets. In particular, key components of the cardiomyocyte calcium-handling pathway show characteristic changes in heart failure. A body of research examining the effect of restoration of these defects in experimental models of heart failure, whether in genetically engineered mouse models or by myocardial gene transfer, very strongly supports the calcium-handling pathway as a target for clinical intervention. C1 [Kaye, David M.] Baker Heart Res Inst, Heart Failure Res Grp, Melbourne, Vic 8008, Australia. [Hoshijima, Masahiko] Univ Calif San Diego, Inst Mol Med, La Jolla, CA 92093 USA. [Chien, Kenneth R.] Harvard Univ, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Harvard Stem Cell Inst,Sch Med, Boston, MA 02114 USA. RP Kaye, DM (reprint author), Baker Heart Res Inst, Heart Failure Res Grp, Melbourne, Vic 8008, Australia. EM david.kayc@baker.edu.au; kchien@partners.org NR 104 TC 29 Z9 30 U1 1 U2 3 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 BN 978-0-8243-0559-8 J9 ANNU REV MED JI Annu. Rev. Med. PY 2008 VL 59 BP 13 EP 28 DI 10.1146/annurev.med.59.052407.103237 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 265YJ UT WOS:000253397600002 PM 18186701 ER PT S AU Moore, AF Florez, JC AF Moore, Allan F. Florez, Jose C. TI Genetic susceptibility to type 2 diabetes and implications for antidiabetic therapy SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE MODY; TCF7L2; KCNf11; PPARG; pharmacogenetics; single-nucleotide polymorphism; genome-wide association ID TRANSCRIPTION-FACTOR-7-LIKE-2 TCF7L2 GENE; HEPATOCYTE NUCLEAR FACTOR-1-BETA; GENOME-WIDE ASSOCIATION; CHANNEL SUBUNIT KIR6.2; INSULIN-RECEPTOR GENE; COMMON VARIANTS; ACTIVATING MUTATIONS; E23K VARIANT; PREVENTION PROGRAM; PRO12ALA VARIANT AB Despite major advances in our knowledge of glycemic pathophysiology and the availability of multiple therapeutic options to confront type 2 diabetes, unraveling the complex link between genetic risk and environmental factors in this burgeoning epidemic has proven difficult. Linkage approaches have clarified the etiology of monogenic diabetic syndromes and congenital lipodystrophies, and candidate gene association studies have identified a number of common variants implicated in type 2 diabetes. This year we have witnessed the advent of genome-wide association scanning: As many as nine genetic loci have now been reproducibly associated with type 2 diabetes in five genome-wide scans. Of particular interest are preliminary explorations of the connections between genetic risk and pharmacologic response. An improved understanding of genetic mechanisms should allow us to test whether behavioral or pharmacologic therapies can be tailored and thus the tremendous disease burden inflicted by type 2 diabetes alleviated. C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Med, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Med, Diabet Unit, Boston, MA 02114 USA. EM jcflorez@partners.org NR 83 TC 27 Z9 27 U1 1 U2 2 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 BN 978-0-8243-0559-8 J9 ANNU REV MED JI Annu. Rev. Med. PY 2008 VL 59 BP 95 EP 111 DI 10.1146/annurev.med.59.090706.135315 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 265YJ UT WOS:000253397600007 PM 17937592 ER PT S AU Sequist, LV Lynch, TJ AF Sequist, Lecia V. Lynch, Thomas J. TI EGFR tyrosine kinase inhibitors in lung cancer: An evolving story SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE EGFR mutations; personalized medicine; non-small cell lung cancer; gefitinib; erlotinib ID GROWTH-FACTOR-RECEPTOR; PREVIOUSLY TREATED PATIENTS; PHASE-III TRIAL; GENE-MUTATIONS; ACTIVATING MUTATIONS; ACQUIRED-RESISTANCE; DIFFERENTIAL EXPRESSION; GEFITINIB SENSITIVITY; MOLECULAR PREDICTORS; PROLONGED SURVIVAL AB Drugs that target the epidermal growth factor receptor (EGFR) have had a major impact on the treatment of non-small cell lung cancer (NSCLC). The use of these drugs has also motivated pivotal advances in the understanding of the molecular biology of NSCLC, including the discovery that mutations in EGFR are associated with dramatic and sustained responses to anti-EGFR treatments. This review summarizes the clinical development of EGFR tyrosine kinase inhibitors, the discovery of molecular predictors of response, and the future directions for research in the field. C1 [Sequist, Lecia V.; Lynch, Thomas J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Sequist, LV (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM Ivsequist@partners.org RI Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 NR 76 TC 81 Z9 86 U1 0 U2 11 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 BN 978-0-8243-0559-8 J9 ANNU REV MED JI Annu. Rev. Med. PY 2008 VL 59 BP 429 EP 442 DI 10.1146/annurev.med.59.090506.202405 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 265YJ UT WOS:000253397600029 PM 17716025 ER PT S AU Leeman, BA Cole, AJ AF Leeman, B. A. Cole, A. J. TI Advancements in the treatment of epilepsy SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE seizures; neuroimaging; anticonvulsants; epilepsy surgery ID ADD-ON THERAPY; PLACEBO-CONTROLLED TRIAL; QUALITY STANDARDS SUBCOMMITTEE; REFRACTORY PARTIAL SEIZURES; CONTROLLED CLINICAL-TRIAL; COMPLEX PARTIAL SEIZURES; PARTIAL-ONSET SEIZURES; TECHNOLOGY-ASSESSMENT SUBCOMMITTEE; LENNOX-GASTAUT-SYNDROME; PREVIOUSLY UNTREATED EPILEPSY AB Diagnostic tools and treatment options for epilepsy have expanded in recent years. Imaging techniques once confined to research laboratories are now routinely used for clinical purposes. Medications that were unavailable a few years ago are now first-line agents. Patients with refractory seizures push for earlier surgical intervention, consider treatment with medical devices, and actively seek nonpharmacologic alternatives. We review some of these recent advances in the management of epilepsy. C1 [Leeman, B. A.; Cole, A. J.] Massachusetts Gen Hosp, Epilepsy Serv, Boston, MA 02114 USA. RP Leeman, BA (reprint author), Massachusetts Gen Hosp, Epilepsy Serv, Boston, MA 02114 USA. EM baleeman@partners.org; cole.andrew@mgh.harvard.edu NR 103 TC 8 Z9 9 U1 2 U2 10 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 BN 978-0-8243-0559-8 J9 ANNU REV MED JI Annu. Rev. Med. PY 2008 VL 59 BP 503 EP 523 DI 10.1146/annurev.med.58.071105.110848 PG 21 WC Medicine, General & Internal SC General & Internal Medicine GA 265YJ UT WOS:000253397600034 PM 17883367 ER PT S AU Cornell, LD Smith, RN Colvin, RB AF Cornell, Lynn D. Smith, R. Neal Colvin, Robert B. TI Kidney transplantation: Mechanisms of rejection and acceptance SO ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE SE Annual Review of Pathology-Mechanisms of Disease LA English DT Review; Book Chapter DE renal allograft; acute rejection; chronic rejection; antibody; accommodation ID RENAL-ALLOGRAFT REJECTION; ANTIBODY-MEDIATED REJECTION; MURINE CARDIAC ALLOGRAFTS; CAPILLARY C4D DEPOSITION; ACUTE HUMORAL REJECTION; TUMOR-NECROSIS-FACTOR; NATURAL-KILLER-CELLS; TO-MESENCHYMAL TRANSITION; GRAFT ARTERIAL-DISEASE; POSITIVE CROSS-MATCH AB We describe the Molecular and cellular mechanisms believed to be responsible for the rejection of renal allografts, including acute T cell-mediated rejection, acute antibody-mediated (humoral) rejection, rejection mediated by the innate immune system, and chronic rejection. We present mechanisms of graft acceptance, including accommodation, regulation, and tolerance. Studies in animals have replicated many pathologic features of acute and chronic rejection. We illuminate the pathogenesis of human pathology by reflection from experimental models. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Cornell, LD (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM cornell.lynn@mayo.edu; rnsmith@partners.org; colvin@helix.mgh.harvard.edu NR 177 TC 98 Z9 105 U1 2 U2 12 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1553-4006 BN 978-0-8243-4303-3 J9 ANNU REV PATHOL-MECH JI Annu. Rev. Pathol.-Mech. Dis. PY 2008 VL 3 BP 189 EP 220 DI 10.1146/annurev.pathol.3.121806.151508 PG 32 WC Pathology SC Pathology GA 275QD UT WOS:000254085800008 PM 18039144 ER PT S AU Lin, JH Walter, P Yen, TSB AF Lin, Jonathan H. Walter, Peter Yen, T. S. Benedict TI Endoplasmic reticulum stress in disease pathogenesis SO ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE SE Annual Review of Pathology-Mechanisms of Disease LA English DT Review; Book Chapter DE protein misfolding; unfolded protein response; IRE1; PERK; ATF-6 ID UNFOLDED PROTEIN RESPONSE; PANCREATIC BETA-CELLS; HEPATITIS-B-VIRUS; FIBROSING CHOLESTATIC HEPATITIS; DOMINANT RETINITIS-PIGMENTOSA; CAPACITATIVE CALCIUM-ENTRY; BZIP TRANSCRIPTION FACTOR; OXIDE-INDUCED APOPTOSIS; LARGE SURFACE PROTEIN; ER STRESS AB The endoplasmic reticulum (ER) is the site of synthesis and folding of membrane and secretory proteins, which, collectively, represent a large fraction of the total protein output of a mammalian cell. Therefore; the protein flux through the ER must be carefully monitored for abnormalities, including the buildup of misfolded proteins. Mammalian cells have. evolved an intricate set of signaling pathways from the ER to the cytosol and nucleus, to allow the cell to respond to the of fold presence misfold proteins within the ER. These pathways, known collectively as-the unfolded protein response, are important for normal cellular homeostasis and organismal development and may also play key roles in the pathogenesis of many diseases. This review provides background information on the unfolded protein response and discusses a selection of diseases whose pathogenesis involves ER stress. C1 [Lin, Jonathan H.; Walter, Peter] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. [Lin, Jonathan H.; Yen, T. S. Benedict] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [Walter, Peter] Howard Hughes Med Inst, Chevy Chase, MD USA. [Yen, T. S. Benedict] San Francisco VA Med Ctr, Pathol Serv, San Francisco, CA 94121 USA. RP Lin, JH (reprint author), Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. EM Jonathan.Lin@ucsf.edu; walter@cgl.ucsf.edu; yen@itsa.ucsf.edu FU Howard Hughes Medical Institute; NEI NIH HHS [K08 EY018313, K08 EY018313-01, R01 EY020846] NR 154 TC 272 Z9 288 U1 0 U2 17 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1553-4006 BN 978-0-8243-4303-3 J9 ANNU REV PATHOL-MECH JI Annu. Rev. Pathol.-Mech. Dis. PY 2008 VL 3 BP 399 EP 425 DI 10.1146/annurev.patho1.3.121806.151434 PG 27 WC Pathology SC Pathology GA 275QD UT WOS:000254085800015 PM 18039139 ER PT S AU Viola, A Luster, AD AF Viola, Antonella Luster, Andrew D. TI Chemokines and their receptors: Drug targets in immunity and inflammation SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY SE Annual Review of Pharmacology and Toxicology LA English DT Review; Book Chapter DE leukocytes; chemotaxis; disease; drug discovery ID SECONDARY LYMPHOID ORGANS; DENDRITIC CELL-MIGRATION; IN-VIVO ACTIVITY; ALLOGRAFT-REJECTION; HIV-1 INFECTION; MONOCLONAL-ANTIBODY; CXC CHEMOKINES; AIRWAY HYPERRESPONSIVENESS; DIFFERENTIAL EXPRESSION; MULTIPLE-SCLEROSIS AB The chemokine system coordinates leukocyte migration in immunity and inflammation and is implicated in the pathogenesis of many human diseases. Although several successful strategies have been identified to develop drugs targeting chemokines and their receptors, this has not yet resulted in many new therapeutics. This is likely due to a complexity of the chemokine system, which was not initially appreciated, that is characterized by redundancy, pleiotropy, and differences among species. Nevertheless, our understanding of chemokine biology is continuing to grow and several promising drugs are currently being tested in late-stage clinical trials. In this review, we examine the role of chemokines in health and diseases and discuss strategies to target the chemokine system. C1 [Viola, Antonella] Univ Milan, Ist Patol Gen, I-20133 Milan, Italy. [Viola, Antonella] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02114 USA. [Viola, Antonella] IRCCS, Ist Clin Humanitas, I-20089 Milan, Italy. RP Viola, A (reprint author), IRCCS, Ist Clin Humanitas, I-20089 Milan, Italy. EM antonella.viola@humanitas.it; luster.andrew@mgh.harvard.edu RI Agatea, Lisa/L-8267-2016 OI Agatea, Lisa/0000-0002-8380-9619 FU Associazione Italiana per la Ricerca sul Cancro NR 120 TC 304 Z9 317 U1 2 U2 26 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0362-1642 BN 978-0-8243-0447-8 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2008 VL 48 BP 171 EP 197 DI 10.1146/annurev.pharmtox.48.121806.154841 PG 27 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 265YD UT WOS:000253396900007 PM 17883327 ER PT J AU Guo, ZY Qiao, ZS Feng, YM AF Guo, Zhan-Yun Qiao, Zhi-Song Feng, You-Min TI The in vitro oxidative folding of the insulin superfamily SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID GROWTH-FACTOR-I; DISULFIDE-FORMING PATHWAY; PROINSULIN C-PEPTIDE; RECEPTOR-BINDING; B-CHAIN/DOMAIN; KINETIC TRAP; IGF-I; PROTEIN; PRECURSOR; CHAIN AB Insulin and related proteins, which have been found not only in mammals, birds, reptiles, amphibians, fish, and cephalochordate, but also in mollusca, insects, and Caenorhabditis elegans, form a large protein family, the insulin superfamily. In comparing their amino acid sequences, a common sequence characteristic, the insulin structural motif, is found in all members of the superfamily. The structural motif is deduced to be the sequence basis of the identical disulfide linkages and similar three-dimensional structures of the superfamily. The insulin superfamily provides a series of disulfide-containing proteins for the studies of in vitro oxidative folding. The in vitro folding pathways of insulin-like growth factor-1 (IGF-1), porcine insulin precursor (PIP), human proinsulin, and Amphioxus insulin-like peptide (AILP) have been established by capture and analysis of the folding intermediates during their in vitro oxidative folding process. The family also provides an excellent system for study of the sequence structure relation: insulin and IGF-1 share high amino acid sequence homology, but they have evolved different folding behaviors. The sequence determinants of their different folding behaviors have been revealed by analyzing the folding behaviors of those global and local insulin/IGF-1 hybrids. C1 Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China. Tongji Univ, Inst Prot Res, Shanghai 200092, Peoples R China. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Zhejiang Sci Tech Univ, Coll Life Sci, Hangzhou, Peoples R China. RP Feng, YM (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China. EM fengym@sunm.shcnc.ac.cn NR 79 TC 13 Z9 14 U1 0 U2 5 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 JAN PY 2008 VL 10 IS 1 BP 127 EP 139 DI 10.1089/ars.2007.1860 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 234LH UT WOS:000251165100011 PM 18004974 ER PT J AU Falutz, J Mamputu, JC Marsolais, C Potvin, D Zoltowska, M Aeschliman, D Kotler, D Grinspoon, S AF Falutz, J. Mamputu, J-C Marsolais, C. Potvin, D. Zoltowska, M. Aeschliman, D. Kotler, D. Grinspoon, S. TI Effects of Tesamorelin (TH9507), a growth hormone-releasing factor (GRF) analogue, on visceral adipose tissue (VAT) in HIV-infected patients with excess abdominal fat: impact of antiretroviral therapy regimen SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 10th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV CY NOV 06-08, 2008 CL London, ENGLAND C1 [Falutz, J.] McGill Univ, Montreal Gen Hosp, Ctr Hlth, Montreal, PQ H3G 1A4, Canada. [Mamputu, J-C; Marsolais, C.; Potvin, D.; Zoltowska, M.; Aeschliman, D.] Theratechnol Inc, Montreal, PQ, Canada. [Kotler, D.] Columbia Univ, Coll Phys & Surg, St Lukes Roosevelt Hosp Ctr, New York, NY USA. [Grinspoon, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Grinspoon, S.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2008 VL 13 IS 8 BP A48 EP A49 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 392ZR UT WOS:000262341200064 ER PT J AU Triant, VA Meigs, JM Grinspoon, SK AF Triant, V. A. Meigs, J. M. Grinspoon, S. K. TI Association of C-reactive protein and HIV infection with acute myocardial infarction SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 10th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV CY NOV 06-08, 2008 CL London, ENGLAND C1 [Triant, V. A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Triant, V. A.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Triant, V. A.; Grinspoon, S. K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Meigs, J. M.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Meigs, J. M.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2008 VL 13 IS 8 BP A17 EP A18 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 392ZR UT WOS:000262341200025 ER PT J AU Tsibris, AMN Arnaout, R Korber, B Russ, C Lo, CC Gaschen, B Leitner, T Paredes, R Su, Z Hughes, MD Gulick, RM Greaves, W Coakley, E Flexner, C Nausbaum, C Birren, B Kuritzkes, DR AF Tsibris, A. M. N. Arnaout, R. Korber, B. Russ, C. Lo, C-C Gaschen, B. Leitner, T. Paredes, R. Su, Z. Hughes, M. D. Gulick, R. M. Greaves, W. Coakley, E. Flexner, C. Nausbaum, C. Birren, B. Kuritzkes, D. R. TI Dynamic HIV-1 escape from vicriviroc therapy in vivo SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 17th International HIV Drug Resistance Workshop CY JUN 10-14, 2008 CL Sitges, SPAIN C1 [Tsibris, A. M. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tsibris, A. M. N.; Paredes, R.; Kuritzkes, D. R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Arnaout, R.; Paredes, R.; Kuritzkes, D. R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Arnaout, R.] Harvard Univ, Program Evolutionary Dynam, Cambridge, MA 02138 USA. [Korber, B.; Lo, C-C; Gaschen, B.; Leitner, T.] Los Alamos Natl Labs, Los Alamos, NM USA. [Korber, B.] Santa Fe Inst, Santa Fe, NM 87501 USA. [Russ, C.; Nausbaum, C.; Birren, B.] Broad Inst MIT, Cambridge, MA USA. [Russ, C.; Nausbaum, C.; Birren, B.] Harvard Univ, Cambridge, MA 02138 USA. [Paredes, R.] Fdn irsiCaixa Lluita Contra SIDA, Badalona, Spain. [Su, Z.; Hughes, M. D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Gulick, R. M.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Greaves, W.] Schering Plough Res Inst, Kenilworth, NJ USA. [Coakley, E.] Monogram Biosci, San Francisco, CA USA. [Flexner, C.] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 3 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2008 VL 13 IS 4 BP A97 EP A97 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 323EY UT WOS:000257428100105 ER PT B AU O'Cleirigh, C Hart, TA James, CA AF O'Cleirigh, Conall Hart, Trevor A. James, Carolyn A. BE Zvolensky, MJ Smits, JAJ TI HIV and Anxiety SO ANXIETY IN HEALTH BEHAVIORS AND PHYSICAL ILLNESS SE Series in Anxiety and Related Disorders LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; POSTTRAUMATIC-STRESS-DISORDER; QUALITY-OF-LIFE; ACTIVE ANTIRETROVIRAL THERAPY; NATIONAL COMORBIDITY SURVEY; AUTONOMIC NERVOUS-SYSTEM; SUBSTANCE USE DISORDERS; CHILDHOOD SEXUAL-ABUSE; INJECTION-DRUG USERS; PSYCHIATRIC-DISORDERS C1 [Hart, Trevor A.; James, Carolyn A.] York Univ, Dept Psychol, Toronto, ON M3J 2R7, Canada. [O'Cleirigh, Conall] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RP O'Cleirigh, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 1 Bowdoin Sq BS-07B, Boston, MA 02114 USA. EM cocleirigh@partners.org NR 131 TC 15 Z9 15 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-74752-1 J9 SER ANXIETY RELAT DI PY 2008 BP 317 EP 340 PG 24 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA BJW55 UT WOS:000267313200013 ER PT J AU Maguen, S Papa, A Litz, BT AF Maguen, Shira Papa, Anthony Litz, Brett T. TI Coping with the threat of terrorism: A review SO ANXIETY STRESS AND COPING LA English DT Review DE terrorism; coping; mental health ID POSTTRAUMATIC-STRESS-DISORDER; NEW-YORK-CITY; ANXIETY-BUFFERING FUNCTION; NATIONAL FIELD EXPERIMENT; MENTAL-HEALTH SYMPTOMS; SEPTEMBER 11; MORTALITY SALIENCE; SURROUNDING SEPTEMBER-11; PSYCHOLOGICAL REACTIONS; REPRESENTATIVE SAMPLE AB Terrorism creates a ripple of fear and uncertainty. Although most individuals are resilient and recover over time, a minority remains functionally and psychologically impaired. In this paper, we examine research on coping strategies employed in the aftermath of terrorist events, theories and empirical findings related to appraisal processes that influence individuals' primary attributions of risk, and normative processes that shape secondary appraisals, which predict specific coping behaviors. We also describe individual diatheses and factors promoting resilience that may influence coping and functioning in the face of terrorism. Finally, we offer suggestions for future research. C1 Univ Calif San Francisco, San Francisco VA Med Ctr, PTSD Program 116 P, San Francisco, CA 94143 USA. Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02215 USA. RP Maguen, S (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, PTSD Program 116 P, 4150 Clement St, San Francisco, CA 94143 USA. EM shira.maguen@va.gov NR 114 TC 23 Z9 23 U1 4 U2 18 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1061-5806 J9 ANXIETY STRESS COPIN JI Anxiety Stress Coping PY 2008 VL 21 IS 1 BP 15 EP 35 DI 10.1080/10615800701652777 PG 21 WC Neurosciences; Psychiatry; Psychology, Multidisciplinary SC Neurosciences & Neurology; Psychiatry; Psychology GA 232OD UT WOS:000251028100002 PM 18027122 ER PT J AU Doyle, PJ McNeil, MR Le, K Hula, WD Ventura, MB AF Doyle, Patrick J. McNeil, Malcolm R. Le, Karen Hula, William D. Ventura, Mary Beth TI Measuring communicative functioning in community-dwelling stroke survivors: Conceptual foundation and item development SO APHASIOLOGY LA English DT Article; Proceedings Paper CT 37th Annual Clinical Aphasiology Conference CY MAY, 2007 CL Scottsdale, AZ ID PSYCHOMETRIC EVALUATION; RASCH ANALYSIS; APHASIA; SCALE; RELIABILITY; VALIDITY AB Background: Studies employing item response theory methods to evaluate communicative functioning assessment items have found that a broad range of communication tasks and activities may fit a unidimensional measurement model, but that additional item content is needed to extend the range of ability effectively measured by the small subset of items that have been evaluated. Aims: To describe the item identification, evaluation, and development process used to substantiate the content relevance and representativeness of a set of communicative functioning assessment items targeting community-dwelling stroke survivors. Methods & Procedures: Electronic and secondary references were searched to identify assessment tools with item content designed to measure communicative functioning in adults with neurogenic communication disorders. Candidate items were evaluated using face-to-face interviewer-assisted survey groups conducted independently with communicatively impaired stroke survivors (n=59) and their communicative partners (n=61). Web-based surveys were employed to evaluate candidate items from the perspective of practising speech-language pathologists (n=114). Outcomes & Results: A total of 673 items were identified from 33 instruments. A total of 426 met the specified concept definition; 211 were determined to be non-redundant; 166 were identified by key stakeholders as unambiguous, relevant, and moderately to very important to daily functioning. Conclusions: The item pool developed samples a representative range of communication behaviours, activities, and life situations that are relevant to community-dwelling stroke survivors. Further research using item response theory methods is required to substantiate the construct dimensionality and range of ability effectively measured by the item pool, and to evaluate dynamic assessment algorithms designed to minimise response burden. C1 [Doyle, Patrick J.; McNeil, Malcolm R.] VA Pittsburgh Hlth Care Syst, Audiol Speech Pathol Serv, Pittsburgh, PA 15260 USA. [Doyle, Patrick J.; McNeil, Malcolm R.; Hula, William D.; Ventura, Mary Beth] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Le, Karen] Univ Connecticut, Storrs, CT USA. RP Doyle, PJ (reprint author), Ctr Geriatr Res Educ & Clin, 7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 23 TC 4 Z9 4 U1 1 U2 4 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PY 2008 VL 22 IS 7-8 BP 718 EP 728 DI 10.1080/02687030701803093 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 318JK UT WOS:000257087200005 ER PT J AU Naleid, AM Grimm, JW Kessler, DA Sipols, AJ Aliakbari, S Bennett, JL Wells, J Figlewicz, DP AF Naleid, Amy M. Grimm, Jeffrey W. Kessler, David A. Sipols, Alfred J. Aliakbari, Sepideh Bennett, Jennifer L. Wells, Jason Figlewicz, Dianne P. TI Deconstructing the vanilla milkshake: The dominant effect of sucrose on self-administration of nutrient-flavor mixtures SO APPETITE LA English DT Article DE self-administration; sucrose; fat; reinforcement; macronutrients; flavor ID PROGRESSIVE RATIO SCHEDULES; NONNUTRITIVE OIL-EMULSIONS; FOOD-INTAKE; NUTRITIONAL-STATUS; FAT APPETITE; BODY-WEIGHT; PLACE PREFERENCE; ENERGY DENSITY; DIETARY-INTAKE; SUGAR AB Rats and humans avidly consume flavored foods that contain sucrose and fat, presumably due to their rewarding qualities. In this study, we hypothesized that the complex mixture of corn oil, sucrose, and flavor is more reinforcing than any of these components alone. We observed a concentration-dependent increase in reinforcers of sucrose solutions received (0%, 3%, 6.25%, and 12.5%) in both fixed ratio and progressive ratio procedures, but with equicaloric corn oil solutions (0%, 1.4%, 2.8%, and 5.6%) this finding was replicated only in the fixed ratio procedure. Likewise, addition of 1.4% oil to 3% or 12.5% sucrose increased fixed ratio, but not progressive ratio, reinforcers received relative to those of sucrose alone. Finally, addition of 3% vanilla flavoring did not change self-administration of 3% sucrose or 3% sucrose + 1.4% oil solutions. These data Suggest that, calorie-for-calorie, sucrose is the dominant reinforcing component of novel foods that contain a mixture of fat, sucrose, and flavor. (c) 2007 Elsevier Ltd. All rights reserved. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Western Washington Univ, Dept Psychol, Bellingham, WA USA. Univ Latvian, Inst Clin & Expt Med, Riga, Latvia. Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. RP Figlewicz, DP (reprint author), VA Puget Sound Hlth Care Syst, 1660 So Columbian Way, Seattle, WA 98108 USA. EM latte@u.washington.edu FU NCRR NIH HHS [P20RR020774, P20 RR020774, P20 RR020774-026031, P20 RR020774-02, P20 RR020774-01]; NIAAA NIH HHS [T32 AA007455, T32 AA007455-20, T32-AA007455]; NIDA NIH HHS [F32 DA020315, R15 DA016285, R15 DA016285-01, F32 DA020315-01A2]; NIDDK NIH HHS [R01 DK040963-19, R01 DK040963, R01 DK040963-18, DK40963, R01 DK040963-20, R01 DK040963-18S1] NR 36 TC 15 Z9 15 U1 1 U2 6 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-6663 J9 APPETITE JI Appetite PD JAN PY 2008 VL 50 IS 1 BP 128 EP 138 DI 10.1016/j.appet.2007.06.011 PG 11 WC Behavioral Sciences; Nutrition & Dietetics SC Behavioral Sciences; Nutrition & Dietetics GA 239IR UT WOS:000251512500015 PM 17707949 ER PT J AU Carlozzi, NE Horner, MD Yang, CW Tilley, BC AF Carlozzi, Noelle E. Horner, Michael David Yang, Chengwu Tilley, Barbara C. TI Factor Analysis of the Repeatable Battery for the Assessment of Neuropsychological Status SO APPLIED NEUROPSYCHOLOGY LA English DT Article DE confirmatory factor analysis; exploratory factor analysis; neuropsychological assessment; neuropsychology; psychometrics repeatable battery for the assessment of neuropsychological status (RBANS) ID VALIDITY AB A sample of 175 veterans' scores on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS; Randolph, 1998) was examined to investigate the factor structure of this scale. First, we attempted to replicate a five-factor model to reflect the five Index Scores of the RBANS (immediate memory, visuospatial/constructional, language, attention, and delayed memory) from the 12 individual subtests, using confirmatory factor analysis (CFA). We were unable to identify a five-factor structure of the RBANS. The RBANS subtests were then subjected to an exploratory factor analysis with a maximum likelihood extraction and orthogonal rotation to determine a new dimensional model. Results indicated a two-factor structure that can roughly be described as memory and visuospatial function. CFA of this new structure indicated an adequate fit for this sample. Findings suggest that it may be appropriate to place more emphasis on the individual subtest scores than the index scores during interpretation. C1 [Carlozzi, Noelle E.] Kessler Med Rehabil Res & Educ Ctr, Outcomes & SCI Res Lab, W Orange, NJ 07052 USA. [Carlozzi, Noelle E.] Med Univ S Carolina, H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. [Horner, Michael David] Med Univ S Carolina, Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Carlozzi, NE (reprint author), Kessler Med Rehabil Res & Educ Ctr, Outcomes & SCI Res Lab, 1199 Pleasant Valley Way, W Orange, NJ 07052 USA. EM ncarlozzi@mrrec.org OI Yang, Chengwu/0000-0003-0561-2340 FU [U01 NS043127]; [3P30 AG021677] FX Work on this manuscript was supported, in part, by grants U01 NS043127 and 3P30 AG021677. NR 9 TC 10 Z9 10 U1 1 U2 3 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0908-4282 J9 APPL NEUROPSYCHOL JI Appl. Neuropsychol. PY 2008 VL 15 IS 4 BP 274 EP 279 AR PII 905793172 DI 10.1080/09084280802325124 PG 6 WC Clinical Neurology; Psychology SC Neurosciences & Neurology; Psychology GA 375DQ UT WOS:000261094300005 PM 19023744 ER PT J AU Werth, VP Fivenson, D Pandya, AG Chen, D Rico, MJ Albrecht, J Jacobus, D AF Werth, Victoria P. Fivenson, David Pandya, Amit G. Chen, Diana Rico, M. Joyce Albrecht, Joerg Jacobus, David TI Multicenter randomized, double-blind, placebo-controlled, clinical trial of dapsone as a glucocorticoid-sparing agent in maintenance-phase pemphigus vulgaris SO ARCHIVES OF DERMATOLOGY LA English DT Article ID MYCOPHENOLATE-MOFETIL; AZATHIOPRINE; PREDNISONE; THERAPY AB Objective: To determine the efficacy of dapsone as a glucocorticoid-sparing agent in maintenance-phase pemphigus vulgaris (PV). Design: A randomized, double-blind, placebo-controlled study with a crossover arm for those who failed treatment. Setting: A US multicenter outpatient study Patients: A total of 19 subjects enrolled among 5 centers, 9 randomized to receive dapsone and 10 to receive placebo. Inclusion criteria were biopsy and direct immunofluorescence-proven PV controlled with glucocorticoids and/or cytotoxic agents, disease in maintenance phase, and aged 18 to 80 years. Physicians had tried at least 2 tapers of glucocorticoids unsuccessfully and had 30 days of stable steroid dosage. Treatment for any patient unable to taper glucocorticoids by more than 25% within 4 months was declared a failure, and the patient was allowed to switch to the opposite medication while maintaining the double-blind. Main Outcome Measure: The ability of patients to taper to 7.5 mg/d or less within 1 year of reaching the maximum dosage of the study drug. Results: Of the 9 patients receiving dapsone, 5 were successfully treated, 3 failed treatment, and 1 dropped out of the study. Of the 10 patients receiving placebo, 3 were successfully treated, and 7 failed treatment. This primary end point favored the dapsone-treated group but was not statistically significant (P=.37). Four patients who failed treatment while receiving placebo were switched to treatment with dapsone. Of these, 3 were successfully treated after switching to dapsone treatment, and 1 failed treatment. We found that, overall, 8 of 11 patients (73%) receiving dapsone vs 3 of 10 (30%) receiving placebo reached the primary outcome of a prednisone dosage of 7.5 mg/d or less. Conclusion: This trial demonstrates a trend to efficacy of dapsone as a steroid-sparing drug in maintenance-phase PV. C1 [Werth, Victoria P.; Albrecht, Joerg] Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19119 USA. [Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Fivenson, David] Henry Ford Hlth Syst, Detroit, MI USA. [Pandya, Amit G.] Univ Texas SW Med Ctr Dallas, Dept Dermatol, Dallas, TX 75390 USA. [Chen, Diana] NW Mem Hosp, Dept Dermatol, Chicago, IL 60611 USA. [Rico, M. Joyce] NYU, Dept Dermatol, New York, NY 10016 USA. [Jacobus, David] Jacobus Pharmaceut Co, Princeton, NJ USA. RP Werth, VP (reprint author), Univ Penn, Sch Med, Dept Dermatol, 2 Rhodes Pavilion,3600 Spruce St, Philadelphia, PA 19119 USA. EM werth@mail.med.upenn.edu FU NIAMS NIH HHS [K24-AR 02207, K24 AR002207] NR 23 TC 43 Z9 44 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JAN PY 2008 VL 144 IS 1 BP 25 EP 32 DI 10.1001/archderm.144.1.25 PG 8 WC Dermatology SC Dermatology GA 252IC UT WOS:000252439200003 PM 18209165 ER PT J AU Perlis, RH Purcell, S Fagerness, J Kirby, A Petryshen, TL Fan, J Sklar, P AF Perlis, Roy H. Purcell, Shaun Fagerness, Jesen Kirby, Andrew Petryshen, Tracey L. Fan, Jinbo Sklar, Pamela TI Family-based association study of lithium-related and other candidate genes in bipolar disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Review ID SEROTONIN TRANSPORTER GENE; WNT SIGNALING PATHWAY; SUBSTANCE-P; SUSCEPTIBILITY LOCUS; PREFRONTAL CORTEX; DYSBINDIN GENE; GENOME SCAN; VALPROIC ACID; SCHIZOAFFECTIVE DISORDER; TRYPTOPHAN-HYDROXYLASE AB Context: Association studies in bipolar disorder have been focused on a relatively narrow pool of candidate genes based on a limited understanding of the underlying pathophysiologic features. Recent developments suggest that a broader pool of genes may be associated with this disorder. Objective: To examine the association between genes related to the lithium mechanism of action, as well as other positional and functional candidates, with bipolar I disorder. Design: We examined a dense set of haplotype-tagging single-nucleotide polymorphisms using a gene-based test of association. Participants: Three hundred seventy-nine parent-affected offspring trios. Results: No genes specifically chosen to probe the action of lithium were associated with bipolar disorder. However, gene-based analysis of sialyltransferase 4A (SIAT4A), tachykinin receptor 1 (TACR1), and gamma-aminobutyric acid(A) beta 2 receptor subunit (GABRB2) yielded evidence of association (empirical P value, < .005). Among 3 genes associated with schizophrenia or bipolar disorder in multiple previous studies, including dysbindin (DTNBP1), neuregulin (NRG1), and disrupted-in-schizophrenia 1 (DISC1), only DISC1 showed evidence of association in this cohort. In a secondary analysis of these 6 genes among parent-proband trios with a history of psychosis, evidence of the association with SIAT4A was strengthened. Conclusions: These results suggest novel candidates and 1 gene (DISC1) previously associated with schizophrenia that merit further study in bipolar disorder. However, polymorphisms in major lithium-signaling genes do not appear to contribute substantially to bipolar liability. C1 [Perlis, Roy H.; Purcell, Shaun; Fagerness, Jesen; Petryshen, Tracey L.; Fan, Jinbo; Sklar, Pamela] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Perlis, Roy H.; Purcell, Shaun; Fagerness, Jesen; Petryshen, Tracey L.; Fan, Jinbo; Sklar, Pamela] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. [Petryshen, Tracey L.; Fan, Jinbo; Sklar, Pamela] Harvard Univ, Sch Med, Boston, MA USA. [Petryshen, Tracey L.; Fan, Jinbo; Sklar, Pamela] Broad Inst Harvard, Boston, MA 02115 USA. [Petryshen, Tracey L.; Fan, Jinbo; Sklar, Pamela] MIT, Cambridge, MA 02139 USA. RP Sklar, P (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, 185 Cambridge St, Boston, MA 02114 USA. EM sklar@chgr.mgh.harvard.edu FU NIMH NIH HHS [MH067060, MH062137] NR 122 TC 44 Z9 46 U1 1 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 2008 VL 65 IS 1 BP 53 EP 61 DI 10.1001/archgenpsychiatry.2007.15 PG 9 WC Psychiatry SC Psychiatry GA 248ST UT WOS:000252176400008 PM 18180429 ER PT J AU Bush, G Spencer, TJ Holmes, J Shin, LM Valera, EM Seidman, LJ Makris, N Surman, C Aleardi, M Mick, E Biederman, J AF Bush, George Spencer, Thomas J. Holmes, Jennifer Shin, Lisa M. Valera, Eve M. Seidman, Larry J. Makris, Nikos Surman, Craig Aleardi, Megan Mick, Eric Biederman, Joseph TI Functional magnetic resonance imaging of methylphenidate and placebo in attention-deficit/hyperactivity disorder during the multi-source interference task SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Review ID DEFICIT HYPERACTIVITY DISORDER; ANTERIOR CINGULATE CORTEX; CEREBRAL-BLOOD-FLOW; EVENT-RELATED FMRI; DOPAMINE TRANSPORTER AVAILABILITY; DECISION-MAKING; ADULT PATIENTS; ORAL METHYLPHENIDATE; RESPONSE-INHIBITION; THERAPEUTIC ACTIONS AB Context: Previous studies have reported hypofunction, structural abnormalities, and biochemical abnormalities of the dorsal anterior midcingulate cortex (daMCC) in attention-deficit/hyperactivity disorder (ADHD). Stimulant medications are effective treatments for ADHD, but their neural effects have not been fully characterized. Objective: To determine whether the methylphenidate hydrochloride osmotic-release oral system (OROS) would increase functional magnetic resonance imaging (fMRI) activation, compared with placebo, in the daMCC and other frontoparietal regions subserving attention during the Multi-Source Interference Task (MSIT). Design: Randomized, placebo-controlled, 6-week, before-after fMRI study. Setting: Academic medical center ambulatory clinic. Patients: Twenty-one adults with ADHD randomized to 6 weeks of treatment with methylphenidate OROS (n=11) or placebo (n=10). Interventions: Patients underwent fMRI twice while performing the MSIT (scan 1 at baseline and scan 2 at 6 weeks). Main Outcome Measures: Group-averaged, randomeffects, repeated-measures, general linear model analyses were used to compare daMCC (and whole-brain) fMRI activation during the MSIT. Individual-based daMCC volume-of- interest confirmatory analyses and behavioral data are also presented. Results: Performance and baseline fMRI measures in the daMCC and other a priori brain regions did not differ between groups. Group comparisons showed a group X scan interaction and t test confirmation of higher activation in the daMCC at 6 weeks in the methylphenidate OROS group than in the placebo group (P < 1 X 10(-4), cluster corrected for multiple comparisons). Individual daMCC volume-of-interest analyses confirmed group-averaged findings and suggested that daMCC activity might be related to clinical response. Methylphenidate OROS also produced higher activation in the dorsolateral prefrontal cortex and the parietal cortex at 6 weeks. Conclusion: Methylphenidate OROS increased daMCC activation during the MSIT and may act, in part, by normalizing daMCC hypofunction in ADHD. C1 [Bush, George; Valera, Eve M.] Massachusetts Gen Hosp E, MGH Psychiat Neuroimaging Program, Cingulate Cortex Res Lab, Charlestown, MA 02129 USA. [Bush, George; Spencer, Thomas J.; Shin, Lisa M.; Valera, Eve M.; Seidman, Larry J.; Surman, Craig; Mick, Eric; Biederman, Joseph] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Makris, Nikos] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Bush, George; Holmes, Jennifer; Shin, Lisa M.; Valera, Eve M.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat Neurosci Div, Boston, MA 02114 USA. [Bush, George; Spencer, Thomas J.; Valera, Eve M.; Seidman, Larry J.; Makris, Nikos; Surman, Craig; Aleardi, Megan; Mick, Eric; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Makris, Nikos] Massachusetts Gen Hosp, Dept Radiol Serv, Ctr Morphometr Anal, Boston, MA 02114 USA. [Bush, George; Valera, Eve M.] Harvard Univ, Sch Med, MIT HMS MGH Athinoula A Martinos Ctr Funct & Stru, MIT, Charlestown, MA USA. [Shin, Lisa M.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Seidman, Larry J.] Massachusetts Mental Hlth Ctr, Public Psychiat Div, Boston, MA 02115 USA. [Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Bush, G (reprint author), Massachusetts Gen Hosp E, MGH Psychiat Neuroimaging Program, Cingulate Cortex Res Lab, CNY-2614,Bldg 149,13th St, Charlestown, MA 02129 USA. EM geo@nmr.mgh.harvard.edu OI Mick, Eric/0000-0001-8505-8145 FU NCRR NIH HHS [P41RR14075]; NICHD NIH HHS [MH/HD 62152]; NIMH NIH HHS [MH-16259, F32 MH065040-01A1, 5 RO1 MH064019] NR 127 TC 124 Z9 125 U1 7 U2 25 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 JAN PY 2008 VL 65 IS 1 BP 102 EP 114 DI 10.1001/archgenpsychiatry.2007.16 PG 13 WC Psychiatry SC Psychiatry GA 248ST UT WOS:000252176400014 PM 18180434 ER PT J AU Smith, EE Egorova, S Blacker, D Killiany, RJ Muzikansky, A Dickerson, BC Tanzi, RE Albert, MS Greenberg, SM Guttmann, CRG AF Smith, Eric E. Egorova, Svetlana Blacker, Deborah Killiany, Ronald J. Muzikansky, Alona Dickerson, Bradford C. Tanzi, Rudolph E. Albert, Marilyn S. Greenberg, Steven M. Guttmann, Charles R. G. TI Magnetic resonance imaging white matter hyperintensities and brain volume in the prediction of mild cognitive impairment and dementia SO ARCHIVES OF NEUROLOGY LA English DT Article ID STROKE RISK PROFILE; MIDLIFE BLOOD-PRESSURE; ALZHEIMERS-DISEASE; CARDIOVASCULAR HEALTH; FOLLOW-UP; ATROPHY; MRI; AD; PROGRESSION; ROTTERDAM AB Objective: To determine whether magnetic resonance imaging (MRI) white matter hyperintensities (WMH), whole-brain atrophy, and cardiovascular risk factors predict the development of cognitive decline and dementia. Design: Subjects were recruited into this prospective cohort study and followed for incident cognitive decline for mean (SD) 6.0 (4.1) years. Magnetic resonance imaging dual-echo sequences, obtained at baseline, were used to determine the volume of WMH and the brain parenchymal fraction (BPF), the proportion of the intracranial cavity occupied by brain. White matter hyperintensity volume was analyzed as the percentage of intracranial volume (WMHr); "high WMH" was defined as a WMHr more than 1 SD above the mean. Setting: General community. Patients: Volunteer sample consisting of 67 subjects with normal cognition and 156 subjects with mild cognitive impairment (MCI). Main Outcome Measures: Time to diagnosis of MCI (among those with normal cognition at baseline) or time to diagnosis of dementia, either all-cause or probable Alzheimer disease (AD) (among those with MCI at base-line). Cox proportional hazards models were used for multivariable analysis. Results: High WMH was a predictor of progression from normal to MCI (adjusted hazard ratio [HR], 3.30; 95% confidence interval [CI], 1.33-8.17; P=.01) but not conversion from MCI to all-cause dementia. Conversely, BPF did not predict progression from normal to MCI but did predict conversion to dementia (adjusted HR, 1.10 for each 1% decrease in BPF; 95% CI, 1.02-1.19; P=.02). When conversion to AD dementia was considered as the outcome, BPF was likewise a predictor (adjusted HR, 1.16 for each 1% decrease in BPF; 95% CI, 1.08-1.24; P <.001), but high WMH was not. Past tobacco smoking was associated with both progression from normal to MCI (adjusted HR, 2.71; 95% CI, 1.12-6.55; P=.03) and conversion to all-cause dementia (adjusted HR, 2.08; 95% CI, 1.13-3.82; P=.02), but not AD dementia. Conclusions: These findings suggest that WMH are associated with the risk of progressing from normal to MCI. In persons whose cognitive abilities are already impaired, BPF predicts the conversion to dementia. C1 [Smith, Eric E.; Greenberg, Steven M.] Massachusetts Gen Hosp, Neurol Clin Trials Unit, Dept Neurol, Boston, MA 02114 USA. [Egorova, Svetlana; Guttmann, Charles R. G.] Brigham & Womens Hosp, Ctr Neurol Imaging, Dept Radiol, Boston, MA 02115 USA. [Blacker, Deborah; Muzikansky, Alona] Massachusetts Gen Hosp, Dept Psychiat, Gerontol Res Unit, Boston, MA 02114 USA. [Killiany, Ronald J.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Dickerson, Bradford C.; Tanzi, Rudolph E.] Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Ctr, Boston, MA 02114 USA. [Albert, Marilyn S.] Johns Hopkins Med Ctr, Baltimore, MD USA. RP Smith, EE (reprint author), Massachusetts Gen Hosp, Neurol Clin Trials Unit, Dept Neurol, 175 Cambridge St,Ste 300, Boston, MA 02114 USA. EM eesmith@partners.org RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 FU NIA NIH HHS [P01-AG-04953] NR 49 TC 98 Z9 100 U1 3 U2 10 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 JAN PY 2008 VL 65 IS 1 BP 94 EP 100 DI 10.1001/archneurol.2007.23 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 250PR UT WOS:000252313000012 PM 18195145 ER PT J AU Fotenos, AF Mintun, MA Snyder, AZ Morris, JC Buckner, RL AF Fotenos, Anthony F. Mintun, Mark A. Snyder, Abraham Z. Morris, John C. Buckner, Randy L. TI Brain volume decline in aging SO ARCHIVES OF NEUROLOGY LA English DT Article ID PRECLINICAL ALZHEIMERS-DISEASE; COGNITIVE DECLINE; CEREBRAL ATROPHY; HEAD SIZE; DEMENTIA; AD; EDUCATION; RESERVE; POPULATION; MEMORY AB Objectives: To assess the relation between socioeconomic status (SES) and structural brain change in nondemented older adults and to ascertain the potential role of preclinical Alzheimer disease (AD). Design: Cross-sectional and longitudinal observation. Setting: Alzheimer's Disease Research Center, St Louis, Missouri. Participants: Volunteer sample of 362 nondemented adults aged 18 to 93 years. The main cohort of 100 was evaluated for dementia and SES; a Clinical Dementia Rating (CDR) of 0 (no dementia) and middle, high-middle, or high SES was required for eligibility. All 362 received magnetic resonance imaging; of the main 100, 91 received follow-up clinical assessment, and 33 received follow-up magnetic resonance imaging over at least a 3-year interval. A separate sample of 58 CDR 0 participants (aged 47 to 86 years) took part in amyloid imaging with Pittsburgh Compound B (PiB) labeled with radioactive carbon (C-11). Main Outcome Measures: Whole-brain volume adjusted for head size (aWBV) and change per year. Results: aWBV declined by 0:22% per year between the ages of 20 and 80 years with accelerated decline in advanced aging. Controlling for effects of age and sex in older adults (> 65 years) with CDR 0, higher SES was associated with smaller aWBV (3.8% difference spanning the sample range from middle to high privilege, P <.01) and more rapid volume loss (0.39% per year to 0.68% per year from middle to high privilege, P <.05). aWBV was reduced by 2.5% in individuals positive for PiB binding (n=9) as compared with individuals negative for PiB binding (n=49, P < .05), supporting an influence of undetected preclinical AD. Follow-up clinical data revealed that brain volume reduction associated with SES was greater in those who later developed very mild dementia (preclinical CDR 0 group, n=19) compared with those who remained nondemented (stable CDR 0 group, n=64; group X SES interaction, P <.05). Conclusions: Privileged nondemented older adults harbor more preclinical brain atrophy, consistent with their having greater reserve against the expression of AD. C1 [Fotenos, Anthony F.; Buckner, Randy L.] Washington Univ, Med Sci Training Program, Sch Med, Div Biol & Biomed Sci, St Louis, MO 63110 USA. [Mintun, Mark A.; Snyder, Abraham Z.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Snyder, Abraham Z.; Morris, John C.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Buckner, Randy L.] Harvard Univ, Howard Hughes Med Inst, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA. [Buckner, Randy L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Martinos Ctr, Boston, MA USA. RP Fotenos, AF (reprint author), Washington Univ, Med Sci Training Program, Sch Med, Div Biol & Biomed Sci, Campus Box 8826,660 S Euclid Ave, St Louis, MO 63110 USA. EM anthony.fotenos@wustl.edu RI Morris, John/A-1686-2012 FU NIA NIH HHS [P01 AG-03991, P50 AG-05681, R01 AG-21910]; NINDS NIH HHS [P30 NS-048056] NR 36 TC 99 Z9 102 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JAN PY 2008 VL 65 IS 1 BP 113 EP 120 DI 10.1001/archneurol.2007.27 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 250PR UT WOS:000252313000015 PM 18195148 ER PT J AU Chen-Plotkin, AS Pau, KT Schmahmann, JD AF Chen-Plotkin, Alice S. Pau, Kaipo T. Schmahmann, Jeremy D. TI Delayed leukoencephalopathy after hypoxic-ischemic injury SO ARCHIVES OF NEUROLOGY LA English DT Editorial Material ID POSTHYPOXIC LEUKOENCEPHALOPATHY C1 [Chen-Plotkin, Alice S.; Pau, Kaipo T.; Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Chen-Plotkin, AS (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. EM alicech-enplotkin@gmail.com NR 4 TC 10 Z9 11 U1 0 U2 0 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 JAN PY 2008 VL 65 IS 1 BP 144 EP 145 DI 10.1001/archneurol.2007.7 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 250PR UT WOS:000252313000021 PM 18195154 ER PT J AU Pasquale, LR AF Pasquale, Louis R. TI Optimizing therapy for newly diagnosed open-angle glaucoma - Lessons learned from the Collaborative Initial Glaucoma Treatment Study SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID QUALITY-OF-LIFE; TRABECULECTOMY; TRIAL; PROGRESSION; PREVALENCE C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Pasquale, LR (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Louis_Pasquale@meei.harvard.edu NR 14 TC 1 Z9 2 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 JAN PY 2008 VL 126 IS 1 BP 125 EP 127 DI 10.1001/archophthalmol.2007.1 PG 3 WC Ophthalmology SC Ophthalmology GA 250PP UT WOS:000252312800019 PM 18195230 ER PT J AU Strasser, DC Falconer, JA Stevens, AB Uomoto, JM Herrin, J Bowen, SE Burridge, AB AF Strasser, Dale C. Falconer, Judith A. Stevens, Alan B. Uomoto, Jay M. Herrin, Jeph Bowen, Susan E. Burridge, Andrea B. TI Team training and stroke rehabilitation outcomes: A cluster randomized trial SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE clinical trial; patient care teams; rehabilitation; stroke; training of trainers; treatment outcome ID MULTIDISCIPLINARY INTERVENTION; MODEL; CARE; MANAGEMENT; HOSPITALS; UNITS AB Objective: To test whether a team training intervention in stroke rehabilitation is associated with improved patient outcomes. Design: A cluster randomized trial of 31 rehabilitation units comparing stroke outcomes between intervention and control groups. Setting: Thirty-one Veterans Affairs medical centers. Participants: A total of 237 clinical staff on 16 control teams and 227 staff on 15 intervention teams. Stroke patients (N=487) treated by these teams before and after the intervention. Intervention: The intervention consisted of a multiphase, staff training program delivered over 6 months, including: an off-site workshop emphasizing team dynamics, problem solving, and the use of performance feedback data; and action plans for process improvement; and telephone and videoconference consultations. Control and intervention teams received site-specific team performance profiles with recommendations to use this information to modify team process. Main Outcome Measures: Three patient outcomes: functional improvement as measured by the change in motor items of the FIM instrument, community discharge, and length of stay (LOS). Results: For both the primary (stroke only) and secondary analyses (all patients), there was a significant difference in improvement of functional outcome between the 2 groups, with the percentage of stroke patients gaining more than a median FIM gain of 23 points increasing significantly more in the intervention group (difference in increase, 13.6%; P=.032). There was no significant difference in LOS or rates of community discharge. Conclusions: Stroke patients treated by staff who participated in a team training program were more likely to make functional gains than those treated by staff receiving information only. Team based clinicians are encouraged to examine their own team. (ClinicalTrials.gov identifier NCT00237757). C1 [Strasser, Dale C.] Emory Univ, Dept Rehabil Med, Atlanta, GA 30322 USA. [Strasser, Dale C.] Atlanta VA Med Ctr, Atlanta, GA USA. [Falconer, Judith A.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Stevens, Alan B.] Texas A&M Univ Syst, Hlth Sci Ctr, Scott & White Mem Hosp, Temple, TX USA. [Uomoto, Jay M.] VA Puget Sound Hlth Care Syst, Seattle Div, Ctr Polytrauma Care, Seattle, WA USA. [Herrin, Jeph] Yale Univ, New Haven, CT USA. [Herrin, Jeph] Flying Buttress Associates, Charlottesville, VA USA. [Bowen, Susan E.] Atlanta VA Med Ctr, TREP HSR&D, Decatur, GA USA. [Burridge, Andrea B.] Univ Houston, Dept Educ Psychol, Houston, TX USA. RP Strasser, DC (reprint author), 1441 Clifton Rd NE, Atlanta, GA 30322 USA. EM Dale.Strasser@emoryhelathcare.org RI Backscheider Burridge, Andrea/D-9332-2015 OI Backscheider Burridge, Andrea/0000-0001-7502-0047 NR 33 TC 52 Z9 55 U1 1 U2 10 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 JAN PY 2008 VL 89 IS 1 BP 10 EP 15 DI 10.1016/j.apmr.2007.08.127 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 249LB UT WOS:000252228600003 PM 18164324 ER PT J AU Strasser, DC Uomoto, JM Smits, SJ AF Strasser, Dale C. Uomoto, Jay M. Smits, Stanley J. TI The interdisciplinary team and polytrauma rehabilitation: Prescription for partnership SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE interdisciplinary health team; rehabilitation; trauma; wounds and injuries ID STROKE REHABILITATION; OUTCOMES; HOSPITALS; PROGRAM AB Optimal outcomes for polytrauma survivors depend on the integration of complex medical, psychosocial, financial, educational, and vocational resources across diverse specialties and multiple medical centers, programs, and organizations and all in a setting of high public visibility and family involvement. Well-functioning teams are critical to service integration, and teams are more effective in supportive hospital environments. Here, we offer a model of team functioning relevant to polytrauma and outline a team training program to improve services. Furthermore, we propose a partnership among the team, hospital administrators, and national leaders and with patients and their families. Integrated care requires partnerships among the various stakeholders, and those working in polytrauma have a unique opportunity to create an updated paradigm of the team approach responsive to the complexities of contemporary health care. C1 [Strasser, Dale C.] Emory Univ, Dept Rehabil Med, Atlanta, GA 30322 USA. [Strasser, Dale C.] VA Med Ctr, Atlanta, GA 30322 USA. [Uomoto, Jay M.] Ctr Polytrauma Care, VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. [Smits, Stanley J.] Georgia State Univ, Robinson Coll Business, Dept Management Sci, Atlanta, GA 30303 USA. RP Strasser, DC (reprint author), 1441 Clifton Rd NE, Atlanta, GA 30322 USA. EM Dale.Strasser@emoryhealthcare.org NR 19 TC 10 Z9 11 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 JAN PY 2008 VL 89 IS 1 BP 179 EP 181 DI 10.1016/j.apmr.2007.06.774 PG 3 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 249LB UT WOS:000252228600030 PM 18164351 ER PT J AU Darkins, A Cruise, C Armstrong, M Peters, J Finn, M AF Darkins, Adam Cruise, Cathy Armstrong, Michael Peters, John Finn, Michael TI Enhancing access of combat-wounded veterans to specialist rehabilitation services: The VA polytrauma Telehealth Network SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE rehabilitation; telecommunication networks; telemedicine; wounds and injuries ID TRAUMATIC BRAIN-INJURY; CASUALTIES AB Operations Iraqi Freedom and Enduring Freedom have resulted in U.S. military personnel sustaining combat wounds of unprecedented severity and complexity that necessitate long-term rehabilitation. To meet what are often conflicting requirements in providing severely wounded veterans with timely and convenient access to specialist rehabilitation care, and to enable them to return to their local communities, the Veterans Health Administration has developed a state-of-the-art Polytrauma Telehealth Network that enhances access to such services by linking Veterans Administration rehabilitation facilities. This article describes the clinical, technical, and business process issues involved in the development of this network. C1 [Darkins, Adam; Peters, John; Finn, Michael] Off Care Coordinat 11CC, Dept Vet Affairs, Vet Hlth Adm, Washington, DC 20420 USA. [Cruise, Cathy] US Dept Vet Affairs, Vet Hlth Adm, Northport, MN USA. [Armstrong, Michael] US Dept Vet Affairs, Vet Hlth Adm, Minneapolis, MN USA. RP Darkins, A (reprint author), Off Care Coordinat 11CC, Dept Vet Affairs, Vet Hlth Adm, 810 Vermont Ave NW, Washington, DC 20420 USA. NR 23 TC 10 Z9 10 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JAN PY 2008 VL 89 IS 1 BP 182 EP 187 DI 10.1016/j.apmr.2007.07.027 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 249LB UT WOS:000252228600031 PM 18164352 ER PT J AU Nademin, E Jobes, DA Pflanz, SE Jacoby, AM Ghahramanlou-Holloway, M Campise, R Joiner, T Wagner, BM Johnson, L AF Nademin, Elicia Jobes, David A. Pflanz, Steven E. Jacoby, Aaron M. Ghahramanlou-Holloway, Marjan Campise, Rick Joiner, Thomas Wagner, Barry M. Johnson, Leigh TI An Investigation of Interpersonal-Psychological Variables in Air Force Suicides: A Controlled-Comparison Study SO ARCHIVES OF SUICIDE RESEARCH LA English DT Article DE Air Force; interpersonal-psychological theory of suicide; military; self-inflicted harm; suicide; suicide prevention AB Joiner's (2005) theory attributes suicide to an individual's acquired capability to enact self-harm, perceived burdensomeness, and thwarted belongingness. This study evaluated whether Joiner's theory could differentiate United States (US) Air Force (AF) personnel (n = 60) who died by suicide from a living active duty AF personnel comparison sample (n = 122). Responses from AF personnel on several scales assessing Joiner's constructs were compared to data from a random sample of postmortem investigatory files of AF personnel who died by suicide between 1996-2006. This research also introduced a newly designed measure, the Interpersonal-Psychological Survey (IPS), designed to assess the three components of Joiner's theory in one, easy-to-administer instrument. Analyses of the psychometric properties of the IPS support initial validation efforts to establish this scale as a predictive measure for suicide. Findings support that one's score on the Acquired Capability to Commit Suicide subscale of the IPS and the IPS overall score reliably distinguished between the two groups. The implications of these findings in relation to suicide prevention efforts in the US military are discussed. C1 [Nademin, Elicia] Midwestern Univ, Dept Clin Psychol, Glendale, AZ 85308 USA. [Jobes, David A.; Wagner, Barry M.] Catholic Univ Amer, Washington, DC 20064 USA. [Pflanz, Steven E.] USAF, Med Operat Agcy, Washington, DC 20330 USA. [Jacoby, Aaron M.] VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. [Ghahramanlou-Holloway, Marjan] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Campise, Rick] USAF, Med Operat Squadron 1, Hampton, VA USA. [Joiner, Thomas] Florida State Univ, Gainesville, FL USA. [Johnson, Leigh] USAF, Newport News, VA USA. RP Nademin, E (reprint author), Midwestern Univ, Dept Clin Psychol, 19555 N 59th Ave, Glendale, AZ 85308 USA. EM EliciaN@Gmail.com NR 35 TC 30 Z9 30 U1 0 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1381-1118 J9 ARCH SUICIDE RES JI Arch. Suicide Res. PY 2008 VL 12 IS 4 BP 309 EP 326 DI 10.1080/13811110802324847 PG 18 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA V11CR UT WOS:000207510200003 PM 18828034 ER PT J AU Gutierrez, PM Brenner, LA Huggins, JA AF Gutierrez, Peter M. Brenner, Lisa A. Huggins, Joseph A. TI A Preliminary Investigation of Suicidality in Psychiatrically Hospitalized Veterans with Traumatic Brain Injury SO ARCHIVES OF SUICIDE RESEARCH LA English DT Article DE suicide; traumatic brain injury; veterans AB The objective of this study was to explore suicidal behaviors documented at time of discharge from acute psychiatric hospitalization. Data from 114 acute psychiatric admissions were reviewed for 22 veterans with a history of traumatic brain injury (TBI). Information extracted included presence of suicidal ideation, nature of suicide attempts, and TBI characteristics. The Lethality of Suicide Attempt Rating Scale was used to classify veterans' non-lethal self-harm behavior. Post-TBI, 6 patients (27.3%) made a total of 14 suicide attempts. Half of those attempts required wounds being sutured, stomach lavage, or other medical attention. Clinicians and researchers are strongly encouraged to focus increased attention on suicide prevention in those with a history of TBI. C1 [Gutierrez, Peter M.; Brenner, Lisa A.] Univ Colorado Denver, Sch Med, Dept Psychiat,Dept Phys Med & Rehabil,Dept Neurol, Denver VA Med Ctr,MIRECC,VA VISN 19, Denver, CO 80220 USA. [Huggins, Joseph A.] Univ Colorado Denver, Sch Med, Dept Family Med, MIRECC,MSW,MSCIS VA VISN 19, Denver, CO 80220 USA. RP Gutierrez, PM (reprint author), Univ Colorado Denver, Sch Med, Dept Psychiat,Dept Phys Med & Rehabil,Dept Neurol, Denver VA Med Ctr,MIRECC,VA VISN 19, 1055 Clermont St, Denver, CO 80220 USA. EM peter.gutierrez@va.gov OI Huggins, Joe/0000-0001-8151-5062 NR 23 TC 19 Z9 19 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1381-1118 J9 ARCH SUICIDE RES JI Arch. Suicide Res. PY 2008 VL 12 IS 4 BP 336 EP 343 DI 10.1080/13811110802324961 PG 8 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA V11CR UT WOS:000207510200005 PM 18828036 ER PT J AU Kinlay, S Schwartz, GG Olsson, AG Rifai, N Szarek, M Waters, DD Libby, P Ganz, P AF Kinlay, Scott Schwartz, Gregory G. Olsson, Anders G. Rifai, Nader Szarek, Michael Waters, David D. Libby, Peter Ganz, Peter CA MIRACL Study Investigators TI Inflammation, statin therapy, and risk of stroke after an acute coronary syndrome in the MIRACL study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE stroke; acute coronary syndromes; inflammation; CRP; statin ID C-REACTIVE PROTEIN; ACUTE MYOCARDIAL-INFARCTION; TRANSIENT ISCHEMIC ATTACK; HIGH-DOSE ATORVASTATIN; ATHEROSCLEROTIC PLAQUE; CAROTID STENOSIS; UNSTABLE ANGINA; CHOLESTEROL; EVENTS; TRIAL AB Objective-Patients with acute coronary syndromes have an increased risk of stroke. We measured markers of inflammation in the MIRACL study, a randomized trial of atorvastatin versus placebo in acute coronary syndromes, to assess the relationship of inflammation to stroke. Methods and Results-Baseline C-reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL-6) were collected in 2926 (95%) subjects. Baseline markers were related to stroke risk over the 16 weeks of the study. Subjects who subsequently experienced a stroke had higher CRP (27.5 versus 10.2 mg/L, P=0.0032), SAA (30.5 versus 16.0 mg/L, P=0.031), IL-6 (11 231 versus 6841 pg/L, P=0.004), and troponin (6.03 versus 3.19 ng/mL P=0.0032). The risk of stroke was related to greater CRP, SAA, and IL-6 in the placebo group only. Similarly, there was a graded increase in risk of stroke across quartiles of inflammatory markers in the placebo patients only. Conclusions-In acute coronary syndromes, the early risk of stroke relates to both heightened inflammation and size of myocardial necrosis. Treatment with atorvastatin abrogated the risk associated with elevated markers of inflammation in this study, a finding that provides a novel rationale for the use of statins in acute coronary syndromes. C1 [Kinlay, Scott; Libby, Peter; Ganz, Peter] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Kinlay, Scott] Div Cardiovasc, West Roxbury, MA USA. [Kinlay, Scott; Rifai, Nader; Libby, Peter; Ganz, Peter] Harvard Univ, Sch Med, Boston, MA USA. [Schwartz, Gregory G.] Vet Affairs Med Ctr, Div Cardiol, Denver, CO USA. [Schwartz, Gregory G.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Olsson, Anders G.] Linkoping Univ, Fac Hlth Sci, S-58183 Linkoping, Sweden. [Rifai, Nader] Childrens Hosp, Boston, MA 02115 USA. [Szarek, Michael] Pfizer Pharmaceut Grp, New York, NY USA. [Waters, David D.] San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94110 USA. [Waters, David D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Kinlay, S (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM skinlay@partners.org NR 31 TC 45 Z9 49 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JAN 1 PY 2008 VL 28 IS 1 BP 142 EP 147 DI 10.1161/ATVBAHA.107.151787 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 248NE UT WOS:000252159500021 PM 17991875 ER PT J AU Fernandes, VRS Polak, JF Cheng, S Rosen, BD Carvalho, B Nasir, K McClelland, R Hundley, G Pearson, G O'Leary, DH Bluemke, DA Lima, JAC AF Fernandes, Veronica Rolim S. Polak, Joseph F. Cheng, Susan Rosen, Boaz D. Carvalho, Benilton Nasir, Khurram McClelland, Robyn Hundley, Gregory Pearson, Greg O'Leary, Daniel H. Bluemke, David A. Lima, Joao A. C. TI Arterial stiffness is associated with regional ventricular systolic and diastolic dysfunction - The multi-ethnic study of atherosclerosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE arterial stiffness; regional ventricular function; heart failure; tagging MRI; strain rate ID HEART-FAILURE; PULSE PRESSURE; CLINICAL-APPLICATIONS; MYOCARDIAL-FUNCTION; SUBCLINICAL ATHEROSCLEROSIS; ASYMPTOMATIC INDIVIDUALS; BLOOD-PRESSURE; OLDER-ADULTS; HARP MRI; HYPERTENSION AB Objective - The pathophysiology of left ventricular (LV) dysfunction, particularly in the setting of a preserved ejection fraction (EF), remains unclear. Few studies have investigated the relationship between arterial compliance and LV function in humans, and none used cardiovascular MRI. Methods and Results - We sought to determine whether arterial compliance is related to regional myocardial function among participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Arterial compliance was assessed using carotid ultrasound measurements to calculate the distensibility coefficient (DC) and Young's modulus (YM). Circumferential systolic (SRS) and diastolic (SRE) strain rates were calculated by harmonic phase ( HARP) from tagged MRI. Associations between arterial compliance and indices of ventricular function were adjusted for cardiovascular risk factors. We found a significant association between arterial compliance and SRS in all myocardial regions (P < 0.05); arterial compliance was also associated with SRE in the lateral and septal wall regions (P < 0.05). Multiple linear regression analyses demonstrated a direct linear relationship between the carotid artery DC and SRS across all LV segments and slices, even after adjustment for cardiovascular risk factors and LV mass. In regression analyses, a significant relationship between arterial compliance and SRE in the septal and antero-apical walls was also found and remained significant after multivariable adjustment. Conclusion - Arterial stiffness is associated with early and asymptomatic impairment of systolic as well as diastolic myocardial function. Further studies are needed to elucidate role of vascular compliance in the development of ventricular dysfunction and failure. C1 [Polak, Joseph F.] Tufts Univ New England Med Ctr, Dept Radiol, Boston, MA USA. [Cheng, Susan] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Carvalho, Benilton] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Fernandes, Veronica Rolim S.; Rosen, Boaz D.; Bluemke, David A.; Lima, Joao A. C.] Johns Hopkins Univ, Div Cardiol, Baltimore, MD USA. [Nasir, Khurram] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McClelland, Robyn] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Hundley, Gregory] Wake Forest Univ Hlth Sci, Dept Internal Med Cardiol, Winston Salem, NC USA. [Pearson, Greg] Columbia Univ, Dept Radiol, New York, NY USA. [Bluemke, David A.; Lima, Joao A. C.] Johns Hopkins Univ, Dept Radiol, Caritas Carney Hosp, Baltimore, MD USA. RP Lima, JAC (reprint author), Johns Hopkins Univ Hosp, Div Cardiol, Blalock 524,600 N Wolfe St, Baltimore, MD 21287 USA. EM jlima@jhmi.edu OI Bluemke, David/0000-0002-8323-8086 FU NHLBI NIH HHS [R01-HL66075-01, N01-HC-95168, N01-HC-95169, N01-HC-9808] NR 39 TC 59 Z9 64 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JAN 1 PY 2008 VL 28 IS 1 BP 194 EP 201 DI 10.1161/ATVBAHA.107.156950 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 248NE UT WOS:000252159500029 PM 17962621 ER PT J AU Helmick, CG Felson, DT Lawrence, RC Gabriel, S Hirsch, R Kwoh, CK Liang, MH Kremers, HM Mayes, MD Merkel, PA Pillemer, SR Reveille, JD Stone, JH AF Helmick, Charles G. Felson, David T. Lawrence, Reva C. Gabriel, Sherine Hirsch, Rosemarie Kwoh, C. Kent Liang, Matthew H. Kremers, Hilal Maradit Mayes, Maureen D. Merkel, Peter A. Pillemer, Stanley R. Reveille, John D. Stone, John H. CA Natl Arthritis Data Workgrp TI Estimates of the prevalence of arthritis and other rheumatic conditions in the United States SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; INFLAMMATORY-BOWEL-DISEASE; PRIMARY SJOGRENS-SYNDROME; ANKYLOSING-SPONDYLITIS; REITERS-SYNDROME; PERIPHERAL ARTHRITIS; OLMSTED COUNTY; PIMA-INDIANS; CARE VISITS; EPIDEMIOLOGY AB Objective. To provide a single source for the best available estimates of the US prevalence of and number of individuals affected by arthritis overall, rheumatoid arthritis, juvenile arthritis, the spondylarthritides, systemic lupus erythematosus, systemic sclerosis, and Sjogren's syndrome. A companion article (part II) addresses additional conditions. Methods. The National Arthritis Data Workgroup reviewed published analyses from available national surveys, such as the National Health and Nutrition Examination Survey and the National Health Interview Survey (NHIS). For analysis of overall arthritis, we used the NHIS. Because data based on national population samples are unavailable for most specific rheumatic conditions, we-derived estimates from published studies of smaller, defined populations. For specific conditions, the best available prevalence estimates were applied to the corresponding 2005 US population estimates from the Census Bureau, to estimate the number affected with each condition. Results. More than 21% of US adults (46.4 million persons) were found to have self-reported doctor-diagnosed arthritis. We estimated that rheumatoid arthritis affects 1.3 million adults (down from the estimate of 2.1 million for 1995), juvenile arthritis affects 294,000 children, spondylarthritides affect from 0.6 million to 2.4 million adults, systemic lupus erythematosus affects from 161,000 to 322,000 adults, systemic sclerosis affects 49,000 adults, and primary Sjogren's syndrome affects from 0.4 million to 3.1 million adults. Conclusion. Arthritis and other rheumatic conditions continue to be a large and growing public health problem. Estimates for many specific rheumatic conditions rely on a few, small studies of uncertain generalizability to the US population. This report provides the best available prevalence estimates for the US, but for most specific conditions, more studies generalizable to the US or addressing understudied populations are needed. C1 [Helmick, Charles G.] CDC, Arthritis Program, Atlanta, GA 30341 USA. [Felson, David T.; Merkel, Peter A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Lawrence, Reva C.] NIH, Bethesda, MD 20892 USA. [Gabriel, Sherine; Kremers, Hilal Maradit] Mayo Clin, Rochester, MN USA. [Hirsch, Rosemarie] CDC, Hyattsville, MD USA. [Kwoh, C. Kent] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Kwoh, C. Kent] Pittsburgh VA Healthcare Syst, Pittsburgh, PA USA. [Liang, Matthew H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Mayes, Maureen D.; Reveille, John D.] Univ Texas Houston, Hlth Sci Ctr, Houston, TX USA. [Pillemer, Stanley R.] Macrogen, Rockville, MD USA. [Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Helmick, CG (reprint author), CDC, Arthritis Program, 4770 Buford Highway,K51, Atlanta, GA 30341 USA. EM CHelmick@cdc.gov FU NIAMS NIH HHS [K24 AR002224] NR 90 TC 811 Z9 825 U1 9 U2 73 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JAN PY 2008 VL 58 IS 1 BP 15 EP 25 DI 10.1002/art.23177 PG 11 WC Rheumatology SC Rheumatology GA 256ML UT WOS:000252733100004 PM 18163481 ER PT J AU Lawrence, RC Felson, DT Helmick, CG Arnold, LM Choi, H Deyo, RA Gabriel, S Hirsch, R Hochberg, MC Hunder, GG Jordan, JM Katz, JN Kremers, HM Wolfe, F AF Lawrence, Reva C. Felson, David T. Helmick, Charles G. Arnold, Lesley M. Choi, Hyon Deyo, Richard A. Gabriel, Sherine Hirsch, Rosemarie Hochberg, Marc C. Hunder, Gene G. Jordan, Joanne M. Katz, Jeffrey N. Kremers, Hilal Maradit Wolfe, Frederick CA Natl Arthritis Data Workgrp TI Estimates of the prevalence of arthritis and other rheumatic conditions in the United States SO ARTHRITIS AND RHEUMATISM LA English DT Article ID GIANT-CELL ARTERITIS; LOW-BACK-PAIN; CARPAL-TUNNEL-SYNDROME; COUNTY OSTEOARTHRITIS PROJECT; GENERAL-POPULATION; POLYMYALGIA-RHEUMATICA; KNEE OSTEOARTHRITIS; NATIONAL-HEALTH; OLMSTED COUNTY; 1990 CRITERIA AB Objective. To provide a single source for the best available estimates of the US prevalence of and number of individuals affected by osteoarthritis, polymyalgia rheumatica and giant cell arteritis, gout, fibromyalgia, and carpal tunnel syndrome, as well as the symptoms of neck and back pain. A companion article (part 1) addresses additional conditions. Methods. The National Arthritis Data Workgroup reviewed published analyses from available national surveys, such as the National Health and Nutrition Examination Survey and the National Health Interview Survey. Because data based on national population samples are unavailable for most specific rheumatic conditions, we derived estimates from published studies of smaller, defined populations. For specific conditions, the best available prevalence estimates were applied to the corresponding 2005 US populaiion estimates from the Census Bureau, to estimate the number affected with each condition. Results. We estimated that among US adults, nearly 27 million have clinical osteoarthritis (up from the estimate of 21 million for 1995), 711,000 have polymyalgia rheumatica, 228,000 have giant cell arteritis, up to 3.0 million have had self-reported gout in the past year (up from the estimate of 2.1 million for 1995), 5.0 million have fibromyalgia, 4-10 million have carpal tunnel syndrome, 59 million have had low back pain in the past 3 months, and 30.1 million have had neck pain in the past 3 months. Conclusion. Estimates for many specific rheumatic conditions rely on a few, small studies of uncertain generalizability to the US population. This report provides the best available prevalence estimates for the US, but for most specific conditions more studies generalizable to the US or addressing understudied populations are needed. C1 [Helmick, Charles G.] CDC, Arthritis Program, Atlanta, GA 30341 USA. [Lawrence, Reva C.] NIH, Bethesda, MD 20892 USA. [Felson, David T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Arnold, Lesley M.] Univ Cincinnati, Cincinnati, OH USA. [Choi, Hyon] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Gabriel, Sherine; Hunder, Gene G.; Kremers, Hilal Maradit] Mayo Clin, Rochester, MN USA. [Hirsch, Rosemarie] CDC, Hyattsville, MD USA. [Hochberg, Marc C.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Jordan, Joanne M.] Univ N Carolina, Chapel Hill, NC USA. [Katz, Jeffrey N.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wolfe, Frederick] Natl Data Bank Rheumat Dis, Wichita, KS USA. RP Helmick, CG (reprint author), CDC, Arthritis Program, 4770 Buford Highway,K51, Atlanta, GA 30341 USA. EM CHelmick@cdc.gov FU NIAMS NIH HHS [P60 AR047782, P60 AR047782-08] NR 65 TC 1564 Z9 1610 U1 20 U2 186 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JAN PY 2008 VL 58 IS 1 BP 26 EP 35 DI 10.1002/art.23176 PG 10 WC Rheumatology SC Rheumatology GA 256ML UT WOS:000252733100005 PM 18163497 ER PT J AU Gaffo, AL Saag, KG AF Gaffo, Angelo L. Saag, Kenneth G. TI Serum urate, menopause, and postmenopausal hormone use: from eminence to evidence-based medicine SO ARTHRITIS RESEARCH & THERAPY LA English DT Editorial Material ID URIC-ACID LEVELS; THERAPY; WOMEN; REPLACEMENT; PLASMA AB The relationship between serum urate, menopause, and aging has not been clearly defined by scientific evidence. In the present issue of Arthritis Research and Therapy, Hak and Choi present a cross-sectional analysis to clarify the effect of menopause and hormone replacement therapy on serum urate in women within the Third National Health and Nutritional Examination Survey. Menopause increased serum urate and hormone replacement therapy significantly decreased serum urate, although the overall level of change was small. The implications of these urate changes on gout and cardiovascular disease outcomes require further study. C1 [Saag, Kenneth G.] Univ Alabama, Div Clin Immunol & Rheumatol, FOT 820, Birmingham, AL 35294 USA. [Gaffo, Angelo L.] Birmingham VA Med Ctr, Birmingham, AL 35233 USA. RP Saag, KG (reprint author), Univ Alabama, Div Clin Immunol & Rheumatol, FOT 820, 1530 3rd Ave S, Birmingham, AL 35294 USA. EM ksaag@uab.edu NR 9 TC 2 Z9 2 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2008 VL 10 IS 5 AR 120 DI 10.1186/ar2524 PG 2 WC Rheumatology SC Rheumatology GA 411JA UT WOS:000263644500005 PM 18983690 ER PT J AU Pessler, F Mayer, CT Jung, SM Behrens, EM Dai, L Menetski, JP Schumacher, HR AF Pessler, Frank Mayer, Christian T. Jung, Sung Mun Behrens, Ed M. Dai, Lie Menetski, Joseph P. Schumacher, H. Ralph TI Identification of novel monosodium urate crystal regulated mRNAs by transcript profiling of dissected murine air pouch membranes SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID INDUCED ACUTE-INFLAMMATION; CUTTING EDGE; NICOTINIC-ACID; IN-VIVO; PUMA-G; RECEPTOR; MACROPHAGES; PROTEIN; GENE; CELLS AB Introduction The murine air pouch is a bursa-like space that resembles the human synovial membrane. Injection of monosodium urate (MSU) crystals into the pouch elicits an acute inflammatory response similar to human gout. We conducted the present study to identify mRNAs that were highly regulated by MSU crystals in the pouch membrane. Methods Air pouch membranes were meticulously dissected away from the overlying skin. Gene expression differences between MSU crystal stimulated and control membranes were determined by oligonucleotide microarray analysis 9 hours after injection of MSU crystals or buffer only. Differential regulation of selected targets was validated by relative quantitative PCR in time course experiments with dissected air pouch membranes and murine peritoneal macrophages. Results Eleven of the 12 most highly upregulated mRNAs were related to innate immunity and inflammation. They included mRNAs encoding histidine decarboxylase (the enzyme that synthesizes histamine), IL-6, the cell surface receptors PUMA-g and TREM-1, and the polypeptides Irg1 and PROK-2. IL-6 mRNA rose 108-fold 1 hour after crystal injection, coinciding with a surge in mRNAs encoding IL-1 beta, tumour necrosis factor alpha and the immediate early transcription factor Egr-1. The other mRNAs rose up to 200-fold within the subsequent 3 to 8 hours. MSU crystals induced these mRNAs in a dose-dependent manner in cultured macrophages, with similar kinetics but lower fold changes. Among the downregulated mRNAs, quantitative PCR confirmed significant decreases in mRNAs encoding TREM-2 (an inhibitor of macrophage activation) and granzyme D (a constituent of natural killer and cytotoxic T cells) within 50 hours after crystal injection. Conclusion This analysis identified several genes that were previously not implicated in MSU crystal inflammation. The marked rise of the upregulated mRNAs after the early surge in cytokine and Egr-1 mRNAs suggests that they may be part of a 'second wave' of factors that amplify or perpetuate inflammation. Transcript profiling of the isolated air pouch membrane promises to be a powerful tool for identifying genes that act at different stages of inflammation. C1 [Pessler, Frank; Behrens, Ed M.] Tech Univ Dresden, Klin & Poliklin Kinder & Jugendmed, Dresden, Germany. [Pessler, Frank] Childrens Hosp Philadelphia, Div Rheumatol, Philadelphia, PA 19104 USA. [Mayer, Christian T.] Tech Univ Munich, Inst Med Mikrobiol Immunol & Hyg, D-81675 Munich, Germany. [Mayer, Christian T.; Jung, Sung Mun; Dai, Lie; Schumacher, H. Ralph] Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA. [Jung, Sung Mun] Kyung Hee Univ, Coll Oriental Med, Dept Herbal Pharmacol, Fac Oriental Med, Seoul 130701, South Korea. [Dai, Lie] Sun Yat Sen Univ, Affiliated Hosp 2, Div Rheumatol, Guangzhou 510120, Guangdong, Peoples R China. [Menetski, Joseph P.] Merck Res Labs, Rahway, NJ 07065 USA. [Schumacher, H. Ralph] Vet Affairs Med Ctr, Div Rheumatol, Philadelphia, PA 19104 USA. RP Pessler, F (reprint author), Tech Univ Dresden, Klin & Poliklin Kinder & Jugendmed, Fetscherstr, Dresden, Germany. EM Frank.pessler@uniklinikum-dresden.de FU National Institutes of Health Training [T32-AR 007442, T32-CA 09140]; 2007-8 American College of Rheumatology Education and Research Foundation Amgen Pediatric Rheumatology Research; 2006 American College of Rheumatology Health Professional Graduate Student Preceptorship Award FX We thank G Clayburne, Nicole Chartrain and Marlin Camps- Ramirez for technical support; Grace Strazewski and Don Baldwin ( University of Pennsylvania Microarray Core) for microarray hybridization; and John Tobias ( University of Pennsylvania Bioinformatics Core) for help with analyzing the microarray data; Dan Martinez and the staff of the histopathology core of The Children's Hospital of Philadelphia for histology support; and Peri DeRitis and the staff of the VA Medical Center Animal Facility for expert animal care. F Pessler was supported by National Institutes of Health Training Grants T32- AR 007442 and T32- CA 09140 and a 2007- 8 American College of Rheumatology Education and Research Foundation Amgen Pediatric Rheumatology Research Award, and CT Mayer by a 2006 American College of Rheumatology Health Professional Graduate Student Preceptorship Award. NR 50 TC 13 Z9 13 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2008 VL 10 IS 3 AR R64 DI 10.1186/ar2435 PG 13 WC Rheumatology SC Rheumatology GA 354IP UT WOS:000259633000025 PM 18522745 ER PT J AU Ting, G Schneeweiss, S Scranton, R Katz, JN Weinblatt, ME Young, M Avorn, J Solomon, DH AF Ting, Gladys Schneeweiss, Sebastian Scranton, Richard Katz, Jeffrey N. Weinblatt, Michael E. Young, Melissa Avorn, Jerry Solomon, Daniel H. TI Development of a health care utilisation data-based index for rheumatoid arthritis severity: a preliminary study SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID ANTITUMOR NECROSIS FACTOR; RECORDS-BASED INDEX; THERAPY; CANCER; RISK; INFECTIONS; PREDICTORS; INFLIXIMAB; LYMPHOMA AB Introduction Health care utilisation ('claims') databases contain information about millions of patients and are an important source of information for a variety of study types. However, they typically do not contain information about disease severity. The goal of the present study was to develop a health care claims index for rheumatoid arthritis (RA) severity using a previously developed medical records-based index for RA severity (RA medical records-based index of severity [RARBIS]). Methods The study population consisted of 120 patients from the Veteran's Administration (VA) Health System. We previously demonstrated the construct validity of the RARBIS and established its convergent validity with the Disease Activity Score (DAS28). Potential claims-based indicators were entered into a linear regression model as independent variables and the RARBIS as the dependent variable. The claims-based index for RA severity (CIRAS) was created using the coefficients from models with the highest coefficient of determination (R(2)) values selected by automated modelling procedures. To compare our claims-based index with our medical records-based index, we examined the correlation between the CIRAS and the RARBIS using Spearman non-parametric tests. Results The forward selection models yielded the highest model R(2) for both the RARBIS with medications (R(2) = 0.31) and the RARBIS without medications (R(2) = 0.26). Components of the CIRAS included tests for inflammatory markers, number of chemistry panels and platelet counts ordered, rheumatoid factor, the number of rehabilitation and rheumatology visits, and Felty's syndrome diagnosis. The CIRAS demonstrated moderate correlations with the RARBIS with medication and the RARBIS without medication sub-scales. Conclusion We developed the CIRAS that showed moderate correlations with a previously validated records-based index of severity. The CIRAS may serve as a potentially important tool in adjusting for RA severity in pharmacoepidemiology studies of RA treatment and complications using health care utilisation data. C1 [Ting, Gladys; Schneeweiss, Sebastian; Avorn, Jerry; Solomon, Daniel H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pharmacoepidemiol,Dept Med, Boston, MA 02120 USA. [Scranton, Richard; Young, Melissa] Masschusetts Vet Epidemiol Res & Informat Ctr, VA Cooperat Studies Program, VA Boston Healthcare Syst, Jamaica Plain, MA 02130 USA. [Katz, Jeffrey N.; Weinblatt, Michael E.; Solomon, Daniel H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA 02115 USA. RP Solomon, DH (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pharmacoepidemiol,Dept Med, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. EM dsolomon@partners.org RI Schneeweiss, Sebastian/C-2125-2013 FU Engalitcheff Arthritis Outcomes Initiative; National Institute of Health [P60 AR47782, K24 AR055989, K24 AR02123]; VA Boston Healthcare System; VA Cooperative Studies Program FX This work was supported by the Engalitcheff Arthritis Outcomes Initiative. Dr. Solomon's work is also supported by National Institute of Health grants (P60 AR47782 and K24 AR055989). Dr Katz's work is supported by National Institute of Health grants (P60 AR47782 and K24 AR02123). This material is the result of work supported with resources and the use of facilities at the VA Boston Healthcare System and VA Cooperative Studies Program. NR 20 TC 22 Z9 22 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2008 VL 10 IS 4 AR R95 DI 10.1186/ar2482 PG 9 WC Rheumatology SC Rheumatology GA 356MB UT WOS:000259781200030 PM 18717997 ER PT J AU Chuckpalwong, B Berkson, EM Theodore, GH AF Chuckpalwong, Bavornrit Berkson, Eric M. Theodore, George H. TI Microfracture for osteochondral lesions of the ankle: Outcome analysis and outcome predictors of 105 cases SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article DE osteochondral defect; ankle arthroscopy; microfracture; ankle ID AUTOLOGOUS CHONDROCYTE TRANSPLANTATION; ARTHROSCOPIC TREATMENT; TREATMENT STRATEGIES; ARTICULAR-CARTILAGE; TALAR DOME; TALUS; DISSECANS; DEFECTS; KNEE; IMPLANTATION AB Purpose: The purpose of this study was to identify outcomes and outcome predictors of arthroscopic debridement with osteochondral bone stimulation (microfracture) for osteochondral lesions of the ankle. Methods: One hundred five consecutive patients with osteochondral lesions of the ankle who underwent ankle arthroscopy with microfracture were prospectively followed up for a mean of 31.6 +/- 12.1 months. Study patients were evaluated at 6 weeks 3 months, 6 months, 12 months, and annually after surgery. Assessments via a visual analog scale for pain during daily activities and sport activity, the Roles and Maudsley score, and the American Orthopaedic Foot & Ankle Society ankle and hindfoot scoring system were obtained at each visit. Outcome predictors were analyzed by logistic regression model. Results: There were no failures of treatment with lesions smaller than 15 m m. In contrast, only 1 patient met the criteria for success in the group of lesions greater than 15 mm. Statistical analysis revealed that increasing age, higher body mass index, history of trauma, and presence of osteophytes negatively affected outcome. The presence of instability and the presence of anterolateral soft-tissue scar were correlated with a successful outcome. Conclusions: This study found a strong correlation between lesion size and success across its entire population. For lesions smaller than 15 mm, regardless of location, excellent results were obtained. In addition, increasing age, higher body mass index, history of trauma, and presence of osteophytes negatively affect outcome. The presence of instability and anterolateral soft-tissue scar correlated with a successful outcome. Level of Evidence: Level IV, prognostic case series, prognostic study. C1 [Chuckpalwong, Bavornrit; Berkson, Eric M.; Theodore, George H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed, Boston, MA USA. RP Chuckpalwong, B (reprint author), Siriraj Hosp, Dept Orthopaed Surg, 2 Prannok St, Bangkok 10700, Thailand. EM chuck003@gmail.com NR 35 TC 110 Z9 119 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD JAN PY 2008 VL 24 IS 1 BP 106 EP 112 DI 10.1016/j.arthro.2007.07.022 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 254KX UT WOS:000252586600018 PM 18182210 ER PT S AU Ullner, E Vicente, R Pipa, G Garcia-Ojalvo, J AF Ullner, Ekkehard Vicente, Raul Pipa, Gordon Garcia-Ojalvo, Jordi BE Kurkova, V Neruda, R Koutnik, J TI yy Contour integration and synchronization in neuronal networks of the visual cortex SO ARTIFICIAL NEURAL NETWORKS - ICANN 2008, PT II SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 18th International Conference on Artificial Neural Networks (ICANN 2008) CY SEP 03-06, 2008 CL Prague, CZECH REPUBLIC ID COHERENCE RESONANCE; SYSTEMS AB The visual perception of contours by the brain is selective. When embedded within a noisy background, closed contours are detected faster, and with higher certainty, than open contours. We investigate this phenomenon theoretically with the paradigmatic excitable FitzHugh-Nagumo model, by considering a set of locally coupled oscillators subject to local uncorrelated noise. Noise is needed to overcome the excitation threshold and evoke spikes. We model one-dimensional structures and consider the synchronization throughout them as a mechanism for contour perception, for various system sizes and local noise intensities. The model with a closed ring structure shows a significantly higher synchronization than the one with the open structure. Interestingly, the effect is most pronounced for intermediate system sizes and noise intensities. C1 [Ullner, Ekkehard; Garcia-Ojalvo, Jordi] Univ Politecn Cataluna, Dept Fis & Engn Nucl, Colom 11, E-08222 Terrassa, Spain. [Vicente, Raul; Pipa, Gordon] Max Planck Inst Brain Res, D-60528 Frankfurt, Germany. [Vicente, Raul; Pipa, Gordon] Frankfurt Inst Adv Stud, D-60438 Frankfurt, Germany. [Pipa, Gordon] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Pipa, Gordon] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Cambridge, MA 02139 USA. RP Ullner, E (reprint author), Univ Politecn Cataluna, Dept Fis & Engn Nucl, Colom 11, E-08222 Terrassa, Spain. RI Garcia-Ojalvo, Jordi/A-4574-2009; Ullner, Ekkehard/C-9331-2011; Vicente, Raul/E-1566-2011 OI Garcia-Ojalvo, Jordi/0000-0002-3716-7520; Vicente, Raul/0000-0002-2497-0007 FU Alexander von Humboldt Foundation; Ministerio de Educacion y Ciencia (Spain) [FIS2006-11452]; GABA project (European Commission,FP6-NEST ) [043309] FX E.U. acknowledges financial support from the Alexander von Humboldt Foundation.This research was supported by the Ministerio de Educacion y Ciencia (Spain) under project FIS2006-11452 and by the GABA project (European Commission,FP6-NEST contract 043309). NR 19 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-540-87558-1 J9 LECT NOTES COMPUT SC PY 2008 VL 5164 BP 703 EP + PG 3 WC Computer Science, Theory & Methods SC Computer Science GA BIH71 UT WOS:000259567200073 ER PT J AU Ganmaa, D Tserendolgor, U Frazier, L Nakamoto, E Jargalsaikhan, N Rich-Edwards, J AF Ganmaa, Davaasambuu Tserendolgor, Uush Frazier, Lindsay Nakamoto, Erika Jargalsaikhan, Nyamjav Rich-Edwards, Janet TI Effects of vitamin D fortified milk on vitamin D status in Mongolian school age children SO ASIA PACIFIC JOURNAL OF CLINICAL NUTRITION LA English DT Article DE milk; vitamin D deficiency; growth; rickets; Mongolia ID MULTIPLE-SCLEROSIS; PROSTATE-CANCER; RICKETS; EXPOSURE; RISK AB Mongolians are at high risk for vitamin D deficiency because of their residence at northern latitude, reduced exposure to UV-B rays during the winter months, and a low availability of vitamin-D fortified foods. We performed a pilot study in May 2005 to estimate the prevalence of hypovitaminosis D in Mongolian school age children and to determine the feasibility of conducting a longer and larger trial with fortified milk and vitamin D supplements. In a group of 46 Mongolian children (22 girls and 24 boys) aged 9-11 years, 76% (35) had levels of 25-hydroxyvitamin D (25(OH)D) below 50nmol/L (20ng/mL) and 32% had levels below 37mnol/L (15ng/mL). After a month of consuming 710 ml of vitamin D-fortified (total 300IU or 7.5 mu g) milk daily, only 3 of the children were below 50nmol/L (20ng/mL) and none below 37nmol/L (15ng/mL). These results reveal prevalent and serious 25(OH)D deficiency among Mongolian prepubertal school age children that appears to be ameliorated by a month of consuming approximately 7.5 mu g of vitamin D3 in fortified milk. C1 [Ganmaa, Davaasambuu] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Frazier, Lindsay] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Cambridge, MA 02138 USA. [Nakamoto, Erika; Rich-Edwards, Janet] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Cambridge, MA 02138 USA. [Rich-Edwards, Janet] Harvard Univ, Sch Med, Dept Epidemiol, Cambridge, MA 02138 USA. RP Ganmaa, D (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM gdavaasa@hsph.harvard.edu FU NCRR NIH HHS [M01-RR02172] NR 20 TC 7 Z9 7 U1 0 U2 1 PU H E C PRESS, HEALTHY EATING CLUB PTY LTD PI SOUTHBANK PA EMERALD HILL CLINIC 157 CLARENDON ST, SOUTHBANK, VIC 3006, AUSTRALIA SN 0964-7058 J9 ASIA PAC J CLIN NUTR JI Asia Pac. J. Clin. Nutr. PY 2008 VL 17 IS 1 BP 68 EP 71 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 286XT UT WOS:000254880400012 PM 18364329 ER PT S AU Maddox, TM Nash, IS Fuster, V AF Maddox, Thomas M. Nash, Ira S. Fuster, Valentin BE Natale, A Jalife, J TI Economic Costs Associated with Atrial Fibrillation SO ATRIAL FIBRILLATION: FROM BENCH TO BEDSIDE SE Contemporary Cardiology LA English DT Article; Book Chapter DE AF hospitalizations; AF cost; Incidence of AF; Prevalence of AF; Stroke ID CORONARY-ARTERY-BYPASS; QUALITY-OF-LIFE; SINUS RHYTHM; RISK-FACTORS; RESOURCE UTILIZATION; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; SPONTANEOUS CONVERSION; ORAL ANTICOAGULATION; RANDOMIZED-TRIAL; STROKE SEVERITY AB As the population ages, the incidence and prevalence of atrial fibrillation (AF) is expected to increase, resulting in significant societal and economic impact. By 2050, AF is projected to affect 15.9 million individuals in the United States. Atrial fibrillation results in a variety of adverse outcomes, including a fivefold increased risk of stroke, impaired quality of life, decreased work productivity, and increased rates of hospitalization. In 2005, there were 470,000 U.S. hospitalizations secondary to AF. In 2004, over 9 million working days were lost because of AF. Costs of AF and its associated complications are enormous. In 2006, costs attributable to AF-associated stroke equaled $12 billion. In addition, $41,000 to $105,000 per patient was spent on aggregate and individual AF care. Because of its increasing prevalence, numerous complications, and large costs, AF presents a significant challenge for patients, clinicians, and health care policymakers. Finding strategies to best care for these patients will become increasingly important. C1 [Maddox, Thomas M.] Univ Colorado, Denver VAMC, Denver, CO 80202 USA. [Maddox, Thomas M.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Nash, Ira S.] Mt Sinai Sch Med, James J Peters VAMC, New York, NY USA. RP Maddox, TM (reprint author), Univ Colorado, Denver VAMC, Denver, CO 80202 USA. NR 82 TC 2 Z9 2 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1191-7601 BN 978-1-59745-163-5; 978-1-58829-856-0 J9 CONTEMP CARDIOL JI Contemp. Cardiol. PY 2008 BP 13 EP 26 DI 10.1007/978-1-59745-163-5_2 D2 10.1007/978-1-59745-163-5 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BLV22 UT WOS:000271134100002 ER PT S AU Saliba, W Ernst, S Reddy, V Kuck, KH AF Saliba, Walid Ernst, Sabine Reddy, Vivek Kuck, Karl-Heinz BE Natale, A Jalife, J TI Remote Catheter Navigation SO ATRIAL FIBRILLATION: FROM BENCH TO BEDSIDE SE Contemporary Cardiology LA English DT Article; Book Chapter DE AF catheter ablation; Remote magnetic navigation; Remote robotic navigation; 3-D mapping systems ID MAGNETIC NAVIGATION; ACCESSORY PATHWAYS; ABLATION; SYSTEM; TACHYCARDIA; SAFETY AB Percutaneous catheter ablation has emerged as a promising curative modality for the treatment of atrial fibrillation (AF). However, the safety and success of this procedure are operator dependent and require precise catheter manipulation and stable contact during ablation. Remote catheter navigation has the potential to remove some of the barriers traditionally associated with percutaneous catheter ablation, such as the need for manual dexterity and long radiation exposure times, thus enabling more physicians to perform these procedures. Initial experience with the remote magnetic navigation system (MNS) shows the safety and feasibility of mapping and ablation of various arrhythmias, including successful ablation of AV Nodal Re-entrant Tachycardia (AVNRT), atrial flutter, and fibrillation as well as ventricular tachycardia. An initial learning curve is suggested, with eventual benefits including decrease in fluoroscopy and ablation time, mainly related to those hard to reach areas. Remote robotic navigation has been assessed predominantly for atrial ablation. In a preclinical animal study, target sites were accurately attained, and radio-frequency (RF) ablation was performed with no complications in both atria. In human trials, remote robotic navigation was shown to be safe and effective for mapping and ablation of atrial fibrillation and flutter as well as atrioventricular (AV) nodal reentrant tachy-cardias. These preliminary results regarding remote catheter navigation appear promising. Their added advantage over the current conventional approach in terms of improving the success rate while minimizing risk for both the patient and the operator remain to be proven in large-scale clinical trials. C1 [Saliba, Walid] Cleveland Clin Fdn, Dept Cardiovasc Med, Sect Cardiac Pacing & Electrophysiol, Electrophysiol Labs, Cleveland, OH 44195 USA. [Reddy, Vivek] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ernst, Sabine; Kuck, Karl-Heinz] Asklepios Klin St Georg, Dept Cardiol, Hamburg, Germany. RP Saliba, W (reprint author), Cleveland Clin Fdn, Dept Cardiovasc Med, Sect Cardiac Pacing & Electrophysiol, Electrophysiol Labs, 9500 Euclid Ave, Cleveland, OH 44195 USA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1191-7601 BN 978-1-59745-163-5 J9 CONTEMP CARDIOL JI Contemp. Cardiol. PY 2008 BP 385 EP 396 DI 10.1007/978-1-59745-163-5_28 D2 10.1007/978-1-59745-163-5 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BLV22 UT WOS:000271134100028 ER PT J AU Dumas, S Troughton, JS Cloutier, NJ Chasse, JM McMurry, TJ Caravan, P AF Dumas, Stephane Troughton, Jeffrey S. Cloutier, Normand J. Chasse, Jaclyn M. McMurry, Thomas J. Caravan, Peter TI A high relaxivity magnetic resonance imaging contrast agent targeted to serum albumin SO AUSTRALIAN JOURNAL OF CHEMISTRY LA English DT Article ID NEPHROGENIC SYSTEMIC FIBROSIS; DRUG BINDING-SITES; WATER EXCHANGE; MR-ANGIOGRAPHY; GADOLINIUM COMPLEXES; PROTEIN-BINDING; MS-325; STABILITY; DYNAMICS AB EP-647 is a serumalbumin-targeted magnetic resonance imaging contrast agent comprising a GdDTPA( DTPA, diethylenetriaminepentaacetate) chelate for magnetic resonance signal generation linked via a phosphodiester to a substituted biphenyl for albumin targeting. Albumin binding and relaxivity are higher than the benchmark magnetic resonance angiographic agent MS-325. EP-647 binds primarily to a unique site on serum albumin that is different from the MS-325 site and the binding sites of other drugs. C1 [Caravan, Peter] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Caravan, Peter] Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Dumas, Stephane; Troughton, Jeffrey S.; Cloutier, Normand J.; Chasse, Jaclyn M.; McMurry, Thomas J.] EPIX Pharmaceut Inc, Lexington, MA 02421 USA. RP Caravan, P (reprint author), Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, 149 13 St,Suite 2301, Charlestown, MA 02129 USA. EM caravan@nmr.mgh.harvard.edu NR 32 TC 9 Z9 9 U1 0 U2 5 PU CSIRO PUBLISHING PI COLLINGWOOD PA 150 OXFORD ST, PO BOX 1139, COLLINGWOOD, VICTORIA 3066, AUSTRALIA SN 0004-9425 J9 AUST J CHEM JI Aust. J. Chem. PY 2008 VL 61 IS 9 BP 682 EP 686 DI 10.1071/CH08164 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 344KP UT WOS:000258926100006 ER PT S AU Herbert, MR Anderson, MP AF Herbert, Martha R. Anderson, Matthew P. BE Zimmerman, AW TI An Expanding Spectrum of Autism Models From Fixed Developmental Defects to Reversible Functional Impairments SO AUTISM: CURRENT THEORIES AND EVIDENCE SE Current Clinical Neurology LA English DT Article; Book Chapter DE Autism; models; pathogenesis; function; brain; plasticity; epigenetics; environment ID COMMON DIETARY PROTEINS; OXIDATIVE STRESS; RETT-SYNDROME; NITRIC-OXIDE; GLIAL-CELLS; IN-VITRO; GASTROINTESTINAL SYMPTOMS; SYNAPTIC PLASTICITY; CYTOKINE PRODUCTION; AUTOIMMUNE-DISEASE AB In this review, we contrast previous models of autism pathogenesis with newer models inspired by some recently appreciated and previously minimally considered pathological and clinical features of the disease. Autism has conventionally been viewed as an incurable behavioral disorder resulting solely from genetic defects impacting brain development. However, emerging evidence suggests that autism affects many organ systems beyond the brain and that some neuropathological and somatic pathophysiological processes are active even Into adulthood. We incorporate these newer observations into a model of how this systemic and persistent disease process might impact brain function and ultimately impair behavior through potentially reversible mechanisms. In particular, observations of substantial transient and sometimes enduring increases in function and even losses of the diagnosis challenge researchers to identify pathophysiological mechanisms consistent with this dynamic course and potential plasticity. This broadened appreciation of the disease phenomenology and prognosis of autism calls for mechanistic models that encompass the full range of its features. To this end, our review contrasts several models of autism pathophysiology and lays out their differing underlying assumptions regarding mechanisms. First, we compare models of autism that are based on different underlying biological and experimental perspectives to addressing the question of autism pathogenesis. We contrast a "bottom-up, modular, genes-brain-behavior" model with a more inclusive "middle-out, multi-system biology" model. We then contrast different models that consider autism's development over time. Beginning with a purely genetic prenatal brain development model, we expand the framework to include early environmental influences, epigenetics, later and ongoing environmental influences, and features consistent with chronic encephalopathy. The implications of these models, particularly the last, are spelled out through a discussion of the functional consequences of one prominent chronic feature, persistent immune activation, and its impact on neural-glial interactions. The implications of these newer models on potential treatments are also discussed. C1 [Herbert, Martha R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Morphometr Anal,Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Herbert, Martha R.] Harvard Univ, Sch Med, Dept Neurol, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Anderson, Matthew P.] Harvard Univ, Sch Med, Dept Neurol, Harvard Inst Med, Charlestown, MA 02129 USA. [Anderson, Matthew P.] Harvard Univ, Sch Med, Dept Pathol, Harvard Inst Med, Charlestown, MA 02129 USA. RP Herbert, MR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Morphometr Anal,Martinos Ctr Biomed Imaging, 149,13th St,Room 10018, Charlestown, MA 02129 USA. EM mherbert1@partners.org NR 121 TC 5 Z9 5 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1559-0585 BN 978-1-60327-488-3 J9 CURR CLIN NEUROL JI Cur. Clin. Neurol. PY 2008 BP 429 EP 463 DI 10.1007/978-1-60327-489-0_20 D2 10.1007/978-1-60327-489-0 PG 35 WC Clinical Neurology SC Neurosciences & Neurology GA BKA00 UT WOS:000267560100021 ER PT J AU Sawalha, AH AF Sawalha, Amr H. TI Epigenetics and T-cell immunity SO AUTOIMMUNITY LA English DT Article DE epigenetics; gene regulation; T-cell immunity; T-cell function; DNA methylation ID LOCUS-CONTROL REGION; RANGE INTRACHROMOSOMAL INTERACTIONS; CYTOKINE GENE-EXPRESSION; IFN-GAMMA PRODUCTION; DNA METHYLATION; TRANSCRIPTION FACTOR; HISTONE ACETYLATION; LINEAGE COMMITMENT; MAMMALIAN DEVELOPMENT; X-INACTIVATION AB Epigenetic mechanisms including DNA methylation and histone modifications are critically involved in immune responses. Antigen stimulation along with a specific cytokine milieu drives helper T-cell differentiation into specific subsets with distinct functional capacities. This process occurs by inducing chromatin remodeling and altering transcriptional accessibility of key cytokine genes such as IFN-, IL-4 and IL-17. These epigenetic changes, by definition, are carried over throughout cell division to ensure selective survival of a cell lineage. Over the past decade, a growing body of literature mechanistically uncovered the central role for epigenetic regulation in immunity. In this review, we focus on epigenetics in T helper cell differentiation, regulatory T-cell function, and IL-2 production. C1 [Sawalha, Amr H.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Sawalha, Amr H.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Sawalha, Amr H.] Oklahoma Med Res Fdn, Arthritis & Immunol Program, Oklahoma City, OK 73104 USA. RP Sawalha, AH (reprint author), 825 NE 13th St,MS 24, Oklahoma City, OK 73104 USA. EM amr-sawalha@omrf.ouhsc.edu FU NCRR NIH HHS [P20-RR015577]; NIAMS NIH HHS [P30 AR053483] NR 71 TC 43 Z9 47 U1 1 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0891-6934 J9 AUTOIMMUNITY JI Autoimmunity PY 2008 VL 41 IS 4 BP 245 EP 252 DI 10.1080/08916930802024145 PG 8 WC Immunology SC Immunology GA 292NV UT WOS:000255274300002 PM 18432405 ER PT J AU Chen, GC Lee, JY Tang, HW Debnath, J Thomas, SM Settleman, J AF Chen, Guang-Chao Lee, Janice Y. Tang, Hong-Wen Debnath, Jayanta Thomas, Sheila M. Settleman, Jeffrey TI Genetic interactions between Drosophila melanogaster Atg1and paxillin reveal a role for paxillin in autophagosome formation SO AUTOPHAGY LA English DT Article DE autophagy; paxillin; Drosophila melanogaster; Atg1; autophagosome; genetics ID FOCAL ADHESION KINASE; PROGRAMMED CELL-DEATH; C-ELEGANS; SACCHAROMYCES-CEREVISIAE; MOLECULAR-MECHANISMS; AXON OUTGROWTH; FAT-BODY; BINDING; COMPARTMENT; INDUCTION AB Autophagy is a conserved cellular process of macromolecule recycling that involves vesicle-mediated degradation of cytoplasmic components. Autophagy plays essential roles in normal cell homeostasis and development, the response to stresses such as nutrient starvation, and contributes to disease processes including cancer and neurodegeneration. Although many of the autophagy components identified from genetic screens in yeast are well conserved in higher organisms, the mechanisms by which this process is regulated in any species are just beginning to be elucidated. In a genetic screen in Drosophila melanogaster, we have identified a link between the focal adhesion protein paxillin and the Atg1 kinase, which has been previously implicated in autophagy. In mammalian cells, we find that paxillin is redistributed from focal adhesions during nutrient deprivation, and paxillin-deficient cells exhibit defects in autophagosome formation. Together, these findings reveal a novel evolutionarily conserved role for paxillin in autophagy. C1 [Settleman, Jeffrey] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [Settleman, Jeffrey] Harvard Univ, Sch Med, Charlestown, MA USA. [Chen, Guang-Chao] Acad Sinica, Inst Biol Chem, Taipei, Taiwan. [Chen, Guang-Chao; Tang, Hong-Wen] Natl Taiwan Univ, Inst Biochem Sci, Taipei, Taiwan. [Lee, Janice Y.; Debnath, Jayanta; Thomas, Sheila M.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149,13th St, Charlestown, MA USA. EM settleman@helix.mgh.harvard.edu FU NCI NIH HHS [R01CA62142] NR 40 TC 29 Z9 29 U1 1 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD JAN 1 PY 2008 VL 4 IS 1 BP 37 EP 45 PG 9 WC Cell Biology SC Cell Biology GA 249FB UT WOS:000252211800005 PM 17952025 ER PT J AU Tuxworth, WJ Shiraishi, H Moschella, PC Yamane, K McDermott, PJ Kuppuswamy, D AF Tuxworth, William J., Jr. Shiraishi, Hirokazu Moschella, Phillip C. Yamane, Kentaro McDermott, Paul J. Kuppuswamy, Dhandapani TI Translational activation of 5'-TOP mRNA in pressure overload myocardium SO BASIC RESEARCH IN CARDIOLOGY LA English DT Article DE cardiac hypertrophy; signal transduction; 5'-TOP mRNA; ribosome; mTOR ID KINASE SIGNALING PATHWAY; CARDIAC-MUSCLE-CELLS; S6 KINASE; PROTEIN-SYNTHESIS; GENE-EXPRESSION; AMINO-ACIDS; COMPLEX-FORMATION; MAMMALIAN-CELLS; RAT-LIVER; HYPERTROPHY AB The present study was conducted to determine the magnitude and duration of ribosomal protein translation in response to pressure overload and determine if additional, paracrine events associated with mechanical transduction, such as integrin activation using a bioactive peptide ligand, RGD or endothelin stimulation lead to ribosomal protein translation. Polysome analysis of ventricular tissue samples obtained from an in vivo model of right-ventricular pressure overload (RVPO) showed a significant shift in the proportion of a 5'-terminal oligopyrimidine (5'-TOP) mRNA, rpL32, associated with the polysomal fraction when compared with non-5'-TOP mRNAs, beta-actin and beta-myosin heavy chain ( -MHQ, in the early stages of the hypertrophic response (2448 h). Furthermore, this increase in polysome-bound rpL32 mRNA was accompanied by the phosphorylation of mammalian target of rapamycin (mTOR), p70 S6 kinase (S6K1), and S6 ribosomal protein. In our in vitro studies, treatment of primary cultures of adult feline cardiomyocytes (cardiocytes) with 100 nM endothelin, 9 mM RGD, 100 nM insulin, or 100 nM TPA activated mTOR via distinct signaling pathways and resulted in an increased proportion of polysome-bound rpL32 mRNA. Pre-treatment of cardiocytes with the mTOR inhibitor rapamycin blocked the agonist-induced rpL32 mRNA mobilization to polysomes. These results show that mechanisms that regulate ribosomal biogenesis in the myocardium are dynamically sensitive to pressure overload. Furthermore, our in vitro studies indicate that distinct pathways are operational during the early course of hypertrophic growth and converge to activate mTOR resulting in the translational activation of 5'-TOP mRNA. C1 [Kuppuswamy, Dhandapani] Gazes Cardiac Res Inst, Storm Thurmond Biomed Res, Charleston, SC 29403 USA. [Tuxworth, William J., Jr.; Shiraishi, Hirokazu; Moschella, Phillip C.; Yamane, Kentaro; McDermott, Paul J.; Kuppuswamy, Dhandapani] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Tuxworth, William J., Jr.; Shiraishi, Hirokazu; Moschella, Phillip C.; Yamane, Kentaro; McDermott, Paul J.; Kuppuswamy, Dhandapani] Med Univ S Carolina, Gazes Cardiac Res Inst, Charleston, SC 29425 USA. [McDermott, Paul J.; Kuppuswamy, Dhandapani] Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. RP Kuppuswamy, D (reprint author), Gazes Cardiac Res Inst, Storm Thurmond Biomed Res, Bldg,Room 213,114 Doughty St, Charleston, SC 29403 USA. EM kuppusd@musc.edu FU NHLBI NIH HHS [HL-07260, HL-48788] NR 46 TC 12 Z9 13 U1 1 U2 2 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0300-8428 J9 BASIC RES CARDIOL JI Basic Res. Cardiol. PD JAN PY 2008 VL 103 IS 1 BP 41 EP 53 DI 10.1007/s00395-007-0682-z PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 242HX UT WOS:000251717300005 PM 17955327 ER PT J AU van den Berg, L Vos-Loohuis, M Schilder, MBH van Oost, BA Hazewinkel, HAW Wade, CM Karlsson, EK Lindblad-Toh, K Liinamo, AE Leegwater, PAJ AF van den Berg, L. Vos-Loohuis, M. Schilder, M. B. H. van Oost, B. A. Hazewinkel, H. A. W. Wade, C. M. Karlsson, E. K. Lindblad-Toh, K. Liinamo, A. E. Leegwater, P. A. J. TI Evaluation of the serotonergic genes htr1A, htr1B, htr2A, and slc6A4 in aggressive behavior of Golden Retriever dogs SO BEHAVIOR GENETICS LA English DT Article DE dog; aggression; serotonin; candidate gene; linkage; association ID T102C POLYMORPHISM; DOMINANCE AGGRESSION; 5-HT1B RECEPTOR; KNOCKOUT MICE; TRANSPORTER; ASSOCIATION; SEQUENCE; ANXIETY; TRAITS; BRAIN AB Aggressive behavior displays a high heritability in our study group of Golden Retriever dogs. Alterations in brain serotonin metabolism have been described in aggressive dogs before. Here, we evaluate whether four genes of the canine serotonergic system, coding for the serotonin receptors 1A, 1B, and 2A, and the serotonin transporter, could play a major role in aggression in Golden Retrievers. We performed mutation screens, linkage analysis, an association study, and a quantitative genetic analysis. There was no systematic difference between the coding DNA sequence of the candidate genes in aggressive and non-aggressive Golden Retrievers. An affecteds-only parametric linkage analysis revealed no strong major locus effect on human-directed aggression related to the candidate genes. An analysis of 41 single nucleotide polymorphisms (SNPs) in the 1 Mb regions flanking the genes in 49 unrelated human-directed aggressive and 49 unrelated non-aggressive dogs did not show association of SNP alleles, genotypes, or haplotypes with aggression at the candidate loci. We completed our analyses with a study of the effect of variation in the candidate genes on a collection of aggression-related phenotypic measures. The effects of the candidate gene haplotypes were estimated using the Restricted Maximum Likelihood method, with the haplotypes included as fixed effects in a linear animal model. We observed no effect of the candidate gene haplotypes on a range of aggression-related phenotypes, thus extending our conclusions to several types of aggressive behavior. We conclude that it is unlikely that these genes play a major role in the variation in aggression in the Golden Retrievers that we studied. Smaller phenotypic effects of these loci could not be ruled out with our sample size. C1 [van den Berg, L.] Vrije Univ Amsterdam, Med Ctr, Sect Med Gen, Dept Clin Genet, NL-1081 BT Amsterdam, Netherlands. [van den Berg, L.; Vos-Loohuis, M.; Hazewinkel, H. A. W.; Leegwater, P. A. J.] Univ Utrecht, Fac Vet Med, Dept Clin Sci Compan Anim, Utrecht, Netherlands. [Schilder, M. B. H.] Univ Utrecht, Fac Vet Med, Dept Anim Sci & Society, Utrecht, Netherlands. [van Oost, B. A.] Amer Univ Caribbean, St Maarten, NA, Netherlands. [Wade, C. M.; Karlsson, E. K.; Lindblad-Toh, K.] MIT, Cambridge, MA 02139 USA. [Wade, C. M.; Karlsson, E. K.; Lindblad-Toh, K.] Broad Inst Harvard, Cambridge, MA USA. [Wade, C. M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA USA. [Liinamo, A. E.] Univ Helsinki, Dept Anim Sci, Helsinki, Finland. RP van den Berg, L (reprint author), Vrije Univ Amsterdam, Med Ctr, Sect Med Gen, Dept Clin Genet, Boechorststr 7, NL-1081 BT Amsterdam, Netherlands. EM L.vandenBerg@vumc.nl OI Karlsson, Elinor/0000-0002-4343-3776 NR 50 TC 24 Z9 25 U1 7 U2 39 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD JAN PY 2008 VL 38 IS 1 BP 55 EP 66 DI 10.1007/s10519-007-9179-7 PG 12 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 254CE UT WOS:000252563200006 PM 18066658 ER PT J AU Teten, AL Miller, LA Bailey, SD Dunn, NJ Kent, TA AF Teten, Andra L. Miller, Lisa A. Bailey, Sara D. Dunn, Nancy Jo Kent, Thomas A. TI Empathic Deficits and Alexithymia in Trauma-Related Impulsive Aggression SO BEHAVIORAL SCIENCES & THE LAW LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; PSYCHOMETRIC PROPERTIES; ANTISOCIAL-BEHAVIOR; PTSD CHECKLIST; SCALE; DISTURBANCES; ADOLESCENTS; PERSONALITY; RELIABILITY; POPULATION AB Our long term interest is to develop a developmental model of impulsive aggression based on a confluence of social psychological and biological features. This approach incorporates neurobiological research, which has identified language processing deficits as a unique characteristic of impulsive aggressors and extends it to include emotional deficits. As an initial test of this hypothesis, we examined whether empathy and alexithymia were associated with impulsive aggression. Regressions were performed to explore the associations among impaired empathy, alexithymia, impulsive aggression, verbal and physical general aggression. Among impulsive aggressive veterans (n = 38) recruited from a VA trauma clinic, alexithymia predicted impulsive aggression and empathic deficits predicted verbal aggression. Neither emotional awareness deficit predicted general physical aggression in this middle-aged sample. Results suggested that empathic deficits were associated with general verbal aggression, but alexithymia was uniquely associated with impulsive aggression. Consideration of alexithymia in impulsive aggression has implications for its etiology, prevention and treatment. Published in 2008 by John Wiley & Sons, Ltd. C1 [Teten, Andra L.; Miller, Lisa A.; Bailey, Sara D.; Dunn, Nancy Jo; Kent, Thomas A.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Teten, Andra L.; Miller, Lisa A.; Bailey, Sara D.; Dunn, Nancy Jo] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Kent, Thomas A.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. RP Teten, AL (reprint author), Ctr Dis Control & Prevent, Div Violence Prevent, Natl Ctr Injury Prevent & Control, 4770 Buford Hwy NE,MS F-63, Atlanta, GA 30341 USA. EM ateten@cdc.gov OI Kent, Thomas/0000-0002-9877-7584 NR 41 TC 28 Z9 28 U1 2 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0735-3936 J9 BEHAV SCI LAW JI Behav. Sci. Law PY 2008 VL 26 IS 6 BP 823 EP 832 DI 10.1002/bsl.843 PG 10 WC Psychology, Applied; Law SC Psychology; Government & Law GA 392AC UT WOS:000262274300010 PM 19039794 ER PT J AU Barnes, KR Blois, J Smith, A Yuan, H Reynolds, F Weissleder, R Cantley, LC Josephson, L AF Barnes, Katie R. Blois, Joseph Smith, Adam Yuan, Hushan Reynolds, Fred Weissleder, Ralph Cantley, Lewis C. Josephson, Lee TI Fate of a bioactive fluorescent wortmannin derivative in cells SO BIOCONJUGATE CHEMISTRY LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE INHIBITOR; SELECTIVE INHIBITOR; ANTITUMOR-ACTIVITY; GLUCOSE-TRANSPORT; IN-VITRO; KINASE; POTENT; PROTEIN; GROWTH; CANCER AB Here, we report on NBD-Wm, a fluorescent wortmannin (Wm) probe that maintains the bioactivity of Wm as an inhibitor of PI3 kinase and as an antiproliferative agent. The attachment of the NBD fluorochrome permits NBD-Wm in cells to be monitored by NBD fluorescence-based methods such as FACS or fluorescence microscopy or with an anti-NBD antibody. The fluorescence of NBD-Wm treated cells reached a peak at 1.5 h and then decreased because of the extrusion of a fluorescent compound into the culture media. Cells accumulated N-BD-Wm to levels about 30-fold higher than those in the media. NBD-Wm modified five major proteins, with the modification of the catalytic subunit of PI3 kinase being a minor band. The bioactivity of NBD-Wm, coupled with a variety of techniques available for determining its disposition, suggest that NBD-Wm can be a useful tool in understanding the mechanism of action of viridins. C1 [Barnes, Katie R.; Blois, Joseph; Smith, Adam; Yuan, Hushan; Reynolds, Fred; Weissleder, Ralph; Josephson, Lee] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [Barnes, Katie R.; Blois, Joseph; Smith, Adam; Yuan, Hushan; Reynolds, Fred; Weissleder, Ralph; Josephson, Lee] Harvard Univ, Sch Med, Dept Syst Biol, Charlestown, MA 02129 USA. [Cantley, Lewis C.] 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; Wang, Gaoqian/K-8528-2015 OI Cantley, Lewis/0000-0002-1298-7653; FU NCI NIH HHS [2P50CA86355]; NIBIB NIH HHS [R01 EB004472, R01EB00662]; NIGMS NIH HHS [R01 GM041890] NR 37 TC 12 Z9 12 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JAN PY 2008 VL 19 IS 1 BP 130 EP 137 DI 10.1021/bc7002204 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 253LS UT WOS:000252520300018 PM 17988080 ER PT J AU Morris, DW Murphy, K Kenny, N Purcell, SM McGhee, KA Schwaiger, S Nangle, JM Donohoe, G Clarke, S Scully, P Quinn, J Meagher, D Baldwin, P Crurnlish, N O'Callaghan, E Waddington, JL Gill, M Corvin, AP AF Morris, Derek W. Murphy, Kevin Kenny, Niarnh Purcell, Shaun M. McGhee, Kevin A. Schwaiger, Siobhan Nangle, Jeanne-Marie Donohoe, Gary Clarke, Sarah Scully, Paul Quinn, John Meagher, David Baldwin, Patrizia Crurnlish, Niall O'Callaghan, Eadbhard Waddington, John L. Gill, Michael Corvin, Aiden P. TI Dysbindin (DTNBP1) and the biogenesis of lysosome-related organelles complex 1 (BLOC-1): Main and epistatic gene effects are potential contributors to schizophrenia susceptibility SO BIOLOGICAL PSYCHIATRY LA English DT Article DE BLOC-1; dysbindin; epistasis; gene; muted; schizophrenia ID MULTIFACTOR-DIMENSIONALITY REDUCTION; RISK HAPLOTYPE; 6P22.3 GENE; ASSOCIATION; PROTEIN; IDENTIFICATION; FAMILIES; PALLIDIN; SNAPIN; LOCUS AB Background: The DTNBP1 gene, encoding dysbindin, has been strongly implicated in schizophrenia (SZ) susceptibility by a series of independent genetic association and gene expression studies. Among its known functions, dysbindin is part of a protein complex, termed the biogenesis of lysosome-related organelles complex 1 (BLOC-1), the molecular components of which might be involved in the regulation of vesicular trafficking and dendrite branching. Methods: A systematic investigation of the other seven BLOC-1 genes (MUTED, PLDN, CNO, SNAPAP, BLOC1S1, BLOC1S2, and BLOC1S3) for evidence of association with SZ was undertaken in a sample of 373 SZ cases and 812 control subjects. Possible epistasis between combinations of BLOC-1 genes, including DTNBP1, was tested with a novel method of investigating for gene-gene interaction. Quality control measures were incorporated into genotyping strategy, and all results were corrected for multiple testing to prevent false positive results. Results: We identified significant evidence of association between BLOC1S3 and SZ (odds ratio = 1.45, confidence interval = 1.13-1.86,p =.0028, corrected p =.0389). We also report evidence for epistatic interaction between DTNBP1 and MUTED contributing to SZ in the absence of a significant main effect at MUTED (p =.0009, corrected p =.0252). Single marker and epistasis results remained significant after correction for multiple testing. Conclusions: Together these data provide evidence for the involvement of the BLOC-1 protein complex in SZ pathogenesis. C1 [Morris, Derek W.; Corvin, Aiden P.] St James Hosp, Inst Mol Med, Neuropsychiat Genet Grp, Dublin 8, Ireland. [Morris, Derek W.; Murphy, Kevin; Kenny, Niarnh; McGhee, Kevin A.; Schwaiger, Siobhan; Nangle, Jeanne-Marie; Donohoe, Gary; Clarke, Sarah; Gill, Michael; Corvin, Aiden P.] Trinity Coll Dublin, Dept Psychiat, Neuropsychiat Genet Grp, Dublin, Ireland. [Morris, Derek W.; Murphy, Kevin; Kenny, Niarnh; McGhee, Kevin A.; Schwaiger, Siobhan; Nangle, Jeanne-Marie; Donohoe, Gary; Clarke, Sarah; Gill, Michael; Corvin, Aiden P.] Trinity Coll Dublin, Inst Mol Med, Dublin, Ireland. [Crurnlish, Niall; O'Callaghan, Eadbhard] Cluain Mhuire Family Ctr, Stanley Res Unit, Dublin, Ireland. [Waddington, John L.] Royal Coll Surgeons Ireland, Dept Clin Pharmacol, Dublin 2, Ireland. [Scully, Paul; Quinn, John; Meagher, David; Baldwin, Patrizia; Waddington, John L.] St Davnets Hosp, Stanley Res Unit, Monaghan, Ireland. [Purcell, Shaun M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA USA. RP Morris, DW (reprint author), St James Hosp, Inst Mol Med, Neuropsychiat Genet Grp, Room 1-10, Dublin 8, Ireland. EM morrisdw@tcd.ie; acorvin@tcd.ie OI Corvin, Aiden/0000-0001-6717-4089; Morris, Derek/0000-0002-3413-570X; Gill, Michael/0000-0003-0206-5337; Donohoe, Gary/0000-0003-3037-7426 FU Wellcome Trust NR 49 TC 40 Z9 42 U1 0 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 JAN 1 PY 2008 VL 63 IS 1 BP 24 EP 31 DI 10.1016/j.biopsych.2006.12.025 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 244KE UT WOS:000251864000006 PM 17618940 ER PT J AU Roffman, JL Weiss, AP Purcell, S Caffalette, CA Freudenreich, O Henderson, DC Bottiglieri, T Wong, DH Halsted, CH Goff, DC AF Roffman, Joshua L. Weiss, Anthony P. Purcell, Shaun Caffalette, Christopher A. Freudenreich, Oliver Henderson, David C. Bottiglieri, Teocloro Wong, Donna H. Halsted, Charles H. Goff, Donald C. TI Contribution of methylenetetrahydrofolate reductase (MTHFR) polymorphisms to negative symptoms in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat DE folate; genetics; homocysteine; MTHFR; negative symptoms; schizophrenia ID PLASMA HOMOCYSTEINE CONCENTRATIONS; FOOD FREQUENCY QUESTIONNAIRE; VAL(108/158) MET GENOTYPE; FOLATE-METABOLIZING GENES; COMMON MUTATION; RISK-FACTOR; C677T POLYMORPHISM; DNA METHYLATION; ASSOCIATION; HYPERHOMOCYSTEINEMIA AB Background: Folate deficiency may contribute to negative symptoms in schizophrenia, but the underlying mechanism remains uncertain. We examined whether the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C functional polymorphisms contribute to negative symptoms. Methods: Outpatients with schizophrenia (n = 200) were evaluated with the Positive and Negative Syndrome Scale (PANSS). Subjects also provided a blood sample for MTHFR genotype and serum chemistries. Comparisons of PANSS symptoms, folate, and homocysteine status were conducted based on genotype. Results: The 677T allele load was associated with negative symptom severity. Contrary to our expectations, the T allele was also found to be protective against positive symptoms. The A1298C polymorphism did not contribute to negative symptoms, and only weakly to positive symptoms. The specific effects of the C677T polymorphism were confirmed with haplotype analysis. Among patients homozygous for the 667T allele, serum folate levels correlated with negative symptom severity. Conclusions: Increased MTHFR 677T allele load confers risk for negative symptoms in schizophrenia, while reducing severity of positive symptoms. Further, the biochemical interaction of low serum folate with 677T-variant MTHFR may induce downstream effects salient to the expression of negative symptoms. C1 Massachusetts Gen Hosp, Schizophrenia Res Program, Dept Psychiat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. Baylor Univ, Inst Biomed Studies, Waco, TX 76798 USA. Univ Calif Davis, Dept Internal Med & Nutr, Davis, CA 95616 USA. RP Roffman, JL (reprint author), Massachusetts Gen Hosp, Schizophrenia Res Program, Dept Psychiat, 149 13th St,Room 2625, Charlestown, MA 02129 USA. EM jroffman@partners.org FU NIDDK NIH HHS [DK56085]; NIMH NIH HHS [MH02025-01A3] NR 51 TC 41 Z9 42 U1 2 U2 5 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 JAN 1 PY 2008 VL 63 IS 1 BP 42 EP 48 DI 10.1016/j.biopsych.2006.12.017 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 244KE UT WOS:000251864000008 PM 17543893 ER PT J AU Yones, RJ Armstrong, SA AF Yones, Richard J. Armstrong, Scott A. TI Cancer stem cells in hematopoietic malignancies SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE leukemia; multiple myeloma; stem cells ID MYELOGENOUS LEUKEMIA STEM; ACUTE MYELOID-LEUKEMIA; REED-STERNBERG CELLS; CIRCULATING B-CELLS; MULTIPLE-MYELOMA; PLASMA-CELL; BONE-MARROW; DIFFERENTIATION; PROGENITORS; EXPRESSION AB Most hematopoietic malignancies are comprised of cells that are functionally heterogeneous, with only a subset being responsible for tumor maintenance. These cancer stem cells are so named because they possess qualities reminiscent of normal tissue stem cells including self-renewal, prolonged survival, and the ability to give rise to cells with more differentiated characteristics. Effort is now focused on identifying cancer stem cells in various hematopoietic malignancies, and defining the cells of origin such that the stepwise accumulation of genetic/epigenetic events necessary for cancer stem cell development can be delineated. A detailed understanding of these processes could lead to development of therapeutics that more effectively treat hematopoietic malignancies and potentially other cancers. (c) 2008 American Society for Blood and Marrow Transplantation. C1 [Armstrong, Scott A.] Childrens Hosp, Boston, MA 02115 USA. [Armstrong, Scott A.] Karp Family Res Lab, Boston, MA 02215 USA. [Yones, Richard J.] Johns Hopkins Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. [Armstrong, Scott A.] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA USA. [Armstrong, Scott A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Armstrong, SA (reprint author), Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM Scott.Armstrong@childrens.harvard.edu NR 23 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2008 VL 14 IS 1 BP 12 EP 16 DI 10.1016/j.bbmt.2007.10.012 PG 5 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 250XB UT WOS:000252333500006 ER PT J AU Cooke, KR Jannin, A Ho, V AF Cooke, Kenneth R. Jannin, Anne Ho, Vincent TI The contribution of endothelial activation and injury to end-organ toxicity following allogeneic hematopoietic stem cell transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE endothelial cell; graft-versus-host disease; idiopathic pneumonia syndrome; veno-occlusive disease; thrombotic microangiopathy; hematopoietic stem cell transplantation; tumor necrosis factor-alpha; cytokines; inflammation; microvasculature ID BONE-MARROW-TRANSPLANTATION; IDIOPATHIC-PNEUMONIA-SYNDROME; THROMBOTIC THROMBOCYTOPENIC PURPURA; VERSUS-HOST-DISEASE; VENOOCCLUSIVE DISEASE; DEFIBROTIDE DF; GROWTH-FACTOR; RISK-FACTORS; IN-VIVO; MICROANGIOPATHY AB Over the last 25 years, allogeneic hematopoietic stem cell transplantation (HSCT) has been used increasingly as a curative treatment option for patients with hematologic and neoplastic diseases. Despite major advances in transplant immunology and improvements in supportive and critical care medicine, HSCT is still plagued by several life-threatening complications. As such, the establishment of effective therapeutic options for these complications will be crucial as increasing numbers of high-risk transplants are performed each year. This brief review will discuss the contribution of vascular endothelial cell activation and injury to inflammation and end-organ toxicity that occurs following allogeneic HSCT, and will highlight translational research efforts that have paved the way to the development of novel strategies to treat and prevent disease. Finally, we will discuss in detail the clinical manifestations and challenges encompassed by the syndrome of thrombotic microangiopathy following HSCT. (c) 2008 American Society for Blood and Marrow Transplantation. C1 [Cooke, Kenneth R.] Case Western Reserve Univ, Sch Med, Dept Pediat, Blood & Marrow Transplantat Program,Case Comprehe, Cleveland, OH 44106 USA. [Cooke, Kenneth R.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Sch Med, Cleveland, OH 44106 USA. [Jannin, Anne] Univ Paris 07, Hosp St Louis, Dept Pathol, Paris, France. [Ho, Vincent] Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA. RP Cooke, KR (reprint author), Case Western Reserve Univ, Sch Med, Dept Pediat, Blood & Marrow Transplantat Program,Case Comprehe, Wolstein Res Bldg,Room 6524,2103 Cornell Rd, Cleveland, OH 44106 USA. EM Kenneth.cooke@uhliospitals.org NR 46 TC 21 Z9 23 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2008 VL 14 IS 1 BP 23 EP 32 DI 10.1016/j.bbmt.2007.10.008 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 250XB UT WOS:000252333500010 PM 18162218 ER PT J AU Armand, P Kim, HT Cutler, CS Ho, VT Koreth, J Ritz, J Alyea, EP Antin, JH Soiffer, RJ AF Armand, Philippe Kim, Haesook T. Cutler, Corey S. Ho, Vincent T. Koreth, John Ritz, Jerome Alyea, Edwin P. Antin, Joseph H. Soiffer, Robert J. TI A prognostic score for patients with acute leukemia or myelodysplastic syndromes undergoing allogeneic stem cell transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE allogeneic stem cell transplantation; acute myeloid leukemia; acute lymphoblastic leukemia; myelodysplastic syndrome; cytogenetics; iron overload ID BONE-MARROW-TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; CYTOGENETIC ABNORMALITIES; RISK-ASSESSMENT; IMPACT; MORTALITY; BLOOD; AGE; REMISSION; TRIAL AB Allogeneic hematopoietic stem cell transplantation (SCT) has the potential to cure patients with acute leukemia or myelodysplastic syndromes (MDS), but a number of prognostic factors can influence the outcome of transplantation. At present, no transplantation-specific risk score exists for this patient population. We propose a simple scoring system for patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), or MDS, based on a retrospective analysis of 445 patients undergoing SCT at our institution (divided into training and validation subsets). The score depends on 5 variables: age, disease, stage at transplantation, cytogenetics, and pretransplantation ferritin. It divides patients into 3 groups of comparable size, with 5-year overall survival (OS) of 56% (low risk), 22% (intermediate risk), and 5% (high risk). This prognostic score could be useful in making treatment decisions for individual patients, in stratifying patients entering clinical trials, and in adjusting transplantation outcomes across centers under the new federal reporting rules. (c) 2008 American Society for Blood and Marrow Transplantation. C1 [Armand, Philippe; Cutler, Corey S.; Ho, Vincent T.; Koreth, John; Ritz, Jerome; Alyea, Edwin P.; Antin, Joseph H.; Soiffer, Robert J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Armand, P (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM parmand@partners.org OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [T32 CA009172]; NHLBI NIH HHS [P01 HL070149, P01 HL070149-050001] NR 32 TC 37 Z9 38 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2008 VL 14 IS 1 BP 28 EP 35 DI 10.1016/j.bbmt.2007.07.016 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 249SI UT WOS:000252249600005 PM 18158958 ER PT J AU Spitzer, TR Ambinder, RF Lee, JY Kaplan, LD Wachsman, W Straus, DJ Aboulafia, DM Scadden, DT AF Spitzer, Thomas R. Ambinder, Richard F. Lee, Jeannette Y. Kaplan, Lawrence D. Wachsman, William Straus, David J. Aboulafia, David M. Scadden, David T. TI Dose-reduced busulfan, cyclophosphamide, and autologous stem cell transplantation for human immunodeficiency virus-associated lymphoma: AIDS malignancy consortium study 020 SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE acquired immunodeficiency syndrome; autologous stem cell transplantation; busulfan; cyclophosphamide; lymphoma ID HIV-ASSOCIATED LYMPHOMA; ACTIVE ANTIRETROVIRAL THERAPY; BONE-MARROW-TRANSPLANTATION; NON-HODGKINS-LYMPHOMA; HEPATIC VENOOCCLUSIVE DISEASE; INTRAVENOUS BUSULFAN; PREPARATIVE REGIMEN; DECREASED INCIDENCE; RANDOMIZED TRIAL; ORAL BUSULFAN AB Intensive chemotherapy for human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) has resulted in durable remissions in a substantial proportion of patients. High-dose chemotherapy and autologous stem cell transplantation (AuSCT), moreover, has resulted in sustained complete remissions in selected patients with recurrent chemosensitive disease. Based on a favorable experience with dose-reduced high-dose busulfan, cyclophosphamide, and AuSCT for older patients with non-HIV-associated aggressive lymphomas, an AIDS Malignancy Consortium multicenter trial was undertaken using the same dose-reduced busulfan and cyclophosphamide preparative regimen with AuSCT for recurrent HIV-associated NHL and HL. Of the 27 patients in the study, 20 received an AuSCT. The median time to achievement of an absolute neutrophil count (ANC) of >= 0.5 x 10(9)/L was 11 days (range, 9-16 days). The median time to achievement of an unsupported platelet count of 20 x 10(9)/L was 13 days (range, 6-57 days). One patient died on day +33 posttransplantation from hepatic veno-occlusive disease (VOD) and multiorgan failure. No other fatal regimen-related toxicity occurred. Ten of 19 patients (53%) were in complete remission at the time of their day + 100 post-AuSCT evaluation. Of the 20 patients, 10 were alive and event-free at a median of 23 weeks post-AuSCT. Median overall survival (OS) was not reached by 13 of the 20 patients alive at the time of last follow-up. This multi-institutional trial demonstrates that a regimen of dose-reduced high-dose busulfan, cyclophosphamide, and AuSCT is well tolerated and is associated with favorable disease-free survival (DFS) and OS probabilities for selected patients with HIV-associated NHL and HL. (c) 2008 American Society for Blood and Marrow Transplantation. C1 [Spitzer, Thomas R.; Scadden, David T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lee, Jeannette Y.] Univ Alabama, Tuscaloosa, AL 35487 USA. [Kaplan, Lawrence D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Wachsman, William] Univ Calif San Diego, VA San Diego Hlthcare Syst, La Jolla, CA 92093 USA. [Straus, David J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Aboulafia, David M.] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Ambinder, Richard F.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. RP Spitzer, TR (reprint author), Massachusetts Gen Hosp, Bone Marrow Transplant Program, 0 Emerson Pl,Suite 118,55 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [U01 CA083035, U01 CA083118, U01 CA071375, U01CA070019, U01 CA070062, U01CA070062, U01CA071375, U01 CA070019, U01CA083035, U01CA083118, U01CA070047, P50 CA096888, R01 CA095423, U01 CA070047, U01 CA070054, U01 CA121947, U01CA070054, U01CA083216] NR 34 TC 46 Z9 46 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2008 VL 14 IS 1 BP 59 EP 66 DI 10.1016/j.bbmt.2007.03.014 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 249SI UT WOS:000252249600009 PM 18158962 ER PT J AU Treister, NS Cook, EF Antin, J Lee, SJ Soiffer, R Woo, SB AF Treister, Nathaniel S. Cook, Earl Francis, Jr. Antin, Joseph Lee, Stephine J. Soiffer, Robert Woo, Sook-Bin TI Clinical evaluation of oral chronic graft-versus-host disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE hematopoietic cell transplantation; graft-versus-host disease; oral mucosal disease; salivar gland disease ID BONE-MARROW-TRANSPLANTATION; CONSENSUS DEVELOPMENT PROJECT; STEM-CELL TRANSPLANTATION; RANDOMIZED TRIAL; MANIFESTATIONS; RECIPIENTS; CRITERIA; THERAPY; LESIONS AB Oral chronic graft-versus-host disease (cGVHD) is a significant and serious complication following allogeneic hematopoietic stem cell transplantation (HSCT). The purpose of this study was to characterize the distribution, type, and extent of lesions and their correlation with patient-reported symptoms such as pain and discomfort. The effect of time since transplantation on these measures was also assessed. Consecutive patients with oral cGVHD referred to the Center for Oral Disease at Brigham and Women's Hospital, Boston, MA, were evaluated over a 2-year period. Subjective data included the responses to 4 targeted symptom questions (yes/no) and a visual analog scale pain score (0-10). Objective data included the location and extent of reticulation, erythema, and ulcerations using a previously published scoring system as well as time since HSCT. Multiple linear regression analyses were performed using SAS. We evaluated 27 patients, for a total of 79 clinic visits (median 2, range: 1-8). The median time since HSCT was 18 months (range: 5-157 months). The buccal and labial mucosa and tongue were the sites of 93 % of all ulcerations, 72% of all erythematous lesions, and 76% of all reticular lesions, and were the most frequently affected sites. The gingiva, floor of mouth, and hard and soft palate were infrequently affected. Although uncommon, ulceration of the soft palate was the objective finding most highly correlated with increased pain (P <.0001), and there was a generalized significant trend for increased pain scores with increased extent of ulceration. Overall, 95% of pain scores were : 5 (scale from 0-10, range: 0-7), with 40% reporting a score of zero. However, 80% admitted to avoiding certain foods because of mouth pain. After controlling for the presence and extent of ulcerations, we found that time since HSCT was inversely related to the pain score (P <.04). There was a statistically significant inverse relationship between the overall presence of ulceration and time since HSCT. We found that oral cGVHD most frequently affects the buccal and labial mucosa and the tongue. The functional impact was significant, as most patients had to restrict oral intake because of discomfort. Both the signs and symptoms associated with oral cGVHD tend to decrease over time. The association between ulceration of the soft palate and patient-reported pain highlights the significance of the location of involvement and the need for targeted approaches to therapy. Our findings, in large part, support the recently introduced National Institutes of Health response criteria for oral cGVHD, which is critical for the conduct of effective and meaningful research in this field; however, prospective application in clinical and investigative settings is necessary for evaluating its utility and efficacy in practice. (c) 2008 American Society for Blood and Marrow Transplantation. C1 [Treister, Nathaniel S.; Cook, Earl Francis, Jr.; Woo, Sook-Bin] Brigham & Womens Hosp, Div Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Soiffer, Robert] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lee, Stephine J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Treister, NS (reprint author), Brigham & Womens Hosp, Div Oral & Maxillofacial Surg, 75 Francis St, Boston, MA 02115 USA. EM ntreister@partners.org NR 27 TC 24 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2008 VL 14 IS 1 BP 110 EP 115 DI 10.1016/j.bbmt.2007.06.017 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 249SI UT WOS:000252249600014 PM 18158967 ER PT J AU Teshima, T Wynn, TA Soiffer, RJ Matsuoka, KI Martin, PJ AF Teshima, Takanori Wynn, Thomas A. Soiffer, Robert J. Matsuoka, Ken-Ichi Martin, Paul J. TI Chronic graft-versus-host disease: How can we release Prometheus? SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article C1 [Martin, Paul J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Teshima, Takanori] Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 812, Japan. [Wynn, Thomas A.] NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH,DHHS, Bethesda, MD 20892 USA. [Soiffer, Robert J.; Matsuoka, Ken-Ichi] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Martin, PJ (reprint author), Fred Hutchinson Canc Res Ctr, POB 19024,1100 Fairview Ave N,D2-100, Seattle, WA 98109 USA. EM pmartin@fhcrc.org RI Wynn, Thomas/C-2797-2011; teshima, takanori/G-1671-2012; OI teshima, takanori/0000-0002-0941-271X NR 0 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2008 VL 14 IS 1 BP 142 EP + DI 10.1016/j.bbmt.2007.10.023 PG 3 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 250XB UT WOS:000252333500032 PM 18162235 ER PT J AU Belleannee, C Da Silva, N Shum, W Marsolais, M Laprade, R Brown, D Breton, S AF Belleannee, Clemence Da Silva, Nicolas Shum, Winnie Marsolais, Mireille Laprade, Raynald Brown, Dennis Breton, Sylvie TI Expression and functional role of the bradykinin type 2 teceptor in epididymal principal cells SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-the-Study-of-Reproduction CY MAY 27-30, 2008 CL Kona, HI SP Soc Study Reprod C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Montreal, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2008 SI SI MA 300 BP 124 EP 124 PG 1 WC Reproductive Biology SC Reproductive Biology GA 347DH UT WOS:000259120300280 ER PT J AU Growdon, W Littell, R Pru, J Lynch, M Guo, LK Rueda, B AF Growdon, Whitfield Littell, Ramey Pru, James Lynch, Maureen Guo, Lankai Rueda, Bo TI Cables 1 mediates progesterone-induced inhibition of endometrial epithelial cell proliferation SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-the-Study-of-Reproduction CY MAY 27-30, 2008 CL Kona, HI SP Soc Study Reprod C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Kaiser Permanente, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2008 SI SI MA 317 BP 129 EP 129 PG 1 WC Reproductive Biology SC Reproductive Biology GA 347DH UT WOS:000259120300297 ER PT J AU Namekawa, S AF Namekawa, Satoshi TI Role of noncoding RNA in X-inactivation from gamete to embryo SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-the-Study-of-Reproduction CY MAY 27-30, 2008 CL Kona, HI SP Soc Study Reprod C1 [Namekawa, Satoshi] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2008 SI SI MA 448 BP 160 EP 160 PG 1 WC Reproductive Biology SC Reproductive Biology GA 347DH UT WOS:000259120300417 ER PT J AU Bodugoz-Senturk, H Choi, J Oral, E Kung, JH Macias, CE Braithwaite, G Muratoglu, OK AF Bodugoz-Senturk, Hatice Choi, Jeeyoung Oral, Ebru Kung, Jean H. Macias, Celia E. Braithwaite, Gavin Muratoglu, Orhun K. TI The effect of polyethylene glycol on the stability of pores in polyvinyl alcohol hydrogels during annealing SO BIOMATERIALS LA English DT Article DE polyvinyl alcohol; hydrogel; cartilage repair; polyethylene glycol; creep resistant; annealing ID ARTICULAR-CARTILAGE REPAIR; X-RAY-DIFFRACTION; POLY(VINYL ALCOHOL); CROSS-LINKING; DEFECTS; KNEE; TRANSPLANTATION; MICROSTRUCTURE; CRYSTALLINITY; MOSAICPLASTY AB Poly(vinyl alcohol) (PVA) hydrogels are candidate biomaterials for cartilage resurfacing or interpositional arthroplasty devices requiring high-creep resistance and high water content to maintain lubricity. Annealing of PVA improves creep resistance but also reduces the water content. We hypothesized that maintaining poly(ethylene glycol) (PEG) within PVA during annealing would prevent the collapse of the pores and thus would result in high equilibrium water content (EWC). Our hypothesis tested positive. The PVA hydrogels containing PEG maintained their opacity through annealing and exhibited large pores under confocal imaging while hydrogels not containing PEG turned translucent and no pores were visible after annealing. The EWC of gels annealed with PEG (83 +/- 1.0%) was higher than that of the gels processed without PEG (55 +/- 4.8). The crystallinity of the former was 8.0 +/- 1.7% and the latter was 27.5 +/- 8.7%. The hydrogels processed in the presence of PEG exhibited a significantly higher total creep strain (69 +/- 3.4%) when compared to the PEG-free hydrogels (17 + 3.7) under an initial contact stress of 0.45 MPa. EWC appeared to be strongly related to the creep resistance of annealed PVA theta-gels. (C) 2007 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Harris Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Harris Orthopaed Biomech & Biomat Lab, 55 Fruit St,GRJ 1206, Boston, MA 02114 USA. EM omuratoglu@partners.org OI Braithwaite, Gavin/0000-0002-6239-0046 NR 26 TC 29 Z9 30 U1 4 U2 19 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 JAN PY 2008 VL 29 IS 2 BP 141 EP 149 DI 10.1016/j.biomaterials.2007.09.015 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 239BG UT WOS:000251492200002 PM 17950839 ER PT J AU Brewster, LP Washington, C Brey, EM Gassman, A Subramanian, A Calceterra, J Wolf, W Hall, CL Velander, WH Burgess, WH Greisler, HP AF Brewster, Luke P. Washington, Cicely Brey, Eric M. Gassman, Andrew Subramanian, Anu Calceterra, Jen Wolf, William Hall, Connie L. Velander, William H. Burgess, Wilson H. Greisler, Howard P. TI Construction and characterization of a thrombin-resistant designer FGF-based collagen binding domain angiogen SO BIOMATERIALS LA English DT Article DE angiogenesis; collagen; endothelial cell; endothelialization; fibroblast growth factor; growth factors ID FIBROBLAST-GROWTH-FACTOR; HUMAN-ENDOTHELIAL CELLS; IN-VITRO ENDOTHELIALIZATION; INFRAINGUINAL EPTFE GRAFTS; SMOOTH-MUSCLE-CELLS; DNA-SYNTHESIS; FIBRIN GLUE; INTIMAL HYPERPLASIA; FUSION PROTEIN; FACTOR TYPE-1 AB Humans demonstrate limited spontaneous endothelialization of prosthetic bypass grafts. However the local application of growth factors to prosthetic grafts or to injured blood vessels can provide an immediate effect on endothelialization. Novel chimeric proteins combining potent angiogens with extracellular matrix binding domains may localize to exposed matrices and provide sustained activity to promote endothelial regeneration after vascular interventions. We have ligated a thrombin-resistant mutant of fibroblast growth factor (FGF)-1 (R136K) with a collagen binding domain (CBD) in order to direct this growth factor to sites of exposed vascular collagen or selected bioengineered scaffolds. While FGF-1 and R136K are readily attracted to a variety of matrix proteins, R136K-CBD demonstrated selective and avid binding to collagen similar to 4x that of FGF-1 or R136K alone (P < 0.05). The molecular stability of R136K-CBD was superior to FGF-1 and R136K. Its chemotactic activity was superior to R136K and FGF-1 (11 +/- 1% vs. 6 +/- 2% and 4 +/- 1%; P<0.01). Its angiogenic activity was similar to R136K and significantly greater than control by day 2 (P<0.01). After day 3, FGF-1-treated endothelial cell's (EC) sprouts had regressed back to levels insignificant compared to the control group (P = 0.17), while both R136K and R136K-CBD continued to demonstrate greater sprout lengthening as compared to control (P<0.0002). The mitogenic, activity of all growth factors was greater than control groups (20% PBS); in all comparisons (P<0.0001). This dual functioning angiogen provides proof of concept for the application of designer angiogens to matrix binding proteins to intelligently promote endothelial regeneration of selected matrices. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Brewster, Luke P.; Gassman, Andrew; Greisler, Howard P.] Loyola Univ, Med Ctr, Dept Surg, Maywood, IL 60153 USA. [Brewster, Luke P.; Greisler, Howard P.] Dept Cell Biol Neurobiol & Anat, Maywood, IL 60153 USA. [Washington, Cicely; Subramanian, Anu; Calceterra, Jen; Velander, William H.] Univ Nebraska, Dept Chem & Biomol Engn, Lincoln, NE 68588 USA. [Brey, Eric M.; Wolf, William; Greisler, Howard P.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, Hines, IL 60141 USA. [Brey, Eric M.; Hall, Connie L.] IIT, Dept Biomed Engn, Chicago, IL 60616 USA. [Burgess, Wilson H.] StatSeal Inc, Belleview, WA USA. [Greisler, Howard P.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Surg Serv, Hines, IL 60141 USA. RP Greisler, HP (reprint author), Loyola Univ, Med Ctr, Dept Surg, 2160 S 1st Ave, Maywood, IL 60153 USA. EM hgreisl@lumc.edu FU NHLBI NIH HHS [F32 HL078151-02, F32 HL074594, F32 HL078151, F32 HL078151-01, HL074594, HL078151-01, R01 HL041272, R01 HL041272-16, R01 HL041272-17, R01 HL041272-18, R01-HL41272] NR 48 TC 16 Z9 17 U1 0 U2 8 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 JAN PY 2008 VL 29 IS 3 BP 327 EP 336 DI 10.1016/j.biomaterials.2007.09.034 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 242CY UT WOS:000251703300008 PM 17950455 ER PT S AU Mroz, P Hamblin, MR AF Mroz, Pawel Hamblin, Michael R. BE Chen, WR TI Photodynamic therapy stimulates anti-tumor immunity in a murine mastocytoma model - art. no. 685706 SO BIOPHOTONICS AND IMMUNE RESPONSES III SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Biophotonics and Immune Responses III CY JAN 21, 2008 CL San Jose, CA SP SPIE DE photodynamic therapy; mastocytoma; tumor-associated antigen; cytotoxic T cells ID CYTOLYTIC T-LYMPHOCYTES; TUMOR-INFILTRATING LYMPHOCYTES; MOUSE GENE P1A; HUMAN-MELANOMA; HLA-A2 MELANOMAS; ANTIGEN; P815; REJECTION; PEPTIDE; ESCAPE AB Photodynamic therapy (PDT) involves the IV administration of photosensitizers followed by illumination of the tumor with red light producing reactive oxygen species that eventually cause vascular shutdown and tumor cell apoptosis. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, recognition of tumor-specific antigens, and induction of heat-shock proteins, while the three commonest cancer therapies (surgery, chemotherapy and radiotherapy) all tend to suppress the immune system. Like many other immunotherapies, the extent of the immune response after PDT tends to depend on the antigenicity of the particular tumor, or in other words, whether the tumor contains proteins with the correct characteristics to provide peptides that can bind to MHC class I molecules and provide a target for cytolytic T lymphocytes. We have described certain mouse tumors containing defined or naturally occurring tumor associated antigens that respond particularly well to PDT, and potent immune responses capable of destroying distant untreated tumors can be induced. In this report we address the induction of immunity after PDT of the DBA2 mastocytoma known as P815. This tumor was the first mouse tumor to be shown to possess a tumor-rejection antigen capable of being recognized by cytotoxic T-cells. C1 [Mroz, Pawel; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Mroz, P (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 NR 35 TC 0 Z9 0 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7032-4 J9 P SOC PHOTO-OPT INS PY 2008 VL 6857 BP 85706 EP 85706 DI 10.1117/12.764922 PG 9 WC Biophysics; Immunology; Optics SC Biophysics; Immunology; Optics GA BHQ93 UT WOS:000255550900004 ER PT J AU Munn, LL AF Munn, L. L. TI Blood dynamics in normal and abnormal vessel networks SO BIORHEOLOGY LA English DT Meeting Abstract C1 [Munn, L. L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Charlestown, MA USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0006-355X J9 BIORHEOLOGY JI Biorheology PY 2008 VL 45 IS 1-2 BP 38 EP 39 PG 2 WC Biophysics; Engineering, Biomedical; Hematology SC Biophysics; Engineering; Hematology GA 344LR UT WOS:000258929100033 ER PT J AU Wang, D Stockard, CR Harkins, L Lott, P Salih, C Yuan, K Buchsbaum, D Hashim, A Zayzafoon, M Hardy, RW Hameed, O Grizzle, W Siegal, GP AF Wang, D. Stockard, C. R. Harkins, L. Lott, P. Salih, C. Yuan, K. Buchsbaum, D. Hashim, A. Zayzafoon, M. Hardy, R. W. Hameed, O. Grizzle, W. Siegal, G. P. TI Immunohistochemistry in the evaluation of neovascularization in tumor xenografts SO BIOTECHNIC & HISTOCHEMISTRY LA English DT Article DE angiogenesis; antigen retrieval; CD31/PECAM-1; endothelial cells; factor; VIII/vWf; immunohistochemistry; microvessel density; xenografts ID CELL LUNG-CANCER; GROWTH-FACTOR EXPRESSION; ANTIGEN RETRIEVAL; VASCULOGENIC MIMICRY; MICROVESSEL DENSITY; ENDOTHELIAL-CELLS; MONOCLONAL-ANTIBODIES; FACTOR-VIII; IN-VIVO; ANGIOGENESIS AB Angiogenesis, or neovascularization, is known to play an important role in the neoplastic progression leading to metastasis. CD31 or Factor VIII-related antigen (F VIII RAg) immunohistochemistry is widely used in experimental studies for quantifying tumor neovascularization in immunocompromised animal models implanted with transformed human cell lines. Quantification, however, can be affected by variations in the methodology used to measure vascularization including antibody selection, antigen retrieval (AR) pretreatment, and evaluation techniques. To examine this further, we investigated the microvessel density (MVD) and the intensity of microvascular staining among five different human tumor xenografts and a mouse syngeneic tumor using anti-CD31 and F VIII RAg immunohistochemical staining. Different AR methods also were evaluated. Maximal retrieval of CD31 was achieved using 0.5 M Tris (pH 10) buffer, while maximum retrieval of F VIII RAg was achieved using 0.05% pepsin treatment of tissue sections. For each optimized retrieval condition, anti-CD31 highlighted small vessels better than F VIII RAg. Furthermore, the MVD of CD31 was significantly greater than that of F VIII RAg decorated vessels (p < 0.001). The choice of antibody and AR method has a significant affect on immunohistochemical findings when studying angiogenesis. One also must use caution when comparing studies in the literature that use different techniques and reagents. C1 [Siegal, G. P.] Univ Alabama, Dept Pathol, Div Anat Pathol, Birmingham, AL 35233 USA. [Wang, D.; Lott, P.; Siegal, G. P.] Univ Alabama, Dept Surg, Birmingham, AL 35233 USA. [Buchsbaum, D.] Univ Alabama, Dept Radiat Oncol, Birmingham, AL 35233 USA. [Siegal, G. P.] Univ Alabama, Dept Cell Biol, Birmingham, AL 35233 USA. [Harkins, L.; Siegal, G. P.] Birmingham VA Med Ctr, Dept Pathol & Lab Med, Birmingham, AL 35233 USA. [Wang, D.; Lott, P.; Salih, C.; Zayzafoon, M.] Ctr Metab Bone Dis, Birmingham, AL 35233 USA. [Buchsbaum, D.; Zayzafoon, M.; Hardy, R. W.; Grizzle, W.; Siegal, G. P.] UAB Comprehens Canc Ctr, Birmingham, AL 35233 USA. RP Siegal, GP (reprint author), Univ Alabama, Dept Pathol, Div Anat Pathol, KB 506 619 19th St S, Birmingham, AL 35233 USA. EM gsiegal@path.uab.edu RI Siegal, Gene/A-8653-2009 FU NIAMS NIH HHS [P30 AR046031-089002, P30 AR046031]; NIDDK NIH HHS [P30 DK074038, P30 DK074038-04] NR 34 TC 53 Z9 53 U1 1 U2 6 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1052-0295 J9 BIOTECH HISTOCHEM JI Biotech. Histochem. PY 2008 VL 83 IS 3-4 BP 179 EP 189 DI 10.1080/10520290802451085 PG 11 WC Biotechnology & Applied Microbiology; Cell Biology SC Biotechnology & Applied Microbiology; Cell Biology GA 363HX UT WOS:000260259500007 PM 18846440 ER PT S AU Soto-Gutierrez, A Basma, H Navarro-Alvarez, N Uygun, BE Yarmush, ML Kobayashi, N Fox, IJ AF Soto-Gutierrez, Alejandro Basma, Hesham Navarro-Alvarez, Nalu Uygun, Basak E. Yarmush, Martin L. Kobayashi, Naoya Fox, Ira J. BE Harding, SE Tombs, MP TI Differentiating Stem Cells into Liver SO BIOTECHNOLOGY AND GENETIC ENGINEERING REVIEWS, VOL 25 SE Biotechnology & Genetic Engineering Reviews LA English DT Review; Book Chapter ID HEPATOCYTE-LIKE CELLS; INTRAHEPATIC BILE-DUCTS; IN-VITRO; TRANSCRIPTION FACTORS; DEFINITIVE ENDODERM; HEPATIC SPECIFICATION; VISCERAL ENDODERM; DRUG DISCOVERY; EXPRESSION; INDUCTION AB Research involving differentiated embryonic stem (ES) cells may revolutionize the study of liver disease, improve the drug discovery process, and assist in the development of stem-cell-based clinical therapies. Generation of ES cell-derived hepatic tissue has benefited from an understanding of the cytokines, growth factors and biochemical compounds that are essential in liver development, and this knowledge has been used to mimic some aspects of embryonic development in vitro. Although great progress has been made in differentiating human ES cells into liver cells, current protocols have not yet produced cells with the phenotype of a mature hepatocyte. There is a significant need to formally establish criteria that would define what constitutes a functional human stem cell-derived hepatocyte. Here, we explore current challenges and future opportunities in development and use of ES cell-derived liver cells. ES-derived hepatocytes could be used to better understand liver biology, begin the process of "personalizing" health care, and to treat some forms of liver disease. C1 [Fox, Ira J.] Childrens Hosp Pittsburgh, Dept Surg, Div Pediat Transplant Surg, Pittsburgh, PA 15213 USA. [Fox, Ira J.] Univ Pittsburgh, Sch Med, McGowan Inst Regenerat Med, Pittsburgh, PA 15213 USA. [Soto-Gutierrez, Alejandro; Uygun, Basak E.; Yarmush, Martin L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. [Soto-Gutierrez, Alejandro; Uygun, Basak E.; Yarmush, Martin L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Soto-Gutierrez, Alejandro; Uygun, Basak E.; Yarmush, Martin L.] Shriners Hosp Children, Boston, MA 02114 USA. [Basma, Hesham] Univ Nebraska Med Ctr, Dept Surg, Omaha, NE 68198 USA. [Navarro-Alvarez, Nalu; Kobayashi, Naoya] Okayama Univ, Grad Sch Med & Dent, Dept Surg, Okayama 7008558, Japan. RP Fox, IJ (reprint author), Childrens Hosp Pittsburgh, Dept Surg, Div Pediat Transplant Surg, Pittsburgh, PA 15213 USA. EM foxi@upmc.edu RI Uygun, Basak/I-1792-2012 OI Uygun, Basak/0000-0002-2600-7900 NR 63 TC 9 Z9 9 U1 0 U2 15 PU NOTTINGHAM UNIVERSITY PRESS PI NOTTINGHAM PA UNIV NOTTINGHAM, KINGS MEADOW CAMPUS, LENTON LN, NOTTINGHAM NG7 2NR, ENGLAND SN 0264-8725 BN 978-1-904761-67-9 J9 BIOTECHNOL GENET ENG JI Biotechnol. Genet. Eng. Rev. PY 2008 VL 25 BP 149 EP 163 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA BTA03 UT WOS:000286187300007 PM 21412354 ER PT J AU Barry, MJ Link, CL McNaughton-Collins, MF McKinlay, JB AF Barry, Michael J. Link, Carol L. McNaughton-Collins, Mary F. McKinlay, John B. CA Hlth, BAC TI Overlap of different urological symptom complexes in a racially and ethnically diverse, community-based population of men and women SO BJU INTERNATIONAL LA English DT Article DE prevalence; prostatic hyperplasia; interstitial cystitis; prostatitis; incontinence ID BENIGN PROSTATIC HYPERPLASIA; URINARY-TRACT SYMPTOMS; QUALITY-OF-LIFE; INDEX; INCONTINENCE; PREVALENCE; BLADDER; QUESTIONNAIRE; IMPACT AB OBJECTIVE To define the prevalence and overlap of symptom patterns traditionally associated with benign prostatic hyperplasia, chronic prostatitis/chronic pelvic pain syndrome, interstitial cystitis/painful bladder syndrome, and incontinence among men and women in a racially and ethnically diverse, community-based population. SUBJECTS AND METHODS In all, 5506 men and women aged 30-79 years were recruited to participate in the Boston Area Community Health Survey, using a stratified-cluster sampling technique to obtain roughly similar representative samples by age group, gender and race/ethnicity (White, Black, Hispanic). Survey data were collected by bilingual interviewers in subjects' homes. Scales measuring symptom patterns were derived from validated instruments, with minor changes to eliminate different recall periods and overlap in items that might have confused subjects. RESULTS About a quarter of men and women of all ages met the definition for one or more of the target symptom patterns; there was no significant variation in the prevalence of any of the symptom patterns by race/ethnicity. Overall, approximate to 16% of men and women had one symptom pattern, while 7% had overlap patterns. Except for urinary incontinence and interstitial cystitis/painful bladder syndrome in both men and women, the prevalence of all symptom complexes were associated with one another significantly more often that would be expected by chance. CONCLUSIONS Overlapping patterns of lower urinary tract symptoms and pelvic pain are common. These overlapping patterns present challenges for clinical practice and research, and require further investigation of their causes, diagnosis and optimum treatment. C1 Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. New England Res Inst, Boston, MA USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. FU NIDDK NIH HHS [U01 DK56842] NR 19 TC 21 Z9 21 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD JAN PY 2008 VL 101 IS 1 BP 45 EP 51 DI 10.1111/j.1464-410X.2007.07191.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 239FA UT WOS:000251503000011 PM 17868419 ER PT J AU Nickel, JC Tripp, DA Chuai, S Litwin, MS McNaughton-Collins, M Landis, JR Alexander, RB Schaeffer, AJ O'Leary, MP Pontari, MA White, P Mullins, C Nyberg, L Kusek, J Grp, NCS AF Nickel, J. Curtis Tripp, Dean A. Chuai, Shannon Litwin, Mark S. McNaughton-Collins, Mary Landis, J. Richard Alexander, Richard B. Schaeffer, Anthony J. O'Leary, Michael P. Pontari, Michel A. White, Paige Mullins, Christopher Nyberg, Leroy Kusek, John Grp, N. I. H. C. P. C. R. N. Study TI Psychosocial variables affect the quality of life of men diagnosed with chronic prostatitis/chronic pelvic pain syndrome SO BJU INTERNATIONAL LA English DT Article DE chronic prostatitis; chronic pelvic pain syndrome; quality of life; psychosocial ID VALIDATION; ADJUSTMENT; SYMPTOMS; COHORT; SCALE AB OBJECTIVE To examine interactions between demographic, pain, urinary, psychological and environmental predictors of quality of life (QOL) in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). PATIENTS AND METHODS In all, 253 men previously enrolled in the National Institutes of Health Chronic Prostatitis Cohort study in North American tertiary-care clinical centres (six in the USA and one in Canada) self-reported with validated instruments, including the QOL subscales of the Short Form-12 (physical, SF12-PCS; and mental, SF12-MCS), demographics, urinary symptoms, depression, current pain, pain coping, 'catastrophising' (catastrophic thinking about pain), pain control, social support and solicitous responses from a partner. Data were collected through a one-time survey. Covariates determined to be significant were entered into a multivariable regression model predicting SF12-PCS and SF12-MCS. RESULTS Adjusting for covariates, regression models showed that poorer SF12-PCS scores were predicted by worse urinary function (P < 0.001) and increased use of pain-contingent resting as a coping strategy (P = 0.026). Further, poorer SF12-MCS scores were predicted by greater pain catastrophizing (P = 0.002) and lower perceptions of social support (P < 0.001). In separate follow-up analyses, helplessness was the significant catastrophizing subscale (P < 0.001), while support from family and friends were the significant social support subscales (P = 0.002 and < 0.001). CONCLUSIONS These data suggest that specific coping and environmental factors (i.e. catastrophizing, pain-contingent resting, social support) are significant in understanding how patients with CP/CPPS adjust. These data can be used to develop specific cognitive-behavioural programmes for men with CP/CPPS who are refractory to standard medical therapy. C1 Queens Univ, Dept Urol, Kingston, ON, Canada. Queens Univ, Dept Psychol, Kingston, ON, Canada. Queens Univ, Dept Anaesthesiol & Urol, Kingston, ON, Canada. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Univ Maryland, Sch Med, VA Maryland Hlth Care Syst, Baltimore, MD USA. N Western Univ, Chicago, IL USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Temple Univ, Philadelphia, PA 19122 USA. Univ Mississippi, University, MS 38677 USA. NIDDK, Bethesda, MD USA. RP Nickel, JC (reprint author), Queens Univ, Dept Urol, Kingston, ON, Canada. RI Landis, J. Richard/A-9330-2010; OI Landis, J Richard/0000-0001-8099-0988 FU NIDDK NIH HHS [U01 DK53732, U01 DK53734, U01 DK53736, U01 DK53730, U01 DK53738, U01 DK53746, U01 DK53752] NR 20 TC 32 Z9 42 U1 1 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD JAN PY 2008 VL 101 IS 1 BP 59 EP 64 DI 10.1111/j.1464-410X.2007.07196.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 239FA UT WOS:000251503000013 PM 17924985 ER PT J AU Raza, A Reeves, JA Feldman, EJ Dewald, GW Bennett, JM Deeg, J Dreisbach, L Schiffer, CA Stone, RM Greenberg, PL Curtin, PT Klimek, VM Shammo, JM Thomas, D Knight, RD Schmidt, M Wride, K Zeldis, JB List, AF AF Raza, Azra Reeves, James A. Feldman, Eric J. Dewald, Gordon W. Bennett, John M. Deeg, Joachim Dreisbach, Luke Schiffer, Charles A. Stone, Richard M. Greenberg, Peter L. Curtin, Peter T. Klimek, Virginia M. Shammo, Jamile M. Thomas, Deborah Knight, Robert D. Schmidt, Michele Wride, Kenton Zeldis, Jerome B. List, Alan F. TI Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1-risk myelodysplastic syndromes with karyotypes other than deletion 5q SO BLOOD LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol ID INTERNATIONAL WORKING GROUP; COLONY-STIMULATING FACTOR; PLUS ERYTHROPOIETIN; RESPONSE CRITERIA; MULTIPLE-MYELOMA; THALIDOMIDE; ANEMIA; CLASSIFICATION; ACTIVATION; PROPOSAL AB Lenalidomide is approved for red blood cell (RBC) transfusion-dependent anemia due to low or intermediate-1 (int-1) risk myelodysplastic syndromes (MDSs) associated with a chromosome 5q deletion with or without additional cytogenetic abnormalities. We report results of a multicenter, phase 2 trial evaluating lenalidomide therapy for transfusion-dependent patients with low-or int-1-risk MDS without deletion 5q. Eligible patients had 50000/mm(3) or more platelets and required 2 U or more RBCs within the previous 8 weeks; 214 patients received 10 mg oral lenalidomide daily or 10 mg on days 1 to 21 of a 28-day cycle. The most common grade 3/4 adverse events were neutropenia (30%) and thrombocytopenia (25%). Using an intention-to-treat analysis, 56 (26%) patients achieved transfusion independence (TI) after a median of 4.8 weeks of treatment with a median duration of TI of 41.0 weeks. In patients who achieved TI, the median rise in hemoglobin was 32 g/L (3.2 g/dL; range, 10-98 g/L [1.0-9.8 g/dL]) from baseline. A 50% or greater reduction in transfusion requirement occurred in 37 additional patients, yielding a 43% overall rate of hematologic improvement (TI response +parallel to >= 50% reduction in transfusion requirement). Lenalidomide has clinically meaningful activity in transfusion-dependent patients with low- or int-1-risk MDS who lack the deletion 5q karyotypic abnormality. This study is registered at www.clinicaltrials.gov as no. NCT00064974. C1 [Raza, Azra; Shammo, Jamile M.] Rush Univ, Med Ctr, Chicago, IL USA. [Feldman, Eric J.] Cornell Univ, Weill Med Coll, New York, NY USA. [Dewald, Gordon W.] Mayo Clin, Rochester, MN USA. [Bennett, John M.] Univ Rochester, Med Ctr, James P Wilmot Canc Ctr, New York, NY USA. [Deeg, Joachim] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Dreisbach, Luke] Eisenhower Med Ctr, Rancho Mirage, CA USA. [Schiffer, Charles A.] Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI USA. [Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Greenberg, Peter L.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Curtin, Peter T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Klimek, Virginia M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Thomas, Deborah] MD Anderson Canc Ctr, Houston, TX USA. [Knight, Robert D.; Schmidt, Michele; Wride, Kenton; Zeldis, Jerome B.] Celgene, Summit, NJ USA. [List, Alan F.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. RP List, AF (reprint author), H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM alan.list@moffitt.org NR 27 TC 226 Z9 235 U1 1 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 2008 VL 111 IS 1 BP 86 EP 93 DI 10.1182/blood-2007-01-068833 PG 8 WC Hematology SC Hematology GA 246IZ UT WOS:000252002000017 PM 17893227 ER PT J AU Yang, G Huang, SC Wu, JY Benz, EJ AF Yang, Guang Huang, Shu-Ching Wu, Jane Y. Benz, Edward J., Jr. TI Regulated Fox-2 isoform expression mediates protein 4.1R splicing during erythroid differentiation SO BLOOD LA English DT Article ID PRE-MESSENGER-RNA; SR PROTEINS; ELEMENTS; GENE; EXON; ERYTHROPOIESIS; MECHANISMS; HOMOLOGS; CELLS; INCLUSION AB A regulated splicing event in protein 4.1R pre-mRNA-the inclusion of exon 16-encoding peptides for spectrin-actin binding-occurs in late erythroid differentiation. We defined the functional significance of an intronic splicing enhancer, UGCAUG, and its cognate splicing factor, mFox2A, on exon 16 splicing during differentiation. UGCAUG displays cell-type-specific splicing regulation in a test neutral reporter and has a dose-dependent enhancing effect. Erythroid cells express 2 UGCAUG-binding mFox-2 isoforms, an erythroid differentiation-inducible mFox-2A and a commonly expressed mFox-2F. When overexpressed, both enhanced internal exon splicing in an UGCAUG-dependent manner, with mFox-2A exerting a much stronger effect than mFox-2F. A significant reciprocal increase in mFox-2A and decrease in mFox-2F occurred during erythroid differentiation and correlated with exon 16 inclusion. Furthermore, isoform-specific expression reduction reversed mFox-2A-enhancing activity, but not that of mFox-2F on exon 16 inclusion. Our results suggest that an erythroid differentiation-inducible mFox-2A isoform is a critical regulator of the differentiation-specific exon 16 splicing switch, and that its up-regulation in late erythroid differentiation is vital for exon 16 splicing. C1 [Yang, Guang; Huang, Shu-Ching; Benz, Edward J., Jr.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Yang, Guang] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Huang, Shu-Ching; Benz, Edward J., Jr.] Dana Faber Harvard Canc Ctr, Boston, MA USA. [Wu, Jane Y.] NE Univ Feinberg, Sch Med, Lurie Canc Ctr, Dept Neurol Ctr Genet Med, Chicago, IL USA. [Benz, Edward J., Jr.] Harvard Med Sch, Dept Pathol, Boston, MA USA. [Benz, Edward J., Jr.] Childrens Hosp, Dept Pediat, Boston, MA USA. RP Huang, SC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM shu-ching_huang@dfci.harvard.edu FU NCI NIH HHS [R01 CA114197]; NHLBI NIH HHS [R01 HL024385, HL24385] NR 43 TC 27 Z9 28 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 JAN 1 PY 2008 VL 111 IS 1 BP 392 EP 401 DI 10.1182/blood-2007-01-068940 PG 10 WC Hematology SC Hematology GA 246IZ UT WOS:000252002000056 PM 17715393 ER PT J AU Cho, PS Messina, DJ Hirsh, EL Chi, N Goldman, SN Lo, DP Harris, IR Popma, SH Sachs, DH Huang, CA AF Cho, Patricia S. Messina, Darin J. Hirsh, Erica L. Chi, Nina Goldman, Stephanie N. Lo, Diana P. Harris, Ian R. Popma, Sicco H. Sachs, David H. Huang, Christene A. TI Immunogenicity of umbilical cord tissue-derived cells SO BLOOD LA English DT Article ID MESENCHYMAL STEM-CELLS; MAJOR HISTOCOMPATIBILITY COMPLEX; MINIATURE SWINE; BONE-MARROW; RENAL-ALLOGRAFTS; PROGENITOR CELLS; IN-VITRO; TRANSPLANTATION; EXPRESSION; TOLERANCE AB Umbilical cord tissue provides a unique source of cells with potential for tissue repair. Umbilical cord tissue-derived cells (UTCs) are MHC class I (MHCI) dull and negative for MHC class II (MHCII), but can be activated to increase MHCI and to express MHCII with IFN-gamma stimulation. Mesenchymal stem cells with similar characteristics have been inferred to be nonimmunogenic; however, in most cases, immunogenicity was not directly assessed. Using UTC from Massachusetts General Hospital MHC-defined miniature swine, we assessed immunogenicity across a full MHC barrier. Immunogenicity was assessed by in vitro assays including mixed lymphocyte reaction (MLR) and flow cytometry to detect serum alloantibody. A single injection of MHC-mismatched unactivated UTCs did not induce a detectable immune response. When injected in an inflamed region, injected repeatedly in the same region or stimulated with IFN-gamma prior to injection, UTCs were immunogenic. As clinical cellular repair strategies may involve injection of allogeneic cells into inflamed regions of damaged tissue or repeated doses of cells to achieve the desired benefit, our results on the immunogenicity of these cells in these circumstances may have important implications for optimal success and functional improvement for this cellular treatment strategy for diseased tissues. C1 [Cho, Patricia S.; Hirsh, Erica L.; Lo, Diana P.; Sachs, David H.; Huang, Christene A.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Messina, Darin J.; Chi, Nina; Goldman, Stephanie N.; Harris, Ian R.; Popma, Sicco H.] Centocor R&D Stem Cell Internal Venture, Radnor, PA USA. RP Huang, CA (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, 149-9019 13th St, Boston, MA 02129 USA. EM huangc@helix.mgh.harvard.edu OI Sabins, Nina/0000-0001-7983-8962 NR 31 TC 101 Z9 130 U1 1 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 2008 VL 111 IS 1 BP 430 EP 438 DI 10.1182/blood-2007-03-078774 PG 9 WC Hematology SC Hematology GA 246IZ UT WOS:000252002000060 PM 17909081 ER PT J AU Freedman, RA Bauer, KA Neuberg, DS Zwicker, JI AF Freedman, Rachel A. Bauer, Kenneth A. Neuberg, Donna S. Zwicker, Jeffrey I. TI Timing of postpartum enoxaparin administration and severe postpartum hemorrhage SO BLOOD COAGULATION & FIBRINOLYSIS LA English DT Article DE enoxaparin; low-molecular-weight heparin; postpartum hemorrhage ID MOLECULAR-WEIGHT HEPARIN; RISK-FACTORS; VENOUS THROMBOEMBOLISM; 3RD STAGE; PREGNANCY; THROMBOPROPHYLAXIS; SAFETY; LABOR; DALTEPARIN; EXPERIENCE AB The appropriate time to restart anticoagulation in the postpartum period is not known. The purpose of the present study was to determine whether the timing of postpartum enoxaparin influences hemorrhagic outcomes. A total of 95 women were treated with peripartum enoxaparin and compared with 303 consecutive deliveries where anticoagulation was not administered. The overall rate of severe postpartum hemorrhage did not differ significantly for women treated with peripartum enoxaparin (4.2%) versus nonanticoagulated control individuals (2.0%, P=0.40) nor for the subgroup of women who underwent vaginal delivery (3.6 versus 1.4%, P=0.55) or cesarean section (5.1 versus 3.4%, P=0.98). We did not observe any severe hemorrhagic events attributable to administration of postpartum enoxaparin. The first dose of enoxaparin was administered less than 24 h following delivery in 75% of vaginal deliveries and in 49% of cesarean sections where enoxaparin was given in the postpartum period. Two incisional hematomas were observed in the group of women who received enoxaparin within 24 h following cesarean section. Severe postpartum hemorrhage is an infrequent complication when enoxaparin is administered to hemostatically intact women between 5 and 24 h following a vaginal delivery or 12 - 36 h following cesarean section. C1 [Freedman, Rachel A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. [Bauer, Kenneth A.; Zwicker, Jeffrey I.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol, Boston, MA 02215 USA. [Neuberg, Donna S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Zwicker, JI (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, 330 Brookline Ave, Boston, MA 02115 USA. EM jzwicker@bidmc.harvard.edu OI Zwicker, Jeffrey/0000-0001-5810-6893 NR 19 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0957-5235 J9 BLOOD COAGUL FIBRIN JI Blood Coagul. Fibrinolysis PD JAN PY 2008 VL 19 IS 1 BP 55 EP 59 PG 5 WC Hematology SC Hematology GA 258AY UT WOS:000252842000010 PM 18180616 ER PT J AU Chauhan, D Bianchi, G Anderson, KC AF Chauhan, Dharminder Bianchi, Giada Anderson, Kenneth C. TI Targeting the UPS as therapy in multiple myeloma SO BMC BIOCHEMISTRY LA English DT Review ID NF-KAPPA-B; PROTEASOME INHIBITOR PS-341; MARROW STROMAL CELLS; PEGYLATED LIPOSOMAL DOXORUBICIN; DEPENDENT PROTEOLYTIC SYSTEM; MOLECULAR-WEIGHT PROTEASES; PANCREATIC-CANCER CELLS; RESISTANCE CAM-DR; GROWTH IN-VIVO; BONE-MARROW AB The coordinated regulation of cellular protein synthesis and degradation is essential for normal cellular functioning. The ubiquitin proteasome system mediates the intracellular protein degradation that is required for normal cellular homeostasis. The 26S proteasome is a multienzyme protease that degrades redundant proteins; conversely, inhibition of proteasomal degradation results in intracellular aggregation of unwanted proteins and cell death. This observation led to the development of proteasome inhibitors as therapeutics for use in cancer. The clinical applicability of targeting proteasomes is exemplified by the recent FDA approval of the first proteasome inhibitor, bortezomib, for the treatment of relapsed/ refractory multiple myeloma. Although bortezomib represents a major advance in the treatment of this disease, it can be associated with toxicity and the development of drug resistance. Importantly, extensive preclinical studies suggest that combination therapies can both circumvent drug resistance and reduce toxicity. In addition, promising novel proteasome inhibitors, which are distinct from bortezomib, and exhibit equipotent anti-multiple myeloma activities, are undergoing clinical evaluation in order to improve patient outcome in multiple myeloma. Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com). C1 [Chauhan, Dharminder; Bianchi, Giada; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. RP Chauhan, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. EM Dharminder_Chauhan@dfci.harvard.edu; kenneth_anderson@dfci.harvard.edu FU NIH [CA 50947, CA 78373, CA100707-01]; Doris Duke Distinguished Clinical Research Scientist Award; The Cure for Myeloma Fund FX This research study was supported by: NIH grants CA 50947, CA 78373, CA100707-01, a Doris Duke Distinguished Clinical Research Scientist Award (KCA), and The Cure for Myeloma Fund. NR 110 TC 28 Z9 28 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2091 J9 BMC BIOCHEM JI BMC Boichem. PY 2008 VL 9 SU 1 AR S1 DI 10.1186/1471-2091-9-S1-S1 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 415QP UT WOS:000263949700001 PM 19007431 ER PT J AU Lin, HH Zhang, GL Tongchusak, S Reinherz, EL Brusic, V AF Lin, Hong Huang Zhang, Guang Lan Tongchusak, Songsak Reinherz, Ellis L. Brusic, Vladimir TI Evaluation of MHC-II peptide binding prediction servers: applications for vaccine research SO BMC BIOINFORMATICS LA English DT Article CT 7th International Conference on Bioinformatics (InCoB2008) CY OCT 20-23, 2008 CL Taipei, TAIWAN ID T-CELL EPITOPES; HLA-DR; THYROGLOBULIN PEPTIDES; MOLECULES; SEQUENCE; CD4(+); GENERATION; COMPLEXES; MATRIX; CONFORMATIONS AB Background: Initiation and regulation of immune responses in humans involves recognition of peptides presented by human leukocyte antigen class II (HLA-II) molecules. These peptides (HLA-II T-cell epitopes) are increasingly important as research targets for the development of vaccines and immunotherapies. HLA-II peptide binding studies involve multiple overlapping peptides spanning individual antigens, as well as complete viral proteomes. Antigen variation in pathogens and tumor antigens, and extensive polymorphism of HLA molecules increase the number of targets for screening studies. Experimental screening methods are expensive and time consuming and reagents are not readily available for many of the HLA class II molecules. Computational prediction methods complement experimental studies, minimize the number of validation experiments, and significantly speed up the epitope mapping process. We collected test data from four independent studies that involved 721 peptide binding assays. Full overlapping studies of four antigens identified binding affinity of 103 peptides to seven common HLA-DR molecules (DRB1*0101, 0301, 0401, 0701, 1101, 1301, and 1501). We used these data to analyze performance of 21 HLA-II binding prediction servers accessible through the WWW. Results: Because not all servers have predictors for all tested HLA-II molecules, we assessed a total of 113 predictors. The length of test peptides ranged from 15 to 19 amino acids. We tried three prediction strategies - the best 9-mer within the longer peptide, the average of best three 9-mer predictions, and the average of all 9-mer predictions within the longer peptide. The best strategy was the identification of a single best 9-mer within the longer peptide. Overall, measured by the receiver operating characteristic method (A(ROC)), 17 predictors showed good (A(ROC) > 0.8), 41 showed marginal (A(ROC) > 0.7), and 55 showed poor performance (A(ROC) < 0.7). Good performance predictors included HLA-DRB1*0101 (seven), 1101 (six), 0401 (three), and 0701 (one). The best individual predictor was NETMHCIIPAN, closely followed by PROPRED, IEDB (Consensus), and MULTIPRED (SVM). None of the individual predictors was shown to be suitable for prediction of promiscuous peptides. Current predictive capabilities allow prediction of only 50% of actual T-cell epitopes using practical thresholds. Conclusion: The available HLA-II servers do not match prediction capabilities of HLA-I predictors. Currently available HLA-II prediction servers offer only a limited prediction accuracy and the development of improved predictors is needed for large-scale studies, such as proteomewide epitope mapping. The requirements for accuracy of HLA-II binding predictions are stringent because of the substantial effect of false positives. C1 [Lin, Hong Huang; Zhang, Guang Lan; Tongchusak, Songsak; Reinherz, Ellis L.; Brusic, Vladimir] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02215 USA. [Brusic, Vladimir] Univ Queensland, Sch Land Crop & Food Sci, Brisbane, Qld, Australia. RP Brusic, V (reprint author), Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02215 USA. EM Honghuang_Lin@dfci.harvard.edu; Guanglan_Zhang@dfci.harvard.edu; Songsak_Tongchusak@dfci.harvard.edu; Ellis_Reinherz@dfci.harvard.edu; vladimir_brusic@dfci.harvard.edu OI Lin, Honghuang/0000-0003-3043-3942 FU NIAID NIH HHS [U19 AI57330] NR 71 TC 114 Z9 116 U1 0 U2 10 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 PY 2008 VL 9 AR S22 DI 10.1186/1471-2105-9-S12-S22 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 390HG UT WOS:000262154300022 PM 19091022 ER PT J AU Miotto, O Tan, TW Brusic, V AF Miotto, Olivo Tan, Tin Wee Brusic, Vladimir TI Rule-based knowledge aggregation for large-scale protein sequence analysis of influenza A viruses SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 6th International Conference on Bioinformatics (InCoB2007) CY AUG 27-30, 2007 CL Hong Kong, PEOPLES R CHINA ID SEMANTIC WEB; BIOLOGY; GENBANK AB Background: The explosive growth of biological data provides opportunities for new statistical and comparative analyses of large information sets, such as alignments comprising tens of thousands of sequences. In such studies, sequence annotations frequently play an essential role, and reliable results depend on metadata quality. However, the semantic heterogeneity and annotation inconsistencies in biological databases greatly increase the complexity of aggregating and cleaning metadata. Manual curation of datasets, traditionally favoured by life scientists, is impractical for studies involving thousands of records. In this study, we investigate quality issues that affect major public databases, and quantify the effectiveness of an automated metadata extraction approach that combines structural and semantic rules. We applied this approach to more than 90,000 influenza A records, to annotate sequences with protein name, virus subtype, isolate, host, geographic origin, and year of isolation. Results: Over 40,000 annotated Influenza A protein sequences were collected by combining information from more than 90,000 documents from NCBI public databases. Metadata values were automatically extracted, aggregated and reconciled from several document fields by applying user-defined structural rules. For each property, values were recovered from >= 88.8% of records, with accuracy exceeding 96% in most cases. Because of semantic heterogeneity, each property required up to six different structural rules to be combined. Significant quality differences between databases were found: GenBank documents yield values more reliably than documents extracted from GenPept. Using a simple set of semantic rules and a reasoner, we reconstructed relationships between sequences from the same isolate, thus identifying 7640 isolates. Validation of isolate metadata against a simple ontology highlighted more than 400 inconsistencies, leading to over 3,000 property value corrections. Conclusion: To overcome the quality issues inherent in public databases, automated knowledge aggregation with embedded intelligence is needed for large-scale analyses. Our results show that user-controlled intuitive approaches, based on combination of simple rules, can reliably automate various curation tasks, reducing the need for manual corrections to approximately 5% of the records. Emerging semantic technologies possess desirable features to support today's knowledge aggregation tasks, with a potential to bring immediate benefits to this field. C1 [Miotto, Olivo] Natl Univ Singapore, Inst Syst Sci, Singapore 117548, Singapore. [Miotto, Olivo; Tan, Tin Wee] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117548, Singapore. [Brusic, Vladimir] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Brusic, Vladimir] Univ Queensland, Sch Land Crop & Food Sci, Brisbane, Qld 4072, Australia. RP Miotto, O (reprint author), Natl Univ Singapore, Inst Syst Sci, 25 Heng Mui Keng Terrace, Singapore 117548, Singapore. EM olivo@nus.edu.sg; tinwee@bic.nus.edu.sg; vladimir_brusic@dfci.harvard.edu RI Tan, Tin Wee/B-8963-2009; OI Tan, Tin Wee/0000-0002-4062-2854; Miotto, Olivo/0000-0001-8060-6771 FU NIAID NIH HHS [U19 AI056541, 5 U19 AI56541]; PHS HHS [HHSN2662-00400085C] NR 24 TC 7 Z9 8 U1 0 U2 7 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 PY 2008 VL 9 SU 1 AR S7 DI 10.1186/1471-2105-9-S1-S7 PG 14 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 345UN UT WOS:000259022700007 PM 18315860 ER PT J AU Miotto, O Heiny, AT Tan, TW August, JT Brusic, V AF Miotto, Olivo Heiny, A. T. Tan, Tin Wee August, J. Thomas Brusic, Vladimir TI Identification of human-to-human transmissibility factors in PB2 proteins of influenza A by large-scale mutual information analysis SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 6th International Conference on Bioinformatics (InCoB2007) CY AUG 27-30, 2007 CL Hong Kong, PEOPLES R CHINA ID HOST-RANGE RESTRICTION; MATHEMATICAL-THEORY; RNA-POLYMERASE; CAP-BINDING; HONG-KONG; VIRUS; VIRULENCE; COMMUNICATION; CONSERVATION; EVOLUTION AB Background: The identification of mutations that confer unique properties to a pathogen, such as host range, is of fundamental importance in the fight against disease. This paper describes a novel method for identifying amino acid sites that distinguish specific sets of protein sequences, by comparative analysis of matched alignments. The use of mutual information to identify distinctive residues responsible for functional variants makes this approach highly suitable for analyzing large sets of sequences. To support mutual information analysis, we developed the AVANA software, which utilizes sequence annotations to select sets for comparison, according to user-specified criteria. The method presented was applied to an analysis of influenza A PB2 protein sequences, with the objective of identifying the components of adaptation to human-to-human transmission, and reconstructing the mutation history of these components. Results: We compared over 3,000 PB2 protein sequences of human-transmissible and avian isolates, to produce a catalogue of sites involved in adaptation to human-to-human transmission. This analysis identified 17 characteristic sites, five of which have been present in human-transmissible strains since the 1918 Spanish flu pandemic. Sixteen of these sites are located in functional domains, suggesting they may play functional roles in host-range specificity. The catalogue of characteristic sites was used to derive sequence signatures from historical isolates. These signatures, arranged in chronological order, reveal an evolutionary timeline for the adaptation of the PB2 protein to human hosts. Conclusion: By providing the most complete elucidation to date of the functional components participating in PB2 protein adaptation to humans, this study demonstrates that mutual information is a powerful tool for comparative characterization of sequence sets. In addition to confirming previously reported findings, several novel characteristic sites within PB2 are reported. Sequence signatures generated using the characteristic sites catalogue characterize concisely the adaptation characteristics of individual isolates. Evolutionary timelines derived from signatures of early human influenza isolates suggest that characteristic variants emerged rapidly, and remained remarkably stable through subsequent pandemics. In addition, the signatures of human-infecting H5N1 isolates suggest that this avian subtype has low pandemic potential at present, although it presents more human adaptation components than most avian subtypes. C1 [Miotto, Olivo; Heiny, A. T.; Tan, Tin Wee] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117595, Singapore. [Miotto, Olivo] Natl Univ Singapore, Inst Syst Sci, Singapore 117595, Singapore. [August, J. Thomas] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. [Brusic, Vladimir] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Brusic, Vladimir] Univ Queensland, Sch Land Food & Crop Sci, Brisbane, Qld 4072, Australia. RP Miotto, O (reprint author), Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, 8 Med Dr, Singapore 117595, Singapore. EM olivo@nus.edu.sg; heiny@nus.edu.sg; tinwee@bic.nus.edu.sg; taugust@jhmi.edu; vladimir_brusic@dfci.harvard.edu RI Tan, Tin Wee/B-8963-2009; OI Tan, Tin Wee/0000-0002-4062-2854; Miotto, Olivo/0000-0001-8060-6771 FU NIAID NIH HHS [5 U19 AI56541, U19 AI056541]; PHS HHS [HHSN2662-00400085C] NR 46 TC 41 Z9 42 U1 2 U2 17 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 PY 2008 VL 9 SU 1 AR S18 DI 10.1186/1471-2105-9-S1-S18 PG 18 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 345UN UT WOS:000259022700018 PM 18315849 ER PT J AU Zhang, GL Khan, AM Srinivasan, KN Heiny, AT Lee, KX Kwoh, CK August, JT Brusic, V AF Zhang, Guang Lan Khan, Asif M. Srinivasan, Kellathur N. Heiny, A. T. Lee, K. X. Kwoh, Chee Keong August, J. Thomas Brusic, Vladimir TI Hotspot Hunter: a computational system for large-scale screening and selection of candidate immunological hotspots in pathogen proteomes SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 6th International Conference on Bioinformatics (InCoB2007) CY AUG 27-30, 2007 CL Hong Kong, PEOPLES R CHINA ID MHC CLASS-I; T-CELL EPITOPES; BINDING PEPTIDES; PROTEASOMAL CLEAVAGE; TAP TRANSPORT; HIV ENVELOPE; HLA-A; PREDICTION; MOLECULES; DATABASE AB Background: T-cell epitopes that promiscuously bind to multiple alleles of a human leukocyte antigen (HLA) supertype are prime targets for development of vaccines and immunotherapies because they are relevant to a large proportion of the human population. The presence of clusters of promiscuous T-cell epitopes, immunological hotspots, has been observed in several antigens. These clusters may be exploited to facilitate the development of epitope-based vaccines by selecting a small number of hotspots that can elicit all of the required T-cell activation functions. Given the large size of pathogen proteomes, including of variant strains, computational tools are necessary for automated screening and selection of immunological hotspots. Results: Hotspot Hunter is a web-based computational system for large-scale screening and selection of candidate immunological hotspots in pathogen proteomes through analysis of antigenic diversity. It allows screening and selection of hotspots specific to four common HLA supertypes, namely HLA class I A2, A3, B7 and class II DR. The system uses Artificial Neural Network and Support Vector Machine methods as predictive engines. Soft computing principles were employed to integrate the prediction results produced by both methods for robust prediction performance. Experimental validation of the predictions showed that Hotspot Hunter can successfully identify majority of the real hotspots. Users can predict hotspots from a single protein sequence, or from a set of aligned protein sequences representing pathogen proteome. The latter feature provides a global view of the localizations of the hotspots in the proteome set, enabling analysis of antigenic diversity and shift of hotspots across protein variants. The system also allows the integration of prediction results of the four supertypes for identification of hotspots common across multiple supertypes. The target selection feature of the system shortlists candidate peptide hotspots for the formulation of an epitope-based vaccine that could be effective against multiple variants of the pathogen and applicable to a large proportion of the human population. Conclusion: Hotspot Hunter is publicly accessible at http://antigen.i2r.a-star.edu.sg/hh/. It is a new generation computational tool aiding in epitope-based vaccine design. C1 [Zhang, Guang Lan] Inst Infocomm Res, Singapore 119613, Singapore. [Zhang, Guang Lan; Kwoh, Chee Keong] Nanyang Technol Univ, Sch Comp Engn, Singapore 639798, Singapore. [Khan, Asif M.; Heiny, A. T.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117597, Singapore. [Khan, Asif M.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Microbiol, Singapore 117597, Singapore. [Srinivasan, Kellathur N.; August, J. Thomas] Johns Hopkins Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. [Srinivasan, Kellathur N.] Hlth Sci Author, Ctr Drug Adm, Prod Evaluat & Registrat Div, Singapore 138667, Singapore. [Brusic, Vladimir] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Brusic, Vladimir] Univ Queensland, Sch Land Crop & Food Sci, Brisbane, Qld 4072, Australia. RP Zhang, GL (reprint author), Inst Infocomm Res, 21 Heng Mui Keng Terrace, Singapore 119613, Singapore. EM guanglanzhang@gmail.com; asifkhan@bic.nus.edu.sg; kellathur_srinivasan@hsa.gov.sg; heiny@nus.edu.sg; leexunjian@gmail.com; asckkwoh@ntu.edu.sg; taugust@jhmi.edu; vladimir_brusic@dfci.harvard.edu RI Khan, Mohammad Asif/F-4663-2010 OI Khan, Mohammad Asif/0000-0001-9202-279X FU NIAID NIH HHS [5 U19 AI56541, U19 AI056541]; PHS HHS [HHSN2662-00400085C] NR 50 TC 18 Z9 18 U1 0 U2 6 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 PY 2008 VL 9 SU 1 AR S19 DI 10.1186/1471-2105-9-S1-S19 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 345UN UT WOS:000259022700019 PM 18315850 ER PT J AU Yang, JY Niemierko, A Yang, MQ Deng, YP AF Yang, Jack Y. Niemierko, Andrzej Yang, Mary Qu Deng, Youping TI Analyzing adjuvant radiotherapy suggests a non monotonic radio-sensitivity over tumor volumes SO BMC GENOMICS LA English DT Article AB Background: Adjuvant Radiotherapy (RT) after surgical removal of tumors proved beneficial in long-term tumor control and treatment planning. For many years, it has been well concluded that radio-sensitivities of tumors upon radiotherapy decrease according to the sizes of tumors and RT models based on Poisson statistics have been used extensively to validate clinical data. Results: We found that Poisson statistics on RT is actually derived from bacterial cells despite of many validations from clinical data. However cancerous cells do have abnormal cellular communications and use chemical messengers to signal both surrounding normal and cancerous cells to develop new blood vessels and to invade, to metastasis and to overcome intercellular spatial confinements in general. We therefore investigated the cell killing effects on adjuvant RT and found that radio-sensitivity is actually not a monotonic function of volume as it was believed before. We present detailed analysis and explanation to justify above statement. Based on EUD, we present an equivalent radio-sensitivity model. Conclusion: We conclude that radio sensitivity is a sophisticated function over tumor volumes, since tumor responses upon radio therapy also depend on cellular communications. C1 [Yang, Jack Y.; Niemierko, Andrzej] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Yang, Jack Y.; Niemierko, Andrzej] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Yang, Mary Qu] Natl Human Genome Res Inst, Natl Inst Hlth, Bethesda, MD 20852 USA. [Deng, Youping] Univ So Mississippi, Dept Biol Sci, Bioinformat & Canc Biol Lab, Hattiesburg, MS 39406 USA. RP Niemierko, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM jyang@bwh.harvard.edu; aniemierko@partners.org; yangma@mail.NIH.gov; youping.deng@usm.edu FU NCI NIH HHS [R01 CA50628, R01 CA050628] NR 16 TC 2 Z9 3 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PY 2008 VL 9 SU 2 AR S9 DI 10.1186/1471-2164-9-S2-S9 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V92JQ UT WOS:000206244200010 PM 18831800 ER PT J AU Keller, C Katz, R Cushman, M Fried, LF Shlipak, M AF Keller, Christopher Katz, Ronit Cushman, Mary Fried, Linda F. Shlipak, Michael TI Association of kidney function with inflammatory and procoagulant markers in a diverse cohort: A cross-sectional analysis from the Multi-Ethnic Study of Atherosclerosis (MESA) SO BMC NEPHROLOGY LA English DT Article AB Background: Prior studies using creatinine-based estimated glomerular filtration rate (eGFR) have found limited associations between kidney function and markers of inflammation. Using eGFR and cystatin C, a novel marker of kidney function, the authors investigated the association of kidney function with multiple biomarkers in a diverse cohort. Methods: The Multi-Ethnic Study of Atherosclerosis consists of 6,814 participants of white, African-American, Hispanic, and Chinese descent, enrolled from 2000-2002 from six U. S. communities. Measurements at the enrollment visit included serum creatinine, cystatin C, and six inflammatory and procoagulant biomarkers. Creatinine-based eGFR was estimated using the four-variable Modification of Diet in Renal Disease equation, and chronic kidney disease was defined by an eGFR < 60 mL/min/1.73 m(2). Results: Adjusted partial correlations between cystatin C and all biomarkers were statistically significant: C-reactive protein (r = 0.08), interleukin-6 (r = 0.16), tumor necrosis factor-alpha soluble receptor 1 (TNF-alpha R1; r = 0.75), intercellular adhesion molecule-1 (r = 0.21), fibrinogen (r = 0.14), and factor VIII (r = 0.11; two-sided p < 0.01 for all). In participants without chronic kidney disease, higher creatinine-based eGFR was associated only with higher TNF-alpha R1 levels. Conclusion: In a cohort characterized by ethnic diversity, cystatin C was directly associated with multiple procoagulant and inflammatory markers. Creatinine-based eGFR had similar associations with these biomarkers among subjects with chronic kidney disease. C1 [Keller, Christopher] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Keller, Christopher; Shlipak, Michael] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. [Katz, Ronit] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA. [Cushman, Mary] Univ Vermont, Dept Med, Burlington, VT USA. [Cushman, Mary] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. [Fried, Linda F.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. RP Keller, C (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. EM Christopher.Keller@ucsf.edu; RKatz@u.washington.edu; Mary.Cushman@uvm.edu; Linda.Fried@va.gov; Michael.Shlipak@ucsf.edu FU National Kidney Foundation; American Heart Association; National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-95159, N01-HC-95169]; [R01 DK066488-01] FX Dr. Keller is funded through a fellowship grant from the National Kidney Foundation. Dr. Shlipak is funded by R01 DK066488-01, as well as by the American Heart Association Established Investigator Award. This research was also supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute (NHLBI). Cystatin C measurements were donated to the NHLBI by Dade Behring Inc., Deer-field, IL. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. NR 33 TC 54 Z9 56 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2369 J9 BMC NEPHROL JI BMC Nephrol. PY 2008 VL 9 AR 9 DI 10.1186/1471-2369-9-9 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA V13KC UT WOS:000207664700009 PM 18681974 ER PT J AU Cho, K Demissie, S Dupuis, J Cupples, LA Kathiresan, S Beck, TJ Karasik, D Kiel, DP AF Cho, K. Demissie, S. Dupuis, J. Cupples, L. A. Kathiresan, S. Beck, T. J. Karasik, D. Kiel, D. P. TI Polymorphisms in the endothelial nitric oxide synthase gene and bone density/ultrasound and geometry in humans SO BONE LA English DT Article DE nitric oxide synthase; bone density/ultrasound; bone geometry; genetic polymorphisms; osteoporosis ID QUANTITATIVE TRAIT LOCI; MINERAL DENSITY; FRAMINGHAM OSTEOPOROSIS; PHYSICAL-ACTIVITY; GENOME SCREEN; FEMORAL-NECK; BLOOD-FLOW; FRACTURES; MASS; WOMEN AB Nitric oxide (NO), produced by endothelial cells, is a signaling molecule synthesized from L-arginine by nitric oxide synthases (NOS). NO is known to reduce the ratio of receptor activator of nuclear factor KappaB (RANKL)/osteoprotegerin (OPG), leading to decreased osteoclastogenesis and a reduction in bone resorption. Endothelial nitric oxide synthase (eNOS or NOS3) is the predominant constitutive isoform of nitric NOS within bone. Recently, a NOS3 polymorphism, Glu298Asp, previously implicated in osteoporosis, failed to demonstrate an association with bone mineral density (BMD), although there was some indication of an association with selected geometry indices. Since a single polymorphism does not capture all of the potential variants in a given gene, we investigated a broader coverage of the NOS3 gene with bone density/ultrasound and geometry indices in a sample of unrelated individuals from the Framingham Offspring Study. Our results indicated that the Glu298Asp polymorphism was not associated with BMD but suggested some haplotype-based associations in the linkage disequilibrium (LD) region that included the Glu298Asp polymorphism with several geometry indices. Although our findings exhibited several associations with selected bone density/ultrasound and geometry indices, the nominally significant associations are regarded as primarily hypothesis generating and suggest that replication in other samples is needed. Thus, NOS3 genetic variation does not appear to be a major contributor to adult bone density/ ultrasound and geometry in our sample. (C) 2007 Elsevier Inc. All rights reserved. C1 [Cho, K.; Demissie, S.; Dupuis, J.; Cupples, L. A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Kathiresan, S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Kathiresan, S.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Kathiresan, S.] Harvard Univ, Cambridge, MA 02138 USA. [Beck, T. J.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. [Karasik, D.; Kiel, D. P.] Hebrew SeniorLife, Inst Aging Res, Boston, MA USA. RP Cho, K (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, 715 Albany St,T4E, Boston, MA 02118 USA. EM kellycho@bu.edu OI Cupples, L. Adrienne/0000-0003-0273-7965; Dupuis, Josee/0000-0003-2871-3603; Kiel, Douglas/0000-0001-8474-0310; Karasik, David/0000-0002-8826-0530 FU NCRR NIH HHS [1S10RR163736-01A1]; NHLBI NIH HHS [N01-HC-25195, N01HC25195]; NIA NIH HHS [R01-AR/AG 41398]; NIAMS NIH HHS [R01 AR041398, R01 AR041398-11A2, R01 AR050066, R01 AR050066-01, R01-AR050066] NR 44 TC 9 Z9 9 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD JAN PY 2008 VL 42 IS 1 BP 53 EP 60 DI 10.1016/j.bone.2007.09.051 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 253KW UT WOS:000252518100007 PM 17980690 ER PT J AU Eriksson, AL Mellstrom, D Lorentzon, M Orwoll, ES Redlund-Johnell, I Grundberg, E Holmberg, A Ljunggren, O Karlsson, MK Ohlsson, C AF Eriksson, Anna L. Mellstrom, Dan Lorentzon, Mattias Orwoll, Eric S. Redlund-Johnell, Inga Grundberg, Elin Holmberg, Anna Ljunggren, Osten Karlsson, Magnus K. Ohlsson, Claes TI The COMT val158met polymorphism is associated with prevalent fractures in Swedish men SO BONE LA English DT Article DE fracture; polymorphism; COMT; men; estrogen ID CATECHOL-O-METHYLTRANSFERASE; BONE-MINERAL DENSITY; ELDERLY-MEN; FREE TESTOSTERONE; OSTEOPOROTIC FRACTURES; PHYSICAL-ACTIVITY; BODY-COMPOSITION; RISK-FACTORS; SELF-REPORT; WOMEN AB Introduction: Sex steroids are important for growth and maintenance of the skeleton. Catechol-O-methyltransferase (COMT) is an estrogen degrading enzyme. The COMT val158met polymorphism results in a 60-75% difference in enzyme activity between the val (high activity=H) and met (low activity=L) variants. We have previously reported that this polymorphism is associated with bone mineral density (BMD) in young men. The aim of this study was to investigate associations between COMT val158met, BMD and fractures in elderly men. Methods: Population-based study of Swedish men 75.4, SD 3.2, years of age. Fractures were reported using standardized questionnaires. Fracture and genotype data were available from 2822 individuals. Results: Total number of individuals with self-reported fracture was 989 (35.0%). Prevalence of >= 1 fracture was 37.2% in COMTLL, 35.7% in COMTHL and 30.4% in COMTHH (p<0.05). Early fractures (<= 50 years of age) were less common in COMTHH than in the combined COMTLL+HL genotype, OR 0.78 (95% CI 0.63-0.97). No associations were found for late fractures (>50 years of age). The OR for fracture of the non-weight bearing skeleton in COMTHH compared with COMTLL+HL was 0.74 (95% CI 0.59-0.92). No associations between COMT val158met and BMD were found in this cohort of elderly men. Conclusions: The COMT val158met polymorphism is associated with life time fracture prevalence in elderly Swedish men. This association is mainly driven by early fractures (<= 50 years of age). (C) 2007 Elsevier Inc. All rights reserved. C1 [Eriksson, Anna L.; Mellstrom, Dan; Lorentzon, Mattias; Ohlsson, Claes] Gothenburg Univ, Sahlgrenska Acad, Dept Internal Med, Ctr Bone Res,Div Clin Pharmacol, SE-41345 Gothenburg, Sweden. [Eriksson, Anna L.; Mellstrom, Dan; Lorentzon, Mattias; Ohlsson, Claes] Gothenburg Univ, Sahlgrenska Acad, Dept Geriatr, Ctr Bone Res, SE-41345 Gothenburg, Sweden. [Redlund-Johnell, Inga] Lund Univ, Dept Radiol, Lund, Sweden. [Orwoll, Eric S.] Oregon Hlth & Sci Univ, Bone & Mineral Res Unit, Portland, OR 97201 USA. [Orwoll, Eric S.] Portland VA Med Ctr, Portland, OR USA. [Grundberg, Elin; Ljunggren, Osten] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Holmberg, Anna] Malmo Univ Hosp, Dept Orthopaed, Malmo, Sweden. [Karlsson, Magnus K.] Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, Lund, Sweden. RP Eriksson, AL (reprint author), Gothenburg Univ, Sahlgrenska Acad, Dept Internal Med, Ctr Bone Res,Div Clin Pharmacol, Vita Straket 11, SE-41345 Gothenburg, Sweden. EM anna.eriksson@pharm.gu.se OI Orwoll, Eric/0000-0002-8520-7355 NR 48 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD JAN PY 2008 VL 42 IS 1 BP 107 EP 112 DI 10.1016/j.bone.2007.08.045 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 253KW UT WOS:000252518100014 PM 17962094 ER PT J AU Battaglino, RA Pham, L Morse, LR Vokes, M Sharma, A Odgren, PR Yang, M Sasaki, H Stashenko, P AF Battaglino, R. A. Pham, L. Morse, L. R. Vokes, M. Sharma, A. Odgren, P. R. Yang, M. Sasaki, H. Stashenko, P. TI NHA-oc/NHA2: A mitochondrial cation-proton antiporter selectively expressed in osteoclasts SO BONE LA English DT Article DE osteoclast; mitochondria; sodium; proton; antiporter ID PROTEIN STRUCTURE PREDICTION; RAT-LIVER MITOCHONDRIA; NA+/H+ EXCHANGER; GENE FAMILY; APOPTOSIS; PHOSPHORYLATION; DIFFERENTIATION; MIP-1-GAMMA; TOPOLOGY; SURVIVAL AB Bone resorption is regulated by a complex system of hormones and cytokines that cause osteoblasts/stromal cells and lymphocytes to produce factors including RANKL, that ultimately result in the differentiation and activation of osteoclasts, the bone resorbing cells. We used a microarray approach to identify genes upregulated in RANKL-stimulated osteoclast precursor cells. Osteoclast expression was confirmed by multiple tissue Northern and in situ hybridization analysis. Gene function studies were carried out by siRNA analysis. We identified a novel gene, which we termed nha-oc/NHA2, which is strongly upregulated during RANK-L-induced osteoclast differentiation in vitro and in vivo. nha-oc/NHA2 encodes a novel cation-proton antiporter (CPA) and is the mouse orthologue of a human gene identified in a database search: HsNHA2. nha-oc/NHA2 is selectively expressed in osteoclasts. NHA-oc/NHA2 protein localizes to the mitochondria, where it mediates Na+-dependent changes in mitochondrial pH and Na+ acetate induced mitochondrial passive swelling. RNA silencing of nha-oc/nha2 reduces osteoclast differentiation and resorption, suggesting a role for NHA-oc/NHA2 in these processes. nha-oc/NHA2 therefore is a novel member of the CPA family and is the first mitochondrial NHA characterized to date. nha-oc/NHA2 is also unique in that it is the first eukaryotic and tissue-specific CPA2 characterized to date. NHA-oc/NHA2 displays the expected activities of a bona fide CPA and plays a key role(s) in normal osteoclast differentiation and function. (C) 2007 Elsevier Inc. All rights reserved. C1 [Battaglino, R. A.; Pham, L.; Vokes, M.; Sharma, A.; Sasaki, H.; Stashenko, P.] Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. [Morse, L. R.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Odgren, P. R.; Yang, M.] Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01655 USA. RP Battaglino, RA (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM rbattaglino@forsyth.org RI battaglino, ricardo/D-2892-2015; Morse, Leslie/C-9442-2015 OI Morse, Leslie/0000-0002-7426-6341 FU NIDCR NIH HHS [R01 DE007378, R01 DE007378-18] NR 38 TC 17 Z9 21 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD JAN PY 2008 VL 42 IS 1 BP 180 EP 192 DI 10.1016/j.bone.2007.09.046 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 253KW UT WOS:000252518100021 PM 17988971 ER PT J AU Nakamura, M Nestor, PG Levitt, JJ Cohen, AS Kawashima, T Shenton, ME McCarley, RW AF Nakamura, Motoaki Nestor, Paul G. Levitt, James J. Cohen, Adam S. Kawashima, Toshiro Shenton, Martha E. McCarley, Robert W. TI Orbitofrontal volume deficit in schizophrenia and thought disorder SO BRAIN LA English DT Article DE schizophrenia; orbitofrontal region; thought disorder; decision making; Iowa gambling task ID MEDIAL PREFRONTAL CORTEX; VOXEL-BASED MORPHOMETRY; MRI-BASED PARCELLATION; DECISION-MAKING; 1ST-EPISODE SCHIZOPHRENIA; DOUBLE DISSOCIATION; FRONTAL-CORTEX; BRAIN; MORPHOLOGY; REGIONS AB Orbitofrontal Cortex (OFC) structural abnormality in schizophrenia has not been well characterized, probably due to marked anatomical variability and lack of consistent definitions. We previously reported OFC sulcogyral pattern alteration and its associations with social disturbance in schizophrenia, but OFC volume associations with psychopathology and cognition have not been investigated. We compared chronically treated schizophrenia patients with healthy control (HC) subjects, using a novel, reliable parcellation of OFC subregions and their association with cognition, especially the Iowa Gambling Task (IGT), and with schizophrenic psychopathology including thought disorder. Twenty-four patients with schizophrenia and 25 age-matched HC subjects underwent MRI. OFC Regions of Interest (ROI) were manually delineated according to anatomical boundaries: Gyrus Rectus (GR); Middle Orbital Gyrus (MiOG); and Lateral Orbital Gyrus (LOG). The OFC sulcogyral pattern was also classified. Additionally, MiOG probability maps were created and compared between groups in a voxel-wise manner. Both groups underwent cognitive evaluations using the IGT, Wisconsin Card Sorting Test, and Trail Making Test (TMT). An 11 bilaterally smaller MiOG volume was observed in schizophrenia, compared with HC (F-1,F-47 = 17.4, P = 0.0001). GR and LOG did not differ, although GR showed a rightward asymmetry in both groups (F-1,F-47 = 19.2, P < 0.0001). The smaller MiOG volume was independent of the OFC sulcogyral pattern, which differed in schizophrenia and HC ( chi(2) = 12.49, P = 0.002). A comparison of MiOG probability maps suggested that the anterior heteromodal region was more affected in the schizophrenia group than the posterior paralimbic region. In the schizophrenia group, a smaller left MiOG was strongly associated with worse positive formal thought disorder (r = -0.638, P = 0.001), and a smaller right MiOG with a longer duration of the illness (r = -0.618, P = 0.002). While schizophrenics showed poorer performance than HC in the IGT, performance was not correlated with OFC volume. However, within the HC group, the larger the right hemisphere MiOG volume, the better the performance in the IGT (r = 0.541, P = 0.005), and the larger the left hemisphere volume, the faster the switching attention performance for the TMT, Trails B (r = -0.608, P = 0.003). The present study, applying a new anatomical parcellation method, demonstrated a subregion-specific OFC grey matter volume deficit in patients with schizophrenia, which was independent of OFC sulcogyral pattern. This volume deficit was associated with a longer duration of illness and greater formal thought disorder. In HC the finding of a quantitative association between OFC volume and IGT performance constitutes, to our knowledge, the first report of this association. C1 [Nakamura, Motoaki; Nestor, Paul G.; Levitt, James J.; Kawashima, Toshiro; Shenton, Martha E.; McCarley, Robert W.] Harvard Med Sch, Veterans Affairs Boston Healthcare Syst, Dept Psychiat, Clin Neurosci Div,Brockton Divis,Lab Neurosci, Brockton, MA USA. [Nakamura, Motoaki; Levitt, James J.; Cohen, Adam S.; Kawashima, Toshiro; Shenton, Martha E.] Brigham & Womens Hosp, Harvard Med Sch, Dept Psychiat, Psychiat Neuroimaging Lab, Boston, MA 02115 USA. [Nestor, Paul G.] Univ Massachusetts, Dept Psychol, Boston, MA USA. RP McCarley, RW (reprint author), Harvard Med Sch, Dept Psychiat, VA Boston Healthcare Syst, Brockton Div, Brockton, MA 02301 USA. EM robert_mccarley@hms.harvard.edu RI McCarley, Robert/N-5562-2014; OI McCarley, Robert/0000-0001-5705-7495; Cohen, Adam/0000-0003-2719-3351 FU NIMH NIH HHS [K02 MH 01110, K02 MH001110, K02 MH001110-10, R01 MH 40799, R01 MH 50747, R01 MH040799] NR 66 TC 99 Z9 99 U1 2 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JAN PY 2008 VL 131 BP 180 EP 195 DI 10.1093/brain/awm265 PN 1 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 244KV UT WOS:000251865700015 PM 18056163 ER PT J AU Kalamarides, M Stemmer-Rachamimov, AO Takahashi, M Han, ZY Chareyre, F Niwa-Kawakita, M Black, PM Carroll, RS Giovannini, M AF Kalamarides, Michel Stemmer-Rachamimov, Anat O. Takahashi, Masaya Han, Zhi-Yan Chareyre, Fabrice Niwa-Kawakita, Michiko Black, Peter M. Carroll, Rona S. Giovannini, Marco TI Natural history of meningioma development in mice reveals: A synergy of Nf2 and p16(Ink4a) mutations SO BRAIN PATHOLOGY LA English DT Article ID SYNTHASE BETA-TRACE; ANAPLASTIC MENINGIOMAS; TUMOR SUPPRESSION; MOUSE MODELS; INK4A LOCUS; PROGRESSION; GENE; INACTIVATION; ACTIVATION; EXPRESSION AB Meningiomas account for approximately 30% of all primary central nervous system tumors and are found in half of neurofibromatosis type 2 patients often causing significant morbidity. Although most meningiomas are benign, 10% are classified as atypical or anaplastic, displaying aggressive clinical behavior. Biallelic inactivation of the neurofibromatosis 2 (NF2) tumor suppressor is associated with meningioma formation in all NF2 patients and 60% of sporadic meningiomas. Deletion of the p16(INK4a)/p14(ARF) locus is found in both benign and malignant meningiomas, while mutation of the p53 tumor suppressor gene is uncommon. Previously, we inactivated Nf2 in homozygous conditional knockout mice by adenoviral Cre delivery and showed that Nf2 loss in arachnoid cells is rate-limiting for meningioma formation. Here, we report that additional nullizygosity for p16(Ink4a) increases the frequency of meningioma and meningothelial proliferation in these mice without modifying the tumor grade. In addition, by using magnetic resonance imaging (MRI) to screen a large cohort of mutant mice, we were able to detect meningothelial proliferation and meningioma development opening the way to future studies in which therapeutic interventions can be tested as preclinical assessment of their potential clinical application. C1 [Kalamarides, Michel; Han, Zhi-Yan; Chareyre, Fabrice; Niwa-Kawakita, Michiko; Giovannini, Marco] INSERM, U 674, Paris, France. [Kalamarides, Michel; Han, Zhi-Yan; Chareyre, Fabrice; Niwa-Kawakita, Michiko; Giovannini, Marco] Univ Paris 07, Inst Univ Hematol, Paris, France. [Kalamarides, Michel] Hop Beaujon, AP HP, Serv Neurochirurg, Clichy, France. [Kalamarides, Michel; Stemmer-Rachamimov, Anat O.; Takahashi, Masaya; Han, Zhi-Yan; Chareyre, Fabrice; Niwa-Kawakita, Michiko; Black, Peter M.; Carroll, Rona S.; Giovannini, Marco] Harvard Univ, Sch Med, Boston, MA USA. [Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Mol Neurooncol & Pathol Dept, Boston, MA USA. [Takahashi, Masaya] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Black, Peter M.; Carroll, Rona S.] Harvard Univ, Sch Med, Dept Neurosurg, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Giovannini, M (reprint author), INSERM, U 674, Paris, France. EM marco.giovannini@cephb.fr NR 30 TC 20 Z9 20 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JAN PY 2008 VL 18 IS 1 BP 62 EP 70 DI 10.1111/j.1750-3639.2007.00105.x PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 254LA UT WOS:000252586900007 PM 17924978 ER PT J AU Green, AR AF Green, Alexander R. TI The globalization of cross-cultural medical education and patient-centered care SO BRATISLAVA MEDICAL JOURNAL-BRATISLAVSKE LEKARSKE LISTY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dispar Solut Ctr, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Green, AR (reprint author), Harvard Univ, Sch Med, Dispar Solut Ctr, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 2 TC 1 Z9 1 U1 2 U2 2 PU COMENIUS UNIV PI BRATISLAVA I PA SCH MEDICINE, SPITALSKA 24, BRATISLAVA I, SK-813 72, SLOVAKIA SN 0006-9248 J9 BRATISL MED J JI Bratisl. Med. J. PY 2008 VL 109 IS 5 BP 238 EP 238 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 317ZP UT WOS:000257059500010 PM 18630809 ER PT J AU Razzak, AR Lin, NU Winer, EP AF Razzak, A. Rab Lin, Nancy U. Winer, Eric P. TI Heterogeneity of breast cancer and implications of adjuvant chemotherapy SO BREAST CANCER LA English DT Article DE Adjuvant therapy; Heterogeneity; Breast cancer subtypes AB Historically, in selecting adjuvant chemotherapy for patients with breast cancer, anatomy, including tumor size and nodal status, has played the primary role. As a result of analyses of genomic and clinical data, breast cancers are now thought to be a family of diseases. Major subtypes of breast cancer include HER-2 positive disease, basal-like or triple negative tumors, and at least two types of hormonally sensitive cancers. Using the nomenclature developed in the gene expression array studies, these two types are often referred to as luminal A and luminal B. Estrogen receptor negative tumors relapse earlier than estrogen receptor positive tumors. In general, estrogen receptor negative cancers are also more responsive to chemotherapy. In contrast, estrogen positive tumors appear to be somewhat less responsive to chemotherapy, but endocrine therapy can be of substantial benefit in decreasing the risk of disease recurrence. Women with HER-2 positive disease derive significant benefit with the use of trastuzumab. The role of chemotherapy in preventing disease recurrence in patients with estrogen receptor positive tumors is being reevaluated. Recent data suggests that chemotherapy has the greatest benefit in those patients with estrogen receptor positive cancers whose tumors are HER-2 positive disease, weakly ER positive, and/or have high nuclear grade. In the future, breast cancer treatment will be more targeted to the tumor and tailored to the individual with the use of genomic and clinical data. C1 [Razzak, A. Rab; Lin, Nancy U.; Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM eric_winer@dfci.harvard.edu NR 15 TC 14 Z9 16 U1 0 U2 0 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1340-6868 J9 BREAST CANCER-TOKYO JI Beast Cancer PD JAN PY 2008 VL 15 IS 1 BP 31 EP 34 DI 10.1007/s12282-007-0007-y PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA V13JU UT WOS:000207663900008 PM 18224391 ER PT J AU Cao, DF Polyak, K Halushka, MK Nassar, H Kouprina, N Iacobuzio-Donahue, C Wu, XY Sukumar, S Hicks, J De Marzo, A Argani, P AF Cao, Dengfeng Polyak, Kornelia Halushka, Marc K. Nassar, Hind Kouprina, Nina Iacobuzio-Donahue, Christine Wu, Xinyan Sukumar, Saraswati Hicks, Jessica De Marzo, Angelo Argani, Pedram TI Serial analysis of gene expression of lobular carcinoma in situ identifies down regulation of claudin 4 and overexpression of matrix metalloproteinase 9 SO BREAST CANCER RESEARCH LA English DT Article ID BREAST-CANCER; E-CADHERIN; PANCREATIC-CANCER; DUCTAL CARCINOMA; FOLLOW-UP; HYPERPLASIA; NEOPLASIA; PROTEINS; CELLS; TWIST AB Introduction Although lobular carcinoma in situ (LCIS) has traditionally been viewed as a marker of breast cancer risk, recent clinical, pathological and genetic analyses have supported the concept that LCIS is a low risk, direct precursor of invasive lobular carcinoma. Global gene expression profiling of LCIS has not been performed. Methods We analysed the comprehensive gene expression profile of a unique case of mass-forming LCIS using serial analysis of gene expression (SAGE). This SAGE library is publicly available online. By comparing the gene expression profile of LCIS to that of benign breast epithelium and stroma, we identified several genes up and down regulated in LCIS. Differential expression of selected genes not previously studied in LCIS was validated at the protein level by immunohistochemistry and at the RNA level by quantitative reverse transcriptase PCR (RT-PCR). Results We identified down regulation of claudin 4 and overexpression of matrix metalloproteinase 9 in LCIS relative to normal breast epithelium and stroma. We validated these findings by immunohistochemistry in a separate series of 11 and 19 LCIS cases, respectively. Overexpression of matrix metalloproteinase 9 was further confirmed by quantitative RTPCR analysis of the index case. Conclusions We have created the first global gene expression profile of LCIS, and demonstrated down regulation of cell junction proteins (an expected result) and overexpression of matrix metalloproteinase 9 (an unexpected result). Additional analysis of this data made available as an online resource should facilitate further molecular characterisation of LCIS. C1 [Halushka, Marc K.; Nassar, Hind; Kouprina, Nina; Iacobuzio-Donahue, Christine; Wu, Xinyan; Sukumar, Saraswati; Hicks, Jessica; De Marzo, Angelo; Argani, Pedram] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. [Polyak, Kornelia] Dana Farber Canc Inst, Dept Oncol, Boston, MA 02115 USA. [Cao, Dengfeng] Washington Univ, Dept Pathol, St Louis, MO 63130 USA. [Cao, Dengfeng] Washington Univ, Dept Immunol, St Louis, MO 63130 USA. [Halushka, Marc K.; Nassar, Hind; Kouprina, Nina; Iacobuzio-Donahue, Christine; Wu, Xinyan; Sukumar, Saraswati; Hicks, Jessica; De Marzo, Angelo; Argani, Pedram] Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21205 USA. RP Argani, P (reprint author), Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. EM pargani@jhmi.edu OI Halushka, Marc/0000-0002-7112-7389 FU NIH [SPORE P50 CA88843]; DOD COE [W81XWH-04-1-0595] FX We thank Jie Lu for performing the MMP-2 and MMP-9 immunohistochemistry. We thank Ralph H. Hruban for critically reviewing this manuscript. We acknowledge the support of the NIH SPORE P50 CA88843 and DOD COE W81XWH-04-1-0595. NR 45 TC 13 Z9 14 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2008 VL 10 IS 5 AR R91 DI 10.1186/bcr2189 PG 10 WC Oncology SC Oncology GA 381TO UT WOS:000261559000028 PM 18954444 ER PT J AU Chambers, AF Goss, PE AF Chambers, Ann F. Goss, Paul E. TI Putative growth characteristics of micrometastatic breast cancer SO BREAST CANCER RESEARCH LA English DT Editorial Material ID MAMMARY-CARCINOMA; RANDOMIZED-TRIAL; HAZARD RATES; CELLS; RECURRENCE; THERAPY; MASTECTOMY; TAMOXIFEN; LETROZOLE; DORMANCY AB The fate of cells that disseminate from a primary breast tumour remains poorly understood. Studies of the kinetics of recurrence in breast cancer patients are raising important questions about the biology of the metastatic process. Where do tumour cells reside once they leave the primary tumour, and what factors influence their dormancy and recurrent growth? Clinical data analyses are leading to hypotheses about the biology of metastasis, dormancy and recurrence. A combined clinical and experimental approach to testing these hypotheses will help to clarify this important issue in breast cancer biology and patient care. C1 [Chambers, Ann F.] London Reg Canc Ctr, London, ON N6A 4L6, Canada. [Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Chambers, AF (reprint author), London Reg Canc Ctr, Commissioners Rd E, London, ON N6A 4L6, Canada. EM ann.chambers@Lhsc.on.ca RI Chambers, Ann/L-6285-2015 OI Chambers, Ann/0000-0002-9509-5123 NR 15 TC 9 Z9 9 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2008 VL 10 IS 6 AR 114 DI 10.1186/bcr2197 PG 2 WC Oncology SC Oncology GA 415GS UT WOS:000263922900002 PM 19090969 ER PT J AU Grewal, J Kesari, S AF Grewal, Jai Kesari, Santosh TI Breast cancer surface receptors predict risk for developing brain metastasis and subsequent prognosis SO BREAST CANCER RESEARCH LA English DT Editorial Material ID SURVIVAL; TRASTUZUMAB; SUBTYPES; HER2 C1 [Kesari, Santosh] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol,Div Canc Neurol, Boston, MA 02115 USA. [Grewal, Jai] Long Isl Ctr Brain & Spine Tumors, Great Neck, NY 11021 USA. [Kesari, Santosh] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA. RP Kesari, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol,Div Canc Neurol, Boston, MA 02115 USA. EM skesari@partners.org RI Kesari, Santosh/E-8461-2013 NR 12 TC 4 Z9 5 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2008 VL 10 IS 2 AR 104 DI 10.1186/bcr1868 PG 2 WC Oncology SC Oncology GA 302BJ UT WOS:000255941100002 PM 18373884 ER PT J AU Moulis, S Sgroi, DC AF Moulis, Sharon Sgroi, Dennis C. TI Re-evaluating early breast neoplasia SO BREAST CANCER RESEARCH LA English DT Article ID ATYPICAL DUCTAL HYPERPLASIA; CARCINOMA IN-SITU; COMPARATIVE GENOMIC HYBRIDIZATION; GENE-EXPRESSION PROFILES; HISTOLOGIC GRADE; CANCER; PROGRESSION; TAMOXIFEN; RATIO; HETEROZYGOSITY AB Historically, histomorphological and epidemiological data suggested that atypical ductal hyperplasia and ductal carcinoma in situ are the earliest recognizable neoplastic stages of breast cancer progression. Over the past several years, detailed high-throughput molecular genetic, gene expression and epigenetic analyses have enhanced our understanding of these early neoplastic lesions and have re- shaped our view of human breast cancer progression to include multiple distinct pathways of evolution. C1 [Moulis, Sharon; Sgroi, Dennis C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Mol Pathol Res Unit, Boston, MA 02129 USA. [Moulis, Sharon; Sgroi, Dennis C.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02129 USA. RP Sgroi, DC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Mol Pathol Res Unit, Boston, MA 02129 USA. EM dsgroi@partners.org FU NCI NIH HHS [R01-1CA112021-01, R01 CA112021] NR 20 TC 13 Z9 14 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2008 VL 10 IS 1 AR 302 DI 10.1186/bcr1853 PG 4 WC Oncology SC Oncology GA 285YF UT WOS:000254811400007 PM 18279539 ER PT J AU Rosner, B Colditz, GA Iglehart, JD Hankinson, SE AF Rosner, Bernard Colditz, Graham A. Iglehart, J. Dirk Hankinson, Susan E. TI Risk prediction models with incomplete data with application to prediction of estrogen receptor-positive breast cancer: prospective data from the Nurses' Health Study SO BREAST CANCER RESEARCH LA English DT Article ID NATIONAL DEATH INDEX; SERUM SEX-HORMONES; POSTMENOPAUSAL WOMEN; LIFE-STYLE; POPULATION; VALIDATION; PREVENTION; TAMOXIFEN; ANDROGEN; ALCOHOL AB Introduction A number of breast cancer risk prediction models have been developed to provide insight into a woman's individual breast cancer risk. Although circulating levels of estradiol in postmenopausal women predict subsequent breast cancer risk, whether the addition of estradiol levels adds significantly to a model's predictive power has not previously been evaluated. Methods Using linear regression, the authors developed an imputed estradiol score using measured estradiol levels (the outcome) and both case status and risk factor data (for example, body mass index) from a nested case-control study conducted within a large prospective cohort study and used multiple imputation methods to develop an overall risk model including both risk factor data from the main cohort and estradiol levels from the nested case-control study. Results The authors evaluated the addition of imputed estradiol level to the previously published Rosner and Colditz logincidence model for breast cancer risk prediction within the larger Nurses' Health Study cohort. The follow-up was from 1980 to 2000; during this time, 1,559 invasive estrogen receptor-positive breast cancer cases were confirmed. The addition of imputed estradiol levels significantly improved risk prediction; the age-specific concordance statistic increased from 0.635 +/- 0.007 to 0.645 +/- 0.007 (P < 0.001) after the addition of imputed estradiol. Conclusion Circulating estradiol levels in postmenopausal women appear to add to other lifestyle factors in predicting a woman's individual risk of breast cancer. C1 [Rosner, Bernard; Colditz, Graham A.; Hankinson, Susan E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Rosner, Bernard; Colditz, Graham A.; Iglehart, J. Dirk; Hankinson, Susan E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Rosner, Bernard] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Colditz, Graham A.] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. [Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Iglehart, J. Dirk] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Iglehart, J. Dirk] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Hankinson, Susan E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Rosner, B (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM stbar@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU National Institutes of Health [P01 CA87969, CA49449, CA089393]; American Cancer Society FX Support for this project was provided by National Institutes of Health grants P01 CA87969, CA49449, and CA089393 (Specialized Programs of Research Excellence in Breast Cancer). GAC was supported in part by a clinical research professorship from the American Cancer Society. We acknowledge Marion McPhee for programming assistance and Jessica Bugg for preparation assistance. NR 34 TC 16 Z9 16 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2008 VL 10 IS 4 AR R55 DI 10.1186/bcr2110 PG 11 WC Oncology SC Oncology GA 360FQ UT WOS:000260043500006 PM 18598349 ER PT J AU Goss, PE AF Goss, Paul E. TI Extending the benefits of adjuvant therapy in early HR plus breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Aromatase inhibitor; Letrozole; Adjuvant; Early breast cancer ID ESTROGEN-RECEPTOR MODULATORS; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; TAMOXIFEN RESISTANCE; UPDATED FINDINGS; LETROZOLE; MECHANISMS; TUMORS AB The benefits of adjuvant tamoxifen are well documented, but therapy is limited to 5 years because of reports of an unfavorable risk: benefit profile in later years. However, the risk of relapse continues beyond the end of therapy. Before the MA.17 trial, no agent given after the standard 5 years of adjuvant tamoxifen had been shown to provide additional benefit, leaving women unprotected against the ongoing risk of late recurrences of breast cancer. In the MA. 17 trial, starting letrozole within 3 months of completing tamoxifen significantly reduced the risk of relapse (including distant metastases) compared with placebo, and also significantly improved survival in patients who had node-positive disease at diagnosis. On the basis of data from the first interim analysis, the MA.17 trial was unblinded, and all patients in the placebo arm were offered letrozole: approximately two-thirds accepted. Early study unblinding left some important questions unanswered (including the long-term safety of extended adjuvant letrozole), but provided an opportunity to assess the benefits of starting letrozole after a prolonged period without active therapy. Even after a prolonged tamoxifen-free period, starting letrozole improved disease-free survival and distant disease-free survival, and reduced the occurrence of new, contralateral primary breast cancer, compared with observation and no active therapy. In subsequent intention-to-treat analyses, the benefit of letrozole persisted, despite a significant proportion of patients in the placebo arm having crossed over onto late extended adjuvant letrozole. In additional pre-unblinding, retrospective analyses derived from the core MA.17 data, the benefits of extended C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Lawrence House,LRH-302, Boston, MA 02114 USA. EM pgoss@partners.org NR 40 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2008 VL 112 BP 45 EP 52 DI 10.1007/s10549-008-0129-8 PG 8 WC Oncology SC Oncology GA 404QP UT WOS:000263168400006 PM 18785006 ER PT J AU Hirsch, AE Atencio, DP Rosenstein, BS AF Hirsch, Ariel E. Atencio, David P. Rosenstein, Barry S. TI Screening for ATM sequence alterations in African-American women diagnosed with breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE ATM; breast cancer; African-American women ID ATAXIA-TELANGIECTASIA; MISSENSE MUTATIONS; OVARIAN-CANCER; HIGH-RISK; RACIAL-DIFFERENCES; BRCA2 MUTATIONS; SUSCEPTIBILITY; FAMILIES; ASSOCIATION; HAPLOTYPES AB Background Women who are heterozygous for variants in the ataxia telangiectasia mutated (ATM) gene, ATM carriers, have been reported to be at increased risk for breast cancer compared with women who do not posses an alteration in this gene. Aside from BRCA1 and BRCA2, there are few data on breast cancer susceptibility genes in African-American women. The goal of this study was to determine whether there is evidence that ATM is a breast cancer susceptibility gene in African-American women. Methods One hundred thirty two African-American women were screened for ATM sequence alterations. Thirty-seven (28%) were women with a histological diagnosis of breast cancer (cases). These women were not selected on the basis of a breast cancer family history. Ninety-five (72%) were age-matched women who had not been diagnosed with breast cancer ( controls). Genetic variants were identified using denaturing high-performance liquid chromatography (DHPLC). Results Twenty-three of the 37 (62%) cases possessed at least one ATM variant. Fifty-eight of the 95 (61%) ( P = 0.54) age-matched controls harbored at least one ATM variant. For subjects specifically possessing missense variants, 46% of cases and 48% of controls had these types of sequence variants. In addition, 19% of cases and 34% of controls possessed multiple ATM sequence variants (P = 0.07). The most common polymorphisms were the 378 T. A which was seen in 19% of cases and 27% of controls (P = 0.22), 5557 G -> A identified in 22% of cases and 18% of controls (p = 0.40), 2685 A -> G which was detected in 11% of cases and 6% of controls (P = 0.22), and 1254 A. G which was found in 3% of cases and 9% of controls (P = 0.36). Hence, there were no significant differences in any of the genetic variants detected between the case and control subjects. Conclusion We found no statistically significant differences in the overall frequency of ATM variants, nor any specific variant type or group, between African-American women who had been diagnosed with breast cancer compared with an age-matched cohort of African-American women who did not have breast cancer. ATM, therefore, does not appear to represent a breast cancer susceptibility gene in the general AfricanAmerican population. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02118 USA. Boston Univ, Med Ctr, Dept Radiat Oncol, Boston, MA 02118 USA. NYU, Ctr Med, Dept Radiat Oncol, New York, NY USA. Mt Sinai Sch Med, Dept Radiat Oncol, New York, NY USA. Mt Sinai Sch Med, Dept Dermatol, New York, NY USA. Mt Sinai Sch Med, Dept Prevent Med & Community, New York, NY USA. RP Hirsch, AE (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 88 E Newton St,EB 11, Boston, MA 02118 USA. EM ahirsch@partners.org RI Rosenstein, Barry/A-7420-2009 NR 45 TC 4 Z9 4 U1 0 U2 1 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 JAN PY 2008 VL 107 IS 1 BP 139 EP 144 DI 10.1007/s10549-007-9531-x PG 6 WC Oncology SC Oncology GA 235LI UT WOS:000251235200017 PM 17333338 ER PT J AU Altschuler, A Nekhlyudov, L Rolnick, SJ Greene, SM Elmore, JG West, CN Herrinton, LJ Harris, EL Fletcher, SW Emmons, KM Geiger, AM AF Altschuler, Andrea Nekhlyudov, Larissa Rolnick, Sharon J. Greene, Sarah M. Elmore, Joann G. West, Carmen N. Herrinton, Lisa J. Harris, Emily L. Fletcher, Suzanne W. Emmons, Karen M. Geiger, Ann M. TI Positive, negative, and disparate - Women's differing long-term psychosocial experiences of bilateral or contralateral prophylactic mastectomy SO BREAST JOURNAL LA English DT Article DE breast cancer; cancer prevention; prophylactic mastectomy; psychosocial outcomes; women's health ID QUALITY-OF-LIFE; BREAST-CANCER; FAMILY-HISTORY; EFFICACY; SURVIVORS; MUTATION; GROWTH; ISSUES; HEALTH; BRCA1 AB Because of recent studies showing strong prevention benefit and acceptable psychosocial outcomes, more women may be considering prophylactic mastectomy. A growing literature shows some positive psychosocial outcomes for women with bilateral prophylactic mastectomy, but less is known about women with contralateral prophylactic mastectomy. Several surveys have shown that a large majority of women with prophylactic mastectomy report satisfaction with their decisions to have the procedure when asked in a quantitative, closed-ended format. We sought to explore the nuances of women's satisfaction with the procedure using a qualitative, open-ended format. We included open-ended questions as part of a mailed survey on psychosocial outcomes of prophylactic mastectomy. The research team coded and analyzed these responses using qualitative methods. We used simple descriptive statistics to compare the demographics of the entire survey sample to those women who answered the open-ended questions; the responses to the open- and closed-ended satisfaction questions, and the responses of women with bilateral and contralateral prophylactic mastectomy. Seventy-one percent of women with prophylactic mastectomy responded to the survey and 48% provided open-ended responses about psychosocial outcomes. Women's open-ended responses regarding psychosocial outcomes could be coded into one of three general categories-positive, negative, and disparate. In the subgroup of women with both open-and closed-ended responses, over 70% of women providing negative and disparate comments to the open-ended question simultaneously indicated satisfaction on a closed-ended question. Negative and disparate open-ended responses were twice as common among women with bilateral prophylactic mastectomy (52%) than women with contralateral prophylactic mastectomy (26%). These findings suggest that even among women who report general satisfaction with their decision to have prophylactic mastectomy via closed-ended survey questions, lingering negative psychosocial outcomes can remain, particularly among women with bilateral prophylactic mastectomy. This dichotomy could be an important factor to discuss in counseling women considering the procedure. C1 [Altschuler, Andrea; Herrinton, Lisa J.] Kaiser Permanente No California, Div Res, Oakland, CA 94612 USA. [Nekhlyudov, Larissa; Fletcher, Suzanne W.] Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA USA. [Rolnick, Sharon J.] Hlth Partners Res Fdn, Minneapolis, MN USA. [Greene, Sarah M.] Grp Hlth, Ctr Hlth Studies, Seattle, WA USA. [Elmore, Joann G.] Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. [West, Carmen N.; Geiger, Ann M.] Kaiser Permanente So California, Evaluat & Res Dept, Pasadena, CA USA. [Harris, Emily L.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA. [Emmons, Karen M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Altschuler, A (reprint author), Kaiser Permanente No California, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM andrea.altschuler@kp.org FU NCI NIH HHS [U19 CA079689-01, U19 CA79689, R01 CA090323] NR 21 TC 44 Z9 44 U1 1 U2 16 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1075-122X J9 BREAST J JI Breast J. PD JAN-FEB PY 2008 VL 14 IS 1 BP 25 EP 32 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 248AX UT WOS:000252124800004 PM 18186862 ER PT J AU Wong, JS Ho, AY Kaelin, CM Bishop, KL Silver, B Gelman, R Harris, JR Hergrueter, CA AF Wong, Julia S. Ho, Alice Y. Kaelin, Carolyn M. Bishop, Karyn L. Silver, Barbara Gelman, Rebecca Harris, Jay R. Hergrueter, Charles A. TI Incidence of major corrective surgery after Post-mastectomy breast reconstruction and radiation therapy SO BREAST JOURNAL LA English DT Article DE corrective surgery; Post-mastectomy; radiation therapy; reconstruction ID SKIN-SPARING MASTECTOMY; IMMEDIATE RECONSTRUCTION; ADJUVANT CHEMOTHERAPY; POSTOPERATIVE RADIOTHERAPY; TISSUE EXPANDER/IMPLANT; RANDOMIZED-TRIAL; CANCER PATIENTS; COMPLICATIONS; WOMEN; TRAM AB To evaluate the likelihood of requiring major corrective surgery (MCS) after modified radical mastectomy (MRM), immediate reconstruction and radiation therapy (RT) to the reconstructed breast. The study population consisted of 62 patients who underwent MRM and immediate breast reconstruction between 1990 and 1999, had postoperative radiation and at least one follow-up visit or procedure >= 2 months after radiation. Reconstruction consisted of a pedicled transverse rectus abdominis myocutaneous flap in 42 patients, latissimus dorsi flap in five, latissimus dorsi plus implant in six, and implant alone in nine. Median follow-up time after reconstruction was 13 months (range: 2-58) for non-implant patients and 10 months (range: 4-57) for implant patients. The primary endpoint was the incidence of major complications requiring MCS. Ten patients (16%) underwent MCS between 1 and 28 months after radiation (median in these patients of 8 months). 4/47 non-implant patients (9%) underwent MCS, compared to 6/15 implant patients (40%). Of patients followed >= 6 months after RT, 0/38 non-implant patients underwent MCS within 6 months compared to 3/13 (23%) implant patients (p = 0.01); of patients followed for >= 12 months after RT, the rates of MCS within 12 months were 1/24 (4%) and 2/7 (29%), respectively (p = 0.12). Patients who undergo immediate reconstruction after mastectomy using an implant followed by radiation have a high rate of subsequent MCS. The difference in the rate of MCS between the implant and non-implant groups is significant in early follow-up. Patients considering an implant followed by RT should be apprised of this increased risk. Prospective studies of these risks and the cosmetic outcomes are warranted. C1 [Wong, Julia S.; Ho, Alice Y.; Bishop, Karyn L.; Silver, Barbara; Gelman, Rebecca; Harris, Jay R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Radiat Oncol, Boston, MA 02115 USA. [Kaelin, Carolyn M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Surg, Boston, MA 02115 USA. [Gelman, Rebecca] Harvard Univ, Sch Med,Dept Biostat & Computat Biol, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. [Hergrueter, Charles A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Plast Surg, Boston, MA 02115 USA. RP Wong, JS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Radiat Oncol, 44 Binney St L2, Boston, MA 02115 USA. EM jwong@lroc.harvard.edu NR 31 TC 28 Z9 28 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1075-122X J9 BREAST J JI Breast J. PD JAN-FEB PY 2008 VL 14 IS 1 BP 49 EP 54 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 248AX UT WOS:000252124800007 PM 18186865 ER PT J AU Singh, M Lin, J Hocker, TL Tsao, H AF Singh, M. Lin, J. Hocker, T. L. Tsao, H. TI Genetics of melanoma tumorigenesis SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article DE genetics; melanoma; therapy ID CUTANEOUS MALIGNANT-MELANOMA; PROTEIN-KINASE KINASE; BRAF MUTATIONS; PTEN/MMAC1 ALTERATIONS; TRANSCRIPTION FACTOR; LINEAGE SURVIVAL; MASTER REGULATOR; MELANOCYTIC NEVI; HUMAN CANCER; CELL LINES AB Melanoma therapy is moving away from combinatorial approaches and towards newer targeted strategies. With the identification of mutations in various RAS pathway genes, there are now tremendous opportunities to bring inhibitors of RAS signalling to the clinical arena. C1 [Singh, M.; Lin, J.] Harvard Med Sch, Dept Dermatol, Boston, MA 02114 USA. [Tsao, H.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Tsao, H.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tsao, H.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Singh, M (reprint author), Harvard Med Sch, Dept Dermatol, Boston, MA 02114 USA. EM htsao@partners.org NR 80 TC 25 Z9 26 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JAN PY 2008 VL 158 IS 1 BP 15 EP 21 DI 10.1111/j.1365-2133.2007.08316.x PG 7 WC Dermatology SC Dermatology GA 240BV UT WOS:000251562900003 PM 18047516 ER PT J AU Salomone, S Potts, EM Tyndall, S Ip, PC Chun, J Brinkmann, V Waeber, C AF Salomone, S. Potts, E. M. Tyndall, S. Ip, P. C. Chun, J. Brinkmann, V. Waeber, C. TI Analysis of sphingosine 1-phosphate receptors involved in constriction of isolated cerebral arteries with receptor null mice and pharmacological tools SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE S1P; basilar artery; JTE-013; FTY720; VPC23019; SEW2871 ID PROTEIN-COUPLED RECEPTOR; ENDOTHELIAL-CELLS; IN-VIVO; SPHINGOSINE-1-PHOSPHATE; S1P(3); ROLES; CONTRACTION; ACTIVATION; PLATELETS; PATHWAYS AB Background and purpose: Sphingosine 1-phosphate (S1P) selectively and potently constricts isolated cerebral arteries, but this response has not been pharmacologically characterized. Experimental approach: The receptor subtype(s) involved in S1P-induced cerebrovascular constriction were characterized using genetic (S1P(2) and S1P(3) receptor null mice) and pharmacological tools (phospho-FTY720, a S1P(1/3/4/5) receptor agonist; SEW2871, a S1P(1) receptor agonist, JTE-013, a S1P(2) receptor antagonist, VPC23019, a S1P(1/3) receptor antagonist). Isolated basilar or peripheral ( femoral, mesenteric resistance) arteries, from either rat or mouse, were studied in a wire myograph. Key results: S1P concentration-dependently constricted basilar artery in rat, wild-type (WT) and S1P(2) null mice, but barely affected vascular tone in S1P(3) null mice. Vasoconstriction to U46619 ( a thromboxane analogue) or to endothelin-1 did not differ between WT, S1P(2) and S1P(3) null mice. JTE-013 inhibited not only S1P-induced vasoconstriction, but also KCl-, U46619- and endothelin-1-induced constriction. This effect was observed in WT as well as in S1P(2) null mice. VPC23019 increased the concentration-dependent vasoconstriction to S1P in both rat and mouse basilar arteries with intact endothelium, but not in rat basilar artery without endothelium. Phospho-FTY720 concentration-dependently constricted rat basilar arteries, but not femoral or mesenteric resistance arteries, while SEW2871 did not induce any response in the same arteries. Conclusions and implications: S1P constricts cerebral arteries through S1P(3) receptors. The purported S1P(2) receptor antagonist JTE-013 does not appear to be selective, at least in rodents. Enhancement of S1P-induced contraction by VPC23019 might be related to blockade of S1P(1) receptors and NO generation. C1 [Salomone, S.; Potts, E. M.; Tyndall, S.; Ip, P. C.; Waeber, C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. [Chun, J.] Scripps Res Inst, Dept Mol Biol, Helen L Dorris Child & Adolescent Neuropsychiat D, La Jolla, CA USA. [Brinkmann, V.] Novartis Res Inst Biomed Res Auto Immun & Transpl, Basel, Switzerland. RP Waeber, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Stroke & Neurovasc Regulat Lab, CNY149 Room 6403,149 13th St, Charlestown, MA 02129 USA. EM waeber@helix.mgh.harvard.edu RI Waeber, Christian/A-8333-2009; OI Waeber, Christian/0000-0001-6078-0027; Salomone, Salvatore/0000-0001-5307-6103 FU NIDA NIH HHS [R01 DA019674, DA019674]; NIMH NIH HHS [MH51699, R01 MH051699]; NINDS NIH HHS [NS052195, R21 NS052195, R01 NS048478, R01 NS049263, NS049263, NS048478] NR 33 TC 73 Z9 74 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JAN PY 2008 VL 153 IS 1 BP 140 EP 147 DI 10.1038/sj.bjp.0707581 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 248CG UT WOS:000252128400015 PM 18026125 ER PT J AU Wu, Y Humphrey, MB Yao, W Lane, N Lanier, LL Nakamura, MC AF Wu, Y. Humphrey, M. B. Yao, W. Lane, N. Lanier, L. L. Nakamura, M. C. TI Regulation of osteoclastogenesis by innate immune co-receptors SO CALCIFIED TISSUE INTERNATIONAL LA English DT Meeting Abstract C1 [Wu, Y.; Nakamura, M. C.] Univ Calif San Francisco, Dept Med, San Francisco VA Med Ctr, San Francisco, CA USA. [Humphrey, M. B.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, OKC VAMC, Oklahoma City, OK USA. [Humphrey, M. B.] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol Immunol, OKC VAMC, Oklahoma City, OK USA. [Yao, W.; Lane, N.] Univ Calif Davis, Dept Med, Sacramento, CA 95817 USA. [Lanier, L. L.] Univ Calif San Francisco, Dept Microbiol Immunol, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PY 2008 VL 82 SU 1 BP S19 EP S20 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 306OS UT WOS:000256258300021 ER PT B AU MacRae, SK Fox, E Slowther, A AF MacRae, Susan K. Fox, Ellen Slowther, Anne BE Singer, PA TI Clinical ethics and systems thinking SO CAMBRIDGE TEXTBOOK OF BIOETHICS LA English DT Article; Book Chapter ID HEALTH-CARE; IMPROVEMENT; SERVICES; QUALITY AB A health region, with multiple hospitals and community healthcare organizations, is faced with increased pressures to improve the ethical care of patients and improve staff experience across the system. Currently the patient satisfaction scores at many of the sites are quite low and recent Health Commission inspections in some hospitals have highlighted management of consent issues and patient-centered care as areas of major concern. The staff's morale is waning and moral distress seems to be increasing. The CEO of the Strategic Health Authority believes that clinical ethics could potentially make a significant difference to the overall culture of the system but feels that the existing mechanisms are not that effective. She begins to consult with experts in the field to discuss how clinical ethics can help her to improve her health system. "ABC Health Care'' has an established clinical ethics program that performs a variety of functions including case consultation, education, policy work, and scholarly writing. Although ABC has received positive accreditation ratings relating to clinical ethics, many within ABC including both administrators and clinical staff - have a general sense that ABC's current clinical ethics program may not be fully addressing the organization's needs. For example, the program tends to focus on a narrow range of ethical concerns, mostly related to high-profile acute situations in the intensive care and emergency units. In contrast, staff experience a much broader range of ethical issues in their work day to day, and many issues and areas go unserved. Although the clinical ethics program devotes many hours to ethics consultation, similar ethical issues continue to recur again and again. At times, ethics program staff seems more concerned about philosophical questions and principles than about the practical realities experienced by patients and healthcare staff. Overall, the clinical ethics program's impact on everyday behavior or on organizational culture is unclear, and no measures exist to evaluate the program's effectiveness. The CEO feels strongly that the clinical ethics program should be held accountable for its effects on the system (or lack thereof). He looks to other organizations for models of how clinical ethics programs can be used to make systems change. C1 [MacRae, Susan K.] Univ Toronto, Joint Ctr Bioeth, Toronto, ON M5S 1A1, Canada. [Fox, Ellen] US Dept Vet Affairs, Natl Ctr Eth Hlth Care, Washington, DC USA. [Slowther, Anne] Univ Warwick, Sch Med, Coventry CV4 7AL, W Midlands, England. RP MacRae, SK (reprint author), Univ Toronto, Joint Ctr Bioeth, Toronto, ON M5S 1A1, Canada. NR 20 TC 4 Z9 4 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-69443-8 PY 2008 BP 313 EP 321 DI 10.1017/CBO9780511545566.047 D2 10.1017/CBO9780511545566 PG 9 WC Medical Ethics; Medicine, Legal SC Medical Ethics; Legal Medicine GA BAN30 UT WOS:000304825200047 ER PT J AU Marder, SR Jones, PB AF Marder, Stephen R. Jones, Peter B. BA Tyrer, P Silk, KR BF Tyrer, P Silk, KR TI Pharmacological treatments for schizophrenia SO CAMBRIDGE TEXTBOOK OF EFFECTIVE TREATMENTS IN PSYCHIATRY LA English DT Article; Book Chapter ID RANDOMIZED CONTROLLED-TRIAL; CONVENTIONAL ANTIPSYCHOTIC-DRUGS; DOUBLE-BLIND; 2ND-GENERATION ANTIPSYCHOTICS; SCHIZOAFFECTIVE DISORDER; RESISTANT SCHIZOPHRENIA; ATYPICAL ANTIPSYCHOTICS; CLOZAPINE; RISPERIDONE; METAANALYSIS C1 [Marder, Stephen R.] W Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. [Jones, Peter B.] Addenbrookes Hosp, Dept Psychiat, Cambridge, England. RP Marder, SR (reprint author), W Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. NR 32 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-52184-228-0 PY 2008 BP 461 EP 468 D2 10.1017/CBO9780511544392 PG 8 WC Psychiatry SC Psychiatry GA BYF84 UT WOS:000298475100027 ER PT J AU Jones, PB Marder, SR AF Jones, Peter B. Marder, Stephen R. BA Tyrer, P Silk, KR BF Tyrer, P Silk, KR TI Psychosocial and pharmacological treatments for schizophrenia SO CAMBRIDGE TEXTBOOK OF EFFECTIVE TREATMENTS IN PSYCHIATRY LA English DT Article; Book Chapter ID RANDOMIZED CONTROLLED-TRIAL; COGNITIVE-BEHAVIORAL THERAPY; PSYCHOLOGICAL TREATMENTS; SOCIAL-INTERVENTION; FOLLOW-UP; FAMILY; PSYCHOTHERAPY; REMEDIATION; MAINTENANCE; 1ST-EPISODE C1 [Jones, Peter B.] Addenbrookes Hosp, Dept Psychiat, Cambridge, England. [Marder, Stephen R.] W Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. RP Jones, PB (reprint author), Addenbrookes Hosp, Dept Psychiat, Cambridge, England. NR 53 TC 2 Z9 2 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-52184-228-0 PY 2008 BP 469 EP 479 DI 10.1017/CBO9780511544392.028 D2 10.1017/CBO9780511544392 PG 11 WC Psychiatry SC Psychiatry GA BYF84 UT WOS:000298475100028 ER PT J AU Chen, RC Clark, JA Manola, J Talcott, JA AF Chen, Ronald C. Clark, Jack A. Manola, Judith Talcott, James A. TI Treatment 'mismatch' in early prostate cancer - Do treatment choices take patient quality of life into account? SO CANCER LA English DT Article DE prostatic neoplasms; outcome assessment; process assessment; quality of life; decision making; quality of health care ID SPARING RADICAL PROSTATECTOMY; RANDOMIZED CONTROLLED-TRIAL; RETROPUBIC PROSTATECTOMY; SEXUAL FUNCTION; OUTCOMES; URINARY; CONTINENCE; RADIATION; COMMUNICATION; BRACHYTHERAPY AB BACKGROUND. Pretreatment urinary, bowel, and sexual dysfunction may increase the toxicity of prostate cancer treatments or preclude potential benefits. Using patient-reported baseline dysfunction from a prospective cohort study, we determined the proportion of patients receiving relatively contraindicated ('mismatched') treatments. METHODS. Baseline obstructive uropathy and bowel dysfunction relatively contraindicate brachytherapy (BT) and external beam radiation therapy (EBRT), respectively, because they increase patients' Vulnerability to treatment-related toxicity. Baseline sexual dysfunction renders moot the intended benefit of nerve-sparing radical prostatectomy (NSRP), which is to preserve sexual function. We categorized patients' clinical circumstances by increasing complexity and counted the mismatches in each, expecting weaker or multiple contraindications to increase mismatched treatments. RESULTS. Of 438 eligible patients, 389 (89%) reported preexisting dysfunction, and more than one-third received mismatched treatments. Mismatches did not significantly increase with clinical complexity, and watchful waiting was very infrequent, even when all treatment options were contraindicated. Patient age and comorbidity, but not preexisting dysfunction, were associated with treatment choice. As expected, mismatched BT and EBRT led to worsened urinary and bowel symptoms, respectively, and NSRP did not improve outcomes after baseline sexual dysfunction. CONCLUSIONS. Pretreatment dysfunction does not appear to reliably influence treatment choices, and patients receiving mismatched treatments had worse outcomes. Further study is needed to determine why mismatched treatments were chosen, including the role of incomplete patient-physician communication of baseline dysfunction, and whether using a validated questionnaire before treatment decision-making would bypass this difficulty. Treatment mismatch may be a useful outcome indicator of the quality of patient-centered decisions. C1 [Chen, Ronald C.; Talcott, James A.] Massachusetts Gen Hosp, MGH Canc Ctr, Ctr Outcomes Res, Boston, MA USA. [Chen, Ronald C.] Harvard Radiat Oncol Program, Boston, MA USA. [Clark, Jack A.] Edith Nourse Rogers Mem Vet Hosp, Ctr Hlth Qual Outcomes Econ Res, Bedford, MA USA. [Clark, Jack A.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Manola, Judith] Dana Farber Canc Inst, Boston, MA 02115 USA. [Talcott, James A.] Harvard Med Sch, Boston, MA USA. RP Talcott, JA (reprint author), Massachusetts Gen Hosp, Ctr Outcomes Res, One hawthorne Pl,Suite 107, Boston, MA 02114 USA. EM jtalcott@partners.org OI Clark, Jack/0000-0002-7424-1670 FU AHRQ HHS [HS08208] NR 26 TC 36 Z9 37 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 2008 VL 112 IS 1 BP 61 EP 68 DI 10.1002/cncr.23138 PG 8 WC Oncology SC Oncology GA 246GB UT WOS:000251994400009 PM 18040996 ER PT J AU Habib, SL Danial, E Nath, S Schneider, J Jenkinson, CP Duggirala, R Abboud, HE Thameem, F AF Habib, Samy L. Danial, Elaine Nath, Subrata Schneider, Jennifer Jenkinson, Christopher P. Duggirala, Ravindranath Abboud, Hanna E. Thameem, Farook TI Genetic polymorphisms in OGG1 and their association with angiomyolipoma, a benign kidney tumor in patients with tuberous sclerosis SO CANCER BIOLOGY & THERAPY LA English DT Article DE TSC2; OGG1; angiomyolipoma; SNPs; 8-oxodG ID OXIDATIVE DNA-DAMAGE; REPAIR; 8-HYDROXYGUANINE; EXPRESSION; CANCER; ENZYME; HOGG1; RISK AB The enzyme 8-oxoguanine glycosylase 1 (OGG1) repairs 8-oxo-2-deoxyguanosine residue (8-oxodG) an oxidatively damaged promutagenic base. Genetic variations in OGG1 gene have been shown to modulate DNA repair capacity and are related risk of tumor development. However, epidemiologic findings have been inconsistent. The purpose of this study is to determine whether genetic variants in OGG1 play a role in susceptibility to angiomyolipoma, a benign kidney tumor associated with tuberous sclerosis complex (TSC) patients. To identify genetic variations, all seven exons of the OGG1 gene were amplified by PCR and sequenced in 22 TSC patients with angiomyolipoma (cases) and 18 controls. By direct sequencing, we identified four missense mutations in OGG1: Arg(45) Gln, Ala(85) Ser, Arg(229) Gln and Ser(326) Cys. Genotypic association with angiomyolipoma was performed using the measured genotype approach as implemented in the variance component analytical tools. Association analysis showed the presence of significant association (p = 0.01) only between the Ser(326) Cys polymorphism of OGG1 and angiomyolipoma. We also assessed the presence of oxidative DNA damage in kidney section from normal healthy subjects, normal kidney tissue from TSC patients and kidney angiomyolipoma tissue from TSC patients by immunostaining for 8-oxodG. 8-OxodG staining was highly abundant in kidney angiomyolipoma tissue from TSC patients compared to weak staining in uninvolved tissue from the same TSC patients or normal kidney from healthy subjects. Taken together, our findings suggest that Ser(326) Cys variant of OGG1 may confer risk for development of angiomyolipomas by increasing oxidative DNA damage. C1 [Habib, Samy L.] Univ Texas Hlth Sci Ctr San Antonio, Div Nephrol, Dept Med, George OBrien Kidney Res Ctr, San Antonio, TX 78229 USA. [Habib, Samy L.; Abboud, Hanna E.] Ctr Geriatr Res Educ & Clin, S Texas Vet Healthcare Syst, San Antonio, TX USA. [Schneider, Jennifer; Duggirala, Ravindranath] SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA. RP Habib, SL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Nephrol, Dept Med, George OBrien Kidney Res Ctr, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM habib@uthscsa.edu FU NIDDK NIH HHS [R01 DK079195] NR 16 TC 11 Z9 11 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JAN PY 2008 VL 7 IS 1 BP 23 EP 27 PG 5 WC Oncology SC Oncology GA 279OR UT WOS:000254365000005 PM 17932460 ER PT J AU Kufe, DW AF Kufe, Donald W. TI Targeting the human MUC1 oncoprotein - A tale of two proteins SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE MUC1; MUCI-C receptor; ovarian cancer; C595; radioimmunotherapy ID GROWTH-FACTOR RECEPTOR; CARCINOMA-ASSOCIATED ANTIGEN; MURINE MONOCLONAL-ANTIBODY; EPITHELIAL OVARIAN-CANCER; BETA-CATENIN; BREAST-CANCER; C-SRC; APOPTOTIC RESPONSE; GENE-TRANSCRIPTION; SURVIVAL RESPONSE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kufe, DW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Donald_Kufe@dfci.harvard.edu NR 49 TC 24 Z9 26 U1 1 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JAN PY 2008 VL 7 IS 1 BP 81 EP 84 PG 4 WC Oncology SC Oncology GA 279OR UT WOS:000254365000015 PM 18347419 ER PT J AU Shipitsin, M Bloushtain-Qimron, N Campbell, L Yao, J Polyak, K AF Shipitsin, Michail Bloushtain-Qimron, Noga Campbell, Lauren Yao, Jun Polyak, Kornelia TI Breast tumor heterogeneity and its clinical relevance SO CANCER BIOMARKERS LA English DT Meeting Abstract C1 [Shipitsin, Michail; Bloushtain-Qimron, Noga; Campbell, Lauren; Yao, Jun; Polyak, Kornelia] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2008 VL 4 IS 3 BP 125 EP 125 PG 1 WC Oncology SC Oncology GA 365JW UT WOS:000260403300007 ER PT J AU Anandasabapathy, S Turgeon, DK Normolle, D Tuck, M Poneros, J Stoffel, E Syngal, S Marcon, N Baron, J Ruffin, M Appelman, H Arber, N Bresalier, R Brenner, D AF Anandasabapathy, Sharmila Turgeon, D. Kim Normolle, Daniel Tuck, Melissa Poneros, John Stoffel, Elena Syngal, Sapna Marcon, Norman Baron, John Ruffin, Mack Appelman, Henry Arber, Nadir Bresalier, Robert Brenner, Dean TI Biorepository for validation of biomarkers predictive of the progression of Barrett's esophagus SO CANCER BIOMARKERS LA English DT Meeting Abstract C1 Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Ctr, Boston, MA USA. St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Dartmouth Coll, Hanover, NH 03755 USA. Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel. Univ Michigan, Med Ctr, Ann Arbor, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2008 VL 4 IS 3 BP 129 EP 129 PG 1 WC Oncology SC Oncology GA 365JW UT WOS:000260403300013 ER PT J AU Barderas, R Ramachandran, N Hainsworth, G Wong, J Raphael, J Cramer, D LaBaer, J Anderson, KS AF Barderas, Rodrigo Ramachandran, Niroshan Hainsworth, Genie Wong, Jessica Raphael, Jacob Cramer, Daniel LaBaer, Joshua Anderson, Karen S. TI Distinct patterns of immunoreactivity from p53-specific autoantibodies in breast and ovarian cancer patient sera SO CANCER BIOMARKERS LA English DT Meeting Abstract C1 [Barderas, Rodrigo; Ramachandran, Niroshan; Hainsworth, Genie; Raphael, Jacob; LaBaer, Joshua] Harvard Univ, Sch Med, Harvard Inst Proteom, Boston, MA USA. [Wong, Jessica; Anderson, Karen S.] Dana Farber Canc Inst, Canc Vaccine Ctr, Dept Med Oncol, Boston, MA 02115 USA. [Cramer, Daniel] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2008 VL 4 IS 3 BP 131 EP 132 PG 2 WC Oncology SC Oncology GA 365JW UT WOS:000260403300018 ER PT J AU Drake, RR Kan, T Karbassi, ID Gucek, M Sato, F Normolle, DP Cazares, LH Syngal, S Bresalier, R Marcon, N Cole, R Semmes, OJ Brenner, D Meltzer, SJ AF Drake, Richard R. Kan, Takatsugu Karbassi, Izabela D. Gucek, Marjan Sato, Fumiaki Normolle, Daniel P. Cazares, Lisa H. Syngal, Sapna Bresalier, Robert Marcon, Norman Cole, Robert Semmes, O. John Brenner, Dean Meltzer, Stephen J. TI A prevalidation study for the evaluation of serum biomarkers of Barrett's esophagus and esophageal adenocarcinoma SO CANCER BIOMARKERS LA English DT Meeting Abstract C1 [Drake, Richard R.; Karbassi, Izabela D.; Cazares, Lisa H.; Semmes, O. John] Eastern Virginia Med Sch, Ctr Biomed Prote, Norfolk, VA 23501 USA. [Kan, Takatsugu; Gucek, Marjan; Sato, Fumiaki; Cole, Robert; Meltzer, Stephen J.] Johns Hopkins Univ, Dept Med, GI Div, Baltimore, MD USA. [Normolle, Daniel P.; Brenner, Dean] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Syngal, Sapna] Dana Farber Canc Ctr, Dept Med, Boston, MA USA. [Syngal, Sapna] Brigham & Womens Med Ctr, Boston, MA USA. [Bresalier, Robert] Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol, Houston, TX 77030 USA. [Marcon, Norman] Univ Toronto, St Michaels Hosp, Dept Med, Toronto, ON M5B 1W8, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2008 VL 4 IS 3 BP 138 EP 139 PG 2 WC Oncology SC Oncology GA 365JW UT WOS:000260403300029 ER PT J AU Tuck, MK Normolle, DP Anan-Dasabapathy, S Turgeon, DK Poneros, J Stoffel, E Marcon, N Appelman, H Ruffin, M Arber, N Bresalier, R Anton, K Thomason, M Baron, JH Syngal, S Brenner, DE AF Tuck, Melissa K. Normolle, Daniel P. Anan-Dasabapathy, Sharmila Turgeon, D. Kim Poneros, John Stoffel, Elena Marcon, Norman Appelman, Henry Ruffin, Mack Arber, Nadir Bresalier, Robert Anton, Kristen Thomason, Mark Baron, John H. Syngal, Sapna Brenner, Dean E. TI Colon and esophagus reference sets SO CANCER BIOMARKERS LA English DT Meeting Abstract C1 Univ Texas MD Anderson Canc Ctr, Great Lakes New England Clin Epidemiol & Validat, Houston, TX 77030 USA. Dartmouth Med Coll, Hanover, NH USA. Dana Farber Canc Ctr, Boston, MA USA. Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel. St Michaels Hosp, Toronto, ON, Canada. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2008 VL 4 IS 3 BP 164 EP 165 PG 2 WC Oncology SC Oncology GA 365JW UT WOS:000260403300077 ER PT J AU Creaney, J Robinson, BWS Segal, A Musk, AW de Klerk, N Pass, HI Skates, SJ AF Creaney, Jenette Robinson, Bruce W. S. Segal, Amanda Musk, Arthur W. de Klerk, Nick Pass, Harvey I. Skates, Steven J. TI Serum mesothelin for early detection of the asbestos-induced cancer malignant mesothelioma SO CANCER BIOMARKERS LA English DT Meeting Abstract C1 [Creaney, Jenette; Robinson, Bruce W. S.; Segal, Amanda; Musk, Arthur W.; de Klerk, Nick] Western Australian Inst Med Res, Natl Res Ctr Asbestos Related Dis, Perth, WA, Australia. [Creaney, Jenette; Robinson, Bruce W. S.] Sir Charles Gairdner Hosp, Australian Mesothelioma Tissue Bank, Perth, WA, Australia. [Creaney, Jenette; Robinson, Bruce W. S.; Musk, Arthur W.] Univ Western Australia, Med Ctr, Sch Med & Pharmacol, Perth, WA 6009, Australia. [Segal, Amanda] Queen Elizabeth II Med Ctr, PathWest Lab Med WA, Perth, WA, Australia. [de Klerk, Nick] Telethon Inst Child Health Res, Biostat & Epidemiol Unit, Subiaco, WA, Australia. [Pass, Harvey I.] NYU, Sch Med & Comprehens Canc Ctr, New York, NY USA. [Skates, Steven J.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RI Robinson, Bruce/N-1900-2014; de Klerk, Nicholas/D-8388-2016 OI de Klerk, Nicholas/0000-0001-9223-0767 NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2008 VL 4 IS 3 BP 169 EP 170 PG 2 WC Oncology SC Oncology GA 365JW UT WOS:000260403300086 ER PT J AU Deisboeck, TS Wang, ZH AF Deisboeck, Thomas S. Wang, Zhihui TI A new concept for cancer therapy: out-competing the aggressor SO CANCER CELL INTERNATIONAL LA English DT Article AB Cancer expansion depends on host organ conditions that permit growth. Since such microenvironmental nourishment is limited we argue here that an autologous, therapeutically engineered and faster metabolizing cell strain could potentially out-compete native cancer cell populations for available resources which in turn should contain further cancer growth. This hypothesis aims on turning cancer progression, and its microenvironmental dependency, into a therapeutic opportunity. To illustrate our concept, we developed a three-dimensional computational model that allowed us to investigate the growth dynamics of native tumor cells mixed with genetically engineered cells that exhibit a higher proliferation rate. The simulation results confirm in silico efficacy of such therapeutic cells to combating cancer cells on site in that they can indeed control tumor growth once their proliferation rate exceeds a certain level. While intriguing from a theoretical perspective, this bold, innovative ecology-driven concept bears some significant challenges that warrant critical discussion in the community for further refinement. C1 [Deisboeck, Thomas S.; Wang, Zhihui] Massachusetts Gen Hosp, Complex Biosyst Modeling Lab, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Charlestown, MA 02129 USA. RP Deisboeck, TS (reprint author), Massachusetts Gen Hosp, Complex Biosyst Modeling Lab, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Charlestown, MA 02129 USA. EM deisboec@helix.mgh.harvard.edu; billwang@nmr.mgh.harvard.edu FU NIH [CA 113004]; Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging; Department of Radiology at Massachusetts General Hospital FX This work has been supported in part by NIH grant CA 113004 and by the Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging and the Department of Radiology at Massachusetts General Hospital. We thank Dr. Caterina Guiot (Dip. Neuroscience-INFM, Universita di Torino) for critical review of the manuscript. NR 27 TC 3 Z9 3 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2867 J9 CANCER CELL INT JI Cancer Cell Int. PY 2008 VL 8 AR 19 DI 10.1186/1475-2867-8-19 PG 9 WC Oncology SC Oncology GA V24IX UT WOS:000208405200019 PM 19077276 ER PT J AU Byers, T Wolf, HJ Franklin, WA Braudrick, S Merrick, DT Shroyer, KR Hirsch, FR Zeng, C Baron, AE Bunn, PA Miller, YE Kennedy, TC AF Byers, Tim Wolf, Holly J. Franklin, Wilbur A. Braudrick, Sarah Merrick, Daniel T. Shroyer, Kenneth R. Hirsch, Fred R. Zeng, Chan Baron, Anna E. Bunn, Paul A. Miller, York E. Kennedy, Timothy C. TI Sputum cytologic atypia predicts incident lung cancer: Defining latency and histologic specificity SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID AIR-FLOW OBSTRUCTION; FOLLOW-UP; COHORT AB Background: There is a need for early detection methods for lung cancer. Radiologic imaging may be more sensitive for peripheral cancers than for cancers arising in the central airways, from which bronchial epithelial cells are exfoliated into the sputum. Methods: Sputum samples were collected at baseline and periodically thereafter in a cohort of smokers and former smokers with chronic obstructive lung disease. The association between cytologic atypia and incident lung cancer was assessed by hazard ratios (HR, 95% confidence intervals) using Cox regression and by odds ratios (95% confidence intervals) using logistic regression, adjusting for potential confounding factors. Results: We observed 174 incident lung cancers in a cohort of 2,521 people over 9,869 person-years of observation. Risk for incident lung cancer was increased among those with cytologic atypia graded as moderate or worse (adjusted HR, 2.37; 1.68-3.34). The association between sputum atypia and lung cancer incidence was greatest for those sputum samples collected 5 months or less before the diagnosis of lung cancer (odds ratio, 10.32; 5.34-19.97). The association was substantially stronger for squamous cell lung cancers (HR, 5.13; 2.89-9.10) than for adenocarcinomas (HR, 1.85; 0.94-3.65). Conclusion: Cytologic atypia is a marker for increased lung cancer risk. These cytologic changes seem to arise from late events that are most apparent for cancers arising in the central respiratory airways. Whether cytologic atypia might complement radiologic imaging in a combined approach to lung cancer, early detection requires additional evaluation of those two methods used together. C1 [Byers, Tim; Wolf, Holly J.; Franklin, Wilbur A.; Braudrick, Sarah; Merrick, Daniel T.; Shroyer, Kenneth R.; Hirsch, Fred R.; Zeng, Chan; Baron, Anna E.; Bunn, Paul A.; Miller, York E.] Univ Colorado, Ctr Comprehens Canc, Sch Med, Hlth Sci Ctr, Aurora, CO 80045 USA. [Merrick, Daniel T.; Miller, York E.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Kennedy, Timothy C.] Lung Canc Inst Colorado, Denver, CO USA. RP Byers, T (reprint author), Univ Colorado, Ctr Comprehens Canc, Sch Med, Hlth Sci Ctr, Box F-519,13001 E 17th Pl, Aurora, CO 80045 USA. EM tim.byers@uchsc.edu FU NCI NIH HHS [P50 CA 58187] NR 19 TC 19 Z9 19 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2008 VL 17 IS 1 BP 158 EP 162 DI 10.1158/1055-9965.EPI-07-0436 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 253FK UT WOS:000252503900020 PM 18199720 ER PT J AU Bradbury, PA Heist, RS Kulke, MH Zhou, W Marshall, AL Miller, DP Su, L Park, S Temel, J Fidias, P Sequist, L Lynch, TJ Wain, JC Shepherd, FA Christiani, DC Liu, G AF Bradbury, Penelope A. Heist, Rebecca Suk Kulke, Matthew H. Zhou, Wei Marshall, Ariela L. Miller, David P. Su, Li Park, Sohee Temel, Jennifer Fidias, Panos Sequist, Lecia Lynch, Thomas J. Wain, John C. Shepherd, Frances A. Christiani, David C. Liu, Geoffrey TI A rapid outcomes ascertainment system improves the quality of prognostic and pharmacogenetic outcomes from observational studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CELL LUNG-CANCER; ADJUVANT CHEMOTHERAPY; GENETIC POLYMORPHISMS; BREAST-CANCER; RISK; SURVIVAL; EPIDEMIOLOGY; PREDICTORS; CARCINOMA; VARIANTS AB Purpose: Case-control and observational studies are popular choices for evaluating molecular prognostic/ pharmacogenetic outcomes, but data quality is rarely tested. Using clinical trial and epidemiologic methods, we assessed the quality of prognostic and outcomes data obtainable from a large case-control study of lung cancer. Methods: We developed an explicit algorithm (set of standard operating procedures forming a rapid outcomes ascertainment system) that encompassed multiple tests of quality assurance, and quality of data for a range of prognostic and outcomes variables, in several cancers, across several centers and two countries were assessed. Based on these assessments, the algorithm was revised and physicians' clinical practice changed. We reevaluated the quality of outcomes after these revisions. Results: Development of an algorithm with internal quality controls showed specific patterns of data collection errors, which were fixable. Although the major discrepancy rate in retrospective data collection was low (0.6%) when compared with external validated sources, complete data were found in <50% of patients for treatment response rate, toxicity, and documentation of patient palliative symptoms. Prospective data collection and changes to clinical practice led to significantly improved data quality. Complete data on response rate increased from 45% to 76% (P = 0.01, Fisher's exact test), for toxicity data, from 26% to 56% (P = 0.02), and for palliative symptoms, from 25% to 70% (P < 0.05), in one large lung cancer case-control study. Conclusions: Observational studies can be a useful source for studying molecular prognostic and pharmacogenetic outcomes. A rapid outcomes ascertainment system with strict ongoing quality control measures is an excellent means of monitoring key variables. C1 [Bradbury, Penelope A.; Shepherd, Frances A.; Liu, Geoffrey] Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M5G 2C4, Canada. [Heist, Rebecca Suk; Kulke, Matthew H.; Marshall, Ariela L.; Temel, Jennifer; Fidias, Panos; Sequist, Lecia; Lynch, Thomas J.; Wain, John C.; Christiani, David C.; Liu, Geoffrey] Harvard Univ, Sch Med, Boston, MA USA. [Heist, Rebecca Suk; Zhou, Wei; Marshall, Ariela L.; Miller, David P.; Su, Li; Park, Sohee; Temel, Jennifer; Fidias, Panos; Christiani, David C.; Liu, Geoffrey] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Heist, Rebecca Suk; Temel, Jennifer; Fidias, Panos; Sequist, Lecia; Lynch, Thomas J.; Wain, John C.; Christiani, David C.; Liu, Geoffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kulke, Matthew H.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Liu, G (reprint author), Princess Margaret Hosp, Ontario Canc Inst, Suite 7-124,610 Univ Ave, Toronto, ON M5G 2C4, Canada. EM Geoffrey.Liu@uhn.on.ca RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [R01 CA 092824, R01 CA 109193, R01 CA 074386] NR 21 TC 8 Z9 8 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2008 VL 17 IS 1 BP 204 EP 211 DI 10.1158/1055-9965.EPI-07-0470 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 253FK UT WOS:000252503900026 PM 18199725 ER PT J AU Mucci, LA Pawitan, Y Demichelis, F Fall, K Stark, JR Adami, HO Andersson, SO Andren, O Eisenstein, AS Holmberg, L Huang, W Kantoff, PW Perner, S Stampfer, MJ Johansson, JE Rubin, MA AF Mucci, Lorelei A. Pawitan, Yudi Demichelis, Francesca Fall, Katja Stark, Jennifer R. Adami, Hans-Olov Andersson, Swen-Olof Andren, Ove Eisenstein, Anna S. Holmberg, Lars Huang, Wei Kantoff, Philip W. Perner, Sven Stampfer, Meir J. Johansson, Jan-Erik Rubin, Mark A. TI Nine-gene molecular signature is not associated with prostate cancer death in a watchful waiting cohort SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RADICAL PROSTATECTOMY; PREOPERATIVE NOMOGRAM; RADIATION-THERAPY; NATURAL-HISTORY; PSA VELOCITY; PROGRESSION; RECURRENCE; RISK AB Tumor molecular markers hold promise to distinguish potentially lethal from indolent prostate cancer and to guide treatment choices. A previous study identified a nine-gene molecular signature in tumors associated with prostate-specific antigen relapse after prostatectomy. We examined this molecular model in relation to prostate cancer death among 172 men with initially localized disease. We quantified protein expression of the nine genes in tumors to classify progression risk. Accounting for clinical prognostic factors, the nine-gene model did not provide discrimination to predict lethal and indolent prostate cancer. C1 [Mucci, Lorelei A.; Stark, Jennifer R.; Eisenstein, Anna S.; Stampfer, Meir J.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Mucci, Lorelei A.; Stark, Jennifer R.; Eisenstein, Anna S.; Stampfer, Meir J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Mucci, Lorelei A.; Stark, Jennifer R.; Adami, Hans-Olov; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mucci, Lorelei A.; Demichelis, Francesca; Huang, Wei; Kantoff, Philip W.; Perner, Sven; Stampfer, Meir J.; Rubin, Mark A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. [Demichelis, Francesca; Huang, Wei; Perner, Sven; Rubin, Mark A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kantoff, Philip W.; Rubin, Mark A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pawitan, Yudi; Fall, Katja; Adami, Hans-Olov] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Demichelis, Francesca] ITC Irst, SRA, Bioinformat Grp, Trenton, NJ USA. [Andersson, Swen-Olof; Andren, Ove; Johansson, Jan-Erik] Orebro Univ Hosp, Dept Urol, Orebro, Sweden. [Holmberg, Lars] Uppsala Univ, Reg Oncol Ctr, Uppsala, Sweden. [Perner, Sven] Univ Ulm, Dept Pathol, Ulm, Germany. [Perner, Sven; Rubin, Mark A.] Cornell Univ, Weill Med Ctr, Dept Pathol, New York, NY USA. RP Mucci, LA (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 3rd Floor,181 Longwood Ave, Boston, MA 02115 USA. EM lmucci@hsph.harvard.edu RI Rider, Jennifer/A-5371-2011; Fall, Katja/A-9186-2012; OI Rubin, Mark/0000-0002-8321-9950; Demichelis, Francesca/0000-0002-8266-8631; Rider, Jennifer/0000-0002-2637-6036; Fall, Katja/0000-0002-3649-2639 FU NCI NIH HHS [P50 CA 090381, T32 CA 009001]; NIA NIH HHS [R01 AG 21404] NR 17 TC 8 Z9 8 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2008 VL 17 IS 1 BP 249 EP 251 DI 10.1158/1055-9965.EPI-07-0722 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 253FK UT WOS:000252503900033 PM 18199732 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Preoperative therapy as a model for translational research in breast cancer SO CANCER INVESTIGATION LA English DT Article ID CHEMOTHERAPY; TAMOXIFEN; ANASTROZOLE; COMBINATION; DOXORUBICIN; WOMEN; CYCLOPHOSPHAMIDE; TRASTUZUMAB; MULTICENTER; PACLITAXEL C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 18 TC 1 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2008 VL 26 IS 3 BP 217 EP 221 DI 10.1080/07357900701784253 PG 5 WC Oncology SC Oncology GA 270OE UT WOS:000253729300001 PM 18317961 ER PT J AU Campos, SM AF Campos, Susana M. TI Anti-epidermal growth factor receptor strategies for advanced breast cancer SO CANCER INVESTIGATION LA English DT Review ID TYROSINE KINASE INHIBITOR; CELL LUNG-CANCER; PHASE-I SAFETY; ZD1839 IRESSA; FACTOR-ALPHA; EGF-R; SIGNAL-TRANSDUCTION; LAPATINIB GW572016; PROGNOSTIC VALUE; ERBB FAMILY C1 Harvard Univ, Dana Farber Canc Inst, Dept Breast & Gynecol, Boston, MA 02115 USA. RP Campos, SM (reprint author), Harvard Univ, Dana Farber Canc Inst, Dept Breast & Gynecol, Boston, MA 02115 USA. NR 129 TC 8 Z9 8 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0735-7907 EI 1532-4192 J9 CANCER INVEST JI Cancer Invest. PY 2008 VL 26 IS 8 BP 757 EP 768 DI 10.1080/07357900801971040 PG 12 WC Oncology SC Oncology GA 359NK UT WOS:000259993600001 PM 18853311 ER PT J AU Tamimi, RM Brugge, JS Freedman, ML Miron, A Iglehart, JD Colditz, GA Hankinson, SE AF Tamimi, Rulla M. Brugge, Joan S. Freedman, Matthew L. Miron, Alexander Iglehart, J. Dirk Colditz, Graham A. Hankinson, Susan E. TI Circulating colony stimulating factor-1 and breast cancer risk SO CANCER RESEARCH LA English DT Article ID ANCHORAGE-INDEPENDENT GROWTH; MAMMARY-GLAND; M-CSF; RECEPTOR; CELLS; TUMOR; XENOGRAFTS; INVASION; SITES; MOUSE AB Colony stimulating factor-1 (CSF1) and its receptor (CSF1-R) are important in mammary gland development and have been implicated in breast carcinogenesis. In a nested case-control study in the Nurses' Heath Study of 726 breast cancer cases diagnosed between June 1, 1992, and June 1, 1998, and 734 matched controls, we prospectively evaluated whether circulating levels of CSF1 (assessed in 1989-1990) are associated with breast cancer risk The association varied by menopausal status (P-heterogeneity = 0.009). CSF1 levels in the highest quartile (versus lowest) were associated with an 85% reduced risk of premenopausal breast cancer [relative risk (RR), 0.15; 95% confidence interval (95% CI), 0.03-0.85; P-trend = 0.02]. In contrast, CSF1 levels in the highest quartile conferred a 33% increased risk of postmenopausal breast cancer (RR, 1.33; 95% CI, 0.96-1.86; P-trend = 0.11), with greatest risk for invasive (RR, 1.45; 95% CI, 1.02-2.07; P-trend = 0.06) and ER+/PR+ tumors (RR, 1.72; 95% CI, 1.11-2.66; P-trend = 0.04). Thus, the association of circulating CSF1 levels and breast cancer varies by menopausal status. C1 [Tamimi, Rulla M.; Hankinson, Susan E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Tamimi, Rulla M.; Brugge, Joan S.; Miron, Alexander; Hankinson, Susan E.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Tamimi, Rulla M.; Colditz, Graham A.; Hankinson, Susan E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Iglehart, J. Dirk] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. RP Tamimi, RM (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM rulla.tamimi@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [R29 CA075016-05, CA049449, CA075016, CA087969, CA089393, P01 CA087969, P01 CA087969-10, P50 CA089393, P50 CA089393-10, R01 CA049449, R01 CA049449-19, U01 CA049449] NR 20 TC 20 Z9 20 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2008 VL 68 IS 1 BP 18 EP 21 DI 10.1158/0008-5472.CAN-07-3234 PG 4 WC Oncology SC Oncology GA 247IP UT WOS:000252072100006 PM 18172291 ER PT J AU Gao, BN Xie, XJ Huang, CX Shames, DS Chen, TTL Lewis, CM Bian, AH Zhang, BF Olopade, OI Garber, JE Euhus, DM Tomlinson, GE Minna, JD AF Gao, Boning Xie, Xian-Jin Huang, Chunxian Shames, David S. Chen, Tina T-L. Lewis, Cheryl M. Bian, Aihua Zhang, Bifeng Olopade, Olufunmilayo I. Garber, Judy E. Euhus, David M. Tomlinson, Gail E. Minna, John D. TI RASSF1A polymorphism A133S is associated with early onset breast cancer in BRCA1/2 mutation carriers SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR RASSF1A; EPIGENETIC INACTIVATION; LUNG; RAS; 3P21.3; GENES; RISK AB The tumor suppressor gene RASSF1A regulates cell cycle progression, apoptosis, and microtubule stability and is inactivated by promoter methylation in similar to 50% of breast cancers. It has been shown previously that the polymorphism A133S in RASSF1A reduces its ability to regulate cell cycle progression and this polymorphism is associated with an increased risk of breast cancer. We analyzed the frequency of RASSF1A A133S in 190 Caucasian women without breast cancer and 653 patients with breast cancer including 138 BRCA1 and BRCA2 (BRCA1/2) mutation carriers, 395 non-BRCA1/2 mutations carriers, and 120 untested for BRCA1/2 mutations. Patients with breast cancer had a higher frequency of A133S than the controls [P = 0.017; odds ratios (OR), 1.71; 95% confidence intervals (95% CI), 1.10-2.66]. There is also a higher frequency of A133S in patients with higher familial breast cancer risk (P = 0.029; OR, 1.76; 95% CI, 1.06-2.92) and patients carrying BRCA1/2 mutations (P = 0.037, OR, 1.82; 95% CI, 1.04-3.18). Importantly, we found that the co-occurrence of a BRCA1 or BRCA2 mutation and A133S in RASSF1A was associated with earlier onset of breast cancer compared with those individuals with either a BRCA-1/2 mutation or the A133S polymorphism alone (36.0 versus 42.0 years old, P = 0.002). Our data suggest that the presence of the RASSF1A A133S polymorphism is associated with breast cancer pathogenesis in general and modifies breast cancer age of onset in BBCA1/2 mutations carriers. Our results warrant a large-scale study to examine the effect of the A133S polymorphism in the development of breast and other types of cancers. C1 [Gao, Boning; Huang, Chunxian; Shames, David S.; Tomlinson, Gail E.; Minna, John D.] Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA. [Gao, Boning; Xie, Xian-Jin; Huang, Chunxian; Shames, David S.; Bian, Aihua; Euhus, David M.; Minna, John D.] Univ Texas SW Med Ctr Dallas, Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA. [Gao, Boning; Huang, Chunxian; Shames, David S.] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA. [Xie, Xian-Jin; Bian, Aihua] Univ Texas SW Med Ctr Dallas, Div Biostat, Dallas, TX 75390 USA. [Chen, Tina T-L.; Tomlinson, Gail E.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Lewis, Cheryl M.; Euhus, David M.] Univ Texas SW Med Ctr Dallas, Dept Surg, Dallas, TX 75390 USA. [Zhang, Bifeng; Olopade, Olufunmilayo I.] Univ Chicago, Med Ctr, Dept Med, Chicago, IL 60637 USA. [Garber, Judy E.] Dana Farber Canc Inst, Dept Oncol, Ctr Populat Sci, Boston, MA 02115 USA. [Tomlinson, Gail E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78284 USA. RP Gao, BN (reprint author), Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, 6000 Harry Hines Blvd, Dallas, TX 75390 USA. EM boning.gao@utsouthwestern.edu FU NCI NIH HHS [P50 CA070907-10, P50 CA70907, R01 CA071618-06, P50 CA070907-12, P50 CA070907-11, P50 CA070907, R01 CA071618-07, R01 CA071618, CA71618] NR 19 TC 27 Z9 30 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 JAN 1 PY 2008 VL 68 IS 1 BP 22 EP 25 DI 10.1158/0008-5472.CAN-07-5183 PG 4 WC Oncology SC Oncology GA 247IP UT WOS:000252072100007 PM 18172292 ER PT J AU Gurumurthy, S Hezel, AF Berger, JH Bosenberg, MW Bardeesy, N AF Gurumurthy, Sushma Hezel, Aram F. Berger, Justin H. Bosenberg, Marcus W. Bardeesy, Nabeel TI LKB1 deficiency sensitizes mice to carcinogen-induced tumorigenesis SO CANCER RESEARCH LA English DT Article ID PEUTZ-JEGHERS-SYNDROME; ACTIVATED PROTEIN-KINASE; ONCOGENE-INDUCED SENESCENCE; SKIN TUMOR-DEVELOPMENT; LUNG-CANCER; HAMARTOMATOUS POLYPOSIS; GLUCOSE-HOMEOSTASIS; ENERGETIC STRESS; IN-VIVO; PATHWAY AB Lkb1 is a central regulator of cell polarity and energy metabolism through its capacity to activate the AMP-activated protein kinase (AMPK)-related family of protein kinases. Germ line-inactivating mutation of Lkb1 leads to Peutz-Jeghers syndrome, which is characterized by benign hamartomas and a susceptibility to malignant epithelial tumors. Mutations in Lkb1 are also found in sporadic carcinomas, most frequently in lung cancers associated with tobacco carcinogen exposure. The basis for Lkb1-dependent tumor suppression is not defined. Here, we uncover a marked sensitivity of Lkb1 mutant mice to the chemical carcinogen 7,12-dimethylbenz(a)anthraacene (DMBA). Lkb1(+/-) mice are highly prone to DMRA-induced squamous cell carcinoma (SCC) of the skin and lung. Confirming a cell autonomous tumor suppressor role of Lkb1, mice with epidermal-specific Lkb1 deletion are also susceptible to DMRA-induced SCC and develop spontaneous SCC with long latency. Restoration of wild-type Lkb1 causes senescence in tumor-derived cell lines, a process that can be partially bypassed by inactivation of the Rb pathway, but not by inactivation of p53 or AMPK. Our data indicate that Lkb1 is a potent suppressor of carcinogen-induced skin and lung cancers and that downstream targets beyond the AMPK-mTOR pathway are likely mediators of Lkb1-dependent tumor suppression. C1 [Gurumurthy, Sushma; Hezel, Aram F.; Berger, Justin H.; Bardeesy, Nabeel] Harvard Univ, Massachusetts Gen Hosp, Massachusetts Gen Hosp Canc Ctr, Ctr Canc,Dept Med,Med Sch, Boston, MA 02114 USA. [Bosenberg, Marcus W.] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. RP Bardeesy, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Massachusetts Gen Hosp Canc Ctr, Ctr Canc,Dept Med,Med Sch, CPZN 4216,Simches Res Bldg, Boston, MA 02114 USA. EM Bardeesy.Nabeel@MGH.Harvard.edu FU NCI NIH HHS [5 P01 CA117969, 5 K01 CA104647, K01 CA104647, P01 CA117969] NR 48 TC 51 Z9 52 U1 1 U2 5 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 JAN 1 PY 2008 VL 68 IS 1 BP 55 EP 63 DI 10.1158/0008-5472.CAN-07-3225 PG 9 WC Oncology SC Oncology GA 247IP UT WOS:000252072100011 PM 18172296 ER PT J AU Jagadeeswaran, R Surawska, H Krishnaswamy, S Janamanchi, V Mackinnon, AC Seiwert, TY Loganathan, S Kanteti, R Reichman, T Nallasura, V Schwartz, S Faoro, L Wang, YC Girard, L Tretiakova, MS Ahmed, S Zumba, O Soulii, L Bindokas, VP Szeto, LL Gordon, GJ Bueno, R Sugarbaker, D Lingen, MW Sattler, M Krausz, T Vigneswaran, W Natarajan, V Minna, J Vokes, EE Ferguson, MK Husain, AN Salgia, R AF Jagadeeswaran, Ramasamy Surawska, Hanna Krishnaswamy, Soundararajan Janamanchi, Varalakshmi Mackinnon, A. Craig Seiwert, Tanguy Y. Loganathan, Sivakumar Kanteti, Rajani Reichman, Trevor Nallasura, Vidya Schwartz, Stuart Faoro, Leonardo Wang, Yi-Ching Girard, Luc Tretiakova, Maria S. Ahmed, Salman Zumba, Osvaldo Soulii, Lioubov Bindokas, Vytas P. Szeto, Livia L. Gordon, Gavin J. Bueno, Raphael Sugarbaker, David Lingen, Mark W. Sattler, Martin Krausz, Thomas Vigneswaran, Wickii Natarajan, Viswanathan Minna, John Vokes, Everett E. Ferguson, Mark K. Husain, Aliya N. Salgia, Ravi TI Paxillin is a target for somatic mutations in lung cancer: Implications for cell growth and invasion SO CANCER RESEARCH LA English DT Article ID FOCAL ADHESION KINASE; FACTOR-RECEPTOR GENE; TYROSINE PHOSPHORYLATION; PROTEIN PAXILLIN; ADAPTER PROTEIN; FACTOR PATHWAY; C-MET; EXPRESSION; MOTILITY; P210(BCR/ABL) AB Lung cancer is characterized by abnormal cell growth and invasion, and the actin cytoskeleton plays a major role in these processes. The focal adhesion protein paxillin is a target of a number of oncogenes involved in key signal transduction and important in cell motility and migration. In lung cancer tissues, we have found that paxillin was highly expressed (compared with normal lung), amplified (12.1%, 8 of 66) and correlated with increased MET and epidermal growth factor receptor (EGFR) gene copy numbers, or mutated (somatic mutation rate of 9.4%, IS of 191). Paxillin mutations (19 of 21) were clustered between LD motifs I and 2 and the LIM domains. The most frequent point mutation (A127T) enhanced lung cancer cell growth, colony formation, focal adhesion formation, and colocalized with Bcl-2 in vitro. Gene silencing from RNA interference of mutant paxillin led to reduction of cell viability. A murine in vivo xenograft model of A127T paxillin showed an increase in tumor growth, cell proliferation, and invasion. These results establish an important role for paxillin in lung cancer. C1 [Jagadeeswaran, Ramasamy; Surawska, Hanna; Krishnaswamy, Soundararajan; Janamanchi, Varalakshmi; Seiwert, Tanguy Y.; Loganathan, Sivakumar; Kanteti, Rajani; Nallasura, Vidya; Faoro, Leonardo; Ahmed, Salman; Zumba, Osvaldo; Soulii, Lioubov; Bindokas, Vytas P.; Szeto, Livia L.; Natarajan, Viswanathan; Vokes, Everett E.; Salgia, Ravi] Univ Chicago, Med Ctr, Dept Med, Div Hematol Oncol,Canc Res Ctr,Pritzker Sch Med, Chicago, IL 60637 USA. [Mackinnon, A. Craig; Tretiakova, Maria S.; Krausz, Thomas] Univ Chicago, Pritzker Sch Med, Dept Pathol, Canc Res Ctr,Med Ctr, Chicago, IL 60637 USA. [Reichman, Trevor; Vigneswaran, Wickii; Ferguson, Mark K.] Univ Chicago, Pritzker Sch Med, Dept Surg, Canc Res Ctr,Med Ctr, Chicago, IL 60637 USA. [Schwartz, Stuart] Univ Chicago, Pritzker Sch Med, Dept Human Genet, Canc Res Ctr,Med Ctr, Chicago, IL 60637 USA. [Wang, Yi-Ching] Natl Cheng Kung Univ, Coll Med, Dept Pharmacol, Tainan 70101, Taiwan. [Girard, Luc; Minna, John] Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA. [Gordon, Gavin J.; Bueno, Raphael; Sugarbaker, David] Brigham & Womens Hosp, Dept Surg, Div Thorac Dis, Boston, MA 02115 USA. [Sattler, Martin] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Salgia, R (reprint author), Univ Chicago, Med Ctr, Dept Med, Div Hematol Oncol,Canc Res Ctr,Pritzker Sch Med, 5841 S Maryland Ave,M255, Chicago, IL 60637 USA. EM rsalgia@medicine.bsd.uchicago.edu RI Nallasura, Vidya/D-8947-2011; Jagadeeswaran, Ramasamy/C-9987-2013 FU NCI NIH HHS [P50 CA070907-10, R01 CA125541, R01 CA100750, CA100750-04, P50 CA070907-11, P50 CA070907, CA125541-01, P50CA70907] NR 44 TC 65 Z9 68 U1 1 U2 5 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 JAN 1 PY 2008 VL 68 IS 1 BP 132 EP 142 DI 10.1158/0008-5472.CAN-07-1998 PG 11 WC Oncology SC Oncology GA 247IP UT WOS:000252072100020 PM 18172305 ER PT J AU Evans, JW Chernikova, SB Kachnic, LA Banath, JP Sordet, O Delahoussaye, YM Treszezamsky, A Chon, BH Feng, Z Gu, Y Wilson, WR Pommier, Y Olive, PL Powell, SN Brown, JM AF Evans, James W. Chernikova, Sophia B. Kachnic, Lisa A. Banath, Judit P. Sordet, Olivier Delahoussaye, Yvette M. Treszezamsky, Alejandro Chon, Brian H. Feng, Zhihui Gu, Yongchuan Wilson, William R. Pommier, Yves Olive, Peggy L. Powell, Simon N. Brown, J. Martin TI Homologous recombination is the principal pathway for the repair of DNA damage induced by tirapazamine in mammalian cells SO CANCER RESEARCH LA English DT Article ID PROTEIN CROSS-LINKS; 3-AMINO-1,2,4-BENZOTRIAZINE 1,4-DIOXIDE TIRAPAZAMINE; NUCLEOTIDE EXCISION-REPAIR; DOUBLE-STRAND BREAKS; IONIZING-RADIATION; BASE DAMAGE; V(D)J RECOMBINATION; CELLULAR-RESPONSE; HYPOXIC CELLS; NECK-CANCER AB Tirapazamine (3-amino-1,2,4-benzotriazine-1,4-dioxide) is a promising hypoxia-selective cytotoxin that has shown significant activity in advanced clinical trials in combination with radiotherapy and cisplatin. The current study aimed to advance our understanding of tirapazamine-induced lesions and the pathways involved in their repair. We show that homologous recombination plays a critical role in repair of tirapazamine-induced damage because cells defective in homologous recombination proteins XRCC2, XRCC3, Rad51D, BRCA1, or BRCA2 are particularly sensitive to tirapazamine. Consistent with the involvement of homologous recombination repair, we observed extensive sister chromatid exchanges after treatment with tirapazamine. We also show that the nonhomologous end-joining pathway, which predominantly deals with frank double-strand breaks (DSB), is not involved in the repair of tirapazamine-induced DSBs. In addition, we show that tirapazamine preferentially kills mutants both with defects in XPF/ERCCI (but not in other nucleotide excision repair factors) and with defects in base excision repair. Tirapazamine also induces DNA-protein cross-links, which include stable DNA-topoisomerase I cleavable complexes. We further show that gamma H2AX an indicator of DNA DSBs, is induced preferentially in cells in the S phase of the cell cycle. These observations lead us to an overall model of tirapazamine damage in which DNA single-strand breaks, base damage, and DNA-protein cross-links (including topoisomerase I and II cleavable complexes) produce stalling and collapse of replication forks, the resolution of which results in DSB intermediates, requiring homologous recombination and XPF/ERCC1 for their repair. C1 [Evans, James W.; Chernikova, Sophia B.; Delahoussaye, Yvette M.; Brown, J. Martin] Stanford Univ, Dept Radiat Oncol, Div Radiat & Canc Biol, Stanford, CA 94305 USA. [Kachnic, Lisa A.] Boston Univ, Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. [Treszezamsky, Alejandro; Chon, Brian H.; Powell, Simon N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. [Banath, Judit P.] British Columbia Canc Res Ctr, Dept Med Biophys, Vancouver, BC V5Z 1L3, Canada. [Sordet, Olivier; Pommier, Yves] Natl Canc Inst, NIH, Ctr Canc Res, Lab Mol Pharmacol, Bethesda, MD USA. [Gu, Yongchuan; Wilson, William R.] Univ Auckland, Auckland Canc Soc Res Ctr, Auckland 1, New Zealand. RP Brown, JM (reprint author), Stanford Univ, Med Ctr, Div Radiat & Canc Biol, Rm 1255,269 Campus Dr, Stanford, CA 94305 USA. EM mbrown@stanford.edu RI Sordet, Olivier/M-3271-2014 FU Intramural NIH HHS; NCI NIH HHS [CA82566, CA107640, CA89393] NR 51 TC 40 Z9 41 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2008 VL 68 IS 1 BP 257 EP 265 DI 10.1158/0008-5472.CAN-06-4497 PG 9 WC Oncology SC Oncology GA 247IP UT WOS:000252072100033 PM 18172318 ER PT J AU Frietze, S Lupien, M Silver, PA Brown, M AF Frietze, Seth Lupien, Mathieu Silver, Pamela A. Brown, Myles TI CARM1 regulates estrogen-stimulated breast cancer growth through up-regulation of E2F1 SO CANCER RESEARCH LA English DT Article ID CELL-CYCLE PROGRESSION; ARGININE METHYLTRANSFERASE CARM1; TRANSCRIPTIONAL COACTIVATOR; GENE-EXPRESSION; PROTEIN METHYLATION; ANDROGEN RECEPTOR; BINDING-SITES; HISTONE H3; PROMOTER; ACTIVATION AB Estrogen receptor alpha (ER alpha) mediates breast cancer proliferation through transcriptional mechanisms involving the recruitment of specific coregulator complexes to the promoters of cell cycle genes. The coactivator-associated arginine methyltransferase CARM1 is a positive regulator of ER alpha-mediated transcriptional activation. Here, we show that CARM1 is essential for estrogen-induced cell cycle progression in the MCF-7 breast cancer cell line. CARM1 is specifically required for the estrogen-induced expression of the critical cell cycle transcriptional regulator E2F1 whereas estrogen stimulation of cyclin D1 is CARM1 independent. Upon estrogen stimulation, the E2F1 promoter is subject to CARM1-dependent dimethylation on histone H3 arginine 17 (H3R17me2) in a process that parallels the recruitment of ER alpha. Additionally, we find that the recruitment of CARM1 and subsequent histone arginine dimethylation are dependent on the presence of the oncogenic coactivator AIB1. Thus, CARM1 is a critical factor in the pathway of estrogen-stimulated breast cancer growth downstream of ER alpha and AIB1 and upstream of the cell cycle regulatory transcription factor E2F1. These studies identify CARM1 as a potential new target in the treatment of estrogen-dependent breast cancer. C1 [Frietze, Seth; Silver, Pamela A.] Harvard Med Sch, Dept Syst Biol, Cambridge, MA 02138 USA. [Lupien, Mathieu; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA USA. [Lupien, Mathieu; Brown, Myles] Brigham & Womens Hosp, Harvard Med Sch, Dept Med, Boston, MA USA. RP Brown, M (reprint author), Dana Farber Canc Inst, Div Mol & Cellular Oncol, 44 Binney St, Boston, MA 02115 USA. EM myles_brown@dfci.harvard.edu RI Myles, Brown/B-6906-2008; OI Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [P01CA8011105]; NIDDK NIH HHS [R56DK074967] NR 36 TC 98 Z9 100 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2008 VL 68 IS 1 BP 301 EP 306 DI 10.1158/0008-5472.CAN-07-1983 PG 6 WC Oncology SC Oncology GA 247IP UT WOS:000252072100038 PM 18172323 ER PT J AU Hirsh, V Major, P Lipton, A Cook, R Langer, C Smith, M Brown, J Coleman, R AF Hirsh, Vera Major, Pierre Lipton, Allan Cook, Richard Langer, Corey Smith, Matthew Brown, Janet Coleman, Robert TI N-Telopeptide of type I collagen (NTX) levels and prognosis in patients with bone metastases from non-small cell lung cancer (NSCLC) receiving zoledronic acid (ZOL) or placebo SO CANCER TREATMENT REVIEWS LA English DT Meeting Abstract CT 7th International Meeting on Cancer Induced Bone Disease CY JUN 29-JUL 02, 2008 CL Heriot Watt Univ, Edinburgh, SCOTLAND SP Canc & Bone Soc, Amgen, Novartis, Merck, Sharp & Dohme HO Heriot Watt Univ C1 [Hirsh, Vera] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Major, Pierre] McMaster Univ, Hamilton, ON, Canada. [Lipton, Allan] Penn State Milton S Hershey Med Ctr, Hershey, PA USA. [Cook, Richard] Univ Waterloo, Waterloo, ON N2L 3G1, Canada. [Langer, Corey] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Smith, Matthew] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Brown, Janet] Univ Leeds, Leeds, W Yorkshire, England. [Coleman, Robert] Weston Pk Hosp, Sheffield, S Yorkshire, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-7372 J9 CANCER TREAT REV JI Cancer Treat. Rev. PY 2008 VL 34 SU 1 BP S85 EP S85 DI 10.1016/j.ctrv.2008.03.118 PG 1 WC Oncology SC Oncology GA 326JW UT WOS:000257655800110 ER PT J AU Garg, HG Cowman, MK Hales, CA AF Garg, Hari G. Cowman, Mary K. Hales, Charles A. BE Garg, HG Cowman, MK Hales, CA TI CARBOHYDRATE CHEMISTRY, BIOLOGY AND MEDICAL APPLICATIONS Preface SO CARBOHYDRATE CHEMISTRY, BIOLOGY AND MEDICAL APPLICATIONS LA English DT Editorial Material; Book Chapter C1 [Garg, Hari G.; Hales, Charles A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA 02115 USA. [Cowman, Mary K.] Polytech Univ, Dept Chem & Biol Sci, Brooklyn, NY 11201 USA. RP Garg, HG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA 02115 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-055814-1 PY 2008 BP XI EP XII DI 10.1016/B978-0-08-054816-6.00018-5 PG 2 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA BEP68 UT WOS:000317647300001 ER PT J AU Ferguson-Yates, BE Li, H Dong, TK Hsiao, JL Oh, DH AF Ferguson-Yates, Bridget E. Li, Hongyan Dong, Tiffany K. Hsiao, Jennifer L. Oh, Dennis H. TI Impaired repair of cyclobutane pyrimidine dimers in human keratinocytes deficient in p53 and p63 SO CARCINOGENESIS LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; SQUAMOUS-CELL CARCINOMA; PIGMENTOSUM DDB2 GENE; GLOBAL GENOMIC REPAIR; DNA-DAMAGE; ULTRAVIOLET-RADIATION; TUMOR-SUPPRESSOR; UV-IRRADIATION; HUMAN FIBROBLASTS; STEM-CELLS AB While many p53-deficient cell types are impaired in global genomic nucleotide excision repair of cyclobutane pyrimidine dimers (CPDs), human epidermal keratinocytes expressing human papillomavirus type 16 E6 and E7 are p53 deficient and yet maintain repair of CPD. We hypothesized that the p53 homolog, p63, may participate in governing global repair instead of p53 in keratinocytes. Following ultraviolet radiation (UVR) of E6/E7 keratinocytes, depletion of p63 but not of p73 impaired global genomic repair of CPD relative to control cells. In all cases, repair of pyrimidine(6-4)pyrimidone photoproducts, the other major UVR-induced DNA lesions, was unaffected. In E6/E7 keratinocytes treated with p63 small interfering RNA, reduced global repair of CPD was associated not with reduced levels of messenger RNA-encoding DNA damage recognition proteins but rather with decreased levels of DDB2 and XPC proteins, suggesting that p63 posttranscriptionally regulates levels of these proteins. These results indicate that global repair may be regulated at multiple levels and suggest a novel role for p63 in modulating repair of DNA damage in human keratinocytes. The results may provide insight into mechanisms of genomic stability in epithelia infected with oncogenic human papilloma viruses and may further explain the lack of increased skin cancer incidence in Li-Fraumeni syndrome. C1 [Ferguson-Yates, Bridget E.; Li, Hongyan; Dong, Tiffany K.; Hsiao, Jennifer L.; Oh, Dennis H.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Ferguson-Yates, Bridget E.; Li, Hongyan; Dong, Tiffany K.; Hsiao, Jennifer L.; Oh, Dennis H.] San Francisco VA Med Ctr, Dermatol Res Unit, San Francisco, CA 94121 USA. RP Oh, DH (reprint author), Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. EM ohd@derm.ucsf.edu FU NCI NIH HHS [CA105958, R01 CA105958]; NIAMS NIH HHS [T32 AR007175] NR 52 TC 11 Z9 11 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2008 VL 29 IS 1 BP 70 EP 75 DI 10.1093/carcin/bgm244 PG 6 WC Oncology SC Oncology GA 258XQ UT WOS:000252904100010 PM 17984111 ER PT J AU Cantwell, CP Gervais, D Mueller, PR AF Cantwell, Colin P. Gervais, Debra Mueller, Peter R. BE Patel, U TI The case for biopsy in the modern management of renal cancer SO CARCINOMA OF THE KIDNEY SE Contemporary Issues in Cancer Imaging LA English DT Article; Book Chapter ID FINE-NEEDLE-ASPIRATION; IMAGING-GUIDED BIOPSY; CELL-CARCINOMA; PERCUTANEOUS BIOPSY; PATHOLOGICAL FINDINGS; UNITED-STATES; MASSES; TUMORS; DIAGNOSIS; KIDNEY C1 [Cantwell, Colin P.; Gervais, Debra; Mueller, Peter R.] Dept Radiol, Div Abdominal Imaging & Intervent Radiol, Boston, MA USA. [Cantwell, Colin P.; Gervais, Debra; Mueller, Peter R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Cantwell, CP (reprint author), Dept Radiol, Div Abdominal Imaging & Intervent Radiol, Boston, MA USA. NR 56 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-87838-8 J9 CONT ISS CANC IMAG PY 2008 BP 112 EP 125 PG 14 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging; Urology & Nephrology SC Oncology; Radiology, Nuclear Medicine & Medical Imaging; Urology & Nephrology GA BAM69 UT WOS:000304758400008 ER PT J AU Jang, IK Hursting, MJ McCollum, D AF Jang, Ik-Kyung Hursting, Marcie J. McCollum, David TI Argatroban therapy in patients with coronary artery disease and heparin-induced thrombocytopenia SO CARDIOLOGY LA English DT Article DE heparin; heparin-induced thrombocytopenia; argatroban; coronary artery disease AB The efficacy of the direct thrombin inhibitor argatroban was investigated in patients who developed heparin-induced thrombocytopenia following heparin therapy for coronary artery disease. The outcome of 121 patients treated with argatroban was compared with that of 26 patients in a historical control (i.e. patients who did not receive direct thrombin inhibition therapy). Argatroban, compared with controls, significantly reduced the 37-day composite of death, amputation or new thrombosis (30 versus 50%, p = 0.043), primarily driven by a significant decrease in new thrombosis (10 versus 31%, p = 0.01), and led to less bleeding (4 versus 15%, p = 0.046). Therefore, in patients with coronary artery disease who develop heparin-induced thrombocytopenia, argatroban provides safe, effective anticoagulation. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. Clin Sci Consulting, Austin, TX USA. CTI Clin Trial & Consulting Serv, Cincinnati, OH USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, Bigelow 800,55 Fruit St, Boston, MA 02114 USA. EM ijang@partners.org NR 11 TC 5 Z9 5 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2008 VL 109 IS 3 BP 172 EP 176 DI 10.1159/000106678 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 232VM UT WOS:000251048400005 PM 17726318 ER PT J AU d'Othee, BJ Morris, MF Powell, RJ Bettmann, MA AF d'Othee, Bertrand Janne Morris, Michael F. Powell, Richard J. Bettmann, Michael A. TI Cost determinants of percutaneous and surgical interventions for treatment of intermittent claudication from the perspective of the hospital SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE angiography; arteries; arteriosclerosis; cost-effectiveness; interventional radiology; stents and prostheses; transluminal angioplasty ID QUALITY-OF-LIFE; PERIPHERAL VASCULAR-DISEASE; RANDOMIZED CONTROLLED TRIAL; REVASCULARIZATION PROCEDURES; SUBINTIMAL RECANALIZATION; ARTERIAL-DISEASE; HEALTH-STATUS; EUROQOL; SURGERY; IMPACT AB Purpose To identify pretreatment predictors of procedural costs in percutaneous and surgical interventions for intermittent claudication due to aortoiliac and/or femoropopliteal disease. Methods A retrospective study was conducted in 97 consecutive patients who underwent percutaneous or surgical interventions over 15 months at a tertiary care center. Nineteen clinical predictive variables were collected at baseline. Procedural costs (outcome) were assessed from the perspective of the hospital by direct calculation, not based on ratios of costs-to-charges. A multivariable regression model was built to identify significant cost predictors. Follow-up information was obtained to provide multidimensional assessment of clinical outcome, including technical success (arteriographic score) and clinical result (changes in ankle-brachial pressure index; cumulative patency, mortality, and complication rates). Results The linear regression model shows that procedural costs per patient are 25% lower in percutaneous patients (versus surgical), 42% lower for patients without rest pain than for those with, 28% lower if treated lesions are unilateral (versus bilateral), 12% lower if the treated lesion is stenotic rather than occlusive, 34% higher in sedentary patients, and 11% higher in patients with a history of cardiac disease. After a mean clinical follow-up > 2 years, between-group differences between percutaneous and surgical patients were small and of limited significance in all dimensions of clinical outcome. Conclusion Predictors of clinical outcome are different from predictors of costs, and one should include both types of variables in the decision-making process. The choice of percutaneous versus surgical strategy, the presence of rest pain, and the bilaterality of the culprit lesions were the main pretreatment determinants of procedural costs. When possible choices of treatment strategy overlap, percutaneous treatment should provide an acceptable result that is less expensive (although not equal to surgery). C1 [d'Othee, Bertrand Janne] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol Cardiovasc Imaging & Intervent, Boston, MA 02114 USA. [Morris, Michael F.] Banner Good Samaritan Hosp, Phoenix, AZ 85006 USA. [Powell, Richard J.] Dartmouth Hitchcock Med Ctr, Dept Surg, Lebanon, NH 03756 USA. [Bettmann, Michael A.] Wake Forest Univ, Baptist Med Ctr, Dept Radiol Sci, Winston Salem, NC 27157 USA. RP d'Othee, BJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol Cardiovasc Imaging & Intervent, 55 Fruit St,GRB-290, Boston, MA 02114 USA. EM bjannedothee@partners.org NR 31 TC 6 Z9 6 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD JAN PY 2008 VL 31 IS 1 BP 56 EP 65 DI 10.1007/s00270-007-9221-4 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 249TI UT WOS:000252252300009 ER PT B AU Russell, SJ Miller, KK AF Russell, Steven Jon Miller, Karen Klahr BE Davies, TF TI Pituitary Apoplexy SO CASED-BASED GUIDE TO CLINICAL ENDOCRINOLOGY SE Contemporary Endocrinology LA English DT Article; Book Chapter C1 [Russell, Steven Jon] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Russell, Steven Jon] Harvard Univ, Sch Med, Boston, MA USA. [Miller, Karen Klahr] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit, Boston, MA USA. RP Russell, SJ (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-58829-815-7 J9 CONTEMP ENDOCRINOL S PY 2008 BP 9 EP 17 DI 10.1007/978-1-60327-103-5_1 D2 10.1007/978-1-60327-103-5 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BJO85 UT WOS:000266931400002 ER PT B AU Hall, JE AF Hall, Janet E. BE Davies, TF TI Female Reproduction Introduction SO CASED-BASED GUIDE TO CLINICAL ENDOCRINOLOGY SE Contemporary Endocrinology LA English DT Editorial Material; Book Chapter ID POLYCYSTIC-OVARY-SYNDROME; WOMEN; AMENORRHEA; HYPERPROLACTINEMIA; PULSATILE; ESTRADIOL; FAILURE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit, Boston, MA 02115 USA. RP Hall, JE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit, Boston, MA 02115 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-58829-815-7 J9 CONTEMP ENDOCRINOL S PY 2008 BP 263 EP 271 D2 10.1007/978-1-60327-103-5 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BJO85 UT WOS:000266931400036 ER PT B AU Welt, CK AF Welt, Corrine K. BE Davies, TF TI Premature Ovarian Failure SO CASED-BASED GUIDE TO CLINICAL ENDOCRINOLOGY SE Contemporary Endocrinology LA English DT Article; Book Chapter C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit, Boston, MA 02115 USA. RP Welt, CK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-58829-815-7 J9 CONTEMP ENDOCRINOL S PY 2008 BP 279 EP 284 DI 10.1007/978-1-60327-103-5_30 D2 10.1007/978-1-60327-103-5 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BJO85 UT WOS:000266931400038 ER PT J AU Walkley, CR Sankaran, VG Orkin, SH AF Walkley, Carl R. Sankaran, Vijay G. Orkin, Stuart H. TI Rb and hematopoiesis: stem cells to anemia SO CELL DIVISION LA English DT Review AB The retinoblastoma protein, Rb, was one of the first tumor suppressor genes identified as a result of the familial syndrome retinoblastoma. In the period since its identification and cloning a large number of studies have described its role in various cellular processes. The application of conditional somatic mutation with lineage and temporally controlled gene deletion strategies, thus circumventing the lethality associated with germ-line deletion of Rb, have allowed for a reanalysis of the in vivo role of Rb. In the hematopoietic system, such approaches have led to new insights into stem cell biology and the role of the microenvironment in regulating hematopoietic stem cell fate. They have also clarified the role that Rb plays during erythropoiesis and defined a novel mechanism linking mitochondrial function to terminal cell cycle withdrawal. These studies have shed light on the in vivo role of Rb in the regulation of hematopoiesis and also prompt further analysis of the role that Rb plays in both the regulation of hematopoietic stem cells and the terminal differentiation of their progeny. C1 [Walkley, Carl R.; Sankaran, Vijay G.; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Div Hematol Oncol, Boston, MA 02115 USA. [Walkley, Carl R.; Sankaran, Vijay G.; Orkin, Stuart H.] Harvard Univ, Sch Med, Stem Cell Program, Childrens Hosp Boston,Harvard Stem Cell Inst, Boston, MA 02115 USA. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Walkley, Carl R.] Univ Melbourne, St Vincents Hosp, Dept Med, St Vincents Inst, Fitzroy, Vic 3065, Australia. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Div Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. EM cwalkley@svi.edu.au; sankaran@bloodgroup.tch.harvard.edu; stuart_orkin@dfci.harvard.edu OI Walkley, Carl/0000-0002-4784-9031 FU NIH FX The authors would like to thank Drs. L Purton, D. Nathan and M. Weiss for helpful discussion; Dr. T. Jacks for the generous provision of the conditional Rb animals and those who have generously shared Cre lines. V.G.S. was supported by MSTP and NRSA awards from the NIH. C.R.W. is a Special Fellow of the Leukemia & Lymphoma Society and S.H.O. is an Investigator of the Howard Hughes Medical Institute. NR 110 TC 12 Z9 13 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1747-1028 J9 CELL DIV JI Cell Div. PY 2008 VL 3 AR 13 DI 10.1186/1747-1028-3-13 PG 9 WC Cell Biology SC Cell Biology GA V14GX UT WOS:000207724000013 PM 18775080 ER PT J AU Leung, Y Ally, S Goldberg, MB AF Leung, Yiuka Ally, Shabeen Goldberg, Marcia B. TI Bacterial actin assembly requires Toca-1 to relieve N-WASP autoinhibition SO CELL HOST & MICROBE LA English DT Article ID ALDRICH-SYNDROME PROTEIN; SHIGELLA-FLEXNERI; LISTERIA-MONOCYTOGENES; ARP2/3 COMPLEX; DEPOLYMERIZING PROTEIN; INTRACELLULAR MOVEMENT; FILOPODIUM FORMATION; RICKETTSIA-CONORII; ESCHERICHIA-COLI; MOTILITY AB Actin polymerization in the mammalian cytosol can be locally activated by mechanisms that relieve the autoinhibited state of N-WASP, an initiator of actin assembly, a process that also requires the protein Toca-1. Several pathogenic bacteria, including Shigella, exploit this host feature to infect and disseminate efficiently. The Shigella outer membrane protein IcsA recruits N-WASP, which upon activation at the bacterial surface mediates localized actin polymerization. The molecular role of Toca-1 in N-WASP activation during physiological or pathological actin assembly processes in intact mammalian cells remains unclear. We show that actin tail initiation by S. flexneri requires Toca-1 for the conversion of N-WASP from a closed inactive conformation to an open active one. While N-WASP recruitment is dependent on IcsA, Toca-1 recruitment is instead mediated by S. flexneri type III secretion effectors. Thus, S. flexneri independently hijacks two nodes of the N-WASP actin assembly pathway to initiate localized actin tail assembly. C1 [Leung, Yiuka; Ally, Shabeen; Goldberg, Marcia B.] Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Cambridge, MA 02139 USA. RP Goldberg, MB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Cambridge, MA 02139 USA. EM mgoldberg1@partners.org FU NIAID NIH HHS [AI052354, R01 AI052354, R01 AI052354-01A1, R01 AI052354-02, R01 AI052354-03, R01 AI052354-04, R01 AI052354-05] NR 41 TC 33 Z9 33 U1 2 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 J9 CELL HOST MICROBE JI Cell Host Microbe PD JAN PY 2008 VL 3 IS 1 BP 39 EP 47 DI 10.1016/j.chom.2007.10.011 PG 9 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 254JW UT WOS:000252583900009 PM 18191793 ER PT J AU Wagers, AJ AF Wagers, Amy J. TI Wnt not, waste not SO CELL STEM CELL LA English DT Editorial Material ID CELL FATE; ACTIVATION; MUSCLE; NOTCH; HETEROGENEITY; MYOGENESIS AB The molecular signals that regulate the regenerative function of satellite cells in the skeletal muscle remain largely obscure. In this issue of Cell Stem Cell, Bracket al. (2008) report that direct molecular crosstalk between stem cell self-renewal and differentiation pathways determines the timing and efficiency of muscle repair. C1 [Wagers, Amy J.] Harvard Stem Cell Inst, Boston, MA 02215 USA. RP Wagers, AJ (reprint author), Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, Boston, MA 02215 USA. EM amy.wagers@joslin.harvard.edu NR 10 TC 3 Z9 3 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD JAN PY 2008 VL 2 IS 1 BP 6 EP 7 DI 10.1016/j.stem.2007.12.005 PG 2 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 254RT UT WOS:000252606400004 PM 18371413 ER PT J AU Lengerke, C Schmitt, S Bowman, TV Jang, IH Maouche-Chretien, L McKinney-Freeman, S Davidson, AJ Hammerschmidt, M Rentzsch, F Green, JBA Zon, LI Daley, GQ AF Lengerke, Claudia Schmitt, Sabine Bowman, Teresa V. Jang, Il Ho Maouche-Chretien, Leila McKinney-Freeman, Shannon Davidson, Alan J. Hammerschmidt, Matthias Rentzsch, Fabian Green, Jeremy B. A. Zon, Leonard I. Daley, George Q. TI BMP and Wnt specify hematopoietic fate by activation of the Cdx-Hox pathway SO CELL STEM CELL LA English DT Article ID EMBRYONIC STEM-CELLS; BONE MORPHOGENETIC PROTEIN-4; ACUTE MYELOID-LEUKEMIA; MOUSE EMBRYO; DEFINITIVE HEMATOPOIESIS; PRIMITIVE STREAK; GENE-EXPRESSION; YOLK-SAC; HEMANGIOBLAST DEVELOPMENT; MESODERM FORMATION AB The formation of blood in the embryo is dependent on bone morphogenetic protein (BMP), but how BMP signaling intersects with other regulators of hematopoietic development is unclear. Using embryonic stem (ES) cells, we show that BMP4 first induces ventral-posterior (V-P) mesoderm and subsequently directs mesodermal cells toward blood fate by activating Wnt3a and upregulating Cdx and Hox genes. When BMP signaling is blocked during this latter phase, enforced expression of either Cdx1 or Cdx4 rescues hematopoietic development, thereby placing BMP4 signaling upstream of the Cdx-Hox pathway. Wnt signaling cooperates in BMP-induced hemogenesis, and the Wnt effector LEF1 mediates BMP4 activation of Cdx genes. Our data suggest that BMP signaling plays two distinct and sequential roles during blood formation, initially as an inducer of mesoderm, and later to specify blood via activation of Wnt signaling and the Cdx-Hox pathway. C1 [Lengerke, Claudia; Schmitt, Sabine; Bowman, Teresa V.; Jang, Il Ho; Maouche-Chretien, Leila; McKinney-Freeman, Shannon; Zon, Leonard I.; Daley, George Q.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Lengerke, Claudia; Schmitt, Sabine; Bowman, Teresa V.; Jang, Il Ho; Maouche-Chretien, Leila; McKinney-Freeman, Shannon; Zon, Leonard I.; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Lengerke, Claudia; Schmitt, Sabine; Bowman, Teresa V.; Jang, Il Ho; Maouche-Chretien, Leila; McKinney-Freeman, Shannon; Zon, Leonard I.; Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Maouche-Chretien, Leila] Univ Paris 05, Inst Cochin, CNRS, F-75014 Paris, France. [Maouche-Chretien, Leila] INSERM, U567, F-75014 Paris, France. [Davidson, Alan J.] Ctr Regenerat Med & Technol, Boston, MA 02114 USA. [Hammerschmidt, Matthias; Rentzsch, Fabian] Max Planck Inst Immunobiol, D-79011 Freiburg, Germany. [Green, Jeremy B. A.] Kings Coll London, Dept Carniofacial Dev, London WC2R 2LS, England. [Lengerke, Claudia] Univ Tubingen, Med Ctr 2, Dept Hematol Oncol, D-72076 Tubingen, Germany. [Lengerke, Claudia; Schmitt, Sabine; Bowman, Teresa V.; Jang, Il Ho; Maouche-Chretien, Leila; McKinney-Freeman, Shannon; Zon, Leonard I.; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Childrens Hosp, Div Pediat Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu RI Green, Jeremy/F-3630-2010; maouche, leila/E-3887-2017; OI Green, Jeremy/0000-0002-6102-2620; Lengerke, Claudia/0000-0001-5442-2805 NR 67 TC 124 Z9 130 U1 2 U2 15 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD JAN PY 2008 VL 2 IS 1 BP 72 EP 82 DI 10.1016/j.stem.2007.10.022 PG 11 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 254RT UT WOS:000252606400013 PM 18371423 ER PT J AU Keene, CD Chang, R Leverenz, JB Kopyov, O Hevner, R Born, D Bird, TD Montine, TJ AF Keene, C. D. Chang, R. Leverenz, J. B. Kopyov, O. Hevner, R. Born, D. Bird, T. D. Montine, T. J. TI Graft overgrowth and ependymal cyst formation despite initial clinical improvement in a Huntington's patient who received fetal neural transplants SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 15th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY MAY 01-03, 2008 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 [Keene, C. D.; Chang, R.; Born, D.; Montine, T. J.] Univ Washington, Med Ctr, Dept Pathol, Div Neuropathol, Seattle, WA 98195 USA. [Bird, T. D.] Univ Washington, Med Ctr, Dept Neurol, Seattle, WA 98195 USA. [Leverenz, J. B.; Bird, T. D.] VA Puget Sound Hlth Care Syst, Dept Neurol, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Geriatr Program, Seattle, WA USA. [Leverenz, J. B.] VA Puget Sound Hlth Care Syst, Mental Illness Program, Seattle, WA USA. [Leverenz, J. B.] VA Puget Sound Hlth Care Syst, Parkinsons Dis Program, Seattle, WA USA. [Keene, C. D.; Hevner, R.] Childrens Hosp, Seattle, WA USA. [Keene, C. D.; Hevner, R.] Reg Med Ctr, Seattle, WA USA. [Kopyov, O.] St Johns Reg Med Ctr, Inst Neurosci, Oxnard, CA USA. RI Keene, Christopher/N-1806-2015 NR 0 TC 3 Z9 3 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2008 VL 17 IS 4 BP 469 EP 469 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 301XT UT WOS:000255930500047 ER PT J AU Wang, JL Orkin, SH AF Wang, Jianlong Orkin, Stuart H. TI A protein roadmap to pluripotency and faithful reprogramming SO CELLS TISSUES ORGANS LA English DT Article; Proceedings Paper CT 1st International Conference on Stem Cells and Tissue Formation CY SEP, 2006 CL Dresden, GERMANY SP German Res Fdn DE embryonic stem cells; pluripotency; proteomics; protein interaction network; reprogramming ID EMBRYONIC STEM-CELLS; MOUSE EMBRYOS; ES CELLS; NUCLEAR TRANSFER; SOMATIC-CELLS; SELF-RENEWAL; NANOG; EXPRESSION; DIFFERENTIATION; GENERATION AB Embryonic stem (ES) cells are of great interest because of their capability of unlimited self-renewal and multilineage differentiation, thus serving as a potentially unlimited source for tissue replacement in regenerative medicine. ES cells possess factors that maintain and induce pluripotency, as demonstrated by successful reprogramming of somatic cells by fusion with ES cells. Understanding the complex molecular mechanisms underlying ES cell pluripotency should illuminate fundamental properties of stem cells and the process of reprogramming. Proteomics has proven to be a powerful approach to gain insight into key intracellular signals governing ES cell self-renewal and differentiation. We have recently employed a proteomics approach to explore the regulatory protein networks in which Nanog, a fundamental ES cell transcription factor, operates and have constructed the first protein interaction network in mouse ES cells. The network is highly enriched for factors known to be critical in ES cell biology and appears to function as a module for pluripotency. Here we will review current ES cell proteomic studies and provide insights into how a pluripotency protein network will advance recent efforts in cellular reprogramming. Copyright (c) 2008 S. Karger AG, Basel. C1 [Wang, Jianlong; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Harvard Stem Cell Inst, Boston, MA 02115 USA. [Wang, Jianlong; Orkin, Stuart H.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Div Hematol Oncol,Childrens Hosp, Boston, MA 02115 USA. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Harvard Stem Cell Inst, 44 Binney St, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu NR 51 TC 6 Z9 6 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2008 VL 188 IS 1-2 BP 23 EP 30 DI 10.1159/000113532 PG 8 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 323PG UT WOS:000257458500004 PM 18196921 ER PT J AU Shin, JM Vagin, O Munson, K Kidd, M Modlin, IM Sachs, G AF Shin, J. M. Vagin, O. Munson, K. Kidd, M. Modlin, I. M. Sachs, G. TI Molecular mechanisms in therapy of acid-related diseases SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE gastric acid secretion; peptic ulcer; gastroesophageal reflux disease; proton pump inhibitors; pharmacology; H,K ATPase ID PROTON-PUMP INHIBITORS; GASTROESOPHAGEAL-REFLUX DISEASE; PEPTIC-ULCER DISEASE; GASTRIC H+/K+-ATPASE; HELICOBACTER-PYLORI INFECTION; HEALTHY MALE-VOLUNTEERS; BETA-SUBUNIT; SARCOPLASMIC-RETICULUM; ALPHA-SUBUNIT; CDNA CLONING AB Inhibition of gastric acid secretion is the mainstay of the treatment of gastroesophageal reflux disease and peptic ulceration; therapies to inhibit acid are among the best-selling drugs worldwide. Highly effective agents targeting the histamine H2 receptor were first identified in the 1970s. These were followed by the development of irreversible inhibitors of the parietal cell hydrogen-potassium ATPase (the proton pump inhibitors) that inhibit acid secretion much more effectively. Reviewed here are the chemistry, biological targets and pharmacology of these drugs, with reference to their current and evolving clinical utilities. Future directions in the development of acid inhibitory drugs include modifications of current agents and the emergence of a novel class of agents, the acid pump antagonists. C1 [Shin, J. M.; Vagin, O.; Munson, K.; Sachs, G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. [Shin, J. M.; Vagin, O.; Munson, K.; Sachs, G.] W LA Med Ctr, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Kidd, M.; Modlin, I. M.] Yale Univ, Sch Med, Dept Surg, New Haven, CT 06520 USA. RP Sachs, G (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. EM gsachs@ucla.edu FU NIDDK NIH HHS [DK058333, DK053642, R01 DK053642-13, R01 DK058333-11, R01 DK077149-02, R01 DK077149-01A1, R01 DK053642, R01 DK053642-12, R01 DK058333, R01 DK077149, R56 DK058333, R56 DK058333-12] NR 89 TC 30 Z9 34 U1 0 U2 5 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD JAN PY 2008 VL 65 IS 2 BP 264 EP 281 DI 10.1007/s00018-007-7249-x PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 255PZ UT WOS:000252671200007 PM 17928953 ER PT J AU Brown, NK McCormick, DJ Brusic, V David, CS Kong, YCM AF Brown, Nicholas K. McCormick, Daniel J. Brusic, Vladimir David, Chella S. Kong, Yi-chi M. TI A novel H2A(-)E(+) transgenic model susceptible to human but not mouse thyroglobulin-induced autoimmune thyroiditis: Identification of mouse pathogenic epitopes SO CELLULAR IMMUNOLOGY LA English DT Article; Proceedings Paper CT 94th Annual Meeting of the American-Association-of-Immunologists CY MAY 18-22, 2007 CL Miami Beach, FL SP Amer Assoc Immunologists DE autoimmunity; class II transgene; experimental autoimmune thyroiditis; H2E transgene; thyroglobulin epitopes ID POTENTIAL ROLE; MICE; MOLECULES; PEPTIDE; SELF; PROTECTION; INDUCTION; DISEASE; MOTIFS; HLA AB The A(-)E(+) transgenic mouse is highly susceptible to human thyroglobulin (hTg)-induced thyroiditis, but strongly tolerant to a challenge by mouse thyroglobulin (mTg), in stark contrast to traditionally susceptible strains, wherein mTg induces stronger thyroiditis. To identify mouse thyroid epitopes recognized by destructive, hTg-primed T cells, we selected the three hTg epitopes known to be presented by H2E(b), as the basis for synthesizing potential mTg epitopes. One 15-mer peptide, mTg409, did prime T cells, elicit Ab, and induce thyroiditis. Moreover, cells primed with corresponding, pathogenic hTg410 cross-reacted with mTg409, and vice versa. mTg409 contained 4/4 anchor residues, similar to the corresponding hTg peptide. Based on this finding, a second mTg epitope, mTg179, was subsequently identified. These mTg autoepitopes, identified by using thyroiditogenic hTg epitopes, help to explain the severe thyroiditis seen in this novel A(-)E(+) transgenic model. (C) 2008 Elsevier Inc. All rights reserved. C1 [Brown, Nicholas K.; Kong, Yi-chi M.] Wayne State Univ, Sch Med, Dept Immunol & Microbiol, Detroit, MI 48201 USA. [McCormick, Daniel J.] Mayo Clin, Coll Med, Dept Biochem & Mol Biol, Rochester, MN 55905 USA. [Brusic, Vladimir] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [David, Chella S.] Mayo Clin, Coll Med, Dept Immunol, Rochester, MN 55905 USA. RP Kong, YCM (reprint author), Wayne State Univ, Sch Med, Dept Immunol & Microbiol, 540 E Canfield Ave, Detroit, MI 48201 USA. EM ykong@med.wayne.edu OI Brown, Nicholas/0000-0002-0046-2315 FU NCI NIH HHS [P30 CA015083, P30 CA015083-309015]; NIDDK NIH HHS [DK 45960, R01 DK045960-13, R01 DK045960] NR 28 TC 8 Z9 8 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PY 2008 VL 251 IS 1 BP 1 EP 7 DI 10.1016/j.cellimm.2008.02.002 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 312FI UT WOS:000256654100001 PM 18489063 ER PT J AU Tonon, G AF Tonon, Giovanni TI From oncogenome mining to functional validation of cancer genes SO CELLULAR ONCOLOGY LA English DT Meeting Abstract CT Meeting of the International-Society-for-Cellular-Oncology (ISCO 2008) CY MAR 05-08, 2008 CL Amsterdam, NETHERLANDS SP Int Soc Cellular Oncol C1 [Tonon, Giovanni] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1570-5870 J9 CELL ONCOL JI Cell. Oncol. PY 2008 VL 30 IS 2 BP 92 EP 92 PG 1 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 278QJ UT WOS:000254301100004 ER PT J AU Morokuma, J Blackiston, D Levin, M AF Morokuma, Junji Blackiston, Douglas Levin, Michael TI KCNQ1 and KCNE1 K+ channel components are involved in early left-right patterning in Xenopus laevis embryos SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY LA English DT Review DE KCNQ1; KCNE1; potassium channel; left-right asymmetry; Xenopus ID LEFT-RIGHT ASYMMETRY; LONG-QT SYNDROME; LEFT-RIGHT AXIS; 1ST CLEAVAGE PLANE; KCNQ1/KCNE1 POTASSIUM CHANNELS; INHERITED CARDIAC-ARRHYTHMIAS; MONOZYGOTIC TWINS; MIRROR-IMAGE; I-KS; ACID-SECRETION AB Several ion transporters have been implicated in left-right (LR) patterning. Here, we characterize a new component of the early bioelectrical circuit: the potassium channel KCNQ1 and its accessory subunit KCNE1. Having cloned the native Xenopus versions of both genes, we show that both are asymmetrically localized as maternal proteins during the first few cleavages of frog embryo development in a process dependent on microtubule and actin organization. Molecular loss-of-function using dominant negative constructs demonstrates that both gene products are required for normal LR asymmetry. We propose a model whereby these channels provide an exit path for K+ ions brought in by the H+, K+-ATPase. This physiological module thus allows the obligate but electroneutral H+, K+-ATPase to generate an asymmetric voltage gradient on the left and right sides. Our data reveal a new, bioelectrical component of the mechanisms patterning a large-scale axis in vertebrate embryogenesis. Copyright (C) 2008 S. Karger AG, Basel. C1 [Levin, Michael] Harvard Sch Dental Med, Ctr Regenerat & Dev Biol, Forsyth Inst, Boston, MA 02115 USA. Harvard Sch Dental Med, Dept Dev Biol, Boston, MA 02115 USA. RP Levin, M (reprint author), Harvard Sch Dental Med, Ctr Regenerat & Dev Biol, Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. EM mlevin@forsyth.org FU NCI NIH HHS [CO6RR11244]; NIDCR NIH HHS [5T32DE007327-07, T32 DE007327]; NIGMS NIH HHS [R01 GM077425, R01-GM07742] NR 148 TC 36 Z9 37 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-8987 EI 1421-9778 J9 CELL PHYSIOL BIOCHEM JI Cell. Physiol. Biochem. PY 2008 VL 21 IS 5-6 BP 357 EP 372 DI 10.1159/000129628 PG 16 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 293UT UT WOS:000255361600004 PM 18453744 ER PT J AU Cao, ZF Huett, A Kuballa, P Giallourakis, C Xavier, RJ AF Cao, Zhifang Huett, Alan Kuballa, Petric Giallourakis, Cosmas Xavier, Ramnik J. TI DLG1 is an anchor for the E3 ligase MARCH2 at sites of cell-cell contact SO CELLULAR SIGNALLING LA English DT Article DE DLG1; MARCH2; PDZ; ubiquitination; endosomal trafficking ID LARGE TUMOR-SUPPRESSOR; UBIQUITIN LIGASES; DOWN-REGULATION; PROTEIN; DROSOPHILA; TRAFFICKING; COMPLEXES; MEMBRANE; POLARITY; SYNAPSE AB PDZ domain containing molecular scaffolds plays a central role in organizing synaptic junctions. Observations in Drosophila and mammalian cells have implicated that ubiquitination and endosomal trafficking, of molecular scaffolds are critical to the development and maintenance of cell-cell junctions and cell polarity. To elucidate if there is a connection between these pathways, we applied an integrative genomic strategy, which combined comparative genomics and proteomics with cell biological assays. Given the importance of ubiquitin in regulating endocytic processes, we first identified the subset of E3 ligases with conserved PDZ binding motifs. Among this subset, the MARCH family ubiquitin ligases account for the largest family and MARCH2 has been previously implicated in endosomal trafficking. Next, we tested in an unbiased fashion, if MARCH2 binds PDZ proteins in vivo using a modified tandem affinity purification strategy followed by mass spectrometry. Of note, DLG1 was co-purified from MARCH2, with subsequent confirmation that MARCH2 interacts with full-length DLG1 in a PDZ domain dependent manner. Furthermore, we demonstrated that MARCH2 co-localized with DLG1 at sites of cell-cell contact. In addition, loss of the MARCH2 PDZ binding motif led to loss of MARCH2 localization at cell-cell contact sites and MARCH2 appeared to localize away from cell-cell junctions. In in vivo ubiquitination assays we show that MARCH2 promotes DLG1 ubiquitination. Overall, these results suggest that PDZ ligands with E3 ligase activity may link PDZ domain containing tumor suppressors to endocytic pathways and cell polarity determination. (C) 2007 Elsevier Inc. All rights reserved. C1 [Cao, Zhifang; Huett, Alan; Kuballa, Petric; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Cao, Zhifang; Huett, Alan; Giallourakis, Cosmas; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Xavier, RJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Simches Res Bldg,Rm 7222, Boston, MA 02114 USA. EM Xavier@molbio.mgh.harvard.edu FU NIAID NIH HHS [R01 AI062773-02, R01 AI062773]; NIDDK NIH HHS [P30 DK043351, P30 DK040561, P30 DK040561-12] NR 31 TC 7 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD JAN PY 2008 VL 20 IS 1 BP 73 EP 82 DI 10.1016/j.cellsig.2007.08.019 PG 10 WC Cell Biology SC Cell Biology GA 254IF UT WOS:000252579600008 PM 17980554 ER PT S AU Rosell, A Foerch, C Murata, Y Lo, EH AF Rosell, A. Foerch, C. Murata, Y. Lo, E. H. BE Zhou, LF Xi, G Chen, XC Keep, RF Huang, FP Hua, Y Lu, YC Muraszko, KM TI Mechanisms and markers for hemorrhagic transformation after stroke SO CEREBRAL HEMORRHAGE SE Acta Neurochirurgica Supplementum LA English DT Proceedings Paper CT 2nd International Symposium on Cerebral Hemorrhage CY NOV 10-11, 2007 CL Shanghai, PEOPLES R CHINA DE Intracerebral hemorrhage; tissue plasminogen activator; hemorrhagic transformation; blood-brain barrier ID TISSUE-PLASMINOGEN ACTIVATOR; ACUTE ISCHEMIC-STROKE; FOCAL CEREBRAL-ISCHEMIA; SYMPTOMATIC INTRACEREBRAL HEMORRHAGE; BRAIN-BARRIER DISRUPTION; THROMBOLYTIC THERAPY; MATRIX-METALLOPROTEINASE; OXIDATIVE STRESS; GENE POLYMORPHISMS; NEUROVASCULAR UNIT AB Intracerebral hemorrhagic transformation is it multifactorial phenomenon in which ischemic brain tissue converts into a hemorrhagic lesion with blood vessel leakage. Hemorrhagic transformation can significantly contribute to additional brain injury after stroke. Especially threatening, are the thrombolytic-induced hemorrhages after reperfusion therapy with tissue plasminogen activator (tPA). the only treatment available for ischemic stroke. [it this context. it is important to understand its underlying mechanisms and identify early markers of hemorrhagic transformation, so that we can both search for new treatments as well its predict clinical outcomes in patients. In this review, we discuss the emerging mechanisms for hemorrhage transformation after stroke, and briefly survey potential molecular. genetic. and neuroimaging markers that might be used for early detection of this challenging clinical problem. C1 [Lo, E. H.] MGH E 149-2401, Charlestown, MA 02129 USA. [Rosell, A.; Foerch, C.; Murata, Y.; Lo, E. H.] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Boston, MA 02114 USA. Harvard Med Sch, Program Neurosci, Boston, MA USA. RP Lo, EH (reprint author), MGH E 149-2401, Charlestown, MA 02129 USA. EM Lo@helix.mgh.harvard.edu FU National Institutes of Health [R01-NS37074, R01-NS48422, R01-NS53560, R01-NS56458, P50-NS10828, P01-NS55104] FX Supported in part by National Institutes of Health grants R01-NS37074,R01-NS48422, R01-NS53560, R01-NS56458, P50-NS10828, and P01-NS55104. NR 55 TC 18 Z9 18 U1 0 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA SN 0065-1419 BN 978-3-211-09468-6 J9 ACTA NEUROCHIR SUPPL JI Acta Neurochir. Suppl. PY 2008 VL 105 BP 173 EP + PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA BIT70 UT WOS:000262636300034 PM 19066105 ER PT J AU Yemisci, M Ay, H Kocaefe, C Qui, J Topalkara, K Ozguc, M Kirazli, S Ozcebe, O Moskowitz, MA Dalkara, T AF Yemisci, Muge Ay, Hakan Kocaefe, Cetin Qui, Jianhua Topalkara, Kamil Oezguec, Meral Kirazli, Serafettin Oezcebe, Osman Moskowitz, Michael A. Dalkara, Turgay TI Statin potentiates human platelet eNOS activity without enhancing eNOS mRNA and protein levels SO CEREBROVASCULAR DISEASES LA English DT Article DE statin; nitric oxide synthase; platelets ID ENDOTHELIAL NITRIC-OXIDE; COA-REDUCTASE INHIBITOR; CORONARY-HEART-DISEASE; L-ARGININE; SUBARACHNOID HEMORRHAGE; PFA-100(TM) SYSTEM; CEREBRAL VASOSPASM; THROMBUS FORMATION; ISCHEMIC STROKE; CLINICAL-TRIAL AB Background/Aims: Experimental studies suggest an enhanced endothelial and platelet nitric oxide (NO) generation after statin treatment, possibly due to increased endothelial NO synthase (eNOS) activity and protein levels. In parallel with experimental research, statins were shown to increase the forearm blood flow independently of serum cholesterol in humans. However, it was not possible to correlate blood flow changes with eNOS levels in these studies due to limitations in obtaining arterial samples. Hence, we investigated changes in eNOS activity, mRNA and protein levels after statin treatment in human platelets, which are readily accessible unlike arteries. Methods: In vitro bleeding times were measured in 22 patients by stimulating platelets with collagen-epinephrine or collagen-ADP. To assess platelet eNOS activity, the bleeding times were also determined after incubating platelets with L-arginine. The measurements were repeated following 14 days of pravastatin (40 mg/day) treatment. Platelet-rich plasma was collected before and after statin treatment to evaluate eNOS mRNA (semiquantitative RT-PCR) and protein levels (Western blotting). Results: The basal bleeding time was prolonged by 24 +/- 3% (mean +/- SE) when the samples were incubated with 500 mu M of L-arginine. The NOS inhibitor L-N-5-(I-iminoethyl) ornithine reversed this effect, suggesting that it was mediated by NO. After statin treatment, the NO-mediated prolongation of the bleeding time with 500 mu M of L-arginine was significantly potentiated (to 44 +/- 10%). Despite enhanced eNOS activity, there was no significant change in platelet eNOS mRNA and protein levels after statin treatment. Conclusion: These data demonstrate that platelet eNOS activity is potentiated after statin treatment in humans in parallel with experimental studies. Copyright (C) 2008 S. Karger AG, Basel. C1 [Yemisci, Muge; Ay, Hakan; Dalkara, Turgay] Hacettepe Univ, Fac Med, Dept Neurol, TR-06100 Ankara, Turkey. [Kocaefe, Cetin; Oezguec, Meral] Hacettepe Univ, Fac Med, Dept Med Biol, TR-06100 Ankara, Turkey. [Kirazli, Serafettin; Oezcebe, Osman] Hacettepe Univ, Fac Med, Dept Internal Med, Hematol Unit, TR-06100 Ankara, Turkey. [Yemisci, Muge; Dalkara, Turgay] Hacettepe Univ, Fac Med, Inst Neurol Sci & Psychiat, TR-06100 Ankara, Turkey. [Qui, Jianhua; Topalkara, Kamil; Moskowitz, Michael A.] Massachusetts Gen Hosp, Dept Radiol, Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. [Qui, Jianhua; Topalkara, Kamil; Moskowitz, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. RP Dalkara, T (reprint author), Hacettepe Univ, Fac Med, Dept Neurol, TR-06100 Ankara, Turkey. EM tdalkara@hacettepe.edu.tr RI YEMISCI, MUGE/I-9928-2013; KOCAEFE, CETIN/I-8336-2013 OI KOCAEFE, CETIN/0000-0003-3216-9399 FU Brain Research Organisation FX Supported by a grant from the Brain Research Organisation. NR 57 TC 13 Z9 13 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2008 VL 26 IS 2 BP 190 EP 198 DI 10.1159/000145327 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 355RG UT WOS:000259725400014 PM 18628618 ER PT J AU Garanger, E Aikawa, E Reynolds, F Weissleder, R Josephson, L AF Garanger, Elisabeth Aikawa, Elena Reynolds, Fred Weissleder, Ralph Josephson, Lee TI Simplified syntheses of complex multifunctional nanomaterials SO CHEMICAL COMMUNICATIONS LA English DT Article ID CONTRAST AGENTS; QUANTUM DOTS; NANOPARTICLES; CONJUGATION; ANTAGONISTS; PROBES AB Multifunctional probes are synthesized in a single step using peptide scaffold-based multifunctional single-attachment-point (MSAP) reagents. C1 [Josephson, Lee] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Josephson, L (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St, Charlestown, MA 02129 USA. EM ljosephson@mgh.harvard.edu FU NCI NIH HHS [P50 CA086355, P50 CA086355-08, U54 CA119349, U54 CA119349-040003, U54 CA126515, U54 CA126515-020002] NR 13 TC 27 Z9 27 U1 0 U2 8 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PY 2008 IS 39 BP 4792 EP 4794 DI 10.1039/b809537j PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 354ZK UT WOS:000259678200036 PM 18830495 ER PT J AU Ali, MM Woods, M Caravan, P Opina, ACL Spiller, M Fettinger, JC Sherry, AD AF Ali, M. Meser Woods, Mark Caravan, Peter Opina, Ana C. L. Spiller, Marga Fettinger, James C. Sherry, A. Dean TI Synthesis and relaxometric studies of a dendrimer-based pH-responsive MRI contrast agent SO CHEMISTRY-A EUROPEAN JOURNAL LA English DT Article DE dendrimers; imaging agents; lanthanide complexes; MRI contrast agents ID MAGNETIC-RESONANCE RELAXATION; AFFINITY FOLATE RECEPTOR; MODEL-FREE APPROACH; GABRIEL SYNTHESIS; ING-MANSKE; PARAMAGNETIC SOLUTIONS; MOLECULAR-DYNAMICS; PAMAM DENDRIMER; WATER EXCHANGE; PRIMARY AMINES AB The design of effective pH responsive MRI contrast agents is a key goal in the development of new diagnostic methods for conditions Such as kidney disease and cancer. A key factor determining the effectiveness of an agent is the difference between the relaxivity of the "on" state compared to that of the "off" state. In this paper, we demonstrate that it is possible to improve the pH-responsive action of a low molecular weight agent by conjugating it to a macromolecular construct. The synthesis of it bifunctional pH responsive agent is reported. As part of that synthetic pathway we examine the Ing-Manske reaction, identifying an undesirable by-product and establishing effective conditions for promoting a clean and effective reaction. Reaction of the bifunctional pH responsive agent with a G5-PAMAM dendrimer yielded a product with an average of 96 chelates per dendrimer. The relaxivity of the dendrimer conjugate rises from 10.8mM(-1)s(-1) (pH 9) to 24.0 mM(-1)s(-1) (pH 6) per Gd(3+) ion. This more than doubles the relaxivity pH response, Art, of our agent from just 51 % for the original low molecular weight chelate to 122% for the dendrimer. C1 [Ali, M. Meser; Woods, Mark; Opina, Ana C. L.; Sherry, A. Dean] Univ Texas Dallas, Dept Chem, Richardson, TX 75083 USA. [Caravan, Peter] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Caravan, Peter] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Spiller, Marga] New York Med Coll, Dept Radiol, Valhalla, NY 10595 USA. [Fettinger, James C.] Univ Calif Davis, Dept Chem, Davis, CA 95616 USA. [Sherry, A. Dean] Univ Texas SW Med Ctr Dallas, Adv Imaging Res Ctr, Dallas, TX 75390 USA. RP Sherry, AD (reprint author), Univ Texas Dallas, Dept Chem, POB 830660, Richardson, TX 75083 USA. EM dean.sherry@utsouthwestern.edu FU National Institutes of Health [RR-02584, CA-126608, CA-115531]; Robert A. Welch Foundation [AT-584] FX The authors thank the National Institutes of Health (RR-02584, CA-126608 and CA-115531), the Robert A. Welch Foundation (AT-584) for financial assistance. NR 47 TC 66 Z9 70 U1 4 U2 37 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0947-6539 J9 CHEM-EUR J JI Chem.-Eur. J. PY 2008 VL 14 IS 24 BP 7250 EP 7258 DI 10.1002/chem.200800402 PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA 342RP UT WOS:000258801500018 PM 18601236 ER PT J AU Walter, RE Wilk, JB Larson, MG Vasan, RS Keaney, JF Lipinska, I O'Connor, GT Benjamin, EJ AF Walter, Robert E. Wilk, Jemma B. Larson, Martin G. Vasan, Ramachandran S. Keaney, John F., Jr. Lipinska, Izabella O'Connor, George T. Benjamin, Emelia J. TI Systemic inflammation and COPD - The Framingham Heart Study SO CHEST LA English DT Article DE CD40 ligand; forced expiratory volume; inflammation; intercellular adhesion molecule-1; interleukin-6; monocyte chemoattractant protein-1; mycloperoxidase; p-selectin; pulmonary disease; chronic obstructive ID OBSTRUCTIVE PULMONARY-DISEASE; C-REACTIVE PROTEIN; AIRWAY-OBSTRUCTION; LUNG-FUNCTION; P-SELECTIN; INTERLEUKIN-6; ASSOCIATION; POPULATION; EXPRESSION; BRONCHITIS AB Background: The current paradigm for the pathogenesis of COPD includes an ultimately maladaptive local inflammatory response to environmental stimuli. We examined the hypothesis that systemic inflammatory biomarkers are associated with impaired lung function, particularly among those with extensive cigarette smoking. Methods: Using data from the Framingham Heart Study, we examined cross-sectional associations of systemic inflammatory biomarkers (CD40 ligand [CD40L], intercellular adhesion molecule [ICAM]-1, interleukin [IL]-6, monocyte chemoattractant protein-1, P-selectin, and myeloperoxidase, in addition to C-reactive protein) to impaired lung function. Results: IL-6 was consistently associated with impaired lung function; a 1-SD higher concentration of IL-6 was associated with a 41-mL lower FEV1 (95% confidence interval [CI], -61 to -20) and a borderline 15% higher odds of COPD (odds ratio, 1.15; 95% CI, 0.99 to 1.34). Additionally, P-selectin was associated with lower FEV1 levels; after adjusting for the other biomarkers, a 1-SD higher concentration of P-selectin predicted an FEV, that was on average 19 mL lower (95% CI, -37 to 0). Including the biomarkers individually as sole exposures in the models generally strengthened the impaired lung function/biomarker association; the relations of ICAM-1 to FEV1, and ICAM and CD40L to COPD became significant. The observed associations did not vary significantly with smoking history, except that the association between CD40L and COPD appeared greater in individuals with more extensive smoking histories. Conclusions: Among participants in the Framingham Heart Study, systemic inflammation was associated with lower levels of pulmonary function. Further research into the role of systemic inflammation in the development of pulmonary dysfunction is merited. C1 [Walter, Robert E.; O'Connor, George T.] Boston Univ, Sch Med, Sect Pulm Allergy & Crit Care Med, Boston, MA 02118 USA. [Wilk, Jemma B.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Pulm & Crit Care Med Sect, Boston, MA 02118 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Keaney, John F., Jr.] Univ Massachusetts, Sch Med, Div Cardiovasc Med, Worcester, MA USA. [Lipinska, Izabella] Whitaker Cardiovasc Inst, Boston, MA USA. RP Walter, RE (reprint author), Ctr Pulm, 80 E Concord,R304, Boston, MA 02118 USA. EM walterb@bu.edu OI Larson, Martin/0000-0002-9631-1254; Walter, Robert/0000-0003-4931-5049; O'Connor, George/0000-0002-6476-3926; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [HL064753, HL076784, N01-HC-25195, N01-HV-28178]; NIA NIH HHS [AG028321] NR 32 TC 114 Z9 116 U1 1 U2 5 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2008 VL 133 IS 1 BP 19 EP 25 DI 10.1378/chest.07-0058 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 251PL UT WOS:000252385600008 PM 17908709 ER PT J AU Holmes, WC AF Holmes, William C. TI Men's self-definitions of abusive childhood sexual experiences, and potentially related risky behavioral and psychiatric outcomes SO CHILD ABUSE & NEGLECT LA English DT Article DE sexual abuse; post-traumatic stress disorder; depression; HIV risk behavior; men ID PARENTAL BONDING INSTRUMENT; RELIABILITY; PREVALENCE; PERCEPTION; ADULTS AB Objectives: To estimate how many heterosexual and gay/bisexual men self-define abusive childhood sexual experiences (CSEs) to be childhood sexual abuse (CSA) and to assess whether CSA self-definition is associated with risky behavioral and psychiatric outcomes in adulthood. Methods: In Philadelphia County, 197 (66%) of 298 recruited men participated in a telephone survey. They were screened for CSEs and then asked if they self-defined abusive CSEs to be CSA; they also were asked about risk behavior histories and post-traumatic stress disorder (PTSD) and depression symptoms. Results: Of 43 (22%) participants with abusive CSEs, 35% did not and 65% did self-define abusive CSEs to be CSA ("Non-Definers" and "Definers," respectively). Heterosexual and gay/bisexual subgroups' CSA self-definition rates did not significantly differ. When self-definition subgroups were compared to those without CSEs ("No-CSEs"), Non-Definers had lower perceived parental care (p =.007) and fewer siblings (p =.03), Definers had more Hispanics and fewer African Americans (p =.04), and No-CSEs had fewer gay/bisexual men (p =.002) and fewer reports of physical abuse histories (p =.02) than comparison groups. Non-Definers reported more sex under the influence (p =.001) and a higher mean number of all lifetime sex partners (p =.004) as well as (only) female sex partners (p =.05). More Non-Definers than Definers reported having experienced penetrative sex as part of their CSA (83% vs. 35%, p =.006). Different explanations about self-definition were provided by subgroups. Conclusions: Many men with abusive CSEs do not self-define these CSEs to be CSA, though not in a way that differs by sexual identity. The process by which men self-define their abusive CSEs to be CSA or not appears to be associated not only with self-explanations that differ by self-definition subgroup, but also with behavioral outcomes that impart risk to Non-Definers. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Holmes, William C.] Univ Penn, Sch Med, Ctr Hlth Equ Res & Promot, Philadelphia Vet Affairs Med Care, Philadelphia, PA 19104 USA. [Holmes, William C.] Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Holmes, William C.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Leonard Davis Inst, Philadelphia, PA 19104 USA. RP Holmes, WC (reprint author), 733 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [DA015635, R03 DA015635, R03 DA015635-02] NR 25 TC 25 Z9 25 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2134 J9 CHILD ABUSE NEGLECT JI Child Abuse Negl. PD JAN PY 2008 VL 32 IS 1 BP 83 EP 97 DI 10.1016/j.chiabu.2007.09.005 PG 15 WC Family Studies; Psychology, Social; Social Work SC Family Studies; Psychology; Social Work GA 263ZM UT WOS:000253255000006 PM 18035415 ER PT J AU Wolff, JC Greene, RW Ollendick, TH AF Wolff, Jennifer C. Greene, Ross W. Ollendick, Thomas H. TI Differential responses of children with varying degrees of reactive and proactive aggression to two forms of psychosocial treatment SO CHILD & FAMILY BEHAVIOR THERAPY LA English DT Article DE oppositional defiant disorder; aggression; treatment; reactive; proactive ID OPPOSITIONAL DEFIANT DISORDER; YOUTH AB This study examined differential treatment effects for children with varying degrees of reactive and proactive aggression who received one of two types of psychosocial treatments that were specifically designed to address the unique characteristics associated with these two subtypes of aggression. Forty-seven affectively dysregulated children with oppositional defiant disorder (ODD) participated in the study and were randomly but proportionately assigned to Collaborative Problem Solving (n = 28) or Parent Training (n = 19) treatment conditions. Results indicate a main effect for type of treatment, modest support for the moderating role of proactive aggression, and no support for reactive aggression as a moderator of treatment outcome. Implications for assessment and treatment of aggression are discussed. C1 [Wolff, Jennifer C.; Ollendick, Thomas H.] Virginia Tech, Dept Psychol, Blacksburg, VA 24060 USA. [Greene, Ross W.] Massachusetts Gen Hosp, Dept Psychiat, Collaborat Problem Solving Inst, Boston, MA 02114 USA. [Greene, Ross W.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Ollendick, Thomas H.] Virginia Tech, Ctr Child Study, Blacksburg, VA 24060 USA. RP Wolff, JC (reprint author), Virginia Tech, Dept Psychol, 460 Turner St,Suite 207, Blacksburg, VA 24060 USA. EM jwolff@vt.edu; tho@vt.edu NR 22 TC 2 Z9 2 U1 5 U2 7 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0731-7107 J9 CHILD FAM BEHAV THER JI Child Fam. Behav. Ther. PY 2008 VL 30 IS 1 BP 37 EP 50 DI 10.1300/J019v30n01_03 PG 14 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 271PM UT WOS:000253801200003 ER PT J AU Keuthen, NJ Flessner, CA Woods, DW Franklin, ME Piacentini, JA Khanna, M Moore, P Cashin, S AF Keuthen, Nancy J. Flessner, Christopher A. Woods, Douglas W. Franklin, Martin E. Piacentini, John A. Khanna, Muniya Moore, Phoebe Cashin, Susan CA TLC-SAB TI Parent-Youth Rating Concordance for Hair Pulling Variables, Functional Impairment, and Anxiety Scale Scores in Trichotillomania SO CHILD & FAMILY BEHAVIOR THERAPY LA English DT Article DE Agreement; rating concordance; trichotillomania ID CHILD AGREEMENT; PSYCHOMETRIC PROPERTIES; STRUCTURED INTERVIEW; DSM-IV; DISORDERS; ISSUES; SCHEDULE AB Knowledge of cross-informant rating concordance is critical for the assessment of child and adolescent problems in clinical and research settings. We explored parent-youth rating concordance for hair pulling variables, functional impairment, and anxiety symptoms in a sample of child and adolescent hair pullers (n = 133) satisfying conservative diagnostic criteria for trichotillomania (TTM). Whole group analyses reveal significant parent-youth agreement on all study variables. Split group analyses, however, reveal superior parent-youth concordance for the adolescent (15-17 years old) versus younger (10-12 years old) hair pullers for awareness of hair pulling and anxiety scale scores. These results highlight the need for both parent and youth ratings when assessing younger children with TTM. C1 [Keuthen, Nancy J.] Massachusetts Gen Hosp, Trichotillomania Clin, Boston, MA 02114 USA. [Keuthen, Nancy J.] Harvard Univ, Sch Med, Boston, MA USA. [Flessner, Christopher A.] Rhode Isl Hosp, Providence, RI USA. [Flessner, Christopher A.] Brown Univ, Sch Med, Providence, RI 02912 USA. [Woods, Douglas W.; Cashin, Susan] Univ Wisconsin, Milwaukee, WI 53201 USA. [Franklin, Martin E.; Khanna, Muniya] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Piacentini, John A.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Moore, Phoebe] Duke Univ, Durham, NC USA. RP Keuthen, NJ (reprint author), Massachusetts Gen Hosp, Trichotillomania Clin, Simches Res Bldg,Floor 2,185 Cambridge St, Boston, MA 02114 USA. EM nkeuthen@partners.org RI Citations, TLC SAB/C-4006-2011; Flessner, Christopher/K-1483-2015 NR 20 TC 2 Z9 2 U1 0 U2 2 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0731-7107 J9 CHILD FAM BEHAV THER JI Child Fam. Behav. Ther. PY 2008 VL 30 IS 4 BP 337 EP 353 DI 10.1080/07317100802483215 PG 17 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 388EO UT WOS:000262003300003 ER PT J AU Albert, CM Nam, EG Rimm, EB Jin, HW Hajjar, RJ Hunter, DJ MacRae, CA Ellinor, PT AF Albert, Christine M. Nam, Edwin G. Rimm, Eric B. Jin, Hong Wei Hajjar, Roger J. Hunter, David J. MacRae, Calum A. Ellinor, Patrick T. TI Cardiac sodium channel gene variants and sudden cardiac death in women SO CIRCULATION LA English DT Article DE death, sudden; epidemiology; genetics; ion channels; women ID LONG-QT SYNDROME; VENTRICULAR-FIBRILLATION; BRUGADA-SYNDROME; UNITED-STATES; SCN5A; MUTATIONS; RISK; REPOLARIZATION; POPULATION; EXPRESSION AB Background-Several cardiac ion channel genes have been implicated in monogenic traits with a high risk of sudden cardiac death (SCD). Mutations or rare variants in these genes have been proposed as potential contributors to more common forms of SCD, but this hypothesis has not been assessed systematically. Methods and Results-We directly sequenced the entire coding region and splice junctions of 5 cardiac ion channel genes, SCN5A, KCNQ1, KCNH2, KCNE1, and KCNE2, in 113 SCD cases from 2 large prospective cohorts of women (Nurses' Health Study) and men (Health Professional Follow-Up Study). Controls from the same population were then screened for the presence of mutations or rare variants identified in cases, and sequence variants without prior functional data were expressed in Xenopus oocytes to assess their biophysical consequences. No mutations or rare variants were identified in any of the 53 subjects who were men. In contrast, in 6 of 60 women (10%), we identified 5 rare missense variants in SCN5A that either had been associated previously with long-QT syndrome (A572D and G615E), had been reported to alter sodium channel function (F2004L), or had not been reported previously in control populations (A572F and W1205C). Of the 4 variants without prior functional data, 3 variants were located in the I-II linker (A572D, A572F, and G615E), and all resulted in significantly shorter recovery times from inactivation. When compared with 733 control samples from the same population, the overall frequency of these rare variants in SCN5A was significantly higher in the SCD cases (6/60, 10.0%) than in controls (12/733, 1.6%; P = 0.001). Conclusion-Functionally significant mutations and rare variants in SCN5A may contribute to SCD risk among women. C1 [Albert, Christine M.] Brigham & Womens Hosp, Ctr Arrhythmia Prevent, Div Prevent Med, Boston, MA 02215 USA. [Albert, Christine M.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02215 USA. [Rimm, Eric B.; Hunter, David J.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02215 USA. [Rimm, Eric B.; Hunter, David J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. [Nam, Edwin G.; MacRae, Calum A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [MacRae, Calum A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Rimm, Eric B.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Jin, Hong Wei; Hajjar, Roger J.] Mt Sinai Sch Med, Cardiovasc Res Ctr, New York, NY USA. RP Albert, CM (reprint author), Brigham & Womens Hosp, Ctr Arrhythmia Prevent, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM calbert@partners.org FU NHLBI NIH HHS [HL068070-04, HL71632, R01 HL075431] NR 47 TC 64 Z9 64 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 1 PY 2008 VL 117 IS 1 BP 16 EP 23 DI 10.1161/CIRCULATIONAHA.107.736330 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 247QJ UT WOS:000252094100006 PM 18071069 ER PT J AU Gaynes, BN Rush, AJ Trivedi, MH Wisniewski, SR Spencer, D Fava, M AF Gaynes, Bradley N. Rush, A. John Trivedi, Madhukar H. Wisniewski, Stephen R. Spencer, Donald Fava, Maurizio TI The STAR*D study: Treating depression in the real world SO CLEVELAND CLINIC JOURNAL OF MEDICINE LA English DT Article ID SEQUENCED TREATMENT ALTERNATIVES; TREATMENT-RESISTANT DEPRESSION; FAILED MEDICATION TREATMENTS; PRIMARY-CARE; 2ND-STEP TREATMENTS; CLINICAL-PRACTICE; MAJOR DEPRESSION; GLOBAL BURDEN; RATING-SCALE; AUGMENTATION AB The Sequenced Treatment Alternatives to Relieve Depression (START) study evaluated feasible treatment strategies to improve clinical outcomes for real-world patients with treatment-resistant depression. Although the study found no clear-cut "winner," it does provide guidance on how to start therapy and how to proceed if initial treatment fails. C1 [Gaynes, Bradley N.] Univ N Carolina, Sch Med, Neurosci Hosp, Dept Psychiat, Chapel Hill, NC 27599 USA. [Wisniewski, Stephen R.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Rush, A. John; Spencer, Donald] Univ Texas Dallas, SW Med Ctr, Dallas, TX USA. [Fava, Maurizio] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gaynes, BN (reprint author), Univ N Carolina, Sch Med, Neurosci Hosp, Dept Psychiat, 1st Floor,Room 10306,CB 7160, Chapel Hill, NC 27599 USA. EM bgaynes@med.unc.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Gaynes, Bradley/0000-0002-8283-5030; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01MH90003] NR 43 TC 51 Z9 53 U1 0 U2 0 PU CLEVELAND CLINIC PI CLEVELAND PA 9500 EUCLID AVE, CLEVELAND, OH 44106 USA SN 0891-1150 J9 CLEV CLIN J MED JI Clevel. Clin. J. Med. PD JAN PY 2008 VL 75 IS 1 BP 57 EP 66 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 250IJ UT WOS:000252292900009 PM 18236731 ER PT J AU Januzzi, JL Lewandrowski, KB Bashirians, G Jackson, S Freyler, D Smith, K Murakami, MM Apple, FS AF Januzzi, James L., Jr. Lewandrowski, Kent B. Bashirians, George Jackson, Shari Freyler, Deb Smith, Katrina Murakami, Maryann M. Apple, Fred S. TI Analytical and clinical performance of the Ortho-Clinical Diagnostics VITROS (R) amino-terminal pro-B type natriuretic peptide assay SO CLINICA CHIMICA ACTA LA English DT Article DE NT-proBNP; heart failure; diagnosis ID EMERGENCY-DEPARTMENT PRIDE; CORONARY-HEART-DISEASE; NT-PROBNP; PULMONARY-HYPERTENSION; CARDIOVASCULAR EVENTS; FAILURE; MORTALITY; BNP; DYSPNEA; PREDICTION AB Background: Measurement of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is useful for evaluating patients with heart failure (HF). Methods: We evaluated the performance of a new automated NT-proBNP assay. Results: The VITROS NT-proBNP assay had mean within-run and total imprecision of 1.0% and 3.4% at NT-proBNP concentrations from 67-27,500 ng/l. Acceptable linearity, functional/analytical sensitivity were demonstrated. Anticoagulant/tube types had no effect on results. Excellent sample stability and no high-dose hook were observed. High correlation between the VITROS and Elecsys methods was demonstrated (r=0.995; P <.001), with 98.3% clinical concordance. VITROS NT-proBNP concentrations were significantly higher in HF subjects than those without (1210 versus 68 ng/l; P <.001) and associated with HF symptom severity (P <.001). The VITROS assay had AUC for HF of 0.95 (P <.001), and had excellent NPV for excluding HF. Conclusions: The automated VITROS NT-proBNP assay demonstrates excellent analytical and clinical performance for evaluating the presence and severity of HE (0 2007 Elsevier B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Labs, Boston, MA USA. Ortho Clin Diagnost, Rochester, NY USA. Hennepin Cty Med Ctr, Dept Lab Med & Pathol, Minneapolis, MN USA. RP Januzzi, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Yawkey 5984,55 Fruit St, Boston, MA 02114 USA. EM JJanuzzi@Partners.org NR 34 TC 2 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JAN PY 2008 VL 387 IS 1-2 BP 48 EP 54 DI 10.1016/j.cca.2007.08.018 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 238VK UT WOS:000251475900008 PM 17915201 ER PT J AU Domizio, S Conte, E Puglielli, C Domizio, R Verrotti, A Pollice, R Casacchia, M Conti, CM Roncone, R Sabatino, G Doyle, R Barbacane, RC Conti, P Sabatino, G AF Domizio, Sergio Conte, Emanuela Puglielli, Cristina Domizio, Roberto Verrotti, Alberto Pollice, Rocco Casacchia, Massimo Conti, Chiara M. Roncone, Rita Sabatino, Giovanni Doyle, Robert Barbacane, Renato C. Conti, Pio Sabatino, Giuseppe TI Epileptic EEG discharges and short non-convulsive crisis: Influence on cognitive and psychobehavioural functions in youths SO CLINICAL AND INVESTIGATIVE MEDICINE LA English DT Article ID CHILDREN; SEIZURES; PSYCHOPATHOLOGY; DETERMINANTS; POPULATION; EXPRESSION; DISEASES; CELLS; AGE AB Purpose: Learning and behavioural difficulties often occur in benign childhood epilepsy. In recent years, several electroencephalogram (EEG) characteristics have been related to the occurrence of learning and behavioral problems. We determined if the cognitive characteristics of epileptic children depend exclusively on illness factors, or if epileptic electroencephalogram discharges during the crisis contribute to these changes. Methods: We studied a randomly selected group of 150 youths with short non-convulsive crises, who completed cognitive testing and electroencephalographic studies. The inclusion criteria were: undefined crisis, variations in cognitive function and/or frequent epileptiform discharges on the electroencephalogram. Results: Previous research indicates that the type of epilepsy and the patient's educational level can influence cognitive functioning. The electroencephalographic epileptic discharges during the crisis has been found to influence cognitive transitory functions such as vigilance or swiftness of mental functions. The type of epilepsy is correlated statistically with impairment of learning ability tests: reading (F, 5.487, P = 0.005) and mathematics (F, 3.007, P = 0.05). In addition, 40% of the epileptic patients had behavioural disordered versus 16% for the control group (P < 0.02). Conclusions: Our results show dissociation between the characteristic directly dependent on epilepsy, particularly the type of epilepsy, on stable cognitive functions, such as the progress in school, and the effect of parosystic anomalies or the immediate effect of crisis and EEG discharges on cognitive processes. C1 [Domizio, Sergio; Conte, Emanuela; Puglielli, Cristina; Domizio, Roberto; Roncone, Rita; Sabatino, Giovanni; Sabatino, Giuseppe] Univ G dAnnunzio, Neonatal Intens Care Unit, Chieti, Italy. [Verrotti, Alberto] Univ G dAnnunzio, Dept Pediat, Chieti, Italy. [Conti, Chiara M.] Univ G dAnnunzio, Sch Psychol, Clin Psychol Div, Chieti, Italy. [Doyle, Robert] Massachusetts Gen Hosp, Div Pediat Psychopharmacol, Boston, MA 02114 USA. [Barbacane, Renato C.] Univ G dAnnunzio, Div Immunol, Chieti, Italy. [Domizio, Roberto; Pollice, Rocco; Casacchia, Massimo] Univ Aquila, Dept Expt Med, I-67100 Laquila, Italy. RP Sabatino, G (reprint author), Univ G dAnnunzio, Neonatal Intens Care Unit, Via dei Vestini, Chieti, Italy. EM gsabatino@unich.it RI Roncone, Rita/H-3095-2012 NR 52 TC 1 Z9 1 U1 0 U2 2 PU CANADIAN SOC CLINICAL INVESTIGATION PI OTTAWA PA CSCI HEAD OFFICE, 774 ECHO DRIVE, OTTAWA, ON K1S 5N8, CANADA SN 0147-958X J9 CLIN INVEST MED JI Clin. Invest. Med. PY 2008 VL 31 IS 1 BP E30 EP E40 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 282TC UT WOS:000254589100005 ER PT J AU Freeman, SR Lundahl, K Schilling, LM Jensen, JD Dellavalle, RP AF Freeman, Scott R. Lundahl, Kristy Schilling, Lisa M. Jensen, J. Daniel Dellavalle, Robert P. TI Human research review committee requirements in medical journals SO CLINICAL AND INVESTIGATIVE MEDICINE LA English DT Article ID BOARD; QUALITY; EDITORS AB Purpose: Independent ethical review committees safeguard participants in human research. The purpose of this study was to describe the current ethical guidelines for human research requirements in the Instructions to Authors of the English language medical journals previously studied in 1995. Methods: The instructions to authors of English language medicine journals from the Abridged Index Medicus were searched for any policies regarding guidance on the ethical treatment of human subjects in research. Results: More medical journals require independent ethics committee approval of human research now [84/101 (83%)] than 10 years ago [48/102 (47%) (P<0.001)], and most journals continue to require that this disclosure appear in the manuscript [71/84 (85%) vs. then 37/48 (77%) (P=0.29)]. Fewer medical journal instructions to authors provide no ethical guidelines for human research now [8/101 (8%)] than 10 years ago [25/102 (24%) (P<0.001)]. No journal required submission of the study approval letter or of the approved protocol. Conclusions: Although medicine journals increasingly require disclosure statements of independent ethics committee approval for human research, they fail to verify such approval beyond taking authors for their word. C1 [Dellavalle, Robert P.] Univ Colorado Denver & Hlth Sci Ctr, Denver Vet Affairs Med Ctr, Sch Med, Denver, CO USA. [Freeman, Scott R.; Lundahl, Kristy; Jensen, J. Daniel; Dellavalle, Robert P.] Univ Colorado Denver & Hlth Sci Ctr, Dept Dermatol, Sch Med, Denver, CO USA. [Schilling, Lisa M.] Univ Colorado Denver & Hlth Sci Ctr, Dept Med, Sch Med, Denver, CO USA. RP Dellavalle, RP (reprint author), 1055 Clermont St,165, Denver, CO 80220 USA. EM robert.dellavalle@uchsc.edu RI Dellavalle, Robert/L-2020-2013 OI Dellavalle, Robert/0000-0001-8132-088X FU NCI NIH HHS [K-07CA92550]; NIAMS NIH HHS [T32 AR07411] NR 22 TC 5 Z9 5 U1 0 U2 2 PU CANADIAN SOC CLINICAL INVESTIGATION PI OTTAWA PA CSCI HEAD OFFICE, 774 ECHO DRIVE, OTTAWA, ON K1S 5N8, CANADA SN 0147-958X J9 CLIN INVEST MED JI Clin. Invest. Med. PY 2008 VL 31 IS 1 BP E49 EP E54 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 282TC UT WOS:000254589100007 PM 18312748 ER PT J AU Counter, SA Buchanan, LH Ortega, F AF Counter, S. Allen Buchanan, Leo H. Ortega, Fernando TI Zinc protoporphyrin levels, blood lead levels and neurocognitive deficits in Andean children with chronic lead exposure SO CLINICAL BIOCHEMISTRY LA English DT Article DE lead; blood; zinc protoporphyrin; neurocognitive; memory; digit span; Andes ID IRON-DEFICIENCY; BREAST-MILK; HEMOGLOBIN; IMPAIRMENT; WORKERS AB Objectives: To investigate the relationship between blood lead (PbB), zinc protoporphyrin (ZPP) levels and performance on a test of auditory memory in Andean children and adolescents with chronic lead (Pb) exposure. Design and methods: PbB and ZPP levels were measured in blood samples from 166 participants (aged 6-16 yrs.) exposed to Pb in a local ceramic glazing cottage industry in Ecuadorian villages. PbB levels and ZPP/heme ratios were analyzed in relation to performance on the Digit Span subtest of the Wechsler IV intelligence scale, a test of auditory memory. Results: Mean PbB level for the study group was 18.0 mu g/dL (S.D.: 15. 1; range: 3.0-86.0), and the mean ZPP/heme ratio was 105.7 mu mol/mol (S.D.: 100.9; range: 36.0-592.0). There was no significant difference in PbB and ZPP levels between the 84 females and the 82 males. The mean Digit Span scale score (DS SS) for the study group was 6.81 (S.D.: 2.95; range: 1.0-17.0), which is below the average score of 10 for the test, with the females performing significantly better than males (t=2.435; p=0.01). Regression analyses revealed statistically significant inverse associations between DS SS and PbB level (r=0.251, p=0.001), and between DS SS and ZPP/heme ratio (r=0.246,p=0.00). Conclusion: Elevated PbB levels, representing acute exposure, and ZPP levels, reflecting chronic Pb exposure in this cohort of Andean inhabitants were associated with poor performance on a test of auditory memory, suggesting that the children and adolescents in the study area have neurocognitive deficits that may affect learning. (c) 2007 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. C1 [Counter, S. Allen] Harvard Univ, Sch Med, Biol Labs, Dept Neurol, Cambridge, MA 02138 USA. [Buchanan, Leo H.] Massachusetts Gen Hosp, Dept Neurophysiol, Boston, MA 02114 USA. [Buchanan, Leo H.] Univ Massachusetts, Sch Med, Shriver Ctr, Dept Pediat, Waltham, MA USA. [Buchanan, Leo H.] Harvard Univ, Hlth Serv, Dept Otolaryngol, Cambridge, MA USA. [Ortega, Fernando] Univ San Francisco, Coll Hlth Sci, Integrated Community Dev Dept, Quito, Ecuador. RP Counter, SA (reprint author), Harvard Univ, Sch Med, Biol Labs, Dept Neurol, 16 Divin Ave, Cambridge, MA 02138 USA. EM allen_Counter@harvard.edu NR 27 TC 18 Z9 19 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0009-9120 J9 CLIN BIOCHEM JI Clin. Biochem. PD JAN PY 2008 VL 41 IS 1-2 BP 41 EP 47 DI 10.1016/j.clinbiochem.2007.10.002 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 244GQ UT WOS:000251854800007 PM 18035344 ER PT J AU Lightner, A Schust, DJ Chen, YBA Barrier, BF AF Lightner, Amy Schust, Danny J. Chen, Yi-Bin A. Barrier, Breton F. TI The fetal allograft revisited: Does the study of an ancient invertebrate species shed light on the role of natural killer cells at the maternal-fetal interface? SO CLINICAL & DEVELOPMENTAL IMMUNOLOGY LA English DT Review ID ASCIDIAN BOTRYLLUS-SCHLOSSERI; LARGE GRANULAR LYMPHOCYTES; CLASS-I; HLA-G; NK CELLS; HISTOCOMPATIBILITY COMPLEX; COLONIAL UROCHORDATE; CYTOKINE PRODUCTION; HUMAN IMPLANTATION; TROPHOBLAST CELLS AB Human pregnancy poses a fundamental immunological problem because the placenta and fetus are genetically different from the host mother. Classical transplantation theory has not provided a plausible solution to this problem. Study of naturally occurring allogeneic chimeras in the colonial marine invertebrate, Botryllus schlosseri, has yielded fresh insight into the primitive development of allorecognition, especially regarding the role of natural killer (NK) cells. Uterine NK cells have a unique phenotype that appears to parallel aspects of the NK-like cells in the allorecognition system of B. schlosseri. Most notably, both cell types recognize and reject "missing self" and both are involved in the generation of a common vascular system between two individuals. Chimeric combination in B. schlosseri results in vascular fusion between two individual colonies; uterine NK cells appear essential to the establishment of adequate maternal-fetal circulation. Since human uterine NK cells appear to de-emphasize primary immunological function, it is proposed that they may share the same evolutionary roots as the B. schlosseri allorecognition system rather than a primary origin in immunity. Copyright (C) 2008 Amy Lightner et al. C1 [Schust, Danny J.; Barrier, Breton F.] Univ Missouri, Sch Med, Dept Obstet Gynecol & Womens Hlth, Columbia, MO 65201 USA. [Lightner, Amy] Boston Univ, Sch Med, Boston, MA 02118 USA. [Chen, Yi-Bin A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. RP Schust, DJ (reprint author), Univ Missouri, Sch Med, Dept Obstet Gynecol & Womens Hlth, Columbia, MO 65201 USA. EM schustd@health.missouri.edu NR 84 TC 6 Z9 6 U1 0 U2 2 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1740-2522 EI 1740-2530 J9 CLIN DEV IMMUNOL JI Clin. Dev. Immunol. PY 2008 AR 631920 DI 10.1155/2008/631920 PG 10 WC Immunology SC Immunology GA 332FL UT WOS:000258067900001 ER EF