FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Chen, D Bruno, J Easlon, E Lin, SJ Cheng, HL Alt, FW Guarente, L AF Chen, Danica Bruno, Joanne Easlon, Erin Lin, Su-Ju Cheng, Hwei-Ling Alt, Frederick W. Guarente, Leonard TI Tissue-specific regulation of SIRT1 by calorie restriction SO GENES & DEVELOPMENT LA English DT Article DE aging; calorie restriction; SIRT1 ID MITOCHONDRIAL-FUNCTION; CELL-SURVIVAL; LIFE-SPAN; P53; PGC-1-ALPHA; COMPLEX; GLUCOSE; HEALTH; LIVER; MICE AB Calorie restriction (CR) has been reported to increase SIRT1 protein levels in mice, rats, and humans, and elevated activity of SIRT1 orthologs extends life span in yeast, worms, and flies. In this study, we challenge the paradigm that CR induces SIRT1 activity in all tissues by showing that activity of this sirtuin in the liver is, in fact, reduced by CR and activated by a high-caloric diet. We demonstrate this change both by assaying levels of SIRT1 and its small molecule regulators, NAD and NADH, as well as assessing phenotypes of a liver-specific SIRT1 knockout mouse on various diets. Our findings suggest that designing CR mimetics that target SIRT1 to provide uniform systemic benefits may be more complex than currently imagined. C1 [Chen, Danica; Bruno, Joanne; Guarente, Leonard] MIT, Dept Biol, Cambridge, MA 02139 USA. [Easlon, Erin; Lin, Su-Ju] Univ Calif Davis, Microbiol Sect, Davis, CA 95616 USA. [Cheng, Hwei-Ling; Alt, Frederick W.] Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst, Boston, MA 02115 USA. [Cheng, Hwei-Ling; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Guarente, L (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM leng@mit.edu FU NIA NIH HHS [AG15339-09, R01 AG011119, R01 AG015339] NR 28 TC 300 Z9 307 U1 2 U2 24 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 JUL 1 PY 2008 VL 22 IS 13 BP 1753 EP 1757 DI 10.1101/gad.1650608 PG 5 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 320QD UT WOS:000257249200007 PM 18550784 ER PT J AU Heusner, CL Beutler, LR Houser, CR Palmiter, RD AF Heusner, Carrie L. Beutler, Lisa R. Houser, Carolyn R. Palmiter, Richard D. TI Deletion of GAD67 in dopamine receptor-1 expressing cells causes specific motor deficits SO GENESIS LA English DT Article DE dopamine; GABA; striatum; behavior; Cre-Iox; recombination ID GLUTAMIC-ACID DECARBOXYLASE; GAMMA-AMINOBUTYRIC-ACID; TEMPORAL-LOBE EPILEPSY; MEDIUM SPINY NEURONS; HUNTINGTONS-DISEASE; MICE LACKING; GABAERGIC NEURONS; NUCLEUS-ACCUMBENS; GENE-EXPRESSION; TRANSGENIC MICE AB The medium spiny neurons (MSNs), which comprise the direct and indirect output pathways from the striatum, use gamma-aminobutyric acid (GABA) as their major fact-acting neurotransmitter. We generated mice carrying a conditional allele of the Gad1 gene, which encodes GAD67, one of the two enzymes responsible for GABA biosynthesis, and bred them to mice expressing Cre recombinase at the dopamine D1 receptor locus (Drd1a) to selectively reduce GABA synthesis in the direct output pathway from the striatum. We show that these mice are deficient in some types of motor skills, but normal for others, suggesting a differential role for GABA release from D1 receptor-containing neurons. C1 [Heusner, Carrie L.; Palmiter, Richard D.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [Beutler, Lisa R.; Palmiter, Richard D.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Palmiter, Richard D.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA. [Houser, Carolyn R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. [Houser, Carolyn R.] VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. RP Palmiter, RD (reprint author), Univ Washington, Dept Biochem, Seattle, WA 98195 USA. EM palmiter@u.washington.edu FU BLRD VA [I01 BX000404]; Howard Hughes Medical Institute NR 47 TC 22 Z9 22 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-954X J9 GENESIS JI Genesis PD JUL PY 2008 VL 46 IS 7 BP 357 EP 367 DI 10.1002/dvg.20405 PG 11 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 334EL UT WOS:000258205000003 PM 18615733 ER PT J AU Lin, AE Basson, CT Goldmuntz, E Magoulas, PL McDermott, DA McDonald-McGinn, DM McPherson, E Morris, CA Noonan, J Nowak, C Pierpont, ME Pyeritz, RE Rope, AF Zackai, E Pober, BR AF Lin, Angela E. Basson, Craig T. Goldmuntz, Elizabeth Magoulas, Pilar L. McDermott, Deborah A. McDonald-McGinn, Donna M. McPherson, Elspeth Morris, Colleen A. Noonan, Jacqueline Nowak, Catherine Pierpont, Mary Ella Pyeritz, Reed E. Rope, Alan F. Zackai, Elaine Pober, Barbara R. TI Adults with genetic syndromes and cardiovascular abnormalities: clinical history and management SO GENETICS IN MEDICINE LA English DT Review DE congenital heart defect; deletion 22q11; Down syndrome; Marfan syndrome; Noonan syndrome; Turner syndrome; Williams-Beuren syndrome ID CONGENITAL HEART-DISEASE; HOLT-ORAM-SYNDROME; HEREDITARY HEMORRHAGIC TELANGIECTASIA; WILLIAMS-BEUREN-SYNDROME; CAUSE NOONAN-SYNDROME; GROWTH-HORMONE TREATMENT; 22Q11 DELETION SYNDROME; PULMONARY ARTERIOVENOUS-MALFORMATIONS; INTERRUPTED AORTIC-ARCH; IN-VITRO FERTILIZATION AB Cardiovascular abnormalities, especially structural congenital heart defects, commonly occur in malformation syndromes and genetic disorders. Individuals with syndromes comprise-a significant proportion of those affected with selected congenital heart defects such as complete atrioventricular canal, interrupted arch type B, supravalvar aortic stenosis, and pulmonary stenosis. As these individuals age, they contribute to the growing population of adults with special health care needs. Although most will require longterm cardiology follow-up, primary care providers, geneticists, and other specialists should be aware of (1) the type and frequency of cardiovascular abnormalities, (2) the range of clinical outcomes, and (3) guidelines for prospective management and treatment of potential complications. This article reviews fundamental genetic, cardiac, medical, and reproductive issues associated with common genetic syndromes that are frequently associated with a cardiovascular abnormality. New data are also provided about the cardiac status of adults with a 22q11.2 deletion and with Down syndrome. C1 [Lin, Angela E.; Pober, Barbara R.] MassGen Hosp Children, Genet Unit, Dept Pediat, Boston, MA 02114 USA. [Basson, Craig T.; McDermott, Deborah A.] Cornell Univ, Weill Med Coll, Greenberg Div Cardiol, Ctr Mol Cardiol, New York, NY 10021 USA. [Goldmuntz, Elizabeth] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Cardiol, Philadelphia, PA 19104 USA. [Magoulas, Pilar L.] Baylor Coll Med, Houston, TX 77030 USA. [McPherson, Elspeth] Marshfield Clin Fdn Med Res & Educ, Dept Med Genet, Marshfield, WI USA. [Morris, Colleen A.] Univ Nevada, Sch Med, Dept Pediat, Div Genet, Las Vegas, NV 89154 USA. [Noonan, Jacqueline] Univ Kentucky, Dept Cardiol, Lexington, KY USA. [Nowak, Catherine] Natl Birth Defects Ctr, Waltham, MA USA. [Pierpont, Mary Ella] Univ Minnesota, Minneapolis, MN USA. [Pierpont, Mary Ella] Childrens Hosp, Dept Genet & Cardiol, Minneapolis, MN USA. [Pyeritz, Reed E.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Pyeritz, Reed E.] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. [Rope, Alan F.] Univ Utah, Sch Med, Div Med Genet, Salt Lake City, UT USA. [Pober, Barbara R.] Childrens Hosp, Dept Surg, Boston, MA 02115 USA. RP Lin, AE (reprint author), MassGen Hosp Children, Genet Unit, Dept Pediat, 185 Cambridge St,Simches 2222, Boston, MA 02114 USA. EM Lin.angela@mgh.harvard.edu FU NHLBI NIH HHS [HL80663, R01 HL080663]; NINDS NIH HHS [R01 NS035102, R01 NS035102-14]; PHS HHS [N535102] NR 277 TC 28 Z9 28 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD JUL PY 2008 VL 10 IS 7 BP 469 EP 494 DI 10.1097/GIM.0b013e3181772111 PG 26 WC Genetics & Heredity SC Genetics & Heredity GA 329EL UT WOS:000257849600001 PM 18580689 ER PT J AU Song, JS Liu, XK Liu, XS He, XW AF Song, Jun S. Liu, Xingkun Liu, X. Shirley He, Xiangwei TI A high-resolution map of nucleosome positioning on a fission yeast centromere SO GENOME RESEARCH LA English DT Article ID CENP-A; CHROMATIN-STRUCTURE; SCHIZOSACCHAROMYCES-POMBE; CHROMOSOME SEGREGATION; SACCHAROMYCES-CEREVISIAE; HISTONE H3; CELL-CYCLE; DNA; KINETOCHORE; PROTEIN AB A key element for defining the centromere identity is the incorporation of a specific histone H3, CENPA, known as Cnp1p in Schizosaccharomyces pombe. Previous studies have suggested that functional S. pombe centromeres lack regularly positioned nucleosomes and may involve chromatin remodeling as a key step of kinetochore assembly. We used tiling microarrays to show that nucleosomes are, in fact, positioned in regular intervals in the core of centromere 2, providing the first high-resolution map of regional centromere chromatin. Nucleosome locations are not disrupted by mutations in kinetochore protein genes cnp1, mis18, mis12, nuf2, mal2; overexpression of cnp1; or the deletion of ams2, which encodes a GATA-like factor participating in CENPA incorporation. Bioinformatics analysis of the centromere sequence indicates certain enriched motifs in linker regions between nucleosomes and reveals a sequence bias in nucleosome positioning. In addition, sequence analysis of nucleosome-free regions identifies novel binding sites of Ams2p. We conclude that centromeric nucleosome positions are stable and may be derived from the underlying DNA sequence. C1 [Liu, Xingkun; He, Xiangwei] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Song, Jun S.; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Song, Jun S.; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Song, Jun S.] Inst Adv Study, Simons Ctr Syst Biol, Princeton, NJ 08540 USA. RP He, XW (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. EM xhe@bcm.tmc.edu FU NHGRI NIH HHS [1R01 HG004069-01, R01 HG004069-02, R01 HG004069]; NIGMS NIH HHS [R01 GM068676] NR 51 TC 21 Z9 23 U1 0 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JUL PY 2008 VL 18 IS 7 BP 1064 EP 1072 DI 10.1101/gr.075374.107 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 320QC UT WOS:000257249100006 PM 18411404 ER PT J AU Banks, PM Chan, JKC Chan, WC Chott, A Favera, RD De Wolf-Peeters, C Delsol, GG Dyer, M Campo, E Falini, B Gascoyne, R Gatter, K Gaulard, P Grogan, T Harris, NL Isaacson, PG Jaffe, ES Kluin, PM Knowles, DM Mori, S Mueller-Hermelink, HK Nakamura, S Pileri, S Piris, M Ralfkiaer, E Siebert, R Stein, H Su, IJ Swerdlow, SH Warnke, R Weiss, L AF Banks, Peter M. Chan, John K. C. Chan, Wing C. (John) Chott, Andreas Favera, Riccardo Dalla De Wolf-Peeters, Christiane Delsol, G. Georges Dyer, Martin Campo, Elias Falini, Brunangelo Gascoyne, Randy Gatter, Kevin Gaulard, Philippe Grogan, Thomas Harris, Nancy Lee Isaacson, Peter G. Jaffe, Elaine S. Kluin, Philip M. Knowles, Daniel M. Mori, Shigeo Mueller-Hermelink, H. Konrad Nakamura, Shigeo Pileri, Stefano Piris, Miguel Ralfkiaer, Elisabeth Siebert, Reiner Stein, Harald Su, Ih-Jen Swerdlow, Steven H. Warnke, Roger Weiss, Lawrence TI David York Mason (1941-2008). Antibody wizard and a founder of modern hemopathology SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Biographical-Item C1 [Banks, Peter M.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Chan, John K. C.] Queen Elizabeth Hosp, Hong Kong, Hong Kong, Peoples R China. [Chan, Wing C. (John)] Univ Nebraska Med Ctr, Omaha, NE 68198 USA. [Chott, Andreas] Univ Vienna, A-1010 Vienna, Austria. [Favera, Riccardo Dalla] Columbia Univ, New York, NY 10027 USA. [De Wolf-Peeters, Christiane] Leuven Univ, Louvain, Belgium. [Delsol, G. Georges] Univ Toulouse, Toulouse, France. [Dyer, Martin] Univ Leicester, Leicester LE1 7RH, Leics, England. [Campo, Elias] Univ Barcelona, E-08007 Barcelona, Spain. [Falini, Brunangelo] Univ Perugia, I-06100 Perugia, Italy. [Gascoyne, Randy] BC Canc Agcy, Vancouver, BC, Canada. [Gatter, Kevin] Univ Oxford, Oxford OX1 2JD, England. [Gaulard, Philippe] Henri Mondor Hosp, Paris, France. [Grogan, Thomas] Univ Arizona, Tucson, AZ USA. [Harris, Nancy Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Isaacson, Peter G.] Univ Coll, London, England. [Jaffe, Elaine S.] Natl Canc Inst, Bethesda, MD USA. [Kluin, Philip M.] Univ Groningen, NL-9700 AB Groningen, Netherlands. [Knowles, Daniel M.] Weill Cornell Med Coll, New York, NY USA. [Mori, Shigeo] Univ Tokyo, Tokyo 1138654, Japan. [Mueller-Hermelink, H. Konrad] Univ Wurzburg, D-97070 Wurzburg, Germany. [Nakamura, Shigeo] Nagoya Univ, Nagoya, Aichi 4648601, Japan. [Pileri, Stefano] Univ Bologna, I-40126 Bologna, Italy. [Piris, Miguel] CNIO, Madrid, Spain. [Ralfkiaer, Elisabeth] Univ Copenhagen, DK-1168 Copenhagen, Denmark. [Siebert, Reiner] Univ Kiel, D-24098 Kiel, Germany. [Stein, Harald] Univ Berlin, Berlin, Germany. [Swerdlow, Steven H.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Warnke, Roger] Stanford Univ, Stanford, CA 94305 USA. [Weiss, Lawrence] City Hope Natl Med Ctr, Duarte, CA 91010 USA. RP Banks, PM (reprint author), Carolinas Med Ctr, Charlotte, NC 28203 USA. EM bankspds@aol.com; jkcchan@ha.org.hk; jchan@unmc.edu; andreas.chott@meduniwien.ac.at; rd10@columbia.edu; christiane.peeters@uz.kuleuven.ac.be; delsol.g@chu-toulouse.fr; mjsd1@le.ac.uk; ecampo@clinic.ub.es; faliniem@unipg.it; rgascoyn@bccancer.bc.ca; kevin.gatter@ndcls.ox.ac.uk; philippe.gaulard@hmn.ap-hop-paris.fr; tmgrogan@u.arizona.edu; nlharris@partners.org; p.isaacson@ucl.ac.uk; elainejaffe@nih.gov; p.m.kluin@path.azg.nl; dknowles@med.cornell.edu; mori@ims.u-tokyo.ac.jp; path062@mail.uni-wuerzburg.de; snaka-mur@med.nagoia-u.ac.jp; pileri@orsola-malpighi.med.unibo.it; mapiris@cnio.es; eral@herlevhosp.kbhamt.dk; rsiebert@medgen.uni-kiel.de; harald.stein@charite.de; suihjen@ha.mc.ntu.edu.tw; swerdlowsh@upmc.edu; rwarnke@stan-ford.edu; lweiss@coh.org RI Siebert, Reiner/A-8049-2010 NR 1 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUL PY 2008 VL 93 IS 7 BP A EP B PG 2 WC Hematology SC Hematology GA 323CI UT WOS:000257421200037 ER PT J AU Gilbert, GE Novakovic, V Cullinan, D Jacquemin, M AF Gilbert, G. E. Novakovic, V. Cullinan, D. Jacquemin, M. TI Human inhibitor antibody LE2E9 against factor VIIIC1 domain influences phospholipid binding and factor xase enzyme complex formation SO HAEMOPHILIA LA English DT Meeting Abstract C1 [Gilbert, G. E.; Novakovic, V.; Cullinan, D.; Jacquemin, M.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Res Inst, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD JUL PY 2008 VL 14 IS 4 BP 877 EP 877 PG 1 WC Hematology SC Hematology GA 328JJ UT WOS:000257794400045 ER PT J AU Pearson, SD Schneider, EC Kleinman, KP Coltin, KL Singer, JA AF Pearson, Steven D. Schneider, Eric C. Kleinman, Ken P. Coltin, Kathryn L. Singer, Janice A. TI The impact of pay-for-performance on health care quality in Massachusetts, 2001-2003 SO HEALTH AFFAIRS LA English DT Article ID PHYSICIAN GROUPS; INCENTIVES AB Pay-for-performance (P4P) has become one of the dominant approaches to improving quality of care, yet few studies have evaluated its effectiveness. We evaluated the impact on quality of all P4P programs introduced into physician group contracts during 2001-2003 by the five major commercial health plans operating in Massachusetts. Overall, P4P contracts were not associated with greater improvement in quality compared to a rising secular trend. Future research is required to determine whether changes to the magnitude, structure, or alignment of P4P incentives can lead to improved quality. C1 [Pearson, Steven D.] Massachusetts Gen Hosp, Inst Clin & Econ Review, Boston, MA 02114 USA. [Schneider, Eric C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Kleinman, Ken P.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Coltin, Kathryn L.] Harvard Pilgrim Hlth Care, External Qual Data Initiat, Wellesley, MA 02481 USA. [Singer, Janice A.] Massachusetts Hlth Qual Partners, Watertown, MA USA. RP Pearson, SD (reprint author), Massachusetts Gen Hosp, Inst Clin & Econ Review, Boston, MA 02114 USA. EM spearson@icer-review.org OI Schneider, Eric/0000-0002-1132-5084 NR 17 TC 40 Z9 40 U1 1 U2 2 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JUL-AUG PY 2008 VL 27 IS 4 BP 1167 EP 1176 DI 10.1377/hlthaff.27.4.1167 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 326CQ UT WOS:000257635900032 PM 18607052 ER PT J AU Senior, R Zabalgoitia, M Monaghan, M Main, M Zamorano, J Tiemann, K Agati, L Weissman, N Klein, AL Marwick, T Ahmad, M DeMaria, A Becher, H Kaul, S Udelson, J Wackers, F Walovitch, R Picard, M AF Senior, R. Zabalgoitia, M. Monaghan, M. Main, M. Zamorano, J. L. Tiemann, K. Agati, L. Weissman, N. J. Klein, A. L. Marwick, T. H. Ahmad, M. DeMaria, A. N. Becher, H. Kaul, S. Udelson, J. E. Wackers, F. J. Walovitch, R. C. Picard, M. H. TI Accurate detection of coronary artery disease by echocardiography using perflubutane polymer microspheres, a novel contrast agent: Comparison with nuclear perfusion imaging in two phase III multicentre clinical trials SO HEART LA English DT Meeting Abstract CT Annual Scientific Conference of the British-Cardiovascular-Society/British-Society-for-Cardiovascular-Resear ch CY JUN 02-04, 2008 CL Manchester, ENGLAND SP British Cardiovasc Soc, British Soc Cardiovasc Res C1 [Senior, R.] Northwick Pk Hosp & Clin Res Ctr, Harrow HA1 3UJ, Middx, England. [Zabalgoitia, M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Monaghan, M.] Kings Coll London, London WC2R 2LS, England. [Main, M.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Zamorano, J. L.] Univ Clin San Carlos, Madrid, Spain. [Tiemann, K.] Univ Bonn, D-5300 Bonn, Germany. [Agati, L.] Univ Roma La Sapienza, Rome, Italy. [Weissman, N. J.] Inst Cardiovasc Res, Washington, DC USA. [Klein, A. L.] Cleveland Clin, Cleveland, OH 44106 USA. [Marwick, T. H.] Princess Alexandra Hosp, Brisbane, Qld 4102, Australia. [Ahmad, M.] Univ Texas Galveston, Galveston, TX 77555 USA. [DeMaria, A. N.] Univ Calif San Diego, San Diego, CA 92103 USA. [Kaul, S.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Udelson, J. E.] Tufts Univ New England Med Ctr, Boston, MA USA. [Wackers, F. J.] Yale Univ, Sch Med, New Haven, CT USA. [Walovitch, R. C.] Accusphere Inc, Watertown, SD USA. [Picard, M. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Marwick, Thomas/C-7261-2013 OI Marwick, Thomas/0000-0001-9065-0899 NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD JUL PY 2008 VL 94 SU 2 BP A20 EP A20 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 306ZI UT WOS:000256286700039 ER PT J AU Rodriguez, KL Appelt, CJ Switzer, GE Sonel, AF Arnold, RM AF Rodriguez, Keri L. Appelt, Cathleen J. Switzer, Galen E. Sonel, Ali F. Arnold, Robert M. TI "They diagnosed bad heart": A qualitative exploration of patients' knowledge about and experiences with heart failure SO HEART & LUNG LA English DT Article ID ELDERLY-PATIENTS; HEALTH OUTCOMES; CHRONIC ILLNESS; CHRONIC DISEASE; OF-LIFE; COMMUNICATION; CARE; SATISFACTION; EDUCATION; CANCER AB BACKGROUND: Patient education is central to the management of individuals with heart failure; therefore, it is important to know what these patients understand and experience both clinically and personally. OBJECTIVES: This study qualitatively explored patients' knowledge regarding a heart failure diagnosis, their understanding of their cardiac care providers' treatment recommendations, and their views concerning the impact of heart failure on their daily lives and prognosis. METHODS: A qualitative study was conducted whereby data were collected through 25 telephone interviews with adults being followed for heart failure at a Veterans Affairs medical center. Subjects were interviewed using semistructured open-ended questions. Audiotaped responses were analyzed using grounded theory methods. RESULTS: The majority of participants were elderly, male, and white, and had New York Heart Association class II disease. Participants without angina typically experienced a lengthy and difficult diagnostic delay, with symptoms misattributed to comorbid diseases. Most understood the importance of self-monitoring and adhering to physician recommendations, and their discussions of life-changing effects typically focused on loss of physical functioning and decreased quality of life. Although participants wanted to know their prognosis, most had not received information about it or about advance care planning. CONCLUSION: Patients require opportunities for enhanced communication with physicians and health care team members during the challenging diagnostic period and subsequently need more information about their medical condition and prognosis. C1 [Rodriguez, Keri L.; Switzer, Galen E.; Sonel, Ali F.] Univ Pittsburgh, Sch Med, Ctr Hlth Equity Res & Promot, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. [Rodriguez, Keri L.; Switzer, Galen E.; Arnold, Robert M.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Dept Med, Pittsburgh, PA 15260 USA. [Appelt, Cathleen J.] Univ Pittsburgh, Sch Med, Vet Affairs Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA 15260 USA. [Switzer, Galen E.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. [Sonel, Ali F.] Univ Pittsburgh, Vet Affairs Pittsburgh Healthcare Syst, Div Cardiol, Pittsburgh, PA 15260 USA. [Sonel, Ali F.] Univ Pittsburgh, Cardiovasc Inst, Pittsburgh, PA 15260 USA. [Arnold, Robert M.] Univ Pittsburgh, Sect Palliat Care & Med Eth, Pittsburgh, PA 15260 USA. [Arnold, Robert M.] Univ Pittsburgh, Inst Enhance Palliat Care, Pittsburgh, PA 15260 USA. RP Rodriguez, KL (reprint author), Univ Pittsburgh, Sch Med, Ctr Hlth Equity Res & Promot, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. FU NCI NIH HHS [3R01 CA100387-03S1] NR 40 TC 38 Z9 38 U1 3 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0147-9563 J9 HEART LUNG JI Heart Lung PD JUL-AUG PY 2008 VL 37 IS 4 BP 257 EP 265 DI 10.1016/i.hrtlng.2007.09.001 PG 9 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA 333DA UT WOS:000258131200002 PM 18620101 ER PT J AU Aleong, R Heist, EK Ruskin, JN Mansour, M AF Aleong, Ryan Heist, E. Kevin Ruskin, Jeremy N. Mansour, Moussa TI Integration of intracardiac echocardiography with magnetic resonance imaging allows visualization of the esophagus during catheter ablation of atrial fibrillation SO HEART RHYTHM LA English DT Editorial Material C1 [Aleong, Ryan; Heist, E. Kevin; Ruskin, Jeremy N.; Mansour, Moussa] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Mansour, M (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, GRB 109,55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org NR 2 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD JUL PY 2008 VL 5 IS 7 BP 1088 EP 1088 DI 10.1016/j.hrthm.2008.02.032 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 324FK UT WOS:000257502900026 PM 18598971 ER PT J AU Johansen, KL AF Johansen, Kirsten L. TI Exercise and dialysis SO HEMODIALYSIS INTERNATIONAL LA English DT Review DE exercise; physical activity; end-stage renal disease; hemodialysis ID STAGE RENAL-DISEASE; QUALITY-OF-LIFE; MAINTENANCE HEMODIALYSIS-PATIENTS; RANDOMIZED CONTROLLED-TRIAL; PHYSICAL-ACTIVITY; PERITONEAL-DIALYSIS; BLOOD-PRESSURE; CARDIOVASCULAR COMPLICATIONS; REHABILITATION PROGRAMS; PROGRESSIVE EXERCISE AB Fortunately, the literature on exercise among patients on hemodialysis has grown too broad to be included in a single review. The focus of this review is on interventional studies, with an emphasis on those studies that included a control group. The good news is that there is ample evidence that exercise can improve fitness (VO2 peak), physical functioning, and some cardiovascular risk factors in the dialysis population. However, there have been few comparative studies, and there is no consensus regarding the most beneficial regimen or the one most acceptable to large numbers of patients. A new set of recommendations from the American College of Sports Medicine and the American Heart Association for older individuals and individuals with chronic diseases is relevant for our patient population and can be used to guide exercise prescription until disease-specific data are available to fill the gap. C1 [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94121 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Nephrol Sect, 111J,4150 Clement St, San Francisco, CA 94121 USA. EM Kirsten.johansen@ucsf.edu NR 85 TC 30 Z9 33 U1 2 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1492-7535 J9 HEMODIAL INT JI Hemodial. Int. PD JUL PY 2008 VL 12 IS 3 BP 290 EP 300 DI 10.1111/j.1542-4758.2008.00269.x PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 327DU UT WOS:000257710600002 PM 18638081 ER PT J AU Hiasa, Y Kuzuhara, H Tokumoto, Y Konishi, I Yamashita, N Matsuura, B Michitaka, K Chung, RT Onji, M AF Hiasa, Yoichi Kuzuhara, Hiroyuki Tokumoto, Yoshio Konishi, Ichiro Yamashita, Nobuyuki Matsuura, Bunzo Michitaka, Kojiro Chung, Raymond T. Onji, Morikazu TI Hepatitis C virus replication is inhibited by 22 beta-methoxyolean-12-ene-3 beta, 24(4 beta)-diol (ME3738) through enhancing interferon-beta SO HEPATOLOGY LA English DT Article ID BLOOD MONONUCLEAR-CELLS; IN-VITRO; LIVER-INJURY; COMBINATION THERAPY; ANTIVIRAL ACTIVITY; HUMAN HEPATOCYTES; ALPHA-INTERFERON; VIRAL-RNA; INFECTION; RIBAVIRIN AB A derivative of soyasapogenol, 22 beta-methoxyolean-12-ene-3 beta, 24(4 beta)-diol (ME3738), ameliorates liver injury induced by Concanavalin A in mice. We examined whether ME3738 has independent antiviral effects against hepatitis C virus (HCV) using an established HCV replication model that expresses the full-length genotype 1a HCV complementary DNA plasmid (pT7-flHCV-Rz) under the control of a replication-defective adenoviral vector expressing T7 polymerase. Hepatocellular carcinoma (HepG2) cells, human hepatoma (Huh7) cells, or monkey kidney (CV-1) cells were transfected with pT7-flHCV-Rz, and infected with adenoviral vector expressing T7 polymerase. ME3738 or interferon-alpha (IFN-alpha) was added thereafter and then protein and RNA were harvested from the cells at 9 days after infection. HCV-positive and HCV-negative strands were measured by real-time reverse-transcription polymerase chain reaction and HCV core protein expression was measured using an enzyme-linked immunosorbent assay. The messenger RNA levels of innate antiviral response-related genes were assessed using real-time reverse-transcription polymerase chain reaction. ME3738 dose-dependently reduced HCV-RNA and core protein in hepatocyte-derived cell lines. The antiviral effect was more pronounced in HepG2 than in Huh7 cells. ME3738 increased messenger RNA levels of interferon-beta (IFN-beta) and of IFN-stimulated genes (2'-5' oligoadenylate synthetase, myxovirus resistance protein A [MxA]). Interferon-beta knockdown by small interfering RNA abrogated the anti-HCV effect of ME3738. Moreover, the anti-HCV effects were synergistic when ME3738 was combined with IFN-alpha. Conclusion: ME3738 has antiviral effects against HCV. The enhancement of autocrine IFN-beta suggests that ME3738 exerts antiviral action along the type I IFN pathway. This anti-HCV action by ME3738 was synergistically enhanced when combined with IFN-alpha. ME3738 might be a useful anti-HCV drug either with or without IFN-alpha. C1 [Hiasa, Yoichi; Tokumoto, Yoshio; Konishi, Ichiro; Matsuura, Bunzo; Michitaka, Kojiro; Onji, Morikazu] Ehime Univ, Grad Sch Med, Dept Gastroenterol & Metabol, Toon, Ehime 7910295, Japan. [Kuzuhara, Hiroyuki; Yamashita, Nobuyuki] Meiji Seika Kaisha Ltd, Pharmaceut Res Ctr, Pharmacol Res Labs, Tokyo, Japan. [Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Onji, M (reprint author), Ehime Univ, Grad Sch Med, Dept Gastroenterol & Metabol, Toon, Ehime 7910295, Japan. EM onjimori@m.ehime-u.ac.jp NR 37 TC 9 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUL PY 2008 VL 48 IS 1 BP 59 EP 69 DI 10.1002/hep.22289 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 321JP UT WOS:000257301100010 PM 18459156 ER PT J AU Harris, RA Sugimoto, K Kaplan, DE Ikeda, F Kmoun, M Chang, KM AF Harris, Rebecca A. Sugimoto, Kazushi Kaplan, David E. Ikeda, Fusao Kmoun, Malek Chang, Kyong-Mi TI Human leukocyte antigen class II associations with hepatitis C virus clearance and virus-specific CD4 T cell response among Caucasians and African Americans SO HEPATOLOGY LA English DT Article ID VIRAL CLEARANCE; RACIAL-DIFFERENCES; IMMUNE-RESPONSE; HCV INFECTION; EX-VIVO; HLA; MHC; ALLELES; GENES; POPULATION AB The outcome of hepatitis C virus (HCV) infection has been associated with antiviral CD4 T cell response, human leukocyte antigens (HLA) class II genotypes, and ethnicity. However, HLA class II molecules restrict the nature of CD4 T cell response, and HLA distributions differ between ethnic groups. In this study, we asked whether HLA class II genotypes associated with HCV clearance are shared between Caucasian and African Americans and whether they contribute to enhanced antiviral CD4 T cell response. In a cohort of 93 HCV-seropositive subjects from Northeast America with defined ethnicity, virological outcome, and HCV-specific CD4 T cell proliferation, we confirm the previously reported associations between HCV clearance and two HILA types (DQB1*03, DRB1*11) while identifying a new association with DRB3*02. Strikingly, these associations were identified only among Caucasian [DQB1*03: odds ratio (OR), 10.4; P = 0.031, DRB1*11: OR, 7.0, P = 0.019; DRB3*02: OR, 8.3, P = 0.005; DQB1*03-DRB3*02: OR, 13.5, P = 0.001) but not among African American patients. Furthermore, although HLA DQB1*03, DRB1*11, and DRB3*02 genotypes were associated with increased HCV-specific CD4 T cell response in univariate analyses, these associations were lost when controlling for virological outcomes. Conclusion: We conclude that the immunogenetic basis for HCV clearance differs between ethnic groups and that the association between HLA class II and HCV clearance is not directly explained by antiviral CD4 T cell response. C1 [Harris, Rebecca A.; Sugimoto, Kazushi; Kaplan, David E.; Ikeda, Fusao; Chang, Kyong-Mi] Univ Penn, Sch Med, Div Gastroenterol, Dept Med, Philadelphia, PA 19014 USA. [Harris, Rebecca A.; Sugimoto, Kazushi; Kaplan, David E.; Ikeda, Fusao; Chang, Kyong-Mi] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Harris, Rebecca A.] Haverford Coll, Haverford, PA 19041 USA. [Kmoun, Malek] Univ Penn, Sch Med, Dept Pathol, Philadelphia, PA 19014 USA. [Kmoun, Malek] Univ Penn, Sch Med, Lab Med, Philadelphia, PA 19014 USA. RP Chang, KM (reprint author), Univ Penn, Sch Med, Div Gastroenterol, Dept Med, 600 CRB,415 Curie Blvd, Philadelphia, PA 19014 USA. EM kmchang@mail.med.upenn.edu OI Kaplan, David E./0000-0002-3839-336X FU Howard Hughes Medical Institute; NCRR NIH HHS [M01 RR000040]; NIAAA NIH HHS [AA12849, R01 AA012849, R01 AA012849-03, R01 AA012849-04, R01 AA012849-05]; NIAID NIH HHS [AI47519, R01 AI047519, R01 AI047519-06, R01 AI047519-07, R01 AI047519-08, R01 AI047519-09]; NIDDK NIH HHS [P30 DK050306, P30 DK050306-09, P30 DK050306-10, P30 DK050306-11, P30 DK050306-12, P30 DK050306-13, P30DK50306] NR 56 TC 36 Z9 36 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUL PY 2008 VL 48 IS 1 BP 70 EP 79 DI 10.1002/hep.22287 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 321JP UT WOS:000257301100011 PM 18537178 ER PT J AU Kayed, H Bekasi, S Keleg, S Welsch, T Esposito, I Shimamura, A Michalski, CW Friess, H Kleeff, J AF Kayed, Hany Bekasi, Sandor Keleg, Shereen Welsch, Thilo Esposito, Irene Shimamura, Akiko Michalski, Christoph W. Friess, Helmut Kleeff, Joerg TI Expression of the Shwachman-Bodian-Diamond syndrome (SBDS) protein in human pancreatic cancer and chronic pancreatitis SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Article DE SBDS; pancreatic adenocarcinoma; chronic; pancreatitis ID MUTATIONS; GENE; PHENOTYPE; LEUKEMIA; PATIENT; ORIGIN; RNA; LOCALIZES; FAMILY AB Background: The Shwachman-Bodian-iamond syndrome (SBDS) protein is a member of a highly conserved family which influences RNA activation and is associated with pancreatic, skeletal and bone marrow deficiencies, as well as hematological malignancies. Methods: In this study, the expression and localization of SBDS were investigated in normal human pancreatic tissues, chronic pancreatitis (CP) tissues, primary and metastatic pancreatic ductal adenocarcinoma (PDAC) tissues, as well as in cultured pancreatic cancer cell lines by immunohistochemistry, immunoblotting and immunocytochemistry. Results: In the normal pancreas, SBDS was localized in the cytoplasm of islet cells and ductal cells. In CP tissues, SBDS was found in the cytoplasm of ductal cells, tubular complexes, stromal fibroblasts and in PanIN1-2 lesions. In PDAC tissues, SBDS exhibited cytoplasmic and occasionally nuclear localization in tubular complexes, PanIN1-3 lesions, cancer cells, and stromal fibroblasts. Different levels of SBDS protein were detected in cultured pancreatic cancer cell lines. Conclusion: SBDS is expressed in normal, CP, and PDAC tissues, as well as in pancreatic cancer cell lines. The different expression and localization patterns suggest a role of SBDS in the pathogenesis of, or response to, inflammatory and neoplastic pancreatic diseases. C1 [Michalski, Christoph W.; Friess, Helmut; Kleeff, Joerg] Tech Univ Munich, Klinikum Rechts Isar, Dept Surg, D-81675 Munich, Germany. [Kayed, Hany; Bekasi, Sandor; Keleg, Shereen; Welsch, Thilo] Univ Heidelberg, Dept Gen Surg, Heidelberg, Germany. [Esposito, Irene] Tech Univ Munich, Klinikum Rechts Isar, Inst Pathol, D-81675 Munich, Germany. [Shimamura, Akiko] Childrens Hosp, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. [Shimamura, Akiko] Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Washington, Dept Pediat Hematol Oncol, Seattle, WA 98195 USA. Childrens Hosp, Seattle, WA USA. RP Kleeff, J (reprint author), Tech Univ Munich, Klinikum Rechts Isar, Dept Surg, Ismaningerstr 22, D-81675 Munich, Germany. EM kleeff@t-online.de RI Kleeff, Jorg/B-2124-2009 OI Kleeff, Jorg/0000-0003-3432-6669 FU NHLBI NIH HHS [R01 HL079582] NR 34 TC 1 Z9 1 U1 0 U2 1 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD JUL PY 2008 VL 23 IS 7 BP 819 EP 826 PG 8 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 292MS UT WOS:000255271300005 PM 18437680 ER PT J AU Villablanca, EJ Russo, V Mora, JR AF Villablanca, Eduardo J. Russo, Vincenzo Mora, J. Rodrigo TI Dendritic cell migration and lymphocyte homing imprinting SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Review DE dendritic cells; homing; gut; skin ID STEADY-STATE CONDITIONS; CD4(+) T-CELLS; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; SKIN-ASSOCIATED CHEMOKINE; ANTIBODY-SECRETING CELLS; PEYERS PATCH; LANGERHANS CELLS; LAMINA-PROPRIA; CUTTING EDGE; B-CELLS AB For an effective adaptive immune response to occur, dendritic cells ( DC), which are the most efficient antigen-presenting cells, must be able to sample the peripheral microenvironment and migrate towards secondary lymphoid organs (SLO) where they activate naive lymphocytes. Upon activation, lymphocytes proliferate and acquire the capacity to migrate to extralymphoid compartments. Although the molecular mechanisms controlling lymphocyte homing to lymphoid and to some extralymphoid tissues have been described in significant detail, it is much less clear how DC migration is controlled. Do DC obey similar adhesion cues that lymphocytes do, or do they have their own "zip codes"? This is relevant from a therapeutic standpoint because effective DC-based vaccines should be able to reach the appropriate tissues in order to generate protective immune responses. Here, we discuss some of the mechanisms used by DC to reach their target tissues. Once DC arrive at their destination, they are exposed to the tissue microenvironment, which likely modulates their functional properties in a tissue-specific fashion. This local DC "education" is probably responsible among other things; for the acquisition of tissue-specific homing imprinting capacity by which DC instruct lymphocytes to migrate to specific tissues. Finally, we discuss how dysregulation of these signals may play a key role in disease. C1 [Villablanca, Eduardo J.; Mora, J. Rodrigo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Villablanca, Eduardo J.; Russo, Vincenzo] Univ Vita Salute San Raffaele, Sci Inst H San Raffaele, Canc Gene Therapy Unit, Milan, Italy. [Villablanca, Eduardo J.] Univ Vita Salute San Raffaele, Int PhD Program Mol Med, Milan, Italy. RP Mora, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM j_rodrigo_mora@hms.harvard.edu RI Villablanca, Eduardo/E-1380-2016; Russo, Vincenzo/K-5650-2016 OI Villablanca, Eduardo/0000-0001-9522-9729; Russo, Vincenzo/0000-0003-1592-5041 NR 141 TC 19 Z9 21 U1 0 U2 2 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD JUL PY 2008 VL 23 IS 7 BP 897 EP 910 PG 14 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 292MS UT WOS:000255271300013 PM 18437688 ER PT J AU Bamberg, SJM Benbasat, AY Scarborough, DM Krebs, DE Paradiso, JA AF Bamberg, Stacy J. Morris Benbasat, Ari Y. Scarborough, Donna Moxley Krebs, David E. Paradiso, Joseph A. TI Gait analysis using a shoe-integrated wireless sensor system SO IEEE TRANSACTIONS ON INFORMATION TECHNOLOGY IN BIOMEDICINE LA English DT Article DE biomedical measurements; body sensor networks; legged locomotion; multisensor systems; telemetry ID DATA-ACQUISITION SYSTEM; PLANTAR PRESSURES; BIOMECHANICS; VARIABILITY; RECOGNITION; PARAMETERS; DYNAMICS; WALKING; FOOT AB We describe a wireless wearable system that was developed to provide quantitative gait analysis outside the confines of the traditional motion laboratory. The sensor suite includes three orthogonal accelerometers, three orthogonal gyroscopes, four force sensors, two bidirectional bend sensors, two dynamic pressure sensors, as well as electric field height sensors. The "GaitShoe" was built to be worn in any shoe, without interfering with gait and was designed to collect data unobtrusively, in any environment, and over long periods. The calibrated sensor outputs were analyzed and validated with results obtained simultaneously from the ssachusetts General Hospital, Biomotion Laboratory. The GaitShoe proved highly capable of detecting heel-strike and toe-off, as well as estimating foot orientation and position, inter alia. C1 [Benbasat, Ari Y.; Paradiso, Joseph A.] MIT, Media Lab, Cambridge, MA 02139 USA. [Scarborough, Donna Moxley] Massachusetts Gen Hosp, Orthoped Biomech & Biomat Lab, Boston, MA 02114 USA. RP Bamberg, SJM (reprint author), Univ Utah, Dept Mech Engn, Salt Lake City, UT 84112 USA. EM sjm@alum.mit.edu; ayb@alum.mit.edu; dscarborough@partners.org; dkrebs@mit.edu; joep@media.mit.edu NR 41 TC 207 Z9 209 U1 23 U2 66 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1089-7771 J9 IEEE T INF TECHNOL B JI IEEE T. Inf. Technol. Biomed. PD JUL PY 2008 VL 12 IS 4 BP 413 EP 423 DI 10.1109/TITB.2007.899493 PG 11 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Mathematical & Computational Biology; Medical Informatics GA 327UP UT WOS:000257754300001 PM 18632321 ER PT J AU Westover, MB AF Westover, M. Brandon TI Asymptotic geometry of multiple hypothesis testing SO IEEE TRANSACTIONS ON INFORMATION THEORY LA English DT Article DE geometry; hypothesis testing; large deviations; pattern recognition AB We present a simple geometrical interpretation for the solution to the multiple hypothesis testing problem in the asymptotic limit. Under this interpretation, the optimal decision rule is a nearest neighbor classifier on the probability simplex. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Westover, MB (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM mb.westover@gmail.com NR 4 TC 9 Z9 11 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9448 J9 IEEE T INFORM THEORY JI IEEE Trans. Inf. Theory PD JUL PY 2008 VL 54 IS 7 BP 3327 EP 3329 DI 10.1109/TIT.2008.924656 PG 3 WC Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA 318SC UT WOS:000257111500041 ER PT J AU Harrington, L Srikanth, CV Antony, R Rhee, SJ Mellor, AL Shi, HN Cherayil, BJ AF Harrington, Lynne Srikanth, Chittur V. Antony, Reuben Rhee, Sue J. Mellor, Andrew L. Shi, Hai Ning Cherayil, Bobby J. TI Deficiency of indoleamine 2,3-dioxygenase enhances commensal-induced antibody responses and protects against Citrobacter rodentium-induced colitis SO INFECTION AND IMMUNITY LA English DT Article ID INTESTINAL DENDRITIC CELLS; T-CELL; TRYPTOPHAN CATABOLISM; IMMUNOGLOBULIN-A; B-CELL; MUCOSAL INFECTION; IMMUNE-RESPONSES; IGA RESPONSE; IFN-GAMMA; GUT AB Indoleamine 2,3-dioxygenase (IDO) is a negative regulator of lymphocyte responses that is expressed predominantly in macrophages and dendritic cells. We detected it at high levels in the small intestine and mesenteric lymph node of young adult mice, suggesting a role in intestinal immunity. Consistent with this idea, we found that IDO-deficient mice had elevated baseline levels of immunoglobulin A (IgA) and IgG in the serum and increased IgA in intestinal secretions. These abnormalities were corrected by a course of broad-spectrum oral antibiotics started at weaning, indicating that they were dependent on the intestinal microbiota. Kynurenine and picolinic acid, two IDO-generated metabolites of tryptophan, were able to inhibit lipopolysaccharide-induced antibody production by splenocytes in vitro, and kynurenine also induced B-cell apoptosis, findings that provide an explanation for the elevated Ig levels in animals lacking IDO. The intestinal secretions of IDO-deficient mice had elevated levels of IgA antibodies that cross-reacted with the gram-negative enteric bacterial pathogen Citrobacter rodentium. In keeping with the functional importance of this natural secretory IgA, the mutant animals were more resistant to intestinal colonization by Citrobacter, developed lower levels of serum Citrobacter-specific IgM and IgG antibodies following oral infection, and had significantly attenuated Citrobacter-induced colitis. Our observations point to an important role for IDO in the regulation of immunity to the gut commensal microbiota that has a significant impact on the response to intestinal pathogens. C1 [Harrington, Lynne; Srikanth, Chittur V.; Antony, Reuben; Rhee, Sue J.; Shi, Hai Ning; Cherayil, Bobby J.] Massachusetts Gen Hosp, Pediat Gastroenterol Unit, Mucosal Immunol Lab, Charlestown, MA 02129 USA. [Shi, Hai Ning; Cherayil, Bobby J.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Mellor, Andrew L.] Med Coll Georgia, Immunotherapy Ctr, Augusta, GA 30912 USA. RP Cherayil, BJ (reprint author), Massachusetts Gen Hosp, Pediat Gastroenterol Unit, Mucosal Immunol Lab, Bldg 114,16th St, Charlestown, MA 02129 USA. EM cherayil@helix.mgh.harvard.edu FU NIAID NIH HHS [R01 AI063402, R01AI63402, R01 AI048815, R01AI48815]; NICHD NIH HHS [R01HD41187, R01 HD041187]; NIDDK NIH HHS [P30 DK040561-13, K01DK05996, P30 DK040561] NR 44 TC 34 Z9 34 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2008 VL 76 IS 7 BP 3045 EP 3053 DI 10.1128/IAI.00193-08 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 319OC UT WOS:000257172300025 PM 18426872 ER PT J AU Hsu, CC Lin, YE Chen, YS Liu, YC Muder, RR AF Hsu, Cheng-Chuan Lin, Yusen E. Chen, Yao-Shen Liu, Yung-Ching Muder, Robert R. TI Validation study of artificial neural network models for prediction of methicillin-resistant Staphylococcus aureus carriage SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID INTENSIVE-CARE-UNIT; ACTIVE SURVEILLANCE CULTURES; MRSA BACTEREMIA; COST; EPIDEMIOLOGY; COLONIZATION; ENTEROCOCCI; INFECTIONS; ADMISSION; PREVENT AB objective. Use of active surveillance cultures for methicillin-resistant Staphylococcus aureus (MRSA) for all patients admitted to the intensive care unit has been shown to reduce nosocomial transmission. However, the cost-effectiveness and the utility of implementing use of active surveillance cultures nationwide remain controversial. We sought to develop an artificial neural network (ANN) model that would predict the likelihood of MRSA colonization. setting. Two acute care hospitals, one in Pittsburgh (hospital A) and one in Kaohsiung, Taiwan (hospital B). methods. Nasal cultures were performed for all patients admitted to the hospitals. A total of 46 potential risk factors in hospital A and 86 potential risk factors in hospital B associated with MRSA colonization were assessed. Culture results were obtained; 75% of the data were used for training our ANN model, and the remaining 25% were used for validating our ANN model. The culture results were the "gold standard" for determining the accuracy of the model predictions. results. The ANN model predictions were accurate 95.2% of the time for hospital A(sensitivity, 94.3%; specificity, 96.0%) and 94.2% of the time for hospital B (sensitivity, 96.6%; specificity, 91.8%), integrating all potential risk factors into the model. Only 17 potential risk factors were needed for the hospital A ANN model (accuracy, 90.9%; sensitivity, 98.5%; specificity, 83.4%), and only 20 potential risk factors were needed for the hospital B ANN model (accuracy, 90.5%; sensitivity, 96.6%; specificity, 84.3%), if the minimal risk factor method was used. Cross-validation analysis showed an average accuracy of 85.6% (sensitivity, 91.3%; specificity, 80.0%). conclusion. Our ANN model can be used to predict with an accuracy of more than 90% which patients carry MRSA. The false-negative rates were significantly lower than the false-positive rates in the ANN predictions, which can serve as a safety buffer in case of patient misclassification. C1 [Hsu, Cheng-Chuan; Lin, Yusen E.; Chen, Yao-Shen] Natl Kaohsiung Normal Univ, Grad Inst Environm Educ, Kaohsiung 824, Taiwan. [Chen, Yao-Shen; Liu, Yung-Ching] Kaohsiung Vet Gen Hosp, Infect Dis Sect, Kaohsiung, Taiwan. [Muder, Robert R.] Vet Affairs Pittsburgh Healthcare Syst, Infect Dis Sect, Pittsburgh, PA USA. RP Lin, YE (reprint author), Natl Kaohsiung Normal Univ, Grad Inst Environm Educ, 62 Shenchong Rd, Kaohsiung 824, Taiwan. EM easonlin@nknucc.nknu.edu.tw NR 26 TC 3 Z9 3 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JUL PY 2008 VL 29 IS 7 BP 607 EP 614 DI 10.1086/588588 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 323NF UT WOS:000257452100005 PM 18549315 ER PT J AU Tongchusak, S Brusic, V Chaiyaroj, SC AF Tongchusak, Songsak Brusic, Vladimir Chaiyaroj, Sansanee C. TI Promiscuous T cell epitope prediction of Candida albicans secretory aspartyl protienase family of proteins SO INFECTION GENETICS AND EVOLUTION LA English DT Article; Proceedings Paper CT 8th International Congress on Molecular Epidemiology and Evolutionary Genetics of Infectious Diseases CY OCT 30-NOV 02, 2006 CL Bangkok, THAILAND DE Candida albicans; immunomics; secretory aspartyl proteinase; T cell epitope; antigenic prediction; interferon ELISpot assay; PBMC proliferation ID VIRULENCE AB Candida albicans is one of the most important opportunistic dimorphic fungi responsible for hospital acquired fungal infection in humans. Candida infection rarely occurs in healthy individuals but it is frequently associated with patients who suffer from acquired immunodeficiency syndromes. To date, there is no effective vaccine against this fungal infection. Herein we demonstrated the use of immunomics to characterize promiscuous T cell epitope of C. albicans virulence factors by utilizing CandiVF, a C. albicans database previously constructed to be equipped with protein sequence analysis tool, three dimensional structure visualization software, sequence variable analysis program and Hotspot Hunter epitope prediction tool. Secretory aspartyl proteinase (Sap) family was chosen as a model to validate the Hotspot Hunter prediction. Analysis of Saps1-10 protein entries from CandiVF database revealed that a consensus T cell epitope was located at the C-terminal region of Saps1-10. The result of the in silico prediction was subsequently validated by conventional immunological methods. By using overlapping peptides span the predicted consensus T cell epitopes of Saps1-10 as stimulators, it was demonstrated that peptides S6 and S7 could stimulate PBMC proliferation in 9 of 12 blood donors. Interestingly, S2, the predicted T cell epitope of Sap2, was able to induce proliferation of all donors' PBMC. ELISpot assay for the detection of gamma-interferon producing clones confirmed that the peptide S2 actually stimulated T cell proliferation. The results suggest that S2 might be a potential candidate for vaccine development against C. albicans infection or to be utilized as an adjuvant to stimulate the preexisting CD4(+) T cell in other vaccine development. (C) 2007 Elsevier B.V. All rights reserved. C1 [Tongchusak, Songsak; Chaiyaroj, Sansanee C.] Mahidol Univ, Fac Sci, Dept Microbiol, Bangkok 10400, Thailand. [Brusic, Vladimir] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Brusic, Vladimir] Univ Queensland, Sch Land Crop & Food Sci, Brisbane, Qld, Australia. [Chaiyaroj, Sansanee C.] Chulabhorn Res Inst, Pharmacol Lab, Bangkok, Thailand. RP Chaiyaroj, SC (reprint author), Mahidol Univ, Fac Sci, Dept Microbiol, Bangkok 10400, Thailand. EM scscy@mahidol.ac.th NR 22 TC 6 Z9 16 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD JUL PY 2008 VL 8 IS 4 BP 467 EP 473 DI 10.1016/j.meegid.2007.09.006 PG 7 WC Infectious Diseases SC Infectious Diseases GA 317EB UT WOS:000257001400011 PM 17974505 ER PT J AU Tongchusak, S Leelayuwat, C Brusic, V Chaiyaroj, SC AF Tongchusak, Songsak Leelayuwat, Chanvit Brusic, Vladimir Chaiyaroj, Sansanee C. TI Development of a novel immunome-based Candida vaccine SO INFECTION GENETICS AND EVOLUTION LA English DT Meeting Abstract DE immunomome; immunomics; T-cell epitope; database and Candida albicans C1 [Tongchusak, Songsak; Chaiyaroj, Sansanee C.] Mahidol Univ, Fac Sci, Dept Microbiol, Bangkok 10700, Thailand. [Leelayuwat, Chanvit] Khon Kaen Univ, Dept Clin Immunol, Fac Assoc Med Sci, Khon Kaen, Thailand. [Brusic, Vladimir] Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD JUL PY 2008 VL 8 IS 4 BP S13 EP S13 PG 1 WC Infectious Diseases SC Infectious Diseases GA 317EB UT WOS:000257001400048 ER PT J AU Yi, JP Yi, JC Vitaliano, PP Weinger, K AF Yi, Joyce P. Yi, Jean C. Vitaliano, Peter P. Weinger, Katie TI How does anger coping style affect glycemic control in diabetes patients? SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE anger coping; psychological distress; glycemic control; diabetes ID QUALITY-OF-LIFE; PSYCHOSOCIAL FACTORS; INTENSIVE TREATMENT; PROBLEM AREAS; MELLITUS; ADULTS; STRESS; HYPOGLYCEMIA; ADHERENCE; DEPRESSION AB Background: Although various forms of anger have been found to influence the psychological and physical health in many chronic illness populations. little is known about the effects of anger in dabetes patients. Purpose: Associations between anger coping style. diabetes-related psychological distress. and glycosylated hemoglobin (HbAlc) were examined in 100 diabetes patients. Method: Participants completed the Problem Areas in Diabetes and Coping Styles questionnaires, and had HbAlc assessments at study entry (Time l = T1), six months (T2), and l2 months after T1 (T3). Results: Linear regression analyses revealed Tl anger coping associated with T3 hbAlc (beta = .22, p < .05), but Tl HbAlc did not associate with T3 anger coping (beta = .13.p = NS). After controlling for significant covariates (of gender, age, education, type and duration of diabetes), regression analyses revealed that T2 diabetes-related psychological distress partially mediated this association. Conclusion: These results suggested that higher levels of anger coping may promote poorer glycemic control in diabetes patients by provoking greater diabetes-related distress. Areas of future research on this topic are discussed. C1 [Weinger, Katie] Harvard Univ, Sch Med, Dept Psychiat, Joslin Diabet Ctr, Boston, MA 02135 USA. [Yi, Joyce P.] Childrens Hosp & Reg Med Ctr, Dept Endocrinol Diabet, Seattle, WA USA. [Yi, Jean C.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Vitaliano, Peter P.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Weinger, K (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Joslin Diabet Ctr, Boston, MA 02135 USA. FU NIDDK NIH HHS [R01 DK042315, R01 DK042315-08, R01 DK060115, R01 DK060115-01A1, R01 DK060115-02, R01 DK060115-03]; NIMH NIH HHS [R01 MH057663, R01 MH57663]; PHS HHS [R01 NIDDK24315, R01NIDDK60115] NR 34 TC 16 Z9 17 U1 6 U2 9 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PD JUL-SEP PY 2008 VL 15 IS 3 BP 167 EP 172 DI 10.1080/10705500802219481 PG 6 WC Psychology, Clinical SC Psychology GA 342YZ UT WOS:000258820800002 PM 18696309 ER PT J AU Rojas, A Meherem, S Kim, YH Washington, MK Willis, JE Markowitz, SD Grady, WM AF Rojas, Andres Meherem, Shereen Kim, Young-Ho Washington, Mary Kay Willis, Joseph E. Markowitz, Sanford D. Grady, William M. TI The aberrant methylation of TSF1 suppresses TGF-beta 1 activation in colorectal cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE thrombospondin; transforming growth factor beta; methylation; colorectal cancer; epigenetics ID GROWTH-FACTOR-BETA; RECEPTOR-TYPE-II; CPG ISLAND METHYLATION; TGF-BETA; COLON-CANCER; EPIGENETIC INACTIVATION; INSTRUCTIVE MECHANISM; GASTRIC-CANCER; GENE; THROMBOSPONDIN-1 AB Colorectal cancer arises from the progressive accumulation of mutations and epigenetic alterations in colon epithelial cells. Such alterations often deregulate signaling pathways that affect the formation of colon cancer, such as the Wnt, RAS-MAPK and TGF-beta pathways. The tumor promoting effects of mutations in genes, such as APC, have been demonstrated in cancer cell lines and in mouse models of intestinal cancer; however, the biological effects of most epigenetic events identified in colorectal cancer remain unknown. Consequently, we assessed whether the aberrant methylation of TSPI, the gene for thrombospondin 1, a regulator of TGF-beta ligand activation, is an epigenetic mechanism for inhibiting the TGF-beta signaling pathway. We found methylated TSPI occurs in colon cancer cell lines (33%), colon adenomas (14%) and colon adenocarcinomas (21%). In primary colorectal cancers, loss of TSPI expression correlated with impaired TGF-beta signaling as indicated by decreased Smad2 phosphorylation and nuclear localization. Furthermore, methylation-induced silencing of TSPI expression reduced the concentration of secreted active TGF-beta 1 and attenuated TGF-beta signaling. Reversal of TSPI methylation resulted in increased TSPI mediated activation of the latent LAP:TGF-beta complex and subsequent TGF-P receptor activation. Our results demonstrate that the aberrant methylation of TSP1 has biological consequences and provide evidence that the aberrant methylation of TSPI is a novel epigenetic mechanism for suppressing TGF-P signaling in colorectal cancer. (C) 2008 Wiley-Liss, Inc. C1 [Rojas, Andres; Grady, William M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Willis, Joseph E.] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. [Meherem, Shereen] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. [Kim, Young-Ho] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Med, Seoul, South Korea. [Washington, Mary Kay] Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37212 USA. [Markowitz, Sanford D.] Howard Hughes Med Inst, Cleveland, OH USA. [Rojas, Andres; Grady, William M.] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37212 USA. [Grady, William M.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Grady, William M.] VA Puget Sound Hlth Care Syst, R&D Serv, Seattle, WA USA. RP Grady, WM (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N D4-100, Seattle, WA 98109 USA. EM wgrady@fhcrc.org FU NCI NIH HHS [R01 CA115513, R01 CA115513-01A2] NR 46 TC 29 Z9 35 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 1 PY 2008 VL 123 IS 1 BP 14 EP 21 DI 10.1002/ijc.23608 PG 8 WC Oncology SC Oncology GA 302MU UT WOS:000255973200004 PM 18425817 ER PT J AU Roseman, AS Kasckow, J Fellows, I Osatuke, K Patterson, TL Mohamed, S Zisook, S AF Roseman, Ashley S. Kasckow, John Fellows, Ian Osatuke, Katerine Patterson, Thomas L. Mohamed, Somaia Zisook, Sidney TI Insight, quality of life, and functional capacity in middle-aged and older adults with schizophrenia SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE schizophrenia; insight; quality of life ID SCHIZOAFFECTIVE DISORDER; SUBJECTIVE RESPONSE; RATING-SCALE; PSYCHOSIS; OUTPATIENTS; MEDICATION; DEPRESSION; ILLNESS; ANTIPSYCHOTICS; SYMPTOMATOLOGY AB Objective The quality of life (QOL) for individuals with schizophrenia is determined by a number of factors, not limited to symptomatology. The current study examined lack of insight as one such factor that may influence subjective QOL or functional capacity. It was hypothesized that insight would significantly interact with symptom severity to influence subjective QOL. Insight was not expected to influence the relation between symptom severity and functional capacity. Methods Participants were middle-aged and older outpatients who met diagnostic criteria for schizophrenia or schizoaffective disorder, and subsyndromal depression. Insight, psychopathology, and subjective QOL were assessed via semi-structured interviews and functional capacity was assessed via performance-based measures. Results Insight interacts with negative symptom severity to predict subjective QOL. Severity of negative symptoms and insight contribute directly to functional capacity. Conclusions Individuals with intact insight may be better able to manage their symptoms, resulting in improved QOL. Treatment implications for improving the QOL of middle age and older adults with schizophrenia are discussed. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Roseman, Ashley S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77230 USA. [Kasckow, John] Vet Affairs Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Kasckow, John] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA 15260 USA. [Fellows, Ian; Patterson, Thomas L.; Zisook, Sidney] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Patterson, Thomas L.; Zisook, Sidney] San Diego Vet Affairs Hlth Serv Ctr, San Diego, CA USA. [Mohamed, Somaia] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. RP Roseman, AS (reprint author), Univ Texas MD Anderson Canc Ctr, Unit 1330,POB 301439, Houston, TX 77230 USA. EM acsenior@hotmail.com FU NIMH NIH HHS [R01 MH063931-01, T32 MH019934, R01 MH063931, R0-1 MH 063931-04, P30 MH066248, MH66248, MH19934, R01 MH6398] NR 44 TC 15 Z9 18 U1 2 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD JUL PY 2008 VL 23 IS 7 BP 760 EP 765 DI 10.1002/gps.1978 PG 6 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 327KZ UT WOS:000257729300015 PM 18205246 ER PT J AU Shapiro, EL Gans, JS AF Shapiro, Elizabeth L. Gans, Jerome S. TI The courage of the group therapist SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Group-Psychotherapy-Association CY FEB 20-25, 2006 CL San Francisco, CA SP Amer Grp Psychotherapy Assoc ID GROUP-PSYCHOTHERAPY; SHAME AB This report strives to legitimize for the field of psychodynamic group therapy the reflection on and study of courage. The authors surveyed g-roup therapy leaders, asking them to describe courageous moments in their own g-roup practice,, and then explored the common themes arising in these examples, including openly confronting their mistakes, facing their own and g-roup members' an anger, and dealing with unexpected moments in g-roup sessions. Attending to courageous leader moments-and the feelings of hope and pride that they engender-help to neutralize the negative emotions that group leaders are constantly invited to contain. Paradoxically, accessing courageous moments can also evoke feelings of shame in the leader. If we are to require ourselves to embrace the sometimes terrifying challenge of journeying into the unknown with our patients, we must learn to be honest not just about our mistakes and our weaknesses, but also about our successes and our strengths. The world is not respectable; it is mortal, tormented, confused, deluded forever, but it is shot through with beauty, with love, with glints of courage and laughter; and in these, the spirit blooms timidly, and struggles to the light amid the thorns. George Santayana, 1905-1906. C1 [Shapiro, Elizabeth L.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Shapiro, Elizabeth L.] Massachusetts Gen Hosp, Ctr Psychoanalyt Studies, Boston, MA 02114 USA. RP Shapiro, EL (reprint author), 25 Dawes Rd, Lexington, MA 02421 USA. EM shapiropowers@rcn.com NR 25 TC 3 Z9 3 U1 1 U2 4 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0020-7284 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD JUL PY 2008 VL 58 IS 3 BP 345 EP 361 DI 10.1521/ijgp.2008.58.3.345 PG 17 WC Psychology, Clinical SC Psychology GA 317RN UT WOS:000257037400004 PM 18573026 ER PT J AU Baker, P Oliva, E AF Baker, Patricia Oliva, Esther TI A practical approach to intraoperative consultation in gynecological pathology SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Review DE intraoperative diagnosis; gynecological tract; ovary; endometrium; myometrium; cervix; vulva; sentinel lymph node ID FROZEN-SECTION DIAGNOSIS; PELVIC LYMPH-NODES; I ENDOMETRIAL ADENOCARCINOMA; EXTRAMAMMARY PAGETS-DISEASE; OVARIAN MUCINOUS TUMORS; SQUAMOUS-CELL CARCINOMA; CORD-STROMAL TUMORS; CLINICOPATHOLOGICAL ANALYSIS; MYOMETRIAL INVASION; CERVICAL CONIZATION AB The use of frozen section in gynecological pathology. has not been emphasized in the literature to the same degree as in other surgical fields. This review focuses on the indications, contraindications, and limitations of frozen-section diagnosis specific to the female genital tract. An intraoperative consultation in gynecological pathology is indicated (a) to ensure that the tissue sampled is adequate for diagnosis, (b) to determine the nature of a disease process, (c) to plan for appropriate ancillary studies, (d) to determine tumor spread, and (e) to assess the margins. In the ovary, mucinous tumors in particular may present a challenge and potential for misdiagnosis at the time of frozen section. It is important to determine the nature of the ovarian involvement, as tumor size greater than 10cm or bilateral involvement strongly suggests a metastatic process. Also, the distinction between ovarian carcinoma and tumors of borderline malignancy may be difficult in a limited sampling. In the germ cell category, an important distinction is that of a dysgerminoma from a large cell lymphoma, due to different treatment regimes. Pregnant and postpartum women present a unique challenge as the effects of high levels of pregnancy-related hormones may result in lesions that closely mimic malignancy. Although intraoperative frozen section should be discouraged as a primary diagnostic procedure for endometrial carcinoma, it can be very helpful to identify those patients who are at risk for extrauterine spread and who may require lymphadenectomy. Analysis of a cone biopsy of the cervix by frozen section may be warranted particularly if the previous biopsy showed equivocal stromal invasion, an uncertain depth of invasion, there are issues related to fertility; however, the process is time consuming and may compromise the permanent sections if the lesion is very small. Frozen-section diagnosis in squamous cell carcinoma and in Paget disease of the vulva is-infrequently requested as these entities are multifocal resulting in an inaccurate frozen-section diagnosis. Lastly, intraoperative evaluation of lymph nodes including the role of sentinel lymph nodes is discussed. C1 [Oliva, Esther] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Baker, Patricia] Univ Manitoba, Winnipeg, MB, Canada. RP Oliva, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 55 Fruit St,Warren 2, Boston, MA 02115 USA. EM eoliva@partners.org NR 113 TC 31 Z9 34 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JUL PY 2008 VL 27 IS 3 BP 353 EP 365 DI 10.1097/PGP.0b013e31815c24fe PG 13 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 321BA UT WOS:000257277900007 PM 18580313 ER PT J AU Khunamornpong, S Lerwill, MF Siriaunkgul, S Suprasert, P Pojchamarnwiputh, S Chiangmai, WN Young, RH AF Khunamornpong, Surapan Lerwill, Melinda F. Siriaunkgul, Sumalee Suprasert, Prapaporn Pojchamarnwiputh, Suwalee Chiangmai, Wittanee Na Young, Robert H. TI Carcinoma of extrahepatic bile ducts and gallbladder metastatic to the ovary: A report of 16 cases SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE ovary; metastasis; cholangiocarcinoma; extrahepatic; bile duct carcinoma-; gallbladder carcinoma; Krukenberg tumor ID RARE KRUKENBERG TUMOR; MUCINOUS TUMORS; CLINICOPATHOLOGICAL ANALYSIS; PSEUDOMYXOMA-PERITONEI; BORDERLINE TUMORS; PRIMARY BILIARY; INTESTINAL-TYPE; ADENOCARCINOMAS; DISTINCTION; EXPRESSION AB Information on ovarian metastasis of carcinoma of the extraltepatic bile ducts and gallbladder is limited. Sixteen examples are reported; 3 primary tumors were hilar cholangiocarcinomas, 5 common bile duct carcinomas, and 8 gallbladder carcinomas. The patients ranged from 21 to 87 years (mean, 59 years); 7 presented to gynecologists with nonspecific pelvic symptoms similar to primary ovarian neoplasms. The primary tumor was identified before the detection of the ovarian lesions in 5 cases, was simultaneously detected with the ovarian metastases in 9, and was diagnosed postoperatively in 2. All but one case had bilateral ovarian involvement. The thirty-one ovarian lesions included twenty-nine grossly abnormal ovaries that were enlarged (range, 3.0-16.5cm, mean, 9.4cm) and 2 ovaries with only microscopic involvement. The sectioned surface was solid in 9, solid-cystic in 15, and multicystic in 5. Microscopically, ovarian surface implants were seen in 66%, multinodular growth in 58%, and infiltrative stromal invasion in 81%. Mucinous epithelial differentiation was seen in 81%, sometimes with foci of benign-like or borderline-like epithelium simulating primary ovarian mucinous neoplasia. Cystadenoma and cystadenofibroma of non-mucinous type was even mimicked strikingly in some cases because of flattening of epithelium lining glands and cysts. Signet ring cells were present in sufficient quantity for a diagnosis of Krukenberg tumor in four tumors. Colloid-type carcinoma was observed at least focally in 3 tumors. Nonmucinous carcinomatous components included adenocarcinoma with high-grade endometrioid-like morphology in 2 cases, papillary adenocarcinoma simulating mixed mullerian epithelial adenocarcinoma in 1, and undifferentiated carcinoma in 2. Immunohistochemical studies in 8 cases showed a positive reaction for cytokeratin 7 in all and for cytokeratin 20 in 4 cases. The high rate of bilaterality, surface involvement, multinodular growth, and heterogeneity of patterns were the most helpful features for indicating a metastatic nature, with signet ring cells also being helpful in the minority of cases in which they were present. Although the diagnosis of a metastatic tumor to the ovary is possible in most of the cases based on standard diagnostic criteria, problems in the differential diagnosis may be posed by morphologic patterns that overlap strikingly with primary ovarian neoplasms, benign, borderline, and malignant, as discussed herein. C1 [Khunamornpong, Surapan; Siriaunkgul, Sumalee] Chiang Mai Univ, Dept Pathol, Fac Med, Chiang Mai 50200, Thailand. [Suprasert, Prapaporn] Chiang Mai Univ, Dept Obstet & Gynecol, Fac Med, Chiang Mai 50200, Thailand. [Pojchamarnwiputh, Suwalee; Chiangmai, Wittanee Na] Chiang Mai Univ, Dept Radiol, Fac Med, Chiang Mai 50200, Thailand. [Lerwill, Melinda F.; Young, Robert H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs,Dept pathol, Boston, MA USA. RP Khunamornpong, S (reprint author), Chiang Mai Univ, Dept Pathol, Fac Med, Chiang Mai 50200, Thailand. EM skhunamo@mail.med.cmu.ac.th NR 38 TC 18 Z9 19 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JUL PY 2008 VL 27 IS 3 BP 366 EP 379 DI 10.1097/PGP.0b013e31815d6903 PG 14 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 321BA UT WOS:000257277900008 PM 18580314 ER PT J AU McCluggage, WG Nielsen, GP Young, RH AF McCluggage, W. Glenn Nielsen, G. P. Young, Robert H. TI Massive vulval edema secondary to obesity and immobilization: A potential mimic of aggressive angiomyxoma SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE vulva; edema ID FEMALE GENITAL-TRACT; ISCHEMIC FASCIITIS; MESENCHYMAL TUMOR; NEOPLASM; LESIONS; SERIES; ANGIOMYOFIBROBLASTOMA; MYOFIBROBLASTOMA; HYPERTROPHY; LYMPHEDEMA AB We report 2 cases of surgically resected vulvar masses in women aged 27 and 40 years. One patient was wheelchair bound and the other was obese, both presented with bilateral vulvar swelling. One specimen measured 45 cm in maximum dimension and the other 5 cm and were described as grossly edematous or gelatinous. Histologically, in both cases, there was edema of the skin overlying the lesion. The lesion itself consisted of markedly edematous connective tissue with widely separated bland spindle-shaped cells and numerous dilated vascular channels, sometimes surrounded by cuffs of lymphocytes and plasma cells. In the larger of the 2 specimens, underlying edematous adipose tissue was present. To some extent, the appearances, especially the morphological features, mimicked aggressive angiomyxoma because of the presence of a mass, the lack of circumscription, the hypocellular, edematous appearance, and the presence of numerous vascular channels. However, a combination of clinical and pathological features, including bilateralism, lack of a true myxoid stroma, the presence of perivascular cuffs of lymphoid cells, and lack of staining with estrogen receptor, is against aggressive angiomyxoma. The appearances were interpreted as those of massive edema. In one case, there was recurrence of the mass after surgery. There has been a single previous report of a similar vulvar case in a quadriplegic female patient and of similar cases involving the upper and lower extremities of obese patients. Clinicians and pathologists should be aware of the existence of this lesion, which is likely due to lymphatic obstruction and lymphedema secondary to immobilization and obesity. C1 [McCluggage, W. Glenn] Royal Grp Hosp Trust, Dept Pathol, Belfast BT12 6BA, Antrim, North Ireland. [McCluggage, W. Glenn] Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA USA. [Nielsen, G. P.; Young, Robert H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP McCluggage, WG (reprint author), Royal Grp Hosp Trust, Dept Pathol, Grosvenor Rd, Belfast BT12 6BA, Antrim, North Ireland. EM glenn.mccluggage@belfasttrust.hscni.net NR 22 TC 13 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JUL PY 2008 VL 27 IS 3 BP 447 EP 452 DI 10.1097/PGP.0b013e31816017a7 PG 6 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 321BA UT WOS:000257277900020 PM 18580326 ER PT J AU Pandolfi, F Cianci, R Lolli, S Dunn, IS Newton, EE Haggerty, TJ Boyle, LA Kurnick, JT AF Pandolfi, F. Cianci, R. Lolli, S. Dunn, I. S. Newton, E. E. Haggerty, T. J. Boyle, L. A. Kurnick, J. T. TI STRATEGIES TO OVERCOME OBSTACLES TO SUCCESSFUL IMMUNOTHERAPY OF MELANOMA SO INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY LA English DT Editorial Material DE malignant melanoma; immunotherapy; cancer vaccines; gene therapy ID TUMOR-INFILTRATING LYMPHOCYTES; REGULATORY T-CELLS; METASTATIC MELANOMA; ANTIGEN-EXPRESSION; IMMUNE RECOGNITION; CLINICAL-RESPONSE; DOWN-MODULATION; THERAPY; CANCER; ANTITUMOR AB The immunogenicity of malignant melanomas has been recognized by the observed recruitment of tumor-specific cytotoxic T-cells (CTL), leading to the identification of several melanoma associated antigen (MAA). However, numerous strategies to treat melanoma with immunotherapy have resulted in only partial success. In this editorial, we discuss recent data related to the ability of tumors to elude immune responses. We therefore discuss different strategies to induce a clinically effective immune response. These approaches include 1) immunostimulation: including peptide/protein based vaccines, dendritic cell vaccines, and adoptive cell transfer; and 2) overcoming immunosuppression, including targeting of checkpoint molecules such as CTLA-4, circumventing the activity of Tregs, and assuring antigen expression by tumor cells (thwarting antigen silencing). Finally, we discuss recent advances in gene therapy, including adoptive therapy with engineered T cell receptors (TCRs). These issues lead to the conclusion that successful immunotherapy in malignant melanoma requires a combination of strategies aimed at both inducing immunostimulation and blocking immunosuppression. C1 [Pandolfi, F.; Cianci, R.; Lolli, S.] Univ Cattolica Sacro Cuore, Inst Internal Med, I-00168 Rome, Italy. [Dunn, I. S.; Haggerty, T. J.; Boyle, L. A.; Kurnick, J. T.] CytoCure LLC, Beverly, MA USA. [Newton, E. E.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Haggerty, T. J.; Boyle, L. A.; Kurnick, J. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Haggerty, T. J.; Boyle, L. A.; Kurnick, J. T.] Harvard Univ, Sch Med, Boston, MA USA. RP Pandolfi, F (reprint author), Univ Cattolica Sacro Cuore, Ist Med Interna & Geriatria, Largo A Gemelli 8, I-00168 Rome, Italy. EM franco.pandolfi@uniroma1.it FU NCI NIH HHS [R43 CA128309, R43 CA128309-01] NR 35 TC 23 Z9 23 U1 0 U2 2 PU BIOLIFE SAS PI SILVA MARINA (TE) PA VIA S STEFANO 39 BIS, 64029 SILVA MARINA (TE), ITALY SN 0394-6320 J9 INT J IMMUNOPATH PH JI Int. J. Immunopathol. Pharmacol. PD JUL-SEP PY 2008 VL 21 IS 3 BP 493 EP 500 PG 8 WC Immunology; Pathology; Pharmacology & Pharmacy SC Immunology; Pathology; Pharmacology & Pharmacy GA 359KR UT WOS:000259986100002 PM 18831916 ER PT J AU Fava, M AF Fava, M. TI Which patients do best with each different 2nd and 3rd step acute treatments? SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Fava, M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUL PY 2008 VL 11 SU 1 BP 35 EP 36 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855500150 ER PT J AU McCarley, R Spencer, K Niznikiewicz, M Salisbury, D AF McCarley, R. Spencer, K. Niznikiewicz, M. Salisbury, D. TI Gamma band neural synchrony abnormalities in schizophrenia and disordered perception and cognition SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [McCarley, R.; Spencer, K.; Niznikiewicz, M.] Harvard Univ, Dept Psychiat, VA Boston Healthcare Syst, Brockton, MA 02401 USA. [Salisbury, D.] Harvard Univ, McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUL PY 2008 VL 11 SU 1 BP 47 EP 47 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855500203 ER PT J AU Nierenberg, AA AF Nierenberg, A. A. TI Severity at baseline and long-term response to treatment in MDD SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Nierenberg, A. A.] Massachusetts Gen Hosp, Bipolar Clin & Res, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUL PY 2008 VL 11 SU 1 BP 70 EP 70 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855500302 ER PT J AU Montgomery, S Fava, M Tourian, K Padmanabhan, SK Guico-Pabia, C AF Montgomery, S. Fava, M. Tourian, K. Padmanabhan, S. K. Guico-Pabia, C. TI Discontinuation symptoms and taper/poststudy-emergent adverse events with desvenlafaxine 50mg/d, 100mg/d, 200 mg/d, and 400 mg/d for major depressive disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Montgomery, S.] Univ London Imperial Coll Sci Technol & Med, Sch Med, London, England. [Tourian, K.; Padmanabhan, S. K.; Guico-Pabia, C.] Wyeth Res, Collegeville, PA USA. [Fava, M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUL PY 2008 VL 11 SU 1 BP 199 EP 199 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855501112 ER PT J AU Warden, D Rush, AJ Trivedi, N Wisniewski, SR Lesser, IM Kornstein, SG Balasubramani, GK Thase, M Preskorn, SH Nierenberg, AA Young, EA AF Warden, D. Rush, A. J. Trivedi, N. Wisniewski, S. R. Lesser, I. M. Kornstein, S. G. Balasubramani, G. K. Thase, M. Preskorn, S. H. Nierenberg, A. A. Young, E. A. TI What predicts attrition in second step medication treatments for depression? A STAR*D report SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Warden, D.; Rush, A. J.; Trivedi, N.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Wisniewski, S. R.; Balasubramani, G. K.] Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA 15260 USA. [Lesser, I. M.] UCLA Harbor City, Torrance, CA USA. [Kornstein, S. G.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Thase, M.] Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Preskorn, S. H.] Clin Res Inst, Wichita, KS USA. [Nierenberg, A. A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Young, E. A.] Univ Michigan, Ann Arbor, MI 48109 USA. RI Preskorn, Sheldon/L-9839-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUL PY 2008 VL 11 SU 1 BP 201 EP 201 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855501117 ER PT J AU Biederman, J Ermer, JC Krishnan, S AF Biederman, J. Ermer, J. C. Krishnan, S. TI Improved interpatient pharmacokinetic variability of lisdexamfetamine compared with mixed amphetamine salts extended release in children aged 6-12 years with attention-deficit/hyperactivity disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Biederman, J.] Massachusetts Gen Hosp, ADHD Program, Boston, MA 02114 USA. [Ermer, J. C.] Shire Dev Inc, Wayne, NJ USA. [Krishnan, S.] Form New River Pharma Inc, Belvedere, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUL PY 2008 VL 11 SU 1 BP 292 EP 292 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855501488 ER PT J AU Goodman, D Adler, L Kollins, SH Weisler, R Krishnan, S Zhang, Y Biederman, J AF Goodman, D. Adler, L. Kollins, S. H. Weisler, R. Krishnan, S. Zhang, Y. Biederman, J. TI Efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Goodman, D.] Johns Hopkins Univ, Baltimore, MD USA. [Adler, L.] NYU, Dept Psychiat, New York, NY 10016 USA. [Kollins, S. H.] Duke Univ, Med Ctr, Duke ADHD Program, Durham, NC USA. [Weisler, R.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Krishnan, S.] Form New River Pharma Inc, Belvedere, CA USA. [Zhang, Y.] Xtiers Consulting, Potomac, WV USA. [Biederman, J.] Massachusetts Gen Hosp, ADHD Program, Boston, MA 02114 USA. RI Kollins, Scott/G-2965-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUL PY 2008 VL 11 SU 1 BP 292 EP 293 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855501489 ER PT J AU Fava, M McCall, WV Wessel, T Amato, D Paska, W Montgomery, S Roth, T AF Fava, M. McCall, W. V. Wessel, T. Amato, D. Paska, W. Montgomery, S. Roth, T. TI Eszopiclone co-administered with fluoxetine for insomnia co-existing with major depressive disorder (MDD): A subgroup analysis SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Fava, M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [McCall, W. V.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Wessel, T.; Amato, D.] Sepracor Inc, Marlborough, MA USA. [Paska, W.] GlaxoSmithKline Inc, Clin Dev, Greenford, Middx, England. [Montgomery, S.] Univ London Imperial Coll Sci Technol & Med, Sch Med, London, England. [Roth, T.] Henry Ford Hosp, Sleep Disorders Ctr, Detroit, MI 48202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUL PY 2008 VL 11 SU 1 BP 306 EP 306 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855501544 ER PT J AU Krystal, A Schaefer, K Rockett, C Fava, M Amato, D Roth, T AF Krystal, A. Schaefer, K. Rockett, C. Fava, M. Amato, D. Roth, T. TI Differential sleep effects of eszopiclone treatment and discontinuation in patients with primary insomnia and insomnia co-existing with major depressive disorder or generalized anxiety disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Krystal, A.] Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. [Schaefer, K.; Amato, D.] Sepracor Inc, Marlborough, MA USA. [Fava, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Roth, T.] Henry Ford Hosp, Sleep Disorders Ctr, Detroit, MI 48202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUL PY 2008 VL 11 SU 1 BP 306 EP 306 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855501545 ER PT J AU Montgomery, S Fava, M Krystal, A Wessel, T Amato, D Cooper, J McCall, WV AF Montgomery, S. Fava, M. Krystal, A. Wessel, T. Amato, D. Cooper, J. McCall, W. V. TI Evaluation of the HAM-D17 following eszopiclone treatment in patients with insomnia co-morbid with major depressive disorder or generalized anxiety disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Montgomery, S.] Univ London Imperial Coll Sci Technol & Med, London, England. [Fava, M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Krystal, A.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Wessel, T.; Amato, D.] Sepracor Inc, Marlborough, MA USA. [Cooper, J.] GlaxoSmithKline Inc, MDC, Greenford, Middx, England. [McCall, W. V.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUL PY 2008 VL 11 SU 1 BP 306 EP 306 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855501546 ER PT J AU Fava, M AF Fava, M. TI Addressing co-morbidities in insomnia SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Fava, M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUL PY 2008 VL 11 SU 1 BP 316 EP 316 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855501586 ER PT J AU Kawano, T Ahmad, R Nogi, H Agata, N Anderson, K Kufe, D AF Kawano, Takeshi Ahmad, Rehan Nogi, Hiroko Agata, Naoki Anderson, Kenneth Kufe, Donald TI MUC1 oncoprotein promotes growth and survival of human multiple myeloma cells SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE MUC1; multiple myeloma; beta-catenin; NF-kappa B; growth; self-renewal ID NF-KAPPA-B; CARCINOMA-ASSOCIATED ANTIGEN; BETA-CATENIN; BONE-MARROW; C-SRC; EXPRESSION; PATHWAY; PROTEIN; ACTIVATION; COMPLEX AB The MUC1 oncoprotein is aberrantly expressed in human multiple myeloma cells by mechanisms that are not understood. Moreover, the functional role of MUC1 in multiple myeloma is not known. The present studies demonstrate that the MUC1 gene locus is amplified in multiple myeloma cell lines and in primary cells from patients. The KMS28PE multiple myeloma cell line, which was found to have MUC1 gene amplification, was stably silenced for MUC1 using different siRNAs. Silencing MUC1 was associated with a decrease in nuclear beta-catenin levels, consistent with the function of MUC1 in stabilizing B-catenin. MUC1 is also known to activate the IKK beta -> NIF-kappa B pathway and KMS28PE cells silenced for MUC1 were found to have downregulation of IKK beta and I kappa B alpha phosphorylation, and decreased nuclear targeting of NF-kappa B p65. The results also demonstrate that MUC1: i) contributes to KMS28PE cell proliferation, and ii) protects against apoptosis and loss of self-renewal in the response to melphalan and dexamethasone. These findings indicate that MUCI activates the B-catenin and NF-kappa B pathways in multiple myeloma cells and contributes to their growth and survival. C1 [Kufe, Donald] Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu FU NCI NIH HHS [CA100707, P50 CA100707, P50 CA100707-01] NR 44 TC 25 Z9 26 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD JUL PY 2008 VL 33 IS 1 BP 153 EP 159 PG 7 WC Oncology SC Oncology GA 321AJ UT WOS:000257276200017 PM 18575761 ER PT J AU Bortfeld, T Craft, D Dempsey, JF Halabi, T Romeijn, HE AF Bortfeld, Thomas Craft, David Dempsey, James F. Halabi, Tarek Romeijn, H. Edwin TI Evaluating target cold spots by the use of tail EUDs SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE radiation therapy; IMRT; optimization; equivalent uniform dose; tumor coverage ID INTENSITY-MODULATED RADIOTHERAPY; FLUENCE MAP OPTIMIZATION; RADIATION-THERAPY; MODELS; TUMOR; IMRT AB Purpose: To propose a new measure of target underdose that can be used in the evaluation and optimization of radiotherapy dose distributions. Methods and Materials: We compare various formulations of the equivalent uniform dose (EUD) and introduce a modification of existing EUD definitions, which we call tail EUD. Tail EUD is a measure of "cold spots" below the prescription dose in the target dose distribution, using units of gray (Gy). We investigate the mathematical properties of various target EUD concepts, including tail EUD. We apply the tail EUD measure retrospectively to intensity modulated radiation therapy (IMRT) treatment plans from our plan database. We also use tail EUD as an optimization objective in the optimization of prostate, pancreas, and head-and-neck plans. Results: Tail EUD has desirable mathematical properties. In particular, it is convex and it leads to convex level sets (i.e., no local minima) if the EUD from which it is derived is concave. The tail EUD value is correlated with the subjective degree of target coverage. Constraining tail EUDs to a certain level in plan optimization leads to comparable target coverage in different plans and treatment sites. Conclusions: The newly introduced concept of tail EUD appears to be useful for both plan evaluation and optimization. In addition it can potentially be applied in the design of new clinical protocols. (C) 2008 Elsevier Inc. C1 [Bortfeld, Thomas; Craft, David; Halabi, Tarek] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Bortfeld, Thomas; Craft, David; Halabi, Tarek] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Dempsey, James F.; Romeijn, H. Edwin] Univ Florida, Dept Radiat Oncol, Gainesville, FL USA. [Romeijn, H. Edwin] Univ Florida, Dept Ind & Syst Engn, Gainesville, FL 32611 USA. RP Bortfeld, T (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. EM tbortfeld@partners.org FU NCI NIH HHS [R01 CA103904, R01 CA103904-05, R01 CA118200, CA 103904, R01 CA118200-02] NR 26 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 2008 VL 71 IS 3 BP 880 EP 889 DI 10.1016/j.ijrobp.2008.01.049 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 311AN UT WOS:000256572400032 PM 18440728 ER PT J AU Cormack, RA Devlin, PM AF Cormack, Robert. A. Devlin, Phillip. M. TI Brachytherapy partial breast irradiation: Analyzing effect of source configurations on dose metrics relevant to toxicity SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE brachytherapy; partial breast irradiation; dosimetry; toxicity ID INTERSTITIAL BRACHYTHERAPY; MAMMOSITE; EXPERIENCE; COSMESIS; CANCER; TRIAL AB Purpose: Recently, the use of partial breast irradiation (PBI) for patients with early-stage breast cancer with low-risk factors has increased. The volume of the high-dose regions has been correlated with toxicity in interstitial treatment. Although no such associations have been made in applicator-based experience, new applicators are being developed that use complex noncentered source configurations. This work studied the effect of noncentered source placements on the volume of the high-dose regions around a spherical applicator. Methods and Materials: Many applicator configurations were numerically simulated for a range of inflation radii. For each configuration, a dose homogeneity index was used as a dose metric to measure the volume of the high-dose region. Results: All multisource configurations examined resulted in an increase of the high-dose region compared with a single-center source. The resulting decrease in the prescription dose homogeneity index was more pronounced for sources further from the center of the applicator, and the effect was reduced as the number of dwell locations was increased. Conclusion: The geometries of particular applicators were not considered to achieve a more general result. On the basis of the calculations of this work, it would appear that treatment using noncentered dwell locations will lead to an increase in the volume of the high-dose regions. (C) 2008 Elsevier Inc. C1 [Cormack, Robert. A.; Devlin, Phillip. M.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Cormack, RA (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. EM rcormack@1roc.harvard.edu OI Cormack, Robert/0000-0001-5553-9984 NR 11 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 2008 VL 71 IS 3 BP 940 EP 944 DI 10.1016/j.ijrobp.2008.03.002 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 311AN UT WOS:000256572400039 PM 18514786 ER PT J AU Parodi, K Bortfeld, T Haberer, T AF Parodi, Katia Bortfeld, Thomas Haberer, Thomas TI Comparison between in-beam and offline positron emission tomography imaging of proton and carbon ion therapeutic irradiation at synchrotron- and cyclotron-based facilities SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE ion therapy; positron emission tomography ID PET MEASUREMENTS; RANDOM COINCIDENCES; TUMOR-THERAPY; VERIFICATION; RADIOTHERAPY; DISTRIBUTIONS; FEASIBILITY; DELIVERY; WASHOUT; RABBIT AB Purpose: The benefit of using dedicated in-beam positron emission tomography (PET) detectors in the treatment room instead of commercial tomographs nearby is an open question. This work quantitatively compares the measurable signal for in-beam and offline PET imaging, taking into account realistic acquisition strategies at different ion beam facilities. Both scenarios of pulsed and continuous irradiation from synchrotron and cyclotron accelerators are considered, because of their widespread use in most carbon ion and proton therapy centers. Methods and Materials: A mathematical framework is introduced to compare the time-dependent amount and spatial distribution of decays from irradiation-induced isotope production. The latter is calculated with Monte Carlo techniques for real proton treatments of head-and-neck and paraspinal tumors. Extrapolation to carbon ion irradiation is based on results of previous phantom experiments. Biologic clearance is modeled taking into account available data from previous animal and clinical studies. Results: Ratios between the amount of physical decays available for in-beam and offline detection range from 40% to 60% for cyclotron-based facilities, to 65% to 110% (carbon ions) and 94% to 166% (protons) at synchrotron-based facilities, and increase when including biologic clearance. Spatial distributions of decays during irradiation exhibit better correlation with the dose delivery and reduced influence of biologic processes. Conclusions: In-beam imaging can be advantageous for synchrotron-based facilities, provided that efficient PET systems enabling detection of isotope decays during beam extraction are implemented. For very short (<2 min) irradiation times at cyclotron-based facilities, a few minutes of acquisition time after the end of irradiation are needed for counting statistics, thus affecting patient throughput. (C) 2008 Elsevier Inc. C1 [Parodi, Katia; Haberer, Thomas] Heidelberg Ion Beam Therapy Ctr, D-69120 Heidelberg, Germany. [Bortfeld, Thomas] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Parodi, K (reprint author), Heidelberg Ion Beam Therapy Ctr, Im Neuenheimer Feld 450, D-69120 Heidelberg, Germany. EM Katia.Parodi@med.uni-heidelberg.de NR 26 TC 47 Z9 47 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 2008 VL 71 IS 3 BP 945 EP 956 DI 10.1016/j.ijrobp.2008.02.033 PG 12 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 311AN UT WOS:000256572400040 PM 18514787 ER PT J AU Fellegara, G Young, RH Kuhn, E Rosai, J AF Fellegara, Giovanni Young, Robert H. Kuhn, Elisabetta Rosai, Juan TI Ovarian mature cystic teratoma with florid vascular proliferation and Wagner-Meissner-like corpuscles SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ovary; teratoma; Wagner-Meissner corpuscles; blood vessels ID TOUCH CORPUSCLES; TUMOR AB An ovarian mature cystic teratoma featuring florid vascular proliferation and Wagner-Meissner-like corpuscles is presented. The vascular proliferation is analogous to that seen in other tumors having a prominent neural component. The Wagner-Meissner-like corpuscles are viewed as evidence of a specialized type of differentiation of this neural component. To the best of our knowledge, they had not been previously reported in this setting. C1 [Fellegara, Giovanni; Kuhn, Elisabetta; Rosai, Juan] CDI, Ctr Consulenze Anat Patol Oncol, I-20147 Milan, Italy. [Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. RP Rosai, J (reprint author), CDI, Ctr Consulenze Anat Patol Oncol, 20 Via St Bon, I-20147 Milan, Italy. EM rosai@cdi.it NR 16 TC 5 Z9 5 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD JUL PY 2008 VL 16 IS 3 BP 320 EP 323 DI 10.1177/1066896907307306 PG 4 WC Pathology; Surgery SC Pathology; Surgery GA 319MR UT WOS:000257168300013 PM 18573789 ER PT J AU Jurkunas, UV Bitar, MS Rawe, I Harris, DL Colby, K Joyce, NC AF Jurkunas, Ula V. Bitar, Maya S. Rawe, Ian Harris, Deshea L. Colby, Kathryn Joyce, Nancy C. TI Increased clusterin expression in Fuchs' endothelial dystrophy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID PROSTATE-CANCER CELLS; OXIDATIVE STRESS; APOLIPOPROTEIN-J; BULLOUS KERATOPATHY; CORNEAL-DYSTROPHY; MACULAR DEGENERATION; ALZHEIMERS-DISEASE; EPITHELIAL-CELLS; VIII COLLAGEN; HEAT-SHOCK AB PURPOSE. To investigate the differential expression of the glycoprotein clusterin/apoJ (CLU) in normal and Fuchs' endothelial dystrophy (FED) corneal endothelium and to compare the expression of various forms of CLU in normal and FED tissue. METHODS. FED and pseudophakic bullous keratopathy (PBK) corneal buttons were removed during transplantation, and normal corneas were obtained from tissue banks. Human corneal endothelial cells and Descemet's membrane (HCEC-DM) complex was dissected from the stroma. Proteins were separated on 2-D gels and subjected to comparative proteomic analysis. Relative expression of presecretory CLU (pre-sCLU), secretory (s) CLU, and nuclear (n) CLU were compared between normal and FED HCEC-DM by Western blot analysis. Expression of CLU mRNA was compared by using RT-PCR. Subcellular localization of CLU was compared in corneal wholemounts from normal eyes and eyes with FED by immunocytochemistry followed by confocal microscopy. RESULTS. Proteomic analysis revealed an apparent increase in CLU expression in FED HCEC-DM compared with the normal control. Western blot analysis demonstrated that pre-sCLU protein expression was 5.2 times higher in FED than in normal samples (P = 3.52E-05), whereas the mature form modified for secretion (sCLU) was not significantly elevated (P = 0.092). Expression of nCLU protein was significantly elevated in FED (P = 0.013). RT-PCR analysis revealed that CLU mRNA was significantly increased (P = 0.002) in FED samples, but not in PBK samples. CLU also had a distinctive localization in FED samples with enhanced intracellular staining around the guttae and in the nuclei of endothelial cells. CONCLUSIONS. CLU expression is markedly elevated in FED-affected tissue, pointing to a yet undiscovered form of dysregulation of endothelial cell function involved in FED pathogenesis. C1 [Jurkunas, Ula V.; Colby, Kathryn] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Jurkunas, Ula V.; Bitar, Maya S.; Rawe, Ian; Harris, Deshea L.; Colby, Kathryn; Joyce, Nancy C.] Schepens Eye Res Inst, Boston, MA USA. [Jurkunas, Ula V.; Bitar, Maya S.; Harris, Deshea L.; Colby, Kathryn; Joyce, Nancy C.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Jurkunas, UV (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM ula_jurkunas@meei.harvard.edu OI Harris, Deshea/0000-0002-8194-1827 FU NEI NIH HHS [K12 EY016335, K12 EY016335-02] NR 55 TC 26 Z9 26 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 2008 VL 49 IS 7 BP 2946 EP 2955 DI 10.1167/iovs.07-1405 PG 10 WC Ophthalmology SC Ophthalmology GA 318WR UT WOS:000257124000022 PM 18378577 ER PT J AU Jurkunas, UV Rawe, I Bitar, MS Zhu, C Harris, DL Colby, K Joyce, NC AF Jurkunas, Ula V. Rawe, Ian Bitar, Maya S. Zhu, Cheng Harris, Deshea L. Colby, Kathryn Joyce, Nancy C. TI Decreased expression of peroxiredoxins in Fuchs' endothelial dystrophy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID THIOL-SPECIFIC ANTIOXIDANT; THIOREDOXIN PEROXIDASE; CORNEAL ENDOTHELIUM; CELL APOPTOSIS; SUBTYPES; KERATOPLASTY; MITOCHONDRIA; DISORDERS; REDUCTASE; MUTATION AB PURPOSE. To compare the relative expression of peroxiredoxin (Prx) proteins in normal human corneal endothelium with endothelium in corneas affected by Fuchs' endothelial dystrophy (FED) and between normal human endothelium and epithelial/ stromal tissue. METHODS. Human corneal endothelial cell-Descemet's membrane (HCEC-DM) complexes from normal and FED corneal buttons were dissected from the epithelium/stroma. For proteomic analysis, HCEC-DM protein extracts were separated by using two-dimensional gel electrophoresis. Relative differences in protein spot density was analyzed. Proteins of interest, including Prx isoforms, were identified by MALDI-TOF (matrix-assisted desorption ionization-time of flight) mass spectrometry. Western blot analysis compared the relative expression of Prx isoforms in normal and FED endothelium and between normal endothelium and normal epithelium/stroma. Expression of Prx-2 mRNA was compared by using real-time PCR. RESULTS. Proteomic analysis identified differences in the relative expression of Prx isoforms between normal and FED endothelium. Western blot analysis confirmed that expression of Prx-2, -3, and -5 was significantly decreased (P < 0.05) in FED cells. Normal HCECs expressed significantly (P < 0.05) higher levels of Prx-2 and -3 than did the epithelium/stroma. Expression of Prx-5 was not significantly different (P > 0.05) in the endothelium versus the epithelium/stroma. Real-time PCR analysis revealed that Prx-2 mRNA was significantly decreased (P = 0.027) in FED samples. CONCLUSIONS. Prx proteins were identified in human corneal endothelium. The fact that Prx-2 and -3 were expressed at significantly higher levels in HCEC-DM compared with the epithelium/stroma reflects the different physiologic activities of individual corneal cell types. Significantly decreased expression of Prx-2, -3, and -5 in FED may suggest an alteration in the ability of endothelial cells to withstand oxidant-induced damage and may be closely related to the pathogenesis of this disease. C1 [Jurkunas, Ula V.; Colby, Kathryn] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Jurkunas, Ula V.; Rawe, Ian; Bitar, Maya S.; Zhu, Cheng; Harris, Deshea L.; Colby, Kathryn; Joyce, Nancy C.] Schepens Eye Res Inst, Boston, MA USA. [Jurkunas, Ula V.; Bitar, Maya S.; Zhu, Cheng; Harris, Deshea L.; Colby, Kathryn; Joyce, Nancy C.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Jurkunas, UV (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM ula_jurkunas@meei.harvard.edu OI Harris, Deshea/0000-0002-8194-1827 FU NEI NIH HHS [K12 EY016335-02, K12 EY016335] NR 32 TC 42 Z9 43 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 2008 VL 49 IS 7 BP 2956 EP 2963 DI 10.1167/iovs.07-1529 PG 8 WC Ophthalmology SC Ophthalmology GA 318WR UT WOS:000257124000023 PM 18378575 ER PT J AU Jun, HJ Rich-Edwards, JW Boynton-Jarrett, R Austin, SB Frazier, AL Wright, RJ AF Jun, Hee-Jin Rich-Edwards, Janet W. Boynton-Jarrett, Renee Austin, S. Bryn Frazier, A. Lindsay Wright, Rosalind J. TI Child abuse and smoking among young women: The importance of severity, accumulation, and timing SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE smoking initiation; childhood abuse; young women ID ADOLESCENT SUBSTANCE USE; NATIONAL-SURVEY; SOCIAL SUPPORT; PSYCHIATRIC-DISORDERS; ADULT RECOLLECTIONS; PULMONARY-FUNCTION; VICTIMIZATION; EXPERIENCES; DEPRESSION; HEALTH AB Purpose: We examined the association between severity, accumulation, and timing of abuse in childhood and adolescence and smoking status among young women. Methods: Retrospective self-reported childhood abuse was ascertained with the modified Conflict Tactics Scale from 91,286 Nurses Health Study 11 participants in 2001 (68,505 returned; 75.0% response rate). Childhood abuse was categorized by severity (mile/moderate/severe), type (physical/sexual), and timing (childhood/adolescence). Smoking status during adolescence was reported at baseline (1989). Logistic regression was used to predict smoking initiation by age 14 and smoking status between the ages of 15 and 19. Results: A graded association between severity of abuse and early initiation of smoking (by age 14 years) was demonstrated (odds ratio [OR] = 1.9, 95% confidence interval [CI] = 1.7-2.1 for severe physical violence). Young women with both physical and sexual abuse were two times more likely to start smoking by age 14 than were those reporting no abuse (OR = 2.0, 95% CI = 1.8-2.3). Although abuse during childhood increased risk for adolescent smoking (OR = 1.7, 95% CI = 1.8-2.1) for those with childhood physical and sexual abuse, inclusion of adolescent physical and sexual abuse (OR = 2.2, 95% CI 2.1-2.4) diminished the impact of childhood abuse (OR = 1.1, 95% CI 1.1-1.2). The degree of familial emotional support was protective against smoking, and reduced the impact of abuse by 40% among those with high emotional support versus those without (p <.0001). Conclusions: A strong and graded association was observed between both severity and accumulation of abuse and the risk of early inifiation of smoking among girls. Smoking status during late adolescence was more strongly associated with adolescent abuse than childhood abuse. Early smoking onset is associated with both heightened risk for disease in adolescence but also increased morbidity and mortality in adulthood. Identifying and intervening in potentially modifiable risk factors for smoking onset in young women, such as early-life physical and sexual abuse, and building familial strengths, such as emotional support, may have significant public health implications. (c) 2008 Society for Adolescent Medicine. All rights reserved. C1 [Jun, Hee-Jin; Rich-Edwards, Janet W.; Austin, S. Bryn; Frazier, A. Lindsay; Wright, Rosalind J.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Jun, Hee-Jin; Rich-Edwards, Janet W.; Austin, S. Bryn; Frazier, A. Lindsay; Wright, Rosalind J.] Harvard Univ, Sch Med, Boston, MA USA. [Rich-Edwards, Janet W.] Brigham & Womens Hosp, Ctr Excellence Women, Boston, MA 02115 USA. [Rich-Edwards, Janet W.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Boynton-Jarrett, Renee] Boston Med Ctr, Dept Gen Pediat, Boston, MA USA. [Austin, S. Bryn] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Austin, S. Bryn; Frazier, A. Lindsay] Childrens Hosp, Div Adolescent & Young Adult Med, Boston, MA 02115 USA. [Frazier, A. Lindsay] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wright, Rosalind J.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Jun, HJ (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM nhhjj@channing.harvard.edu OI Boynton-Jarrett, Renee/0000-0002-5392-6443 FU NHLBI NIH HHS [R01 HL064108, HL64108-04] NR 49 TC 43 Z9 43 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD JUL PY 2008 VL 43 IS 1 BP 55 EP 63 DI 10.1016/j.jadohealth.2007.12.003 PG 9 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 316JV UT WOS:000256946600010 PM 18565438 ER PT J AU Hunninghake, GM Soto-Quiros, ME Lasky-Su, J Avila, L Ly, NP Liang, C Klanderman, BJ Raby, BA Gold, DR Weiss, ST Celedon, JC AF Hunninghake, Gary M. Soto-Quiros, Manuel E. Lasky-Su, Jessica Avila, Lycliana Ly, Ngoc P. Liang, Catherine Klanderman, Barbara J. Raby, Benjamin A. Gold, Diane R. Weiss, Scott T. Celedon, Juan C. TI Dust mite exposure modifies the effect of functional IL10 polymorphisms on allergy and asthma exacerbations SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE IL10; asthma; IgE; dust mite; interaction; exacerbations; Costa Rica; CAMP ID SINGLE-NUCLEOTIDE POLYMORPHISMS; FAMILY-BASED ASSOCIATION; CHILDHOOD ASTHMA; DIFFERENTIAL EXPRESSION; MANAGEMENT PROGRAM; EPITHELIAL-CELLS; COSTA-RICA; EARLY-LIFE; IL-10; RISK AB Background: The allergenicity of dust mite exposure might be dependent on variants in the gene for IL-10 (IL10). Objectives: To evaluate whether dust mite exposure modifies the effect of single nucleotide polymorphisms (SNPs) in IL10 on allergy and asthma exacerbations. Methods: We genotyped 6 SNPs in IL10 in 417 Costa Rican children and 503 white children in the Childhood Asthma Management Program (CAMP) with asthma and their parents. We used family-based and population-based approaches to test for interactions between IL10 SNPs and dust mite allergen on serum IgE to dust mite in Costa Rica and on asthma exacerbations in Costa Rica and CAMP. Results: Dust mite exposure significantly modified the relation between 3 SNPs in IL10 (rs1800896, rs3024492, and rs3024496) and IgE to dust mite in Costa Rica (P for interaction, .0004 for SNP rs1800896). For each of these SNPs, homozygosity for the minor allele was associated with increased levels of IgE to dust mite with increased dust mite exposure. Homozygosity for the minor allele of each of the 3 SNPs was associated with increased risk of occurrence (similar to 3-fold to 39-fold increase) and frequency of asthma exacerbations among children exposed to >= 10 mu g/g dust mite allergen in Costa Rica. Similar results were obtained for 2 of these SNPs (rs1800896 and rs3024496) among white children in CAMP. Conclusion: Our findings suggest that dust mite allergen levels modify the effect of IL10 SNPs on allergy and asthma exacerbations and may partly explain conflicting findings in this field. C1 [Hunninghake, Gary M.; Lasky-Su, Jessica; Ly, Ngoc P.; Liang, Catherine; Klanderman, Barbara J.; Raby, Benjamin A.; Gold, Diane R.; Weiss, Scott T.; Celedon, Juan C.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Hunninghake, Gary M.; Raby, Benjamin A.; Celedon, Juan C.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Hunninghake, Gary M.; Lasky-Su, Jessica; Ly, Ngoc P.; Klanderman, Barbara J.; Raby, Benjamin A.; Gold, Diane R.; Weiss, Scott T.; Celedon, Juan C.] Harvard Univ, Sch Med, Boston, MA USA. [Soto-Quiros, Manuel E.; Avila, Lycliana] Hosp Nacl Ninos Dr Carlos Saenz Herrera, Div Pediat Pulmonol, San Jose, Costa Rica. [Lasky-Su, Jessica] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Ly, Ngoc P.] Massachusetts Gen Hosp, Pediat Pulm Div, Boston, MA 02114 USA. RP Celedon, JC (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM juan.celedon@channing.harvard.edu FU NHLBI NIH HHS [T32HL07427, F32 HL083634, HL66289, N01-HR-16049, P01HL083069, U01 HL065899, U01HL65899, U01HL075419, R01HL086601, HL074193, HL04370, F32 HL083634-02, 1F32HL083634] NR 46 TC 36 Z9 37 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUL PY 2008 VL 122 IS 1 BP 93 EP 98 DI 10.1016/j.jaci.2008.03.015 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 325RD UT WOS:000257605100015 PM 18440625 ER PT J AU Meeker, JD Singh, NP Hauser, R AF Meeker, John D. Singh, Narendra P. Hauser, Russ TI Serum concentrations of estradiol and free T-4 are inversely correlated with sperm DNA damage in men from an infertility clinic SO JOURNAL OF ANDROLOGY LA English DT Article DE chromatin; comet assay; epidemiology; hormone; human ID HUMAN SEMEN PARAMETERS; THYROID-HORMONE; COMET ASSAY; CHROMATIN-STRUCTURE; EMBRYO DEVELOPMENT; OXIDATIVE STRESS; ELDERLY-MEN; IN-VITRO; SPERMATOGENESIS; ESTROGEN AB Sperm DNA damage adversely affects male fertility and contributes to poorer embryo development and lower pregnancy rates. Endogenous hormones are critical to spermatogenesis and maintenance of male reproductive function and likely play an important role in human sperm DNA integrity, but this relationship is not fully understood. The present study measured serum hormone levels and sperm DNA damage with the neutral comet assay in 362 male partners of infertile couples. When sperm concentration and other potential confounding variables were included in multiple linear regression, serum estradiol and free T-4 levels were inversely associated with sperm DNA damage. Among other statistically significant associations that were observed, an interquartile range (IQR) increase in estradiol was associated with a 6.3% decline (95% confidence intervals: -9.7%, -2.9%) in comet extent and a 16.2% (-22.4%, -9.2%) decline in the percentage of DNA in the comet tail Tail%), whereas an IQR increase in free T-4 was associated with a 24.4% (-31.5%, -17.4%) decline in Tail%. Likewise, in multiple logistic regression, men in the highest estradiol quartile had an 81% reduced risk of having a comet extent value in the highest quartile compared with men in the lowest estradiol quartile. Men in the highest free T-4 quartile had 92% decreased odds of being categorized in the highest Tail% quartile compared with men in the lowest free T-4 quartile. These results suggest that estradiol and free T-4 may have a protective effect against sperm DNA damage, but future mechanistic and epidemiologic studies are needed to confirm these findings. C1 [Meeker, John D.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Singh, Narendra P.] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Androl Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, In Vitro Fertilizat Unit, Boston, MA 02114 USA. RP Meeker, JD (reprint author), Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, 6635 SPH Tower,109 S Observ St, Ann Arbor, MI 48109 USA. EM meekerj@umich.edu OI Meeker, John/0000-0001-8357-5085 FU NIEHS NIH HHS [ES000002, ES09718, R01 ES009718-05, R01 ES009718] NR 53 TC 13 Z9 13 U1 0 U2 2 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 EI 1939-4640 J9 J ANDROL JI J. Androl. PD JUL-AUG PY 2008 VL 29 IS 4 BP 379 EP 388 DI 10.2164/jandrol.107.004416 PG 10 WC Andrology SC Endocrinology & Metabolism GA 313KE UT WOS:000256738700003 PM 18359755 ER PT J AU Biederman, J Ball, SW Monuteaux, MC Kaiser, R Faraone, SV AF Biederman, Joseph Ball, Sarah W. Monuteaux, Michael C. Kaiser, Roselinde Faraone, Stephen V. TI CBCL Clinical Scales Discriminate ADHD Youth With Structured-Interview Derived Diagnosis of Oppositional Defiant Disorder (ODD) SO JOURNAL OF ATTENTION DISORDERS LA English DT Article DE ODD; CBCL; screening AB Objective: To evaluate the association between the clinical scales of the child behavior checklist (CBCL) and the comorbid diagnosis of oppositional defiant disorder (ODD) in a large sample of youth with attention deficit hyperactivity disorder (ADHD). Method: The sample consisted of 101 girls and 106 boys ages 6 to 17 with ADHD. Conditional probability analysis was used to examine the correspondence between CBCL Clinical Scales with the structured-interview derived diagnosis of ODD. Results: Conditional probability analysis showed that the CBCL Aggression Scale best predicted a structured-interview derived diagnosis of ODD in boys and girls with ADHD. Conclusion: These findings suggest that the CBCL Aggression Scale could serve as a rapid and cost-effective screening instrument to help identify cases likely to meet clinical criteria for ODD in the context of ADHD (J. of Att. Dis. 2008; 12(1) 76-82) C1 [Biederman, Joseph; Ball, Sarah W.; Monuteaux, Michael C.; Kaiser, Roselinde] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, New York, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, New York, NY USA. [Ball, Sarah W.; Monuteaux, Michael C.; Kaiser, Roselinde] Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Boston, MA 02114 USA. [Faraone, Stephen V.] Massachusetts Gen Hosp, Pediat Psychopharmacol Res Program, Boston, MA 02114 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Warren 705,55 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU National Institute of Mental Health, Bethesda, Maryland [R01 MH050657, R01 HD036317] FX Authors' Note: This work was supported in part by grants R01 MH050657 and R01 HD036317 from the National Institute of Mental Health, Bethesda, Maryland (Dr. Biederman). NR 33 TC 13 Z9 13 U1 1 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0547 J9 J ATTEN DISORD JI J. Atten. Disord. PD JUL PY 2008 VL 12 IS 1 BP 76 EP 82 DI 10.1177/1087054707299404 PG 7 WC Psychology, Developmental; Psychiatry SC Psychology; Psychiatry GA V11GS UT WOS:000207520700008 PM 17494835 ER PT J AU Biederman, J Petty, CR Fried, R Black, S Faneuil, A Doyle, AE Seidman, LJ Faraone, SV AF Biederman, Joseph Petty, Carter R. Fried, Ronna Black, Sarah Faneuil, Alicia Doyle, Alysa E. Seidman, Larry J. Faraone, Stephen V. TI Discordance Between Psychometric Testing and Questionnaire-Based Definitions of Executive Function Deficits in Individuals With ADHD SO JOURNAL OF ATTENTION DISORDERS LA English DT Article DE ADHD; adults; executive function deficits AB Objective: One suspected source of negative outcomes associated with ADHD has been deficits in executive functions. Although both psychometrically defined and self-reported executive function deficits (EFDs) have been shown to be associated with poor academic and occupational outcomes, whether these two approaches define the same individuals remains unknown. Method: Participants were 194 adults with ADHD from a case-control study of ADHD. Empirically based cutoffs were ascertained for an EFD diagnosis on both psychometric tests and scores on the Current Behavior Scale. Results: Results showed a modest overlap between the psychometric and self-reported definitions of EFDs. Whereas neuropsychological testing largely identified individuals with lower IQ and achievement testing, the behavioral questionnaire largely identified individuals with higher levels of ADHD symptoms, psychiatric comorbidity, and interpersonal deficits. Conclusion: Results indicate that behavioral questionnaires cannot be used interchangeably with neuropsychological testing for the assessment of EFDs in adults with ADHD. (J. of Att. Dis. 2008; 12(1) 92-102) C1 [Biederman, Joseph; Petty, Carter R.; Black, Sarah; Faneuil, Alicia] Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Boston, MA 02114 USA. [Fried, Ronna; Doyle, Alysa E.] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Fried, Ronna] Massachusetts Gen Hosp, Clin & Res Program Adult ADHD, Boston, MA 02114 USA. [Seidman, Larry J.] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, 55 Fruit St,Yawkey Bldg 6900, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU National Institute of Health [R01MH57934]; McNeil Consumer & Specialty Pharmaceuticals; Shire; Eli Lilly; Pfizer; McNeil; Abbott; Bristol-Myers-Squibb; New River Pharmaceuticals; Cephalon; Janssen; Novartis; UCB Pharma; Astra-Zeneca; Forest Laboratories; Glaxo-SmithKline; Neurosearch; Stanley Medical Institute, Inc.; Lilly Foundation; Prechter Foundation; National Institute of Mental Health; National Institute of Child Health and Human Development; National Institute on Drug Abuse; Shire U.S., Inc.; National Institute of Neurological Diseases and Stroke FX This work was supported in part by grants to Dr. Stephen V. Faraone from the National Institute of Health (R01MH57934) and McNeil Consumer & Specialty Pharmaceuticals. Dr. Joseph Biederman has received research support from, has been a speaker for, or has been on the advisory board for the following pharmaceutical companies: Shire, Eli Lilly, Pfizer, McNeil, Abbott, Bristol-Myers-Squibb, New River Pharmaceuticals, Cephalon, Janssen, Novartis, UCB Pharma, Astra-Zeneca, Forest Laboratories, Glaxo-SmithKline, Neurosearch, Stanley Medical Institute, Inc., Lilly Foundation, Prechter Foundation, National Institute of Mental Health, National Institute of Child Health and Human Development, and National Institute on Drug Abuse. Dr. Faraone receives research support from Eli Lilly and Company, McNeil Consumer & Specialty Pharmaceuticals, Shire U.S., Inc., NICHD, NIMH, and the National Institute of Neurological Diseases and Stroke. Dr. Faraone is on the speaker's bureaus of Eli Lilly and Company, McNeil Consumer & Specialty Pharmaceuticals, Shire U.S., Inc., and Cephalon. Dr. Alysa E. Doyle is a member of the cognition advisory board for Novartis Pharmaceuticals. Dr. Faraone has had an advisory or consulting relationship with Eli Lilly and Company, McNeil Consumer & Specialty Pharmaceuticals, Shire U. S., Inc., Noven Pharmaceuticals, and Cephalon. All of the remaining authors have no conflicts or financial relationships to disclose. NR 27 TC 41 Z9 43 U1 1 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0547 J9 J ATTEN DISORD JI J. Atten. Disord. PD JUL PY 2008 VL 12 IS 1 BP 92 EP 102 DI 10.1177/1087054707305111 PG 11 WC Psychology, Developmental; Psychiatry SC Psychology; Psychiatry GA V11GS UT WOS:000207520700010 PM 17934182 ER PT J AU Chau, AH Motz, JT Gardecki, JA Waxman, S Bouma, BE Tearney, GJ AF Chau, Alexandra H. Motz, Jason T. Gardecki, Joseph A. Waxman, Sergio Bouma, Brett E. Tearney, Guillermo J. TI Fingerprint and high-wavenumber Raman spectroscopy in a human-swine coronary xenograft in vivo SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE Raman spectroscopy; intravascular catheter; atherosclerosis; coronary artery; xenograft; fiber optic probe ID ATHEROSCLEROSIS; DIAGNOSIS; DISEASE; MODEL AB Intracoronary Raman spectroscopy could open new avenues for the study and management of coronary artery disease due to its potential to measure the chemical and molecular composition of coronary atherosclerotic lesions. We have fabricated and tested a 1.5-mm-diameter (4.5 Fr) Raman catheter capable of collecting Raman spectra in both the fingerprint (400 - 1800 cm(-1)) and high-wavenumber (2400 - 3800 cm(-1)) regions. Spectra were acquired in vivo, using a human-swine xenograft model, in which diseased human coronary arteries are grafted onto a living swine heart, replicating the disease and dynamic environment of the human circulatory system, including pulsatile flow and motion. Results show that distinct spectral differences, corresponding to the morphology and chemical composition of the artery wall, can be identified by intracoronary Raman spectroscopy in vivo. (C) 2008 Society of Photo-Optical Instrumentation Engineers. C1 [Chau, Alexandra H.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Chau, Alexandra H.; Motz, Jason T.; Gardecki, Joseph A.; Bouma, Brett E.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Motz, Jason T.; Bouma, Brett E.; Tearney, Guillermo J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Waxman, Sergio] Lahey Clin Fdn, Burlington, MA 01805 USA. [Waxman, Sergio] Tufts Univ, Sch Med, Boston, MA 02110 USA. [Bouma, Brett E.; Tearney, Guillermo J.] Harvard MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Tearney, Guillermo J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Chau, AH (reprint author), MIT, Dept Mech Engn, Cambridge, MA 02139 USA. EM tearney@helix.mgh.harvard.edu FU Prescient Medical, Inc.; National Institute of Biomedical Imaging and Bioengineering [F31EB007169] FX This study was supported by Prescient Medical, Inc. A.H.C. was supported by a Ruth L. Kirschstein individual fellowship (Grant no. F31EB007169) from the National Institute of Biomedical Imaging and Bioengineering. NR 14 TC 13 Z9 13 U1 1 U2 6 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JUL-AUG PY 2008 VL 13 IS 4 AR 040501 DI 10.1117/1.2960015 PG 3 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 358EX UT WOS:000259901000001 PM 19021305 ER PT J AU Deliolanis, NC Kasmieh, R Wurdinger, T Tannous, BA Shah, K Ntziachristos, V AF Deliolanis, Nikolaos C. Kasmieh, Randa Wurdinger, Thomas Tannous, Bakhos A. Shah, Khalid Ntziachristos, Vasilis TI Performance of the red-shifted fluorescent proteins in deep-tissue molecular imaging applications SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE fluorescent proteins; optical tomography; whole-body imaging ID IN-VIVO; SMALL ANIMALS; WHOLE-BODY; CANCER; TOMOGRAPHY; TUMORS; CELLS; ANGIOGENESIS; METASTASIS; MICROSCOPY AB The discovery of new fluorescent proteins (FPs) that emit in the far-red part of the spectrum, where light absorption from tissue is significantly lower than in the visible, offers the possibility for noninvasive biological interrogation at the entire organ or small animal level in vivo. The performance of FPs in deep-tissue imaging depends not only on their optical characteristics, but also on the wavelength-dependent tissue absorption and the depth of the fluorescence activity. To determine the optimal choice of FP and illumination wavelength, we compared the performance of five of the most promising FPs: tdTomato, mCherry, mRaspberry, mPlum, and Katushka. We experimentally measured the signal strength through mice and employed theoretical predictions to obtain an understanding of the performance of different illumination scenarios, especially as they pertain to tomographic imaging. It was found that the appropriate combination of red-shifted proteins and illumination wavelengths can improve detection sensitivity in small animals by at least two orders of magnitude compared with green FP. It is also shown that the steep attenuation change of the hemoglobin spectrum around the 600-nm range may significantly affect the detection sensitivity and, therefore, necessitates the careful selection of illumination wavelengths for optimal imaging performance. (C) 2008 Society of Photo-Optical Instrumentation Engineers. C1 [Deliolanis, Nikolaos C.] Massachusetts Gen Hosp, Lab Bioopt & Mol Imaging, Ctr Mol Imaging Res, Charlestown, MA 02139 USA. [Deliolanis, Nikolaos C.; Ntziachristos, Vasilis] Harvard Univ, Lab Bioopt & Mol Imaging, Ctr Mol Imaging Res, Sch Med, Charlestown, MA 02139 USA. [Wurdinger, Thomas; Tannous, Bakhos A.] Harvard Univ, Lab Bioopt & Mol Imaging, Mol Neurogen Unit, Charlestown, MA 02139 USA. [Ntziachristos, Vasilis] Tech Univ Munich, Munich, Germany. [Ntziachristos, Vasilis] Helmholtz Ctr Munich, Inst Biol & Med Imaging, Munich, Germany. RP Deliolanis, NC (reprint author), Massachusetts Gen Hosp, Lab Bioopt & Mol Imaging, Ctr Mol Imaging Res, 149 13th St, Charlestown, MA 02139 USA. EM ndeliolanis@yahoo.com OI Deliolanis, Nikolaos/0000-0002-6392-3035 FU National Institutes of Health [1R01EB00438201, 1R21CA110167] FX The authors would like to thank Jason Gaglia for useful discussions. This research was supported in part by National Institutes of Health Grants No. 1R01EB00438201 and 1R21CA110167. NR 27 TC 65 Z9 67 U1 1 U2 25 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JUL-AUG PY 2008 VL 13 IS 4 AR 044008 DI 10.1117/1.2967184 PG 9 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 358EX UT WOS:000259901000032 PM 19021336 ER PT J AU Jones, PB Shin, HK Boas, DA Hyman, BT Moskowitz, MA Ayata, C Dunn, AK AF Jones, Phill B. Shin, Hwa Kyoung Boas, David A. Hyman, Bradley T. Moskowitz, Michael A. Ayata, Cenk Dunn, Andrew K. TI Simultaneous multispectral reflectance imaging and laser speckle flowmetry of cerebral blood flow and oxygen metabolism in focal cerebral ischemia SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE laser speckle; multispecktral imaging; ischemia; peri-infarct depolarizations; depolarizations; Beer-Lambert ID POSITRON-EMISSION-TOMOGRAPHY; RAT SOMATOSENSORY CORTEX; CONSUMPTION FOLLOWING ACTIVATION; CORTICAL SPREADING DEPRESSION; ARTERY OCCLUSION; BARREL CORTEX; PERIINFARCT DEPOLARIZATIONS; FUNCTIONAL ACTIVATION; HEMOGLOBIN CONCENTRATION; SPECTROSCOPIC ANALYSIS AB Real-time investigation of cerebral blood flow (CBF), and oxy-and deoxyhemoglobin concentration (HbO, HbR) dynamics has been difficult until recently due to limited spatial and temporal resolution of techniques like laser Doppler flowmetry and magnetic resonance imaging (MRI). The combination of laser speckle flowmetry (LSF) and multispectral reflectance imaging (MSRI) yields high-resolution spatiotemporal maps of hemodynamic and metabolic changes in response to functional cortical activation. During acute focal cerebral ischemia, changes in HbO and HbR are much larger than in functional activation, resulting in the failure of the Beer-Lambert approximation to yield accurate results. We describe the use of simultaneous LSF and MSRI, using a nonlinear Monte Carlo fitting technique, to record rapid changes in CBF, HbO, HbR, and cerebral metabolic rate of oxygen (CMRO(2)) during acute focal cerebral ischemia induced by distal middle cerebral artery occlusion (dMCAO) and reperfusion. This technique captures CBF and CMRO(2) changes during hemodynamic and metabolic events with high temporal and spatial resolution through the intact skull and demonstrates the utility of simultaneous LSF and MSRI in mouse models of cerebrovascular disease. (C) 2008 Society of Photo-Optical Instrumentation Engineers. C1 [Jones, Phill B.; Boas, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Shin, Hwa Kyoung; Moskowitz, Michael A.; Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. [Hyman, Bradley T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Disorders, Charlestown, MA 02129 USA. [Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Stroke Serv, Charlestown, MA 02129 USA. [Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Intens Care Unit, Charlestown, MA 02129 USA. [Dunn, Andrew K.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. RP Jones, PB (reprint author), Harvard Univ, Sch Med, MassGen Inst Neurodegenerat Disorders, A Martinos Ctr Biomed Imaging, 114 16th St, Charlestown, MA 02129 USA. EM phill.jones@physics.org RI Moskowitz, Michael/D-9916-2011; Dunn, Andrew/I-9527-2014; OI Jones, Phillip/0000-0003-0525-6323 FU National Institutes of Health [NS10828, MAM, NS035611, MAM, NS041291, AKD, NS050150, AKD]; National Science Foundation [0644638 AKD]; American Heart Association [0335519N, CA, 0735136N, AKD]; National Institute of Biomedical Imaging and Engineering [R01EB00790, DAB] FX This work was supported by the National Institutes of Health (Grant Nos. NS10828, MAM; NS035611, MAM; NS041291, AKD; and NS050150, AKD), National Science Foundation (Grant No. 0644638 AKD), American Heart Association (Grant Nos. 0335519N, CA; and 0735136N, AKD), and National Institute of Biomedical Imaging and Engineering (Grant No. R01EB00790, DAB). NR 57 TC 53 Z9 54 U1 1 U2 5 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JUL-AUG PY 2008 VL 13 IS 4 AR 044007 DI 10.1117/1.2950312 PG 11 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 358EX UT WOS:000259901000031 PM 19021335 ER PT J AU Slover, JD Tosteson, ANA Bozic, KJ Rubash, HE Malchau, H AF Slover, James D. Tosteson, Anna N. A. Bozic, Kevin J. Rubash, Harry E. Malchau, Henrik TI Impact of hospital volume on the economic value of computer navigation for total knee replacement SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID TOTAL HIP-REPLACEMENT; REVISION TOTAL HIP; STATES MEDICARE POPULATION; SURGEON PROCEDURE VOLUME; UNITED-STATES; ASSISTED NAVIGATION; COST-EFFECTIVENESS; ARTHROPLASTY; OUTCOMES; ASSOCIATION AB Background: An aim of the use of computer navigation is to reduce rates of revisions of total knee replacements by improving the alignment achieved at the surgery. However, the decision to adopt this technology may be difficult for some centers, especially low-volume centers, where the Cost Of Purchasing this equipment may be high. The purpose of this study was to examine the impact of hospital volume on the cost-effectiveness of this new technology in order to determine its feasibility and the level of evidence that should be sought prior to its adoption. Methods: A Markov decision model was used to evaluate the impact of hospital volume on the cost-effectiveness of computer-assisted knee arthroplasty in a theoretical cohort of sixty-five-year-old patients with end-stage arthritis of the knee to coincide with the peak incidence of knee arthroplasty in the United States. Results: Computer-assisted surgery becomes less cost-effective as the annual hospital volume decreases, as the cost of the navigation increases, and as the impact on revision rates decreases. Centers at which 250, 150, and twenty-five computer-navigated total knee arthroplasties are performed per year will require a reduction of the annual revision rate of 2%, 2.5%, and 13%, respectively, per year over a twenty-year period for computer navigation to be cost-effective. Conclusions: Computer navigation is less likely to be a cost-effective investment in health-care improvement in centers with a low volume of joint replacements, where its benefit is most likely to be realized. However, it may be a cost-effective technology for centers with a higher volume of joint replacements, where the decrease in the rate of knee revision needed to make the investment cost-effective is modest, if improvements in revision rates with the use of this technology can be realized. Level of Evidence: Economic and decision analysis, Level II. See Instructions to Authors for a complete description of levels of evidence. C1 [Slover, James D.; Tosteson, Anna N. A.; Bozic, Kevin J.; Rubash, Harry E.; Malchau, Henrik] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Slover, JD (reprint author), NYU, Hosp Joint Dis, Dept Orthopaed Surg, 301 E 17th St,Suite 1616, New York, NY 10010 USA. EM james.slover@nyumc.org FU NIAMS NIH HHS [P60 AR048094] NR 36 TC 42 Z9 43 U1 0 U2 4 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JUL PY 2008 VL 90A IS 7 BP 1492 EP 1500 DI 10.2106/JBJS.G.00888 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 323KV UT WOS:000257445900014 PM 18594098 ER PT J AU Schneider, JC Holavanahalli, R Helm, P O'Neil, C Goldstein, R Kowalske, K AF Schneider, Jeffrey C. Holavanahalli, Radha Helm, Phala O'Neil, Carina Goldstein, Richard Kowalske, Karen TI Contractures in burn injury part II: Investigating joints of the hand SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID POSTBURN CONTRACTURES; 10-YEAR EXPERIENCE; MANAGEMENT; FINGER; REHABILITATION; CHILDREN; EXERCISE; PROGRAM; WRIST AB This study prospectively examines the incidence and severity of hand contractures after burn injury and determines predictors of contracture development. Data were collected prospectively from 1993 to 2002 for adult burn survivors admitted to a regional burn center. Demographic and medical data were collected on each subject. Primary outcome measures include presence of contractures, number of contractures, and the severity of contractures at each of the hand joints at hospital discharge. The metacarpal-phalangeal, proximal interphalangeal (PIP), and distal inter-phalangeal joints of all digits and the wrist joints are included in this study. Regression analysis was performed to determine predictors of the presence, severity, and number of contractures. Of the 985 study patients, 23% demonstrated at least one hand contracture at hospital discharge. Those with a contracture averaged ten contractures per person. Most contractures were mild (48%) or moderate (41%) in severity. The wrist was the most frequently affected joint (22%). Statistically significant predictors of contracture development include concomitant medical problems, total body surface area grafted and presence of hand burn and hand grafting (P <.05). Predictors of the number of contractures include length of stay, concomitant medical problems, burn size and presence of hand burn and grafting (P <.05). Contractures of the hand are a significant complication of burn injury. Clinicians can use the contracture predictors to help target interventions for those patients most at risk of developing hand contractures. Given the functional importance of the hand in daily living, the burn care community is challenged to find new ways of preventing and treating hand contractures. C1 [Schneider, Jeffrey C.; Goldstein, Richard] Harvard Univ, Massachusetts Gen Hosp, Spaulding Rehabil Hosp,Sch Med, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Holavanahalli, Radha; Helm, Phala; O'Neil, Carina; Kowalske, Karen] Univ Texas SW Med Ctr Dallas, Dept Phys Med & Rehabil, Dallas, TX 75390 USA. RP Schneider, JC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Spaulding Rehabil Hosp,Sch Med, Dept Phys Med & Rehabil, 125 Nashua St, Boston, MA 02114 USA. OI Schneider, Jeffrey/0000-0002-7861-2854 NR 45 TC 28 Z9 28 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD JUL-AUG PY 2008 VL 29 IS 4 BP 606 EP 613 DI 10.1097/BCR.0b013e31817db8e1 PG 8 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 325OA UT WOS:000257597000007 PM 18535473 ER PT J AU Rosen, J Lynch, T AF Rosen, Julie Lynch, Thomas, Jr. TI The talking cure: Schwartz Center Rounds foster compassion and collaboration SO JOURNAL OF CANCER EDUCATION LA English DT Article AB For those readers who do not know about the Schwartz Center and their good works, I hope you'll benefit from this Short piece, visit their Web site, and contact them to get Schwartz Rounds started at Your institution. From my own personal experience, this is a great asset to promote compassion, communication, collaboration, and better care for both patients and the caregivers. C1 [Rosen, Julie] Kenneth B Schwartz Ctr, Boston, MA 02114 USA. [Lynch, Thomas, Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rosen, J (reprint author), Kenneth B Schwartz Ctr, 205 Portland St,6th Floor, Boston, MA 02114 USA. EM schwartzcenter@partners.org NR 1 TC 1 Z9 1 U1 3 U2 4 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD JUL-SEP PY 2008 VL 23 IS 3 BP 195 EP 196 DI 10.1080/08858190802244330 PG 2 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 353BS UT WOS:000259541700014 PM 18709593 ER PT J AU Stwald, SK Swank, PR Khan, MM AF Stwald, Sharon K. Swank, Paul R. Khan, Myrna M. TI Predictors of functional independence and stress level of stroke survivors at discharge from inpatient rehabilitation SO JOURNAL OF CARDIOVASCULAR NURSING LA English DT Article DE depression; recovery of function; rehabilitation; stress; stroke ID SELF-RATED HEALTH; IMPACT SCALE; DEPRESSION; COMORBIDITY; RELIABILITY; MORTALITY; COMMUNITY; VETERANS; SYSTEM AB Background and Research Objective: Stroke is the primary cause of long-term disability among older adults. This study identifies predictors of functional independence and perceived stress for stroke survivors discharged home from inpatient rehabilitation with a spousal caregiver. Subjects and Methods: Stroke survivors (N = 97) were interviewed immediately after discharge to obtain scores on the National Institutes of Health Stroke Scale, Functional Independence Measure (FIM), Stroke Impact Scale, Geriatric Depression Scale-15, Perceived Stress Scale, and Perceived Health Status. Demographic and stroke-related data were abstracted from their inpatient rehabilitation charts. Descriptive and regression analyses determined the relationships among variables and the models that best predicted functional independence and perceived stress. Results: Stroke survivors perceived a 50% recovery in their function upon discharge from inpatient rehabilitation. National Institutes of Health Stroke Scale, age, socioeconomic status, and number of complications predicted 63% of the variance of the total FIM score (F(6,88)= 24.64; P <.0001). Total FIM, depression, and Stroke Impact Scale Emotion subscale predicted 45% of the Perceived Stress Scale score (F(6,88) = 12.04; P <.0001). Conclusions: Variables that predict the stroke survivors' recovery are complex as the severity of the stroke combines with demographic and economic variables and depression to predict functional independence and perceived stress. These factors need to be considered when preparing a discharge plan for stroke survivors who are discharged home from rehabilitation. C1 [Stwald, Sharon K.] Univ Texas Houston, Sch Nursing, Ctr Aging, Isla Carroll Turner Chair Gerontol Nursing, Houston, TX 77030 USA. [Swank, Paul R.] Univ Texas Houston, Sch Med, Houston, TX USA. [Khan, Myrna M.] Baylor Coll Med, Michael E De Bakey VA Med Ctr, Houston, TX 77030 USA. RP Stwald, SK (reprint author), Univ Texas Houston, Sch Nursing, Ctr Aging, Isla Carroll Turner Chair Gerontol Nursing, SONSCC Room 644,6901 Bertner St, Houston, TX 77030 USA. EM Sharon.K.Ostwald@uth.tmc.edu NR 32 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0889-4655 J9 J CARDIOVASC NURS JI J. Cardiovasc. Nurs. PD JUL-AUG PY 2008 VL 23 IS 4 BP 371 EP 377 PG 7 WC Cardiac & Cardiovascular Systems; Nursing SC Cardiovascular System & Cardiology; Nursing GA 322YG UT WOS:000257410600011 ER PT J AU Chen, LJ Chang, YJ Kuo, JC Rajagopal, R Azar, DT AF Chen, Li-Ju Chang, Yun-Jau Kuo, Jonathan C. Rajagopal, Rama Azar, Dimitri T. TI Metaanalysis of cataract development after phakic intraocular lens surgery SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Review ID IMPLANTABLE CONTACT-LENS; IN-SITU KERATOMILEUSIS; CORRECT HIGH MYOPIA; IRIS-CLAW LENS; POSTERIOR CHAMBER LENS; ADMINISTRATION CLINICAL-TRIAL; RESIDUAL REFRACTIVE ERROR; MODERATELY HIGH MYOPIA; BLUE MOUNTAINS EYE; 2-YEAR FOLLOW-UP AB We performed a systematic literature review to determine the incidence of and predisposing factors for cataract after phakic intraocular lens (pIOL) implantation. Of the 6338 eyes reported, 4.35% were noted to have new-onset or preexisting progressive cataract. The incidence of cataract formation was 1.29%, 1.11%, and 9.60% with anterior chamber, iris-fixated, and posterior chamber (PC) pIOLs, respectively. In the PC pIOL group, early cataract formation was related to surgical trauma and late-onset cataract was related to IOL-crystalline lens contact. Analysis of cataract progression in eyes with preexisting cataract showed a progression rate of 29.5% after pIOL surgery. These results suggest that cataract formation is most likely to occur after PC pIOL implantation. Patients with preexisting progressive cataract should be informed about the possibility of cataract progression and possible need for cataract surgery after pIOL implantation. Cataract surgical intervention resulted in restoration of visual acuity. C1 [Azar, Dimitri T.] Univ Illinois, Dept Ophthalmol & Visual Sci, Illinois Eye & Ear Infirm, Chicago, IL 60612 USA. [Chen, Li-Ju; Kuo, Jonathan C.; Rajagopal, Rama; Azar, Dimitri T.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Corneal & Refract Surg Serv, Boston, MA USA. [Chen, Li-Ju; Kuo, Jonathan C.; Rajagopal, Rama; Azar, Dimitri T.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. [Chen, Li-Ju] Natl Taiwan Univ, Coll Publ Hlth, Taipei City Hosp, Heping Branch, Taipei 10764, Taiwan. [Chang, Yun-Jau] Natl Taiwan Univ, Coll Publ Hlth, Inst Hlth Care Org Adm, Taipei 10764, Taiwan. RP Azar, DT (reprint author), Univ Illinois, Dept Ophthalmol & Visual Sci, Illinois Eye & Ear Infirm, 1855 W Taylor St, Chicago, IL 60612 USA. EM dazar@uic.edu FU NEI NIH HHS [EY10101] NR 190 TC 47 Z9 50 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD JUL PY 2008 VL 34 IS 7 BP 1181 EP 1200 DI 10.1016/j.jcrs.2008.03.029 PG 20 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 323MI UT WOS:000257449800029 PM 18571089 ER PT J AU Thiagalingam, S Tarongoy, P Hamrah, P Lobo, AM Nagao, K Barsam, C Bellows, R Pineda, R AF Thiagalingam, Sureka Tarongoy, Pamela Hamrah, Pedram Lobo, Ann-Marie Nagao, Karina Barsam, Charles Bellows, Robert Pineda, Roberto TI Complications of cosmetic iris implants SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID MYOPIA; ARTISAN; LENSES AB Cosmetic intraocular iris implants for the purpose of changing iris color have recently been developed; however, little is known about their safety. We report a patient who had bilateral implantation of colored silicone iris implants solely for cosmetic reasons. The rapid development of uveitis, corneal decompensation, and ocular hypertension resulted in the need for explantation of the implants. Placement of these devices should require specific medical indications and meticulous surgery with early and long-term evaluation. C1 [Thiagalingam, Sureka; Hamrah, Pedram; Lobo, Ann-Marie; Bellows, Robert; Pineda, Roberto] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Tarongoy, Pamela; Nagao, Karina; Bellows, Robert] Ophthalm Consultants Boston, Boston, MA USA. [Barsam, Charles] Univ Utah, John A Moran Eye Ctr, Salt Lake City, UT USA. RP Pineda, R (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM robertopineda@meei.harvard.edu NR 4 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD JUL PY 2008 VL 34 IS 7 BP 1222 EP 1224 DI 10.1016/j.jcrs.2008.02.035 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 323MI UT WOS:000257449800035 PM 18571095 ER PT J AU Bischoff, DS Zhu, JH Makhijani, NS Yamaguchi, DT AF Bischoff, David S. Zhu, Jian-Hua Makhijani, Nalini S. Yamaguchi, Dean T. TI Acidic pH stimulates the production of the angiogenic CXC chemokine, CXCL8 (interieukin-8), in human adult mesenchymal stem cells via the extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and NF-kappa B pathwavs SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE ELR+ CXC chemokines; human mesenchymal stem cells; acidic extracellular pH; osteoblastic differentiation ID ENDOTHELIAL GROWTH-FACTOR; INTERLEUKIN-1-BETA-INDUCED IL-8 EXPRESSION; INTERLEUKIN-8 GENE-EXPRESSION; G-BETA-GAMMA; STROMAL CELLS; CARCINOMA CELLS; GRANULE CELLS; IN-VIVO; RECEPTORS; ACIDOSIS AB Bloodvessel injury results in limited oxygen tension and diffusion leading to hypoxia, increased anaerobic metabolism, and elevated production of acidic metabolites that cannot be easily removed due to the reduced blood flow. Therefore, an acidic extracellular pH occurs in the local microenvironment of disrupted bone. The potential role of acidic pH and glu-leu-arg (ELR+) CXC chemokines in early events in bone repair was studied in human mesenchymal stem cells (hMSCs) treated with medium of decreasing pH (7.4, 7.0, 6.7, and 6.4). The cells showed a reciprocal increase in CXCL8(interleukin-8, IL-8) mRNA levels as extracellular pH decreased. At pH 6.4, CXCL8 mRNA was induced >60x in comparison to levels at pH 7.4. hMSCs treated with osteogenic medium (OGM) also showed an increase in CXCL8 mRNA with decreasing pH; although, at a lower level than that seen in cells grown in non-OGM. CXCL8 protein was secreted into the medium at all pHs with maximal induction at pH 6.7. Inhibition of the G-protein-coupled receptor alpha, G(alpha i), suppressed CXCL8 levels in response to acidic pH; whereas phospholipase C inhibition had no effect on CXCL8. The use of specific mitogen-activated protein kinase (MAPK) signal transduction inhibitors indicated that the pH-dependent increase in CXCL8 mRNA is due to activation of ERK and p38 pathways. The JNK pathway was not involved. NF-kappa B inhibition resulted in a decrease in CXCL8 levels in hMSCs grown in non-OGM. However, OGM-differentiated hMSCs showed an increase in CXCL8 levels when treated with the NF-kappa B inhibitor PDTC, a pyrrolidine derivative of dithiocarbamate. C1 [Bischoff, David S.; Zhu, Jian-Hua; Makhijani, Nalini S.; Yamaguchi, Dean T.] VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. [Bischoff, David S.; Yamaguchi, Dean T.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90073 USA. RP Yamaguchi, DT (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv 151, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM dean.yamaguchi@med.va.gov NR 58 TC 12 Z9 15 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JUL 1 PY 2008 VL 104 IS 4 BP 1378 EP 1392 DI 10.1002/jcb.21714 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 325DA UT WOS:000257567300021 PM 18275043 ER PT J AU Pardee, AB Qiao, M AF Pardee, Arthur B. Qiao, Meng TI A devious cube of cancer SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Editorial Material ID DORMANCY; CELLS C1 [Pardee, Arthur B.; Qiao, Meng] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pardee, AB (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM arthur_pardee@dfci.harvard.edu NR 8 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUL PY 2008 VL 216 IS 1 BP 1 EP 2 DI 10.1002/jcp.21425 PG 2 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 311LD UT WOS:000256600800001 PM 18338337 ER PT J AU Tikh, EI Fenton, RA Chen, JF Schwarzschild, MA Dobson, JG AF Tikh, Eugene I. Fenton, Richard A. Chen, Jiang-Fan Schwarzschild, Michael A. Dobson, James G., Jr. TI Adenosine A(1) and A(2A) receptor regulation of protein phosphatase 2A in the murine heart SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID RAT VENTRICULAR MYOCYTES; CARDIAC-FUNCTION; A(2A) RECEPTOR; INTERSTITIAL ADENOSINE; SARCOPLASMIC-RETICULUM; PHOSPHORYLASE ACTIVITY; INDUCED INCREASE; CALCIUM-RELEASE; P38 MAPK; CONTRACTILITY AB Adenosine plays a role in regulating the contractile function of the heart. This includes a positive ionotropic action via the adenosine A(2A) receptor (A(2A)R) and an inhibition of beta(1)-adrenergic receptor-induced ionotropy (antiadrenergic action) via the adenosine A(1) receptor (A(1)R). Phosphatase activity has also been shown to influence contractile function by affecting the level of protein phosphorylation. Protein phosphatase 2A (PP2A) plays a significant role in mediating the A(1)R antiadrenergic effect. The purpose of this study was to investigate the effects of A(2A)R and A(1)R on the activities of PP2A in hearts obtained from wild-type (WT) and A(2A)R knockout (A(2A)R-KO) mice. PP2A activities were examined in myocardial particulate and cytoplasmic extract fractions. Treatment of wild-type hearts with the A(1)R agonist CCPA increased the total PP2A activity and increased the particulate:cytoplasmic PP2A activity ratio. Treatment with the A(2A)R agonist CGS-21680 (CGS) decreased the total PP2A activity and decreased the particulate:cytoplasmic PP2A activity ratio. This indicated a movement of PP2A activity between cell fractions. The effect of CCPA was inhibited by CGS. In A(2A)R-KO hearts the response to A(1)R activation was markedly enhanced whereas the response to A(2A)R activation was absent. These data show that A(2A)R and A(1)R regulate PP2A activity, thus suggesting an important mechanism for modulating myocardial contractility. C1 [Tikh, Eugene I.; Fenton, Richard A.; Dobson, James G., Jr.] Univ Massachusetts, Sch Med, Dept Physiol, Worcester, MA 01655 USA. [Chen, Jiang-Fan] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Fenton, RA (reprint author), Univ Massachusetts, Sch Med, Dept Physiol, 55 Lake Ave N, Worcester, MA 01655 USA. EM richard.fenton@umassmed.edu FU NHLBI NIH HHS [HL-66045]; NIA NIH HHS [AG-11491] NR 51 TC 12 Z9 12 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUL PY 2008 VL 216 IS 1 BP 83 EP 90 DI 10.1002/jcp.21375 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 311LD UT WOS:000256600800010 PM 18181173 ER PT J AU Kim, HH Sawada, N Soydan, G Lee, HS Zhou, ZP Hwang, SK Waeber, C Moskowitz, MA Liao, JK AF Kim, Hyung-Hwan Sawada, Naoki Soydan, Guray Lee, Ho-Seong Zhou, Zhipeng Hwang, Seo-Kyoung Waeber, Christian Moskowitz, Michael A. Liao, James K. TI Additive effects of statin and dipyridamole on cerebral blood flow and stroke protection SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE aspirin; blood flow; cerebral ischemia; endothelium; nitric oxide synthase; stroke ID ENDOTHELIAL NITRIC-OXIDE; TRANSIENT ISCHEMIC ATTACK; HIGH-RISK PATIENTS; ACETYLSALICYLIC-ACID; PLATELET-AGGREGATION; REDUCTASE INHIBITORS; SECONDARY PREVENTION; DOSE ATORVASTATIN; CONTROLLED-TRIAL; SYNTHASE AB Recent studies suggest that dipyridamole (DP) may exert stroke protective effects beyond platelet inhibition. The purpose of this study is to determine whether statin and DP could enhance stroke protection through nitric oxide (NO)-dependent vascular effects. Mice were pretreated with DP (10 to 60 mg/kg, q 12h, 3 days) alone or in combination with a statin (simvastatin; 0.1 to 20 mg/kg per day, 14 days) before transient intraluminal middle cerebral artery occlusion. Although simvastatin (1 mg/kg per day, 14 days) increased endothelial NO synthase (eNOS) activity by 25% and DP (30 mg/kg, q12 h, 3 days) increased aortic cGMP levels by 55%, neither statin nor DP alone, at these subtherapeutic doses, increased absolute cerebral blood flow (CBF) or conferred stroke protection. However, the combination of subtherapeutic doses of simvastatin and DP increased CBF by 50%, decreased stroke volume by 54%, and improved neurologic motor deficits, all of which were absent in eNOS-deficient mice. In contrast, treatment with aspirin (10 mg/kg per day, 3 days) did not augment the neuroprotective effects of DP and/or simvastatin. These findings indicate that statin and DP exert additive NO-dependent vascular effects and suggest that the combination of C1 [Kim, Hyung-Hwan; Sawada, Naoki; Lee, Ho-Seong; Hwang, Seo-Kyoung; Liao, James K.] Brigham & Womens Hosp, Dept Med, Vasc Med Res Unit, Boston, MA 02115 USA. [Kim, Hyung-Hwan; Sawada, Naoki; Lee, Ho-Seong; Hwang, Seo-Kyoung; Liao, James K.] Harvard Univ, Sch Med, Boston, MA USA. [Soydan, Guray; Zhou, Zhipeng; Waeber, Christian; Moskowitz, Michael A.] Massachusetts Gen Hosp, Dept Neurol & Radiol, Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. [Soydan, Guray; Zhou, Zhipeng; Waeber, Christian; Moskowitz, Michael A.] Harvard Univ, Sch Med, Charlestown, MA USA. RP Liao, JK (reprint author), Brigham & Womens Hosp, Dept Med, Vasc Med Res Unit, 65 Landsdowne St,Room 275, Cambridge, MA 02139 USA. EM jliao@rics.bwh.harvard.edu RI Waeber, Christian/A-8333-2009; Moskowitz, Michael/D-9916-2011 OI Waeber, Christian/0000-0001-6078-0027; FU NHLBI NIH HHS [R01 HL080187-03, HL052233, R01 HL052233, R01 HL052233-11, R01 HL052233-12, R01 HL070274, R01 HL070274-05, R01 HL080187, R01 HL080187-02]; NINDS NIH HHS [F32 NS010828, NS010828, NS055104, P01 NS010828, P01 NS010828-330036, P01 NS055104, P50 NS010828] NR 37 TC 31 Z9 31 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUL PY 2008 VL 28 IS 7 BP 1285 EP 1293 DI 10.1038/jcbfm.2008.24 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 318DZ UT WOS:000257073100002 PM 18382469 ER PT J AU Sukhotinsky, I Dilekoz, E Moskowitz, MA Ayata, C AF Sukhotinsky, Inna Dilekoz, Ergin Moskowitz, Michael A. Ayata, Cenk TI Hypoxia and hypotension transform the blood flow response to cortical spreading depression from hyperemia into hypoperfusion in the rat SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE cerebral blood flow; electrophysiology; hypotension; hypoxia; laser Doppler flowmetry; spreading depression ID ISCHEMIC NEUROLOGICAL DEFICITS; NITRIC-OXIDE SYNTHASE; SUBARACHNOID HEMORRHAGE; CEREBRAL-CORTEX; AUTOREGULATION; DEPOLARIZATIONS; BRAIN; K+; INHIBITION; POTASSIUM AB Cortical spreading depression (CSD) evokes a large cerebral blood flow (CBF) increase in normal rat brain. In contrast, in focal ischemic penumbra, CSD-like periinfarct depolarizations (PID) are mainly associated with hypoperfusion. Because PIDs electrophysiologically closely resemble CSD, we tested whether conditions present in ischemic penumbra, such as tissue hypoxia or reduced perfusion pressure, transform the CSD-induced CBF response in nonischemic rat cortex. Cerebral blood flow changes were recorded using laser Doppler flowmetry in rats subjected to hypoxia, hypotension, or both. Under normoxic normotensive conditions, CSD caused a characteristic transient CBF increase (74 +/- 7%) occasionally preceded by a small hypoperfusion (-4 +/- 2%). Both hypoxia (pO(2) 45 +/- 3mmHg) and hypotension (blood pressure 42 +/- 2mmHg) independently augmented this initial hypoperfusion (-14 +/- 2% normoxic hypotension; -16 +/- 6% hypoxic normotension; -21 +/- 5% hypoxic hypotension) and diminished the magnitude of hyperemia (44 +/- 10% normoxic hypotension; 43 +/- 9% hypoxic normotension; 27 +/- 6% hypoxic hypotension). Hypotension and, to a much lesser extent, hypoxia increased the duration of hypoperfusion and the DC shift, whereas CSD amplitude remained unchanged. These results suggest that hypoxia and/or hypotension unmask a vasoconstrictive response during CSD in the rat such that, under nonphysiologic conditions (i.e., mimicking ischemic penumbra), the hyperemic response to CSD becomes attenuated resembling the blood flow response during PIDs. C1 [Sukhotinsky, Inna; Dilekoz, Ergin; Moskowitz, Michael A.; Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab,Dept Radiol, Charlestown, MA USA. [Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke Serv,Dept Neurol, Boston, MA USA. [Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Intens Care Unit,Dept Neurol, Boston, MA USA. RP Ayata, C (reprint author), Stroke & Neurovasc Regulat Lab, 149 13th St,Room 6403, Charlestown, MA 02129 USA. EM cayata@partners.org RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [R01 NS061505, 1R01NS61505, P01NS055104] NR 38 TC 37 Z9 40 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUL PY 2008 VL 28 IS 7 BP 1369 EP 1376 DI 10.1038/jcbfm.2008.35 PG 8 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 318DZ UT WOS:000257073100010 PM 18446167 ER PT J AU Biller, BMK Grossman, AB Stewart, PM Melmed, S Bertagna, X Bertherat, J Buchfelder, M Colao, A Hermus, AR Hofland, LJ Klibanski, A Lacroix, A Lindsay, JR Newell-Price, J Nieman, LK Petersenn, S Sonino, N Stalla, GK Swearingen, B Vance, ML Wass, JAH Boscaro, M AF Biller, B. M. K. Grossman, A. B. Stewart, P. M. Melmed, S. Bertagna, X. Bertherat, J. Buchfelder, M. Colao, A. Hermus, A. R. Hofland, L. J. Klibanski, A. Lacroix, A. Lindsay, J. R. Newell-Price, J. Nieman, L. K. Petersenn, S. Sonino, N. Stalla, G. K. Swearingen, B. Vance, M. L. Wass, J. A. H. Boscaro, M. TI Treatment of adrenocorticotropin-dependent Cushing's syndrome: A consensus statement SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID PPAR-GAMMA RECEPTOR; TERM-FOLLOW-UP; BILATERAL LAPAROSCOPIC ADRENALECTOMY; SOMATOSTATIN ANALOG SMS-201-995; GROWTH-HORMONE-SECRETION; TRANS-SPHENOIDAL SURGERY; TRANSSPHENOIDAL SURGERY; NELSONS-SYNDROME; PITUITARY IRRADIATION; MEDICAL THERAPY AB Objective: Our objective was to evaluate the published literature and reach a consensus on the treatment of patients with ACTH-dependent Cushing's syndrome, because there is no recent consensus on the management of this rare disorder. Participants: Thirty-two leading endocrinologists, clinicians, and neurosurgeons with specific expertise in the management of ACTH-dependent Cushing's syndrome representing nine countries were chosen to address 1) criteria for cure and remission of this disorder, 2) surgical treatment of Cushing's disease, 3) therapeutic options in the event of persistent disease after transsphenoidal surgery, 4) medical therapy of Cushing's disease, and 5) management of ectopic ACTH syndrome, Nelson's syndrome, and special patient populations. Evidence: Participants presented published scientific data, which formed the basis of the recommendations. Opinion shared by a majority of experts was used where strong evidence was lacking. Consensus Process: Participants met for 2 d, during which there were four chaired sessions of presentations, followed by general discussion where a consensus was reached. The consensus statement was prepared by a steering committee and was then reviewed by all authors, with suggestions incorporated if agreed upon by the majority. Conclusions: ACTH-dependent Cushing's syndrome is a heterogeneous disorder requiring a multidisciplinary and individualized approach to patient management. Generally, the treatment of choice for ACTH-dependent Cushing's syndrome is curative surgery with selective pituitary or ectopic corticotroph tumor resection. Second-line treatments include more radical surgery, radiation therapy (for Cushing's disease), medical therapy, and bilateral adrenalectomy. Because of the significant morbidity of Cushing's syndrome, early diagnosis and prompt therapy are warranted. C1 [Biller, B. M. K.; Klibanski, A.; Swearingen, B.] Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Boston, MA 02114 USA. [Grossman, A. B.] St Bartholomews Hosp, Dept Endocrinol, London EC1A 7BE, England. [Stewart, P. M.] Univ Birmingham, Queen Elizabeth Hosp, Div Med Sci, Birmingham B29 6JD, W Midlands, England. [Melmed, S.] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. [Bertagna, X.; Bertherat, J.] Hop Cochin, Dept Endocrinol, Fac Med Paris Descartes, AP HP, F-75014 Paris, France. [Buchfelder, M.] Univ Erlangen Nurnberg, Neurochirurg Klin, D-91054 Erlangen, Germany. [Colao, A.] Univ Naples Federico II, Dipartimento Endocrinol & Oncol Mol & Clin, I-80131 Naples, Italy. [Hermus, A. R.] Univ Med Ctr Nijmegen, Dept Endocrinol, NL-6000500 Nijmegen, Netherlands. [Hofland, L. J.] Erasmus MC, Div Endocrinol, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. [Lacroix, A.] Univ Montreal, Ctr Hosp, Dept Med, Div Endocrinol, Montreal, PQ H2W 1T8, Canada. [Newell-Price, J.] Univ Sheffield, Sch Med, Sheffield S10 2TN, S Yorkshire, England. [Nieman, L. K.] NIH, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. [Petersenn, S.] Univ Essen Gesamthsch, Div Endocrinol, D-45122 Essen, Germany. [Sonino, N.] Univ Padua, Dept Stat Sci, I-35122 Padua, Italy. [Stalla, G. K.] Max Planck Inst Psychiat, Dept Endocrinol, D-80804 Munich, Germany. [Vance, M. L.] Univ Virginia Hlth Syst, Charlottesville, VA 22903 USA. [Wass, J. A. H.] Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Dept Endocrinol, Oxford OX3 7LJ, England. [Boscaro, M.] Polytech Univ Marche, Div Endocrinol, Inst Internal Med, I-60126 Ancona, Italy. RP Boscaro, M (reprint author), Polytech Univ Marche, Sch Med, Div Endocrinol, Inst Internal Med, I-60020 Ancona, Italy. EM m.boscaro@univpm.it RI Hermus, A.R.M.M./H-8043-2014; OI BOSCARO, MARCO/0000-0003-2596-1652 FU Intramural NIH HHS [Z01 HD008833-02] NR 107 TC 377 Z9 397 U1 1 U2 16 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL 1 PY 2008 VL 93 IS 7 BP 2454 EP 2462 DI 10.1210/jc.2007-2734 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 324JA UT WOS:000257513700006 PM 18413427 ER PT J AU Utz, AL Yamamoto, A Hemphill, L Miller, KK AF Utz, Andrea L. Yamamoto, Ami Hemphill, Linda Miller, Karen K. TI Growth hormone deficiency by growth hormone releasing hormone-arginine testing criteria predicts increased cardiovascular risk markers in normal young overweight and obese women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INTIMA-MEDIA THICKNESS; PLACEBO-CONTROLLED TRIAL; ABDOMINAL VISCERAL FAT; C-REACTIVE PROTEIN; BODY-MASS INDEX; GH DEFICIENCY; HYPOPITUITARY ADULTS; INCREASED PREVALENCE; PLASMINOGEN-ACTIVATOR; POSTMENOPAUSAL WOMEN AB Context: Little is known about the relationship between GH and cardiovascular risk markers in women without organic hypothalamic/pituitary disease. Objective: The objective of the study was to determine whether healthy young overweight and obese women, who would be classified as having GH deficiency (GHD) based on standard criteria used in hypopituitarism (peak GH after stimulation with GHRH and arginine < 5 ng/ml), have increased cardiovascular risk markers. Design: This was a cross-sectional study. Setting: The study was conducted at the General Clinical Research Center. Study Participants: Forty-five women of reproductive age, mean age 33.1 +/- 1.2 yr and mean body mass index (BMI) 30.9 +/- 1.0 kg/m(2). Intervention: There was no intervention. Main Outcome Measures: Measures included carotid intima-medial thickness, high-sensitivity C-reactive protein (hsCRP), total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein, triglycerides, E-selectin, soluble intercellular adhesion molecule-1, TNF-alpha receptor I, TNF-alpha receptor II, fasting insulin levels, and oral glucose tolerance testing. Results: Twenty-six percent of overweight or obese subjects and none with BMI less than 25 kg/m(2) met criteria for GHD. Subjects who met GHD criteria had a mean BMI of 37.0 +/- 1.7 kg/m2 (range 28.6-43.6 kg/m2), and their mean waist circumference (110.1 +/- 3.5 cm) was higher than in over-weight/ obese women with GH sufficiency (P = 0.007). Mean carotid intima-media thickness, hsCRP, soluble intercellular adhesion molecule-1, TNF-alpha receptor I, and TNF-alpha receptor II levels were higher, and HDL lower, in women meeting GHD criteria than in GH sufficiency. Differences in HDL, hsCRP, and TNF-alpha receptor II remained after controlling for age plus BMI, waist circumference, or trunk fat. There were no differences in measures of insulin resistance. Conclusions: There may be a relative GHD syndrome in overweight and obese women without organic pituitary or hypothalamic disease that confers increased cardiovascular risk, independent of weight. C1 [Utz, Andrea L.; Yamamoto, Ami; Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Hemphill, Linda] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM kkmiller@partners.org FU NCRR NIH HHS [M01 RR 01066, M01 RR001066]; NHLBI NIH HHS [R01 HL077674, HL 077674] NR 51 TC 37 Z9 37 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL 1 PY 2008 VL 93 IS 7 BP 2507 EP 2514 DI 10.1210/jc.2008-0169 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 324JA UT WOS:000257513700017 PM 18445664 ER PT J AU Pitteloud, N Dwyer, AA DeCruz, S Lee, H Boepple, PA Crowley, WF Hayes, FJ AF Pitteloud, Nelly Dwyer, Andrew A. DeCruz, Suzzunne Lee, Hang Boepple, Paul A. Crowley, William F., Jr. Hayes, Frances J. TI The relative role of gonadal sex steroids and gonadotropin-releasing hormone pulse frequency in the regulation of follicle-stimulating hormone secretion in men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RAT PITUITARY-CELLS; LUTEINIZING-HORMONE; NEGATIVE FEEDBACK; DEFICIENT MEN; INHIBIN-B; BETA-TRANSCRIPTION; FSH-SECRETION; TESTOSTERONE; AROMATIZATION; ESTRADIOL AB Objective: Our objective was to determine the importance of testosterone (T), estradiol (E-2), and GnRH pulse frequency to FSH regulation in men. Design: This was a prospective study with four arms. Setting: The study was performed at the General Clinical Research Center. Patients or Other Participants: There were 20 normal (NL) men and 15 men with idiopathic hypogonadotropic hypogonadism (IHH) who completed the study. Intervention: Medical castration and inhibition of aromatase were achieved using ketoconazole x 7 d with: 1) no sex steroid addback, 2) T addback starting on d 4, and 3) E-2 addback starting on d 4. IHH men in these arms received GnRH every 120 min. In a further six IHH men receiving ketoconazole with no addback, GnRH frequency was increased to 35 min for d 4-7. Blood was drawn every 10 min x 12 h at baseline, overnight on d 3-4 and 6-7. Main Outcome Measures: Mean FSH was calculated from the pool of each frequent sampling study. Results: In NL men FSH levels increased from 5.1 +/- 0.7 to 8.7 +/- 1.3 and 9.7 +/- 1.5 IU/liter (P < 0.0001). T caused no suppression of FSH. E-2 reduced FSH from 12.4 +/- 1.8 to 9.3 +/- 1.3 IU/liter (P < 0.05). In IHH men on GnRH every 120 min, FSH levels went from 6.0 +/- 1.6 to 9.0 +/- 3.0 and 11.9 +/- 4.3 (P = 0.07). T caused no suppression of FSH. E-2 decreased FSH such that levels on d 6-7 were similar to baseline. Increasing GnRH frequency to 35 min had no impact on FSH. Conclusions: The sex steroid component of FSH negative feedback in men is mediated by E2. Increasing GnRH frequency to castrate levels has no impact on FSH in the absence of sex steroids. When inhibin B levels are NL, sex steroids exert a modest effect on FSH. C1 [Pitteloud, Nelly; Dwyer, Andrew A.; DeCruz, Suzzunne; Boepple, Paul A.; Crowley, William F., Jr.; Hayes, Frances J.] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. RP Hayes, FJ (reprint author), Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, 55 Fruit St, Boston, MA 02114 USA. EM Hayes.Frances@MGH.Harvard.edu RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014 OI Dwyer, Andrew/0000-0002-7023-6794; FU NCRR NIH HHS [M01 RR 01066, M01 RR001066]; NICHD NIH HHS [R01 HD 15788-15, R01 HD015788, U54 HD028138, U54 HD029164] NR 35 TC 25 Z9 25 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL 1 PY 2008 VL 93 IS 7 BP 2686 EP 2692 DI 10.1210/jc.2007-2548 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 324JA UT WOS:000257513700041 PM 18445673 ER PT J AU Claud, EC Walker, WA AF Claud, Erika C. Walker, W. Allan TI Bacterial colonization, probiotics, and necrotizing enterocolitis SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Workshop on Advances in Clinical Use of Probiotics CY 2007 CL Yale Univ, New Haven, CT HO Yale Univ DE intestinal microflora; probiotics; preterm infant; necrotizing enterocolitis ID BIRTH-WEIGHT INFANTS; NF-KAPPA-B; RAT SMALL-INTESTINE; FECAL MICROFLORA; PRETERM INFANTS; PLANT POLYSACCHARIDES; EPITHELIAL-CELLS; HOST-DEFENSE; PANETH CELLS; HUMAN COLON AB The intestinal microflora has a significant role in intestinal health and gut function. The neonatal population is unique in that intestinal colonization is not established and is known to be influenced by delivery method, feeding, gestational age, and medical interventions. The preterm infant is particularly sensitive to colonization patterns as inherent intestinal defense mechanisms are immature and immature intestinal epithelial cells are known to have exaggerated inflammatory responses to both commensal and pathogenic bacteria. These responses contribute to the development of neonatal necrotizing enterocolitis in this patient population. As certain bacteria are known to influence intestinal maturation and down-regulate intestinal inflammation, it has been suggested that influencing the intestinal flora of preterm infants may be beneficial. Clinical studies indicate that probiotic therapy may decrease the incidence of necrotizing enterocolitis and studies are ongoing to elucidate the mechanism of action of different probiotic organisms. Although concerns remain and further study is necessary, probiotics are a plausible means of optimizing intestinal colonization and influencing outcome of these vulnerable infants. C1 [Walker, W. Allan] Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA USA. [Claud, Erika C.] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. RP Walker, WA (reprint author), Massachusetts Gen Hosp Children, Pediat Gastroenterol & Nutr Unit, Mucosal Immunol Lab, 114 16th St 114-3503, Charlestown, MA 02129 USA. EM wwalker@partners.org FU NICHD NIH HHS [K08 HD043839, R37 HD012437]; NIDDK NIH HHS [P01 DK033506, P30 DK040561, P30 DK040561-13, R01 DK070260] NR 60 TC 46 Z9 48 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD JUL PY 2008 VL 42 IS 6 SU S BP S46 EP S52 DI 10.1097/MCG.0b013e31815a57a8 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 324AY UT WOS:000257491200002 PM 18520617 ER PT J AU Ramsay, AG Johnson, AJ Lee, AM Gorgun, G Le Dieu, R Blum, W Byrd, JC Gribben, JG AF Ramsay, Alan G. Johnson, Amy J. Lee, Abigail M. Gorgun, Gullu Le Dieu, Rifca Blum, William Byrd, John C. Gribben, John G. TI Chronic lymphocytic leukemia T cells show impaired immunological synapse formation that can be reversed with an immunomodulating drug SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID B-CELLS; ACTIN POLYMERIZATION; GENE-EXPRESSION; LYTIC FUNCTION; LENALIDOMIDE; ACTIVATION; RESPONSES; CANCER; IMMUNOTHERAPY; MALIGNANCIES AB Cancer is associated with immune deficiency, but the biologic basis of this is poorly defined. Here we demonstrate that impaired actin polymerization results in CD4(+) and CD8(+) T cells from patients with chronic lymphocytic leukemia (CLL) exhibiting defective immunological synapse formation with APCs. Although this synapse dysfunction was in part a result of the CLL cells having poor APC function, defective actin polymerization was also identified in T cells from patients with CLL. We further demonstrate that, following contact with CLL cells, defects in immune synapse formation were induced in healthy allogeneic T cells. This required direct contact and was inhibited by blocking adhesion molecules on CLL B cells. In T cells from patients with CLL and in T cells from healthy individuals that had been in contact with CLL cells, recruitment of key regulatory proteins to the immune synapse was inhibited. Treatment of autologous T cells and CLL cells with the immunomodulating drug lenalidomide resulted in improved synapse formation. These results define what we believe to be a novel immune dysfunction in T cells from patients with CLL that has implications for both autologous and allogeneic immunotherapy approaches and identifies repair of immune synapse defects as an essential step in improving cancer immunotherapy approaches. C1 [Ramsay, Alan G.; Lee, Abigail M.; Le Dieu, Rifca; Gribben, John G.] Univ London, Inst Canc, Ctr Med Oncol, Barts & London Sch Med, London EC1M 6BQ, England. [Johnson, Amy J.; Blum, William; Byrd, John C.] Ohio State Univ, Coll Med, Dept Internal Med, Div Hematol & Oncol, Columbus, OH 43210 USA. [Gorgun, Gullu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Gribben, JG (reprint author), Univ London, Inst Canc, Ctr Med Oncol, Barts & London Sch Med, Charterhouse Sq, London EC1M 6BQ, England. EM john.gribben@cancer.org.uk RI Johnson, Amy/A-5662-2009; Blum, William/E-2769-2011; Ramsay, Alan/A-8374-2015 OI Ramsay, Alan/0000-0002-0452-0420 FU NCI NIH HHS [P01 CA095426, P01 CA81538, P01 CA95426] NR 45 TC 279 Z9 283 U1 1 U2 13 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2008 VL 118 IS 7 BP 2427 EP 2437 DI 10.1172/JCI35017 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 326KL UT WOS:000257657400011 PM 18551193 ER PT J AU Guix, M Faber, AC Wang, SE Olivares, MG Song, Y Qu, S Rinehart, C Seidel, B Yee, D Arteaga, CL Engelman, JA AF Guix, Marta Faber, Anthony C. Wang, Shizhen Emily Olivares, Maria Graciela Song, Youngchul Qu, Sherman Rinehart, Cammie Seidel, Brenda Yee, Douglas Arteaga, Carlos L. Engelman, Jeffrey A. TI Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGF-binding proteins SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GROWTH-FACTOR-RECEPTOR; LUNG-CANCER; BREAST-CANCER; GEFITINIB SENSITIVITY; ANTITUMOR-ACTIVITY; T790M MUTATIONS; GENE-MUTATIONS; TUMOR-CELLS; IN-VIVO; ERLOTINIB AB Although some cancers are initially sensitive to EGFR tyrosine kinase inhibitors (TKIs), resistance invariably develops. We investigated mechanisms of acquired resistance to the EGFR TKI gefitinib by generating gefitinib-resistant (GR) A431 squamous cancer cells. in GR cells, gefitinib reduced phosphorylation of EGFR, ErbB-3, and Erk but not Akt. These cells also showed hyperphosphorylation of the IGFI receptor (IGFIR) and constitutive association of IRS-1 with PI3K. Inhibition of IGFIR signaling disrupted the association of IRS-1 with PI3K and restored the ability of gefitinib to downregulate PI3K/Akt signaling and to inhibit GR cell growth. Gene expression analyses revealed that GR cells exhibited markedly reduced IGF-binding protein 3 (IGFBP-3) and IGFBP-4 RNA. Addition of recombinant IGFBP-3 restored the ability of gefitinib to downregulate PI3K/Akt signaling and to inhibit cell growth. Finally, gefitinib treatment of mice with A431 xenografts in combination with an IGFIR-specific monoclonal antibody prevented tumor recurrence, whereas each drug given alone was unable to do so. These data suggest that loss of expression of IGFBPs in tumor cells treated with EGFR TKIs derepresses IGFIR signaling, which in turn mediates resistance to EGFR antagonists. Moreover, combined therapeutic inhibition of EGFR and IGFIR may abrogate this acquired mechanism of drug resistance and is thus worthy of prospective clinical investigation. C1 [Guix, Marta; Olivares, Maria Graciela; Qu, Sherman; Rinehart, Cammie; Arteaga, Carlos L.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. [Faber, Anthony C.; Song, Youngchul; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [Wang, Shizhen Emily; Arteaga, Carlos L.] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Comprehens Canc Ctr, Dept Canc Biol, Nashville, TN 37212 USA. [Wang, Shizhen Emily; Olivares, Maria Graciela; Arteaga, Carlos L.] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Comprehens Canc Ctr, Breast Canc Res Program, Nashville, TN 37212 USA. [Seidel, Brenda; Yee, Douglas] Univ Minnesota, Ctr Canc, Minneapolis, MN USA. RP Arteaga, CL (reprint author), Vanderbilt Univ, Med Ctr, Div Oncol, 2200 Pierce Ave,777 PRB, Nashville, TN 37232 USA. EM carlos.arteaga@vanderbilt.edu; jengelman@partners.org FU NCI NIH HHS [R01 CA080195, K08 CA120060, K08 CA120060-01, P30 CA068485, P30 CA68485, P50 CA098131, P50 CA127003, P50 CA98131, R00 CA125892, R01 CA80195] NR 49 TC 338 Z9 347 U1 5 U2 25 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2008 VL 118 IS 7 BP 2609 EP 2619 DI 10.1172/JCI34588 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 326KL UT WOS:000257657400028 PM 18568074 ER PT J AU Riedel, S Bourbeau, P Swartz, B Brecher, S Carroll, KC Stamper, PD Dunne, WM McCardle, T Walk, N Fiebelkorn, K Sewell, D Richter, SS Beekmann, S Doern, GV AF Riedel, Stefan Bourbeau, Paul Swartz, Brandi Brecher, Steven Carroll, Karen C. Stamper, Paul D. Dunne, W. Michael McCardle, Timothy Walk, Nathan Fiebelkorn, Kristin Sewell, David Richter, Sandra S. Beekmann, Susan Doern, Gary V. TI Timing of specimen collection for blood cultures from febrile patients with bacteremia (vol 46, pg 1381, 2008) SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Correction C1 [Riedel, Stefan] Univ Iowa, Coll Med, Iowa City, IA 52242 USA. Geisinger Med Ctr, Danville, PA 17822 USA. VA Boston Healthcare Syst, W Roxbury, MA USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Washington Univ, Sch Med, Barnes Jewish Hosp, St Louis, MO USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. VA Med Ctr, Portland, OR USA. RP Riedel, S (reprint author), Univ Iowa, Coll Med, Iowa City, IA 52242 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 2008 VL 46 IS 7 BP 2475 EP 2475 DI 10.1128/JCM.01025-08 PG 1 WC Microbiology SC Microbiology GA 344DS UT WOS:000258906800068 ER PT J AU Lacy, MQ Alsina, M Fonseca, R Paccagnella, ML Melvin, CL Yin, D Sharma, A Sarano, ME Pollak, M Jagannath, S Richardson, P Gualberto, A AF Lacy, Martha Q. Alsina, Melissa Fonseca, Rafael Paccagnella, M. Luisa Melvin, Carrie L. Yin, Donghua Sharma, Amarnath Sarano, M. Enriquez Pollak, Michael Jagannath, Sundar Richardson, Paul Gualberto, Antonio TI Phase I, pharmacokinetic and pharmacodynamic study of the anti-insulinlike growth factor type 1 receptor monoclonal antibody CP-751,871 in patients with multiple myeloma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol ID DEXAMETHASONE-INDUCED APOPTOSIS; CELL-LINE; TYROSINE KINASE; TUMOR-GROWTH; MAMMALIAN TARGET; INHIBITS GROWTH; SOLID TUMORS; MOUSE MODEL; PROLIFERATION; VIVO AB Purpose A phase I first-in-human study was conducted to characterize the safety, tolerability, pharmacokinetic, and pharmacodynamic properties of the anti-insulinlike growth factor 1 receptor (IGF-IR) monoclonal antibody CP-751,871. Patients and Methods After informed consent and screening, 47 patients with multiple myeloma in relapse or refractory phase were enrolled into 11 dose-escalation cohorts of CP-751,871 at doses from 0.025 to 20 mg/kg for 4 weeks. Patients with less than a partial response to CP-751,871 treatment were eligible to receive CP-751,871 in combination with oral dexamethasone at the discretion of the investigator. Treatment with CP-751,871 and rapamycin with or without dexamethasone was also offered to patients enrolled in the 10 and 20 mg/kg cohorts with less than a partial response to initial therapy with single-agent CP-751,871. Results No CP-751,871-related dose-limiting toxicities were identified. Plasma CP-751,871 concentrations increased with dose and concentration-time profiles were consistent with those of antibodies with target-mediated disposition. Importantly, CP-751,871 administration led to a decrease in granulocyte IGF-IR expression and serum insulinlike growth factor 1 accumulation at high doses, suggesting systemic IGF-IR inhibition. Tumor response was assessed according to the European Group for Blood and Marrow Transplantation criteria. Nine responses were reported in 27 patients treated with CP-751,871 in combination with dexamethasone. Of interest, two of the patients with a partial response were progressing from dexamethasone treatment at study entry. Conclusion These data indicate that CP-751,871 is well tolerated and may constitute a novel agent in the treatment of multiple myeloma. C1 Pfizer Global Res & Dev, New London, CT 06320 USA. Mayo Clin, Div Hematol, Rochester, MN USA. Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Tampa, FL USA. Mayo Clin, Div Hematol, Scottsdale, AZ USA. St Vincents Comprehens Canc Ctr, New York, NY USA. Dana Farber Canc Inst Boston, Boston, MA USA. McGill Univ, Montreal, PQ H3A 2T5, Canada. Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada. RP Gualberto, A (reprint author), Pfizer Global Res & Dev, 50 Pequot Ave,MS6025-A3266, New London, CT 06320 USA. EM antonio.gualberto@pfizer.com RI Pollak, Michael/G-9094-2011; OI Pollak, Michael/0000-0003-3047-0604; Fonseca, Rafael/0000-0002-5938-3769 NR 51 TC 112 Z9 118 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 1 PY 2008 VL 26 IS 19 BP 3196 EP 3203 DI 10.1200/JCO.2007.15.9319 PG 8 WC Oncology SC Oncology GA 323AM UT WOS:000257416400016 PM 18474873 ER PT J AU Wolpin, BM Wei, EK Ng, K Meyerhardt, JA Chan, JA Selhub, J Giovannucci, EL Fuchs, CS AF Wolpin, Brian M. Wei, Esther K. Ng, Kimmie Meyerhardt, Jeffrey A. Chan, Jennifer A. Selhub, Jacob Giovannucci, Edward L. Fuchs, Charles S. TI Prediagnostic plasma folate and the risk of death in patients with colorectal cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FOLIC-ACID FORTIFICATION; NESTED CASE-CONTROL; HOMOCYSTEINE; SUPPLEMENTS; PREVENTION AB Purpose Although previous studies have demonstrated an inverse relationship between folate intake and colorectal cancer risk, a recent trial suggests that supplemental folic acid may accelerate tumorigenesis among patients with a history of colorectal adenoma. Therefore, high priority has been given to research investigating the influence of folate on cancer progression in patients with colorectal cancer. Patients and Methods To investigate whether prediagnostic levels of plasma folate are associated with colorectal cancer-specific and overall mortality, we performed a prospective, nested observational study within two large US cohorts: the Nurses' Health Study and Health Professionals Follow-Up Study. We measured folate levels among 301 participants who developed colorectal cancer 2 or more years after their plasma was collected and compared participants using Cox proportional hazards models by quintile of plasma folate. Results Higher levels of plasma folate were not associated with an increased risk of colorectal cancer specific or overall mortality. Compared with participants in the lowest quintile of plasma folate, those in the highest quintile experienced a multivariable-adjusted hazard ratio for colorectal cancer-specific mortality of 0.42 (95% CI, 0.20 0.88) and overall mortality of 0.46 ( 95% CI, 0.24 0.88). When the analysis was limited to participants whose plasma was collected within 5 years of cancer diagnosis, no detrimental effect of high plasma folate was noted. In subgroup analyses, no subgroup demonstrated worse survival among participants with higher plasma folate levels. Conclusion In two large prospective cohorts, higher prediagnostic levels of plasma folate were not associated with an increased risk of colorectal cancer-specific or overall mortality. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, Cambridge, MA 02138 USA. Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Medford, MA 02155 USA. Harvard Univ, Dept Epidemiol & Nutr, Harvard Sch Publ Hlth, Boston, MA 02115 USA. RP Wolpin, BM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM bwolpin@partners.org FU NCI NIH HHS [CA108341, CA118553, CA87969, T32 CA009001, R01 CA118553, R03 CA108341, CA09001, P01 CA087969, T32 CA009172] NR 23 TC 24 Z9 25 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 1 PY 2008 VL 26 IS 19 BP 3222 EP 3228 DI 10.1200/JCO.2008.16.1943 PG 7 WC Oncology SC Oncology GA 323AM UT WOS:000257416400019 PM 18591557 ER PT J AU Meropol, NJ Niedzwiecki, D Shank, B Colacchio, TA Ellerton, J Valone, F Budinger, S Day, JM Hopkins, J Tepper, J Goldberg, RM Mayer, RJ AF Meropol, Neal J. Niedzwiecki, Donna Shank, Brenda Colacchio, Thomas A. Ellerton, John Valone, Frank Budinger, Susan Day, Jeannette M. Hopkins, Judy Tepper, Joel Goldberg, Richard M. Mayer, Robert J. TI Induction therapy for poor-prognosis anal canal carcinoma: A phase II study of the cancer and leukemia group B (CALGB 9281) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT Symposium on Gastrointestinal Cancer of the American-Society-of-Clinical-Oncology CY JAN 27-29, 2005 CL Hollywood, FL SP Amer Soc Clin Oncol ID RADIOTHERAPY; TRIALS; CHEMOTHERAPY; INTERGROUP; CISPLATIN; MITOMYCIN AB Purpose Although most patients with anal canal cancer are cured with sphincter-preserving, nonsurgical, combined-modality therapy, those with large tumors and lymph node involvement have a poor prognosis. To establish the safety and efficacy of induction chemotherapy with infusional fluorouracil (FU) plus cisplatin followed by FU plus mitomycin C with concurrent radiation in patients with poor-prognosis squamous cell cancers of the anal canal. Methods Patients with previously untreated anal canal cancers with T3 or T4 tumors and/or extensive nodal involvement (bulky N2 or N3) received two 28-day cycles of induction treatment with infusional FU plus cisplatin followed by two 28-day cycles of FU plus mitomycin C with concurrent split-course radiation. A third cycle of FU and cisplatin with radiation boost was given to patients with persistent primary site disease or bulky N2 or N3 disease at presentation. Results Forty-five assessable patients received protocol therapy. Treatment was generally well tolerated, and gastrointestinal and hematologic toxicities were the most common. Induction chemotherapy resulted in eight complete and 21 partial responses. After induction, combined-modality, and boost therapy, 37 (82%) of 45 assessable high-risk patients achieved a complete response. After 4 years of follow-up, 68% of patients are alive, 61% are disease-free, and 50% are colostomy-and disease-free. Conclusion A combined-modality approach that includes induction treatment with FU and cisplatin followed by combined-modality therapy with FU, mitomycin C, and concurrent radiation results in long-term disease control in the majority of patients with poor-prognosis anal canal cancer. C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Duke Univ, Canc & Leukemia Grp B Stat Ctr, Med Ctr, Durham, NC 27706 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Doctors Med Ctr, San Pablo, CA USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. So Nevada Canc Res Fdn Community, Clin Oncol Program, Las Vegas, NV USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Meropol, NJ (reprint author), Fox Chase Canc Ctr, 333 Cott Man Ave, Philadelphia, PA 19111 USA. EM neal.meropol@fccc.edu RI Goldberg , Richard/M-1311-2013 FU NCI NIH HHS [CA04326, CA31946, CA32291, CA03927, CA33601, CA35421, CA47559] NR 13 TC 32 Z9 33 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 1 PY 2008 VL 26 IS 19 BP 3229 EP 3234 DI 10.1200/JCO.2008.16.2339 PG 6 WC Oncology SC Oncology GA 323AM UT WOS:000257416400020 PM 18490648 ER PT J AU Kesari, S Drappatz, J Akar, S Vergilio, JA Wen, PY Soiffer, RJ Stone, RM DeAngelo, DJ AF Kesari, Santosh Drappatz, Jan Akar, Serra Vergilio, Jo-Anne Wen, Patrick Y. Soiffer, Robert J. Stone, Richard M. DeAngelo, Daniel J. TI Recurrent acute promyelocytic leukemia presenting as a sacral nerve root mass SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TRANS-RETINOIC ACID; EXTRAMEDULLARY RELAPSE; SYSTEM RELAPSE; INVOLVEMENT; HEMORRHAGE; REMISSION; ADHESION; ATRA C1 [Kesari, Santosh; Drappatz, Jan; Wen, Patrick Y.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Neurol, Boston, MA 02115 USA. [Akar, Serra] Hacettepe Univ, Sch Med, Ankara, Turkey. [Vergilio, Jo-Anne] Harvard Univ, Sch Med, Boston, MA USA. [Soiffer, Robert J.; Stone, Richard M.; DeAngelo, Daniel J.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. RP Kesari, S (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. RI Kesari, Santosh/E-8461-2013 NR 22 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 1 PY 2008 VL 26 IS 19 BP 3279 EP 3281 DI 10.1200/JCO.2007.15.6729 PG 3 WC Oncology SC Oncology GA 323AM UT WOS:000257416400027 PM 18591563 ER PT J AU Petersen, TJ Huffman, JC Weiss, AP Blais, MA Andreotti, CF Horwitz, MB Birnbaum, RJ AF Petersen, Timothy J. Huffman, Jeff C. Weiss, Anthony P. Blais, Mark A. Andreotti, Charissa F. Horwitz, Madeline B. Birnbaum, Robert J. TI Reach of benchmark psychiatric trial results to community-based providers: A case study of CATIE SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID CONTINUING MEDICAL-EDUCATION; RANDOMIZED CONTROLLED-TRIAL; STAR-ASTERISK-D; CLINICAL-TRIALS; GENERAL-PRACTITIONERS; BIPOLAR DEPRESSION; HEALTH-CARE; STEP-BD; DESIGN; IMPACT AB Objective: To evaluate the familiarity of front-line clinicians with findings from the Clinical Antipsychotic Trial, of Intervention Effectiveness (CATIE), the influence of didactic continuing medical education on provider knowledge about key details of CATIE, and how location-related factors affect rates of pre-event knowledge and intraevent learning about CATIE. Method: Data derived from the Massachusetts General Hospital Psychiatry Academy (MGH-PA) semester II live symposia provided in different cities nationally between September and December 2006 were analyzed to evaluate providers' self-assessment of their knowledge about CATIE. In addition, participants were also asked a preactivity and postactivity question to assess learning of material presented during the live event psychosis lecture. Descriptive statistics were utilized to characterize participants' self-assessment of knowledge about CATIE, while parametric and nonparametric statistical tests were used to evaluate the degree of observed learning and the effect of lecture location on the results. Results: 3333 participants (mean attendance: N = 278 per event) attended I of the 12 MGH-PA live symposia. Of the subsample of providers who treat schizophrenia, 51% indicated that either they had never heard of CATIE or they were not familiar enough with its results to change their practice. Overall, the proportion of correct answers on the postactivity question was 65%, compared with 24% prior to the lecture (chi(2) = 48.68, df = 1, p < .001). Degree of learning did not differ among symposium locations. Conclusion: In this sample, the CATIE study had very limited dissemination to, and impact on, a geographically and occupationally diverse sample of mental health practitioners. Robust learning of a key methodologic detail of this trial was evidenced across symposium locations. C1 [Petersen, Timothy J.; Huffman, Jeff C.; Weiss, Anthony P.; Blais, Mark A.; Andreotti, Charissa F.; Horwitz, Madeline B.; Birnbaum, Robert J.] Massachusetts Gen Hosp, Dept Psychiat, Div Postgrad Educ, Boston, MA 02114 USA. RP Petersen, TJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Div Postgrad Educ, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM tpetersen@partners.org NR 34 TC 1 Z9 1 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 2008 VL 69 IS 7 BP 1081 EP 1086 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 331JE UT WOS:000258007700006 PM 18605813 ER PT J AU Biederman, J Seidman, LJ Petty, CR Fried, R Doyle, AE Cohen, DR Kenealy, DC Faraone, SV AF Biederman, Joseph Seidman, Larry J. Petty, Carter R. Fried, Ronna Doyle, Alysa E. Cohen, Daniel R. Kenealy, Deborah C. Faraone, Stephen V. TI Effects of stimulant medication on neuropsychological functioning in young adults with attention-deficit/hyperactivity disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DEFICIT-HYPERACTIVITY DISORDER; OSTERRIETH COMPLEX FIGURE; EXECUTIVE FUNCTION; CHILDREN; METHYLPHENIDATE; ADHD; PERFORMANCE; ADOLESCENTS; MEMORY AB Objective: The main goal of this study was to evaluate the impact of stimulant medication on executive function deficits in a group of adolescents and young adults with attention-deficit/hyperactivity disorder (ADHD; DSM-III-R criteria). Method: Male and female subjects aged 15 to 25 years were divided into 3 groups: subjects with ADHD treated with stimulants who took their medication at the time of testing (ADHD active stimulant treatment: N = 26), subjects with ADHD who had not taken stimulant medication in the past month (ADHD no stimulant treatment: N = 94), and non-ADHD control subjects (controls: N = 133). The neuropsychological battery assessed domains of cognitive functioning known to be relevant in ADHD, including tests of executive functions and learning and memory. Data were collected from July 1998 to April 2003. Results: The ADHD no stimulant treatment group had significantly lower aggregate scores compared with the controls for the total aggregate, working memory, interference control, processing speed, sustained attention, and verbal learning domains (all p < .001). The ADHD active stimulant treatment group had significantly poorer scores on the total aggregate (p = .002), interference control (p < .001), and processing speed (p = .003) domains compared with the controls. The ADHD active stimulant treatment subjects scored significantly higher on the domains of sustained attention (p = .04) and verbal learning (p = .03) compared with the ADHD no stimulant treatment subjects. Conclusions: Our study showed that subjects with ADHD who took stimulant medication had higher neuropsychological measures of attention compared with subjects with ADHD who did not take stimulant medication, but differences were not found for other measures of executive function. C1 [Biederman, Joseph; Seidman, Larry J.; Petty, Carter R.; Fried, Ronna; Doyle, Alysa E.; Cohen, Daniel R.; Kenealy, Deborah C.] Massachusetts Gen Hosp, Pediat Psychopharmacol Program, Dept Psychiat, Boston, MA 02114 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, 55 Fruit St,Warren 705, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [5R01 HD-36317-07] NR 38 TC 43 Z9 43 U1 0 U2 9 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 2008 VL 69 IS 7 BP 1150 EP 1156 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 331JE UT WOS:000258007700015 PM 18517288 ER PT J AU Bergevin, C Freeman, DM Saunders, JC Shera, CA AF Bergevin, Christopher Freeman, Dennis M. Saunders, James C. Shera, Christopher A. TI Otoacoustic emissions in humans, birds, lizards, and frogs: evidence for multiple generation mechanisms SO JOURNAL OF COMPARATIVE PHYSIOLOGY A-NEUROETHOLOGY SENSORY NEURAL AND BEHAVIORAL PHYSIOLOGY LA English DT Article DE OAE; non-mammal; lizard; chicken; frog ID COCHLEAR MICROMECHANICAL PROPERTIES; BULLFROG AMPHIBIAN PAPILLA; BASILAR-MEMBRANE MOTION; RANA-PIPIENS-PIPIENS; OUTER HAIR-CELLS; INNER-EAR; TONOTOPIC ORGANIZATION; TECTORIAL MEMBRANE; SOMATIC MOTILITY; ADULT CHICKENS AB Many non-mammalian ears lack physiological features considered integral to the generation of otoacoustic emissions in mammals, including basilar-membrane traveling waves and hair-cell somatic motility. To help elucidate the mechanisms of emission generation, this study systematically measured and compared evoked emissions in all four classes of tetrapod vertebrates using identical stimulus paradigms. Overall emission levels are largest in the lizard and frog species studied and smallest in the chicken. Emission levels in humans, the only examined species with somatic hair cell motility, were intermediate. Both geckos and frogs exhibit substantially higher levels of high-order intermodulation distortion. Stimulus frequency emission phase-gradient delays are longest in humans but are at least 1 ms in all species. Comparisons between stimulus-frequency emission and distortion-product emission phase gradients for low stimulus levels indicate that representatives from all classes except frog show evidence for two distinct generation mechanisms analogous to the reflection- and distortion-source (i.e., place- and wave-fixed) mechanisms evident in mammals. Despite morphological differences, the results suggest the role of a scaling-symmetric traveling wave in chicken emission generation, similar to that in mammals, and perhaps some analog in the gecko. C1 [Bergevin, Christopher] Univ Arizona, Dept Math, Tucson, AZ 85705 USA. [Bergevin, Christopher] Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02138 USA. [Freeman, Dennis M.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Saunders, James C.] Univ Penn, Dept Othorhinolaryngol, Philadelphia, PA 19104 USA. [Shera, Christopher A.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. [Shera, Christopher A.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Bergevin, C (reprint author), Univ Arizona, Dept Math, Tucson, AZ 85705 USA. EM cbergevin@math.arizona.edu FU NIDCD NIH HHS [R01 DC003687, T32 DC00038, R01 DC003687-10, T32 DC000038, R01 DC000238, R01 DC000710] NR 79 TC 25 Z9 25 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7594 J9 J COMP PHYSIOL A JI J. Comp. Physiol. A -Neuroethol. Sens. Neural Behav. Physiol. PD JUL PY 2008 VL 194 IS 7 BP 665 EP 683 DI 10.1007/s00359-008-0338-y PG 19 WC Behavioral Sciences; Neurosciences; Physiology; Zoology SC Behavioral Sciences; Neurosciences & Neurology; Physiology; Zoology GA 322KR UT WOS:000257374400007 PM 18500528 ER PT J AU Ma, XZ Setty, B Uppot, RN Sahani, DV AF Ma, Xiaozhou Setty, Bindu Uppot, Raul N. Sahani, Dushyant V. TI Multiple-Detector Computed Tomographic Angiography of Pancreatic Neoplasm for Presurgical Planning: Comparison of Low- and High-Concentration Nonionic Contrast Media SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE 16-row MDCT; angiography; contrast media; pancreatic neoplasm; resectability ID PHASE HELICAL CT; MULTIDETECTOR-ROW CT; HEPATIC ENHANCEMENT; IODINE CONCENTRATION; PORCINE MODEL; ADENOCARCINOMA; RESECTABILITY; MDCT; CANCER; LIVER AB Objective: To evaluate the degree of contrast enhancement, image quality, and accuracy of predicting resectability of pancreatic neoplasm with 16-row multiple-detector computed tomography (MDCT) angiography using low- and high-concentration (300 and 370 mg of iodine per milliliter, respectively) contrast media (CMs). Materials and Methods: Forty patients who had undergone pancreatic CT angiography (CTA) on 16-MDCT scanner and had surgery were included. Contrast medium of 2 iodine concentrations (group A, 300 mg/mL, n = 20; group B, 370 mg/mL, n = 20) from the same vendor (Isovue; Bracco Diagnostics), with iodine dose of 550 to 600 mg/kg of body weight, was injected at a rate of 5 mL/s. Dualphase 16-row MDCT was performed using 1.25- and 5-mm collimation for the arterial and portal phases, respectively. For the quantitative analysis, Hounsfield units values in the aorta, superior mesenteric artery, portal vein, and pancreas during arterial and venous phases were measured. Two readers subjectively rated the overall image enhancement, 3-dimensional image quality, and lesion and pancreatic duct conspicuity. Accuracy of lesion resectability was also established for each patient. The data were compared using Student t test for statistical analysis. Results: The quantitative analysis for the degree of enhancement (Hounsfield unit) of the aorta, superior mesenteric artery, and pancreas during the arterial phase demonstrated similar values in groups A (low-concentration CM) and B (high-concentration CM), with no statistically significant difference with each other (P > 0.05). During the portal venous phase, we found superior enhancements in the superior mesenteric and portal veins in group A (P < 0.05). The qualitative assessments of the overall image enhancement and 3-dimensional image quality on a 5-point scale were 4.3 and 4.65, respectively (P < 0.05), in group A and 4.6 and 4.75, respectively, in group B, whereas on a 3-point scale, the pancreatic duct display and lesion conspicuity were 2.75 and 2.85, respectively, in group A and 2.9 and 2.9, respectively, in group B. The accuracy for lesion resectability was 95% (19/20) in group A and 100% (20/20) in group B (P > 0.05). Conclusion: Both CMs demonstrated comparable performance for 16-row MDCT of the pancreas for presurgical planning. However, high-concentration CM (370 mg of iodine per milliliter) provides higher overall enhancement and superior-quality 3-dimensional images with a shorter injection duration. C1 [Ma, Xiaozhou; Setty, Bindu; Uppot, Raul N.; Sahani, Dushyant V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, WHT 2-270,55 Fruit St, Boston, MA 02114 USA. EM dsahani@partners.org NR 35 TC 5 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JUL-AUG PY 2008 VL 32 IS 4 BP 511 EP 517 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 336UL UT WOS:000258390000003 PM 18664834 ER PT J AU Li, CS Harisinghani, MG Lin, WC Braschi, M Hahn, PF Mueller, PR AF Li, Chao-Shiang Harisinghani, Mukesh G. Lin, Wen-Chiung Braschi, Martha Hahn, Peter F. Mueller, Peter R. TI Enhancement Characteristics of Ultrasmall Superparamagnetic Iron Oxide Particle Within the Prostate Gland in Patients With Primary Prostate Cancer SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE magnetic resonance imaging (MRI); contrast media; prostate cancer; ultrasmall superparamagnetic iron oxide (USPIO) ID CENTRAL-NERVOUS-SYSTEM; LYMPH-NODE METASTASES; CONTRAST AGENT; MACROPHAGE INFILTRATION; SIGNAL INTENSITY; MR SPECTROSCOPY; BRAIN-TUMORS; NANOPARTICLES; ANGIOGENESIS; GROWTH AB Objective: To analyze the enhancement of the prostate using ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging in patients with prostate cancer. Methods: Sixty patients were enrolled. The signal-to-noise ratios (SNRs) of the central and peripheral zones (CZ and PZ, respectively) of the prostate were evaluated on T2- and T2*-weighted magnetic resonance imaging before and 24 hours after USPIO-enhanced MRI. The changes in SNR after USPIO-enhanced MRI were analyzed and correlated with serum prostate-specific antigen and histopathologic Gleason scoring based on surgically removed prostate gland. Results: Decrease in SNR was noted in each zone of the prostate after USPIO-enhanced MRI (P < 0.001). Mean SNR decrease in the CZ was higher than that in the PZ (P < 0.05). High-grade prostate cancer was associated with a higher decrease in SNR (P < 0.05). The SNR change was negatively correlated with serum prostate-specific antigen at low or intermediate levels (P < 0.05). Conclusions: Enhancement of the prostate gland after USPIO administration may be associated with primary prostate cancer. C1 [Li, Chao-Shiang] Taipei City Hosp, Renai Branch, Dept Radiol, Taipei 106, Taiwan. [Li, Chao-Shiang; Harisinghani, Mukesh G.; Lin, Wen-Chiung; Braschi, Martha; Hahn, Peter F.; Mueller, Peter R.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Lin, Wen-Chiung] Tri Serv Gen Hosp, Dept Radiol, Taipei, Taiwan. [Lin, Wen-Chiung] Natl Def Med Ctr, Taipei, Taiwan. RP Li, CS (reprint author), Taipei City Hosp, Renai Branch, Dept Radiol, 10,Sect 4,Ren Ai Rd, Taipei 106, Taiwan. EM li4563@yahoo.com.tw NR 37 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 EI 1532-3145 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JUL-AUG PY 2008 VL 32 IS 4 BP 523 EP 528 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 336UL UT WOS:000258390000005 PM 18664836 ER PT J AU Markiewicz, MR Margarone, JE AF Markiewicz, Michael R. Margarone, Joseph E. TI Modified channel retractor for the sagittal split ramus osteotomy: A technical note SO JOURNAL OF CRANIO-MAXILLOFACIAL SURGERY LA English DT Article DE sagittal split osteotomy; channel retractor; mandibular advancement; oral surgical procedures; osteotomy; orthognathic surgery; surgical instruments ID FORT-I OSTEOTOMY; ORTHOGNATHIC SURGERY AB The authors describe a modification of the commonly used inferior border channel retractor for the sagittal split osteotomy of the mandible. We modified this instrument by hollowing out the shank and working surface allowing improved access during the vertical cut through the inferior border of the mandible. Advantages of this modification over the original design include less dulling of the cutting instrument, less damage to the channel retractor, less debris in the surgical wound, and most importantly, less damage to the surrounding soft tissue. In our experience with this instrument, there have been no incidences of excessive blood loss requiring transfusion, avascular necrosis, bony nonunion or permanent nerve injury. We believe this modification improves manouverability during orthognathic surgery thereby decreasing morbidity and operating time, thereby making a successful outcome more likely. (C) 2008 European Association for Cranio-Maxillofacial Surgery. C1 [Markiewicz, Michael R.] Massachusetts Gen Hosp, Ctr Appl Clin Invest, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. SUNY Buffalo, Sch Dent Med, Dept Oral & Maxillofacial Surg, Buffalo, NY USA. RP Markiewicz, MR (reprint author), 6490 Main St,Suite 3, Williamsville, NY 14221 USA. EM michaelmarkiewicz@gmail.com NR 20 TC 4 Z9 4 U1 3 U2 4 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1010-5182 J9 J CRANIO MAXILL SURG JI J. Cranio-MaxilloFac. Surg. PD JUL PY 2008 VL 36 IS 5 BP 269 EP 272 DI 10.1016/j.jcms.2008.02.002 PG 4 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA 324LD UT WOS:000257519200003 PM 18394912 ER PT J AU Basile, J Thiers, B Maize, J Lathers, DMR AF Basile, Jeff Thiers, Bruce Maize, John, Sr. Lathers, Deanne M. R. TI Chemokine receptor expression in non-melanoma skin cancer SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID LANGERHANS CELL HISTIOCYTOSIS; CXCR4 EXPRESSION; BASAL-CELL; METASTASIS; CARCINOMA; MELANOMA; CCR6; INVOLVEMENT; PATTERN; NECK AB Background: Previous studies suggest that chemokines and chemokine receptors have a role in the metastatic process. A correlation exists between the specific expression of these chemoattractive, pro-inflammatory cytokines and the ability of cancer to disseminate. Prior studies have shown that in metastatic melanoma and squamous cell carcinoma of the head and neck upregulation of CXC (alpha) chemokine receptor (CXCR)4 and CC (beta) chemokine receptor (CCR)7 expression is accompanied by downregulation of the chemokine receptor CCR6. However, the expression patterns of CCR6, CCR7 and CXCR4 in non-melanoma skin cancer have yet to be elucidated. Methods: The expression patterns of CCR6, CCR7 and CXCR4 were determined using an immunohistochemical approach on formalin-fixed, paraffin-embedded normal, pre-cancerous actinic (solar) keratosis, squamous cell carcinoma and basal cell carcinoma tissues. Results: Analysis of chemokine receptor expression showed downregulation of CCR6 and upregulation of CCR7 and CXCR4 in potentially metastatic non-melanoma skin cancer, invasive squamous cell carcinoma, but this pattern did not exist in non-melanoma skin cancer with no metastatic potential, basal cell carcinoma; or actinic keratosis, when compared with normal skin. Conclusions: Chemokine receptor expression may influence the biological behavior of non-melanoma skin cancer. The exact mechanism by which this occurs requires further study. C1 [Lathers, Deanne M. R.] Res Serv, Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. [Basile, Jeff] Med Univ S Carolina, Dept Grad Studies, Coll Med, Charleston, SC USA. [Thiers, Bruce; Maize, John, Sr.] Dept Dermatol, Charleston, SC USA. [Thiers, Bruce; Maize, John, Sr.] Dept Otolaryngol, Charleston, SC USA. RP Lathers, DMR (reprint author), Res Serv, Ralph H Johnson VA Med Ctr, 109 Bee St MS 151, Charleston, SC 29401 USA. EM lathers@musc.edu NR 20 TC 9 Z9 10 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JUL PY 2008 VL 35 IS 7 BP 623 EP 629 DI 10.1111/j.1600-0560.2007.00879.x PG 7 WC Dermatology; Pathology SC Dermatology; Pathology GA 311PY UT WOS:000256613300002 PM 18312436 ER PT J AU Baldassarri, M Margolis, HC Beniash, E AF Baldassarri, M. Margolis, H. C. Beniash, E. TI Compositional determinants of mechanical properties of enamel SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE dental enamel; fracture toughness; hardness; structure; hydroxyapatite ID HUMAN TEETH; TOOTH ENAMEL; PRISMATIC ENAMEL; ELASTIC-MODULUS; DENTIN; JUNCTION; INDENTATION; FRACTURE; TOUGHNESS; PROTEIN AB Dental enamel is comprised primarily of carbonated apatite, with less than 1% w/w organic matter and 4-5% w/w water. To determine the influence of each component on the microhardness and fracture toughness of rat incisor enamel, we mechanically tested specimens in which water and organic matrix were selectively removed. Tests were performed in mid-sagittal and transverse orientations to assess the effect of the structural organization on enamel micromechanical properties. While removal of organic matrix resulted in up to a 23% increase in microhardness, and as much as a 46% decrease in fracture toughness, water had a significantly lesser effect on these properties. Moreover, removal of organic matrix dramatically weakened the dentino-enamel junction (DEJ). Analysis of our data also showed that the structural organization of enamel affects its micromechanical properties. We anticipate that these findings will help guide the development of bio-inspired nanostructured materials for mineralized tissue repair and regeneration. C1 [Baldassarri, M.; Margolis, H. C.; Beniash, E.] Forsyth Inst, Dept Biomineralizat, Boston, MA USA. [Baldassarri, M.; Margolis, H. C.; Beniash, E.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. RP Beniash, E (reprint author), Univ Pittsburgh, Sch Dent Med, 589 Salk Hall,3501 Terrace St, Pittsburgh, PA 15261 USA. EM ebeniash@pitt.edu FU NIDCR NIH HHS [R01 DE016703-01A1, R56 DE016703, DE16703, R56 DE016376, R01 DE016703, DE016376, R01 DE016376] NR 26 TC 50 Z9 51 U1 4 U2 14 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUL PY 2008 VL 87 IS 7 BP 645 EP 649 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 317KT UT WOS:000257019800008 PM 18573984 ER PT J AU Bair-Merritt, MH Holmes, WC Holmes, JH Feinstein, J Feudtner, C AF Bair-Merritt, Megan H. Holmes, William C. Holmes, John H. Feinstein, Jamie Feudtner, Chris TI Does intimate partner violence epidemiology differ between homes with and without children? A population-based study of annual prevalence and associated risk factors SO JOURNAL OF FAMILY VIOLENCE LA English DT Article DE intimate partner violence; risk factors; children; prevalence ID DOMESTIC VIOLENCE; BEHAVIORS; WOMEN AB We sought to determine whether intimate partner violence (IPV) risk factors differed depending upon the presence of children in the home, and to estimate the annual prevalence of IPV first in the general population and then in homes with and without children. We analyzed data from a cross-sectional random sample of 6,836 women in southeastern Pennsylvania interviewed by telephone in 2004. The magnitude of association between IPV and risk factors varied between homes with and without children for women's alcohol problems (with children, odds ratio (OR) 7.7; 95% confidence interval (CI) 2.9, 20.9; without children, OR 2.4; 95% CI 0.9, 6.0), and mental health problems (with children, OR 4.0; 95% CI 1.8, 8.9; without children, OR 3.0; 95% CI 1.6, 5.7). Poverty was significantly associated with IPV only in homes without children (OR 3.6; 95% CI 1.9, 7.2). Annual IPV prevalence was 1.2% overall, 1.4% in homes with children, and 1.1% in homes without children. One in 63 children lived in a home with IPV. Differences in IPV risk factors in homes with and without children suggest distinct underlying IPV mechanisms or consequences in these contexts. C1 [Bair-Merritt, Megan H.] Johns Hopkins Univ, Sch Med, Div Gen Pediat & Adolescent Med, Baltimore, MD 21218 USA. [Holmes, William C.] Philadelphia Vet Adm Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. [Holmes, William C.; Holmes, John H.; Feudtner, Chris] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Holmes, William C.] Hosp Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Feudtner, Chris] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Bair-Merritt, Megan H.; Feinstein, Jamie; Feudtner, Chris] Childrens Hosp Philadelphia, Div Gen Pediat, Pediat Generalist Res Grp, Philadelphia, PA 19104 USA. RP Bair-Merritt, MH (reprint author), Johns Hopkins Univ, Sch Med, Div Gen Pediat & Adolescent Med, Baltimore, MD 21218 USA. EM mbairme1@jhmi.edu OI Bair-Merritt, Megan/0000-0002-1876-9817 NR 25 TC 14 Z9 14 U1 3 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7482 J9 J FAM VIOLENCE JI J. Fam. Violence PD JUL PY 2008 VL 23 IS 5 BP 325 EP 332 DI 10.1007/s10896-008-9154-y PG 8 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 296UM UT WOS:000255571300004 ER PT J AU Bowen, JL Cook, DA Gerrity, M Kalet, AL Kogan, JR Spickard, A Wayne, DB AF Bowen, Judith L. Cook, David A. Gerrity, Martha Kalet, Adina L. Kogan, Jennifer R. Spickard, Anderson Wayne, Diane B. TI Navigating the JGIM special issue on medical education SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material C1 [Bowen, Judith L.; Gerrity, Martha] Oregon Hlth & Sci Univ, Dept Med, Div Gen Internal Med & Geriatr, Portland VA Med Ctr, Portland, OR 97201 USA. [Cook, David A.] Mayo Clin, Coll Med, Off Educ Res, Div Gen Internal Med, Rochester, MN USA. [Wayne, Diane B.] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Spickard, Anderson] Vanderbilt Univ Sch Med, Dept Med & Biomed Informat, Nashville, TN USA. [Kogan, Jennifer R.] Univ Penn Hlth Syst, Div Gen Internal Med, Philadelphia, PA USA. [Kalet, Adina L.] NYU, Sch Med, Dept Med, Div Gen Internal Med,Div Educ Informat, New York, NY 10003 USA. RP Bowen, JL (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Gen Internal Med & Geriatr, Portland VA Med Ctr, Portland, OR 97201 USA. EM bowenj@ohsu.edu NR 44 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2008 VL 23 IS 7 BP 899 EP 902 DI 10.1007/s11606-008-0675-0 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 324AH UT WOS:000257489400001 PM 18612714 ER PT J AU Cook, DA Bowen, JL Gerrity, MS Kalet, AL Kogan, JR Spickard, A Wayne, DB AF Cook, David A. Bowen, Judith L. Gerrity, Martha S. Kalet, Adina L. Kogan, Jennifer R. Spickard, Anderson Wayne, Diane B. TI Proposed standards for medical education submissions to the journal of general internal medicine SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE medical education; scholarship; research design; research methods; writing ID HEALTH-SERVICES RESEARCH; QUALITATIVE RESEARCH; SYSTEMATIC REVIEWS; RANDOMIZED-TRIALS; OUTCOMES RESEARCH; USERS GUIDES; VALIDITY; STATEMENT; GUIDELINES; EPIDEMIOLOGY AB To help authors design rigorous studies and prepare clear and informative manuscripts, improve the transparency of editorial decisions, and raise the bar on educational scholarship, the Deputy Editors of the Journal of General Internal Medicine articulate standards for medical education submissions to the Journal. General standards include: (1) quality questions, (2) quality methods to match the questions, (3) insightful interpretation of findings, (4) transparent, unbiased reporting, and (5) attention to human subjects' protection and ethical research conduct. Additional standards for specific study types are described. We hope these proposed standards will generate discussion that will foster their continued evolution. C1 [Cook, David A.] Mayo Clin Coll Med, Div Gen Internal Med, Rochester, MN 55905 USA. [Cook, David A.] Mayo Clin Coll Med, Off Educ Res, Rochester, MN 55905 USA. [Bowen, Judith L.] Oregon Hlth & Sci Univ, Dept Med, Div Gen Internal Med & Geriatr, Portland, OR 97201 USA. [Gerrity, Martha S.] Oregon Hlth & Sci Univ, Dept Med, Portland VA Med Ctr, Portland, OR 97201 USA. [Kalet, Adina L.] NYU, Sch Med, Dept Med, Div Educ Informat, New York, NY USA. [Kalet, Adina L.] NYU, Sch Med, Dept Med, Div Gen Internal Med, New York, NY USA. [Kogan, Jennifer R.] Univ Penn Hlth Syst, Div Gen Internal Med, Philadelphia, PA USA. [Spickard, Anderson] Vanderbilt Univ Sch Med, Dept Med & Biomed Informat, Nashville, TN USA. [Wayne, Diane B.] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. RP Cook, DA (reprint author), Mayo Clin Coll Med, Off Educ Res, Baldwin 4-A,200 1st St SW, Rochester, MN 55905 USA. EM cook.david33@mayo.edu NR 79 TC 14 Z9 15 U1 4 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2008 VL 23 IS 7 BP 908 EP 913 DI 10.1007/s11606-008-0676-z PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 324AH UT WOS:000257489400003 PM 18612716 ER PT J AU Eckstrom, E Desai, SS Hunter, AJ Allen, E Tanner, CE Lucas, LM Joseph, CL Ririe, MR Doak, MN Humphrey, LL Bowen, JL AF Eckstrom, Elizabeth Desai, Sima S. Hunter, Alan J. Allen, Elizabeth Tanner, Craig E. Lucas, Linda M. Joseph, Carol L. Ririe, Marnie R. Doak, Melanie N. Humphrey, Linda L. Bowen, Judith L. TI Aiming to improve care of older adults: An innovative faculty development workshop SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE Continuing Medical Education workshop; geriatrics; standardized learners; Graduate Medical Education AB INTRODUCTION/AIMS: Internists care for older adults and teach geriatrics to trainees, but they often feel ill-prepared for these tasks. The aims of our 1-day Continuing Medical Education workshop were to improve the knowledge and self-perceived competence of general internists in their care of older adults and to increase their geriatrics teaching for learners. SETTING:Two internal medicine training programs encompassing University, Veterans Affairs, and a community-based hospital in Portland, OR, USA. PROGRAM DESCRIPTION:Course faculty identified gaps in assessment of cognition, function, and decisional capacity; managing care transitions; and treatment of behavioral symptoms. To address these gaps, our workshop provided geriatric content discussions followed by small group role plays to apply newly learned content. Forty teaching faculty participated. PROGRAM EVALUATION:Participants completed 13-item multiple-choice pre- and post-workshop geriatric knowledge tests, pre- and post-workshop surveys of self-perceived competence to care for older adults, and completed an open-ended 'commitment to change' prompt after the intervention. Knowledge scores improved following the intervention (61% to 72%, p < .0001), as did self-perceived competence (11 of 14 items significant). Seventy-one percent of participants reported success in meeting their commitment to change goals. DISCUSSION:A 1-day intervention improved teaching faculty knowledge and self-perceived competence to care for older patients and led to self-perceived changes in teaching behaviors. C1 [Eckstrom, Elizabeth; Desai, Sima S.; Hunter, Alan J.; Bowen, Judith L.] Oregon Hlth & Sci Univ, Dept Med, Div Gen Internal Med & Geriatr, Portland, OR 97239 USA. [Allen, Elizabeth; Lucas, Linda M.; Joseph, Carol L.; Doak, Melanie N.; Humphrey, Linda L.] Portland VA Med Ctr, Portland, OR USA. [Tanner, Craig E.] Univ Arizona, Coll Med, Tucson, AZ USA. [Ririe, Marnie R.] St Lukes Hlth Syst, Boise, ID USA. RP Eckstrom, E (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Gen Internal Med & Geriatr, L475,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM eckstrom@ohsu.edu NR 11 TC 4 Z9 4 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2008 VL 23 IS 7 BP 1053 EP 1056 DI 10.1007/s11606-008-0593-1 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 324AH UT WOS:000257489400031 PM 18612743 ER PT J AU Castiglioni, A Shewchuk, RM Willett, LL Heudebert, GR Centor, RM AF Castiglioni, Analia Shewchuk, Richard M. Willett, Lisa L. Heudebert, Gustavo R. Centor, Robert M. TI A pilot study using nominal group technique to assess residents' perceptions of successful attending rounds SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc Gen Internal Med DE attending physicians; interns; nominal group technique; residents; ward rounds ID WARD ROUNDS AB BACKGROUND: Ward attending rounds are fundamental for internal medicine residency training. An improved understanding of interns' and residents' perceptions of attending rounds should inform training programs and attending physicians. OBJECTIVES:The aim of this study was to assess residents' perceptions of successful attending rounds. DESIGN:We convened two groups of interns and two groups of residents, to elicit their perceptions on attending rounds. SUBJECTS: Participants were recruited by e-mail and conference announcements from the 49 interns and 80 residents in the internal medicine and medicine-pediatrics residency programs. MEASUREMENTS:The nominal group technique (NGT) uses a structured group process to elicit and prioritize answers to a carefully articulated question. MAIN RESULTS:Seven interns (14%) identified 27 success factors and ranked attending approachability and enthusiasm and high quality teaching as most important. A second group of six (12%) interns identified 40 detractors and ranked having "mean attendings," receiving disrespectful comments, and too long or too short rounds as the most significant detractors. Nine (11%) residents identified 32 success factors and ranked attention to length of rounds, house staff autonomy, and establishing goals/expectations as the most important success factors. A second group of six (8%) residents identified 34 detractors and ranked very long rounds, interruptions and time constraints, and poor rapport between team members as the most significant detractors). CONCLUSIONS:Although there was some overlap in interns' and residents' perceptions of attending rounds, interns identified interpersonal factors as the most important factors; whereas residents viewed structural factors as most important. These findings should assist attending physicians improve the way they conduct rounds targeting both interns and residents needs. C1 [Castiglioni, Analia; Willett, Lisa L.; Heudebert, Gustavo R.; Centor, Robert M.] Univ Alabama, Div Gen Internal Med, Birmingham, AL USA. [Shewchuk, Richard M.] Univ Alabama, Dept Hlth Serv Adm, Birmingham, AL USA. [Castiglioni, Analia; Heudebert, Gustavo R.; Centor, Robert M.] Birmingham VAMC, Birmingham, AL USA. RP Castiglioni, A (reprint author), Univ Alabama, Div Gen Internal Med, FOT 720,1530 3rd Ave, Birmingham, AL 35294 USA. EM acastigl@uab.edu NR 19 TC 27 Z9 27 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2008 VL 23 IS 7 BP 1060 EP 1065 DI 10.1007/s11606-008-0668-z PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 324AH UT WOS:000257489400033 PM 18612745 ER PT J AU Geller, AC Brooks, DR Powers, CA Brooks, KR Rigotti, NA Bognar, B McIntosh, S Zapka, J AF Geller, Alan C. Brooks, Daniel R. Powers, Catherine A. Brooks, Katie R. Rigotti, Nancy A. Bognar, Bryan McIntosh, Scott Zapka, Jane TI Tobacco cessation and prevention practices reported by second and fourth year students at US medical schools SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE tobacco; medical schools; medical students; curriculum; 5As; smoking cessation ID SMOKING-CESSATION; CARE SURVEY; CURRICULUM; PEDIATRICIANS; DEPENDENCE; PHYSICIANS; SKILLS; QUIT AB BACKGROUND: Tobacco dependence counseling is recommended to be included as core curriculum for US medical students. To date, there has been little information on students' self-reported skills and practice opportunities to provide 5A's (Ask, Advise, Assess, Assist, and Arrange) counseling for tobacco cessation. METHODS:We conducted anonymous surveys of second year and fourth year students at multiple US medical schools between February 2004 and March 2005 (overall response rate 70%). We report on the tobacco control practices of the 860 second year and 827 fourth year students completing the survey. MEASUREMENTS AND MAIN RESULTS:Fourth year students reported multiple opportunities to learn tobacco counseling in case-based discussions, simulated patient encounters, and clinical skills courses. They reported more instruction in family medicine (79%) and Internal Medicine (70%) than Pediatrics (54%), Obstetrics/Gynecology (41%), and Surgery clerkships (16%). Compared with asking patients about smoking, advising smokers to quit, and assessing patient willingness to quit, fourth year students were less likely to have multiple practice opportunities to assist the patient with a quit plan and arrange follow-up contact. More than half of second year students reported multiple opportunities for asking patients about smoking but far fewer opportunities for practicing the other 4 As. CONCLUSIONS:By the beginning of their fourth year, most students in this group of medical schools reported multiple opportunities for training and practicing basic 5A counseling, although clear deficits for assisting patients with a quit plan and arranging follow-up care exist. Addressing these deficits and integrating tobacco teaching through tailored specific instruction across all clerkships, particularly in Surgery, Pediatrics, and Obstetrics/Gynecology is a challenge for medical school education. C1 [Geller, Alan C.; Powers, Catherine A.; Brooks, Katie R.] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. [Geller, Alan C.; Brooks, Daniel R.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. [Rigotti, Nancy A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tobacco Res & Treatment Ctr, Boston, MA USA. [Bognar, Bryan] Univ S Florida, Dept Med, Tampa, FL USA. [McIntosh, Scott] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Zapka, Jane] Univ S Carolina, Sch Med, Columbia, SC USA. RP Geller, AC (reprint author), Boston Univ, Sch Med, Dept Dermatol, 720 Harrison Ave,DOB 801A, Boston, MA 02118 USA. EM ageller@bu.edu OI Brooks, Daniel/0000-0001-6220-6889 FU NCI NIH HHS [R25 CA091958, 1-R25-CA91958-05] NR 24 TC 22 Z9 23 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2008 VL 23 IS 7 BP 1071 EP 1076 DI 10.1007/s11606-008-0526-z PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 324AH UT WOS:000257489400035 PM 18612747 ER PT J AU Glasheen, JJ Siegal, EM Epstein, K Kutner, J Prochazka, AV AF Glasheen, Jeffrey J. Siegal, Eric M. Epstein, Kenneth Kutner, Jean Prochazka, Allan V. TI Fulfilling the promise of hospital medicine: Tailoring internal medicine training to address hospitalists' needs SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE medical education; hospitalist training; hospitalist; hospital medicine; residency redesign ID LENGTH-OF-STAY; CONTROLLED-TRIAL; HIP FRACTURE; CARE; PATIENT; SERVICE; COSTS; EXPERIENCE; OUTCOMES; SYSTEM AB Categorical internal medicine (IM) residency training has historically effectively prepared graduates to manage the medical needs of acutely ill adults. The development of the field of hospital medicine, however, has resulted in hospitalists filling clinical niches that have been traditionally ignored or underemphasized in categorical IM training. Furthermore, hospitalists are increasingly leading inpatient safety, quality and efficiency initiatives that require understanding of hospital systems, multidisciplinary care and inpatient quality assessment and performance improvement. Taken in this context, many graduating IM residents are under-prepared to practice as effective hospitalists. In this paper, we outline the rationale for targeted training in hospital medicine and discuss the content and methods for delivering this training. C1 [Glasheen, Jeffrey J.] Univ Colorado, Denver Sch Med, Internal Med Residency Training Program, Aurora, CO 80045 USA. [Glasheen, Jeffrey J.; Kutner, Jean] Univ Colorado, Denver Sch Med, Div Gen Internal Med, Dept Med, Aurora, CO 80045 USA. [Glasheen, Jeffrey J.] Univ Colorado, Denver Sch Med, Hosp Med Serv, Aurora, CO 80045 USA. [Siegal, Eric M.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Epstein, Kenneth] Univ Colorado, Denver Sch Med, IPC Hospitalist Co, Med Affairs & Clin Res, Aurora, CO 80045 USA. [Prochazka, Allan V.] Univ Colorado, Denver Sch Med, Denver VA Med Ctr, Aurora, CO 80045 USA. RP Glasheen, JJ (reprint author), Univ Colorado, Denver Sch Med, Hosp Med Serv, Mailstop F-782,12401 E 17th Ave,POB 6510, Aurora, CO 80045 USA. EM jeffrey.glasheen@uchsc.edu NR 37 TC 14 Z9 14 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2008 VL 23 IS 7 BP 1110 EP 1115 DI 10.1007/s11606-008-0646-5 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 324AH UT WOS:000257489400042 PM 18612754 ER PT J AU Haidet, P AF Haidet, Paul TI Where we're headed: A new wave of scholarship on educating medical professionalism SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE education, medical, physician's role; education, medical, undergraduate; education, medical, graduate; social environment, organizational culture; schools, medical; internship and residency; professional practice; ethics, professional; professional-patient relations; learning; teaching; psychology, educational C1 [Haidet, Paul] DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Haidet, Paul] Baylor Coll Med, Houston, TX 77030 USA. RP Haidet, P (reprint author), 2002 Holcombe Blvd,152, Houston, TX 77030 USA. EM phaidet@bcm.tmc.edu NR 11 TC 9 Z9 9 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2008 VL 23 IS 7 BP 1118 EP 1119 DI 10.1007/s11606-008-0670-5 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 324AH UT WOS:000257489400044 PM 18612756 ER PT J AU Lefkimmiatis, K Roy, J Srikanthan, M Moyer, MP Curci, S Hofer, AM AF Lefkimmiatis, Konstantinos Roy, Jessica Srikanthan, Meera Moyer, Mary Pat Curci, Silvana Hofer, Aldebaran M. TI Development of an intracellular cAMP "Sponge" SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-of-General-Physiologists CY SEP 03-07, 2008 CL Marine Biol Lab, Woods Hole, MA SP Soc Gen Physiol HO Marine Biol Lab C1 [Lefkimmiatis, Konstantinos; Roy, Jessica; Srikanthan, Meera; Curci, Silvana; Hofer, Aldebaran M.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, W Roxbury, MA 02132 USA. [Lefkimmiatis, Konstantinos; Roy, Jessica; Srikanthan, Meera; Curci, Silvana; Hofer, Aldebaran M.] Harvard Univ, Sch Med, Dept Surg, Brigham & Womens Hosp, W Roxbury, MA 02132 USA. [Moyer, Mary Pat] NCELL Corp LLC, San Antonio, TX 78249 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2008 VL 132 IS 1 MA 9 BP 6A EP 6A PG 1 WC Physiology SC Physiology GA 354JC UT WOS:000259634900014 ER PT J AU Lefkimmiatis, K Srikanthan, M Moyer, M Curci, S Hofer, AM AF Lefkimmiatis, Konstantinos Srikanthan, Meera Moyer, Marypat Curci, Silvana Hofer, Aldebaran M. TI Store-operated cyclic AMP signaling mediated by STIM1 and STIM2 SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-of-General-Physiologists CY SEP 03-07, 2008 CL Marine Biol Lab, Woods Hole, MA SP Soc Gen Physiol HO Marine Biol Lab C1 [Lefkimmiatis, Konstantinos; Srikanthan, Meera; Curci, Silvana; Hofer, Aldebaran M.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02132 USA. [Lefkimmiatis, Konstantinos; Srikanthan, Meera; Curci, Silvana; Hofer, Aldebaran M.] Harvard Univ, Sch Med, Dept Surg, Brigham & Womens Hosp, Boston, MA 02132 USA. [Moyer, Marypat] INCELL Corp LLC, San Antonio, TX 78249 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2008 VL 132 IS 1 MA 60 BP 26A EP 27A PG 2 WC Physiology SC Physiology GA 354JC UT WOS:000259634900064 ER PT J AU Lindenhovius, A Henket, M Gilligan, BP Lozano-Calderon, S Jupiter, JB Ring, D AF Lindenhovius, Anneluuk Henket, Marjolijn Gilligan, Brendan P. Lozano-Calderon, Santiago Jupiter, Jesse B. Ring, David TI Injection of dexamethasone versus placebo for lateral elbow pain: A prospective, double-blind, randomized clinical trial SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE depression; dexamethasone; injection; lateral elbow pain; placebo ID CHRONIC TENNIS ELBOW; SHOCK-WAVE THERAPY; LOCAL INJECTION; PRIMARY-CARE; CORTICOSTEROID INJECTIONS; CATASTROPHIZING SCALE; EPICONDYLITIS; ACUPUNCTURE; PHYSIOTHERAPY; DISABILITY AB Purpose We tested the hypthesis that there is no difference in disability, pain, and grip strength 1 and 6 months after corticosteroid and lidocaine injection compared with lidocaine injection alone (placebo) Methods Sixty-four patients were randomly assigned to dexamethasone (n = 3 1) or placebo (n = 33) injection. At enrollment, disability (Disabilities of the Arm, Shoulder, and Hand [DASH] questionnaire), pain on a visual analog scale, grip strength, depression (the Center for Epidemiologic Studies Depression Scale; CESD), and ineffective coping skills (the Pain Catastrophizing Scale; PCS) were comparable between treatment groups. At I and 6 months, DASH, pain, and grip strength measures were repeated. Univariate and multivariate analyses were used to determine predictors of disability. Analysis was by intention to treat. Results One month after injection, DASH scores averaged 24 versus 27 points (dexamethasone vs placebo), pain 3.7 versus 4.3 cm, and grip strength 83% versus 87%. At 6 months, DASH scores averaged 18 versus 13 points, pain 2.4 versus 1.7 cm, and grip strength 98% versus 97%. CESD and PCS scores correlated with disability as measured by the DASH questionnaire. The best multivariate models included CESD at I month and PCS scores at 6 months and explained the majority of variability in DASH scores. Conclusions Corticosteroid injection did not affect the apparently self-limited course of lateral elbow pain. In secondary analyses in a subset of patients, perceived disability associated with lateral elbow pain correlated with depression and ineffective coping skills. C1 [Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 50 TC 44 Z9 45 U1 1 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JUL-AUG PY 2008 VL 33A IS 6 BP 909 EP 919 DI 10.1016/j.jhsa.2008.02.004 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 337IU UT WOS:000258430600018 PM 18656765 ER PT J AU Lindenhovius, ALC Jupiter, JB Ring, D AF Lindenhovius, Anneluuk L. C. Jupiter, Jesse B. Ring, David TI Comparison of acute versus subacute treatment of terrible triad injuries of the elbow SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE coronoid; dislocation; elbow; fracture; lateral collateral ligament; operative treatment; radial head; terrible triad injury ID RADIAL HEAD; FRACTURE-DISLOCATIONS; INSTABILITY; ARTHROPLASTY AB Purpose To test the null hypothesis that there is no difference in flexion arc or Broberg and Morrey rating between patients treated within 2 weeks of the injury (acute treatment) and those treated 3 weeks or more after injury with persistent or recurrent dislocation or subluxation (subocute treatment). Methods The acute cohort consisted of 18 patients treated an average 6 days after injury. The radial head was replaced in 17 patients and repaired with screw in 1, the coronoid was secured with suture in all patients and with an additional screw in 2, and the lateral collateral ligament was reattached in all patients. No external fixators were applied. Four of 14 patients in the subacute cohort had 5 operative procedures before presenting to us. All patients presented with instability and were treated an average 7 weeks after injury. Except for I patient who presented with an active infection, all patients were treated with radial head replacement and lateral collateral ligament repair, and fixation or reconstruction of the coronoid occurred in 9 patients. Stability was protected with a hinged external fixator for an average of 6 weeks. Results Five patients in the acute cohort and I in the subacute cohort had 8 subsequent surgeries (addressing stiffness in 3 patients). Prior to subsequent surgeries, the flexion arc averaged 116 degrees in the acute cohort and 93 degrees in the subacute cohort and improved to an average 119 degrees in the acute cohort and 100 degrees in the subacute cohort after all subsequent surgeries. Broberg and Morrey scores were comparable between cohorts (90 vs 87 points). Conclusions Stability and strength were restored with both acute and subacute treatment, but earlier treatment is more straightforward and is associated with a better flexion arc. C1 [Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org FU Annafonds, Stichting Professor Michael van Vloten Fonds, Stichting Wetenschappelijk Onderzoek Orthopaedische Chirurgie, AO Foundation, Small Bone Innovations, Smith & Nephew Richards, Wright Medical, Joint Active Systems; Biomet (A.L.C.L.) FX Unrestricted research support were received from Annafonds, Stichting Professor Michael van Vloten Fonds, Stichting Wetenschappelijk Onderzoek Orthopaedische Chirurgie, AO Foundation, Small Bone Innovations, Smith & Nephew Richards, Wright Medical, Joint Active Systems, and Biomet (A.L.C.L.) NR 18 TC 28 Z9 36 U1 0 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JUL-AUG PY 2008 VL 33A IS 6 BP 920 EP 926 DI 10.1016/j.jhsa.2008.02.007 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 337IU UT WOS:000258430600019 PM 18656766 ER PT J AU Ring, D AF Ring, David TI An introduction SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Yawkey Ctr Outpatient Care, Hand & Upper Extrem Serv,Dept Orthopaed Surg, Boston, MA 02115 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Yawkey Ctr Outpatient Care, Hand & Upper Extrem Serv,Dept Orthopaed Surg, Boston, MA 02115 USA. 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JUL-AUG PY 2008 VL 33A IS 6 BP 952 EP 953 DI 10.1016/j.jhsa.2008.04.035 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 337IU UT WOS:000258430600024 ER PT J AU Ring, D Lozano-Calderon, S AF Ring, David Lozano-Calderon, Santiago TI Imaging for suspected scaphoid fracture SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Editorial Material ID COMPUTED-TOMOGRAPHY; COST-EFFECTIVENESS; RADIOGRAPHY; DIAGNOSIS C1 [Ring, David] Massachusetts Gen Hosp, Yawkey Ctr, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 14 TC 29 Z9 29 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JUL-AUG PY 2008 VL 33A IS 6 BP 954 EP 957 DI 10.1016/j.jhsa.2008.04.016 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 337IU UT WOS:000258430600025 PM 18656772 ER PT J AU Vranceanu, AM Ring, D AF Vranceanu, Ana-Maria Ring, David TI Value of psychological evaluation of the hand surgical patient SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Editorial Material ID CHRONIC PAIN; HYPOCHONDRIASIS; VALIDATION C1 [Ring, David] Massachusetts Gen Hosp, Behav Med Serv, Orthopaed Hand & Upper Extrem Serv, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Behav Med Serv, Orthopaed Hand & Upper Extrem Serv, Dept Orthopaed Surg, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 15 TC 9 Z9 9 U1 1 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JUL-AUG PY 2008 VL 33A IS 6 BP 985 EP 987 DI 10.1016/j.jhsa.2008.05.007 PG 3 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 337IU UT WOS:000258430600031 PM 18656778 ER PT J AU Vogt, DS Barry, AA King, LA AF Vogt, Dawne S. Barry, Amy A. King, Lynda A. TI Toward gender-aware health care - Evaluation of an intervention to enhance care for female patients in the VA setting SO JOURNAL OF HEALTH PSYCHOLOGY LA English DT Article DE female patients; gender awareness; health-care workers ID CLINICAL DECISION-MAKING; WOMEN VETERANS; SATISFACTION; SENSITIVITY; KNOWLEDGE; ATTITUDES; OUTCOMES; WORKERS; MEN AB In response to identified deficits in the provision of health care to female patients, we sought to improve health-care workers' gender awareness conceptualized as gender-role ideology, sensitivity, and knowledge related to female patients - through the application of a brief computerized educational intervention. This study, conducted in the Veterans Affairs (VA) health-care setting, involved a pretest - posttest equivalent control group design. We evaluated hypotheses using random coefficients regression, a technique that offers a number of advantages relative to repeated-measures ANOVA. Findings revealed significant improvements in sensitivity and knowledge for participants in the treatment condition compared to the control condition. With several exceptions, the intervention was similarly effective across employee groups. C1 [Vogt, Dawne S.] Natl Ctr PTSD, VA Boston Healthcare Syst, Womens Hlth Sci Div, Boston, MA 02130 USA. [Vogt, Dawne S.] Boston Univ, Sch Med, Boston, MA 02215 USA. [King, Lynda A.] Massachusetts Vet Epidemiol Res & Informat Ctr, VA Boston Healthcare Syst, Boston, MA USA. RP Vogt, DS (reprint author), Natl Ctr PTSD, VA Boston Healthcare Syst, Womens Hlth Sci Div, 116B-38,150 S Huntington Ave, Boston, MA 02130 USA. EM Dawne.Vogt@va.gov NR 50 TC 14 Z9 14 U1 3 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1359-1053 J9 J HEALTH PSYCHOL JI J. Health Psychol. PD JUL PY 2008 VL 13 IS 5 BP 624 EP 638 DI 10.1177/1359105308090934 PG 15 WC Psychology, Clinical SC Psychology GA 318TD UT WOS:000257114800005 PM 18519436 ER PT J AU Iezzoni, LI AF Iezzoni, Lisa I. TI Tracking disability disparities: the data dilemma SO JOURNAL OF HEALTH SERVICES RESEARCH & POLICY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St, Boston, MA 02114 USA. NR 9 TC 5 Z9 6 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 1355-8196 J9 J HEALTH SERV RES PO JI J. Health Serv. Res. Policy PD JUL PY 2008 VL 13 IS 3 BP 129 EP 130 DI 10.1258/jhsrp.2008.008034 PG 2 WC Health Policy & Services SC Health Care Sciences & Services GA 353JS UT WOS:000259563200001 PM 18573759 ER PT J AU Anderson, ML Glasheen, JJ AF Anderson, Mel L. Glasheen, Jeffrey J. TI Critical literature 2007: Clinical topics SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID CONTRAST-INDUCED NEPHROPATHY; RANDOMIZED CONTROLLED-TRIAL; SODIUM-BICARBONATE; HEART-FAILURE; N-ACETYLCYSTEINE; PREVENTION; METRONIDAZOLE; THERAPY; DISEASE C1 [Anderson, Mel L.] Denver VA Med Ctr, Dept Med, Med Serv, Denver, CO 80220 USA. [Glasheen, Jeffrey J.] Univ Colorado, Hosp Med Sect, Denver, CO 80202 USA. RP Anderson, ML (reprint author), Denver VA Med Ctr, Dept Med, Med Serv, 1055 Clermont St, Denver, CO 80220 USA. EM melver.anderson@va.gov NR 15 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD JUL-AUG PY 2008 VL 3 IS 4 BP 333 EP 341 DI 10.1002/jhm.345 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 339GW UT WOS:000258567100009 PM 18698593 ER PT J AU Conen, D Bamberg, F AF Conen, David Bamberg, Fabian TI Noninvasive 24-h ambulatory blood pressure and cardiovascular disease: a systematic review and meta-analysis SO JOURNAL OF HYPERTENSION LA English DT Article DE ambulatory; blood pressure; blood pressure monitoring; cardiovascular diseases; hypertension; meta-analysis ID WHITE-COAT HYPERTENSION; 10-YEAR FOLLOW-UP; PROGNOSTIC VALUE; OLDER PATIENTS; LONG-TERM; SYSTOLIC HYPERTENSION; MASKED HYPERTENSION; RISK; POPULATION; MORTALITY AB Objective We systematically assessed the evidence regarding the association between noninvasive 24-h systolic blood pressure and incident cardiovascular events. Methods We searched PubMed, EMBASE, and the Cochrane Library through April 2007. Studies that prospectively followed at least 100 individuals for at least 1 year, and that reported at least one effect estimate of interest were included. Two independent investigators abstracted information on study design, subject characteristics, blood pressure measurements, outcome assessment, effect estimates, and adjustment for potential confounders. Results We identified 20 eligible articles based on 15 independent cohort studies. The association between 24-h systolic blood pressure and a combined cardiovascular endpoint was assessed in nine cohort studies, including 9299 participants who were followed up to 11.1 years and had 881 outcome events. The summary hazard ratio (95% confidence interval) per 10-mmHg increase of 24-h systolic blood pressure was 1.27 (1.18-1.38) (P<0.001). Further adjustment for office blood pressure in four studies with 4975 participants and 499 outcome events provided a similar summary estimate [hazard ratio (95% confidence interval) per 10-mmHg increase of 24-systolic blood pressure 1.21 (1.10-1.33) (P<0.001)]. Office blood pressure was usually assessed on a single occasion. We found no significant variability according to age, sex, population origin, baseline office blood pressure, follow-up time, diabetes, or study quality. There was a consistent association between 24-h systolic blood pressure and stroke, cardiovascular mortality, total mortality, and cardiac events with hazard ratio (95% confidence interval) per 10mmHg increase of 24-h systolic blood pressure of 1.33 (1.22-1.44), 1.19 (1.13-1.26), 1.12 (1.07-1.17), and 1.17 (1.09-1.25), respectively. Conclusion 24-h systolic blood pressure is a strong predictor of cardiovascular events, providing prognostic information independent of conventional office blood pressure. C1 [Conen, David] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02215 USA. [Bamberg, Fabian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Cardiac MR PET CT Program, Boston, MA 02215 USA. RP Conen, D (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM conend@uhbs.ch NR 47 TC 76 Z9 80 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JUL PY 2008 VL 26 IS 7 BP 1290 EP 1299 DI 10.1097/HJH.0b013e3282f97854 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 322PJ UT WOS:000257387500003 PM 18550999 ER PT J AU Fehr, T Haspot, F Mollov, J Chittenden, M Hogan, T Sykes, M AF Fehr, Thomas Haspot, Fabienne Mollov, Joshua Chittenden, Meredith Hogan, Timothy Sykes, Megan TI Alloreactive CD8 T cell tolerance requires recipient B cells, dendritic cells, and MHC class III SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; IN-VIVO; REGULATORY-CELLS; COSTIMULATORY BLOCKADE; ANTIGEN PRESENTATION; INDIRECT RECOGNITION; MIXED CHIMERISM; CUTTING EDGE; ANTIBODY; EXPRESSION AB Allogeneic bone marrow chimerism induces robust systemic tolerance to donor alloantigens. Achievement of chimerism requires avoidance of marrow rejection by pre-existing CD4 and CD8 T cells, either of which can reject fully MHC-mismatched marrow. Both barriers are overcome with a minimal regimen involving anti-CD154 and low dose (3 Gy) total body irradiation, allowing achievement of mixed chimerism and tolerance in mice. CD4 cells are required to prevent marrow rejection by CD8 cells via a novel pathway, wherein recipient CD4 cells interacting with recipient class II MHC tolerize directly alloreactive CD8 cells. We demonstrate a critical role for recipient MHC class II, B cells, and dendritic cells in a pathway culminating in deletional tolerance of peripheral alloreactive CD8 cells. C1 [Fehr, Thomas; Haspot, Fabienne; Mollov, Joshua; Chittenden, Meredith; Hogan, Timothy; Sykes, Megan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. EM megan.sykes@tbrc.mgh.harvard.edu FU NHLBI NIH HHS [P01 HL018646, R01 HL049915-14, P01 HL018646-280014, R01 HL049915-13A1, P01 HL018646-300014, R01 HL049915, P01 HL018646-290014, R01 HL049915-15] NR 47 TC 25 Z9 27 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 JUL 1 PY 2008 VL 181 IS 1 BP 165 EP 173 PG 9 WC Immunology SC Immunology GA 322WB UT WOS:000257404900021 PM 18566381 ER PT J AU Vasir, B Wu, ZK Crawford, K Rosenblatt, J Zarwan, C Bissonnette, A Kufe, D Avigan, D AF Vasir, Baldev Wu, Zekui Crawford, Keith Rosenblatt, Jacalyn Zarwan, Corrine Bissonnette, Adam Kufe, Donald Avigan, David TI Fusions of dendritic cells with breast carcinoma stimulate the expansion of regulatory T cells while concomitant exposure to IL-12, CpG oligodeoxynucleotides, and anti-CD3/CD28 promotes the expansion of activated tumor reactive cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID KAPPA-B ACTIVATION; KINASE-C-THETA; PHASE-I TRIAL; ANTITUMOR IMMUNITY; CD3/CD28 COSTIMULATION; CANCER-IMMUNOTHERAPY; ANTIGEN PRESENTATION; CLINICAL-RESPONSES; MULTIPLE-MYELOMA; PERIPHERAL-BLOOD AB Vaccination of patients with dendritic cell (DC)/breast carcinoma fusions stimulated antitumor immune responses in a majority of patients with metastatic disease but only a subset demonstrate evidence of tumor regression. To define the factors that limit vaccine efficacy, we examined the biological characteristics of DC/breast carcinoma fusions as APCs and the nature of the vaccine-mediated T cell response. We demonstrate that fusion of DCs with breast carcinoma cells up-regulates expression of costimulatory and maturation markers and results in high levels of expression of IL-12 consistent with their role as activated APCs. Fusion cells also express the chemokine receptor CCR7, consistent with their ability to migrate to the draining lymph node. However, DC/breast cancer fusions stimulate a mixed T cell response characterized by the expansion of both activated and regulatory T cell populations, the latter of which is characterized by expression of CTLA-4, FOXP3, IL-10, and the suppression of T cell responses. Our results demonstrate that IL-12, IL-18, and TLR 9 agonist CpG oligodeoxynucleotides reduce the level of fusion-mediated regulatory T cell expansion. Our results also demonstrate that sequential stimulation with DC[breast carcinoma fusions and anti-CD3/CD28 results in the marked expansion of activated tumor-specific T cells. These findings suggest that DC[breast carcinoma fusions are effective APCs, but stimulate inhibitory T cells that limit vaccine efficacy. In contrast, exposure to TLR agonists, stimulatory cytokines, and anti-CD3/CD28 enhances vaccine efficacy by limiting the regulatory T cell response and promoting expansion of activated effector cells. C1 [Avigan, David] Beth Israel Deaconess Med Ctr, Hematol Malignancy Bone Marrow Transplant Program, Boston, MA 02115 USA. [Vasir, Baldev; Wu, Zekui; Bissonnette, Adam; Kufe, Donald] Dana Farber Harvard Canc Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. [Crawford, Keith] Brigham & Womens Hosp, Ctr Mol Orthopaed, Boston, MA 02115 USA. RP Avigan, D (reprint author), Beth Israel Deaconess Med Ctr, Hematol Malignancy Bone Marrow Transplant Program, 330 Brookline Ave,KS-135, Boston, MA 02115 USA. EM davigan@bidmc.harvard.edu FU NCI NIH HHS [P50 CA105009, P50 CA105009-040005, P50CA105009-04] NR 67 TC 33 Z9 38 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2008 VL 181 IS 1 BP 808 EP 821 PG 14 WC Immunology SC Immunology GA 322WB UT WOS:000257404900087 PM 18566447 ER PT J AU Bosque, PJ Tyler, KL AF Bosque, P. J. Tyler, K. L. TI Prions' travels - Feces and transmission of prion diseases SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID INFECTION; SCRAPIE; BLOOD; EXCRETION; HAMSTERS; DEER C1 [Bosque, P. J.; Tyler, K. L.] Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. [Tyler, K. L.] Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. [Tyler, K. L.] Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA. [Bosque, P. J.] Denver Hlth Med Ctr, Dept Med Neurol, Denver, CO USA. [Tyler, K. L.] Denver Vet Affairs Med Ctr, Neurol Serv, Denver, CO USA. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol, 4200 E 9th Ave, Denver, CO 80262 USA. EM ken.tyler@uchsc.edu OI Tyler, Kenneth/0000-0003-3294-5888 NR 13 TC 1 Z9 1 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JUL 1 PY 2008 VL 198 IS 1 BP 8 EP 9 DI 10.1086/588194 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 311XD UT WOS:000256632800004 PM 18505382 ER PT J AU Catano, G Agan, BK Kulkarni, H Telles, V Marconi, VC Dolan, MJ Ahuja, SK AF Catano, Gabriel Agan, Brian K. Kulkarni, Hemant Telles, Vanessa Marconi, Vincent C. Dolan, Matthew J. Ahuja, Sunil K. TI Independent effects of genetic variations in mannose-binding lectin influence the course of HIV disease: The advantage of heterozygosity for coding mutations SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Experimental Biology 2004 Annual Meeting CY APR 17-21, 2004 CL Washington, DC ID HUMAN-IMMUNODEFICIENCY-VIRUS; DELAYED-TYPE HYPERSENSITIVITY; COMPLEMENT ACTIVATION; TYPE-1 INFECTION; PROTEIN GENE; ANTITUMOR-ACTIVITY; AIDS PROGRESSION; MODIFIER GENES; VIRAL-LOAD; IN-VITRO AB Background. The in vivo impact of mannose-binding lectin (MBL), a molecule involved in innate immunity, on the pathogenesis of human immunodeficiency virus (HIV)-1 infection and AIDS is unknown. Methods. A total of 1102 HIV-positive and 2213 HIV-negative adult subjects were screened for polymorphisms in the coding and promoter regions of MBL2, the gene that encodes MBL. Results. Variations in MBL2 did not influence the risk of acquiring HIV-1. Heterozygosity for coding mutations (O allele) and homozygosity for the-221 promoter polymorphism (X allele) in MBL2 were associated with a delay in and an accelerated rate of disease progression, respectively. MBL2 variations influenced the rate of progression to AIDS-defining illnesses. In a multivariate model, the effects of MBL2 variations were independent of several parameters known to influence disease progression, including steady-state viral load, baseline CD4(+) T cell counts, and delayed-type hypersensitivity skin test responses, an in vivo marker of cell-mediated immunity. The effects of MBL2 variations were most evident in those who possessed protective genotypes of CCR5 and a high copy number of CCL3L1, the most potent HIV-suppressive CCR5 ligand. Conclusions. MBL2 genotypes are independent determinants of HIV disease progression and heterozygosity for MBL2 coding mutations confer disease-retarding effects. MBL-dependent immune responses may play a role in the pathogenesis of HIV infection. C1 [Catano, Gabriel; Kulkarni, Hemant; Telles, Vanessa; Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Vet Administrat Res Ctr AIDS & HIV 1 Infect, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Catano, Gabriel; Kulkarni, Hemant; Telles, Vanessa; Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol, San Antonio, TX 78229 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Immunol, San Antonio, TX 78229 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Agan, Brian K.; Marconi, Vincent C.; Dolan, Matthew J.] Wilford Hall USAF Med Ctr, Infect Dis Serv, Lackland AFB, TX 78236 USA. [Agan, Brian K.; Dolan, Matthew J.] Wilford Hall USAF Med Ctr, Henry M Jackson Fdn, Lackland AFB, TX 78236 USA. [Agan, Brian K.; Marconi, Vincent C.; Dolan, Matthew J.] San Antonio Mil Med Ctr, San Antonio, TX USA. [Catano, Gabriel; Marconi, Vincent C.; Dolan, Matthew J.] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD USA. RP Ahuja, SK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, VA HIV AIDS Ctr, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM mdolan@idcrp.org; ahujas@uthscsa.edu RI Marconi, Vincent/N-3210-2014; OI Marconi, Vincent/0000-0001-8409-4689; Agan, Brian/0000-0002-5114-1669 FU NIAID NIH HHS [R01 AI043279, HU0001-05-2-0011, R37 AI046326]; NIMH NIH HHS [R01 MH069270] NR 48 TC 28 Z9 31 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JUL 1 PY 2008 VL 198 IS 1 BP 72 EP 80 DI 10.1086/588712 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 311XD UT WOS:000256632800014 PM 18498240 ER PT J AU Antonini, D Dentice, M Mahtani, P De Rosa, L Della Gatta, G Mandinova, A Salvatore, D Stupka, E Missero, C AF Antonini, Dario Dentice, Monica Mahtani, Parvesh De Rosa, Laura Della Gatta, Giusy Mandinova, Anna Salvatore, Domenico Stupka, Elia Missero, Caterina TI Tprg, a gene predominantly expressed in skin, is a direct target of the transcription factor p63 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID P53 FAMILY-MEMBERS; INDUCED APOPTOSIS; DOWN-REGULATION; SAM DOMAIN; STEM-CELLS; DIFFERENTIATION; DELTA-NP63-ALPHA; KERATINOCYTES; BINDING; P73 AB p63 and p73 are highly homologous members of the p53 family that originated by gene duplication at the invertebrate-to-vertebrate transition. We characterize here a previously unreported gene, Transformation-related protein 63 regulated (Tprg), located upstream of the p63 gene in the vertebrate genome, with striking similarity to Transformation related protein 63 regulated like (Tprgl), an uncharacterized gene located upstream of p73, suggesting that p63/Tprg and p73/Tprgl are embedded in a paralogue region originated from a single duplication event. Tprg is predominantly expressed in the epithelial compartment of the skin, more abundantly in differentiated cells. Consistent with its relative higher expression in differentiated keratinocytes, finely tuned p63 expression levels are required for optimal Tprg expression in primary keratinocytes. p63 is essential for Tprg expression as shown in p63-knockdown keratinocytes; however, high levels of p63 result in Tprg down-regulation. p63 directly binds in vivo to a canonical p63-binding site in an evolutionary conserved genomic region located in Tprg intron 4. This genomic region is sufficient to function as a p63-inducible enhancer in promoter studies. Thus, we demonstrate that the Tprg gene is predominantly expressed in skin, is physically associated with the p63 gene during evolution, and directly regulated by p63 through a long-distance enhancer located within the Tprg locus. C1 [Stupka, Elia] CBM Scrl, Trieste, Italy. [Antonini, Dario; De Rosa, Laura; Missero, Caterina] CEINGE Biotecnol Avanzate, Naples, Italy. [Dentice, Monica; Salvatore, Domenico] Univ Naples Federico 2, Dept Mol & Clin Endocrinol & Oncol, Naples, Italy. [Mahtani, Parvesh] Natl Univ Singapore, Sch Biol Sci, Singapore, Singapore. [Della Gatta, Giusy] Telethon Inst Genet & Med, Naples, Italy. [Mandinova, Anna] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Mandinova, Anna] Harvard Univ, Sch Med, Charlestown, MA USA. RP Stupka, E (reprint author), CBM Scrl, C-O AREA Sci Pk,Basovizza,SS 14 Km,163,5, Trieste, Italy. EM elia.stupka@cbm.fvg.it; missero@ceinge.unina.it RI Stupka, Elia/J-6279-2012; Salvatore, Domenico/D-4881-2013; De Rosa, Laura/H-7504-2015; OI De Rosa, Laura/0000-0001-9020-8451; Missero, Caterina/0000-0003-0905-5123; Stupka, Elia/0000-0003-3154-4011; SALVATORE, DOMENICO/0000-0002-4556-7620 FU NIAMS NIH HHS [AR-01-004]; Telethon [GGP06243] NR 45 TC 10 Z9 10 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2008 VL 128 IS 7 BP 1676 EP 1685 DI 10.1038/jid.2008.12 PG 10 WC Dermatology SC Dermatology GA 312HM UT WOS:000256659900012 PM 18256694 ER PT J AU Cuadrado, E Ortega, L Hernandez-Guillamon, M Penalba, A Fernandez-Cadenas, I Rosell, A Montaner, J AF Cuadrado, Eloy Ortega, Laura Hernandez-Guillamon, Mar Penalba, Anna Fernandez-Cadenas, Israel Rosell, Anna Montaner, Joan TI Tissue plasminogen activator (t-PA) promotes neutrophil degranulation and MMP-9 release SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE stroke; hemorrhage; TIRF; TIMP-2; plasmin ID FOCAL CEREBRAL-ISCHEMIA; MATRIX-METALLOPROTEINASE EXPRESSION; HEMORRHAGIC TRANSFORMATION; CARDIOEMBOLIC STROKE; MATRIX-METALLOPROTEINASE-9; LEUKOCYTE; GRANULES; BRAIN; THROMBOLYSIS; ENDOTOXIN AB Recombinant tissue plasminogen activator (t-PA), the only approved stroke treatment, is used for clot lysis within the occluded brain artery. Unfortunately, matrix metalloproteinase-9 (MMP-9) concentration increases after t-PA treatment and has been related to hemorrhagic transformation after ischemic stroke. Although the exact cellular source of brain MMP-9 remains unknown, invading, inflammatory cells, such as neutrophils, release MMP-9 to cross the blood brain barrier. Therefore, we hypothesize that the most feared side effect of stroke reperfusion therapy, brain hemorrhage, is related to t-PA-induced MMP-9 release by neutrophils. We show by means of ELISA that t-PA treatment promotes MMP-9, MMP-8, and tissue inhibitor metalloproteinase-2 release from human neutrophils ex vivo within 10 and 30 min. Moreover, by zymography and Western blot, we observed that neutrophils are emptied of MMP-9 content after t-PA treatment at those times. Finally, total internal reflection fluorescent imaging allowed us to observe the t-PA effect on neutrophils, showing the promotion of degranulation on these cells in vivo. Our data suggest that neutrophils are good candidates to be the main source of MMP-9 following t-PA stroke treatment and in consequence, partially responsible for thrombolysis-related brain bleedings. C1 [Cuadrado, Eloy; Ortega, Laura; Hernandez-Guillamon, Mar; Penalba, Anna; Fernandez-Cadenas, Israel; Rosell, Anna; Montaner, Joan] Univ Autonoma Barcelona, Hosp Vall Hebron, Neurovasc Unit,Dept Neurol, Neurovasc Res Lab,Inst Recerca, Barcelona 08035, Spain. [Rosell, Anna] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Boston, MA 02114 USA. [Rosell, Anna] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Montaner, J (reprint author), Univ Autonoma Barcelona, Hosp Vall Hebron, Neurovasc Unit,Dept Neurol, Neurovasc Res Lab,Inst Recerca, Pg Vall Hebron 119-129, Barcelona 08035, Spain. EM 31862jmv@comb.es RI Montaner, Joan/D-3063-2015; IBIS, NEUROVASCULAR/O-1855-2015 NR 37 TC 62 Z9 66 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUL 1 PY 2008 VL 84 IS 1 BP 207 EP 214 DI 10.1189/jlb.0907606 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 331NZ UT WOS:000258020200020 PM 18390930 ER PT J AU Surkan, PJ Steineck, G Kreicbergs, U AF Surkan, P. J. Steineck, G. Kreicbergs, U. TI Perceptions of a mental health questionnaire: the ethics of using population-based controls SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID DEPRESSION; ANXIETY AB Mental health surveys are used extensively in epidemiological research worldwide. The ethical questions that arise regarding their risk of causing psychological distress or other potential harm have not been studied in the general population. We have investigated how study participants serving as controls in a population-based study perceived an anonymous postal questionnaire focusing on mental health and wellbeing. Parents were contacted from the Swedish Census Bureau as part of a larger follow-up study on palliative care conducted in 2001. Eligible parents had a child of the same gender, year of birth and were from the same counties in Sweden as parents who had lost a child to cancer. Five percent reported being negatively affected. The principle negative effect on participants was that self-reflection reminded them of their difficulties. Of the 418 respondents, 52% reported that they were positively affected by study participation and 95% perceived the inquiry as valuable. These findings support the use of population-based controls in future research. C1 [Surkan, P. J.] Harvard Univ, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Landmark Ctr,Dept Environm Hlth, Boston, MA 02215 USA. [Surkan, P. J.; Steineck, G.; Kreicbergs, U.] Karolinska Inst, Dept Pathol & Oncol, Stockholm, Sweden. [Steineck, G.] Sahlgrens Univ Hosp, Sahlgrenska Acad, Div Clin Canc Epidemiol, Dept Oncol, Gothenburg, Sweden. [Kreicbergs, U.] Karolinska Inst, Dept Woman & Child Hlth, Childhood Canc Res Unit, Stockholm, Sweden. [Kreicbergs, U.] Dana Farber Canc Inst, Phyllis F Cantor Ctr, Boston, MA 02115 USA. RP Surkan, PJ (reprint author), Harvard Univ, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Landmark Ctr,Dept Environm Hlth, 401 Pk Dr,4th Floor W,Rm 415, Boston, MA 02215 USA. EM psurkan@hsph.harvard.edu OI Steineck, Gunnar/0000-0002-0787-3969 NR 11 TC 3 Z9 3 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD JUL PY 2008 VL 34 IS 7 AR 545 DI 10.1136/jme.2007.022418 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 321FC UT WOS:000257289100009 PM 18591291 ER PT J AU Adonizio, A Leal, SM Ausubel, FM Mathee, K AF Adonizio, Allison Leal, Sixto M., Jr. Ausubel, Frederick M. Mathee, Kalai TI Attenuation of Pseudomonas aeruginosa virulence by medicinal plants in a Caenorhabditis elegans model system SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID QUORUM; PATHOGENESIS; INFECTIONS; EXPRESSION; RESISTANCE; PAO1; INHIBITION; REGULATORS; BIOFILMS; FLORIDA AB Expression of a myriad of virulence factors and innate antibiotic resistance enables the opportunistic human pathogen Pseudomonas aeruginosa to create intractable infections. Using a nematode model, we screened for novel inhibitors of this pathogen. Aqueous extracts of three plants, Conocarpus erectus, Callistemon viminalis and Bucida buceras, were examined for their effects on P. aeruginosa killing of the nematode Caenorhabditis elegans. The results were evaluated in toxin-based and infection-based assays using P. aeruginosa strains PAO1 and PA14. The tested plant extracts prevented mortality via gut infection in approximately 60% of the worms and caused a 50-90% reduction in death from toxin production. All extracts inhibited nematode death by P. aeruginosa without host toxicity, indicating their potential for further development as anti-infectives. C1 [Adonizio, Allison; Leal, Sixto M., Jr.; Mathee, Kalai] Florida Int Univ, Dept Biol Sci, Coll Arts & Sci, Miami, FL 33199 USA. [Mathee, Kalai] Florida Int Univ, Dept Mol Microbiol & Immunol, Coll Med, Miami, FL 33199 USA. [Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Mathee, K (reprint author), Florida Int Univ, Dept Biol Sci, Coll Arts & Sci, Miami, FL 33199 USA. EM Kalai.Mathee@fiu.edu RI Schwermer, Carsten /B-1274-2010 FU NCCIH NIH HHS [1R15 AT 002626-01, 1T32 AT 01060-01]; NIAID NIH HHS [R01 AI064332, R01 AI 064332, R01 AI 072508, R01 AI072508]; NIGMS NIH HHS [R25 GM 61347] NR 37 TC 27 Z9 29 U1 1 U2 5 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-2615 J9 J MED MICROBIOL JI J. Med. Microbiol. PD JUL PY 2008 VL 57 IS 7 BP 809 EP 813 DI 10.1099/jmm.0.47802-0 PG 5 WC Microbiology SC Microbiology GA 324LM UT WOS:000257520100003 PM 18566137 ER PT J AU Iafrate, AJ Louis, DN AF Iafrate, A. John Louis, David N. TI "MGMT for pt mgmt": Is methylguanine-DNA methyltransferase testing ready for patient management? SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Editorial Material ID ISLAND METHYLATOR PHENOTYPE; PROMOTER HYPERMETHYLATION; COLORECTAL-CANCER; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; MICROSATELLITE INSTABILITY; GLIOBLASTOMA-MULTIFORME; GLIOMA; TEMOZOLOMIDE; SPECIMENS; MUTATION C1 Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Louis, DN (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Dept Pathol, 55 Fruit St,Warren 225, Boston, MA 02114 USA. EM dlouis@partners.org.zemailx NR 27 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD JUL PY 2008 VL 10 IS 4 BP 308 EP 310 DI 10.2353/jmoldx.2008.080043 PG 3 WC Pathology SC Pathology GA 320VE UT WOS:000257262400004 PM 18556768 ER PT J AU Franko, DL Dorer, DJ Keel, PK Jackson, S Manzo, MP Herzog, DB AF Franko, Debra L. Dorer, David J. Keel, Pamela K. Jackson, Safia Manzo, Mary Pat Herzog, David B. TI Interactions between eating disorders and drug abuse SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE eating disorder; comorbidity; drug abuse; longitudinal; alcohol abuse ID BULIMIA-NERVOSA; SUBSTANCE USE; FOLLOW-UP; ANOREXIA-NERVOSA; COMORBIDITY; ALCOHOL; PERSONALITY; WOMEN; ASSOCIATIONS; RELIABILITY AB To examine the relationship between drug abuse and eating disorders in a longitudinal sample. In a prospective study, women diagnosed with either DSM-IV anorexia nervosa (n = 136) or bulimia nervosa (n = 110) were interviewed and assessed for research diagnostic criteria drug use disorder (DUD) every 6-12 months over 8.6 years. Contrary to expectation, DUD did not influence recovery from either eating disorder. Multivariate analyses indicated that alcohol use and suicide attempts over the course of the study, as well as hospitalization for an affective disorder before the study, predicted DUD in anorexia nervosa. For bulimia nervosa, multivariate predictors included the severity of alcohol use and the severity of bulimic symptoms over the course of the study, and a hospitalization before study entry for a nonaffective disorder. Drug abuse in women with eating disorders is an area of clinical concern and should be monitored routinely. C1 [Franko, Debra L.] Massachusetts Gen Hosp, Dept Psychiat, Harris Ctr Eating Disorders, Boston, MA 02114 USA. [Franko, Debra L.] Northeastern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. [Keel, Pamela K.] Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. RP Franko, DL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Harris Ctr Eating Disorders, YAW6900,15 Parkman St, Boston, MA 02114 USA. EM d.franko@neu.edu NR 41 TC 12 Z9 13 U1 4 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JUL PY 2008 VL 196 IS 7 BP 556 EP 561 DI 10.1097/NMD.0b013e31817d0153 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 327JF UT WOS:000257724700006 PM 18626296 ER PT J AU Nicholas, AP Lubin, FD Hallett, PJ Vattem, P Ravenscroft, P Bezard, E Zhou, S Fox, SH Brotchie, JM Sweatt, JD Standaert, DG AF Nicholas, A. P. Lubin, F. D. Hallett, P. J. Vattem, P. Ravenscroft, P. Bezard, E. Zhou, S. Fox, S. H. Brotchie, J. M. Sweatt, J. D. Standaert, D. G. TI Striatal histone modifications in models of levodopa-induced dyskinesia SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE acetylation; dyskinesia; epigenetics; histone deacetylase inhibitors; macaque; Parkinson's disease ID DOPA-INDUCED DYSKINESIA; PARKINSONS-DISEASE; MEMORY FORMATION; DEACETYLASE INHIBITORS; EPIGENETIC MECHANISMS; SUBTHALAMIC NUCLEUS; SUBSTANTIA-NIGRA; GLOBUS-PALLIDUS; FOSB EXPRESSION; ALPHA-SYNUCLEIN AB Despite recent advances in the treatment of Parkinson disease (PD), levodopa remains the most effective and widely used therapy. A major limitation to the use of levodopa is the development of abnormal involuntary movements, termed levodopa-induced dyskinesia (LDID), following chronic levodopa treatment. Since recent studies have suggested that modifications of chromatin structure may be responsible for many long-lasting changes in brain function, we have examined post-translational modifications of striatal histones in two models of LDID: an acute murine model and a chronic macaque monkey model, both exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the primate model, which closely resembles human LDID, we observed that chronic levodopa and the appearance of LDID was associated with marked deacetylation of histone H4, hyperacetylation and dephosphorylation of histone H3, and enhancement of the phosphorylation of extracellular signal-regulated kinase (ERK). In the murine model of acutely rather than chronically induced LDID, dopamine depletion and levodopa treatment also induced deacetylation of histone H4 and phosphorylation of ERK, but histone H3 exhibited decreased trimethylation and reduced rather than enhanced acetylation. These data demonstrate striking changes in striatal histones associated with the induction of LDID in both animal models. The pattern of changes observed, as well as the behavioral features, differed in the two models. However, both models exhibit marked deacetylation of histone H4, suggesting that inhibitors of H4 deacetylation may be useful in preventing or reversing LDID. C1 [Nicholas, A. P.; Vattem, P.; Standaert, D. G.] Univ Alabama, Ctr Neurodegenerat & Expt Therapeut, Dept Neurol, Birmingham, AL 35294 USA. [Nicholas, A. P.] Birmingham VA Med Ctr, Birmingham, AL USA. [Lubin, F. D.; Sweatt, J. D.] Univ Alabama, Dept Neurobiol, Birmingham, AL USA. [Hallett, P. J.] Massachusetts Gen Hosp, Mass Gen Inst Neurodegenerat Dis, Charlestown, MA USA. [Hallett, P. J.] Harvard Univ, Sch Med, Charlestown, MA USA. [Ravenscroft, P.; Zhou, S.] Univ Manchester, Sch Biol Sci, Manchester, Lancs, England. [Bezard, E.] Univ Victor Segalen Bordeaux 2, CNRS, Bordeaux Inst Neurosci, UMR 5227, Bordeaux, France. [Fox, S. H.; Brotchie, J. M.] Toronto Western Hosp, Toronto Western Res Inst, Toronto, ON M5T 2S8, Canada. RP Nicholas, AP (reprint author), Univ Alabama, Ctr Neurodegenerat & Expt Therapeut, Dept Neurol, SC 360G2,1530 3rd Ave S, Birmingham, AL 35294 USA. EM nicholas@uab.edu OI zhou, shaobo/0000-0001-5214-2973; Hallett, Penelope/0000-0002-8858-9096; Bezard, Erwan/0000-0002-0410-4638; Sweatt, J. David/0000-0003-3567-485X; Standaert, David/0000-0003-2921-8348 NR 50 TC 38 Z9 38 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2008 VL 106 IS 1 BP 486 EP 494 DI 10.1111/j.1471-4159.2008.05417.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 313CL UT WOS:000256718600041 PM 18410512 ER PT J AU Kahn, I Andrews-Hanna, JR Vincent, JL Snyder, AZ Buckner, RL AF Kahn, Itamar Andrews-Hanna, Jessica R. Vincent, Justin L. Snyder, Abraham Z. Buckner, Randy L. TI Distinct cortical anatomy linked to subregions of the medial temporal lobe revealed by intrinsic functional connectivity SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID HUMAN BRAIN; CEREBRAL-CORTEX; PARAHIPPOCAMPAL CORTICES; AUTOBIOGRAPHICAL MEMORY; EPISODIC MEMORY; MACAQUE MONKEY; BASE-LINE; FMRI; FLUCTUATIONS; RETRIEVAL AB The hippocampus and adjacent cortical structures in the medial temporal lobe (MTL) contribute to memory through interactions with distributed brain areas. Studies of monkey and rodent anatomy suggest that parallel pathways converge on distinct subregions of the MTL. To explore the cortical areas linked to subregions of the MTL in humans, we examined cortico-cortical and hippocampal-cortical correlations using high-resolution, functional connectivity analysis in 100 individuals. MTL seed regions extended along the anterior to posterior axis and included hippocampus and adjacent structures. Results revealed two separate brain pathways that correlated with distinct subregions within the MTL. The body of the hippocampus and posterior parahippocampal cortex correlated with lateral parietal cortex, regions along the posterior midline including posterior cingulate and retrosplenial cortex, and ventral medial prefrontal cortex. By contrast, anterior hippocampus and the perirhinal/entorhinal cortices correlated with distinct regions in the lateral temporal cortex extending into the temporal pole. The present results are largely consistent with known connectivity in the monkey and provide a novel task-independent dissociation of the parallel pathways supporting the MTL memory system in humans. The cortical pathways include regions that have undergone considerable areal expansion in humans, providing insight into how the MTL memory system has evolved to support a diverse array of cognitive domains. C1 [Kahn, Itamar] Harvard Univ, Howard Hughes Med Inst, Dept Psychol, Cambridge, MA 02138 USA. [Kahn, Itamar; Andrews-Hanna, Jessica R.; Vincent, Justin L.; Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Kahn, Itamar; Andrews-Hanna, Jessica R.; Vincent, Justin L.; Buckner, Randy L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Snyder, Abraham Z.] Washington Univ, Sch Med, Edward Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Kahn, Itamar; Buckner, Randy L.] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA. RP Kahn, I (reprint author), Harvard Univ, Howard Hughes Med Inst, Dept Psychol, 33 Kirkland St,WJH 270, Cambridge, MA 02138 USA. EM kahn@nmr.mgh.harvard.edu RI Vincent, Justin/B-5033-2012 FU Howard Hughes Medical Institute; NIA NIH HHS [AG-021910] NR 71 TC 210 Z9 212 U1 0 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUL PY 2008 VL 100 IS 1 BP 129 EP 139 DI 10.1152/jn.00077.2008 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 326CL UT WOS:000257635400013 PM 18385483 ER PT J AU Lewis, RF Haburcakova, C Merfeld, DM AF Lewis, Richard F. Haburcakova, Csilla Merfeld, Daniel M. TI Roll tilt psychophysics in rhesus monkeys during vestibular and visual stimulation SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID QUALITATIVELY DIFFERENT MECHANISMS; GRAVITO-INERTIAL CUES; HUMAN OCULAR TORSION; VESTIBULOOCULAR REFLEX; LINEAR ACCELERATION; BODY-TILT; PERCEPTUAL RESPONSES; SEMICIRCULAR CANALS; SQUIRREL-MONKEY; ORIENTATION AB How does the brain calculate the spatial orientation of the head relative to gravity? Psychophysical measurements are critical to investigate this question, but such measurements have been limited to humans. In non-human primates, behavioral measures have focused on vestibular-mediated eye movements, which do not reflect percepts of head orientation. We have therefore developed a method to measure tilt perception in monkeys, derived from the subjective visual vertical (SVV) task. Two rhesus monkeys were trained to align a light bar parallel to gravity and performed this task during roll tilts, centrifugation, and roll optokinetic stimulation. The monkeys accurately aligned the light bar with gravity during static roll tilts but also demonstrated small orientation-dependent misperceptions of the tilt angle analogous to those measured in humans. When the gravito-inertial force (GIF) rotated dynamically in the roll plane, SVV responses remained closely aligned with the GIF during roll tilt of the head (coplanar canal rotational cues present), lagged slightly behind the GIF during variable-radius centrifugation (no canal cues present), and shifted gradually during fixed-radius centrifugation (orthogonal yaw canal cues present). SVV responses also deviated away from the earth-vertical during roll optokinetic stimulation. These results demonstrate that rotational cues derived from the semicircular canals and visual system have prominent effects on psychophysical measurements of roll tilt in rhesus monkeys and therefore suggest that a central synthesis of graviceptive and rotational cues contributes to percepts of head orientation relative to gravity in non-human primates. C1 [Lewis, Richard F.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Jenks Vestibular Phys Lab, Boston, MA 02114 USA. [Lewis, Richard F.; Haburcakova, Csilla; Merfeld, Daniel M.] Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02115 USA. [Lewis, Richard F.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Lewis, RF (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Jenks Vestibular Phys Lab, 243 Charles St, Boston, MA 02114 USA. EM richard_lewis@meei.harvard.edu FU NIDCD NIH HHS [DC-4158, DC-6909, R01 DC006909, R01 DC004158] NR 48 TC 17 Z9 17 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUL PY 2008 VL 100 IS 1 BP 140 EP 153 DI 10.1152/jn.01012.2007 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 326CL UT WOS:000257635400014 PM 18417632 ER PT J AU Tehranian, R Rose, ME Vagni, V Pickrell, AM Griffith, RP Liu, H Clark, RSB Dixon, CE Kochanek, PM Graham, SH AF Tehranian, Roya Rose, Marie E. Vagni, Vincent Pickrell, Alicia M. Griffith, Raymond P. Liu, Hao Clark, Robert S. B. Dixon, C. Edward Kochanek, Patrick M. Graham, Steven H. TI Disruption of Bax protein prevents neuronal cell death but produces cognitive impairment in mice following traumatic brain injury SO JOURNAL OF NEUROTRAUMA LA English DT Article DE apoptosis; Bax; TBI; transgenic mice ID CYTOCHROME-C RELEASE; PERMEABILITY TRANSITION PORE; TRANSGENIC MICE; BCL-2 PROTEIN; CEREBRAL-ISCHEMIA; GLOBAL-ISCHEMIA; APOPTOSIS; RATS; MITOCHONDRIA; EXPRESSION AB Apoptosis contributes to delayed neuronal cell death in traumatic brain injury (TBI). To investigate if Bax plays a role in neuronal cell death and functional outcome after TBI, Bax gene disrupted (null) mice and wild-type (WT) controls were subjected to the controlled cortical impact (CCI) model of TBI. Motor function in WT and Bax null mice was evaluated using the round beam balance and the wire grip test on days 0-5. Spatial memory was assessed using a Morris Water Maze adopted for mice on days 14-18 post-injury. For histopathological analysis, animals were sacrificed 24 h and 21 days post-injury. In all three behavioral tests, the sham and TBI-injured Bax null mice performed significantly worse than their WT sham and TBI-injured counterparts. However, Bax null mice exhibited a higher percentage of surviving neurons in the CA1 and CA3 regions of hippocampus measured at 21 days post-injury. At 24 h after trauma, Bax null mice had fewer TUNEL positive cells in the CA1 and dentate regions of hippocampus as compared to WT mice, suggesting that deletion of the Bax gene ameliorates hippocampal cell death after TBI. Sham-operated Bax null mice had significantly greater brain volume as compared to WT mice. Thus, it is possible that Bax deficiency in the transgenic mice produces developmental behavioral effects, perhaps due to Bax's role in regulating cell death during development. C1 [Tehranian, Roya; Rose, Marie E.; Pickrell, Alicia M.; Liu, Hao; Graham, Steven H.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15206 USA. [Tehranian, Roya; Rose, Marie E.; Liu, Hao; Graham, Steven H.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Griffith, Raymond P.; Dixon, C. Edward] Univ Pittsburgh, Dept Neurosurg, Pittsburgh, PA USA. [Vagni, Vincent; Clark, Robert S. B.; Kochanek, Patrick M.] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA USA. [Clark, Robert S. B.; Kochanek, Patrick M.] Univ Pittsburgh, Dept Pediat, Pittsburgh, PA 15260 USA. RP Graham, SH (reprint author), VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, 7108 Highland Dr, Pittsburgh, PA 15206 USA. EM sgra@pitt.edu RI Kochanek, Patrick/D-2371-2015 OI Kochanek, Patrick/0000-0002-2627-913X FU NINDS NIH HHS [P50 NS030318-10, NS30318] NR 50 TC 29 Z9 36 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JUL PY 2008 VL 25 IS 7 BP 755 EP 767 DI 10.1089/neu.2007.0441 PG 13 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 326BX UT WOS:000257634000004 PM 18627254 ER PT J AU Giri, S Prasad, R Khan, M Singh, A Singh, I AF Giri, Shailendra Prasad, Rama Khan, Mushfiquddin Singh, Avtar Singh, Inderjit TI 15-deoxy-delta 12, 14-prostaglandin J2 attenuates endothelial-monocyte interaction: Implication for inflammatory diseases SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 26th Annual National-Neurotrauma-Society Symposium CY JUL 27-30, 2008 CL Orlando, FL SP Natl Neurotrauma Soc C1 [Giri, Shailendra; Prasad, Rama; Khan, Mushfiquddin; Singh, Inderjit] Med Univ S Carolina, Charleston, SC 29425 USA. [Singh, Avtar] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JUL PY 2008 VL 25 IS 7 MA P9 BP 856 EP 856 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 326BX UT WOS:000257634000020 ER PT J AU Khan, M Hoda, N Giri, S Singh, I Singh, A AF Khan, Mushfiquddin Hoda, Nasrul Giri, Shailendra Singh, Inderjit Singh, Avtar TI Protection of endothelial function by S-nitrosoglutathione following acute injury in a rat model of experimental stroke SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 26th Annual National-Neurotrauma-Society Symposium CY JUL 27-30, 2008 CL Orlando, FL SP Natl Neurotrauma Soc C1 [Khan, Mushfiquddin; Hoda, Nasrul; Giri, Shailendra; Singh, Inderjit] Med Univ S Carolina, Charleston, SC 29425 USA. [Singh, Avtar] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JUL PY 2008 VL 25 IS 7 MA P50 BP 866 EP 866 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 326BX UT WOS:000257634000062 ER PT J AU Wallis, RA Panizzon, K AF Wallis, Roi Ann Panizzon, Kimberly TI Treatment with mono-ADP-ribosylation inhibitors protect against the increased susceptibility seen in CA1 hippocampal neurons in aged rats SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 26th Annual National-Neurotrauma-Society Symposium CY JUL 27-30, 2008 CL Orlando, FL SP Natl Neurotrauma Soc C1 [Panizzon, Kimberly] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Wallis, Roi Ann] Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JUL PY 2008 VL 25 IS 7 MA P67 BP 870 EP 870 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 326BX UT WOS:000257634000076 ER PT J AU Boyer, PJ Massimini, DF Gill, TJ Papannagari, R Stewart, SL Warner, JP Li, GA AF Boyer, Patrick J. Massimini, Daniel F. Gill, Thomas J. Papannagari, Ramprasad Stewart, Susan L. Warner, Jon P. Li, Guoan TI In vivo articular cartilage contact at the glenohumeral joint: preliminary report SO JOURNAL OF ORTHOPAEDIC SCIENCE LA English DT Article ID HUMAN SHOULDER; HUMERAL HEAD; KINEMATICS; THICKNESS; PATTERNS; MOTION; TRANSLATION; ELEVATION; MECHANICS; GEOMETRY AB Background. Little is known about normal in vivo mechanics of the glenohumeral joint. Such an understanding would have significant implications for treating disease conditions that disrupt shoulder function. The objective of this study was to determine articular contact locations between the glenoid and humeral articular surfaces in normal subjects during shoulder abduction with neutral, internal, and external rotations. We hypothesized that glenohumeral articular contact is not perfectly centered and is variable in normal subjects tested under physiological loading conditions. Methods. Orthogonal fluoroscopic images and magnetic resonance image-based computer models were used to characterize the centroids of articular cartilage contact of the glenohumeral joint at various static, actively stabilized abduction and rotation positions in five healthy shoulders. The shoulder was investigated at 0 degrees, 45 degrees, and 90 degrees abduction with neutral rotation and then at 90 degrees abduction combined with active maximal external rotation and active maximal internal rotation. Results. For all the investigated positions, the centroid of contact on the glenoid surface for each individual, on average, was more than 5 mm away from the geometric center of the glenoid articular surface. Intersubject variation of the centroid of articular contact on the glenoid surface was observed with each investigated position, and 90 degrees abduction with maximal internal rotation showed the least variability. On the humeral head surface, the centroids of contact were located at the superomedial quarter for all investigated positions, except in two subjects' positions at 0 degrees abduction, neutral rotation. Conclusions. The data showed that the in vivo glenohumeral contact locations were variable among subjects, but in all individuals they were not at the center of the glenoid and humeral head surfaces. This confirms that "ball-in-socket" kinematics do not govern normal shoulder function. These insights into glenohumeral articular contact may be relevant to an appreciation of the consequences of pathology such as rotator cuff disease and instability. C1 [Boyer, Patrick J.; Massimini, Daniel F.; Gill, Thomas J.; Papannagari, Ramprasad; Stewart, Susan L.; Warner, Jon P.; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab, Boston, MA 02114 USA. [Massimini, Daniel F.] MIT, Cambridge, MA 02139 USA. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab, GRJ-1215,55 Fruit St, Boston, MA 02114 USA. FU NFL Charity Foundation; Department of Orthopaedic Surgery, Massachusetts General Hospital FX This work was supported by a research grant from the NFL Charity Foundation and the Department of Orthopaedic Surgery, Massachusetts General Hospital. Technical assistance by Lou "Dawg" DeFrate and Elizabeth "Betsy" Desouza are greatly appreciated. NR 27 TC 13 Z9 13 U1 0 U2 1 PU SPRINGER JAPAN KK PI TOKYO PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065, JAPAN SN 0949-2658 J9 J ORTHOP SCI JI J. Orthop. Sci. PD JUL PY 2008 VL 13 IS 4 BP 359 EP 365 DI 10.1007/s00776-008-1237-3 PG 7 WC Orthopedics SC Orthopedics GA 337RY UT WOS:000258454400012 PM 18696196 ER PT J AU Whitehead, AJ Dobscha, SK Morasco, BJ Ruimy, S Blissell, C Hauser, P AF Whitehead, Ashlee J. Dobscha, Steven K. Morasco, Benjamin J. Ruimy, Samantha Blissell, Cara Hauser, Peter TI Pain, substance use disorders and opioid analgesic prescription patterns in veterans with hepatitis C SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE opioids; hepatitis C; pain management; medication misuse; veterans ID MEDICALLY ILL PATIENTS; PSYCHIATRIC-DISORDERS; MUSCULOSKELETAL PAIN; UNITED-STATES; MANAGEMENT; PREVALENCE; INFECTION; ADDICTION; ISSUES; CARE AB To examine the prevalence of pain, substance use disorder (SUD) diagnoses, and opioid analgesic prescription patterns among veterans infected with the hepatitis C virus (HCV), a retrospective review of the medical records of 8,224 HCV-positive (HCV+) veterans was performed. Twenty-nine percent and 46% of HCV+ patients were prescribed opioids in the prior one and three years, respectively. Sixty-seven percent of HCV+ patients had documented pain diagnoses and 56% had SUD diagnoses. Patients with co-occurring pain and SUD were less likely to be prescribed opioids than patients with pain only (prior year: 36% vs. 43%, P < 0.001; three years: 56% vs. 60%, P < 0.01). There, were no differences in numbers of early opioid prescription fills or numbers of opioid prescribers when comparing patients with co-occurring pain and SUD to patients with pain only. Veterans with co-occurring pain and opioid use disorder had fewer early opioid fills than veterans with pain only (prior year: 2.6 vs. 5.3 days, P < 0.01; three years: 6.1 vs. 13.4 days, P < 0.001). These data demonstrate that pain and SUD diagnoses were common among HCV+ patients, and that opioids were frequently prescribed. Co-occurring SUD was not associated with indicators of prescription opioid misuse. C1 [Whitehead, Ashlee J.; Morasco, Benjamin J.; Ruimy, Samantha; Blissell, Cara; Hauser, Peter] Portland VA Med Ctr, NW Hepatitis C Resource Ctr, Portland, OR 97207 USA. [Whitehead, Ashlee J.; Dobscha, Steven K.; Morasco, Benjamin J.; Ruimy, Samantha; Blissell, Cara; Hauser, Peter] Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR 97207 USA. [Dobscha, Steven K.] Portland VA Med Ctr, Columbia Ctr Study Chron Comorbid Mental & Phys D, Portland, OR 97207 USA. [Hauser, Peter] Portland VA Med Ctr, JENS Lab, Portland, OR 97207 USA. [Dobscha, Steven K.; Morasco, Benjamin J.; Hauser, Peter] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Hauser, Peter] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Hauser, Peter] Oregon Hlth & Sci Univ, Dept Internal Med, Portland, OR 97201 USA. RP Whitehead, AJ (reprint author), Portland VA Med Ctr, NW Hepatitis C Resource Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. EM ashlee.whitehead@va.gov NR 34 TC 22 Z9 22 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JUL PY 2008 VL 36 IS 1 BP 39 EP 45 DI 10.1016/j.jpainsymman.2007.08.013 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 326VY UT WOS:000257688400005 PM 18358690 ER PT J AU Hansra, NK Berger, TG O'Sullivan, P Chittenden, EH AF Hansra, Nina K. Berger, Timothy G. O'Sullivan, Patricia Chittenden, Eva H. TI Skin findings in palliative care patients SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID QUALITY-OF-LIFE; PERFORMANCE SCALE; HERPES-SIMPLEX; DISEASE; UNIT AB The prevalence of dermatologic disease and its effect on quality of life has not been well studied in patients with advanced illness. We sought to describe skin findings in inpatient palliative care patients and determine how often they are addressed by the primary or palliative care teams. We collected patient demographic and clinical data from the medical record, performed total body skin examinations, and determined how often significant cutaneous findings were documented in the chart. We also characterized skin findings as uncomfortable and treatable. Twenty palliative care patients participated in the study over a 2-month period. Common findings included skin breakdown (20/54; 37%), skin infections (14/54; 26%), inflammatory dermatoses (9/54; 17%), and skin conditions related to systemic disease (7/54; 13%) or treatment of systemic disease (4/54; 7%). Most of these conditions were not documented by primary or palliative care clinicians. Eighty percent of the patients had uncomfortable, but treatable skin conditions of which 62% (13/21) were undocumented or incorrectly documented. These limited data suggest the need for palliative care clinicians to conduct more complete skin examinations, and to improve their knowledge of common skin abnormalities in patients with serious illness. A larger scale investigation of skin disease and its effect on quality of life in the palliative care population is warranted. C1 [Hansra, Nina K.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Berger, Timothy G.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [O'Sullivan, Patricia; Chittenden, Eva H.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Chittenden, EH (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM echittenden@partners.org OI O'Sullivan, Patricia/0000-0002-8706-4095 FU Dean's Office Medical Student Research Program; UCSF Medical Education Research Fellowship; UCSF Office of Medical Education and Academy of Medical Educators FX Concepts about quality of life in this setting were discussed with Mary-Margaret Chren, M. D., from the UCSF Department of Dermatology. This study was supported by the UCSF Quarterly Research Grant through the Dean's Office Medical Student Research Program. Dr. Chittenden's time was supported by the UCSF Medical Education Research Fellowship, sponsored jointly by the UCSF Office of Medical Education and Academy of Medical Educators. NR 13 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD JUL-AUG PY 2008 VL 11 IS 6 BP 834 EP 837 DI 10.1089/jpm.2008.0009 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 343ZX UT WOS:000258896100009 PM 18715173 ER PT J AU Williams, BR Sawyer, P Roseman, JM Allman, RM AF Williams, Beverly R. Sawyer, Patricia Roseman, Jeffrey M. Allman, Richard M. TI Marital status and health: Exploring pre-widowhood SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID OLDER-ADULTS; PHYSICAL HEALTH; ANTICIPATORY GRIEF; MARRIED-WOMEN; DEPRESSIVE SYMPTOMATOLOGY; PSYCHOLOGICAL ADJUSTMENT; HEART-FAILURE; MENTAL-HEALTH; SPOUSAL LOSS; MORTALITY AB Background: Health and function vary by marital status across the life-course, but little is known about older adults approaching spousal loss (pre-widowed). Objective: To explore health and function by marital status focusing on the pre-widowed and to examine factors associated with shorter time to spousal loss. Participants, design, and measurements: We used 3 years of data from African American and white community-dwelling older adults in the UAB Study of Aging (N = 1000). Participants were categorized as "continuously married" (married at baseline and 3 years), "widowed" (widowed at baseline), "single" (never married/divorced); and " pre-widowed" (married at baseline and widowed within 3 years). Assessments included sociodemographic characteristics, and measures of depression, anxiety, life-space mobility, and self-reported health. chi(2) and analysis of variance (ANOVA) were used to examine baseline differences. Using Cox regression, we explored factors having independent and significant associations with shorter time to spousal loss among married older adults. Results: There were significant differences by marital status category for sociodemographic factors, health, and function. Pre-widows differed from other categories by sociodemographic characteristics as well as levels of depression, anxiety and self-reported health. Among married older adults, being female and having lower self-reported health at baseline were independent significant hazards for shorter time to widowhood; while rural residence and providing spousal care were independent significant hazards for a longer progression to widowhood. Conclusions: Health deficits associated with spousal bereavement may be evident earlier in the marital transition than previously thought, warranting attention to the health of elderly persons whose spouses have chronic/life-limiting conditions. C1 [Williams, Beverly R.; Allman, Richard M.] Birmingham VA Med Ctr, Birmingham Atlanta VA Geriatr Res Educ & Clin Ctr, Birmingham, AL 35233 USA. [Sawyer, Patricia] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Sawyer, Patricia] Univ Alabama, Dept Gerontol, Birmingham, AL USA. [Sawyer, Patricia] Univ Alabama, Dept Geriatr, Birmingham, AL USA. [Sawyer, Patricia] Univ Alabama, Dept Palliat Care, Birmingham, AL USA. [Roseman, Jeffrey M.] Univ Alabama, Dept Epidemiol, Birmingham, AL USA. RP Williams, BR (reprint author), Birmingham VA Med Ctr, Birmingham Atlanta VA Geriatr Res Educ & Clin Ctr, 700 19th St S, Birmingham, AL 35233 USA. EM beverly.williams3@va.gov FU NIA NIH HHS [R01 AG015062] NR 74 TC 11 Z9 11 U1 3 U2 15 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD JUL-AUG PY 2008 VL 11 IS 6 BP 848 EP 856 DI 10.1089/jpm.2007.0190 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 343ZX UT WOS:000258896100013 PM 18715177 ER PT J AU Jackson, VA Mack, J Matsuyama, R Lakoma, MD Sullivan, AM Arnold, RM Weeks, JC Block, SD AF Jackson, Vicki A. Mack, Jennifer Matsuyama, Robin Lakoma, Mathew D. Sullivan, Amy M. Arnold, Robert M. Weeks, Jane C. Block, Susan D. TI A qualitative study of oncologists' approaches to end-of-life care SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID COMMUNICATION-SKILLS; HEALTH-CARE; JOB STRESS; CANCER; BURNOUT; SATISFACTION; PHYSICIANS; DOCTORS; DEATH AB Purpose: To understand how oncologists provide care at the end of life, the emotions they experience in the provision of this care, and how caring for dying patients may impact job satisfaction and burnout. Participants and methods: A face-to-face survey and in-depth semistructured interview of 18 academic oncologists who were asked to describe the most recent inpatient death on the medical oncology service. Physicians were asked to describe the details of the patient death, their involvement with the care of the patient, the types and sequence of their emotional reactions, and their methods of coping. Grounded theory qualitative methods were utilized in the analysis of the transcripts. Results: Physicians, who viewed their physician role as encompassing both biomedical and psychosocial aspects of care, reported a clear method of communication about end-of-life (EOL) care, and an ability to positively influence patient and family coping with and acceptance of the dying process. These physicians described communication as a process, made recommendations to the patient using an individualized approach, and viewed the provision of effective EOL care as very satisfying. In contrast, participants who described primarily a biomedical role reported a more distant relationship with the patient, a sense of failure at not being able to alter the course of the disease, and an absence of collegial support. In their descriptions of communication encounters with patients and families, these physicians did not seem to feel they could impact patients' coping with and acceptance of death and made few recommendations about EOL treatment options. Conclusion: Physicians' who viewed EOL care as an important role described communicating with dying patients as a process and reported increased job satisfaction. Further research is necessary to determine if educational interventions to improve physician EOL communication skills could improve physician job satisfaction and decrease burnout. C1 [Jackson, Vicki A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Jackson, Vicki A.] Massachusetts Gen Hosp, Dept Palliat Care, Boston, MA 02114 USA. [Lakoma, Mathew D.; Sullivan, Amy M.; Block, Susan D.] Brigham & Womens Hosp, Div Psychosocial Oncol & Palliat Care, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mack, Jennifer] Brigham & Womens Hosp, Dept Pediat Hematol Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mack, Jennifer; Weeks, Jane C.] Brigham & Womens Hosp, Ctr Outcomes & Policy Res, Dana Farber Canc Inst, Boston, MA 02115 USA. [Weeks, Jane C.] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Sullivan, Amy M.; Block, Susan D.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Mack, Jennifer] Childrens Hosp, Boston, MA 02115 USA. [Jackson, Vicki A.; Mack, Jennifer; Sullivan, Amy M.; Block, Susan D.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Arnold, Robert M.] Univ Pittsburgh, Med Ctr, Sect Palliat Care & Med Eth, Inst Enhance Palliat Care,Ctr Res Hlth Care, Pittsburgh, PA USA. [Matsuyama, Robin] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA. RP Jackson, VA (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St,Founders 600, Boston, MA 02114 USA. EM vjackson@partners.org FU Nathan Cummings Foundation; National Cancer Institute; AHRQ; LHAS Trust FX This work was supported by a grant from the Nathan Cummings Foundation. During the preparation of this manuscript, Dr. Jackson was supported by a National Cancer Institute research-training grant. Dr. Mack was supported by an AHRQ research training grant. Dr. Arnold was a Faculty Scholar of the Open Society Institute's Project on Death in America and is supported by the LHAS Trust. NR 25 TC 65 Z9 65 U1 3 U2 12 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD JUL-AUG PY 2008 VL 11 IS 6 BP 893 EP 906 DI 10.1089/jpm.2007.2480 PG 14 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 343ZX UT WOS:000258896100018 PM 18715182 ER PT J AU Duro, D Bechard, LJ Feldman, HA Klykov, A O'Leary, A Guinan, EC Duggan, C AF Duro, Debora Bechard, Lori J. Feldman, Henry A. Klykov, Arkady O'Leary, Alice Guinan, Eva C. Duggan, Christopher TI Weekly measurements accurately represent trends in resting energy expenditure in children undergoing hematopoietic stem cell transplantation SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article DE energy expenditure; parenteral nutrition; hematopoietic stem cell transplantation; pediatrics ID ACUTE LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; CHILDHOOD AB Background: Resting energy expenditure (BEE) measurements are optimal for accurate assessment of energy requirements and precise provision of parenteral nutrients. We previously observed significant reduction in BEE during a 4-week period in children undergoing hematopoietic stem cell transplantation (HSCT). The goal of this study was to determine if weekly BEE measurements could accurately represent changes in BEE in the peritransplant period compared with a more frequent standard of daily measurements. Methods: Data are presented from a previously described cohort of 37 children undergoing HSCT. We performed weekly indirect calorimetry on 25 patients; of those 25, we performed daily measurements on a convenience sample of 5 children. The time course of BEE was analyzed in each sample by repeated measures regression. Results: The BEE trend of the 20 weekly participants was similar to that of the 5 daily participants, reaching about 80% of predicted BEE at 4 weeks posttransplant, with an average decline of 3.4% per week during 4 weeks. Conclusion: The results suggest that weekly BEE measurements accurately characterize BEE changes 4 weeks after HSCT compared with daily measurements. Characterization of these trends using weekly measurements may help guide clinical and nutrition care of these patients. C1 [Duggan, Christopher] Childrens Hosp, Clin Nutr Serv, Div GI Nutr, Boston, MA 02115 USA. [Bechard, Lori J.; Guinan, Eva C.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Duggan, C (reprint author), Childrens Hosp, Clin Nutr Serv, Div GI Nutr, 300 Longwood Ave, Boston, MA 02115 USA. EM christopher.duggan@childrens.harvard.edu FU NICHD NIH HHS [T32 HD043034, T32 HD 43034-05A1]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-13] NR 12 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0148-6071 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD JUL-AUG PY 2008 VL 32 IS 4 BP 427 EP 432 DI 10.1177/0148607108319804 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 325OW UT WOS:000257599200010 PM 18596314 ER PT J AU Krasnoff, JB Kohn, MA Choy, FKK Doyle, J Johansen, K Painter, PL AF Krasnoff, Joanne B. Kohn, Michael A. Choy, Frankie K. K. Doyle, Julie Johansen, Kirsten Painter, Patricia L. TI Interunit and Intraunit Reliability of the RT3 Triaxial Accelerometer SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE physical activity measurement; reproducibility; accelerometry ID INTENSITY PHYSICAL-ACTIVITY; ACTIVITY MONITORS; ENERGY-EXPENDITURE; VALIDITY; CALIBRATION; VALIDATION; FIELD; VARIABILITY; WOMEN AB Background: Interest in the quantification of physical activity is on the rise. Triaxial accelerometry has frequently been used; however, research on the reliability of these devices is limited. We examine the interunit and intraunit reliability of 22 RT3 triaxial accelerometers using a performance-documented laboratory agitator. Methods: The RT3 units were tested while moving in 2 directions (antero-posterior, medio-lateral) and speeds (150 and 275 RPM) on a shaker with simultaneous documented performance output for three 24-hour periods. Results: Minimal shaker variance was recorded for all trials (coefficients of variation [CVs] < 0.52%). Our data demonstrate good reliability within RT3s (CVs < 1.81%) but poor reliability among the 22 units (CVs range = 9.5% to 34.7%). Conclusions: In longitudinal studies, each subject should use the same RT3 unit at each assessment. The use of multiple RT3 units in cross-sectional studies is not recommended because data interpretation would be compromised by the high between-unit variability. C1 [Krasnoff, Joanne B.] Univ Calif San Francisco, Dept Med, Exercise Physiol & Body Composit Lab, San Francisco, CA 94143 USA. [Kohn, Michael A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Choy, Frankie K. K.] San Francisco Vet Adm Med Ctr, NCIRE Biomed Engn, San Francisco, CA 94121 USA. [Doyle, Julie; Johansen, Kirsten] San Francisco Vet Adm Med Ctr, Div Nephrol, San Francisco, CA 94121 USA. [Painter, Patricia L.] Univ Minnesota, Dept Med, Div Renal Dis, Minneapolis, MN 55455 USA. RP Krasnoff, JB (reprint author), Univ Calif San Francisco, Dept Med, Exercise Physiol & Body Composit Lab, San Francisco, CA 94143 USA. FU NCRR NIH HHS [M01 RR-0079]; NINR NIH HHS [R01NR008286] NR 30 TC 23 Z9 24 U1 0 U2 0 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD JUL PY 2008 VL 5 IS 4 BP 527 EP 538 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V18OZ UT WOS:000208015400005 PM 18648118 ER PT J AU Rho, JH Qin, SZ Wang, JY Roehrl, MHA AF Rho, Jung-hyun Qin, Shuzhen Wang, Julia Y. Roehrl, Michael H. A. TI Proteomic expression analysis of surgical human colorectal cancer tissues: Up-regulation of PSB7, PRDX1, and SRP9 and hypoxic adaptation in cancer SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE colorectal carcinoma; low-abundance proteome; heparin affinity fractionation enrichment; two-dimensional gel electrophoresis; mass spectrometry; immunohistochemistry; proteasome subunit beta type 7; peroxiredoxin-1; signal recognition particle 9 kDa protein; hypoxic adaptation ID SIGNAL RECOGNITION PARTICLE; HUMAN COLON-CANCER; PEROXIREDOXIN-I EXPRESSION; MHC CLASS-I; ARGININOSUCCINATE SYNTHETASE; PROTEASOME SUBUNITS; DOWN-REGULATION; LUNG-CANCER; DIFFERENTIAL EXPRESSION; AFFINITY-CHROMATOGRAPHY AB Colorectal adenocarcinoma is one of the worldwide leading causes of cancer deaths. Discovery of specific biomarkers for early detection of cancer progression and the identification of underlying pathogenetic mechanisms are important tasks. Global proteomic approaches have thus far been limited by the large dynamic range of molecule concentrations in tissues and the lack of selective enrichment of the low-abundance proteome. We studied paired cancerous and normal clinical tissue specimens from patients with colorectal adenocarcinomas by heparin affinity fractionation enrichment (HAFE) followed by 2-D PAGE and tandem mass spectrometric (MS/MS) identification. Fifty-six proteins were found to be differentially expressed, of which 32 low-abundance proteins were only detectable after heparin affinity enrichment. MS/MS was used to identify 5 selected differentially expressed proteins as proteasome, subunit beta type 7 (PSB7), hemoglobin a subunit (HBA), peroxiredoxin-1 (PRDX1), argininosuccinate synthase (ASSY), and signal recognition particle 9 kDa protein (SRP9). This is the first proteomic study detecting the differential expression of these proteins in human colorectal cancer tissue. Several of the proteins are functionally related to tissue hypoxia and hypoxic adaptation. The relative specificities of PSB7, PRDX1, and SRP9 overexpression in colon cancer were investigated by Western blot analysis of patients with colon adenocarcinomas and comparison with a control cohort of patients with lung adenocarcinomas. Furthermore, immunohistochemistry on tissue sections was used to define the specific locations of PSB7, PRDX1, and SRP9 up-regulation within heterogeneous primary human tumor tissue. Overexpression of the three proteins was restricted to the neoplastic cancer cell population within the tumors, demonstrating both cytoplasmic and nuclear localization of PSB7 and predominantly cytoplasmic localization of PRDX1 and SRP9. In summary, we describe heparin affinity fractionation enrichment (HAFE) as a prefractionation tool for the study of the human primary tissue proteome and the discovery of PSB7, PRDX1, and SRP9 up-regulation as candidate biomarkers of colon cancer. C1 [Rho, Jung-hyun; Wang, Julia Y.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Rho, Jung-hyun; Qin, Shuzhen; Wang, Julia Y.; Roehrl, Michael H. A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Qin, Shuzhen] Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. [Roehrl, Michael H. A.] Massachusetts Gen Hosp, Dept Pathol & Lab Med, Boston, MA 02115 USA. RP Wang, JY (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM julia_wang@rics.bwh.harvard.edu; michael_roehrl@hms.harvard.edu FU NIAID NIH HHS [R01 AI057926, R01 AI057926-05, R01 AI068826, R01 AI068826-01A2]; PHS HHS [R01] NR 58 TC 48 Z9 53 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD JUL PY 2008 VL 7 IS 7 BP 2959 EP 2972 DI 10.1021/pr8000892 PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 323MF UT WOS:000257449500036 PM 18549262 ER PT J AU Mooney, JJ Samson, JA Hennen, J Pappalardo, K McHale, N Alpert, J Koutsos, M Schildkraut, JJ AF Mooney, John J. Samson, Jacqueline A. Hennen, John Pappalardo, Kathleen McHale, Nancy Alpert, Jonathan Koutsos, Martha Schildkraut, Joseph J. TI Enhanced norepinephrine output during long-term desipramine treatment: A possible role for the extraneuronal monoamine transporter (SLC22A3) SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE extraneuronal monoamine transporter; SLC22A3; norepinephrine; desipramine; depression ID PERFORMANCE LIQUID-CHROMATOGRAPHY; URINARY MHPG LEVELS; ELECTROCHEMICAL DETECTION; RAT-BRAIN; BIOCHEMICAL CLASSIFICATION; DEPRESSIVE-DISORDERS; MAJOR DEPRESSION; LOCUS-COERULEUS; NORADRENALINE; CATECHOLAMINES AB To study the delay (2-6 weeks) between initial administration of norepinephrine reuptake inhibitor antidepressants and onset of clinical antidepressant action, we examined the effects of desipramine treatment on urinary and plasma catecholamines and their metabolites during the initial 6 weeks of treatment in depressed patients. Catecholamines and metabolites in 24-h urine collections and 8:00 a.m. plasma samples were measured at baseline and after 1, 4, and 6 weeks of desipramine treatment. Desipramine treatment produced significant increases in urinary norepinephrine (NE) and normetanephrine (NMN) and plasma NE at Weeks 4 and 6, but not at Week 1. The ratio of urinary NE/NMN was increased at Weeks 4 and 6, suggesting a reduction in the metabolism of NE to NMN at extraneuronal sites by Weeks 4 and 6. The increases in urinary NE and NMN and plasma NE at Weeks 4 and 6 of desipramine treatment were associated with a reduction in the conversion of NE to NMN. This would be compatible with a blockade of the extraneuronal monoamine transporter (organic cation transporter 3; SLC22A3) by NMN. Inhibition of the extraneuronal monoamine transporter may be ail important component in the clinical pharmacology of the norepinephrine reuptake inhibitor antidepressant drugs, such as desipramine. The ClinicalTrials.gov Identifier for this study is NCT00320632. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Mooney, John J.; Samson, Jacqueline A.; Hennen, John; Pappalardo, Kathleen; McHale, Nancy; Alpert, Jonathan; Koutsos, Martha; Schildkraut, Joseph J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Mooney, John J.; Samson, Jacqueline A.; Pappalardo, Kathleen; McHale, Nancy; Schildkraut, Joseph J.] Massachusetts Mental Hlth Ctr, Neuropsychopharmacol Psychiat Chem Lab, Boston, MA 02115 USA. [Mooney, John J.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Samson, Jacqueline A.; Hennen, John] McLean Hosp, Belmont, MA 02178 USA. [Alpert, Jonathan] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Koutsos, Martha] Lahey Clin Fdn, Dept Psychiat, Burlington, MA USA. RP Mooney, JJ (reprint author), BIDMC Psychiatry, 330 Brookline Ave Rabb-2, Boston, MA 02215 USA. EM jmooney@bidmc.harvard.edu OI Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [MH-15413, R01 MH015413-25] NR 48 TC 10 Z9 10 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD JUL PY 2008 VL 42 IS 8 BP 605 EP 611 DI 10.1016/j.psychires.2007.07.009 PG 7 WC Psychiatry SC Psychiatry GA 304NV UT WOS:000256117100001 PM 17727882 ER PT J AU Kaysen, GA Johansen, KL Cheng, SC Jin, CS Chertow, GM AF Kaysen, George A. Johansen, Kirsten L. Cheng, Su-Chen Jin, Chengshi Chertow, Glenn M. TI Trends and outcomes associated with serum albumin concentration among incident dialysis patients in the United States SO JOURNAL OF RENAL NUTRITION LA English DT Article ID C-REACTIVE PROTEIN; HEMODIALYSIS-PATIENTS; PERITONEAL-DIALYSIS; ENERGY-EXPENDITURE; MORTALITY; INFLAMMATION; CREATININE; RISK; INTERLEUKIN-6; DETERMINANTS AB Objective and Methods: Serum albumin concentrations are associated with mortality, and respond to nutritional and inflammatory states. To explore whether changing demographics and practice patterns in dialysis have influenced serum albumin concentrations, we analyzed trends in serum albumin among incident patients on dialysis from 1995 through 2004. Results: Mean serum albumin concentrations declined significantly over time, even after accounting for changes in age, diabetes, body size, and other factors. Although laboratory assays were not uniform within or across years, serum albumin declined over time, regardless of the reported laboratory lower limit of normal. Moreover, serum albumin retained its potent association with mortality over time. Lower serum albumin was especially hazardous among younger patients and blacks, and was less hazardous among persons with diabetes as a primary cause of kidney disease. Conclusions: Despite higher body weights and the initiation of dialysis earlier in the course of progressive chronic kidney disease, hypoalbuminemia remains common and hazardous to persons starting dialysis. (C) 2008 by the National Kidney Foundation, Inc. All rights reserved. C1 [Chertow, Glenn M.] Stanford Univ, Sch Med, Div Nephrol, Dept Med, Stanford, CA 94305 USA. [Kaysen, George A.] Univ Calif Davis, Div Nephrol, Dept Med, Davis, CA 95616 USA. [Kaysen, George A.] Univ Calif Davis, Dept Biochem & Mol Med, Davis, CA 95616 USA. [Kaysen, George A.] VA No Calif, Sacramento, CA USA. [Johansen, Kirsten L.] San Francisco VA Med Ctr, Div Nephrol, San Francisco, CA USA. [Johansen, Kirsten L.; Cheng, Su-Chen; Jin, Chengshi] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Chertow, GM (reprint author), Stanford Univ, Sch Med, Div Nephrol, Dept Med, Grant Bldg,S-161, Stanford, CA 94305 USA. EM gchertow@stanford.edu FU NIDDK NIH HHS [K24 DK085446, N01 DK022498, N01 DK022498-002, N01-DK-7-5007, T32 DK007357] NR 30 TC 20 Z9 20 U1 0 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 1051-2276 J9 J RENAL NUTR JI J. Renal Nutr. PD JUL PY 2008 VL 18 IS 4 BP 323 EP 331 DI 10.1053/j.jrn.2008.04.002 PG 9 WC Nutrition & Dietetics; Urology & Nephrology SC Nutrition & Dietetics; Urology & Nephrology GA 326DI UT WOS:000257637800001 PM 18558296 ER PT J AU Maresz, K Ponomarev, ED Arteneva, NB Tan, YP Mann, MK Dittel, BN AF Maresz, Katarzyna Ponomarev, Eugene D. Arteneva, Natasha B. Tan, Yanping Mann, Monica K. Dittel, Bonnie N. TI IL-13 induces the expression of the alternative activation marker Ym1 in a subset of testicular macrophages SO JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE immune privilege; Th2 immunity; lung; testis; immunosuppressive ID DENDRITIC CELLS; MURINE YM1; RECEPTOR; INTERLEUKIN-13; RESPONSES; IDENTIFICATION; PROLIFERATION; INFLAMMATION; ROLES; GENE AB Macrophages are thought to play an important role in the maintenance of immune privilege in the testis, which functions to prevent immune responses to developing sperm. Two populations of macrophages are known to exist in the testis, one of which exhibits immunosuppressive activity. Macrophages that are alternatively activated with either IL-4 or IL-13 have been shown to be anti-inflammatory and promote wound healing. Expression of the Ym1 protein is an established marker of alternatively activated macrophages. Testicular macrophages were examined for expression of Ym1 protein, and it was found to be highly expressed in a subpopulation of CD11b(+) cells. Furthermore, we have shown that Ym1 protein expression in the testis is dependent upon IL-13R signaling, and that IL-13 is produced in the testis. These data suggest that IL-13 plays a role in testicular immune privilege by the maintenance of an alternatively activated macrophage population. (c) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Maresz, Katarzyna; Ponomarev, Eugene D.; Tan, Yanping; Mann, Monica K.; Dittel, Bonnie N.] BloodCtr Wiscosin, Blood Res Inst, Milwaukee, WI 53226 USA. [Arteneva, Natasha B.] Harvard Univ, Sch Med, Immune Dis Inst, Flow & Imaging Cytometry Facil, Boston, MA 02115 USA. [Mann, Monica K.; Dittel, Bonnie N.] Med Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA. RP Dittel, BN (reprint author), BloodCtr Wiscosin, Blood Res Inst, 8727 Watertown Plank Rd,POB 2178, Milwaukee, WI 53226 USA. EM bonnie.dittel@bcw.edu FU NINDS NIH HHS [R01 NS046662, R01 NS046662-01A1] NR 34 TC 20 Z9 23 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-0378 J9 J REPROD IMMUNOL JI J. Reprod. Immunol. PD JUL PY 2008 VL 78 IS 2 BP 140 EP 148 DI 10.1016/j.jri.2008.01.001 PG 9 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 326EV UT WOS:000257642000007 PM 18329106 ER PT J AU Berkowitz, RS Goldstein, DP AF Berkowitz, Ross S. Goldstein, Donald P. TI Gestational trophoblastic disease - Presentations from the XIVth World Congress on Gestational Trophoblastic Diseases SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Editorial Material DE chemotherapy; gestational trophoblastic neoplasms C1 [Berkowitz, Ross S.] Harvard Univ, Dept Obstet & Gynecol,Brigham & Womens Hosp, Div Gynecol Oncol,Dana Farber Canc Inst, New England Trophoblast Dis Ctr,Sch Med, Boston, MA 02115 USA. [Goldstein, Donald P.] Harvard Univ, Dept Obstet & Gynecol,Brigham & Womens Hosp, Div Gynecol Oncol,Dana Farber Canc Inst, Trophoblast Tumor Registry,Sch Med, Boston, MA 02115 USA. RP Berkowitz, RS (reprint author), Harvard Univ, Dept Obstet & Gynecol,Brigham & Womens Hosp, Div Gynecol Oncol,Dana Farber Canc Inst, New England Trophoblast Dis Ctr,Sch Med, 75 Francis St, Boston, MA 02115 USA. EM rberkowitz@partners.org NR 0 TC 1 Z9 1 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD JUL PY 2008 VL 53 IS 7 BP 455 EP 456 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 326WO UT WOS:000257690000002 PM 18720918 ER PT J AU Garrett, LA Garner, EIO Feltmate, CM Goldstein, DP Berkowitz, RS AF Garrett, Leslie A. Garner, Elizabeth I. O. Feltmate, Colleen M. Goldstein, Donald P. Berkowitz, Ross S. TI Subsequent pregnancy outcomes in patients with molar pregnancy and persistent gestational trophoblastic neoplasia SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article; Proceedings Paper CT 14th World Congress on Gestational Trophoblastic Diseases CY NOV 11-14, 2007 CL Fukuoka, JAPAN DE complete mole; molar pregnancy; partial mole; trophoblastic tumor ID RECURRENT HYDATIDIFORM MOLE; DISEASE-CENTER; CHEMOTHERAPY; EXPERIENCE; TUMORS; ENGLAND; RISK AB OBJECTIVE: To evaluate the subsequent reproductive outcomes in patients with complete and partial molar pregnancy and gestational trophoblastic neoplasia (GTN) at the New England trophoblastic Disease Center between June 1, 1965, and December 31, 2007. STUDY DESIGN: Questionnaires regarding subsequent pregnancies were mailed to all patients with current mailing addresses at the New England Trophoblastic Disease Center. RESULTS: The subsequent reproductive outcomes in patients with complete and partial molar pregnancies and persistent GTN were in general the same as those in the general population. However, after an episode of molar pregnancy the incidence of molar pregnancy in a later gestation was similar to 1%. Additionally, after successful chemotherapy for GTN, the incidence of stillbirth was 1.4% in later pregnancies. CONCLUSION: Patients with molar pregnancies and GTN should be reassured that they can in general expect a normal future reproductive outcome. C1 [Garrett, Leslie A.; Garner, Elizabeth I. O.; Feltmate, Colleen M.; Berkowitz, Ross S.] Harvard Univ, Div Gynecol Oncol, Brigham & Womens Hosp,Dept Obstet & Gynecol, New England Trophoblast Dis Ctr,Sch Med, Boston, MA 02115 USA. [Goldstein, Donald P.] Harvard Univ, Div Gynecol Oncol, Brigham & Womens Hosp,Dept Obstet & Gynecol, Trophoblast Tumor Registry,Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Berkowitz, RS (reprint author), Harvard Univ, Div Gynecol Oncol, Brigham & Womens Hosp,Dept Obstet & Gynecol, New England Trophoblast Dis Ctr,Sch Med, 75 Francis St, Boston, MA 02115 USA. EM rberkowitz@partners.org NR 33 TC 29 Z9 29 U1 1 U2 1 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD JUL PY 2008 VL 53 IS 7 BP 481 EP 486 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 326WO UT WOS:000257690000006 PM 18720922 ER PT J AU Fleming, EL Garrett, L Growdon, WB Callahan, M Nevadunsky, N Ghosh, S Goldstein, DP Berkowitz, RS AF Fleming, Evelyn L. Garrett, Leslie Growdon, Whitfield B. Callahan, Michael Nevadunsky, Nicole Ghosh, Sue Goldstein, Donald P. Berkowitz, Ross S. TI The changing role of thoracotomy in gestational trophoblastic neoplasia at the New England Trophoblastic Disease Center SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article; Proceedings Paper CT 14th World Congress on Gestational Trophoblastic Diseases CY NOV 11-14, 2007 CL Fukuoka, JAPAN DE gestational trophoblastic neoplasms; thoracotomy ID MANAGEMENT; CHORIOCARCINOMA; SITE; METASTASES; RESECTION; TUMORS AB OBJECTIVE: To review our experience with thoracotomy in gestational trophoblastic neoplasia (GTN). STUDY DESIGN: Nineteen thoracotomy patients from our database were identified. Thoracotomy was performed for therapeutic reasons in 11 patients and to clarify the diagnosis in eight. RESULTS: Among the 11 patients with chemotherapy-resistant pulmonary tumors, 10 of 11 (90.9%) achieved remission with thoracotomy. Thoracotomy was more likely to be done to clarify diagnosis before 1980 (83%) than after 1980 (23%) (p = 0.04), when it became more likely to be done for therapeutic indications. Ten patients had solitary lung lesions and 9 had multiple lesions. Four patients died (21%), with an average survival after thoracotomy of 149 days; patients had bilateral or multiple lung lesions, median preoperative hCG was 58,000 mIU/mL and all were stage IV. Survivors had lower stage disease, were more likely to have solitary lesions and had lower preoperative hCG levels. CONCLUSION: There have been several temporal changes in the indications for thoracotomy for GTN. In general, the optimal patient to achieve remission with thoracotomy will have stage III disease, a preoperative hCG of <1,500 mIU/mL, and a solitary lung nodule resistant to chemotherapy. Likelihood of remission after thoracotomy is high in properly selected patients. C1 [Fleming, Evelyn L.; Garrett, Leslie; Growdon, Whitfield B.; Callahan, Michael; Nevadunsky, Nicole; Ghosh, Sue; Berkowitz, Ross S.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Dana Farber Canc Inst,New England Trophoblast Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. [Goldstein, Donald P.] Massachusetts Gen Hosp, Trophoblast Tumor Registry, Div Gynecol Oncol, Boston, MA 02114 USA. RP Berkowitz, RS (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Dana Farber Canc Inst,New England Trophoblast Dis, 75 Francis St, Boston, MA 02115 USA. EM rberkowitz@partners.org NR 14 TC 15 Z9 19 U1 0 U2 1 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD JUL PY 2008 VL 53 IS 7 BP 493 EP 498 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 326WO UT WOS:000257690000008 PM 18720924 ER PT J AU Nagymanyoki, Z Butler, MO Callahan, MJ Parast, MM Fulop, V Mok, SC Berkowitz, RS AF Nagymanyoki, Zoltan Butler, Marcus O. Callahan, Michael J. Parast, Mana M. Fulop, Vilmos Mok, Samuel C. Berkowitz, Ross S. TI Antigen-specific T cell immune response detected by skewed T cell receptor usage in normal placenta and complete molar pregnancy SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article; Proceedings Paper CT 14th World Congress on Gestational Trophoblastic Diseases CY NOV 11-14, 2007 CL Fukuoka, JAPAN DE complete mole; gestatational trophoblastic disease; pregnancy; T cell receptor; variable beta chain ID V(D)J RECOMBINATION; RHEUMATOID-ARTHRITIS; SEQUENCE MOTIFS; CDR3 SEQUENCE; INVASION; DECIDUA AB OBJECTIVE: To investigate the antigenicity of normal placenta and complete molar trophoblastic tissue. STUDY DESIGN: T cell receptor (TCR) variable beta chain (VBC) gene expression was analyzed utilizing fresh frozen tissues. Real-time polymerase chain reactions (RT-PCR) were performed on cDNA samples from 10 normal buffy coats (BC), 7 normal placentas (NP) and 14 complete molar pregnancies (CM) using a TCR beta chain and 25 variable TCR beta chain primers. Relative expressions were calculated for each individual gene. RESULTS: Significant changes were noted in most of the gene expressions in NP and CM as compared to the buffy coat samples. The relative expression of most genes was significantly decreased in NP and CM, but VBC gene number 4 was increased in both NP and CM, however, a significant difference was noted only between BC and CM (p = 0.023). Comparing NP to CM, 5 other VBC gene expressions were decreased significantly in the CM tissues (p < 0.05). CONCLUSION: In normal placenta and CM pregnancies, T cells appear to express certain TCR VBC genes in a different manner than in BC. These genes and the VBC gene profile difference found between NP and CM may play an important role in the immunobiology of CM pregnancy. C1 [Berkowitz, Ross S.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Lab Gynecol Oncol,New England Trophoblast Dis Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst,Brigham & Womens Hosp, Trophoblast Tumor Registry,Dept Obstet & Gynecol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. State Hlth Ctr, Dept Obstet & Gynecol, Budapest, Hungary. Semmelweis Univ, H-1085 Budapest, Hungary. RP Berkowitz, RS (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Lab Gynecol Oncol,New England Trophoblast Dis Ctr, 75 Francis St, Boston, MA 02115 USA. EM rberkowitz@partners.org NR 27 TC 1 Z9 1 U1 0 U2 1 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD JUL PY 2008 VL 53 IS 7 BP 528 EP 534 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 326WO UT WOS:000257690000013 PM 18720929 ER PT J AU Fulop, V Szigetvari, I Szepesi, J Torok, M Berkowitz, RS AF Fueloep, Vilmos Szigetvari, Ivan Szepesi, Janos Toeroek, Miklos Berkowitz, Ross S. TI Diagnosis and treatment of high-risk metastatic gestational trophoblastic neoplasia in Hungary SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article; Proceedings Paper CT 14th World Congress on Gestational Trophoblastic Diseases CY NOV 11-14, 2007 CL Fukuoka, JAPAN DE chemotherapy; gestational trophoblastic neoplasia; prognostic score; staging ID ACTINOMYCIN-D; DISEASE; METHOTREXATE; ETOPOSIDE; REGIMEN; TUMORS AB OBJECTIVE: To review results in treatment of high-risk metastatic gestational trophoblastic neoplasia (GTN) in Hungary. STUDY DESIGN: Between January 1, 1977, and December 31, 2006, 142 patients with high-risk metastatic GIN were treated. Patients were 14-51 years of age primary chemotherapy based on patient GTN stage and prognostic score. RESULTS: Methotrexate, actinomycin-D and cyclophosphamide (MAC) as a primary therapy was used in 100 cases and as second-line chemotherapy in 6 cases. Of the 100 cases, 95 achieved complete remission. Twenty-one high-risk patients were treated with etoposide, high-dose methotrexate with folinic acid rescue, actinomycin-D, cyclophosphamide and vincristine (EMA-CO). Of 17 primary therapies, 13 patients achieved complete remission. Primary cisplatin, etoposide and bleomycin (CEB) was successful in 12 of 14 high-risk cases. Hysterectomy was performed in 42 of 142 high-risk patients; metastases were resected in 26 of 142 of high-risk patients. Comparison of mean prognostic scores resulted in significant differences between CEB and MAC, CEB and EMA-CO and MAC and EMA-CO. CONCLUSION: Results support that Patients with high-risk metastatic GTN should primarily be treated with combination chemotherapy. Our data support the effectiveness of MAC, EMA-CO and CEB regimens. C1 [Fueloep, Vilmos] State Hlth Ctr, Dept Obstet & Gynecol, H-1062 Budapest, Hungary. Gyula Nyiro Hosp, Dept Obstet & Gynecol, Budapest, Hungary. Harvard Univ, Sch Med, Dana Farber Canc Inst,Brigham & Womens Hosp, New England Trophoblast Dis Ctr,Div Gynecol Oncol, Boston, MA 02115 USA. RP Fulop, V (reprint author), State Hlth Ctr, Dept Obstet & Gynecol, 111 Podmaniczky St, H-1062 Budapest, Hungary. EM fulopvilmos@freemail.hu NR 13 TC 0 Z9 0 U1 0 U2 2 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD JUL PY 2008 VL 53 IS 7 BP 541 EP 546 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 326WO UT WOS:000257690000015 PM 18720931 ER PT J AU Coates, LC Anderson, RR Fitzgerald, O Gottlieb, AB Kelly, SG Lubrano, E Mcgonagle, DG Olivieri, I Ritchlin, CT Tan, AL de Vlam, K Helliwell, PS AF Coates, Laura C. Anderson, R. Rox Fitzgerald, Oliver Gottlieb, Alice B. Kelly, Stephen G. Lubrano, Ennio Mcgonagle, Dennis G. Olivieri, Ignazio Ritchlin, Christopher T. Tan, Ai Lyn de Vlam, Kurt Helliwell, Philip S. TI Clues to the pathogenesis of psoriasis and psoriatic arthritis from imaging: A literature review SO JOURNAL OF RHEUMATOLOGY LA English DT Review DE psoriatic arthritis; psoriasis; dactylitis; enthesitis; nail psoriasis ID DISTAL INTERPHALANGEAL JOINT; RHEUMATOID-ARTHRITIS; ANKYLOSING-SPONDYLITIS; POWER-DOPPLER; INFLAMMATORY ARTHRITIS; IN-VIVO; MRI; DACTYLITIS; ULTRASOUND; DISEASE AB This article summarizes a presentation on imaging of skin and joints in patients with psoriasis and psoriatic arthritis (PsA) from the 2007 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Plain radiography provides valuable insights into the pathogenesis of PsA but is limited because only calcified tissue can be imaged. Newer techniques such as magnetic resonance imaging (MRI) and ultrasound (US) provide additional clues to the pathogenesis of this peripheral, axial, and dermatologic disease. MRI and to a lesser extent US allow visualization of articular and periarticular structures, showing widespread juxtaarticular inflammation in PsA. Bone edema, a surrogate marker of inflammation, can occur throughout the digit in psoriatic dactylitis. Localization of inflammatory change at the juxtaarticular entheses suggests this as the primary site of inflammation. Recent imaging studies provide insights into the relationship between nail and articular disease, demonstrating extension of inflammation from entheseal structures at the distal interphalangeal joint to the nail bed, but the temporal or anatomical progression of these changes remains elusive. Imaging of the skin lags behind that of the articular structures, partly because the skin is readily available for biopsy; however, newer techniques such as laser Doppler imaging provide insights into angiogenesis at the advancing edge of psoriatic plaques. Future work will explore the relationship between immunohistology and imaging of skin and joints. Improvements in imaging articular soft tissues with ultra-short echo time MRI and skin with multiphoton fluorescence microscopy promise insights into anatomical and functional changes. C1 [Helliwell, Philip S.] Univ Leeds, Acad Unit Musculoskeletal & Rehabil Med, Acad Sect Musculoskeletal Dis, Leeds LS2 9NZ, W Yorkshire, England. [Anderson, R. Rox] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Fitzgerald, Oliver] St Vincents Univ Hosp, Dept Rheumatol, Dublin 4, Ireland. [Gottlieb, Alice B.] Tufts Univ New England Med Ctr, Dept Dermatol, Boston, MA USA. [Gottlieb, Alice B.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Olivieri, Ignazio] San Carlo Hosp Potenza, Rheumatol Dept Lucania, Matera, Italy. [Olivieri, Ignazio] Madonna Grazie Hosp Matera, Matera, Italy. [Ritchlin, Christopher T.] Univ Rochester, Med Ctr, Clin Immunol Res Unit, Rochester, NY USA. [de Vlam, Kurt] Katholieke Univ Leuven Hosp, Dept Rheumatol, Louvain, Belgium. RP Helliwell, PS (reprint author), Univ Leeds, Acad Unit Musculoskeletal & Rehabil Med, Acad Sect Musculoskeletal Dis, 36 Clarendon Rd, Leeds LS2 9NZ, W Yorkshire, England. EM p.helliwell@leeds.ac.uk OI LUBRANO DI SCORPANIELLO, Ennio/0000-0001-6189-5328 NR 43 TC 19 Z9 22 U1 0 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUL PY 2008 VL 35 IS 7 BP 1438 EP 1442 PG 5 WC Rheumatology SC Rheumatology GA 324YD UT WOS:000257554400040 PM 18609741 ER PT J AU Wang, ML Hanfelt, JJ AF Wang, Molin Hanfelt, John J. TI Robust modified profile estimating function with application to the generalized estimating equation SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE bias correction; generalized estimating equation; information unbiasedness; Neyman-Scott problem; nuisance parameter; profile estimating function; sparse data ID APPROXIMATE CONDITIONAL INFERENCE; LONGITUDINAL DATA-ANALYSIS; NUISANCE PARAMETERS; MODELS; LIKELIHOOD AB We consider methods for reducing the effect of fitting nuisance parameters on a general estimating function, when the estimating function depends on not only a vector of parameters of interest, theta, but also on a vector of nuisance parameters lambda. We propose a class of modified profile estimating functions with plug-in bias reduced by two orders. A robust version of the adjustment term does not require any information about the probability mechanism beyond that required by the original estimating function. An important application of this method is bias correction for the generalized estimating equation in analyzing stratified longitudinal data, where the stratum-specific intercepts are considered as fixed nuisance parameters, the dependence of the expected outcome on the covariates is of interest, and the intracluster correlation structure is unknown. Furthermore, when the quasi-scores for theta and lambda are available, we propose an additional multiplicative adjustment term such that the modified profile estimating function is approximately information unbiased. This multiplicative adjustment term can serve as an optimal weight in the analysis of stratified studies. A brief simulation study shows that the proposed method considerably reduces the impact of the nuisance parameters. (C) 2007 Elsevier B.V. All rights reserved. C1 [Wang, Molin] Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. [Wang, Molin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hanfelt, John J.] Emory Univ, Dept Biostat, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. RP Wang, ML (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. EM mwang@jimmy.harvard.edu NR 21 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD JUL 1 PY 2008 VL 138 IS 7 BP 2029 EP 2044 DI 10.1016/j.jspi.2007.08.007 PG 16 WC Statistics & Probability SC Mathematics GA 295AT UT WOS:000255448100010 ER PT J AU Izard, J Hsieh, CE Limberger, RJ Mannella, CA Marko, M AF Izard, Jacques Hsieh, Chyong-Ere Limberger, Ronald J. Mannella, Carmen A. Marko, Michael TI Native cellular architecture of Treponema denticola revealed by cryo-electron tomography SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE intermediate-like filament; flagella; motility; cell division; spirochetes; electron microscopy; septation ID FILAMENT-DEFICIENT MUTANT; ELECTRON TOMOGRAPHY; ESCHERICHIA-COLI; CYTOPLASMIC FILAMENTS; PERIPLASMIC FLAGELLA; MICROSCOPY; MORPHOLOGY; MECHANISM; MOTILITY; RECONSTRUCTION AB Using cryo-electron tomography, we are developing a refined description of native cellular structures in the pathogenic spirochete Treponema denticola. Tightly organized bundles of periplasmic flagella were readily observed in intact plunge-frozen cells. The periplasmic space was measured in both wild-type and aflagellate strains, and found to widen by less than the diameter of flagella when the latter are present. This suggests that a structural change occurs in the peptidoglycan layer to accommodate the presence of the flagella. In dividing cells, the flagellar filaments were found to bridge the cytoplasmic cylinder constriction site. Cytoplasmic filaments, adjacent to the inner membrane, run parallel to the tightly organized flagellar filaments. The cytoplasmic filaments may be anchored by a narrow plate-like structure. The tapering of the cell ends was conserved between cells, with a patella-shaped structure observed in the periplasm at the tip of each cytoplasmic cylinder. Several incompletely characterized structures have been observed in the periplasm between dividing cells, including a cable-like structure linking two cytoplasmic cylinders and complex foil-shaped structures. (C) 2008 Elsevier Inc. All rights reserved. C1 [Izard, Jacques] Forsyth Inst, Dept Mol Genet, Boston, MA 02135 USA. [Izard, Jacques] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Izard, Jacques; Limberger, Ronald J.; Mannella, Carmen A.] Sch Publ Hlth, Dept Biomed Sci, Albany, NY 12201 USA. [Hsieh, Chyong-Ere; Limberger, Ronald J.; Mannella, Carmen A.; Marko, Michael] New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA. RP Izard, J (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02135 USA. EM JIzard@forsyth.org RI Izard, Jacques/A-6074-2012; OI Izard, Jacques/0000-0002-5904-5436 FU NCRR NIH HHS [P41 RR001219, P41 RR001219-180043, P41 RR001219-19A10043, P41 RR001219-19A1S10043, P41 RR001219-200043, P41 RR001219-210043, P41 RR001219-230084, P41 RR001219-230096, P41 RR001219-257214, P41 RR001219-257228, P41 RR001219-266252, P41 RR001219-266267, P41 RR001219-27, P41 RR01219]; NIAID NIH HHS [R01 AI034354-09, AI35354, R01 AI034354-06A1, R01 AI034354-07, R01 AI034354-08]; NIDCR NIH HHS [DE07106, R21 DE017106, R21 DE017106-01A1, R21 DE017106-02] NR 56 TC 27 Z9 27 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD JUL PY 2008 VL 163 IS 1 BP 10 EP 17 DI 10.1016/j.jsb.2008.03.009 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 326WU UT WOS:000257690600002 PM 18468917 ER PT J AU Eberlin, KR McCormack, MC Nguyen, JT Tatlidede, HS Randolph, MA Austen, WG AF Eberlin, Kyle R. McCormack, Michael C. Nguyen, John T. Tatlidede, H. Soner Randolph, Mark A. Austen, William G., Jr. TI Ischemic preconditioning of skeletal muscle mitigates remote injury and mortality SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT 52nd Annual Meeting of the Plastic-Surgical-Research-Council CY JUN 20-23, 2007 CL Stanford, CA SP Plast Surg Res Council DE ischemic preconditioning; ischemia-reperfusion injury; remote injury; mortality; skeletal muscle ID REPERFUSION INJURY; OXYGEN RADICALS; NITRIC-OXIDE; SKIN FLAPS; RAT MODEL; ADENOSINE; MYOCARDIUM; CARDIOPROTECTION; RECEPTORS; PROTECTS AB Background. Ischemic preconditioning (IPC) mitigates ischemia-reperfusion (I/R) injury in experimental models. However, the clinical significance of this protection has been unclear and a mortality reduction has not been previously reported in noncardiac models. This study examined the local and remote protection afforded by skeletal muscle IPC and sought to determine the significance of this protection on mortality. Methods. Mice subjected to 2 h hindlimb ischemia/24 h reperfusion (standard I/R injury) were compared with those undergoing a regimen of two 20-min cycles of IPC followed by standard I/R injury. Local injury was assessed via gastrocnemius histology, and remote injury was evaluated via intestinal histology and pulmonary neutrophil infiltration (n = 7). Mortality was compared in parallel groups for 1 week (n = 6). Groups were analyzed using an unpaired Student's t-test for gastrocnemius and pulmonary injury, and a Mann-Whitney rank sum test for intestinal injury. Mortality differences were interpreted through a hazard ratio. Results. Significant protection was observed in preconditioned animals. There was a 35% local injury reduction in skeletal muscle (71.2% versus 46.0%, P < 0.01), a 50% reduction in remote intestinal injury (2.3 versus 1.1, P < 0.01), and a 43% reduction in remote pulmonary injury (14.9 versus 8.5, P < 0.01) compared with standard injury controls. Preconditioned animals were also significantly protected from mortality, demonstrating a 66.7% survival at 1 wk compared with 0% survival after standard injury alone (hazard ratio 0.20, 95% CI: 0.02-0.59). Conclusions. We have developed a murine model of IPC that demonstrates local and remote protection against LIR injury, and exhibits significant mortality reduction. This model demonstrates the powerful effect of IPC on local and remote tissues and will facilitate further study of potential mechanisms and therapies. (C) 2008 Elsevier Inc. All rights reserved. C1 [Eberlin, Kyle R.; McCormack, Michael C.; Nguyen, John T.; Tatlidede, H. Soner; Randolph, Mark A.; Austen, William G., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Plast Surg Res Lab,Div Plast Surg, Boston, MA 02114 USA. RP Austen, WG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, Wang Bldg,ACC-435,15 Parkman St, Boston, MA 02114 USA. EM wausten@partners.org NR 38 TC 18 Z9 20 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUL PY 2008 VL 148 IS 1 BP 24 EP 30 DI 10.1016/j.jss.2008.01.040 PG 7 WC Surgery SC Surgery GA 316FZ UT WOS:000256936000005 PM 18570927 ER PT J AU Ravicz, ME Cooper, NP Rosowski, JJ AF Ravicz, Michael E. Cooper, Nigel P. Rosowski, John J. TI Gerbil middle-ear sound transmission from 100 Hz to 60 kHz SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID MONGOLIAN GERBIL; INTRACOCHLEAR PRESSURE; INPUT IMPEDANCE; MERIONES-UNGUICULATUS; EXTERNAL-EAR; RADIATION IMPEDANCE; AUDITORY PERIPHERY; POWER COLLECTION; HEARING; CAT AB Middle-ear sound transmission was evaluated as the middle-ear transfer admittance H-MY (the ratio of stapes velocity to ear-canal sound pressure near the umbo) in gerbils during closed-field sound stimulation at frequencies from 0.1 to 60 kHz, a range that spans the gerbil's audiometric range. Similar measurements were performed in two laboratories. The H-MY magnitude (a) increased with frequency below 1 kHz, (b) remained approximately constant with frequency from 5 to 35 kHz, and (c) decreased substantially from 35 to 50 kHz. The H-MY phase increased linearly with frequency from 5 to 35 kHz, consistent with a 20-29 mu s delay, and flattened at higher frequencies. Measurements from different directions showed that stapes motion is predominantly pistonlike except in a narrow frequency band around 10 kHz. Cochlear input impedance was estimated from H-MY and previously-measured cochlear sound pressure. Results do not support the idea that the middle ear is a lossless matched transmission line. Results support the ideas that (1) middle-ear transmission is consistent with a mechanical transmission line or multiresonant network between 5 and 35 kHz and decreases at higher frequencies, (2) stapes motion is pistonlike over most of the gerbil auditory range, and (3) middle-ear transmission properties are a determinant of the audiogram. (c) 2008 Acoustical Society of America. C1 [Ravicz, Michael E.; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Ravicz, Michael E.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Cooper, Nigel P.] Univ Keele, Sch Life Sci, Keele ST5 5BG, Staffs, England. [Rosowski, John J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Rosowski, John J.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Ravicz, ME (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM mike_ravicz@meei.harvard.edu FU NIDCD NIH HHS [R01 DC000194, R01 DC000194-25A1, R01-DC00194]; Wellcome Trust NR 47 TC 34 Z9 34 U1 0 U2 2 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JUL PY 2008 VL 124 IS 1 BP 363 EP 380 DI 10.1121/1.2932061 PG 18 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 327ZW UT WOS:000257768000035 PM 18646983 ER PT J AU Shera, CA Tubis, A Talmadge, CL AF Shera, Christopher A. Tubis, Arnold Talmadge, Carrick L. TI Testing coherent reflection in chinchilla: Auditory-nerve responses predict stimulus-frequency emissions SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID SPONTANEOUS OTOACOUSTIC EMISSIONS; MEMBRANE CLICK RESPONSES; BASILAR-MEMBRANE; MIDDLE-EAR; MOSSBAUER TECHNIQUE; ACOUSTIC EMISSIONS; GROUP DELAY; GUINEA-PIG; COCHLEA; WAVE AB Coherent-reflection theory explains the generation of stimulus-frequency and transient-evoked otoacoustic emissions by showing how they emerge from the coherent "backscattering" of forward-traveling waves by mechanical irregularities in the cochlear partition. Recent published measurements of stimulus-frequency otoacoustic emissions (SFOAEs) and estimates of near-threshold basilar-membrane (BM) responses derived from Wiener-kernel analysis of auditory-nerve responses allow for comprehensive tests of the theory in chinchilla. Model predictions are based on (1) an approximate analytic expression for the SFOAE signal in terms of the BM traveling wave and its complex wave number, (2) an inversion procedure that derives the wave number from BM traveling waves, and (3) estimates of BM traveling waves obtained from the Wiener-kernel data and local scaling assumptions. At frequencies above 4 kHz, predicted median SFOAE phase-gradient delays and the general shapes of SFOAE magnitude-versus-frequency curves are in excellent agreement with the measurements. At frequencies below 4 kHz, both the magnitude and the phase of chinchilla SFOAEs show strong evidence of interference between short- and long-latency components. Approximate unmixing of these components, and association of the long-latency component with the predicted SFOAE, yields close agreement throughout the cochlea. Possible candidates for the short-latency SFOAE component, including wave-fixed distortion, are considered. Both empirical and predicted delay ratios (long-latency SFOAE delay/BM delay) are significantly less than 2 but greater than 1. Although these delay ratios contradict models in which SFOAE generators couple primarily into cochlear compression waves, they are consistent with the notion that forward and reverse energy propagation in the cochlea occurs predominantly by means of traveling pressure-difference waves. The compelling overall agreement between measured and predicted delays suggests that the coherent-reflection model captures the dominant mechanisms responsible for the generation of reflection-source otoacoustic emissions. (c) 2008 Acoustical Society of America. C1 [Shera, Christopher A.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. [Shera, Christopher A.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Tubis, Arnold] Purdue Univ, Dept Phys, W Lafayette, IN 47907 USA. [Tubis, Arnold] Univ Calif San Diego, Inst Nonlinear Sci, La Jolla, CA 92093 USA. [Talmadge, Carrick L.] Univ Mississippi, Natl Ctr Phys Acoust, University, MS 38677 USA. RP Shera, CA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. EM shera@epl.meei.harvard.edu FU NIDCD NIH HHS [R01 DC003687, R01 DC003687-10] NR 72 TC 28 Z9 29 U1 0 U2 0 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JUL PY 2008 VL 124 IS 1 BP 381 EP 395 DI 10.1121/1.2917805 PG 15 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 327ZW UT WOS:000257768000036 PM 18646984 ER PT J AU Gallun, FJ Durlach, NI Colburn, HS Shinn-Cunningham, BG Best, V Mason, CR Kidd, G AF Gallun, Frederick J. Durlach, Nathaniel I. Colburn, H. Steven Shinn-Cunningham, Barbara G. Best, Virginia Mason, Christine R. Kidd, Gerald, Jr. TI The extent to which a position-based explanation accounts for binaural release from informational masking SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article; Proceedings Paper CT 30th Midwinter Meeting of the Association-for-Reseach-in-Otolaryngology CY FEB 10-15, 2007 CL Denver, CO SP Assoc Res Otolaryngol ID LEVEL DIFFERENCES; INTERAURAL FLUCTUATIONS; CANCELLATION THEORY; SPATIAL SEPARATION; GATED-NOISE; SPEECH; MASKERS; FREQUENCY; UNMASKING; TIME AB Detection was measured for a 500 Hz tone masked by noise (an "energetic" masker) or sets of ten randomly drawn tones (an "informational" masker). Presenting the maskers diotically and the target tone with a variety of interaural differences (interaural amplitude ratios and/or interaural time delays) resulted in reduced detection thresholds relative to when the target was presented diotically ("binaural release from masking"). Thresholds observed when time and amplitude differences applied to the target were "reinforcing" (favored the same ear, resulting in a lateralized position for the target) were not significantly different from thresholds obtained when differences were "opposing" (favored opposite ears, resulting in a centered position for the target). This irrelevance of differences in the perceived location of the target is a classic result for energetic maskers but had not previously been shown for informational maskers. However, this parallellism between the patterns of binaural release for energetic and informational maskers was not accompanied by high correlations between the patterns for individual listeners, supporting the idea that the mechanisms for binaural release from energetic and informational masking are fundamentally different. (c) 2008 Acoustical Society of America. C1 [Gallun, Frederick J.; Durlach, Nathaniel I.; Colburn, H. Steven; Shinn-Cunningham, Barbara G.; Best, Virginia; Mason, Christine R.; Kidd, Gerald, Jr.] Boston Univ, Hearing Res Ctr, Boston, MA 02215 USA. RP Gallun, FJ (reprint author), Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM frederick.gallun@va.gov RI Gallun, Frederick/G-3792-2012 OI Gallun, Frederick/0000-0002-4145-2199 FU NIDCD NIH HHS [DC00100, DC04545, DC04663, F32 DC006526, F32 DC006526-03, P30 DC004663, P30 DC004663-03, R01 DC000100, R01 DC000100-33, R01 DC004545, R01 DC004545-08, R03 DC008395, R03 DC008395-02] NR 44 TC 7 Z9 7 U1 0 U2 3 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JUL PY 2008 VL 124 IS 1 BP 439 EP 449 DI 10.1121/1.2924127 PG 11 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 327ZW UT WOS:000257768000040 PM 18646988 ER PT J AU Vaughan, N Storzbach, D Furukawa, I AF Vaughan, Nancy Storzbach, Daniel Furukawa, Izumi TI Investigation of Potential Cognitive Tests for Use with Older Adults in Audiology Clinics SO JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY LA English DT Article; Proceedings Paper CT Annual Convention of the American-Speech-Language-Hearing-Association CY NOV 16-18, 2006 CL Miami, FL SP Amer Speech Language Hearing Assoc DE Neurocognitive tests; principal components analysis; speech recognition ID WORKING-MEMORY; ELDERLY LISTENERS; SPEECH RECOGNITION; HEARING-LOSS; AGE; COMPREHENSION; ATTENTION; CAPACITY; DEFICITS; TASKS AB Background: Cognitive declines in working memory and processing speed are hallmarks of aging. Deficits in speech understanding also are seen in aging individuals. A clinical test to determine whether the cognitive aging changes contribute to aging speech understanding difficulties would be helpful for determining rehabilitation strategies in audiology clinics. Purpose: To identify a clinical neurocognitive test or battery of tests that could be used in audiology clinics to help explain deficits in speech recognition in some older listeners. Research Design: A correlational study examining the association between certain cognitive test scores and speech recognition performance. Speeded (time-compressed) speech was used to increase the cognitive processing load. Study Sample: Two hundred twenty-five adults aged 50 through 75 years were participants in this study. Both batteries of tests were administered to all participants in two separate sessions. Data Collection and Analysis: A selected battery of neurocognitive tests and a time-compressed speech recognition test battery using various rates of speech were administered. Principal component analysis was used to extract the important component factors from each set of tests, and regression models were constructed to examine the association between tests and to identify the neurocognitive test most strongly associated with speech recognition performance. Results: A sequencing working memory test (Letter-Number Sequencing [LNS]) was most strongly associated with rapid speech understanding. The association between the LNS test results and the compressed sentence recognition scores (CSRS) was strong even when age and hearing loss were controlled. Conclusions: The LNS is a sequencing test that provides information about temporal processing at the cognitive level and may prove useful in diagnosis of speech understanding problems, and in the development of aural rehabilitation and training strategies. C1 [Vaughan, Nancy; Storzbach, Daniel; Furukawa, Izumi] Portland VA Med Ctr, Vet Affairs Natl Ctr Rehabilitat Auditory Res, Portland, OR 97239 USA. RP Storzbach, D (reprint author), Portland VA Med Ctr, Vet Affairs Natl Ctr Rehabilitat Auditory Res, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM Daniel.Storzbach@med.va.gov NR 31 TC 6 Z9 8 U1 1 U2 9 PU AMER ACAD AUDIOLOGY PI RESTON PA 11730 PLAZA DR, STE 300, RESTON, VA 20190 USA SN 1050-0545 J9 J AM ACAD AUDIOL JI J. Am. Acad. Audiol. PD JUL-AUG PY 2008 VL 19 IS 7 BP 533 EP 541 DI 10.3766/jaaa.19.7.2 PG 9 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 386IG UT WOS:000261876300002 PM 19248729 ER PT J AU Stewart, SE Rosario, MC Baer, L Carter, AS Brown, TA Scharf, JM Illmann, C Leckman, JF Sukhodolsky, D Katsovich, L Rasmussen, S Goodman, W Delorme, R Leboyer, M Chabane, N Jenike, MA Geller, DA Pauls, DL AF Stewart, S. Evelyn Rosario, Maria C. Baer, Lee Carter, Alice S. Brown, Timothy A. Scharf, Jeremiah M. Illmann, Cornelia Leckman, James F. Sukhodolsky, Denis Katsovich, Lilya Rasmussen, Steven Goodman, Wayne Delorme, Richard Leboyer, Marion Chabane, Nadia Jenike, Michael A. Geller, Daniel A. Pauls, David L. TI Four-factor structure of obsessive-compulsive disorder symptoms in children, adolescents, and adults SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE obsessive-compulsive disorder; age; factor analysis; symptom dimension; quantitative trait ID MISCELLANEOUS SYMPTOMS; PERSONALITY-DISORDERS; YOUNG-CHILDREN; DIMENSIONS; FAMILIALITY; PHENOTYPES; SCALE; OCD; STABILITY; GENETICS AB Objective: To determine whether the four-factor category-based obsessive-compulsive disorder (OCD) symptom structure from a previous confirmatory factor analysis (CFA) may be appropriately used in child, adolescent, and adult groups. Symptom dimensions are increasingly used as quantitative traits in genetic, neuroimaging, and treatment studies of OCD across all ages. Identification of a category-based OCD symptom dimension structure that is validated for use across child, adolescent, and adult age groups is necessary to guide ongoing translational research. Method: Four OCD samples comprising 356 individuals were divided into child, adolescent, and adult groups. The fit of the only CFA-defined four-factor model was compared across these independent age group samples. Multiple-group CFA using maximum likelihood estimation assessed adequacy of fit comparing unconstrained and measurement weight-constrained models. The fit of previous exploratory factor analysis-defined three- and five-factor models on adults was also examined using CFA. Results: A four-factor solution provided adequate but imperfect fit across age groups, with comparable indices to the only previous OCD CFA: factor 1 (aggressive/sexual/religious/somatic/checking); factor 2 (symmetry/ordering/counting/ repeating); factor 3 (contamination/cleaning), and factor 4 (hoarding). Models in which factor loadings were constrained and unconstrained across the three age groups yielded comparable model fit. Factors were highly correlated and were not mutually exclusive. The four-factor solution provided an improved fit to both three- and five-factor solutions using CFA across the three age groups. Conclusions: A four-factor, CFA-defined, category-based model of OCD symptom dimensions is adequate for use in children, adolescents, and adult age groups. The factor structure of this multiple age group sample has limitations and is imperfect, but current findings support the comparability of the defined latent OCD dimensions across age groups. Further work is needed to optimize a comprehensive symptom dimension model reflecting clinical heterogeneity for use in emergent translational studies. C1 [Stewart, S. Evelyn; Baer, Lee; Scharf, Jeremiah M.; Illmann, Cornelia; Geller, Daniel A.; Pauls, David L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rosario, Maria C.] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Brown, Timothy A.] Boston Univ, Boston, MA 02215 USA. [Leckman, James F.; Sukhodolsky, Denis; Katsovich, Lilya] Yale Univ, New Haven, CT 06520 USA. [Carter, Alice S.] Univ Massachusetts, Amherst, MA 01003 USA. [Rasmussen, Steven] Brown Univ, Providence, RI 02912 USA. [Goodman, Wayne] Natl Inst Hlth, Bethesda, MD 20892 USA. [Delorme, Richard; Chabane, Nadia] Hop Robert Debre, F-75019 Paris, France. [Leboyer, Marion] Mondor Chenevier Hosp, Creteil, France. RP Pauls, DL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 185 Cambridge St, Boston, MA 02114 USA. EM pauls@pngu.mgh.harvard.edu RI Stewart, Evelyn/K-6961-2014; do Rosario, Maria Conceicao/E-5213-2012; OI do Rosario, Maria Conceicao/0000-0002-9687-0072; Sukhodolsky, Denis/0000-0002-5401-792X; Stewart, S. Evelyn/0000-0002-0994-6383 FU NIMH NIH HHS [K08-MH01481, MH49351]; NINDS NIH HHS [R01-NS16648] NR 48 TC 48 Z9 49 U1 2 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 2008 VL 47 IS 7 BP 763 EP 772 DI 10.1097/CHI.0b013e318172ef1e PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 319HC UT WOS:000257153700007 PM 18520961 ER PT J AU Antshel, KM Faraone, SV Maglione, K Doyle, A Fried, R Seidman, L Biederman, J AF Antshel, Kevin M. Faraone, Stephen V. Maglione, Katharine Doyle, Alysa Fried, Ronna Seidman, Larry Biederman, Joseph TI Temporal stability of ADHD in the high-IQ population: Results from the MGH Longitudinal Family Studies of ADHD SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; IQ; gifted; diagnosis; intelligence ID ATTENTION-DEFICIT HYPERACTIVITY; WECHSLER INTELLIGENCE SCALE; AGE-DEPENDENT DECLINE; LONG-TERM STABILITY; FOLLOW-UP; CIGARETTE-SMOKING; WISC-R; DISORDER; CHILDREN; APPOINTMENTS AB Objective: The diagnosis of attention-deficit/hyperactivity disorder (ADHD) in high-IQ youths remains controversial. Method: To further explore the diagnostic validity of ADHD in this population, we studied two cohorts of high-IQ youths, both with and without ADHD, across a 4.5-year period. Results: Compared to those without ADHD, high-IQ youths with ADHD had significantly higher rates of mood, anxiety, and disruptive behavior disorders at follow-up. In addition, ADHD status was a significant predictor for higher impairments across most social, academic, and family functional domains. Associations between baseline and follow-up IQ scores did not differ between groups. Syndromal persistence rates of ADHD were similar between high-IQ and average-IQ youths with ADHD. Conclusions: These results provide further support for the predictive validity of ADHD in high-IQ youths. C1 [Antshel, Kevin M.; Faraone, Stephen V.; Maglione, Katharine] SUNY Upstat Med Univ, Dept Psychiat & Behav Sci, New York, NY USA. [Doyle, Alysa; Fried, Ronna; Seidman, Larry; Biederman, Joseph] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Doyle, Alysa; Fried, Ronna; Seidman, Larry; Biederman, Joseph] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Biederman, J (reprint author), ACC 725,15 Parkman St, Boston, MA 02114 USA. EM biederman@helix.mgh.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [501 HD-36317]; NIMH NIH HHS [R01 MH41314] NR 46 TC 17 Z9 17 U1 3 U2 22 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 2008 VL 47 IS 7 BP 817 EP 825 DI 10.1097/CHI.0b013e318172eecf PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 319HC UT WOS:000257153700013 PM 18520956 ER PT J AU Lott, JP Werth, VP Kovarik, CL AF Lott, Jason P. Werth, Victoria P. Kovarik, Carrie L. TI Cutaneous Mycobacterium haemopbhilum infection in iatrogenically immunocompromised patients without transplantation SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID HAEMOPHILUM INFECTION; SP-NOV; SKIN; HUMANS AB Cutaneous Mycobacterium haemophilum infections are most often the result of HIV or transplantation-associated immunosuppression. Rarely, M haemophilum, may infect healthy patients or iatrogenically immunosuppressed patients without transplantation. We herein report two cases of cutaneous M haemophilum infection in HIV-negative patients without transplantation undergoing iatrogenic immunosuppression. Our cases and a literature review highlight the various clinical contexts in which M haemophilum may arise in this patient population. Accordingly, we emphasize that a high index of suspicion is needed for diagnosis, which ultimately relies on skin biopsy, histopathologic examination, and culture. C1 [Lott, Jason P.; Werth, Victoria P.; Kovarik, Carrie L.] Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19130 USA. [Kovarik, Carrie L.] Univ Penn, Sch Med, Dept Internal Med, Div Infect Dis, Philadelphia, PA 19130 USA. [Werth, Victoria P.; Kovarik, Carrie L.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Kovarik, CL (reprint author), Univ Penn, Sch Med, Dept Dermatol, 3600 Spruce St,2 Maloney Bldg, Philadelphia, PA 19130 USA. EM carrie.kovarik@uphs.upenn.edu NR 22 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUL PY 2008 VL 59 IS 1 BP 139 EP 142 DI 10.1016/j.jaad.2008.01.023 PG 4 WC Dermatology SC Dermatology GA 318UM UT WOS:000257118300018 PM 18328595 ER PT J AU White, JV Ayoob, KT Benedict, MA Chynoweth, MD Gregoire, M Howard, RL McCool, A Parrott, S Ramsey, SH Thiessen, C Thomsen, KN Bender, T Myers, E Michael, P AF White, Jane V. Ayoob, Keith T. Benedict, Melinda A. Chynoweth, Michele D. Gregoire, Mary Howard, Robert L. McCool, Audrey Parrott, Scott Ramsey, Susan H. Thiessen, Charlotte Thomsen, Kim N. Bender, Tori Myers, Esther Michael, Pam TI Registered dietitians' coding practices and patterns of code use SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article AB Coding, coverage, and reimbursement are vital to the clinical segment of our profession. The objective of this study was to assess understanding and use of the medical nutrition therapy (MNT) procedure codes. Its design was a targeted, cross-sectional, Internet survey. Participants were registered dietitians (RDs) preselected based on Medicare Part B provider status, randomly selected RDs from the American Dietetic Association database based on clinical practice designation, and self-selected RDs. Parameters assessed were knowledge and use of existing MNT and/or alternative procedure codes, barriers to code use/compensation, need for additional codes for existing/emerging services, and practice demographics. Results suggest that MNT is being reimbursed for a variety of diseases and conditions. Many RDs working in clinic settings are undereducated about code use of any kind, reporting that code selection frequently is determined not by the RD providing the service, but by "someone else." Self-employed RDs are less likely to rely on others to administrate paperwork required for reimbursement, including selection of procedure codes for billable nutrition. services. Self-employed RDs are more likely to be reimbursed by private or commercial payers and RDs working in clinic settings are more likely to be reimbursed by Medicare; however, the proportion of Medicare providers in both groups is high. RDs must be knowledgeable and accountable for both the business and clinical side of their nutrition practices; using correct codes and following payers' claims processing policies and procedures. This survey and analysis is a first step in understanding the complex web of relationships between clinical practice, MNT code use, and reimbursement. C1 [White, Jane V.] Univ Tennessee, Dept Family Med, Knoxville, TN 37920 USA. [Ayoob, Keith T.] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. [Gregoire, Mary] Rush Univ, Med Ctr, Food & Nutr Serv, Chicago, IL 60612 USA. [Howard, Robert L.] Midtown Nutr, New York, NY USA. [McCool, Audrey] Univ Nevada, William F Harrah Coll Hotel Adm, Las Vegas, NV 89154 USA. [Ramsey, Susan H.] Sodexho Hlth Care Serv, Washington Crossing, PA USA. [Thiessen, Charlotte] US Dept Vet Affairs, Nebraska Western Iowa Healthcare Syst, Omaha, NE USA. [Thomsen, Kim N.] USA, Med Command Headquarters, Ft Sam Houston, TX USA. [Bender, Tori; Michael, Pam] Amer Dietet Assoc, Nutr Serv Coverage Team, Chicago, IL USA. [Myers, Esther] Amer Dietet Assoc, Sci Affairs & Res Team, Chicago, IL USA. RP White, JV (reprint author), Univ Tennessee, Dept Family Med, 1924 Alcoa Hwy, Knoxville, TN 37920 USA. EM jwhite13@utk.edu NR 2 TC 1 Z9 1 U1 0 U2 0 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JUL PY 2008 VL 108 IS 7 BP 1242 EP 1248 DI 10.1016/j.jada.2008.04.015 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 321KG UT WOS:000257303000030 PM 18589037 ER PT J AU Boockvar, KS Gruber-Baldini, AL Stuart, B Zimmerman, S Magaziner, J AF Boockvar, Kenneth S. Gruber-Baldini, Ann L. Stuart, Bruce Zimmerman, Sheryl Magaziner, Jay TI Medicare expenditures for nursing home residents triaged to nursing home or hospital for acute infection SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE infection; nursing homes; health expenditures; Medicare ID RANDOMIZED CONTROLLED-TRIAL; LONG-TERM-CARE; FACILITY RESIDENTS; PROPENSITY SCORES; RISK ADJUSTMENT; PNEUMONIA; DEMENTIA; EVERCARE; OUTCOMES; PAYMENT AB OBJECTIVES: To compare Medicare payments of nursing home residents triaged to nursing home with those of nursing home residents triaged to the hospital for acute infection care. DESIGN: Observational study with propensity score matching. SETTING: Fifty-nine nursing homes in Maryland. PARTICIPANTS: Two thousand two hundred eighty-five individuals admitted to the 59 nursing homes and followed between 1992 and 1997. MEASUREMENTS: Demographic and clinical data were obtained from interviews and medical record review and linked to Medicare payment records. Incident infection was ascertained according to medical record review for new infectious diagnoses or prescription of antibiotics. Hospital triage was defined as hospital transfer within 3 days of infection onset. Hospital triage patients were paired with similar nursing home triage patients using propensity score matching. Medicare expenditures for triage groups were compared in 1997 dollars. RESULTS: Of 3,618 infection cases, 28% were genitourinary infections, 20% skin, 14% upper respiratory, 12% lower respiratory, 4% gastrointestinal, and 2% bloodstream. Two hundred fifty-six pairs of hospital and nursing home triage cases fulfilled matching criteria. Mean Medicare payments +/- standard deviation were $5,202 +/- 7,310 and $996 +/- 2,475 per case in the hospital and nursing home triage groups, respectively, for a mean difference of $4,206 (95% confidence interval=$3,260-5,151). Mean payments per case in the hospital triage group were $3,628 higher in inpatient expenditures, $482 higher in physician visit expenditures, $161 higher in emergency department expenditures, and $147 higher in skilled nursing day expenditures. CONCLUSION: Per-case Medicare expenditures are higher with hospital triage than for nursing home triage for nursing home residents with acute infection. This result may be used to estimate cost savings to Medicare of interventions designed to reduce hospital use by nursing home residents. C1 [Stuart, Bruce] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. [Gruber-Baldini, Ann L.; Magaziner, Jay] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. [Zimmerman, Sheryl] Univ N Carolina, Sch Social Work, Chapel Hill, NC USA. [Zimmerman, Sheryl] Univ N Carolina, Cecil G Sheps Ctr Hlth Serv Res, Chapel Hill, NC USA. [Boockvar, Kenneth S.] James J Peters VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY 10468 USA. RP Boockvar, KS (reprint author), James J Peters VA Med Ctr, Ctr Geriatr Res Educ & Clin, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM kenneth.boockvar@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 FU NIA NIH HHS [R01 AG008211, R0L AG8211, R29 AG11407] NR 35 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUL PY 2008 VL 56 IS 7 BP 1206 EP 1212 DI 10.1111/j.1532-5415.2008.01748.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 332HJ UT WOS:000258073800006 PM 18482299 ER PT J AU Turchin, A Hamann, C Schnipper, JL Graydon-Baker, E Millar, SG McCarthy, PC Coley, CM Gandhi, TK Broverman, CA AF Turchin, Alexander Hamann, Claus Schnipper, Jeffrey L. Graydon-Baker, Erin Millar, Sally G. McCarthy, Patricia C. Coley, Christopher M. Gandhi, Tejal K. Broverman, Carol A. TI Evaluation of an inpatient computerized medication reconciliation system SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID ADVERSE DRUG EVENTS; ELECTRONIC SYSTEM; IMPLEMENTATION; ERRORS AB We designed the Pre-Admission Medication List (PAML) Builder medication reconciliation application and implemented it at two academic hospitals. We asked 1,714 users to complete a survey of their satisfaction with the application and analyzed factors associated with user efficiency. The survey was completed by 626 (36.5%) users. Most (64%) responders agreed that medication reconciliation improves patient care. Improvement requests included better medication information sources and propagation of medication information to order entry. Sixty-nine percent of admitting clinicians reported a typical time to build a PAML of < 10 min. Decreased reported time to build a PAML was associated with reported experience with the application and ease of use but not the average number of medications on the PAML. Most users agreed that medication reconciliation improves patient care but requested tighter integration of the different stages of the medication reconciliation process. Further training may be helpful in improving user efficiency. C1 [Turchin, Alexander; Schnipper, Jeffrey L.; Graydon-Baker, Erin; Gandhi, Tejal K.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Turchin, Alexander; Hamann, Claus; Broverman, Carol A.] Partners Informat Syst, Wellesley, MA USA. [Hamann, Claus; Millar, Sally G.; McCarthy, Patricia C.; Coley, Christopher M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Turchin, Alexander; Hamann, Claus; Schnipper, Jeffrey L.; Coley, Christopher M.; Gandhi, Tejal K.] Harvard Univ, Sch Med, Boston, MA USA. RP Turchin, A (reprint author), Clin Informat Res & Dev, Suite 201,93 Worcester St, Wellesley, MA 02481 USA. EM aturchin@partners.org NR 9 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL-AUG PY 2008 VL 15 IS 4 BP 449 EP 452 DI 10.1197/jamia.M2561 PG 4 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 328JM UT WOS:000257794700007 PM 18436909 ER PT J AU Zai, AH Grant, RW Estey, G Lester, WT Andrews, CT Yee, R Mort, E Chueh, HC AF Zai, Adrian H. Grant, Richard W. Estey, Greg Lester, William T. Andrews, Carl T. Yee, Ronnie Mort, Elizabeth Chueh, Henry C. TI Lessons from implementing a combined workflow-informaties system for diabetes management SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Medical-Informatics-Association CY NOV 10-14, 2007 CL Chicago, IL SP Amer Med Informat Assoc ID IMPROVING PRIMARY-CARE; CHRONIC ILLNESS; DISEASE; PREVALENCE; PROGRAMS; IDENTIFY AB Shortcomings surrounding the care of patients with diabetes have been attributed largely to a fragmented, disorganized, and duplicative health care system that focuses more on acute conditions and complications than on managing chronic disease. To address these shortcomings, we developed a diabetes registry population management application to change the way our staff manages patients with diabetes. Use of this new application has helped us coordinate the responsibilities for intervening and monitoring patients in the registry among different users. Our experiences using this combined workflow-informatics intervention system suggest that integrating a chronic disease registry into clinical workflow for the treatment of chronic conditions creates a useful and efficient tool for managing disease. C1 [Zai, Adrian H.; Estey, Greg; Lester, William T.; Andrews, Carl T.; Yee, Ronnie; Chueh, Henry C.] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. [Grant, Richard W.] Clin Res Program, Gen Med Unit, Boston, MA USA. [Mort, Elizabeth] Ctr Qual & Safety, Boston, MA USA. [Mort, Elizabeth] Massachusetts Gen Hosp, Massachusetts Gen Physicians Org, Boston, MA 02114 USA. [Zai, Adrian H.; Grant, Richard W.; Andrews, Carl T.; Yee, Ronnie; Mort, Elizabeth; Chueh, Henry C.] Harvard Univ, Sch Med, Boston, MA USA. RP Zai, AH (reprint author), Massachusetts Gen Hosp, Comp Sci Lab, 50 Staniford St, Boston, MA 02114 USA. EM azai@partners.org OI Zai, Adrian/0000-0002-2972-6839 FU NIDDK NIH HHS [K23 DK067452, K23 DK067452-05]; NLM NIH HHS [T15 LM007092, 2T15LM007092-16] NR 37 TC 14 Z9 15 U1 2 U2 5 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL-AUG PY 2008 VL 15 IS 4 BP 524 EP 533 DI 10.1197/jamia.M2598 PG 10 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 328JM UT WOS:000257794700016 PM 18436907 ER PT J AU Neilan, TG Pradhan, AD Weyman, AE AF Neilan, Tomas G. Pradhan, Aruna D. Weyman, Arthur E. TI Derivation of a size-independent variable for scaling of cardiac dimensions in a normal adult population SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE echocardiography; left atrium; allometric modelling ID LEFT-VENTRICULAR MASS; LEFT ATRIAL SIZE; BODY-SIZE; HYPERTENSIVE MEN; NORMAL CHILDREN; SURFACE-AREA; GROWTH; WEIGHT; ECHOCARDIOGRAPHY; CHAMBER AB Objective: Most current methods for normalizing cardiac dimensions for differences in body size assume a linear isometric relationship between variables. This approach may be flawed. We therefore compared the isometric and allometric modeling approach to assess the optimal scaling method (using the left atrial dimension [LAD] as an example) in a large group of adults with normal echocardiograms. Methods: We studied 15,667 consecutive echocardiographically normal adults. Their mean age was 40 +/- 14 years; LAD was 32 +/- 4 mm; body weight (BW) was 72 +/- 17 kg; height (HT) was 1.7 +/- 0.2 m; body surface area (BSA) was 1.8 +/- 0.2 m(2); and body mass index was 25 +/- 6 kg/m(2). The LAD in the anterior-posterior dimension was indexed by each size variable using both isometric and allometric methods. Results: LAD correlated with all size variables (r = 0.20 to r = 0.45). Simple isometric indices (e. g., LAD/BSA), rather than removing, actually increased the correlation with all body size variables (r = -0.27 to -0.80). Normalization by the optimal allometric exponent (BW = 0.262; HT = 0.428; BSA = 0.449; body mass index = 0.266) eliminated the association of the indexed variable with body size. Indexation by BW best removed the influence of all measures of body size. The proportion of variance of LAD explained by BW was 21.4% compared with only 3.9% for HT. There were minor, but statistically significant, age-, gender-, and obesity-related differences in the indexed left atrial size (e. g., optimal allometric exponent for BW in male patients = 0.257 vs. in female patients = 0.253). Conclusion: The standard isometric corrections for body size fail to adequately account for the associations between LAD and body size, and in fact increase the relationship of the indexed parameter to all body size measures. Normalization using the optimal allometric exponent removes the effect of that variable, with BW best removing the effect of body size. C1 [Neilan, Tomas G.; Weyman, Arthur E.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, Dept Med, Boston, MA 02115 USA. [Neilan, Tomas G.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Pradhan, Aruna D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Neilan, Tomas G.; Pradhan, Aruna D.; Weyman, Arthur E.] Harvard Univ, Sch Med, Boston, MA USA. RP Weyman, AE (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, Dept Med, 55 Fruit St,YAW-5E, Boston, MA 02115 USA. EM aeweyman@partners.org FU NHLBI NIH HHS [HL 082740] NR 25 TC 13 Z9 14 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD JUL PY 2008 VL 21 IS 7 BP 779 EP 785 DI 10.1016/j.echo.2007.12.003 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 320AE UT WOS:000257205300002 PM 18329846 ER PT J AU Wolf, M Betancourt, J Chang, Y Shah, A Teng, M Tamez, H Gutierrez, O Camargo, CA Melamed, M Norris, K Stampfer, MJ Powe, NR Thadhani, R AF Wolf, Myles Betancourt, Joseph Chang, Yuchiao Shah, Anand Teng, Ming Tamez, Hector Gutierrez, Orlando Camargo, Carlos A., Jr. Melamed, Michal Norris, Keith Stampfer, Meir J. Powe, Neil R. Thadhani, Ravi TI Impact of activated vitamin D and race on survival among hemodialysis patients SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; CHRONIC KIDNEY-DISEASE; RACIAL-DIFFERENCES; UNITED-STATES; SECONDARY HYPERPARATHYROIDISM; DIALYSIS PATIENTS; SOCIOECONOMIC-STATUS; ETHNIC-DIFFERENCES; D DEFICIENCY; MORTALITY AB Contrary to most examples of disparities in health outcomes, black patients have improved survival compared with white patients after initiating hemodialysis. Understanding potential explanations for this observation may have important clinical implications for minorities in general. This study tested the hypothesis that greater use of activated vitamin D therapy accounts for the survival advantage observed in black and Hispanic patients on hemodialysis. In a prospective cohort of non-Hispanic white (n = 5110), Hispanic white (n = 979), and black (n = 3214) incident hemodialysis patients, higher parathyroid hormone levels at baseline were the primary determinant of prescribing activated vitamin D therapy. Median parathyroid hormone was highest among black patients, who were most likely to receive activated vitamin D and at the highest dosage. One-year mortality was lower in black and Hispanic patients compared with white patients (16 and 16 versus 23%; P < 0.01), but there was significant interaction between race and ethnicity, activated vitamin D therapy, and survival. In multivariable analyses of patients treated with activated vitamin D, black patients had 16% lower mortality compared with white patients, but the difference was lost when adjusted for vitamin D dosage. In contrast, untreated black patients had 35% higher mortality compared with untreated white patients, an association that persisted in several sensitivity analyses. In conclusion, therapy with activated vitamin D may be one potential explanation for the racial differences in survival among hemodialysis patients. Further studies should determine whether treatment differences based on biologic differences contribute to disparities in other conditions. C1 [Wolf, Myles; Shah, Anand; Teng, Ming; Tamez, Hector; Gutierrez, Orlando; Thadhani, Ravi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Boston, MA 02114 USA. [Betancourt, Joseph; Chang, Yuchiao] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med,Dept Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. [Melamed, Michal] Albert Einstein Coll Med, Div Nephrol, Dept Med, New York, NY USA. [Norris, Keith] Charles R Drew Univ Med & Sci, Los Angeles, CA 90059 USA. [Stampfer, Meir J.] Harvard Univ, Sch Med, Channing Lab, Dept Med,Brigham & Womens Hosp, Boston, MA 02115 USA. [Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Powe, Neil R.] Johns Hopkins Sch Med & Publ Hlth, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. RP Thadhani, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Bulfinch 127,55 Fruit St, Boston, MA 02114 USA. EM rthadhani@partners.org FU NCRR NIH HHS [K23 RR017376, RR017376]; NIDDK NIH HHS [DK071674, DK076116, DK078774, R01 DK076116, R21 DK071674, K23 DK078774] NR 56 TC 118 Z9 120 U1 2 U2 6 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUL PY 2008 VL 19 IS 7 BP 1379 EP 1388 DI 10.1681/ASN.2007091002 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 320VG UT WOS:000257262600020 PM 18400938 ER PT J AU Shi, J Pipe, SW Rasmussen, JT Heegaard, CW Gilbert, GE AF Shi, J. Pipe, S. W. Rasmussen, J. T. Heegaard, C. W. Gilbert, G. E. TI Lactadherin blocks thrombosis and hemostasis in vivo: correlation with platelet phosphatidylserine exposure SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE annexin; factor V; factor VIII; lactadherin; phosphatidylserine; platelets ID FACTOR-X ACTIVATION; IXA ENZYME COMPLEX; ANNEXIN-V; FACTOR-VIII; BINDING-SITES; L-SERINE; PROCOAGULANT ACTIVITY; BLOOD-COAGULATION; MEMBRANE-BINDING; SCOTT SYNDROME AB Background: Platelet membrane phosphatidylserine (PS) is considered to be essential for hemostasis and thrombosis, but the in vivo topography of platelet PS has not been characterized. We hypothesized that platelet PS exposure would be identified on adherent platelets at the site of vascular injury and that blockade of PS would impede hemostasis and thrombosis. Objective: To localize and estimate the extent of platelet PS exposure and evaluate the impact of PS blockade in vivo. Methods: Lactadherin, a PS-binding milk protein, was utilized together with annexin V to detect both partial and complete membrane PS exposure on platelets in a mouse model of thrombosis and to evaluate the functional need for PS. Preliminary experiments were performed with synthetic membranes and with purified platelets. Results: The number of lactadherin-binding sites on synthetic membranes was proportional to PS content, whereas annexin V required a threshold of 2.5-8% PS. Approximately 95% of thrombin-stimulated platelets exposed PS, but the quantity was below the threshold for annexin V binding at physiologic Ca(2+) concentrations. In mice, most adherent and aggregated platelets on the walls of ferric chloride-treated mesenteric veins exposed low levels of PS, rather than having complete exposure. In mice, blockade of PS with lactadherin inhibited platelet prothrombinase and factor Xase activity, and prolonged tail bleeding time and the time to carotid artery thrombosis. Conclusions: In vivo PS exposure contributes to both hemostasis and thrombosis. In this model of vascular injury, most platelets exhibit partial rather than complete PS exposure. C1 [Shi, J.; Gilbert, G. E.] Brigham & Womens Hosp, Dept Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Shi, J.; Gilbert, G. E.] Harvard Univ, Sch Med, Boston, MA USA. [Pipe, S. W.] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. [Rasmussen, J. T.; Heegaard, C. W.] Univ Aarhus, Prot Chem Lab, Dept Mol Biol, Aarhus, Denmark. RP Gilbert, GE (reprint author), VA Boston Healthcare Ctr, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM ggilbert@rics.bwh.harvard.edu NR 44 TC 51 Z9 51 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2008 VL 6 IS 7 BP 1167 EP 1174 DI 10.1111/j.1538-7836.2008.03010.x PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 315DA UT WOS:000256856900015 PM 18485093 ER PT J AU Briggs, SM AF Briggs, Susan M. TI Intra-abdominal injury as a result of high-pressure water injection - Comment SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Briggs, SM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD JUL PY 2008 VL 65 IS 1 BP 224 EP 224 PG 1 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 327ZP UT WOS:000257767300037 ER PT J AU Hamer, DH Ruffing, R Callahan, MV Lyons, SH Abdullah, ASM AF Hamer, Davidson H. Ruffing, Ronald Callahan, Michael V. Lyons, Stephen H. Abdullah, Abu Saleh M. TI Knowledge and use of measures to reduce health risks by corporate expatriate employees in western Ghana SO JOURNAL OF TRAVEL MEDICINE LA English DT Article ID LONG-TERM TRAVELERS; INFECTIOUS-DISEASE RISKS; TROPICAL COUNTRIES; MALARIA; MEDICINE; DIARRHEA AB Background. Expatriate corporate workers stationed in remote regions of developing countries with limited health care resources are at substantial risk for a variety of infectious diseases. Methods. A survey was carried out among expatriates working at a large power plant construction site in western Ghana in 1998 to evaluate their use of pretravel medical services, current knowledge, and behavioral practices in relation to food- and waterborne disease prevention, diarrhea, malaria, respiratory infections, alcohol use, and high-risk sexual activity. An anonymous, structured, and pretested questionnaire was used. Results. The response rate was 42 of 60 (70%). Most respondents were men (39 of 42, 93%) with previous international construction experience. Adherence to food and water safety recommendations decreased with time. Expatriates (15 of 23, 65%) from developed countries reported at least one episode of diarrhea, whereas no expatriates (0 of 9) from resource-poor countries reported diarrhea (p < 0.001). Use of malaria chemoprophylaxis deteriorated with increasing duration of time on the job site. None of the expatriates (0 of 9) who had been on the site for more than a year was still taking an antimalarial compared to those who had been there for 3 months or less (13 of 16) (p < 0.01). Forty-three percent (18 of 42) of the respondents reported having had a respiratory infection in the past 3 months. Only 38% (15 of 39) received preplacement education on human immunodeficiency virus (HIV) risk. A higher proportion of those who received pretravel HIV education used condoms always (4 of 5) than those who did not receive HIV education (1 of 5). Discussion. The use of health advice and preventive measures was generally low among the expatriate corporate survey respondents. Adherence to preventive measures declined with the increase in length of stay. Corporations need to develop appropriate health promotion strategies targeting their expatriates in developing countries. C1 Boston Univ, Sch Publ Hlth, Ctr Int Hlth & Dev, Dept Int Hlth, Boston, MA 02118 USA. Boston Univ, Infect Dis Sect, Dept Med, Sch Med, Boston, MA 02118 USA. Tufts Univ New England Med Ctr, Dept Emergency Med, Boston, MA USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Rescue Med Inc, Airlift One, Washington, DC USA. Santa Fe Commun Coll, Gainesville, FL USA. RP Hamer, DH (reprint author), Boston Univ, Sch Publ Hlth, Ctr Int Hlth & Dev, Dept Int Hlth, Crosstown 3rd Floor,715 Albany St, Boston, MA 02118 USA. EM dhamer@bu.edu OI Hamer, Davidson/0000-0002-4700-1495 NR 18 TC 17 Z9 17 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1195-1982 J9 J TRAVEL MED JI J. Travel Med. PD JUL-AUG PY 2008 VL 15 IS 4 BP 237 EP 242 DI 10.1111/j.1708-8305.2008.00214.x PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 328KT UT WOS:000257798000005 PM 18666923 ER PT J AU Cantwell, CP Wah, TM Gervais, DA Eisner, BH Arellano, R Uppot, RN Samir, AE Irving, HC McGovern, F Mueller, PR AF Cantwell, Colin P. Wah, Tze M. Gervais, Debra A. Eisner, Brian H. Arellano, Ronald Uppot, Raul N. Samir, Anthony E. Irving, Henry C. McGovern, Francis Mueller, Peter R. TI Protecting the ureter during radiofrequency ablation of renal cell cancer: A pilot study of retrograde pyeloperfusion with cooled dextrose 5% in water SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID COLLECTING SYSTEM; CARCINOMA; PROPHYLAXIS; HYPOTHERMIA; INJURY; TUMOR AB PURPOSE: To describe early experience with cooled dextrose 5% in water (D5W) solution retrograde pyeloperfusion during radiofrequency (RF) ablation of renal cell carcinoma (RCC) within 1.5 cm of the ureter with respect to feasibility, safety, and incidence of residual/recurrent tumor in proximity to the cooled collecting system. MATERIALS AND METHODS: Between November 2004 and April 2007, 17 patients underwent 19 RF ablation sessions of RCCs within 1.5 cm of the ureter during cooled D5W pyeloperfusion (nine men, eight women; mean tumor size, 3.5 cm; mean age, 73 y; mean distance to ureter, 7 mm). RF ablation was performed with pulsed impedance control current. The records and imaging studies of patients treated with this technique were reviewed for demographics, indication, technique, complications, and tumor recurrence. RESULTS: All 19 RF ablation and ureteral catheter placement procedures were technically successful. No patient developed a ureteral stricture or hydronephrosis during a mean of 14 months of follow-up (range, 4-32 months). Three patients had residual tumor on the first follow-up imaging study, but all three tumors were completely ablated after a second RF ablation session. No complications or deaths occurred. No recurrent tumor was seen anywhere in the treated tumors, and there was complete ablation of the tumor margin in proximity to the collecting system. CONCLUSIONS: RF ablation of RCC within 1.5 cm of the ureter is feasible with cooled D5W retrograde pyeloperfusion and is not associated with reduced efficacy, ureteral injury, or early recurrence. C1 [Cantwell, Colin P.; Gervais, Debra A.; Arellano, Ronald; Uppot, Raul N.; Samir, Anthony E.; Mueller, Peter R.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. [Eisner, Brian H.; McGovern, Francis] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Wah, Tze M.; Irving, Henry C.] St James Univ Hosp, Dept Radiol, Leeds LS9 7TF, W Yorkshire, England. RP Mueller, PR (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, White Bldg,Room 270, Boston, MA 02114 USA. EM pmueller@partners.org OI Samir, Anthony/0000-0002-7801-8724 NR 17 TC 50 Z9 50 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JUL PY 2008 VL 19 IS 7 BP 1034 EP 1040 DI 10.1016/j.jvir.2008.04.005 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 324FV UT WOS:000257504000011 PM 18589317 ER PT J AU Kalva, SP Chlapoutaki, C Wicky, S Greenfield, AJ Waltman, AC Athanasoulis, CA AF Kalva, Sanjeeva P. Chlapoutaki, Chrysanthi Wicky, Stephan Greenfield, Alan J. Waltman, Arthur C. Athanasoulis, Christos A. TI Suprarenal inferior vena cava filters: A 20-year single-center experience SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article; Proceedings Paper CT 93rd Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America (RSNA) CY NOV 25-30, 2007 CL Chicago, IL SP Radiol Soc N Amer (RSNA) ID VENOUS THROMBOEMBOLISM; GREENFIELD FILTER; VERTEBRAL PENETRATION; CLINICAL-EXPERIENCE; FOLLOW-UP; PLACEMENT; PERFORATION; MANAGEMENT; TRAPEASE; DIAMETER AB PURPOSE: To assess the clinical safety and efficacy of suprarenal inferior vena cava (IVC) filters during long-term follow-up. MATERIALS AND METHODS: In this retrospective study, the authors collected the following data about patients who underwent suprarenal IVC filter placement at their institution between 1988 and 2007: demographics, clinical presentation, indications for filter placement, reasons for placing the filter in the suprarenal IVC, type of filter, frequency of pulmonary embolism (PE) after filter placement, and filter-related problems during follow-up. RESULTS: Seventy patients (32 male and 38 female patients; mean age, 60 years) had suprarenal IVC filters. Sixty-two patients presented with symptoms of venous thromboembolism (VTE) and eight had incidental asymptomatic VTE at imaging. Indications for filter placement were as follows: contraindication to anticoagulation (n = 48), complications and/or failure of anticoagulation (n = 12), added protection (n = 8), and prophylaxis (n = 2). Suprarenal placement was chosen due to IVC thrombus (n = 41), intrinsic and/or extrinsic narrowing of the infrarenal IVC (n = 9), renal and/or gonadal vein thrombus (n = 3), congenital IVC anomalies (n = 6), pelvic mass (n = 5), pregnancy (n = 3), and other reasons (n = 3). The following filters were used: Greenfield (n = 29), Simon Nitinol (n = 5), Vena-Tech (n = 3), TrapEase (n = 22), OptEase (n = 3), Tulip (n = 6), Bird's Nest (n = 1), and Recovery (n = 1). During follow-up (mean, 573 days +/- 953), postfilter PE was suspected in 10 patients; eight patients underwent computed tomography (CT), one of whom had PE at CT. None developed new symptoms of caval thrombosis. Abdominal CT (performed in 30 patients at a mean of 543 days 768) showed thrombus in the filter in three patients, fracture in one patient, and penetration of the IVC wall in two patients. CONCLUSIONS: Suprarenal filters are safe and effective in preventing PE. The placement of IVC filters above the renal veins does not carry an added risk of complications. C1 [Kalva, Sanjeeva P.; Chlapoutaki, Chrysanthi; Wicky, Stephan; Greenfield, Alan J.; Waltman, Arthur C.; Athanasoulis, Christos A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Kalva, SP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, GRB-290,55 Fruit St, Boston, MA 02114 USA. EM skalva@partners.org NR 30 TC 32 Z9 37 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JUL PY 2008 VL 19 IS 7 BP 1041 EP 1047 DI 10.1016/j.jvir.2008.03.026 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 324FV UT WOS:000257504000012 PM 18589318 ER PT J AU Liu, ZJ Ahmed, M Gervais, D Humphries, S Goldberg, SN AF Liu, Zhengjun Ahmed, Muneeb Gervais, Debra Humphries, Stanley Goldberg, S. Nahum TI Computer modeling of factors that affect the minimum safety distance required for radiofrequency ablation near adjacent nontarget structures SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-Interventional-Radiology (SIR) CY MAR 01-06, 2007 CL Seattle, WA SP Soc Intervent Radiol ID RENAL-CELL CARCINOMA; TUMOR ABLATION; HEPATOCELLULAR-CARCINOMA; THERMAL-CONDUCTIVITY; TISSUE ABLATION; LIVER-TUMORS; BLOOD-FLOW; PERFUSION; COAGULATION; TEMPERATURE AB PURPOSE: To use computer modeling of radiofrequency (RF) ablation to evaluate the effects of (i) composition and varying perfusion of intervening tissue and (ii) electrode orientation and type on the required distance to avoid heating damage of adjacent nontarget structures. MATERIALS AND METHODS: Systematic three-dimensional finite-element computer simulation of RF heating (6-20 minutes) was performed (3,128 simulations). The distance (5-25 mm) between the electrode and the potentially injured structure and tissue composition as layers of tumor/soft tissue, fat, and/or fluid was varied (thermal conductivity, 0.46, 0.23, and 0.7 W/m-degrees C; electrical conductivity, 0.5, 0.1, and 1 S/m, respectively). Varying perfusion (0-5 kg/m(3)-s), electrode orientation (parallel or perpendicular), and electrode type (ie, noncooled and internally cooled 3-cm single or 2.5-cm cluster) were also studied. The time required to reach various temperatures (eg, the time to reach 50 C designated as t50) and the distances at which the temperatures occurred and the distances required to avoid threshold temperatures at the margin of adjacent structures were compared. RESULTS: In all cases, increasing the amount of intervening fat increased t50 compared with tumor/soft tissue and/or fluid. With no perfusion, 9 mm of fat or 14 mm of tumor/soft tissue or fluid was required for perpendicular insertion (internally cooled single electrode) to prevent a temperature of 50 C with 12 minutes of heating, compared with 12 mm of fat or 23 mm of tumor/soft tissue or fluid for parallel insertion. Less intervening fat was needed for noncooled electrodes (< 8 mm parallel, < 5 mm perpendicular), with more intervening tissue required for cluster electrodes (> 13 mm) for an RF application of 20 minutes. Finally, the amount of intervening tissue required to prevent damage also decreased linearly with increasing perfusion for each tissue and electrode (r(2) = 0.74 for parallel; r(2) = 0.98 for perpendicular). CONCLUSIONS: In the computer model described in the present study, thermal and perfusion characteristics between the electrode and adjacent nontarget structures (specifically the presence of fat) and the electrode characteristics themselves (including parallel versus perpendicular insertion) have been shown to affect the minimum safe distance required for the prevention of thermal injury. C1 [Liu, Zhengjun; Ahmed, Muneeb; Goldberg, S. Nahum] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, Boston, MA 02215 USA. [Gervais, Debra] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Humphries, Stanley] Univ New Mexico, Dept Elect Engn, Albuquerque, NM 87131 USA. RP Goldberg, SN (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. EM sgoldber@caregroup.harvard.edu FU NCI NIH HHS [R01 CA 87992-01A1] NR 39 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JUL PY 2008 VL 19 IS 7 BP 1079 EP 1086 DI 10.1016/j.jvir.2008.04.003 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 324FV UT WOS:000257504000017 PM 18589323 ER PT J AU Greenberg, RK Chuter, TAM Cambria, RP Sternbergh, WC Fearnot, NE AF Greenberg, Roy K. Chuter, Timothy A. M. Cambria, Richard P. Sternbergh, W. Charles, III Fearnot, Neal E. TI Zenith abdominal aortic aneurysm endovascular graft SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID STENT-GRAFT; MULTICENTER TRIAL; CLINICAL-TRIAL; REPAIR; ENDOGRAFT; DEVICE; BIFURCATION; EXPERIENCE; MIGRATION; UPDATE AB Purpose: The safety and efficacy of the Zenith (Cook Inc, Bloomington, Ind) endovascular graft was assessed based on the United States multicenter trial through 5 years of follow-up. Methods: Between 2000 and 2003, the pivotal study, enrolled patients to open surgery (control) or the Zenith endovascular graft (endovascular). A separate continued access study arm enrolled endovascular patients using the same inclusion/exclusion criteria. Both studies were designed for 2-year follow-up, and the pivotal endovascular patients had the option of extending the study follow-up through 5 years. All endovascular patients were stratified by physiologic risk into high-risk and standard-risk groups to assess overall mortality, rupture, conversion, endoleaks, secondary interventions, and sac enlargement. The entire endovascular cohort was pooled to assess device integrity, limb occlusion, component separation, and migration. The suboptimal endovascular result (SER) was established as an end point to assess late adverse outcomes. Statistical analyses included Kaplan-Meier estimations and Cox regression to assess factors contributing to sac enlargement and SER. Results. The study enrolled 739 endovascular patients (352 pivotal, 387 continued access); 158 patients in the pivotal study reconsented to be followed up for 5 years. For the patients at standard and high risk at 5 years, the respective survival estimate was 83% and 61%, aneurysm-related death was 2% and 4%, and freedom from rupture was 100% and 99.6%, respectively. Cumulative risk of conversion, limb occlusion, migration > 10 mm, or component separation was <= 3% at 5 years. Cumulative risk of late endoleak was 12% to 15%, representing the primary indication for secondary interventions which occurred in 20% of standard-risk patients and 25% of high-risk patients through 5 years. Sac enlargement was very rare and associated with advanced age and larger aneurysms. SER was predicted by advanced age and internal iliac artery occlusion. Conclusion: These middle- and long-term data support long-term durability of the Zenith endovascular graft. Risk of aneurysm-related death or rupture was exceptionally low, and complications of migration, limb occlusion, and device integrity issues were uncommon. Incidence of late endoleaks and association of endoleaks with sac growth underscore the need for long-term follow-up of patients treated with endovascular grafts, although the sequelae of such events are unknown. C1 [Greenberg, Roy K.] Cleveland Clin Fdn, Dept Vasc & Cardiothorac Surg & Biomed Engn, Cleveland, OH 44195 USA. [Chuter, Timothy A. M.] Univ San Francisco, Dept Vasc Surg, San Francisco, CA 94117 USA. [Cambria, Richard P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sternbergh, W. Charles, III] Oschner Clin, New Orleans, LA USA. [Fearnot, Neal E.] Inst MED, W Lafayette, IN USA. RP Greenberg, RK (reprint author), Cleveland Clin Fdn, Dept Vasc & Cardiothorac Surg & Biomed Engn, Desk S-40, Cleveland, OH 44195 USA. EM greenbr@ccf.org RI Sternbergh, W. Charles/B-3227-2011 NR 27 TC 62 Z9 65 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUL PY 2008 VL 48 IS 1 BP 1 EP 9 DI 10.1016/j.jvs.2008.02.051 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 320IS UT WOS:000257227500001 PM 18486418 ER PT J AU Abbruzzese, TA Kwolck, CJ Brewster, DC Chung, TK Kang, J Conrad, MF LaMuraglia, GM Cambria, RP AF Abbruzzese, Thomas A. Kwolck, Christopher J. Brewster, David C. Chung, Thomas K. Kang, Jeanwan Conrad, Mark F. LaMuraglia, Glenn M. Cambria, Richard P. TI Outcomes following endovascular abdominal aortic aneurysm repair (EVAR): An anatomic and device-specific analysis SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the New-England-Society-for-Vascular-Surgery CY OCT 05-06, 2007 CL Ledyard, CT ID RANDOMIZED CONTROLLED-TRIAL; MULTICENTER TRIAL; STENT-GRAFT; MIGRATION; EUROSTAR; GENDER; TERM; ENDOGRAFTS; DIAMETER; EXPERIENCE AB Objective: We performed a device-specific comparison of long-term outcomes following endovascular abdominal aortic aneurysm repair (EVAR) to determine the effect(s) of device type on early and late clinical outcomes In addition, the impact of performing EVAR both within and outside of specific instructions for use (IFU) for each device was examined. Methods. Between January 8, 1999 and December 31, 2005, 565 patients underwent EVAR utilizing one of three commercially available stent graft devices. Study outcomes included perioperative (<= 30 days) mortality, intraoperative technical complications and need for adjunctive procedures, aneurysm rupture, aneurysm - related mortality, conversion to open repair, reintervention, development and/or resolution of endoleak, device related adverse events (migration, thrombosis, or kinking), and a combined endpoint of any graft-related adverse event (GRAE). Study outcomes were correlated by aneurysm morphology that was within or outside of the recommended device IFU. chi(2) and Kaplan Meier methods were used for analysis. Results: Grafts implanted included 177 Cook Zenith (CZ, 31%), 111 Core Excluder (GE, 20%), and 277 Medtronic AneuRx (MA, 49%); 39.3% of grafts were placed outside of at least one IFU parameter. Mean follow-up was 30 +/- 21 months and was shorter for CZ (20 months CZ vs 35 and 31 months for GE and MA, respectively; P < .001). Overall actuarial 5-year freedom from aneurysm-related death, reintervention, and GRAE was similar among devices. CZ had a lower number of graft migration events (0 CZ vs I GE and 9 MA); however, there was no difference between devices on actuarial analysis. Combined GRAE was lowest for CZ (29% CZ, 35% GE, and 43% MA; P = .01). Graft placement outside of IFU was associated with similar 5-year freedom from aneurysm -related death, migration, and reintervention (P > .05), but a lower freedom from GRAE (74% outside IFU vs 86% within IFU; P = .026), likely related to a higher incidence of graft thrombosis (2.3% outside IFU vs 0.3% within IFU; P = .026). The differences in outcome for grafts placed within vs outside IFU were not device-specific. Conclusion: EVAR performed with three commercially available devices provided similar clinically relevant outcomes at 5 years, although no graft migration occurred with a suprarenal fixation device. As anticipated, application outside of anatomically specific IFU variables had an incremental negative effect on late results, indicating that adherence to such IFU guidelines is appropriate clinical practice. C1 [Kwolck, Christopher J.; Brewster, David C.; Chung, Thomas K.; Kang, Jeanwan; Conrad, Mark F.; LaMuraglia, Glenn M.; Cambria, Richard P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. EM tabbruzzese@partners.org OI Chung, Thomas/0000-0001-6148-1184 NR 32 TC 130 Z9 135 U1 0 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUL PY 2008 VL 48 IS 1 BP 19 EP 28 DI 10.1016/j.jvs.2008.02.003 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 320IS UT WOS:000257227500004 PM 18440182 ER PT J AU Conrad, MF Ye, JY Chung, TK Davison, JK Cambria, RP AF Conrad, Mark F. Ye, Jason Y. Chung, Thomas K. Davison, J. Kenneth Cambria, Richard P. TI Spinal cord complications after thoracic aortic surgery: Long-term survival and functional status varies with deficit severity SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 61st Annual Meeting of the Society-for-Vascular-Surgery CY JUN 06-10, 2007 CL Baltimore, MD SP Soc Vasc Surg ID THORACOABDOMINAL ANEURYSM REPAIR; OPEN-SURGICAL REPAIR; CEREBROSPINAL-FLUID DRAINAGE; CLINICAL-EXPERIENCE; PREVENT PARAPLEGIA; NEUROLOGIC DEFICIT; RISK; PROTECTION; INJURY; OPERATIONS AB Objective: Paraplegia after thoracoabdominal aneurysm (TAA) repair has been associated with poor survival. Little information exists concerning the spectrum of severity that characterizes spinal cord ischemic (SCI) complications. This study stratified SCI by deficit severity to determine its impact on late survival and functional outcomes. Methods. A review of our prospectively maintained thoracic aortic database was performed from May 1987 through December 2005 to identify patients who experienced SCI of any extent after TAA repair. During this period, 576 patients underwent descending thoracic aortic repair (93 open, 105 endovascular [TEVAR]) or open TAA repair (279 extent I to III; 99 extent IV). To stratify severity of SCI, we created a spinal cord ischemia deficit (SCID) scale, which is defined as: I, flaccid paralysis; II, average neurologic muscle grade indicating <50% function; and III, average neurologic muscle grade indicating > 50% function. Long-term outcomes were evaluated in relation to these groups by actuarial methods. Results. During the study period, 64 (11.1%) patients developed SCI of any severity (7 of 105 [6.6%] TEVAR, 57 of 471 [12%] open). These were stratified by SCID level: I, 24 (37.5%); II, 31 (48.4%); and III, 9 (14.1%). SCI was immediate in 33 (54.1%) and delayed in 28 (45.9%). Most SCI (6 of 7) associated with TEVAR was delayed. The 30-day mortality was significantly higher in the SCI group than the overall patient cohort (15 of 64 [23.4%] vs 41 of 512 [8%], P < .001) and varied by SCID level: I, II of 24 (45.8%); II, 4 of 31 (12.9%); and III, 0 of 9 (0%; P = .001). The 5-year actuarial survival for all SCI was lower than for non-SCI patients (25% +/- 6% vs 51% +/- 3%, P < .001) and varied linearly with SCID level but was similar between SCID II/III and the non-SCI patients (41% +/- 10% vs 51% +/- 3%, P = .281). No SCID I patients were alive at 5 years. No patients with SCID I recovered the ability to walk, but eight of 11 (73%) with SCID II and the nine (100%) with SCID III could ambulate with or without assistance at last follow-up. Conclusion: Survival and functional outcomes correlate with SCI severity. Patients with SCID I have a poor long-term outlook. Survival of SCID II/III patients is similar to non-SCI patients; most recover the ability to ambulate. C1 Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Gen Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Conrad, MF (reprint author), 15 Parkman St,WAC 4, Boston, MA 02114 USA. EM mconrad@partners.org OI Chung, Thomas/0000-0001-6148-1184 NR 37 TC 42 Z9 43 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUL PY 2008 VL 48 IS 1 BP 47 EP 53 DI 10.1016/j.jvs.2008.02.047 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 320IS UT WOS:000257227500008 PM 18486422 ER PT J AU Rousseau, CM Daniels, MG Carlson, JM Kadie, C Crawford, H Prendergast, A Matthews, P Payne, R Rolland, M Raugi, DN Maust, BS Learn, GH Nickle, DC Coovadia, H Ndung'u, T Frahm, N Brander, C Walker, BD Goulder, PJR Bhattacharya, T Heckerman, DE Korber, BT Mullins, JI AF Rousseau, Christine M. Daniels, Marcus G. Carlson, Jonathan M. Kadie, Carl Crawford, Hayley Prendergast, Andrew Matthews, Philippa Payne, Rebecca Rolland, Morgane Raugi, Dana N. Maust, Brandon S. Learn, Gerald H. Nickle, David C. Coovadia, Hoosen Ndung'u, Thumbi Frahm, Nicole Brander, Christian Walker, Bruce D. Goulder, Philip J. R. Bhattacharya, Tanmoy Heckerman, David E. Korber, Bette T. Mullins, James I. TI HLA class I-driven evolution of human immunodeficiency virus type 1 subtype C proteome: Immune escape and viral load SO JOURNAL OF VIROLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; STRUCTURALLY CONSTRAINED EPITOPE; CTL ESCAPE; CELL RESPONSES; PRIMARY INFECTION; DISEASE PROGRESSION; CHILD TRANSMISSION; HIV POLYMORPHISMS; FITNESS COST; GAG EPITOPE AB Human immunodeficiency virus type 1 (HIV-1) mutations that confer escape from cytotoxic T-lymphocyte (CTL) recognition can sometimes result in lower viral fitness. These mutations can then revert upon transmission to a new host in the absence of CTL-mediated immune selection pressure restricted by the HLA alleles of the prior host. To identify these potentially critical recognition points on the virus, we assessed HLA-driven viral evolution using three phylogenetic correction methods across full HIV-1 subtype C proteomes from a cohort of 261 South Africans and identified amino acids conferring either susceptibility or resistance to CTLs. A total of 558 CTL-susceptible and -resistant HLA-amino acid associations were identified and organized into 310 immunological sets (groups of individual associations related to a single HLA/epitope combination). Mutations away from seven susceptible residues, including four in Gag, were associated with lower plasma viral-RNA loads (q < 0.2 [where q is the expected false-discovery rate]) in individuals with the corresponding HLA alleles. The ratio of susceptible to resistant residues among those without the corresponding HLA alleles varied in the order Vpr > Gag > Rev > Pol > Nef > Vif > Tat > Env > Vpu (Fisher's exact test; P <= 0.0009 for each comparison), suggesting the same ranking of fitness costs by genes associated with CTL escape. Significantly more HLA-B (chi(2); p = 3.59 x 10(-5)) and HLA-C (chi(2); p = 4.71 x 10(-6)) alleles were associated with amino acid changes than HLA-A, highlighting their importance in driving viral evolution. In conclusion, specific HIV-1 residues (enriched in Vpr, Gag, and Rev) and HLA alleles (particularly B and Q confer susceptibility to the CTL response and are likely to be important in the development of vaccines targeted to decrease the viral load. C1 [Rousseau, Christine M.; Rolland, Morgane; Raugi, Dana N.; Maust, Brandon S.; Learn, Gerald H.; Nickle, David C.; Heckerman, David E.; Mullins, James I.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Daniels, Marcus G.; Bhattacharya, Tanmoy; Korber, Bette T.] Los Alamos Natl Lab, Los Alamos, NM USA. [Daniels, Marcus G.; Bhattacharya, Tanmoy; Korber, Bette T.] Univ Washington, Dept Comp Sci & Engn, Seattle, WA 98195 USA. [Carlson, Jonathan M.; Kadie, Carl; Heckerman, David E.] Microsoft Res, Machine Learning & Appl Stat Grp, Redmond, WA USA. [Crawford, Hayley; Prendergast, Andrew; Matthews, Philippa; Payne, Rebecca; Goulder, Philip J. R.] Nuffield Dept Med, Dept Pediat, Oxford, England. [Coovadia, Hoosen; Ndung'u, Thumbi; Goulder, Philip J. R.] Univ KwaZulu Natal, Nelson Mandela Sch Med, HIV Pathogenesis Program, Durban, South Africa. [Frahm, Nicole; Brander, Christian; Walker, Bruce D.; Goulder, Philip J. R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chavy Chase, MD USA. [Bhattacharya, Tanmoy; Korber, Bette T.] Santa Fe Inst, Santa Fe, NM 87501 USA. [Mullins, James I.] Univ Washington, Dept Med, Seattle, WA USA. RP Rousseau, CM (reprint author), Univ Washington, Dept Microbiol, 1959 NE Pacific St,Box 358070, Seattle, WA 98195 USA. EM cmr@u.washington.edu RI Bhattacharya, Tanmoy/J-8956-2013; OI Bhattacharya, Tanmoy/0000-0002-1060-652X; Brander, Christian/0000-0002-0548-5778; Matthews, Philippa/0000-0002-4036-4269; Ndung'u, Thumbi/0000-0003-2962-3992; Korber, Bette/0000-0002-2026-5757 FU Medical Research Council [G0500384]; NIAID NIH HHS [AI27005, AI047734, AI058894, AI061734, AI067077, AI11514, AI27757, N01-AI-15422, P01 AI061734, P30 AI027757, R01 AI047734, R01 AI058894, R01 AI067077, R37 AI047734] NR 68 TC 102 Z9 103 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2008 VL 82 IS 13 BP 6434 EP 6446 DI 10.1128/JVI.02455-07 PG 13 WC Virology SC Virology GA 316KC UT WOS:000256947300032 PM 18434400 ER PT J AU Zhang, MY Vu, BK Choudhary, A Lu, H Humbert, M Ong, H Alam, M Ruprecht, RM Quinnan, G Jiang, S Montefiori, DC Mascola, JR Broder, CC Haynes, BF Dimitrov, DS AF Zhang, Mei-Yun Vu, Bang K. Choudhary, Anil Lu, Hong Humbert, Michael Ong, Helena Alam, Munir Ruprecht, Ruth M. Quinnan, Gerald Jiang, Shibo Montefiori, David C. Mascola, John R. Broder, Christopher C. Haynes, Barton F. Dimitrov, Dimiter S. TI Cross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody that recognizes a novel conformational epitope on gp41 and lacks reactivity against self-antigens SO JOURNAL OF VIROLOGY LA English DT Article ID NEUTRALIZING ANTI-GP41 2F5; PROXIMAL EXTERNAL REGION; ENVELOPE GLYCOPROTEIN; PHAGE LIBRARY; HIV-1 GP41; PHOSPHATIDYLINOSITOL PHOSPHATE; BINDING; FUSION; DIVERSE; INFECTION AB Broadly cross-reactive human immunodeficiency virus (HIV)-neutralizing antibodies are infrequently elicited in infected humans. The two best-characterized gp41-specific cross-reactive neutralizing human monoclonal antibodies, 4E10 and 2F5, target linear epitopes in the membrane-proximal external region (MPER) and bind to cardiolipin and several other autoantigens. It has been hypothesized that, because of such reactivity to self-antigens, elicitation of 2F5 and 4E10 and similar antibodies by vaccine immunogens based on the MPER could be affected by tolerance mechanisms. Here, we report the identification and characterization of a novel anti-gp41 monoclonal antibody, designated m44, which neutralized most of the 22 HIV type 1 (HIV-1) primary isolates from different clades tested in assays based on infection of peripheral blood mononuclear cells by replication-competent virus but did not bind to cardiolipin and phosphatidylserine in an enzyme-linked immunosorbent assay and a Biacore assay nor to any protein or DNA autoantigens tested in Luminex assays. m44 bound to membrane-associated HIV-1 envelope glycoproteins (Envs), to recombinant Envs lacking the transmembrane domain and cytoplasmic tail (gp140s), and to gp41 structures containing five-helix bundles and six-helix bundles, but not to N-heptad repeat trimers, suggesting that the C-heptad repeat is involved in m44 binding. In contrast to 2F5, 4E10, and Z13, m44 did not bind to any significant degree to denatured gp140 and linear peptides derived from gp41, suggesting a conformational nature of the epitope. This is the first report of a gp41-specific cross-reactive HIV-1-neutralizing human antibody that does not have detectable reactivity to autoantigens. Its novel conserved conformational epitope on gp41 could be helpful in the design of vaccine immunogens and as a target for therapeutics. C1 [Zhang, Mei-Yun; Vu, Bang K.; Dimitrov, Dimiter S.] NCI, CCRNP, CCR, NIH, Frederick, MD 21702 USA. [Zhang, Mei-Yun] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. [Choudhary, Anil; Quinnan, Gerald; Broder, Christopher C.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Lu, Hong; Jiang, Shibo] New York Blood Ctr, Lindsley F Kimball Res Inst, New York, NY 10021 USA. [Humbert, Michael; Ong, Helena; Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Humbert, Michael; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Alam, Munir; Montefiori, David C.; Haynes, Barton F.] Duke Univ, Med Ctr, Durham, NC USA. [Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Zhang, MY (reprint author), NCI, CCRNP, CCR, NIH, Bldg 469,Rm 131,POB B,Miller Dr, Frederick, MD 21702 USA. EM zhangm@ncifcrf.gov; dimitrov@ncifcrf.gov RI Jiang, Shibo/L-4500-2014 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400]; NIAID NIH HHS [P01 AI048280, AI46221, AI47434, AI48280, R01 AI046221, R21 AI046221, R37 AI034266, R37 AI34266] NR 52 TC 34 Z9 36 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2008 VL 82 IS 14 BP 6869 EP 6879 DI 10.1128/JVI.00033-08 PG 11 WC Virology SC Virology GA 324UQ UT WOS:000257545300009 PM 18480433 ER PT J AU Pollin, IS Kral, BG Shattuck, T Sadler, MD Boyle, JR McKillop, L Campbell, C Ashen, MD Nasir, K Redberg, RF BrintzenhofeSzoc, K Blumenthal, RS Michos, ED AF Pollin, Irene S. Kral, Brian G. Shattuck, Teresa Sadler, Michele Debarthe Boyle, Jennifer R. McKillop, Laurene Campbell, Catherine Ashen, M. Dominique Nasir, Khurram Redberg, Rita F. BrintzenhofeSzoc, Karlynn Blumenthal, Roger S. Michos, Erin D. TI High prevalence of cardiometabolic risk factors in women considered low risk by traditional risk assessment SO JOURNAL OF WOMENS HEALTH LA English DT Article ID CORONARY-HEART-DISEASE; CARDIOVASCULAR-DISEASE; FRAMINGHAM RISK; WAIST CIRCUMFERENCE; METABOLIC SYNDROME; ATHEROSCLEROSIS; DISPARITIES; ADHERENCE; DIAGNOSIS; AWARENESS AB Background: Cardiovascular disease (CVD) is the leading cause of death in women in the United States. The purpose of this study was to characterize the prevalence and awareness of traditional CVD risk factors, obesity, and coronary heart disease (CHD) risk classification using the Framingham Risk Score (FRS) among women attending the 2006 Sister to Sister National Woman's Heart Day event. Results: A total of 8936 participants (mean age 49 +/- 14 years) were evaluated. There was a modest prevalence of traditional risk factors on screening, including non-high-density lipoprotein-cholesterol (HDL-C) > 160 mg/dL (27%), HDL-C <40 mg/dL (16%), random glucose level >140 mg/dL (6%), uncontrolled blood pressure >= 140/90 mm Hg (12%), current smoking (6%), and a positive family history of CHD (21%). There was a high prevalence of overweight (39%) or obese individuals (35%) (body mass index [BMI] 25 - 30 and >= 30 kg/m(2), respectively), as well as those with high waist circumference (>= 35 inches) (55%). Women were classified by FRS as low (85%), intermediate (6%), and high risk (9%). When cardiometabolic risk analyses included waist circumference in addition to the FRS, 59% of low-risk and 50% of intermediate-risk women had 1 or 2 risk factors, and 19% and 41% had >= 3 risk factors, respectively. Women were often unaware of risk factors on screening; among women without a previous diagnosis of dyslipidemia or hypertension, 48% and 7%, respectively, were given new diagnoses. Conclusions: Women participating in the 2006 Sister to Sister National Woman's Heart Day event have a high prevalence of cardiometabolic risk factors, especially dyslipidemia, obesity, and high central adiposity, that place them at higher risk for the development of CVD and other comorbidities. The newly identified multiple risk factors in this population support the value of community health screening in women. C1 [Kral, Brian G.; Campbell, Catherine; Ashen, M. Dominique; Blumenthal, Roger S.; Michos, Erin D.] Johns Hopkins Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA. [Shattuck, Teresa; Sadler, Michele Debarthe; Boyle, Jennifer R.] Shattuck & Assoc Inc, Mt Airy, MD USA. [Nasir, Khurram] Massachusetts Gen Hosp, Cardiac MRI PET CT Program, Boston, MA 02114 USA. [Redberg, Rita F.] Univ Calif San Francisco, Div Cardiol, San Francisco, CA 94143 USA. [BrintzenhofeSzoc, Karlynn] Catholic Univ Amer, Natl Catholic Sch Social Serv, Washington, DC 20064 USA. RP Michos, ED (reprint author), Johns Hopkins Ciccarone Ctr Prevent Heart Dis, Carneige 568,600 N Wolfe St, Baltimore, MD 21287 USA. EM edonnell@jhmi.edu FU Heart Foundation, Bethesda, MD; Schafer Memorial Cardiovascular Research Fund FX This work was supported by the nonprofit Sister to Sister, Everyone Has a Heart Foundation, Bethesda, MD. E. D. M. is partially funded by the P.J. Schafer Memorial Cardiovascular Research Fund. NR 22 TC 11 Z9 11 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD JUL-AUG PY 2008 VL 17 IS 6 BP 947 EP 953 DI 10.1089/jwh.2007.0640 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 344AG UT WOS:000258897000006 PM 18582174 ER PT J AU Kamat, A Ghosh, PM Glover, RL Zhu, B Yeh, CK Choudhury, GG Katz, MS AF Kamat, Amrita Ghosh, Paramita M. Glover, Renee L. Zhu, Bing Yeh, Chih-Ko Choudhury, Goutam Ghosh Katz, Michael S. TI Reduced expression of epidermal growth factor receptors in rat liver during aging SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE extracellular signal-regulated kinase; hepatocytes; receptor dimerization; receptor tyrosine kinase ID AGE-RELATED DECLINE; EGF RECEPTOR; DNA-SYNTHESIS; TYROSINE KINASE; THYROID-HORMONE; LIGAND-BINDING; HEPATOCYTES; ACTIVATION; TRANSCRIPTION; REGENERATION AB Proliferative responsiveness of hepatocytes to epidermal growth factor (EGF) declines during aging. The role of EGF receptors in mediating age-dependent changes of EGF-induced mitogenic signaling in liver remains incompletely understood. We assessed EGF receptor expression levels in whole liver specimens as well as in freshly isolated and cultured hepatocytes from young adult and senescent Fischer 344 male rats. Hepatic EGF receptor messenger RNA and protein levels, and the number of high- and low-affinity receptor binding sites, decreased with aging. Ligand-induced EGF receptor activation, determined by receptor dimerization and tyrosine phosphorylation, was reduced in old animals in parallel with the age-related decline in receptor expression. Stimulation of the extracellular signal-regulated kinase pathway by EGF was also attenuated in hepatocytes from old animals. Our results implicate decreased expression of EGF receptors as a key determinant of reduced mitogenic signaling responsive to EGF stimulation of liver during aging. C1 S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. [Kamat, Amrita; Glover, Renee L.; Choudhury, Goutam Ghosh; Katz, Michael S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Ghosh, Paramita M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, San Antonio, TX 78229 USA. [Zhu, Bing; Yeh, Chih-Ko] Univ Texas Hlth Sci Ctr San Antonio, Dept Dent Diagnost Sci, San Antonio, TX 78229 USA. RP Kamat, A (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr 182, San Antonio, TX 78229 USA. EM kamat@uthscsa.edu FU NCI NIH HHS [R21 CA109057]; NIDDK NIH HHS [R01 DK 50190] NR 43 TC 5 Z9 6 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 2008 VL 63 IS 7 BP 683 EP 692 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 336UE UT WOS:000258389300005 PM 18693222 ER PT J AU Thadhani, R AF Thadhani, Ravi TI Targeted ablation of the vitamin D 1 alpha-hydroxylase gene: getting to the heart of the matter SO KIDNEY INTERNATIONAL LA English DT Editorial Material ID D DEFICIENCY; HEMODIALYSIS; MICE; SURVIVAL; SKELETAL; RICKETS; KIDNEY; MOUSE; D-3 AB Targeted gene ablation technology has uncovered biological mechanisms that have led to important therapeutics in humans. In a study by Zhou et al., ablation of the 1 alpha-hydroxylase gene led to hypertension, cardiac hypertrophy, and systolic dysfunction, and this cardiac phenotype was rescued with exogenous 1,25-dihydroxyvitamin D administration. C1 [Thadhani, Ravi] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. [Thadhani, Ravi] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr D Receptor Activat Res, Boston, MA 02114 USA. RP Thadhani, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit, Bullfinch 127,55 Fruit St, Boston, MA 02114 USA. EM thadhani.ravi@mgh.harvard.edu NR 21 TC 7 Z9 8 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUL PY 2008 VL 74 IS 2 BP 141 EP 143 DI 10.1038/ki.2008.219 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 320YA UT WOS:000257269900001 PM 18591942 ER PT J AU Jonker, SS Anderson, DF Davis, LE Yang, Q Faber, JJ Giraud, GD AF Jonker, S. S. Anderson, D. F. Davis, L. E. Yang, Q. Faber, J. J. Giraud, G. D. TI Persistent changes in arterial blood gases in fetal sheep SO LABORATORY ANIMALS LA English DT Article DE fetal surgery; anaesthesia; pregnancy; sheep ID AMNIOTIC-FLUID; ANESTHESIA AB Two anaesthetic protocols were compared using pregnant sheep. In both groups of animals, anaesthesia was induced using an intravenous (i.v.) injection of diazepam and ketamine. The ewes were then intubated for positive pressure ventilation using 0.8 L/min of nitrous oxide and 2 L/min oxygen with 1.1-1.8% halothane. If the ewe showed any signs of awakening, one of two protocols was followed. First, the halothane concentration was increased to 2-3 until the ewe was completely anaesthetized. Second, the halothane concentration was not altered, but the ewe was given doses of i.v. diazepam (0.1 mg/kg) and ketamine (1 mg/kg) until again completely anaesthetized. At the completion of surgery, maternal recovery was rapid and similar between the two groups. However, five days after surgery, the fetal arterial Po-2 and oxygen content of the fetuses receiving additional halothane (1.9 +/- 0.2 kPa and 4.4 +/- 1.0 mL/100 mL) were statistically significantly depressed when compared with the fetuses receiving additional diazepam and ketamine (2.9 +/- 0.1 kPa and 7.0 +/- 0.5 mL/100 mL). These results led us to conclude that certain anaesthetic protocols, in spite of good maternal recovery, can lead to deleterious effects upon the fetus that persist for at least five days after surgery. C1 [Jonker, S. S.; Anderson, D. F.; Faber, J. J.; Giraud, G. D.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. [Davis, L. E.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA. [Yang, Q.] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97201 USA. [Giraud, G. D.] Portland VA Med Ctr, Portland, OR USA. RP Jonker, SS (reprint author), Univ Iowa, 1270 CBRB,285 Newton Rd, Iowa City, IA 52242 USA. EM sonnet-jonker@uiowa.edu RI Yang, Qin/O-8508-2015; OI Jonker, Sonnet/0000-0002-1097-2562 FU NHLBI NIH HHS [HL 45043, R01 HL045043, R01 HL045043-15]; NICHD NIH HHS [5P01 HD 34430, HD 37376, P01 HD034430, P01 HD034430-12, R01 HD037376, R01 HD037376-05] NR 8 TC 3 Z9 3 U1 0 U2 4 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0023-6772 J9 LAB ANIM-UK JI Lab. Anim. PD JUL PY 2008 VL 42 IS 3 BP 326 EP 330 DI 10.1258/la.2007.06005e PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 333VH UT WOS:000258180400009 PM 18625587 ER PT J AU Lewis, CM Deschler, DG AF Lewis, Carol M. Deschler, Daniel G. TI Desirudin Reduces the Rate of Microvenous Thrombosis in a Rat Model SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Eastern Section Meeting of the Triologic-Society CY JAN 25-27, 2008 CL Philadelphia, PA SP Triol Soc DE Microvascular; free flap; desirudin; thrombosis ID MOLECULAR-WEIGHT HEPARIN; NECK RECONSTRUCTION; RECOMBINANT HIRUDIN; HIP-REPLACEMENT; FREE FLAPS; ASPIRIN; HEAD; ANASTOMOSIS; INHIBITION; ARTERIAL AB Objectives: In an effort to evaluate pharmacologic agents for optimal anticoagulant prophylaxis in patients undergoing free tissue transfer, we evaluated the efficacy of desirudin (Canyon Pharmaceuticals, Hunt Valley, MD), a recombinant hirudin that acts as a direct thrombin inhibitor, using a rat model of microvenous thrombosis. Study Design: Randomized, blinded study using an in vivo rat model of microvenous failure. Methods: Thirty-two rats received either desirudin or saline in a randomized, blinded fashion 30 minutes prior to performance of a standardized thrombogenic procedure on rat femoral veins. Bleeding time, vessel patency, and presence of clot within the anastomosis were subsequently assessed. Appropriate statistical analyses were then performed. Results: There was a significant increase in vessel patency in rats treated preoperatively with desirudin compared to controls receiving saline (96.9% vs. 53.1%, P < .001). In evaluating patent vessels for non-occluding clot, 41.2% of control rats had non-obstructive clot at the site of anastomosis, versus 3.2% of rats treated with desirudin (P = .002). Bleeding times were longer in desirudin-treated rats than those that received saline (7.17 +/- 3 minutes vs. 5.15 +/- 1.2 minutes, P = .027). Conclusions: The use of preoperative desirudin increases the rate of microvascular anastomotic patency, decreases the occurrence of non-occluding clot, and increases bleeding time in an in vivo rat model, indicating potential efficacy C1 [Lewis, Carol M.; Deschler, Daniel G.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Lewis, Carol M.; Deschler, Daniel G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Deschler, DG (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Daniel_Deschler@meei.harvard.edu NR 22 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUL PY 2008 VL 118 IS 7 BP 1149 EP 1152 DI 10.1097/MLG.0b013e31816d727c PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 368ZN UT WOS:000260662400003 PM 18401270 ER PT J AU Shammas, MA Koley, H Bertheau, RC Neri, P Fulciniti, M Tassone, P Blotta, S Protopopov, A Mitsiades, C Batchu, RB Anderson, KC Chin, A Gryaznov, S Munshi, NC AF Shammas, M. A. Koley, H. Bertheau, R. C. Neri, P. Fulciniti, M. Tassone, P. Blotta, S. Protopopov, A. Mitsiades, C. Batchu, R. B. Anderson, K. C. Chin, A. Gryaznov, S. Munshi, N. C. TI Telomerase inhibitor GRN163L inhibits myeloma cell growth in vitro and in vivo SO LEUKEMIA LA English DT Article DE telomerase; telomere; myeloma; cancer ID QUADRUPLEX-INTERACTIVE AGENT; MULTIPLE-MYELOMA; IMMORTAL CELLS; ADENOCARCINOMA CELLS; TELOMESTATIN SOT-095; LEUKEMIA-CELLS; CANCER-CELLS; DNA-DAMAGE; APOPTOSIS; ARREST AB Human telomerase, the reverse transcriptase which extends the life span of a cell by adding telomeric repeats to chromosome ends, is expressed in most cancer cells but not in the majority of normal somatic cells. Inhibition of telomerase therefore holds great promise as anticancer therapy. We have synthesized a novel telomerase inhibitor GRN163L, a lipid-attached phosphoramidate oligonucleotide complementary to template region of the RNA subunit of telomerase. Here, we report that GRN163L is efficiently taken up by human myeloma cells without any need of transfection and is resistant to nucleolytic degradation. The exposure of myeloma cells to GRN163L led to an effective inhibition of telomerase activity, reduction of telomere length and apoptotic cell death after a lag period of 2-3 weeks. Mismatch control oligonucleotides had no effect on growth of myeloma cells. The in vivo efficacy of GRN163L was confirmed in two murine models of human multiple myeloma. In three independent experiments, significant reduction in tumor cell growth and better survival than control mice was observed. Furthermore, GRN163L-induced myeloma cell death could be significantly enhanced by Hsp90 inhibitor 17AAG. These data provide the preclinical rationale for clinical evaluation of GRN163L in myeloma and in combination with 17AAG. C1 [Shammas, M. A.; Bertheau, R. C.; Neri, P.; Fulciniti, M.; Tassone, P.; Blotta, S.; Protopopov, A.; Mitsiades, C.; Anderson, K. C.; Munshi, N. C.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Adult Oncol, Boston, MA 02115 USA. [Shammas, M. A.; Koley, H.; Bertheau, R. C.; Fulciniti, M.; Tassone, P.; Blotta, S.; Batchu, R. B.; Munshi, N. C.] VA Boston Healthcare Syst, Dept Med, Boston, MA USA. [Shammas, M. A.; Koley, H.; Bertheau, R. C.; Neri, P.; Fulciniti, M.; Tassone, P.; Blotta, S.; Protopopov, A.; Mitsiades, C.; Batchu, R. B.; Anderson, K. C.; Munshi, N. C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Chin, A.; Gryaznov, S.] Geron Corp, Menlo Pk, CA USA. RP Munshi, NC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Adult Oncol, 44 Binney St,D1B25, Boston, MA 02115 USA. EM Nikhil_Munshi@DFCI.Harvard.edu FU NCI NIH HHS [P01 CA078378, P01 CA078378-06A1, P50 CA100707, P50 CA100707-01, R01 CA124929, R01 CA124929-01A2, R01 CA125711, R01-CA124929]; PHS HHS [P01-78378, P050-100007, P50-100007] NR 33 TC 56 Z9 62 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUL PY 2008 VL 22 IS 7 BP 1410 EP 1418 DI 10.1038/leu.2008.81 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 326HF UT WOS:000257648500013 PM 18449204 ER PT J AU Ehrenfeld, JM Sandberg, WS AF Ehrenfeld, Jesse M. Sandberg, Warren S. TI INCIDENCE OF INTRAOPERATIVE GAPS IN PATIENT MONITORING DURING LIVER TRANSPLANATION SO LIVER TRANSPLANTATION LA English DT Meeting Abstract CT Joint International Congress of the ILTS, ELITA, AND LICAGE CY JUL 09-12, 2008 CL Paris, FRANCE SP ILTS, ELITA, LICAGE C1 [Ehrenfeld, Jesse M.; Sandberg, Warren S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD JUL PY 2008 VL 14 IS 7 BP S81 EP S81 PG 1 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 418JO UT WOS:000264144700050 ER PT J AU Guckelberger, O Micheal, MD Biddinger, SB Schoebel, C Reuter, S Neuhaus, P Kahn, CR Robson, SC AF Guckelberger, Olaf Micheal, M. D. Biddinger, S. B. Schoebel, C. Reuter, S. Neuhaus, P. Kahn, C. R. Robson, S. C. TI HEPATIC INSULIN-RESISTANCE DE CREASES IGF-I-mRNA AND DELAYS LIVER REGENERATION IN MICE. SO LIVER TRANSPLANTATION LA English DT Meeting Abstract CT Joint International Congress of the ILTS, ELITA, AND LICAGE CY JUL 09-12, 2008 CL Paris, FRANCE SP ILTS, ELITA, LICAGE C1 [Guckelberger, Olaf; Schoebel, C.; Reuter, S.; Neuhaus, P.] Charite Campus Virchow Klinikum, Dept Gen Visceral & Transplantat Surg, Berlin, Germany. [Micheal, M. D.; Biddinger, S. B.; Kahn, C. R.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Robson, S. C.] Beth Israel Deaconess Med Ctr, Dept Gastroenterol, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD JUL PY 2008 VL 14 IS 7 BP S235 EP S235 PG 1 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 418JO UT WOS:000264144700590 ER PT J AU Kawai, T Ko, D Yeh, H Markmann, J Chung, R Hertl, M Cosimi, AB Elias, N AF Kawai, T. Ko, D. Yeh, H. Markmann, J. Chung, R. Hertl, M. Cosimi, A. B. Elias, N. TI STEROID-FREE VERSUS CORTICOSTEROID INDUCTION AND MAINTENANCE FOLLOWING ORTHOTOPIC LIVER TRANSPLANTATION FOR HEPATITIS C VIRUS. SO LIVER TRANSPLANTATION LA English DT Meeting Abstract CT Joint International Congress of the ILTS, ELITA, AND LICAGE CY JUL 09-12, 2008 CL Paris, FRANCE SP ILTS, ELITA, LICAGE C1 [Kawai, T.; Ko, D.; Yeh, H.; Markmann, J.; Chung, R.; Hertl, M.; Cosimi, A. B.; Elias, N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Transplantat Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD JUL PY 2008 VL 14 IS 7 BP S107 EP S107 PG 1 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 418JO UT WOS:000264144700144 ER PT J AU Asomaning, K Miller, DP Liu, G Wain, JC Lynch, TJ Su, L Christiani, DC AF Asomaning, Kofi Miller, David P. Liu, Geoffrey Wain, John C. Lynch, Thomas J. Su, Li Christiani, David C. TI Second hand smoke, age of exposure and tung cancer risk SO LUNG CANCER LA English DT Article DE second hand smoke; active smoking; age of exposure; lung cancer risk; lung growth; case control study ID ENVIRONMENTAL TOBACCO-SMOKE; PARENTAL CIGARETTE-SMOKING; CHILDHOOD BRAIN-TUMORS; GERM-CELL TUMORS; LUNG-CANCER; NONSMOKING WOMEN; PASSIVE SMOKING; PULMONARY-FUNCTION; PRENATAL EXPOSURE; DNA-DAMAGE AB Background: Exposure to second hand smoke (SHS) has been identified as a risk factor for lung cancer for three decades. It is also known that the lung continues to grow from birth to adulthood, when lung growth stops. We hypothesize that after adjusting for active cigarette smoking, if SHS exposure took place during the period of growth, i.e. in the earlier part of life (0-25 years of age) the risk of lung cancer is greater compared to an exposure occurring after age 25. Method: Second hand smoke exposure was self-reported for three different activities (leisure, work and at home) for this study population of 1669 cases and 1263 controls. We created variables that captured location of exposure and timing of first exposure with respect to a study participant's age (0-25, > 25 years of age). Multiple logistic regressions were used to study the association between SHS exposure and lung cancer, adjusting for age, gender and active smoking variables. Result: For study participants that were exposed to SHS at both activities (work and leisure) and compared to one or no activity, the adjusted odds ratio (AOR) for lung cancer was 1.30 (1.08-1.57) when exposure occurred between birth and age 25 and 0.66 (0.21-1.57) if exposure occurred after age 25 years. Respective results for non-smokers were 1.29 (0.82-2.02) and 0.87 (0.22-3.38), and current and ex-smokers combined 1.28 (1.04-1.58) and 0.66 (0.15-2.85). Conclusion: All individuals exposed to SHS have a higher risk of lung cancer. Furthermore, this study suggests that subjects first exposed before age 25 have a higher lung cancer risk compared to those for whom first exposure occurred after age 25 years. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Asomaning, Kofi; Miller, David P.; Liu, Geoffrey; Su, Li; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. [Wain, John C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Thorac Surg Unit, Boston, MA 02114 USA. [Lynch, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Oncol Unit, Boston, MA 02114 USA. [Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, 665 Huntington Ave,Bldg 1,Room 1402, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [R01 CA074386, CA74386, R01 CA074386-10, R01 CA092824, R01 CA092824-06]; NIEHS NIH HHS [ES00002, P30 ES000002] NR 58 TC 29 Z9 29 U1 1 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD JUL PY 2008 VL 61 IS 1 BP 13 EP 20 DI 10.1016/j.lungcan.2007.11.013 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 330IN UT WOS:000257934400002 PM 18191495 ER PT J AU Grant, RW AF Grant, Richard W. TI Next generation of health information tools: Where do we go from here? SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material ID DECISION-SUPPORT-SYSTEMS; CARE; TECHNOLOGY; QUALITY C1 [Grant, Richard W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Grant, Richard W.] Harvard Univ, Sch Med, Boston, MA USA. RP Grant, RW (reprint author), Mayo Clin & Mayo Fdn, 50-9 Staniford St, Boston, MA USA. EM Rgrant@partners.org OI Grant, Richard/0000-0002-6164-8025 NR 12 TC 1 Z9 1 U1 0 U2 0 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JUL PY 2008 VL 83 IS 7 BP 745 EP 746 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 319XJ UT WOS:000257198000002 PM 18613990 ER PT J AU Becker, DJ Gordon, RY Morris, PB Yorko, J Gordon, YJ Li, MY Iqbal, N AF Becker, David J. Gordon, Ram Y. Morris, Patti B. Yorko, Jacqueline Gordon, Y. Jerold Li, Mingyao Iqbal, Nayyar TI Simvastatin vs therapeutic lifestyle changes and supplements: Randomized primary prevention trial SO MAYO CLINIC PROCEEDINGS LA English DT Article ID CORONARY-ARTERY-DISEASE; FAMILIAL HYPERCHOLESTEROLEMIA; MYOCARDIAL-INFARCTION; DIETARY-SUPPLEMENTS; MEDITERRANEAN DIET; WEIGHT-REDUCTION; HEART-DISEASE; RISK-FACTORS; CHOLESTEROL; OMEGA-3-FATTY-ACIDS AB OBJECTIVE: To compare the lipid-lowering effects of an alternative regimen (lifestyle changes, red yeast rice, and fish oil) with a standard dose of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin). PATIENTS AND METHODS: This randomized trial enrolled 74 patients with hypercholesterolemia who met Adult Treatment Panel III criteria for primary prevention using statin therapy. All participants were randomized to an alternative treatment group (AG) or to receive simvastatin (40 mg/d) in this open-label trial conducted between April 1, 2006, and June 30, 2006. The alternative treatment included therapeutic lifestyle changes, Ingestion of red yeast rice, and fish oil supplements for 12 weeks. The simvastatin group received medication and traditional counseling. The primary outcome measure was the percentage change in low-density lipoprotein cholesterol (LDL-C). Secondary measures were changes in other lipoproteins and weight loss. RESULTS: There was a statistically significant reduction in LDL-C levels in both the AG (-42.4%+/- 15%) (P <.001) and the simvastatin group (-39.6%+/- 20%) (P <.001). No significant differences were noted between groups. The AG also demonstrated significant reductions in triglycerides (-29% vs -9.3%; 95% confidence interval, -61 to -11.7; P=.003) and weight (-5.5% vs -0.4%; 95% confidence interval, -5.5 to -3.4; P <.001) compared with the simvastatin group. CONCLUSION: Lifestyle changes combined with ingestion of red yeast rice and fish oil reduced LDL-C in proportions similar to standard therapy with shrivastatin. Pending confirmation in larger trials, this multifactorial, alternative approach to lipid lowering has promise for a subset of patients unwilling or unable to take statins. C1 [Becker, David J.; Gordon, Ram Y.; Morris, Patti B.; Yorko, Jacqueline] Univ Penn Hlth Syst, Chestnut Hill Hosp, Div Cardiol, Philadelphia, PA USA. [Gordon, Y. Jerold] Univ Pittsburgh, Sch Med, Dept Ophthalmol, Pittsburgh, PA 15261 USA. [Li, Mingyao] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Iqbal, Nayyar] Univ Penn, Philadelphia VA Med Ctr, Div Endocrinol, Philadelphia, PA 19104 USA. RP Becker, DJ (reprint author), Mayo Clin & Mayo Fdn, 1722 Bethlehem Pike, Flourtown, PA 19095 USA. EM dbeckerchcardiology@hotmail.com NR 44 TC 46 Z9 47 U1 2 U2 8 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JUL PY 2008 VL 83 IS 7 BP 758 EP 764 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 319XJ UT WOS:000257198000004 PM 18613992 ER PT J AU Newman-Toker, DE Hsieh, YH Camargo, CA Pelletier, AJ Butchy, GT Edlow, JA AF Newman-Toker, David E. Hsieh, Yu-Hsiang Camargo, Carlos A., Jr. Pelletier, Andrea J. Butchy, Gregary T. Edlow, Jonathan A. TI Spectrum of dizziness visits to US emergency departments: Cross-sectional analysis from a nationally representative sample SO MAYO CLINIC PROCEEDINGS LA English DT Article ID SYMPTOM QUALITY; COMPUTED-TOMOGRAPHY; AORTIC DISSECTION; DIZZY PATIENT; VERTIGO; PREVALENCE; CARE; PHYSICIANS; COMMUNITY; HEADACHE AB OBJECTIVE: To describe the spectrum of visits to US emergency departments (EDs) for acute dizziness and determine whether ED patients with dizziness are diagnosed as having a range of benign and dangerous medical disorders, rather than predominantly vestibular ones. PATIENTS AND METHODS: A cross-sectional study of ED visits from the National Hospital Ambulatory Medical Care Survey (NHAMCS) used a weighted sample of US ED visits (1993-2005) to measure patient and hospital demographics, ED diagnoses, and resource use in cases vs controls without dizziness. Dizziness In patients 16 years or older was defined as an NHAMCS reason-for-visit code of dizziness/vertigo (1225.0) or a final International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis of dizziness/vertigo (780.4) or of a vestibular disorder (386.x). RESULTS: A total of 9472 dizziness cases (3.3% of visits) were sampled over :13 years (weighted 33.6 million). Top diagnostic groups were otologic/vestibular (32.9%), cardiovascular (21.1%], respiratory (11.5%), neurologic (11.2%, including 4% cerebrovascular), metabolic: (11.0%), injury/poisoning (10.6%), psychiatric (7.2%), digestive (7.0%), genitourinary (5.1%), and Infectious (2.9%). Nearly half of the cases (49.2%) were given a medical diagnosis, and 22.1% were given only a symptom diagnosis. Predefined dangerous disorders were diagnosed In 15%, especially among those older than 50 years (20.9% vs 9.3%; P <.001). Dizziness cases were evaluated longer (mean 4.0 vs 3.4 hours), Imaged disproportionately (18.0% vs 6.9% undergoing computed tomography or magnetic resonance Imaging), and admitted more often (18.8% vs 14.8%) (all P <.001). CONCLUSION: Dizziness is not attributed to a vestibular disorder in most ED cases and often is associated with cardiovascular or other medical causes, including dangerous ones. Resource use is substantial, yet many patients remain undiagnosed. C1 [Newman-Toker, David E.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Hsieh, Yu-Hsiang] Johns Hopkins Univ, Sch Med, Dept Emergency Med, Baltimore, MD 21205 USA. [Butchy, Gregary T.] Johns Hopkins Univ, Sch Med, Div Hlth Sci Informat, Baltimore, MD 21205 USA. [Camargo, Carlos A., Jr.; Pelletier, Andrea J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Edlow, Jonathan A.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Emergency Mediiine, Boston, MA USA. RP Newman-Toker, DE (reprint author), Johns Hopkins Univ Hosp, Pathol Bldg 2-210,600 N Wolfe St, Baltimore, MD 21287 USA. EM tolker@jhu.edu RI Newman-Toker, David/C-6083-2008 OI Newman-Toker, David/0000-0003-2789-4115 FU NCRR NIH HHS [K23 RR 17324-01, K23 RR017324] NR 37 TC 90 Z9 97 U1 0 U2 5 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JUL PY 2008 VL 83 IS 7 BP 765 EP 775 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 319XJ UT WOS:000257198000005 PM 18613993 ER PT J AU Xu, G Herzig, M Rotrekl, V Walter, CA AF Xu, Guogang Herzig, Maryanne Rotrekl, Vladimir Walter, Christi A. TI Base excision repair, aging and health span SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Review DE base excision repair; aging; DNA damage; mutagenesis; health span ID DNA-POLYMERASE-BETA; STRAND BREAK REPAIR; AMYOTROPHIC-LATERAL-SCLEROSIS; OXIDATIVELY DAMAGED DNA; LACI TRANSGENIC MICE; HOGG1 SER326CYS POLYMORPHISM; MULTIPLE COLORECTAL ADENOMA; GAMMA-RADIATION SENSITIVITY; INDUCED CYTIDINE DEAMINASE; ALZHEIMERS-DISEASE BRAIN AB DNA damage and mutagenesis are suggested to contribute to aging through their ability to mediate cellular dysfunction. The base excision repair (BER) pathway ameliorates a large number of DNA lesions that arise spontaneously. Many of these lesions are reported to increase with age. Oxidized guanine, repaired largely via base excision repair, is particularly well studied and shown to increase with age. Spontaneous mutant frequencies also increase with age which suggests that mutagenesis may contribute to aging. It is widely accepted that genetic instability contributes to age-related occurrences of cancer and potentially other age-related pathologies. BER activity decreases with age in multiple tissues. The specific BER protein that appears to limit activity varies among tissues. DNA polymerase-p is reduced in brain from aged mice and rats while AP endonuclease is reduced in spermatogenic cells obtained from old mice. The differences in proteins that appear to limit BER activity among tissues may represent true tissue-specific differences in activity or may be due to differences in techniques, environmental conditions or other unidentified differences among the experimental approaches. Much remains to be addressed concerning the potential role of BER in aging and age-related health span. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Xu, Guogang; Herzig, Maryanne; Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Rotrekl, Vladimir] Masaryk Univ, Inst Expt Med, Dept Mol Embryol, Fac Med,Dept Biol, Brno 62500, Czech Republic. [Walter, Christi A.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Walter, CA (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, Mail Code 7762,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM walter@uthscsa.edu FU NIA NIH HHS [AG 21163, AG 24364, R01 AG021163, R01 AG021163-05, R01 AG024364, R01 AG024364-04] NR 271 TC 53 Z9 55 U1 0 U2 14 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD JUL-AUG PY 2008 VL 129 IS 7-8 BP 366 EP 382 DI 10.1016/j.mad.2008.03.001 PG 17 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 328RS UT WOS:000257816100003 PM 18423806 ER PT J AU Lamiani, G Meyer, EC Rider, EA Browning, DM Vegni, E Mauri, E Moja, EA Truog, RD AF Lamiani, Giulia Meyer, Elaine C. Rider, Elizabeth A. Browning, David M. Vegni, Elena Mauri, Emanuela Moja, Egidio A. Truog, Robert D. TI Assumptions and blind spots in patient-centredness: action research between American and Italian health care professionals SO MEDICAL EDUCATION LA English DT Article DE patient-centred care; Boston; Italy; cost-benefit analysis; culture; physician-patient relations; emotions; clinical competence, standards; multicentre study [publication type]; hospitals, teaching ID QUALITATIVE RESEARCH; UNITED-STATES; COMMUNICATION; PHYSICIANS; CONSULTATIONS; REFLECTION; MEDICINE; DOCTORS AB OBJECTIVE To examine how patient-centredness is understood and enacted in an American (US) and an Italian group of health care professionals. METHODS An action research methodology was used. Two interprofessional groups of US (n = 4) and Italian (n = 5) health care professionals independently wrote a patient-centred dialogue between a doctor and a patient based on the same scenario. The dialogues were then translated and exchanged. Both groups independently commented on the patient-centred aspects of the other's dialogue by completing a written questionnaire. Their respective comments were then shared by international videoconference. The transcript of the videoconference was analysed via content analysis. The participants' opinions about the study were then evaluated. RESULTS Exploring the patient's illness experience and handling the patient's emotions were identified as core components of patient-centred care by both the US and Italian groups, but were expressed differently in their respective dialogues. Respecting the patient's autonomy was recognised as a component of patient-centred care only by the US group. The Italian group demonstrated a more implicitly paternalistic approach. Participants highlighted the usefulness of one another's feedback to uncover cultural assumptions of patient-centred care and increase self-awareness. CONCLUSIONS Results suggest that the concept and practice of patient-centred care is variable and may be influenced by culture. The study methodology improved participants' self-awareness of cultural values, and has potential as a cost-effective, experiential educational approach. C1 [Lamiani, Giulia; Vegni, Elena; Mauri, Emanuela; Moja, Egidio A.] Univ Milan, San Paolo Hosp, Inst Med Psychol, Dept Med Surg & Dent, I-20142 Milan, Italy. [Lamiani, Giulia; Meyer, Elaine C.; Rider, Elizabeth A.; Browning, David M.; Truog, Robert D.] Childrens Hosp, Inst Professionalism & Eth Practice, Div Crit Care Med, Boston, MA 02115 USA. [Meyer, Elaine C.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Rider, Elizabeth A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Rider, Elizabeth A.] Massachusetts Gen Hosp, John D Stoeckle Ctr Primary Care Innovat, Boston, MA 02114 USA. [Browning, David M.] Initiat Pediat Palliat Care Educ Dev Ctr Inc, Newton, MA USA. [Truog, Robert D.] Harvard Univ, Sch Med, Div Med Eth, Boston, MA USA. RP Lamiani, G (reprint author), Univ Milan, San Paolo Hosp, Inst Med Psychol, Dept Med Surg & Dent, Via Rudini 8, I-20142 Milan, Italy. EM giulialamiani@libero.it OI Vegni, Elena/0000-0002-4785-5837; Giulia, Lamiani/0000-0002-1943-3282 NR 30 TC 16 Z9 17 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0308-0110 J9 MED EDUC JI Med. Educ. PD JUL PY 2008 VL 42 IS 7 BP 712 EP 720 DI 10.1111/j.1365-2923.2008.03038.x PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 311SQ UT WOS:000256620300010 PM 18588650 ER PT J AU Berbeco, RI Hacker, F Zatwarnicki, C Park, SJ Ionascu, D O'Farrell, D Mamon, HJ AF Berbeco, Ross I. Hacker, Fred Zatwarnicki, Chris Park, Sang-June Ionascu, Dan O'Farrell, Desmond Mamon, Harvey J. TI A novel method for estimating SBRT delivered dose with beam's-eye-view images SO MEDICAL PHYSICS LA English DT Article DE SBRT; EPID; delivered dose; liver; radiotherapy ID TRANSTHORACIC NEEDLE-BIOPSY; CINE MODE; PULMONARY NODULES; RADIATION-THERAPY; LUNG-TUMORS; CT; VERIFICATION; RADIOTHERAPY; PNEUMOTHORAX; FEASIBILITY AB Stereotactic body radiation therapy is predicated on a high degree of targeting accuracy. However, inaccurate patient setup as well as intra-fractional motion can hinder the delivery of high doses preferentially to the target. To ensure that the coverage delivered to the patient is as planned, an image-guided verification system has been created to estimate the delivered dose retrospectively. This will not only aid the assessment of treatment techniques, but will also allow for more accurate dose response analysis. Patients with limited hepatic metastases from solid tumors were treated with SBRT. Implanted gold markers were used as target surrogates and a body frame and compression plate provided stereotactic localization and target immobilization, respectively. During treatment, an electronic portal imaging device (EPID), operating in cine mode, collected the exit dose. The sequences of images for each field were processed off-line using in-house software for registration and seed localization. The beam's-eye-view seed positions in the treatment images were compared to those in the DRR's to determine the target shifts in the imaging plane. These target shifts were then imported into the treatment planning software. Each original field was multiplied by the number of images taken during treatment. The calculated shift from each image was then applied to each of the new subfields. Summing all of these subfields together gives the dose distribution that was actually delivered to the patient. The dose-volume histograms for the planned and delivered distributions for four patients' complete treatments are shown. For two of the patients, underdosing due to a setup error or intra-fractional drift was not wholly resolved by subsequent fractions. For one of these patients two alternative corrective strategies have been applied, retrospectively, and the prescribed target coverage recovered for both. The delivered dose can be estimated using the information contained in cine EPID images acquired during irradiation. Calculating the dose actually delivered to the target will allow us to assess treatment procedures as well as more accurately report clinical results. (C) 2008 American Association of Physicists in Medicine. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. RP Berbeco, RI (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM rberbeco@lroc.harvard.edu OI Hacker, Fred/0000-0001-7535-7598 NR 20 TC 17 Z9 17 U1 0 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUL PY 2008 VL 35 IS 7 BP 3225 EP 3231 DI 10.1118/1.2938514 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 320KF UT WOS:000257231700025 PM 18697547 ER PT J AU Cai, WL Zalis, ME Nappi, J Harris, GJ Yoshida, H AF Cai, Wenli Zalis, Michael E. Naeppi, Janne Harris, Gordon J. Yoshida, Hiroyuki TI Structure-analysis method for electronic cleansing in cathartic and noncathartic CT colonography SO MEDICAL PHYSICS LA English DT Article DE electronic cleansing; CT colonography; virtual colonoscopy; fecal tagging; noncathartic preparation ID VIRTUAL COLONOSCOPY; COLORECTAL-CANCER; COLONIC POLYPS; IMAGES; PREFERENCES; ADULTS AB Electronic cleansing (EC) is an emerging method for segmentation of fecal material in CT colonography (CTC) that is used for reducing or eliminating the requirement for cathartic bowel preparation and hence for improving patients' adherence to recommendations for colon cancer screening. In EC, feces tagged by an x-ray-opaque oral contrast agent are removed from the CTC images, effectively cleansing the colon after image acquisition. Existing EC approaches tend to suffer from the following cleansing artifacts: degradation of soft-tissue structures because of pseudo-enhancement caused by the surrounding tagged fecal materials, and pseudo soft-tissue structures and false fistulas caused by partial volume effects at the boundary between the air lumen and the tagged regions, called the air-tagging boundary (AT boundary). In this study, we developed a novel EC method, called structure-analysis cleansing, which effectively avoids these cleansing artifacts. In our method, submerged soft-tissue structures are recognized by their local morphologic signatures that are characterized based on the eigenvalues of a three-dimensional Hessian matrix. A structure-enhancement function is formulated for enhancing of the soft-tissue structures. In addition, thin folds sandwiched between the air lumen and tagged regions are enhanced by analysis of the local roughness based on multi-scale volumetric curvedness. Both values of the structure-enhancement function and the local roughness are integrated into the speed function of a level set method for delineating the tagged fecal materials. Thus, submerged soft-tissue structures as well as soft-tissue structures adhering to the tagged regions are preserved, whereas the tagged regions are removed along with the associated AT boundaries from CTC images. Evaluation of the quality of the cleansing based on polyps and folds in a colon phantom, as well as on polyps in clinical cathartic and noncathartic CTC cases with fluid and stool tagging, showed that our structure-analysis cleansing method is significantly superior to that of our previous thresholding-based EC method. It provides a cleansed colon with substantially reduced subtraction artifacts. (C) 2008 American Association of Physicists in Medicine. C1 [Cai, Wenli; Zalis, Michael E.; Naeppi, Janne; Harris, Gordon J.; Yoshida, Hiroyuki] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Cai, WL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. EM cai.wenli@mgh.harvard.edu RI Nappi, Janne/B-9424-2008 OI Nappi, Janne/0000-0002-0108-0992 FU NCI NIH HHS [CA095279, R01 CA095279, R56 CA095279] NR 32 TC 30 Z9 32 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUL PY 2008 VL 35 IS 7 BP 3259 EP 3277 DI 10.1118/1.2936413 PG 19 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 320KF UT WOS:000257231700029 PM 18697551 ER PT J AU Trott, CM El Fakhri, G AF Trott, Cathryn M. El Fakhri, Georges TI Sequential and simultaneous dual-isotope brain SPECT: Comparison with PET for estimation and discrimination tasks in early Parkinson disease SO MEDICAL PHYSICS LA English DT Article DE Parkinson disease; Cramer-Rao bound; simultaneous dual-isotope SPECT; activity and size estimation ID ABSOLUTE ACTIVITY QUANTITATION; DOPAMINE TRANSPORTERS; ITERATIVE RECONSTRUCTION; VARIABILITY; PERFORMANCE; TC-99M; TIME AB Parkinson disease (PD) is the second most frequently occurring cerebral degenerative disease, after Alzheimer disease. Treatments are available, but their efficacy is diminished unless they are administered in the early stages. Therefore, early identification of PD is crucial. In addition to providing perfectly registered studies, simultaneous (99m)Tc/(123)I imaging makes possible the assessment of pre- and postsynaptic neurotransmission functions under identical physiological conditions, while doubling the number of counts for the same total imaging time. These advantages are limited, however, by cross talk between the two radionuclides due to the close emission energies of (99m)Tc (140 keV) and (123)I (159 keV). PET, on the other hand, provides good temporal and spatial resolution and sensitivity but usually requires the use of a single radionuclide. In the present work, the authors compared brain PET with sequential and simultaneous dual-isotope SPECT for the task of estimating striatal activity concentration and striatal size for a normal brain and two stages of early PD. Realistic Monte Carlo simulations of a time-of-flight PET scanner and gamma cameras were performed while modeling all interactions in the brain, collimator (gamma camera) and crystal (detector block in PET), as well as population biological variability of pre- and postsynaptic uptake. For SPECT imaging, we considered two values of system energy resolution and scanners with two and three camera heads. The authors used the Cramer-Rao bound, as a surrogate for the best theoretical performance, to optimize the SPECT acquisition energy windows and objectively compare PET and SPECT. The authors determined the discrimination performance between 500 simulated subjects in every disease stage as measured by the area under the ROC curve (AUC). The discrimination accuracy between a normal subject and a subject in the prodromal disease stage was AUC=0.924 with PET, compared to 0.863 and 0.831 with simultaneous and sequential SPECT, respectively. The significant improvement in performance obtained with simultaneous dual-isotope SPECT compared to sequential imaging (p=0.019) was due primarily to the increased number of counts detected and resulted in comparable performance when performing simultaneous SPECT on a two-head camera with 9.2% energy resolution to that obtained with sequential SPECT on a three-head camera with 6.2% energy resolution. (C) 2008 American Association of Physicists in Medicine. C1 [Trott, Cathryn M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Trott, CM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM ctrott@partners.org RI Trott, Cathryn/B-5325-2013 OI Trott, Cathryn/0000-0001-6324-1766 FU NIBIB NIH HHS [R01 EB005876] NR 29 TC 2 Z9 2 U1 0 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUL PY 2008 VL 35 IS 7 BP 3343 EP 3353 DI 10.1118/1.2940605 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 320KF UT WOS:000257231700036 PM 18697558 ER PT J AU Thompson, WL Kosslyn, SM Hoffman, MS van der Kooij, K AF Thompson, William L. Kosslyn, Stephen M. Hoffman, Michael S. van der Kooij, Katinka TI Inspecting visual mental images: Can people "see" implicit properties as easily in imagery and perception? SO MEMORY & COGNITION LA English DT Article ID PROPOSITIONS AB Can people "see" previously unnoticed properties in objects that they visualize, or are they locked into the organization of the pattern that was encoded during perception? To answer this question, we first asked a group to describe letters of the alphabet and found that some properties (such as the presence of a diagonal line) are often mentioned, whereas others (such as symmetry) are rarely if ever mentioned. Then we showed not only that other participants could correctly detect both kinds of properties in visualized letters, but also that the relative differences in the ease of detecting these two types of properties are highly similar in perception (when the letters are actually visible) and imagery (when the letters are merely visualized). These findings provide support for the view that images can be reinterpreted in ways much like what occurs during perception and speak to the wider issue of the long-standing debate about the format of mental images. C1 [Kosslyn, Stephen M.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Kosslyn, Stephen M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hoffman, Michael S.] Univ Pittsburgh, Pittsburgh, PA USA. [van der Kooij, Katinka] Univ Utrecht, Utrecht, Netherlands. RP Kosslyn, SM (reprint author), Harvard Univ, Dept Psychol, 830 William James Hall,33 Kirkland St, Cambridge, MA 02138 USA. EM smkosslyn@wjh.harvard.edu OI van der Kooij, Katinka/0000-0002-4190-7827 FU NIMH NIH HHS [2 R01 MH060734-05A1] NR 22 TC 14 Z9 16 U1 0 U2 5 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 USA SN 0090-502X J9 MEM COGNITION JI Mem. Cogn. PD JUL PY 2008 VL 36 IS 5 BP 1024 EP 1032 DI 10.3758/MC.36.5.1024 PG 9 WC Psychology, Experimental SC Psychology GA 320JM UT WOS:000257229500012 PM 18630208 ER PT J AU Caffee, MW Faestermann, T Hertenberger, R Herzog, GF Korschinek, G Leya, I Reedy, RC Sisterson, JM AF Caffee, M. W. Faestermann, T. Hertenberger, R. Herzog, G. F. Korschinek, G. Leya, I. Reedy, R. C. Sisterson, J. M. TI Ca-41 production in the solar system SO METEORITICS & PLANETARY SCIENCE LA English DT Meeting Abstract CT Workshop on Antarctic Meteorites - Search, Recovery, and Classification CY JUL 26-27, 2008 CL Inst Polar Res, Antarctic Meteorite Res Ctr, Matsue, JAPAN SP Natl Inst Polor Res, SOKENDAI, Graduate Univ Adv Studies, Lunar & Planetary Inst, Shimane Prefecture HO Inst Polar Res, Antarctic Meteorite Res Ctr C1 [Caffee, M. W.] Purdue Univ, Dept Phys, W Lafayette, IN 47907 USA. [Faestermann, T.; Korschinek, G.] Tech Univ Munich, Fak Phys, D-85748 Garching, Germany. [Hertenberger, R.] LMU Munchen, Fak Phys, D-85748 Garching, Germany. [Herzog, G. F.] Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ USA. [Leya, I.] Univ Bern, Inst Phys, CH-3012 Bern, Switzerland. [Reedy, R. C.] Univ New Mexico, Albuquerque, NM 87131 USA. [Sisterson, J. M.] Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. EM herzog@rutchem.rutgers.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU METEORITICAL SOC PI FAYETTEVILLE PA DEPT CHEMISTRY/BIOCHEMISTRY, UNIV ARKANSAS, FAYETTEVILLE, AR 72701 USA SN 1086-9379 J9 METEORIT PLANET SCI JI Meteorit. Planet. Sci. PD JUL PY 2008 VL 43 IS 7 SU S BP A30 EP A30 PG 1 WC Geochemistry & Geophysics SC Geochemistry & Geophysics GA 326TZ UT WOS:000257683100038 ER PT J AU Hunt, SC Orsborn, M Checkoway, H Biggs, ML McFall, M Takaro, TK AF Hunt, Stephen C. Orsborn, Mack Checkoway, Harvey Biggs, Mary L. McFall, Miles Takaro, Tim K. TI Later life disability status following incarceration as a prisoner of war SO MILITARY MEDICINE LA English DT Article ID FORMER PRISONERS; KOREAN CONFLICT; MORTALITY; TRAUMA; PREVALENCE; RESILIENCE; CAPTIVITY; SURVIVORS; VETERANS; PACIFIC AB Objective: Incarceration-related predictors of later life disability in former prisoners of war (POWs) have not been previously described. The objective of this project was to identify aspects of POW incarceration which are associated with later life disability status. Methods: Cross-sectional retrospective study of 328 former U.S. military personnel held as POWs (World War II and Korean and Vietnam Wars) who presented for evaluations at a Veterans Affairs medical center between January 1, 1997 and December 31, 2004 outcome measures were: (1) total number of later life disability conditions attributable to incarceration and (2) cumulative percentage later life disability attributable to these conditions. Results: We found significant associations between later life disability and POW experiences, including experiencing or witnessing torture, solitary confinement, forced marches, dysentry, pellagra, vitamin deficiencies, scabies, depression, and suicidal thoughts. Conclusions: Conditions of captivity and health concerns or emotional distress during captivity may contribute to long-term adverse health outcomes as measured by later life disabilities in individuals incarcerated as POWs. C1 [Hunt, Stephen C.; Orsborn, Mack; McFall, Miles] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Checkoway, Harvey; Biggs, Mary L.] Univ Washington, Dept Epidemiol Biostat, Seattle, WA 98195 USA. [Takaro, Tim K.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. RP Hunt, SC (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 22 TC 10 Z9 10 U1 0 U2 1 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD JUL PY 2008 VL 173 IS 7 BP 613 EP 618 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 328CH UT WOS:000257774600001 PM 18700592 ER PT J AU Hagan, GN Lin, YS Magnuson, MA Avruch, J Czech, MP AF Hagan, G. Nana Lin, Yenshou Magnuson, Mark A. Avruch, Joseph Czech, Michael P. TI A Rictor-Myo1c complex participates in dynamic cortical actin events in 3T3-L1 adipocytes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AKT/PROTEIN-KINASE-B; CELL-GROWTH CONTROL; GLUCOSE-TRANSPORTER; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; INSULIN-RECEPTOR; MTOR COMPLEX; MYOSIN MYO1C; PHOSPHORYLATION; AKT/PKB; PATHWAY AB Insulin signaling through phosphatidylinositol 3-kinase (PI3-kinase) activates the protein kinase Akt through phosphorylation of its threonine 308 and serine 473 residues by the PDK1 protein kinase and the Rictor-mammalian target of rapamycin complex (mTORC2), respectively. Remarkably, we show here that the Rictor protein is also present in cultured adipocytes in complexes containing Myo1c, a molecular motor that promotes cortical actin remodeling. Interestingly, the Rictor-Myo1c complex is biochemically distinct from the previously reported mTORC2 and can be immunoprecipitated independently of mTORC2. Furthermore, while RNA interference-directed silencing of Rictor results in the expected attenuation of Akt phosphorylation at serine 473, depletion of Myo1c is without effect. In contrast, loss of either Rictor or Myo1c inhibits phosphorylation of the actin filament regulatory protein paxillin at tyrosine 118. Furthermore, Myo1c-induced membrane ruffling of 3T3-L1 adipocytes is also compromised following Rictor knockdown. Interestingly, neither the mTORC2 inhibitor rapamycin nor the PI 3-kinase inhibitor wortmannin affects paxillin tyrosine 118 phosphorylation. Taken together, our findings suggest that the Rictor-Myo1c complex is distinct from mTORC2 and that Myo1c, in conjunction with Rictor, participates in cortical actin remodeling events. C1 [Hagan, G. Nana; Czech, Michael P.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. [Lin, Yenshou; Avruch, Joseph] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Lin, Yenshou; Avruch, Joseph] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Lin, Yenshou; Avruch, Joseph] Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. [Magnuson, Mark A.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Sch Med, Nashville, TN 37232 USA. [Magnuson, Mark A.] Vanderbilt Univ, Ctr Stem Cell Biol, Sch Med, Nashville, TN 37232 USA. RP Czech, MP (reprint author), Univ Massachusetts, Sch Med, Program Mol Med, 373 Plantat St, Worcester, MA 01605 USA. EM Michael.Czech@umassmed.edu RI Lin, Jerry/F-1235-2010; Magnuson, Mark/B-1335-2009 OI Lin, Jerry/0000-0001-5905-8336; Magnuson, Mark/0000-0002-8824-6499 FU NIDDK NIH HHS [DK17776, P30 DK040561-13, DK30898, R01 DK030898, P30 DK040561, R37 DK017776, R37 DK030898, R01 DK063023, DK063023] NR 33 TC 33 Z9 34 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2008 VL 28 IS 13 BP 4215 EP 4226 DI 10.1128/MCB.00867-07 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 318NS UT WOS:000257099400001 PM 18426911 ER PT J AU Jo, H Jia, YH Subramanian, KK Hattori, H Luo, HBR AF Jo, Hakryul Jia, Yonghui Subramanian, Kulandayan K. Hattori, Hidenori Luo, Hongbo R. TI Cancer cell-derived clusterin modulates the phosphatidylinositol 3 '-kinase-Akt pathway through attenuation of insulin-like growth factor 1 during serum deprivation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INSULIN-RECEPTOR SUBSTRATE-1; EPITHELIAL-CELLS; STROMAL FIBROBLASTS; CYCLE PROGRESSION; INDUCED APOPTOSIS; GROWTH-FACTORS; T-ANTIGEN; PROSTATE; HYPOXIA; PROTEIN AB Cancer cells in their respective microenvironments must endure various growth-constraining stresses. Under these conditions, the cancer cell-derived factors are thought to modulate the signaling pathways between cell growth and dormancy. Here, we describe a cancer cell-derived regulatory system that modulates the phosphatidylinositol 3'-kinase (PI3K)-Akt pathway under serum deprivation stress. Through the use of biochemical purification, we reveal that cancer cell-secreted insulin-like growth factor 1 (IGF-1) and clusterin, an extracellular stress protein, constitute this regulatory system. We show that secreted clusterin associates with IGF-1 and inhibits its binding to the IGF-1 receptor and hence negatively regulates the PI3K-Akt pathway during serum deprivation. This inhibitory function of clusterin appears to prefer IGF-1, as it fails to exert any effects on epidermal growth factor signaling. We demonstrate furthermore that the constitutive activation of oncogenic signaling downstream of IGF-1 confers insensitivity to the inhibitory effects of clusterin. Thus, the interplay between cancer cell-derived clusterin and IGF-1 may dictate the outcome of cell growth and dormancy during tumorigenic progression. C1 [Jo, Hakryul; Jia, Yonghui; Subramanian, Kulandayan K.; Hattori, Hidenori; Luo, Hongbo R.] Harvard Univ, Childrens Hosp, Dept Pathol,Dana Farber Harvard Canc Ctr,Sch Med, Dept Lab Med,Stem Cell Program,Joint Program Tran, Boston, MA 02115 USA. RP Luo, HBR (reprint author), Karp Family Res Bldg,Room 10214,1 Blackfan Circle, Boston, MA 02115 USA. EM Hongbo.Luo@childrens.harvard.edu FU NIGMS NIH HHS [R01 GM076084, GM076084]; NINDS NIH HHS [NS052200, R21 NS052200] NR 51 TC 23 Z9 25 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2008 VL 28 IS 13 BP 4285 EP 4299 DI 10.1128/MCB.01240-07 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 318NS UT WOS:000257099400007 PM 18458059 ER PT J AU Chun, DK McEwen, JM Burbea, M Kaplan, JM AF Chun, Denise K. McEwen, Jason M. Burbea, Michelle Kaplan, Joshua M. TI UNC-108/Rab2 regulates postendocytic trafficking in Caenorhabditis elegans SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID GLR-1 GLUTAMATE RECEPTORS; VENTRAL NERVE CORD; AMPA RECEPTORS; C-ELEGANS; ENDOPLASMIC-RETICULUM; MULTIVESICULAR BODY; SACCHAROMYCES-CEREVISIAE; SYNAPTIC-TRANSMISSION; RECYCLING ENDOSOMES; HIPPOCAMPAL-NEURONS AB After endocytosis, membrane proteins are often sorted between two alternative pathways:a recycling pathway and a degradation pathway. Relatively little is known about how trafficking through these alternative pathways is differentially regulated. Here, we identify UNC-108/Rab2 as a regulator of postendocytic trafficking in both neurons and coelomocytes. Mutations in the Caenorhabditis elegans Rab2 gene unc-108, caused the green fluorescent protein (GFP)- tagged glutamate receptor GLR-1 (GLR-1::GFP) to accumulate in the ventral cord and in neuronal cell bodies. In neuronal cell bodies of unc-108/Rab2 mutants, GLR-1::GFP was found in tubulovesicular structures that colocalized with markers for early and recycling endosomes, including Syntaxin-13 and Rab8. GFP-tagged Syntaxin-13 also accumulated in the ventral cord of unc-108/Rab2 mutants. UNC-108/Rab2 was not required for ubiquitin-mediated sorting of GLR-1::GFP into the multivesicular body (MVB) degradation pathway. Mutations disrupting the MVB pathway and unc-108/Rab2 mutations had additive effects on GLR-1::GFP levels in the ventral cord. In coelomocytes, postendocytic trafficking of the marker Texas Red-bovine serum albumin was delayed. These results demonstrate that UNC-108/Rab2 regulates postendocytic trafficking, most likely at the level of early or recycling endosomes, and that UNC-108/Rab2 and the MVB pathway define alternative postendocytic trafficking mechanisms that operate in parallel. These results define a new function for Rab2 in protein trafficking. C1 [Kaplan, Joshua M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Kaplan, JM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM kaplan@molbio.mgh.harvard.edu FU National Institutes of Health [NS32196] FX We thank the following for strains, reagents and advice: B. Grant, P. Juo, and C. elegans Genetics Stock Center. We also thank members of the Kaplan laboratory for critical comments on this manuscript. This work was supported by grant NS32196 from the National Institutes of Health ( to J.M.K.). NR 69 TC 37 Z9 41 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUL PY 2008 VL 19 IS 7 BP 2682 EP 2695 DI 10.1091/mbc.E07-11-1120 PG 14 WC Cell Biology SC Cell Biology GA 347RH UT WOS:000259158200001 PM 18434599 ER PT J AU Barr, VA Bernot, KM Srikanth, S Gwack, Y Balagopalan, L Regan, CK Helman, DJ Sommers, CL Oh-hora, M Rao, A Samelson, LE AF Barr, Valarie A. Bernot, Kelsie M. Srikanth, Sonal Gwack, Yousang Balagopalan, Lakshmi Regan, Carole K. Helman, Daniel J. Sommers, Connie L. Oh-hora, Masatsugu Rao, Anjana Samelson, Lawrence E. TI Dynamic movement of the calcium sensor STIM1 and the calcium channel Orai1 in activated T-cells: Puncta and distal caps SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID OPERATED CA2+ ENTRY; STROMAL INTERACTION MOLECULE-1; PLASMA-MEMBRANE; IMMUNOLOGICAL SYNAPSE; ENDOPLASMIC-RETICULUM; CRAC CHANNEL; ANTIGEN RECEPTOR; SIGNAL-TRANSDUCTION; LYMPHOCYTE-ACTIVATION; INTRACELLULAR CALCIUM AB The proteins STIM1 and Orai1 are the long sought components of the store-operated channels required in T-cell activation. However, little is known about the interaction of these proteins in T-cells after engagement of the T-cell receptor. We found that T-cell receptor engagement caused STIM1 and Orai1 to colocalize in puncta near the site of stimulation and accumulate in a dense structure on the opposite side of the T-cell. FRET measurements showed a close interaction between STIM1 and Orai1 both in the puncta and in the dense cap-like structure. The formation of cap-like structures did not entail rearrangement of the entire endoplasmic reticulum. Cap formation depended on TCR engagement and tyrosine phosphorylation, but not on channel activity or Ca2+ influx. These caps were very dynamic in T-cells activated by contact with superantigen pulsed B-cells and could move from the distal pole to an existing or a newly forming immunological synapse. One function of this cap may be to provide preassembled Ca2+ channel components to existing and newly forming immunological synapses. C1 [Barr, Valarie A.; Bernot, Kelsie M.; Balagopalan, Lakshmi; Regan, Carole K.; Helman, Daniel J.; Sommers, Connie L.; Samelson, Lawrence E.] NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. [Srikanth, Sonal; Gwack, Yousang; Oh-hora, Masatsugu; Rao, Anjana] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Srikanth, Sonal; Gwack, Yousang; Oh-hora, Masatsugu; Rao, Anjana] Immune Dis Inst, Boston, MA 02115 USA. RP Samelson, LE (reprint author), NCI, Cellular & Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA. EM samelson@helix.nih.gov FU National Institutes of Health (NIH) [AI40127, GM075256]; National Cancer Institute; Center for Cancer Research FX We thank Dr. Alex Braiman for help with FRET calculations, Dr. Mark Philips for the tagged M1 constructs, Dr. Arthur Weiss for the JCam1.6 and Lck reconstituted JCam1.6 cell lines, and Barbara J. Taylor at the FACS CORE Facility. This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research and by NIH Grants AI40127 and GM075256 to A. R.. NR 77 TC 76 Z9 76 U1 1 U2 4 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUL PY 2008 VL 19 IS 7 BP 2802 EP 2817 DI 10.1091/mbc.E08-02-0146 PG 16 WC Cell Biology SC Cell Biology GA 347RH UT WOS:000259158200011 PM 18448669 ER PT J AU Luttrell, LM AF Luttrell, Louis M. TI Reviews in molecular biology and biotechnology: Transmembrane signaling by G protein-coupled receptors SO MOLECULAR BIOTECHNOLOGY LA English DT Review DE G protein-coupled receptors; heterotrimeric GTP-binding proteins; signal transduction; second messenger systems; G protein-coupled receptor kinases; arrestins ID GROWTH-FACTOR RECEPTOR; HETEROTRIMERIC G-PROTEINS; BETA-ADRENERGIC-RECEPTOR; CLATHRIN-MEDIATED ENDOCYTOSIS; GTPASE-ACTIVATING PROTEINS; NUCLEAR EXPORT SIGNAL; MAP KINASE ACTIVATION; TERNARY COMPLEX MODEL; PHOSPHOLIPASE-C-BETA; BETA(2)-ADRENERGIC RECEPTOR AB As the most diverse type of cell surface receptor, the importance heptahelical G protein-coupled receptors (GPCRs) to clinical medicine cannot be overestimated. Visual, olfactory and gustatory sensation, intermediary metabolism, cell growth and differentiation are all influenced by GPCR signals. The basic receptor-G protein-effector mechanism of GPCR signaling is tuned by a complex interplay of positive and negative regulatory events that amplify the effect of a hormone binding the receptor or that dampen cellular responsiveness. The association of heptahelical receptors with a variety of intracellular partners other than G proteins has led to the discovery of potential mechanisms of GPCR signaling that extend beyond the classical paradigms. While the physiologic relevance of many of these novel mechanisms of GPCR signaling remains to be established, their existence suggests that the mechanisms of GPCR signaling are even more diverse than previously imagined. C1 [Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. [Luttrell, Louis M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Luttrell, LM (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, 96 Jonathan Lucas St,816 CSB,POB 250624, Charleston, SC 29425 USA. EM luttrell@musc.edu RI Marion-Poll, Frederic/D-8882-2011 OI Marion-Poll, Frederic/0000-0001-6824-0180 NR 227 TC 60 Z9 61 U1 2 U2 19 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD JUL PY 2008 VL 39 IS 3 BP 239 EP 264 DI 10.1007/s12033-008-9031-1 PG 26 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 311TD UT WOS:000256622400008 PM 18240029 ER PT J AU Jin, YZ Wu, MX AF Jin, YongZhu Wu, Mei X. TI Requirement of G alpha i in thymic homing and early T cell development SO MOLECULAR IMMUNOLOGY LA English DT Article DE G alpha proteins; thymopoiesis; thymic homing ID SINGLE-POSITIVE THYMOCYTES; PERTUSSIS-TOXIN; PROGENITOR LOCALIZATION; POSTNATAL THYMUS; MICE; MIGRATION; CHEMOKINES; EXPRESSION; RECEPTORS; BINDING AB Demonstration of thymic homing dependent on G alpha i proteins is one of the keys to determine whether thymic entrance of blood-borne progenitors is a highly selective process. The present study provides compelling evidence of an indispensable role for G alpha i proteins in this process. Absence of either G alpha i2 or G alpha i3 significantly abrogated thymic homing, with an effect of G alpha i3 being greater than that of G alpha i2. Pertussis toxin treatment that blocks both G alpha i2 and G alpha i3 almost completely blocked thymic seeding in the thymus. Null mutation of G alpha i3 also hindered bone marrow cell development and thus reduced production of pre-thymic progenitors. In contrast, G alpha i2 exhibited a more prominent role than G alpha i3 in guidance of CD4-CD8- double negative (DN) 1 cell migration and early thymic differentiation. The G alpha i-deficiency-induced defects might be compensated for in part via augmented function of thymic stromal cells so that a nearly normal output of mature T cells could be maintained in these G alpha i-deficient mice. These studies underscore the importance of G alpha i in regulating thymic homing and pre-thymic and early thymocyte differentiation. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Jin, YongZhu; Wu, Mei X.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Jin, YongZhu; Wu, Mei X.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. RP Wu, MX (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Edwards 222,50 Blossom St, Boston, MA 02114 USA. EM mwu2@partners.org FU NIAID NIH HHS [R01 AI050822, AI070785, AI050822, K02 AI070785-02, R01 AI050822-05, K02 AI070785] NR 40 TC 10 Z9 10 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JUL PY 2008 VL 45 IS 12 BP 3401 EP 3410 DI 10.1016/j.molimm.2008.04.007 PG 10 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 325FY UT WOS:000257575500010 PM 18501427 ER PT J AU Drouin, EE Glickstein, L Kwok, WW Nepom, GT Steere, AC AF Drouin, Elise E. Glickstein, Lisa Kwok, William W. Nepom, Gerald T. Steere, Allen C. TI Searching for Borrelial T cell Epitopes associated with antibiotic-refractory lyme arthritis (vol 45, pg 2323, 2008) SO MOLECULAR IMMUNOLOGY LA English DT Correction C1 [Drouin, Elise E.; Glickstein, Lisa; Steere, Allen C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Centerfor Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Kwok, William W.; Nepom, Gerald T.] Virginia Mason Med Ctr, Benaroya Res Inst, Seattle, WA 98101 USA. RP Drouin, EE (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, 149,13th St,Room 8301, Charlestown, MA 02129 USA. EM edrouin@partners.org NR 1 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JUL PY 2008 VL 45 IS 12 BP 3508 EP 3508 DI 10.1016/j.molimm.2008.04.009 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 325FY UT WOS:000257575500024 ER PT J AU van Vlerken, LE Duan, Z Little, SR Seiden, MV Amiji, MM AF van Vlerken, Lilian E. Duan, Zhenfeng Little, Steven R. Seiden, Michael V. Amiji, Mansoor M. TI Biodistribution and pharmacokinetic analysis of paclitaxel and ceramide administered in multifunctional polymer-blend nanoparticles in drug resistant breast cancer model SO MOLECULAR PHARMACEUTICS LA English DT Article; Proceedings Paper CT 7th International Symposium on Polymer Therapeutics CY MAY 26-28, 2007 CL Ctr Invest Principe Felipe, Valencia, SPAIN HO Ctr Invest Principe Felipe DE multidrug resistant tumors; polymer-blend nanoparticles; paclitaxel; ceramide; biodistribution; noncompartmental pharmacokinetics ID MULTIDRUG-RESISTANCE; GLYCOSPHINGOLIPID METABOLISM; TARGETED DELIVERY; TAMOXIFEN; CELLS; SYSTEM; PH AB In this study, we have investigated the biodistribution and pharmacokinetic analysis of paclitaxel (PTX) and the apoptotic signaling molecule, C-6-ceramide (CER), when administered in a multifunctional polymer-blend nanoparticle formulation to female nude mice bearing an orthotopic drug sensitive MCF7 and multidrug resistant MCF7(TR) (MDR-1 positive) human breast adenocarcinoma. A polymer-blend nanoparticle system was engineered to incorporate temporally controlled sequential release of the combination drug payload. Hereby, PTX was encapsulated in the pH-responsive rapid releasing polymer, poly(beta-amino ester) (PbAE), while CER was present in the slow releasing polymer, poly(D,L-lactide-co-glycolide) (PLGA) with n these blend nanoparticles. When particle formulations were administered intravenously to MCF7 and MCF7TR tumor bearing mice, higher concentrations of PTX were found in the blood due to longer retention time and an enhanced tumor accumulation relative to administration of free drug. In addition, the PLGA/PbAE blend nanoparticles were effective in enhancing the residence time of both drugs at the tumor site by reducing systemic clearance. Overall, these results are highly encouraging for development of multifunctional polymer-blend nanoparticle formulations that can be used for temporal -controlled administration of two drugs from a single formulation. C1 [van Vlerken, Lilian E.; Amiji, Mansoor M.] Northeastern Univ, Dept Pharmaceut Sci, Boston, MA 02115 USA. [Duan, Zhenfeng] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Little, Steven R.] Univ Pittsburgh, Dept Chem Engn, Pittsburgh, PA 15261 USA. [Seiden, Michael V.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Amiji, MM (reprint author), Northeastern Univ, Dept Pharmaceut Sci, 110 Mugar Life Sci Bldg,360 Huntington Ave, Boston, MA 02115 USA. EM m.amiji@neu.edu RI Amiji, Mansoor/A-4365-2014; OI Amiji, Mansoor/0000-0001-6170-881X; Little, Steven/0000-0002-7000-3931 FU NCI NIH HHS [R01 CA119617, R01-CA119617] NR 23 TC 58 Z9 58 U1 2 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD JUL-AUG PY 2008 VL 5 IS 4 BP 516 EP 526 DI 10.1021/mp800030k PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 334MQ UT WOS:000258226300006 PM 18616278 ER PT J AU Sagotsky, JA Zhang, L Wang, ZH Martin, S Deisboeck, TS AF Sagotsky, Jonathan A. Zhang, Le Wang, Zhihui Martin, Sean Deisboeck, Thomas S. TI Life Sciences and the web: a new era for collaboration SO MOLECULAR SYSTEMS BIOLOGY LA English DT Article DE AJAX; OWL; RDF; Semantic Web; SPARQL; web 2.0 ID SEMANTIC WEB; GENE-ONTOLOGY; INFORMATION; KNOWLEDGE; SOFTWARE; TOOL; RDF; BIOINFORMATICS; IMPLEMENTATION; TECHNOLOGIES AB The World Wide Web has revolutionized how researchers from various disciplines collaborate over long distances. This is nowhere more important than in the Life Sciences, where interdisciplinary approaches are becoming increasingly powerful as a driver of both integration and discovery. Data access, data quality, identity, and provenance are all critical ingredients to facilitate and accelerate these collaborative enterprises and it is here where Semantic Web technologies promise to have a profound impact. This paper reviews the need for, and explores advantages of as well as challenges with these novel Internet information tools as illustrated with examples from the biomedical community. C1 [Sagotsky, Jonathan A.; Zhang, Le; Wang, Zhihui; Deisboeck, Thomas S.] Massachusetts Gen Hosp East, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Complex Biosyst Modeling Lab, Boston, MA 02129 USA. [Martin, Sean] Cambridge Semant Inc, Cambridge, MA USA. RP Deisboeck, TS (reprint author), Massachusetts Gen Hosp East, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Complex Biosyst Modeling Lab, 2301,Bldg 149,13th St, Boston, MA 02129 USA. EM deisboec@helix.mgh.harvard.edu FU NCI NIH HHS [CA 113004, U56 CA113004] NR 48 TC 22 Z9 22 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1744-4292 J9 MOL SYST BIOL JI Mol. Syst. Biol. PD JUL PY 2008 VL 4 AR 201 DI 10.1038/msb.2008.39 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 336SJ UT WOS:000258384600010 PM 18594519 ER PT J AU Cathomen, T Joung, JK AF Cathomen, Toni Joung, J. Keith TI Zinc-finger nucleases: The next generation emerges SO MOLECULAR THERAPY LA English DT Review ID DNA-BINDING PROTEINS; ARTIFICIAL TRANSCRIPTION FACTORS; DOUBLE-STRAND BREAKS; SEVERE COMBINED IMMUNODEFICIENCY; ADENOASSOCIATED VIRUS VECTORS; GENE-THERAPY; HOMOLOGOUS RECOMBINATION; MAMMALIAN-CELLS; RESTRICTION ENZYMES; CHIMERIC NUCLEASES AB Methods of modifying the human genome precisely and efficiently hold great promise for revolutionizing the gene therapy arena. One particularly promising technology is based on the homologous recombination (HR) pathway and is known as gene targeting. Until recently, the low frequency of HR in mammalian cells, and the resulting dependence on selection to identify these rare events, has prevented gene targeting from being applied in a therapeutic context. However, recent advances in generating customized zinc-finger nucleases (ZFNs) that can create a DNA double-strand break (DSB) at preselected sites in the human genome have paved the way for HR-based strategies in gene therapy. By introducing a DSB into a target locus of interest, ZFNs stimulate gene targeting by several orders of magnitude through activation of cellular DNA repair pathways. The capability of this technology to achieve gene conversion frequencies of up to 29% in the absence of selection demonstrates its potential power. In this paper we review recent advances in, and upcoming challenges for, this emerging technology and discuss future experimental work that will be needed to bring ZFNs safely into a clinical setting. C1 [Cathomen, Toni] Charite Univ Med Berlin, Inst Virol CBF, D-12203 Berlin, Germany. [Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA. [Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Cathomen, T (reprint author), Charite Univ Med Berlin, Inst Virol CBF, Hindenburgdamm 27, D-12203 Berlin, Germany. EM toni.cathomen@charite.de OI Cathomen, Toni/0000-0002-7757-4630 NR 89 TC 175 Z9 191 U1 2 U2 39 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JUL PY 2008 VL 16 IS 7 BP 1200 EP 1207 DI 10.1038/mt.2008.114 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 318KF UT WOS:000257089600004 PM 28178480 ER PT J AU Collier, AY Lee, JW Turley, SJ AF Collier, A. Y. Lee, J-W Turley, S. J. TI Self-encounters of the third kind: lymph node stroma promotes tolerance to peripheral tissue antigens SO MUCOSAL IMMUNOLOGY LA English DT Article ID T-CELL TOLERANCE; THYMIC EPITHELIAL-CELLS; AIRE; EXPRESSION; AUTOIMMUNITY; REVEALS AB Multiple mechanisms have evolved to maintain tolerance among CD8(+) T cells to innocuous antigens that arise in cutaneous and mucosal tissues. In the thymus, medullary thymic epithelial cells directly present peripheral tissue antigens (PTAs) and incite the deletion of self-reactive thymocytes. Cross-presentation of PTAs by functionally immature, CD8 alpha(+) dendritic cells can lead to the deletion of self-reactive CD8(+) T cells in secondary lymphoid organs. A third mechanism of deletional tolerance has recently been uncovered in which lymph node-resident stromal cells of non-hematopoietic origin present endogenously expressed PTAs to circulating CD8(+) T cells. Emerging data suggest that lymph node stroma is a unique niche for controlling self-reactive T cells. C1 [Collier, A. Y.; Turley, S. J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Collier, A. Y.] Harvard MIT Div Hlth Sci & Technol, Boston, MA USA. [Lee, J-W] CGK Co Ltd, Drug Res & Dev Ctr, Taejon, South Korea. [Turley, S. J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Turley, SJ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM shannon_turley@dfci.harvard.edu NR 16 TC 5 Z9 5 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD JUL PY 2008 VL 1 IS 4 BP 248 EP 251 DI 10.1038/mi.2008.19 PG 4 WC Immunology SC Immunology GA 366HI UT WOS:000260470900002 PM 19079186 ER PT J AU Cudkowicz, ME Shefner, JM Simpson, E Grasso, D Yu, H Zhang, H Shui, A Schoenfeld, D Brown, RH Wieland, S Barber, JR AF Cudkowicz, Merit E. Shefner, Jeremy M. Simpson, Elizabeth Grasso, Daniela Yu, Hong Zhang, Hui Shui, Amy Schoenfeld, David Brown, Robert H. Wieland, Scott Barber, Jack R. CA NORTHEAST ALS CONSORTIUM TI Arimoclomol at dosages up to 300 mg/day is well tolerated and safe in amyotrophic lateral sclerosis SO MUSCLE & NERVE LA English DT Article DE amyotrophic lateral sclerosis; arimoclomol; clinical trial; protein aggregation ID HEAT-SHOCK PROTEINS; UP-REGULATION; VENOUS THROMBOSIS; SERUM CREATININE; ALS; DISMUTASE; UBIQUITIN; INCLUSIONS; COINDUCER; RILUZOLE AB Arimoclomol is an investigational drug for amyotrophic lateral sclerosis (ALS) that amplifies heat shock protein gene expression during cell stress. The objectives of the present study were to assess the safety, tolerability, and pharmacokinetics of arimoclomol in ALS. Eighty-four participants with ALS received arimoclomol at one of three oral doses (25, 50, or 100 ring three times daily) or placebo. The primary outcome measure was safety and tolerability. A subset of 44 participants provided serum and cerebrospinal fluid (CSF) samples for pharmacokinetic analysis. Participants who completed 12 weeks of treatment could enroll in a 6-month open-label study. Arimoclomol at doses up to 300 mg/day was well tolerated and safe. Arimoclomol resulted in dose-linear pharmacologic exposures and the half-life did not change with continued treatment. Arimoclomol CSF levels increased with dose. Arimoclomol was shown to be safe, and it crosses the blood-brain barrier. Serum pharmacokinetic profiles support dosing of three times per day. An efficacy study in ALS is planned. C1 [Cudkowicz, Merit E.; Simpson, Elizabeth; Grasso, Daniela; Yu, Hong] Massachusetts Gen Hosp, Neurol Clin Trials Unit, Charlestown, MA 02129 USA. [Shefner, Jeremy M.] SUNY Upstate Med Univ, Syracuse, NY USA. [Zhang, Hui; Shui, Amy; Schoenfeld, David] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Brown, Robert H.] Massachusetts Gen Hosp, Day Lab, Charlestown, MA 02129 USA. [Wieland, Scott; Barber, Jack R.] CytRx Corp, Los Angeles, CA USA. RP Cudkowicz, ME (reprint author), Massachusetts Gen Hosp, Neurol Clin Trials Unit, Bldg 149,13th St,Room 2274, Charlestown, MA 02129 USA. EM mcudkowicz@partners.org FU NCRR NIH HHS [M01 RR 01066, 5M01 RR 0082729, M01 RR 01346, M01 RR 023940, M01 RR 10732] NR 27 TC 52 Z9 54 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD JUL PY 2008 VL 38 IS 1 BP 837 EP 844 DI 10.1002/mus.21059 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 319MP UT WOS:000257168100002 PM 18551622 ER PT J AU Vallat, JM Magy, L Richard, L Piaser, M Sindou, P Calvo, J Ghorab, K Cros, D AF Vallat, Jean-Michel Magy, Laurent Richard, Laurence Piaser, Martine Sindou, Philippe Calvo, Judith Ghorab, Karima Cros, Didier TI Intranervous immunoglobulin deposits: An underestimated mechanism of neuropathy SO MUSCLE & NERVE LA English DT Article DE diagnosis; lymphoma; monoclonal gammopathy; pathophysiology; peripheral neuropathy; nerve biopsy ID WALDENSTROMS MACROGLOBULINEMIA; CRYOGLOBULIN DEPOSITS; MONOCLONAL GAMMOPATHY; PERIPHERAL NEUROPATHY; POLYNEUROPATHY AB There are several pathogenic mechanisms of peripheral nerve involvement in patients with monoclonal dysglobulinemia. Intranervous proliferation of malignant cells, immunoglobulin, or amyloid deposits in the endoneurial space can only be determined by examination of nerve biopsy specimens. We present clinical, electrophysiological, and histological data from seven patients whose polyneuropathy was induced by immunoglobulin deposits in the endoneurial space. As these lesions cannot be demonstrated on clinical and electrophysiological grounds, the indication for nerve biopsy derives from careful analysis of each patient presenting with a polyneuropathy and a monoclonal dysglobulinemia. To visualize and clearly characterize these deposits, electron microscopic examination is indispensable. Immunocytochemical methods using both light and electron microscopy for ultrastructural analysis are of great value. Demonstration of endoneurial immunoglobulin deposits may have major therapeutic consequences. Indeed, identification of these deposits prompted the use of aggressive treatment, which was quite effective in five of our seven patients. C1 [Vallat, Jean-Michel; Magy, Laurent; Richard, Laurence; Piaser, Martine; Sindou, Philippe; Calvo, Judith; Ghorab, Karima] Univ Hosp, Dept Neurol, Limoges, France. [Vallat, Jean-Michel; Magy, Laurent; Richard, Laurence; Piaser, Martine; Sindou, Philippe; Calvo, Judith; Ghorab, Karima] Univ Hosp, Ctr Natl Reference Neuropathies Peripheriques Rar, Limoges, France. [Cros, Didier] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Vallat, JM (reprint author), CHU Dupuytren, Serv Neurol, 2 Ave Martin Luther King, F-87042 Limoges, France. EM jean-michel.vallat@unilim.fr OI Magy, Laurent/0000-0003-1784-2901; sindou, p/0000-0003-1938-8319 NR 14 TC 16 Z9 16 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD JUL PY 2008 VL 38 IS 1 BP 904 EP 911 DI 10.1002/mus.21057 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 319MP UT WOS:000257168100011 PM 18563720 ER PT J AU Benny, O Fainaru, O Adini, A Cassiola, F Bazinet, L Adini, I Pravda, E Nahmias, Y Koirala, S Corfas, G D'Amato, RJ Folkman, J AF Benny, Ofra Fainaru, Ofer Adini, Avner Cassiola, Flavia Bazinet, Lauren Adini, Irit Pravda, Elke Nahmias, Yaakov Koirala, Samir Corfas, Gabriel D'Amato, Robert J. Folkman, Judah TI An orally delivered small-molecule formulation with antiangiogenic and anticancer activity SO NATURE BIOTECHNOLOGY LA English DT Article ID ANGIOGENESIS INHIBITOR TNP-470; BLOCK-COPOLYMER MICELLES; CELL-CYCLE INHIBITION; SOLID TUMORS; PHASE-I; POLYMERIC MICELLES; DRUG-DELIVERY; GROWTH; CANCER; AGM-1470 AB Targeting angiogenesis, the formation of blood vessels, is an important modality for cancer therapy. TNP-470, a fumagillin analog, is among the most potent and broad-spectrum angiogenesis inhibitors. However, a major clinical limitation is its poor oral availability and short half-life, necessitating frequent, continuous parenteral administration. We have addressed these issues and report an oral formulation of TNP-470, named Lodamin. TNP-470 was conjugated to monomethoxy-polyethylene glycol polylactic acid to form nanopolymeric micelles. This conjugate can be absorbed by the intestine and selectively accumulates in tumors. Lodamin significantly inhibits tumor growth, without causing neurological impairment in tumor-bearing mice. Using the oral route of administration, it first reaches the liver, making it especially efficient in preventing the development of liver metastasis in mice. We show that Lodamin is an oral nontoxic antiangiogenic drug that can be chronically administered for cancer therapy or metastasis prevention. C1 [Benny, Ofra; Fainaru, Ofer; Adini, Avner; Cassiola, Flavia; Bazinet, Lauren; Adini, Irit; Pravda, Elke; D'Amato, Robert J.; Folkman, Judah] Harvard Univ, Sch Med, Childrens Hosp, Vasc Biol Program, Boston, MA 02215 USA. [Nahmias, Yaakov] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Charlestown, MA 02129 USA. [Koirala, Samir; Corfas, Gabriel] Harvard Univ, Childrens Hosp, Sch Med, FM Kirby Neurobiol Ctr,Dept Neurol, Boston, MA 02115 USA. [D'Amato, Robert J.] Harvard Univ, Sch Med, Childrens Hosp, Dept Ophthalmol, Boston, MA 02215 USA. RP Benny, O (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Vasc Biol Program, 1 Blackfan Circle,St Karp Res Bldg, Boston, MA 02215 USA. EM ofra.bennyratsaby@childrens.harvard.edu RI Nahmias, Yaakov/H-4725-2013; OI Nahmias, Yaakov/0000-0002-6051-616X FU NIDDK NIH HHS [K01 DK080241, K01 DK080241-01] NR 41 TC 89 Z9 91 U1 1 U2 30 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUL PY 2008 VL 26 IS 7 BP 799 EP 807 DI 10.1038/nbt1415 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 324BC UT WOS:000257491600025 PM 18587385 ER PT J AU Page, ST Amory, JK Matsumoto, AM AF Page, Stephanie T. Amory, John K. Matsumoto, Alvin M. TI Des testosterone supplementation improve health and function in elderly men? SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material DE aging; androgen; supplementation; testosterone ID OLDER MEN; MORTALITY C1 [Page, Stephanie T.; Amory, John K.; Matsumoto, Alvin M.] Univ Washington, Sch Med, Seattle, WA USA. RP Matsumoto, AM (reprint author), VA Puget Sound Hlth Care Syst, Clin Res Unit, Educ & Clin Ctr, S-182-GRECC,1660 S Columbian Way, Seattle, WA 98108 USA. EM alvin.matsumoto@med.va.gov FU NIA NIH HHS [K23 AG027238-03, K23 AG027238]; NICHD NIH HHS [K23 HD045386] NR 6 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8366 J9 NAT CLIN PRACT ENDOC JI Nat. Clin. Pract. Endocrinol. Metab. PD JUL PY 2008 VL 4 IS 7 BP 374 EP 375 DI 10.1038/ncpendmet0840 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 315YX UT WOS:000256917200006 PM 18493229 ER PT J AU Crandall, JP Knowler, WC Kahn, SE Marrero, D Florez, JC Bray, GA Haffner, SM Hoskin, M Nathan, DM AF Crandall, Jill P. Knowler, William C. Kahn, Steven E. Marrero, David Florez, Jose C. Bray, George A. Haffner, Steven M. Hoskin, Mary Nathan, David M. CA Diabet Prevention Program Res Grp TI The prevention of type 2 diabetes SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Review DE impaired glucose tolerance; prediabetes; prevention; type 2 diabetes ID IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE INTERVENTION; RANDOMIZED CONTROLLED-TRIAL; BETA-CELL FUNCTION; 10-YEAR FOLLOW-UP; COST-EFFECTIVENESS; HIGH-RISK; INSULIN-RESISTANCE; FASTING GLUCOSE; CARDIOVASCULAR-DISEASE AB Type 2 diabetes mellitus (T2DM) affects more than 7% of adults in the Us and leads to substantial personal and economic burden. In prediabetic states insulin secretion and action-potential targets of preventive interventions-are impaired. In trials lifestyle modification (i.e. weight loss and exercise) has proven effective in preventing incident T2DM in high-risk groups, although weight loss has the greatest effect. Various medications (e.g. metformin, thiazolidinediones and acarbose) can also prevent or delay T2DM. Whether diabetes-prevention strategies also ultimately prevent the development of diabetic vascular complications is unknown, but cardiovascular risk factors are favorably affected. Preventive strategies that can be implemented in routine clinical settings have been developed and evaluated. Widespread application has, however, been limited by local financial considerations, even though cost-effectiveness might be achieved at the population level. C1 [Crandall, Jill P.] Albert Einstein Coll Med, Diabet Res Ctr, Bronx, NY 10461 USA. [Hoskin, Mary] NIDDK, Diabet Epidemiol & Clin Res Sect, Diabet Prevent Program Outcomes Study, Phoenix, AZ USA. [Kahn, Steven E.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Marrero, David] Indiana Univ, Bloomington, IN 47405 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res & Diabet Unit, Boston, MA 02114 USA. [Bray, George A.] Louisiana State Univ, Baton Rouge, LA 70803 USA. [Haffner, Steven M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Haffner, Steven M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Clin Epidemiol, San Antonio, TX 78229 USA. [Nathan, David M.] Harvard Univ, Sch Med, Ctr Diabet, Boston, MA USA. [Nathan, David M.] Harvard Univ, Sch Med, Gen Clin Res Ctr, Boston, MA USA. RP Crandall, JP (reprint author), Albert Einstein Coll Med, Diabet Res Ctr, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM crandall@aecom.yu.edu OI Kahn, Steven/0000-0001-7307-9002 FU Intramural NIH HHS [Z01 DK069000-42]; NIDDK NIH HHS [U01 DK048489, U01 DK048489-06] NR 99 TC 101 Z9 103 U1 1 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8366 J9 NAT CLIN PRACT ENDOC JI Nat. Clin. Pract. Endocrinol. Metab. PD JUL PY 2008 VL 4 IS 7 BP 382 EP 393 DI 10.1038/ncpendmet0843 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 315YX UT WOS:000256917200010 PM 18493227 ER PT J AU Lawson, EA Klibanski, A AF Lawson, Elizabeth A. Klibanski, Anne TI Endocrine abnormalities in anorexia nervosa SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Review DE anorexia nervosa; appetite; hypothalamic dysregulation; osteopenia ID EATING-DISORDER PATIENTS; BONE-MINERAL DENSITY; ADOLESCENT GIRLS; SECRETORY DYNAMICS; YOUNG-WOMEN; WEIGHT-GAIN; LEPTIN LEVELS; PEPTIDE YY; HYPOTHALAMIC AMENORRHEA; HEALTHY ADOLESCENTS AB Anorexia nervosa (AN) is a psychiatric disease associated with notable medical complications and increased mortality. Endocrine abnormalities, including hypogonadotropic hypogonadism, hypercortisolemia, growth hormone resistance and sick euthyroid syndrome, mediate the clinical manifestations of this disease. Alterations in anorexigenic and orexigenic appetite-regulating pathways have also been described. Decreases in fat mass result in adipokine abnormalities. Although most of the endocrine changes that occur in AN represent physiologic adaptation to starvation, some persist after recovery and might contribute to susceptibility to AN recurrence. In this Review, we summarize key endocrine alterations in AN, with a particular focus on the profound bone loss that can occur in this disease. Although AN is increasingly prevalent among boys and men, the disorder predominantly affects girls and women who are, therefore, the focus of this Review. C1 [Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Med, 55 Fruit St,BUL457B, Boston, MA 02114 USA. [Klibanski, Anne] Harvard Univ, Sch Med, Boston, MA USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Med, 55 Fruit St,BUL457B, Boston, MA 02114 USA. EM akilbanski@partners.org NR 64 TC 61 Z9 61 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1745-8366 J9 NAT CLIN PRACT ENDOC JI Nat. Clin. Pract. Endocrinol. Metab. PD JUL PY 2008 VL 4 IS 7 BP 407 EP 414 DI 10.1038/ncpendmet0872 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 315YX UT WOS:000256917200012 PM 18542109 ER PT J AU Henson, JW AF Henson, John W. TI Neurology patients online: perceptions and reality SO NATURE CLINICAL PRACTICE NEUROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. [Henson, John W.] Harvard Univ, Sch Med, Boston, MA USA. RP Henson, JW (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-834X J9 NAT CLIN PRACT NEURO JI Nat. Clin. Pract. Neurol. PD JUL PY 2008 VL 4 IS 7 BP 347 EP 347 DI 10.1038/ncpneuro0852 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 322LB UT WOS:000257375400001 PM 18600254 ER PT J AU Munshi, NC Mitsiades, C Richardson, PG Anderson, KC AF Munshi, Nikhil C. Mitsiades, Constantine Richardson, Paul G. Anderson, Kenneth C. TI Lenalidomide plus dexamethasone is efficacious in patients with relapsed or refractory multiple myeloma SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Editorial Material DE dexamethasone; efficacy; lenalidomide; multiple myeloma; relapsed C1 [Munshi, Nikhil C.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Div Hematol Neoplasia, Boston, MA USA. [Munshi, Nikhil C.] Boston VA Healthcare Syst, Boston, MA USA. RP Munshi, NC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM nikhil_munshi@dfci.harvard.edu NR 6 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD JUL PY 2008 VL 5 IS 7 BP 374 EP 375 DI 10.1038/ncponc1151 PG 2 WC Oncology SC Oncology GA 319BU UT WOS:000257138500005 PM 18542118 ER PT J AU El-Din, MAA Feng, JK Taghian, AG AF El-Din, Mohamed A. Alm Feng, Jennifer K. Taghian, Alphonse G. TI Lumpectomy and partial breast irradiation for early-stage breast cancer following mantle irradiation for Hodgkin's lymphoma SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Article DE breast cancer; Hodgkin's lymphoma; lumpectomy; mantle; partial breast irradiation ID RADIATION-THERAPY; DISEASE; RADIOTHERAPY; RISK; EXPERIENCE; CARCINOMA; SURVIVORS; WOMEN AB Background A 57-year-old woman who received treatment with mantle irradiation and systemic chemotherapy for Hodgkin's lymphoma diagnosed at the age of 42 underwent screening mammography, which revealed abnormal density at the upper outer quadrant of the left breast. Investigations Left breast ultrasound and MRI, ultrasound-guided biopsy, immunohistochemistry, chest X-ray. Diagnosis Stage T1bN0M0 left breast cancer. Management Lumpectomy, sentinel lymph-node biopsy and fractionated partial breast irradiation using 3-dimensional conformal technique. C1 [Feng, Jennifer K.; Taghian, Alphonse G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Breast Oncol Unit, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Breast Oncol Unit, 100 Blossom St, Boston, MA 02114 USA. EM ataghian@partners.org NR 15 TC 10 Z9 10 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD JUL PY 2008 VL 5 IS 7 BP 426 EP 429 DI 10.1038/ncponc1135 PG 4 WC Oncology SC Oncology GA 319BU UT WOS:000257138500011 ER PT J AU Allen, NC Bagade, S McQueen, MB Ioannidis, JPA Kavvoura, FK Khoury, MJ Tanzi, RE Bertram, L AF Allen, Nicole C. Bagade, Sachin McQueen, Matthew B. Ioannidis, John P. A. Kavvoura, Fotini K. Khoury, Muin J. Tanzi, Rudolph E. Bertram, Lars TI Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database SO NATURE GENETICS LA English DT Article ID METHYLENETETRAHYDROFOLATE REDUCTASE; PUBLISHED RESEARCH; BIPOLAR DISORDER; COMMON MUTATION; RISK-FACTOR; SUSCEPTIBILITY; DISEASE; COMPLEX; TRIALS; POLYMORPHISMS AB In an effort to pinpoint potential genetic risk factors for schizophrenia, research groups worldwide have published over 1,000 genetic association studies with largely inconsistent results. To facilitate the interpretation of these findings, we have created a regularly updated online database of all published genetic association studies for schizophrenia ('SzGene'). For all polymorphisms having genotype data available in at least four independent case-control samples, we systematically carried out random-effects meta-analyses using allelic contrasts. Across 118 meta-analyses, a total of 24 genetic variants in 16 different genes (APOE, COMT, DAO, DRD1, DRD2, DRD4, DTNBP1, GABRB2, GRIN2B, HP, IL1B, MTHFR, PLXNA2, SLC6A4, TP53 and TPH1) showed nominally significant effects with average summary odds ratios of similar to 1.23. Seven of these variants had not been previously meta-analyzed. According to recently proposed criteria for the assessment of cumulative evidence in genetic association studies, four of the significant results can be characterized as showing 'strong' epidemiological credibility. Our project represents the first comprehensive online resource for systematically synthesized and graded evidence of genetic association studies in schizophrenia. As such, it could serve as a model for field synopses of genetic associations in other common and genetically complex disorders. C1 [Allen, Nicole C.; Bagade, Sachin; Tanzi, Rudolph E.; Bertram, Lars] Massachusetts Gen Hosp, MIND, Dept Neurol, Genet & Aging Res Unit, Charlestown, MA 02129 USA. [McQueen, Matthew B.] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. [Ioannidis, John P. A.; Kavvoura, Fotini K.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Clin & Mol Epidemiol Unit, GR-45110 Ioannina, Greece. [Ioannidis, John P. A.] Fdn Res & Technol Hellas, Inst Biomed Res, Ioannina 45110, Greece. [Ioannidis, John P. A.] Tufts Univ, Sch Med, Dept Med, Boston, MA 02110 USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Natl Off Publ Hlth Gen, Atlanta, GA 30341 USA. RP Bertram, L (reprint author), Massachusetts Gen Hosp, MIND, Dept Neurol, Genet & Aging Res Unit, Charlestown, MA 02129 USA. EM bertram@helix.mgh.harvard.edu RI Ioannidis, John/G-9836-2011; Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X FU NICHD NIH HHS [R01 HD060726] NR 39 TC 633 Z9 656 U1 6 U2 64 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 2008 VL 40 IS 7 BP 827 EP 834 DI 10.1038/ng.171 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 319MA UT WOS:000257166500015 PM 18583979 ER PT J AU Lu, CW Yabuuchi, A Chen, LY Viswanathan, S Kim, K Daley, GQ AF Lu, Chi-Wei Yabuuchi, Akiko Chen, Lingyi Viswanathan, Srinivas Kim, Kitai Daley, George Q. TI Ras-MAPK signaling promotes trophectoderm formation from embryonic stem cells and mouse embryos SO NATURE GENETICS LA English DT Article ID PREIMPLANTATION DEVELOPMENT; DIFFERENTIATION; LINEAGE; KINASE; SPECIFICATION; REQUIREMENT; BLASTOCYSTS; BLASTOMERES; EXPRESSION; ENDODERM AB In blastocyst chimeras, embryonic stem (ES) cells contribute to embryonic tissues but not extraembryonic trophectoderm. Conditional activation of HRas1(Q61L) in ES cells in vitro induces the trophectoderm marker Cdx2 and enables derivation of trophoblast stem (TS) cell lines that, when injected into blastocysts, chimerize placental tissues. Erk2, the downstream effector of Ras-mitogen-activated protein kinase (MAPK) signaling, is asymmetrically expressed in the apical membranes of the 8-cell-stage embryo just before morula compaction. Inhibition of MAPK signaling in cultured mouse embryos compromises Cdx2 expression, delays blastocyst development and reduces trophectoderm outgrowth from embryo explants. These data show that ectopic Ras activation can divert ES cells toward extraembryonic trophoblastic fates and implicate Ras-MAPK signaling in promoting trophectoderm formation from mouse embryos. C1 [Lu, Chi-Wei; Yabuuchi, Akiko; Chen, Lingyi; Viswanathan, Srinivas; Kim, Kitai; Daley, George Q.] Childrens Hosp, Div Pediat Hematol & Oncol, Boston, MA 02115 USA. [Lu, Chi-Wei; Yabuuchi, Akiko; Chen, Lingyi; Viswanathan, Srinivas; Kim, Kitai; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lu, Chi-Wei; Yabuuchi, Akiko; Chen, Lingyi; Kim, Kitai] Harvard Univ, Stem Cell Inst, Boston, MA 02115 USA. [Viswanathan, Srinivas] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Hematol, 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 Chen, Lingyi/G-6309-2013 FU Howard Hughes Medical Institute; NIDDK NIH HHS [R01 DK059279, R01 DK059279-06, R01 DK070055, R01 DK070055-01]; NIH HHS [DP1 OD000256, DP1 OD000256-01] NR 30 TC 79 Z9 79 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 2008 VL 40 IS 7 BP 921 EP 926 DI 10.1038/ng.173 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 319MA UT WOS:000257166500030 PM 18536715 ER PT J AU Biddinger, SB Haas, JT Yu, BB Bezy, O Jing, EX Zhang, WW Unterman, TG Carey, MC Kahn, CR AF Biddinger, Sudha B. Haas, Joel T. Yu, Bian B. Bezy, Olivier Jing, Enxuan Zhang, Wenwei Unterman, Terry G. Carey, Martin C. Kahn, C. Ronald TI Hepatic insulin resistance directly promotes formation of cholesterol gallstones SO NATURE MEDICINE LA English DT Article ID ELEMENT-BINDING PROTEIN-1C; UNITED-STATES; ABCG8; LIVER; MICE; EXPRESSION; DISEASE; SECRETION; OBESITY; GENES AB Despite the well-documented association between gallstones and the metabolic syndrome(1,2), the mechanistic links between these two disorders remain unknown. Here we show that mice solely with hepatic insulin resistance, created by liver-specific disruption of the insulin receptor (LIRKO mice)(3) are markedly predisposed toward cholesterol gallstone formation due to at least two distinct mechanisms. Disinhibition of the forkhead transcription factor FoxO1, increases expression of the biliary cholesterol transporters Abcg5 and Abcg8, resulting in an increase in biliary cholesterol secretion. Hepatic insulin resistance also decreases expression of the bile acid synthetic enzymes, particularly Cyp7b1, and produces partial resistance to the farnesoid X receptor, leading to a lithogenic bile salt profile. As a result, after twelve weeks on a lithogenic diet, all of the LIRKO mice develop gallstones. Thus, hepatic insulin resistance provides a crucial link between the metabolic syndrome and increased cholesterol gallstone susceptibility. C1 [Biddinger, Sudha B.; Haas, Joel T.; Bezy, Olivier; Jing, Enxuan; Kahn, C. Ronald] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Biddinger, Sudha B.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Yu, Bian B.; Carey, Martin C.; Kahn, C. Ronald] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Zhang, Wenwei; Unterman, Terry G.] Univ Illinois, Coll Med, Dept Med, Chicago, IL 60612 USA. [Zhang, Wenwei; Unterman, Terry G.] Univ Illinois, Coll Med, Dept Physiol & Biophys, Chicago, IL 60612 USA. [Zhang, Wenwei; Unterman, Terry G.] Jesse Brown VA Med Ctr, Chicago, IL 60612 USA. [Carey, Martin C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Biddinger, SB (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM sudha.biddinger@joslin.harvard.edu FU NIDDK NIH HHS [R37 DK036588, DK031036, DK036588, DK036836-20, DK063695-05, DK073687, DK45935, K08 DK073358, K08 DK073358-01A1, K12 DK063696, P30 DK036836, R01 DK031036, R01 DK036588, R01 DK045935, R01 DK073687, R01 DK073687-01, R37 DK031036, R37 DK036588-22] NR 30 TC 113 Z9 122 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 2008 VL 14 IS 7 BP 778 EP 782 DI 10.1038/nm1785 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 323NL UT WOS:000257452700027 PM 18587407 ER PT J AU Salehi-Ashtiani, K Yang, XP Derti, A Tian, WD Hao, T Lin, CW Makowski, K Shen, L Murray, RR Szeto, D Tusneem, N Smith, DR Cusick, ME Hill, DE Roth, FP Vidal, M AF Salehi-Ashtiani, Kourosh Yang, Xinping Derti, Adnan Tian, Weidong Hao, Tong Lin, Chenwei Makowski, Kathryn Shen, Lei Murray, Ryan R. Szeto, David Tusneem, Nadeem Smith, Douglas R. Cusick, Michael E. Hill, David E. Roth, Frederick P. Vidal, Marc TI Isoform discovery by targeted cloning, 'deep-well' pooling and parallel sequencing SO NATURE METHODS LA English DT Article ID OPEN READING FRAMES; HUMAN GENES; GENOME; RESOURCE AB Describing the 'ORFeome' of an organism, including all major isoforms, is essential for a system-level understanding of any species; however, conventional cloning and sequencing approaches are prohibitively costly and labor-intensive. We describe a potentially genome-wide methodology for efficiently capturing new coding isoforms using reverse transcriptase (RT)-PCR recombinational cloning, 'deep-well' pooling and a next-generation sequencing platform. This ORFeome discovery pipeline will be applicable to any eukaryotic species with a sequenced genome. C1 [Salehi-Ashtiani, Kourosh; Yang, Xinping; Derti, Adnan; Tian, Weidong; Hao, Tong; Lin, Chenwei; Murray, Ryan R.; Szeto, David; Cusick, Michael E.; Hill, David E.; Roth, Frederick P.; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Salehi-Ashtiani, Kourosh; Yang, Xinping; Hao, Tong; Lin, Chenwei; Murray, Ryan R.; Szeto, David; Cusick, Michael E.; Hill, David E.; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Derti, Adnan; Tian, Weidong; Roth, Frederick P.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Makowski, Kathryn; Shen, Lei; Tusneem, Nadeem; Smith, Douglas R.] Agencourt Biosci Corp, Beverly, MA 01915 USA. RP Salehi-Ashtiani, K (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Ctr Canc Syst Biol, 44 Binney St, Boston, MA 02115 USA. EM kourosh_salehi-ashtiani@dfci.harvard.edu; fritz_roth@hms.harvard.edu; marc_vidal@dfci.harvard.edu RI Hill, David/B-6617-2011; Roth, Frederick/H-6308-2011 OI Salehi-Ashtiani, Kourosh/0000-0002-6521-5243; Roth, Frederick/0000-0002-6628-649X; FU NHGRI NIH HHS [HG003224, R01 HG003224, R01 HG003224-01A2, R01 HG003224-02, R01 HG003224-03]; NHLBI NIH HHS [HL081341, U01 HL081341, U01 HL081341-01, U01 HL081341-02, U01 HL081341-03]; NIDDK NIH HHS [DK070078, T90 DK070078, T90 DK070078-03]; NINDS NIH HHS [NS054052, R01 NS054052, R01 NS054052-01A1, R01 NS054052-02] NR 18 TC 22 Z9 22 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD JUL PY 2008 VL 5 IS 7 BP 597 EP 600 DI 10.1038/nmeth.1224 PG 4 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 319MC UT WOS:000257166700010 PM 18552854 ER PT J AU Djebali, S Kapranov, P Foissac, S Lagarde, J Reymond, A Ucla, C Wyss, C Drenkow, J Dumais, E Murray, RR Lin, CW Szeto, D Denoeud, F Calvo, M Frankish, A Harrow, J Makrythanasis, P Vidal, M Salehi-Ashtiani, K Antonarakis, SE Gingeras, TR Guigo, R AF Djebali, Sarah Kapranov, Philipp Foissac, Sylvain Lagarde, Julien Reymond, Alexandre Ucla, Catherine Wyss, Carine Drenkow, Jorg Dumais, Erica Murray, Ryan R. Lin, Chenwei Szeto, David Denoeud, France Calvo, Miquel Frankish, Adam Harrow, Jennifer Makrythanasis, Periklis Vidal, Marc Salehi-Ashtiani, Kourosh Antonarakis, Stylianos E. Gingeras, Thomas R. Guigo, Roderic TI Efficient targeted transcript discovery via array-based normalization of RACE libraries SO NATURE METHODS LA English DT Article ID GENE-EXPRESSION; CDNA LIBRARY; CAP ANALYSIS; HUMAN GENOME; MOUSE; IDENTIFICATION; PROJECT; ANNOTATION; COLLECTION; ELEMENTS AB Rapid amplification of cDNA ends (RACE) is a widely used approach for transcript identification. Random clone selection from the RACE mixture, however, is an ineffective sampling strategy if the dynamic range of transcript abundances is large. To improve sampling efficiency of human transcripts, we hybridized the products of the RACE reaction onto tiling arrays and used the detected exons to delineate a series of reverse-transcriptase (RT)-PCRs, through which the original RACE transcript population was segregated into simpler transcript populations. We independently cloned the products and sequenced randomly selected clones. This approach, RACEarray, is superior to direct cloning and sequencing of RACE products because it specifically targets new transcripts and often results in overall normalization of transcript abundance. We show theoretically and experimentally that this strategy leads indeed to efficient sampling of new transcripts, and we investigated multiplexing the strategy by pooling RACE reactions from multiple interrogated loci before hybridization. C1 [Djebali, Sarah; Lagarde, Julien; Denoeud, France; Guigo, Roderic] Univ Pompeu Fabra, Grp Recerca Informat Biomed, Inst Municipal Invest Med, Barcelona 08003, Spain. [Kapranov, Philipp; Drenkow, Jorg; Dumais, Erica; Gingeras, Thomas R.] Affymetrix Inc, Santa Clara, CA 95051 USA. [Foissac, Sylvain; Guigo, Roderic] Ctr Genom Regulat, Barcelona 08003, Spain. [Reymond, Alexandre] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland. [Ucla, Catherine; Wyss, Carine; Makrythanasis, Periklis; Antonarakis, Stylianos E.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. [Murray, Ryan R.; Lin, Chenwei; Szeto, David; Vidal, Marc; Salehi-Ashtiani, Kourosh] Harvard Univ, Sch Med, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Murray, Ryan R.; Lin, Chenwei; Szeto, David; Vidal, Marc; Salehi-Ashtiani, Kourosh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Murray, Ryan R.; Lin, Chenwei; Szeto, David; Vidal, Marc; Salehi-Ashtiani, Kourosh] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Calvo, Miquel] Univ Barcelona, Dept Estadist, E-08028 Barcelona, Spain. [Frankish, Adam; Harrow, Jennifer] Wellcome Trust Sanger Inst, Human & Vertebrate Anal & Annotat Grp, Hinxton CB10 1HH, England. RP Guigo, R (reprint author), Univ Pompeu Fabra, Grp Recerca Informat Biomed, Inst Municipal Invest Med, Dr Aiguader 88, Barcelona 08003, Spain. EM roderic.guigo@crg.es RI Frankish, Adam/G-6545-2011; Antonarakis, Stylianos/N-8866-2014; Djebali, Sarah/O-9817-2014; Guigo, Roderic/D-1303-2010; OI Antonarakis, Stylianos/0000-0001-8907-5823; Djebali, Sarah/0000-0002-0599-1267; Guigo, Roderic/0000-0002-5738-4477; Gingeras, Thomas/0000-0001-9106-3573; Calvo LLorca, Miguel/0000-0002-4016-3336; Foissac, Sylvain/0000-0002-2631-5356; Salehi-Ashtiani, Kourosh/0000-0002-6521-5243 FU NCI NIH HHS [N01-CO-12400, N01CO12400]; NHGRI NIH HHS [U54 HG004557-01, U01 HG003147, U01 HG003147-01, U01 HG003147-02, U01 HG003147-02S1, U01 HG003147-02S2, U01 HG003147-02S3, U01 HG003150, U01 HG003150-01, U01 HG003150-02, U01 HG003150-03, U01 HG003150-03S1, U01 HG003150-03S2, U01HG003147, U01HG003150, U54 HG004555, U54 HG004557, U54 HG004557-02, U54 HG004557-02S1, U54 HG004557-03]; Wellcome Trust [077198] NR 24 TC 27 Z9 29 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD JUL PY 2008 VL 5 IS 7 BP 629 EP 635 DI 10.1038/nmeth.1216 PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 319MC UT WOS:000257166700016 PM 18500348 ER PT J AU Ng, DPK Nurbaya, S Choo, S Koh, D Chia, KS Krolewski, AS AF Ng, Daniel P. K. Nurbaya, Siti Choo, Serena Koh, David Chia, Kee-seng Krolewski, Andrzej S. TI Genetic variation at the SLC12A3 locus is unlikely to explain risk for advanced diabetic nephropathy in Caucasians with type 2 diabetes SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE end-stage renal disease; genetic susceptibility; haplotype block; multiple hypothesis testing; proteinuria ID ASSOCIATION; POLYMORPHISMS; METAANALYSIS; MEMBER-3; DISEASE; GENOME AB Background. Large-scale genotyping efforts performed on Japanese subjects with type 2 diabetes have implicated polymorphisms in solute carrier family 12 (sodium/chloride transporters) member 3 (SLC12A3) as being associated with advanced diabetic nephropathy. However, it is not known whether these polymorphisms confer a risk for this complication in type 2 diabetic Caucasians. Methods. A case-control study was conducted that consisted of 295 cases with advanced diabetic nephropathy and 174 controls who have remained normoalbuminuric despite >= 7 years of diabetes. A total of 11 single nucleotide polymorphisms (SNPs) spanning the SLC12A3 locus was analysed including +34372G > A (Arg913Gln) that was the marker previously showing the strongest evidence for disease association in type 2 diabetic Japanese. Power calculations indicated that with an alpha of 0.05, our study has > 90% power to detect disease associations of the magnitude previously reported for +34372G > A (Arg913Gln). Results. Allele and genotype distributions for all 11 SNPs were found to be comparable between cases and controls, consistent with the absence of disease association. This negative result was reiterated in subgroup analysis after taking into account potentially important covariates including gender, diabetes duration, blood pressure and glycaemic control. No significant disease associations were likewise found for SLC12A3 haplotypes. Allele, genotype and haplotype distributions were similar in cases regardless of whether they were proteinuric or had developed chronic renal failure/end-stage renal disease. Conclusions. Genetic variation at the SLC12A3 locus is unlikely to explain the risk for advanced diabetic nephropathy among type 2 diabetic Caucasians. C1 [Ng, Daniel P. K.; Koh, David; Chia, Kee-seng] Natl Univ Singapore, Dept Community Occupat & Family Med, Singapore 117548, Singapore. [Ng, Daniel P. K.; Nurbaya, Siti; Choo, Serena; Koh, David; Chia, Kee-seng] Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117548, Singapore. [Krolewski, Andrzej S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Krolewski, Andrzej S.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02115 USA. RP Ng, DPK (reprint author), Natl Univ Singapore, Dept Community Occupat & Family Med, Singapore 117548, Singapore. EM cofnpkd@nus.edu.sg RI CHIA, Kee Seng/C-5790-2011 FU NIDDK NIH HHS [DK058549] NR 12 TC 7 Z9 9 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD JUL PY 2008 VL 23 IS 7 BP 2260 EP 2264 DI 10.1093/ndt/gfm946 PG 5 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 322ZK UT WOS:000257413600027 PM 18263927 ER PT J AU Borghesani, PR Johnson, LC Shelton, AL Peskind, ER Aylward, EH Schellenberg, GD Cherrier, MM AF Borghesani, Paul R. Johnson, L. Clark Shelton, Amy L. Peskind, Elaine R. Aylward, Elizabeth H. Schellenberg, Gerard D. Cherrier, Monique M. TI Altered medial temporal lobe responses during visuospatial encoding in healthy APOE*4 carriers SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer; apolipoprotein; hippocampus; APOE*4; perspective; visuospatial learning; encoding; recognition; fMRI; route; survey ID APOLIPOPROTEIN-E GENOTYPE; E TYPE-4 ALLELE; CEREBRAL GLUCOSE-METABOLISM; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; BRAIN ACTIVATION; EPISODIC MEMORY; GENETIC RISK; EPSILON-4 ALLELE; WORKING-MEMORY AB The apolipoprotein epsilon 4 allele (APOE*4) is a major genetic risk factor for Alzheimer's disease (AD) and has been associated with altered cortical activation as assessed by functional neuroimaging in cognitively normal younger and older carriers. We chose to evaluate medial temporal lobe (MTL) activation during encoding and recognition using a perspective-dependent (route or survey) visuospatial memory task by monitoring the blood-oxygen-level -dependent (BOLD) fMRI response in older, non-demented APOE*4 carriers (APOE*4+) and non-carriers (APOE*4-). During encoding, the APOE*4- group had greater average task-associated BOLD responses in ventral visual pathways, including the MTLs, as compared to the APOE*4+ group. Furthermore, MTL activation was greater during route encoding than survey encoding on average in APOE*4-, but not APOE*4+, subjects. During recognition, both groups performed similarly and no BOLD signal differences were found. Finally, within-group analysis revealed MTL activation during encoding was correlated with recognition performance in APOE*4-, but not APOE*4+ subjects. Reduced task-associated MTL activation that does not correlate with either visuospatial perspective or task performance suggests that MTL dysregulation occurs prior to clinical symptoms of dementia in APOE*4 carriers. (C) 2007 Elsevier Inc. All rights reserved. C1 [Borghesani, Paul R.; Peskind, Elaine R.] VAPSHCS, MIRECC, Seattle, WA 98108 USA. [Borghesani, Paul R.; Peskind, Elaine R.; Cherrier, Monique M.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Johnson, L. Clark] Univ Washington, Sch Nursing, Dept Psychosocial & Community Hlth Nursing, Seattle, WA 98195 USA. [Shelton, Amy L.] Johns Hopkins Univ, Dept Psychol & Brain Sci, Baltimore, MD 21218 USA. [Aylward, Elizabeth H.] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. [Peskind, Elaine R.; Schellenberg, Gerard D.; Cherrier, Monique M.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. RP Borghesani, PR (reprint author), VAPSHCS, MIRECC, S-116 6East,1660 Columbian Way, Seattle, WA 98108 USA. EM paulrb@u.washington.edu FU NIA NIH HHS [T32 AG000258, P50 AG005136-17, P50 AG05136, P50 AG005136, T32 AG000258-01A1, T32 AG00258, P50 AG005136-16]; PHS HHS [AGO5136, AGO0258] NR 72 TC 28 Z9 28 U1 4 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2008 VL 29 IS 7 BP 981 EP 991 DI 10.1016/j.neurobiolaging.2007.01.012 PG 11 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 309JR UT WOS:000256457000003 PM 17350142 ER PT J AU Labus, JS Naliboff, BN Fallon, J Berman, SM Suyenobu, B Bueller, JA Mandelkern, M Mayer, EA AF Labus, J. S. Naliboff, B. N. Fallon, J. Berman, S. M. Suyenobu, B. Bueller, J. A. Mandelkern, M. Mayer, E. A. TI Sex differences in brain activity during aversive visceral stimulation and its expectation in patients with chronic abdominal pain: A network analysis SO NEUROIMAGE LA English DT Article ID IRRITABLE-BOWEL-SYNDROME; PARTIAL LEAST-SQUARES; EVENT-RELATED FMRI; PHYSIOLOGICAL CONDITION; ORBITOFRONTAL CORTEX; CEREBRAL ACTIVATION; GENDER-DIFFERENCES; RECTAL DISTENSION; CINGULATE GYRUS; IBS PATIENTS AB Differences in brain responses to aversive visceral stimuli may underlie previously reported sex differences in symptoms as well as perceptual and emotional responses to such stimuli in patients with irritable bowel syndrome (IBS). The goal of the current study was to identify brain networks activated by expected and delivered aversive visceral stimuli in male and female patients with chronic abdominal pain, and to test for sex differences in the effective connectivity of the circuitry comprising these networks. Network analysis was applied to assess the brain response of 46 IBS patients (22 men and 24 women) recorded using [O-15] water positron emission tomography during rest/ baseline and expected and delivered aversive rectal distension. Functional connectivity results from partial least squares analyses provided support for the hypothesized involvement of 3 networks corresponding to: 1) visceral afferent information processing (thalamus, insula and dorsal anterior cingulate cortex, orbital frontal cortex), 2) emotionalarousal (amygdala, rostral and subgenual cingulate regions, and locus coeruleus complex) and 3) cortical modulation (frontal and parietal cortices). Effective connectivity results obtained via structural equation modeling indicated that sex-related differences in brain response are largely due to alterations in the effective connectivity of emotionalarousal circuitry rather than visceral afferent processing circuits. Sex differences in the cortico-limbic circuitry involved in emotionalarousal, pain facilitation and autonomic responses may underlie the observed differences in symptoms, and in perceptual and emotional responses to aversive visceral stimuli. (C) 2008 Elsevier Inc. All rights reserved. C1 [Labus, J. S.; Naliboff, B. N.; Berman, S. M.; Suyenobu, B.; Bueller, J. A.; Mandelkern, M.; Mayer, E. A.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobiol Stress, Dept Med, Los Angeles, CA 90095 USA. [Labus, J. S.; Naliboff, B. N.; Berman, S. M.; Mayer, E. A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Labus, J. S.; Berman, S. M.; Mayer, E. A.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. [Naliboff, B. N.] VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073 USA. Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92697 USA. [Fallon, J.; Mandelkern, M.] Univ Calif Irvine, Dept Phys, Irvine, CA 92697 USA. RP Labus, JS (reprint author), Ctr Neurovisceral Sci & Womens Hlth, Peter V Ueberroth Bldg,Rm 2338C2,10945 Leconte Av, Los Angeles, CA 90095 USA. EM jlabus@ucla.edu FU NCCIH NIH HHS [R24 AT002681]; NIDDK NIH HHS [K08 DK071626-02, P50 DK064539, R01 DK 48351, R01 DK048351, K08 DK071626] NR 73 TC 74 Z9 76 U1 7 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUL PY 2008 VL 41 IS 3 BP 1032 EP 1043 DI 10.1016/j.neuroimage.2008.03.009 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 306TW UT WOS:000256271700030 PM 18450481 ER PT J AU Tobin, JE Latourelle, JC Lew, MF Klein, C Suchowersky, O Shill, HA Golbe, LI Mark, MH Growdon, JH Wooten, GF Racette, BA Perlmutter, JS Watts, R Guttman, M Baker, KB Goldwurm, S Pezzoli, G Singer, C Saint-Hilaire, MH Hendricks, AE Williamson, S Nagle, MW Wilk, JB Massood, T Laramie, JM DeStefano, AL Litvan, I Nicholson, G Corbett, A Isaacson, S Burn, DJ Chinnery, PF Pramstaller, PP Sherman, S Al-Hinti, J Drasby, E Nance, M Moller, AT Ostergaard, K Roxburgh, R Snow, B Slevin, JT Cambi, F Gusella, JF Myers, RH AF Tobin, J. E. Latourelle, J. C. Lew, M. F. Klein, C. Suchowersky, O. Shill, H. A. Golbe, L. I. Mark, M. H. Growdon, J. H. Wooten, G. F. Racette, B. A. Perlmutter, J. S. Watts, R. Guttman, M. Baker, K. B. Goldwurm, S. Pezzoli, G. Singer, C. Saint-Hilaire, M. H. Hendricks, A. E. Williamson, S. Nagle, M. W. Wilk, J. B. Massood, T. Laramie, J. M. DeStefano, A. L. Litvan, I. Nicholson, G. Corbett, A. Isaacson, S. Burn, D. J. Chinnery, P. F. Pramstaller, P. P. Sherman, S. Al-Hinti, J. Drasby, E. Nance, M. Moller, A. T. Ostergaard, K. Roxburgh, R. Snow, B. Slevin, J. T. Cambi, F. Gusella, J. F. Myers, R. H. TI Haplotypes and gene expression implicate the MAPT region for Parkinson disease - The GenePD Study SO NEUROLOGY LA English DT Article ID PROGRESSIVE SUPRANUCLEAR PALSY; TAU GENE; NEURODEGENERATIVE DISEASES; PROTEIN-TAU; ASSOCIATION; BRAIN; TAUOPATHIES; MUTATIONS; SYNUCLEIN; PATTERNS AB Background: Microtubule-associated protein tau ( MAPT) has been associated with several neurode-generative disorders including forms of parkinsonism and Parkinson disease (PD). We evaluated the association of the MAPT region with PD in a large cohort of familial PD cases recruited by the GenePD Study. In addition, postmortem brain samples from patients with PD and neurologically normal controls were used to evaluate whether the expression of the 3-repeat and 4-repeat isoforms of MAPT, and neighboring genes Saitohin (STH) and KIAA1267, are altered in PD cerebellum. Methods: Twenty-one single-nucleotide polymorphisms ( SNPs) in the region of MAPT on chromosome 17q21 were genotyped in the GenePD Study. Single SNPs and haplotypes, including the H1 haplotype, were evaluated for association to PD. Relative quantification of gene expression was performed using real-time RT-PCR. Results: After adjusting for multiple comparisons, SNP rs1800547 was significantly associated with PD affection. While the H1 haplotype was associated with a significantly increased risk for PD, a novel H1 subhaplotype was identified that predicted a greater increased risk for PD. The expression of 4-repeat MAPT, STH, and KIAA1267 was significantly increased in PD brains relative to controls. No difference in expression was observed for 3-repeat MAPT. Conclusions: This study supports a role for MAPT in the pathogenesis of familial and idiopathic Parkinson disease ( PD). Interestingly, the results of the gene expression studies suggest that other genes in the vicinity of MAPT, specifically STH and KIAA1267, may also have a role in PD and suggest complex effects for the genes in this region on PD risk. C1 [Tobin, J. E.; Latourelle, J. C.; Saint-Hilaire, M. H.; Hendricks, A. E.; Williamson, S.; Nagle, M. W.; Wilk, J. B.; Massood, T.; Laramie, J. M.; DeStefano, A. L.; Myers, R. H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Tobin, J. E.; Saint-Hilaire, M. H.; Hendricks, A. E.; Williamson, S.; Nagle, M. W.; Wilk, J. B.; Massood, T.; Laramie, J. M.; DeStefano, A. L.; Myers, R. H.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02215 USA. [Hendricks, A. E.; DeStefano, A. L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Laramie, J. M.] Boston Univ, Dept Bioinformat, Boston, MA 02215 USA. [Lew, M. F.] Univ So Calif, Dept Neurol, Los Angeles, CA USA. [Klein, C.] Med Univ Lubeck, Dept Neurol, Lubeck, Germany. [Suchowersky, O.] Univ Calgary, Dept Clin Neurosci, Calgary, AB T2N 1N4, Canada. [Suchowersky, O.] Univ Calgary, Dept Med Genet, Calgary, AB T2N 1N4, Canada. [Shill, H. A.] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Golbe, L. I.; Mark, M. H.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, New Brunswick, NJ 08903 USA. [Gusella, J. F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Mol Neurogenet Unit, Boston, MA USA. [Growdon, J. H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Wooten, G. F.] Univ Virginia Hlth System, Dept Neurol, Charlottesville, VA USA. [Racette, B. A.; Perlmutter, J. S.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Watts, R.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Guttman, M.] Univ Toronto, Dept Med, Toronto, ON M5S 1A1, Canada. [Baker, K. B.; Goldwurm, S.; Pezzoli, G.] Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA. [Baker, K. B.] Cleveland Clin Fdn, Dept Neurosci, Cleveland, OH 44195 USA. [Singer, C.] Univ Miami, Dept Neurol, Coral Gables, FL 33124 USA. [Litvan, I.] Univ Louisville, Sch Med, Dept Neurol, Louisville, KY 40292 USA. [Nicholson, G.; Corbett, A.] Univ Sydney, ANZAC Res Inst, Concord Hosp, Dept Neurol, Sydney, NSW 2006, Australia. [Isaacson, S.] Parkinsons Dis & Movement Disorder Ctr Boca Raton, Boca Raton, FL USA. [Burn, D. J.; Chinnery, P. F.] Univ Newcastle, Reg Neurosci Ctr, Newcastle Upon Tyne, Tyne & Wear, England. [Pramstaller, P. P.] Gen Reg Hosp Bolzano, Dept Neurol, Bolzano, Italy. [Sherman, S.] Univ Arizona, Dept Neurol, Tucson, AZ USA. [Al-Hinti, J.] Univ Arkansas Med Sci, Dept Neurol, Little Rock, AR 72205 USA. [Drasby, E.] Port City Neurol, Scarborough, ME USA. [Nance, M.] Pk Nicollet Clin, St Louis Pk, MN USA. [Moller, A. T.; Ostergaard, K.] Aarhus Univ Hosp, Dept Neurol, Aarhus, Denmark. [Roxburgh, R.; Snow, B.] Auckland City Hosp, Auckland, New Zealand. [Slevin, J. T.; Cambi, F.] Univ Kentucky, Coll Med, Dept Neurol, Lexington, KY 40506 USA. RP Tobin, JE (reprint author), Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Room B2039,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM jetobinphd@gmail.com RI Pramstaller, Peter/C-2357-2008; Hendricks, Audrey/I-4127-2016; Goldwurm, Stefano/Q-8978-2016; OI Hendricks, Audrey/0000-0002-7152-0287; Goldwurm, Stefano/0000-0002-1651-567X; Roxburgh, Richard/0000-0002-8930-7003; Litvan, Irene/0000-0002-3485-3445 FU NHLBI NIH HHS [N01HC25195, N01-HC 25195]; NIA NIH HHS [5-T32-AG00277-05, 5R01-AG 16495, 5R01-AG08122, P30 AG013846, P30 AG13846, R01 AG008122, R01 AG016495, T32 AG000277]; NIMH NIH HHS [R24 MH 068855, R24 MH068855]; NINDS NIH HHS [2R01-NS17950, R01 NS017950, R01 NS036711, R01 NS041509, R01 NS041509-08A2, R01 NS041509-09, R01 NS050425, R01 NS050425-05, R01 NS058714, R01 NS058714-02, R01 NS058714-03, R01 NS36711-05]; Telethon [GTF04007] NR 41 TC 62 Z9 62 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL 1 PY 2008 VL 71 IS 1 BP 28 EP 34 DI 10.1212/01.wnl.0000304051.01650.23 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 321FH UT WOS:000257289600007 PM 18509094 ER PT J AU Tanzi, RE AF Tanzi, Rudolph E. TI Novel therapeutics for Alzheimer's disease SO NEUROTHERAPEUTICS LA English DT Editorial Material ID HYPOTHESIS C1 Massachusetts Gen Hosp, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA USA. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA USA. FU NIMH NIH HHS [R37 MH060009, R37 MH060009-09] NR 2 TC 1 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JUL PY 2008 VL 5 IS 3 BP 377 EP 380 DI 10.1016/j.nurt.2008.05.012 PG 4 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 332JM UT WOS:000258079300001 PM 18625448 ER PT J AU Bush, AI Tanzi, RE AF Bush, Ashley I. Tanzi, Rudolph E. TI Therapeutics for Alzheimer's disease based on the Metal Hypothesis SO NEUROTHERAPEUTICS LA English DT Review DE copper; zinc; amyloid; free radical; oxidation; PBT2 ID AMYLOID-BETA-PEPTIDE; GROWTH-INHIBITORY FACTOR; A-BETA; PRECURSOR-PROTEIN; TRANSGENIC MICE; OXIDATIVE STRESS; IN-VITRO; COGNITIVE IMPAIRMENT; HIPPOCAMPAL-NEURONS; HYDROGEN-PEROXIDE AB Alzheimer's disease is the most common form of dementia in the elderly, and it is characterized by elevated brain iron levels and accumulation of copper and zinc in cerebral beta-amyloid deposits (e. g., senile plaques). Both ionic zinc and copper are able to accelerate the aggregation of A beta, the principle component of beta-amyloid deposits. Copper (and iron) can also promote the neurotoxic redox activity of A beta and induce oxidative cross-linking of the peptide into stable oligomers. Recent reports have documented the release of A beta together with ionic zinc and copper in cortical glutamatergic synapses after excitation. This, in turn, leads to the formation of A beta oligomers, which, in turn, modulates long-term potentiation by controlling synaptic levels of the NMDA receptor. The excessive accumulation of A beta oligomers in the synaptic cleft would then be predicted to adversely affect synaptic neurotransmission. Based on these findings, we have proposed the "Metal Hypothesis of Alzheimer's Disease," which stipulates that the neuropathogenic effects of A beta in Alzheimer's disease are promoted by (and possibly even dependent on) A beta-metal interactions. Increasingly sophisticated pharmaceutical approaches are now being implemented to attenuate abnormal A beta-metal interactions without causing systemic disturbance of essential metals. Small molecules targeting A beta-metal interactions (e. g., PBT2) are currently advancing through clinical trials and show increasing promise as disease-modifying agents for Alzheimer's disease based on the " metal hypothesis.". C1 [Bush, Ashley I.] Mental Hlth Res Inst, Parkville, Vic 3052, Australia. [Bush, Ashley I.] Univ Melbourne, Dept Pathol, Parkville, Vic 3010, Australia. [Tanzi, Rudolph E.] Massachusetts Gen Hosp, Genet & Aging Res Unit, Mass Gen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA 02129 USA. RP Bush, AI (reprint author), Mental Hlth Res Inst, 155 Oak St, Parkville, Vic 3052, Australia. EM bush@helix.mgh.harvard.edu; tanzi@helix.mgh.harvard.edu RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 FU NIA NIH HHS [R01 AG012686, R01 AG012686-10] NR 129 TC 267 Z9 274 U1 7 U2 68 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JUL PY 2008 VL 5 IS 3 BP 421 EP 432 DI 10.1016/j.nurt.2008.05.001 PG 12 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 332JM UT WOS:000258079300007 PM 18625454 ER PT J AU Jones, SE Aziz, K Yasuda, T Gewirtz, H Scott, JA AF Jones, Stephen E. Aziz, Kusal Yasuda, Tsunehiro Gewirtz, Henry Scott, James A. TI Importance of systematic review of rotating projection images from Tc99m-sestamibi cardiac perfusion imaging for noncardiac findings SO NUCLEAR MEDICINE COMMUNICATIONS LA English DT Article DE incidental findings; lung cancer; myocardial perfusion imaging; noncardiac findings; Tc99m-sestamibi ID MYOCARDIAL-PERFUSION; TC-99M SESTAMIBI; INCIDENTAL DETECTION; RADIOTRACER UPTAKE; SPECT; PATIENT; ABNORMALITIES; SCINTIGRAPHY; TECHNETIUM-99M-MIBI; CARCINOMA AB Purpose To test the hypothesis that the observed incidence of important noncardiac findings (NCFs) on myocardial perfusion imaging increases significantly when readers systematically review all rotating projectional images. Methods We prospectively studied NCF reported from a population of 7658 stress cardiac perfusion studies using a single-agent same-day protocol by a review of rotating projectional images. The incidence of NCF was evaluated for both an ensemble of general clinical readers and for a subset of readers who systematically review all rotating projectional images. The clinical validation of NCF was determined first from an evaluation of the electronic medical record and then after direct communication with the primary physicians. Results NCF incidence for general clinical readers was 0.08%, increasing significantly to 0.82% for readers who systematically review all rotating projectional images (P= 0.0013). The spectrum of pathology was diverse, particularly including significant findings such as previously unknown cancers. A total of 53 NCFs were detected, of which clinical follow-up found a corresponding diagnosis in 35 cases (66%). Of these, 43% were previously known, 20% new, and 37% false positives. Thirty-four percent of all NCF had no follow-up, mainly because of lack of additional diagnostic tests. Conclusion NCFs are infrequent but often clinically important findings, whose detection is significantly enhanced by systematic reviews of all rotating projectional images. C1 [Jones, Stephen E.; Scott, James A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Aziz, Kusal; Yasuda, Tsunehiro; Gewirtz, Henry] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. RP Jones, SE (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM joness@ccf.org NR 40 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0143-3636 J9 NUCL MED COMMUN JI Nucl. Med. Commun. PD JUL PY 2008 VL 29 IS 7 BP 607 EP 613 DI 10.1097/MNM.0b013e3282f813f3 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 313KW UT WOS:000256740500005 PM 18528182 ER PT J AU Mansour, WY Schumacher, S Rosskopf, R Rhein, T Schmidt-Petersen, F Gatzemeier, F Haag, F Borgmann, K Willers, H Dahm-Daphi, J AF Mansour, Wael Y. Schumacher, Sabine Rosskopf, Raphael Rhein, Tim Schmidt-Petersen, Filip Gatzemeier, Fruszina Haag, Friedrich Borgmann, Kerstin Willers, Henning Dahm-Daphi, Jochen TI Hierarchy of nonhomologous end-joining, single-strand annealing and gene conversion at site-directed DNA double-strand breaks SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CHROMOSOMAL TRANSLOCATION MECHANISMS; HOMOLOGOUS RECOMBINATION; MAMMALIAN-CELLS; SACCHAROMYCES-CEREVISIAE; KU80-DEFICIENT CELLS; PATHWAY CHOICE; REPAIR; KU; PROTEIN; RAD52 AB In mammalian cells, DNA double-strand breaks (DSBs) are repaired by three pathways, nonhomologous end-joining (NHEJ), gene conversion (GC) and single-strand annealing (SSA). These pathways are distinct with regard to repair efficiency and mutagenic potential and must be tightly controlled to preserve viability and genomic stability. Here, we employed chromosomal reporter constructs to characterize the hierarchy of NHEJ, GC and SSA at a single I-SceI-induced DSB in Chinese hamster ovary cells. We discovered that the use of GC and SSA was increased by 6- to 8-fold upon loss of Ku80 function, suggesting that NHEJ is dominant over the other two pathways. However, NHEJ efficiency was not altered if GC was impaired by Rad51 knockdown. Interestingly, when SSA was made available as an alternative mode for DSB repair, loss of Rad51 function led to an increase in SSA activity at the expense of NHEJ, implying that Rad51 may indirectly promote NHEJ by limiting SSA. We conclude that a repair hierarchy exists to limit the access of the most mutagenic mechanism, SSA, to the break site. Furthermore, the cellular choice of repair pathways is reversible and can be influenced at the level of effector proteins such as Ku80 or Rad51. C1 [Mansour, Wael Y.; Schumacher, Sabine; Rosskopf, Raphael; Rhein, Tim; Schmidt-Petersen, Filip; Gatzemeier, Fruszina; Borgmann, Kerstin; Dahm-Daphi, Jochen] Univ Hamburg, Sch Med, Lab Radiobiol & Expt Radiat Oncol, Dept Radiotherapy & Radiat Oncol, D-20246 Hamburg, Germany. [Haag, Friedrich] Univ Hamburg, Sch Med, Inst Immunol, D-20246 Hamburg, Germany. [Willers, Henning] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Lab Cellular & Mol Radiat Oncol, Boston, MA 02129 USA. RP Dahm-Daphi, J (reprint author), Univ Hamburg, Sch Med, Lab Radiobiol & Expt Radiat Oncol, Dept Radiotherapy & Radiat Oncol, Martinistr 52, D-20246 Hamburg, Germany. EM dahm@uke.uni-hamburg.de NR 60 TC 81 Z9 81 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL PY 2008 VL 36 IS 12 BP 4088 EP 4098 DI 10.1093/nar/gkn347 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 325HA UT WOS:000257578600021 PM 18539610 ER PT J AU Garcia-Boronat, M Diez-Rivero, CM Reinherz, EL Reche, PA AF Garcia-Boronat, Maria Diez-Rivero, Carmen M. Reinherz, Ellis L. Reche, Pedro A. TI PVS: a web server for protein sequence variability analysis tuned to facilitate conserved epitope discovery SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CLASS-I; CRYSTAL-STRUCTURE; PEPTIDE BINDING; MHC MOLECULES; PREDICTION; RESIDUES; ANTIBODY; DESIGN; ALIGNMENTS; ANTIGEN AB We have developed PVS ( Protein Variability Server), a web-based tool that uses several variability metrics to compute the absolute site variability in multiple protein-sequence alignments ( MSAs). The variability is then assigned to a user-selected reference sequence consisting of either the first sequence in the alignment or a consensus sequence. Subsequently, PVS performs tasks that are relevant for structure-function studies, such as plotting and visualizing the variability in a relevant 3D-structure. Neatly, PVS also implements some other tasks that are thought to facilitate the design of epitope discovery-driven vaccines against pathogens where sequence variability largely contributes to immune evasion. Thus, PVS can return the conserved fragments in the MSA - as defined by a user-provided variability threshold - and locate them in a relevant 3D-structure. Furthermore, PVS can return a variability-masked sequence, which can be directly submitted to the RANKPEP server for the prediction of conserved T-cell epitopes. PVS is freely available at: http://imed.med.ucm.es/PVS/. C1 [Garcia-Boronat, Maria; Diez-Rivero, Carmen M.; Reche, Pedro A.] Univ Complutense Madrid, Fac Med, Div Immunol, Dept Microbiol 1,Immunomed Grp, Madrid 28040, Spain. [Reinherz, Ellis L.] Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. [Reinherz, Ellis L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Reinherz, Ellis L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Reche, PA (reprint author), Univ Complutense Madrid, Fac Med, Div Immunol, Dept Microbiol 1,Immunomed Grp, Ave Complutense S-N, Madrid 28040, Spain. EM parecheg@med.ucm.es RI Reche, Pedro/B-1881-2013 OI Reche, Pedro/0000-0003-3966-5838 NR 38 TC 48 Z9 49 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL PY 2008 VL 36 SU S BP W35 EP W41 DI 10.1093/nar/gkn211 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 333GZ UT WOS:000258142300009 PM 18442995 ER PT J AU Buerhaus, PL Ulrich, B Donelan, K DesRoches, C AF Buerhaus, Peter L. Ulrich, Beth Donelan, Karen DesRoches, Catherine TI Registered Nurses' Perspectives on Health Care and the 2008 Presidential Election SO NURSING ECONOMICS LA English DT Article ID WORK-ENVIRONMENT AB As this historic presidential election draws near, what do RNs think of our nation's priorities? Which candidates do they think will be most effective in shaping our health care system and addressing the most pressing issues of our time? The results of this survey show that RNs do not identify overwhelmingly with one political ideology or party and, in fact, they closely resemble the public on these political dimensions. The data also show that RNs identify health care issues as the most important problem facing the nation. RNs who believe that it is the responsibility of the government to provide health insurance to those without it, have more confidence in the government to achieve this outcome, and are more likely to be Democrats than Republicans. The presidential election is expected to be highly contested and could be determined by a relatively small margin of votes and, thus, nurses should recognize their chances of influencing the outcome of the election. The data from this survey provide baseline information potentially useful to increasing the political influence of the nursing profession, informing other organizations about where they might align with nurses, and helping candidates and the political parties compete more effectively in seeking the support of roughly 3 million RN voters. C1 [Buerhaus, Peter L.] Vanderbilt Univ, Med Ctr, Ctr Interdisciplinary Hlth Workforce Studies, Inst Med & Publ Hlth, Nashville, TN USA. [Ulrich, Beth] Gannett Healthcare Grp, Consulting Serv, Pearland, TX USA. [Donelan, Karen; DesRoches, Catherine] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. RP Buerhaus, PL (reprint author), Vanderbilt Univ, Med Ctr, Ctr Interdisciplinary Hlth Workforce Studies, Inst Med & Publ Hlth, Nashville, TN USA. NR 12 TC 7 Z9 7 U1 0 U2 0 PU JANNETTI PUBLICATIONS, INC PI PITMAN PA EAST HOLLY AVENUE, BOX 56, PITMAN, NJ 08071-0056 USA SN 0746-1739 J9 NURS ECON JI Nurs. Econ. PD JUL-AUG PY 2008 VL 26 IS 4 BP 227 EP + PG 10 WC Nursing SC Nursing GA 366SB UT WOS:000260502600004 PM 18777971 ER PT J AU Elahi, D Egan, JM Shannon, RP Meneilly, GS Khatri, A Habener, JF Andersen, DK AF Elahi, Dariush Egan, Josephine M. Shannon, Richard P. Meneilly, Graydon S. Khatri, Ashok Habener, Joel F. Andersen, Dana K. TI GLP-1 (9-36) amide, cleavage product of GLP-1 (7-36) amide, is a glucoregulatory peptide SO OBESITY LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; DEPENDENT INSULINOTROPIC POLYPEPTIDE; METFORMIN-TREATED PATIENTS; TYPE-2 DIABETES-MELLITUS; MEDIATED GLUCOSE-UPTAKE; BETA-CELL FUNCTION; IN-VIVO; METABOLITE; SECRETION; RECEPTOR AB Objective: Glucagon-like peptide-1 (GLP-1) (7-36) amide is a glucoregulatory hormone with insulinotropic and insulinomimetic actions. We determined whether the insulinomimetic effects of GLP-1 are mediated through its principal metabolite, GLP-1 (9-36) amide (GLP-1m). Methods and Procedures: Glucose turnover during two, 2-h, euglycemic clamps was measured in 12 lean and 12 obese (BMI 25 or 30 kg/m(2)) male and female subject volunteers with normal oral glucose tolerance test. Saline or GLP-1m were infused from 0 to 60 min in each study. Additionally, seven lean and six obese subjects underwent a third clamp in which the GLP-1 receptor (GLP-1R) antagonist, exendin (9-39) amide was infused from -60 to 60 min with GLP-1m from 0 to 60 min. Results: No glucose infusion was required in lean subjects to sustain euglycemia ( glucose clamp) during saline or GLP-1m infusions. However, in obese subjects glucose infusion was necessary during GLP-1m infusion alone in order to compensate for a marked (>50%) inhibition of hepatic glucose production (HGP). Plasma insulin levels remained constant in lean subjects but rose significantly in obese subjects after termination of the peptide infusions. During GLP-1R blockade, infusion of glucose was immediately required upon starting GLP-1m infusions in all subjects due to a more dramatic reduction in HGP, as well as a delpayed and modest insulinotropic response. Discussion: We conclude that GLP-1m potently inhibits HGP and is a weak insulinotropic agent. These properties are particularly apparent and pronounced in obese but only become apparent in lean subjects during GLP-1 (7-36) receptor blockade. These previously unrecognized antidiabetogenic actions of GLP-1m may have therapeutic usefulness. C1 [Elahi, Dariush; Andersen, Dana K.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. [Elahi, Dariush; Khatri, Ashok; Habener, Joel F.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Elahi, Dariush; Khatri, Ashok; Habener, Joel F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Egan, Josephine M.] NIA, Clin Invest Lab, Diabet Sect, Baltimore, MD 21224 USA. [Shannon, Richard P.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Meneilly, Graydon S.] Univ British Columbia, Dept Med, Sch Med, Vancouver, BC, Canada. RP Elahi, D (reprint author), Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. EM delahi1@jhmi.edu FU Intramural NIH HHS; NIA NIH HHS [AG 00599, AG 623175, P01 AG000599]; NIDDK NIH HHS [DK 30834] NR 51 TC 51 Z9 58 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD JUL PY 2008 VL 16 IS 7 BP 1501 EP 1509 DI 10.1038/oby.2008.229 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 321RX UT WOS:000257325300005 PM 18421270 ER PT J AU Jenkinson, CP Coletta, DK Flechtner-Mors, M Hu, SL Fourcaudot, MJ Rodriguez, LM Schneider, J Arya, R Stern, MP Blangero, J Duggirala, R DeFronzo, RA AF Jenkinson, Christopher P. Coletta, Dawn K. Flechtner-Mors, Marion Hu, Shirley L. Fourcaudot, Marcel J. Rodriguez, Lenore M. Schneider, Jennifer Arya, Rector Stern, Michael P. Blangero, John Duggirala, Ravindranath DeFronzo, Ralph A. TI Association of genetic variation in ENPP1 with obesity-related phenotypes SO OBESITY LA English DT Article ID K121Q POLYMORPHISM; INSULIN-RESISTANCE; MEXICAN-AMERICANS; LINKAGE ANALYSIS; PLASMA-GLUCOSE; VARIANTS; PC-1; PREDISPOSE; CHILDHOOD; GENOTYPE AB Ectonucleotide pyrophosphatase phosphodiesterase (ENPP1) is a positional candidate gene at chromosome 6q23 where we previously detected strong linkage with fasting-specific plasma insulin and obesity in Mexican Americans from the San Antonio Family Diabetes Study (SAFDS). We genotyped 106 single-nucleotide polymorphisms (SNPs) within ENPP1 in all 439 subjects from the linkage study, and measured association with obesity and metabolic syndrome (MS)-related traits. Of 72 polymorphic SNPs, 24 were associated, using an additive model, with at least one of eight key metabolic traits. Three traits were associated with at least four SNPs. They were high-density lipoprotein cholesterol (HDL-C), leptin, and fasting plasma glucose (FPG). HDL-C was associated with seven SNPs, of which the two most significant P values were 0.0068 and 0.0096. All SNPs and SNP combinations were analyzed for functional contribution to the traits using the Bayesian quantitative-trait nucleotide (BQTN) approach. With this SNP-prioritization analysis, HDL-C was the most strongly associated trait in a four-SNP model (P = 0.00008). After accounting for multiple testing, we conclude that ENPP1 is not a major contributor to our previous linkage peak with MS-related traits in Mexican Americans. However, these results indicate that ENPP1 is a genetic determinant of these traits in this population, and are consistent with multiple positive association findings in independent studies in diverse human populations. C1 [Jenkinson, Christopher P.; Coletta, Dawn K.; Fourcaudot, Marcel J.; Rodriguez, Lenore M.; DeFronzo, Ralph A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Diabetes, San Antonio, TX 78229 USA. [Jenkinson, Christopher P.; Schneider, Jennifer; Blangero, John] SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA. [Jenkinson, Christopher P.; Hu, Shirley L.; DeFronzo, Ralph A.] S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX USA. [Flechtner-Mors, Marion] Univ Ulm, Dept Med, Ulm, Baden Wurttembe, Germany. [Arya, Rector; Stern, Michael P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Clin Epidemiol, San Antonio, TX 78229 USA. RP Jenkinson, CP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Diabetes, San Antonio, TX 78229 USA. EM jenkinsonc@uthscsa.edu RI Coletta, Dawn/G-6382-2016; OI Coletta, Dawn/0000-0001-5819-5152 FU NCRR NIH HHS [M01-RR-01346, M01 RR001346]; NIDDK NIH HHS [DK024092, DK053889-06, R01 DK067690, R01 DK079195, R01 DK047482, DK047482, R01 DK024092, R56 DK024092, R01 DK053889, DK067690] NR 24 TC 10 Z9 10 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD JUL PY 2008 VL 16 IS 7 BP 1708 EP 1713 DI 10.1038/oby.2008.262 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 321RX UT WOS:000257325300035 PM 18464750 ER PT J AU Langenau, DM Keefe, MD Storer, NY Jette, CA Smith, ACH Ceol, CJ Bourque, C Look, AT Zon, LI AF Langenau, D. M. Keefe, M. D. Storer, N. Y. Jette, C. A. Smith, A. C. H. Ceol, C. J. Bourque, C. Look, A. T. Zon, L. I. TI Co-injection strategies to modify radiation sensitivity and tumor initiation in transgenic Zebrafish SO ONCOGENE LA English DT Article DE Myc; ras; heat-shock; T-cell acute lymphoblastic leukemia; rhabdomyosarcoma ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CELLS; TRANSPLANTATION; EXPRESSION; APOPTOSIS; GENESIS; MODEL AB The zebrafish has emerged as a powerful genetic model of cancer, but has been limited by the use of stable transgenic approaches to induce disease. Here, a co-injection strategy is described that capitalizes on both the numbers of embryos that can be microinjected and the ability of transgenes to segregate together and exert synergistic effects in forming tumors. Using this mosaic transgenic approach, gene pathways involved in tumor initiation and radiation sensitivity have been identified. C1 [Langenau, D. M.; Keefe, M. D.; Storer, N. Y.; Smith, A. C. H.; Ceol, C. J.; Bourque, C.; Zon, L. I.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Langenau, D. M.; Keefe, M. D.; Storer, N. Y.; Smith, A. C. H.; Ceol, C. J.; Bourque, C.; Zon, L. I.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Langenau, D. M.; Keefe, M. D.; Storer, N. Y.; Smith, A. C. H.; Ceol, C. J.; Bourque, C.; Zon, L. I.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Langenau, DM (reprint author), Childrens Hosp, Stem Cell Program, 1 Blackfan Circle,Karp 7, Boston, MA 02115 USA. EM dlangenau@enders.tch.harvard.edu FU Howard Hughes Medical Institute; NCI NIH HHS [1R01 CA119066-01, 5R01 CA103846-02, CA104605-03, CA68484-11, CA93152-05, P01 CA068484, R01 CA093152, R01 CA103846, R01 CA104605, R01 CA119066]; NHLBI NIH HHS [HL-088664, R01 HL088664]; NIDDK NIH HHS [1KO1 DK074555-01, K01 DK074555]; NIGMS NIH HHS [T32 GM007753] NR 20 TC 32 Z9 32 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 2008 VL 27 IS 30 BP 4242 EP 4248 DI 10.1038/onc.2008.56 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 324DB UT WOS:000257496800011 PM 18345029 ER PT J AU Aghi, M Visted, T DePinho, RA Chiocca, EA AF Aghi, M. Visted, T. DePinho, R. A. Chiocca, E. A. TI Oncolytic herpes virus with defective ICP6 specifically replicates in quiescent cells with homozygous genetic mutations in p16 SO ONCOGENE LA English DT Article DE oncolytic virus; gene therapy; glioma; brain tumor; mechanism of replication; tumor-suppressor gene ID RIBONUCLEOTIDE REDUCTASE; GLIOBLASTOMA-MULTIFORME; HUMAN GLIOMAS; THERAPY; CANCER; PATHWAY; DELETION; KINASE; MUTANT; PERMISSIVENESS AB Oncolytic herpes simplex viruses (HSVs), in clinical trials for the treatment of malignant gliomas, are assumed to be selective for tumor cells because their replication is strongly attenuated in quiescent cells, but not in cycling cells. Oncolytic selectivity is thought to occur because mutations in viral ICP6 (encoding a viral ribonucleotide reductase function) and/or gamma 34.5 function are respectively complemented by mammalian ribonucleotide reductase and GADD34, whose genes are expressed in cycling cells. However, it is estimated that only 5-15% of malignant glioma cells are in mitosis at any one time. Therefore, effective replication of HSV oncolytic viruses might be limited to a subpopulation of tumor cells, since at any one time the majority of tumor cells would not be cycling. However, we report that an HSV with defective ICP6 function replicates in quiescent cultured murine embryonic fibroblasts obtained from mice with homozygous p16 deletions. Furthermore, intracranial inoculation of this virus into the brains of p16-/- mice provides evidence of viral replication that does not occur when the virus is injected into the brains of wild-type mice. These approaches provide in vitro and in vivo evidence that ICP6-negative HSVs are 'molecularly targeted,' because they replicate in quiescent tumor cells carrying specific oncogene deletions, independent of cell cycle status. C1 [Chiocca, E. A.] Ohio State Univ, Dept Neurosurg, Med Ctr, Dardinger Lab Neurooncol & Neurosci, Columbus, OH 43210 USA. [Chiocca, E. A.] Ohio State Univ, James Comprehens Canc Ctr, Med Ctr, Columbus, OH 43210 USA. [Aghi, M.; Visted, T.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [DePinho, R. A.] Harvard Univ, Sch Med,Belfer Inst Innovat Canc Sci, Dana Farber Canc Inst,Ctr Appl Canc sci, Dept Med Oncol & Med Genet, Boston, MA 02115 USA. RP Chiocca, EA (reprint author), Ohio State Univ, Dept Neurosurg, Med Ctr, Dardinger Lab Neurooncol & Neurosci, Wiseman Hall,400 W 10th Ave, Columbus, OH 43210 USA. EM EA.Chiocca@osumc.edu FU NCI NIH HHS [R01 CA85139, P01 CA095616, P01 CA69246, U01 CA084628]; NINDS NIH HHS [R01 NS41571] NR 31 TC 32 Z9 33 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 2008 VL 27 IS 30 BP 4249 EP 4254 DI 10.1038/onc.2008.53 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 324DB UT WOS:000257496800012 PM 18345032 ER PT J AU Boyajian, RN AF Boyajian, Richard N. TI Physical late effects in adult cancer survivors - The Stricker/Jacobs article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 Dana Farber Canc Inst, Perini Family Survivors Ctr, Lance Armstrong Fdn Adult Survivorship Clin, Boston, MA 02115 USA. RP Boyajian, RN (reprint author), Dana Farber Canc Inst, Perini Family Survivors Ctr, Lance Armstrong Fdn Adult Survivorship Clin, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUL PY 2008 VL 22 IS 8 SU S BP 41 EP 42 PG 2 WC Oncology SC Oncology GA 335IA UT WOS:000258282800006 PM 19856571 ER PT J AU Owen-Smith, A Hathaway, J Roche, M Gioiella, ME Whall-Strojwas, D Silverman, J AF Owen-Smith, Ashli Hathaway, Jeanne Roche, Maria Gioiella, Marie Elena Whall-Strojwas, Denise Silverman, Jay TI Screening for domestic violence in an oncology clinic: Barriers and potential solutions SO ONCOLOGY NURSING FORUM LA English DT Article ID INTIMATE PARTNER VIOLENCE; CERVICAL NEOPLASIA; HEALTH CONSEQUENCES; PHYSICAL HEALTH; WOMEN; CANCER; ABUSE; STRESS; IMPACT; BREAST AB Purpose/Objectives: To evaluate the implementation of a domestic violence screening protocol in an oncology clinic. Design: A retrospective review of a random sample of clinic medical records and qualitative surveys of nursing staff. Setting: A gynecologic oncology clinic in a large teaching hospital. Sample: 204 charts were abstracted and six oncology nurses completed surveys. Methods: A random sample of patients from clinic appointment schedules was selected 6 and 12 months after the implementation of a 11 domestic violence screening protocol. A brief written survey of nursing staff also was conducted. Main Research variables: Documentation of domestic violence screening, barriers to screening and documentation, and potential solutions to the barriers. Findings: Sixty-three percent of the charts reviewed had a domestic violence screening record present, but only 12% of the charts with a screening record had documentation. Patients with domestic violence; screening documentation were more likely to have had five or more clinic visits during the study period. The most frequent barriers to protocol implementation cited by nursing staff were forgetting to screen or document domestic violence screening. Nursing staff recommended adding domestic violence screening questions to forms and providing reminders to screen. Conclusions: Several barriers to successful implementation of a domestic violence screening protocol in a gynecologic oncology clinic, including documentation issues, were encountered. Implications for Nursing: Nurses interested in implementing a domestic violence screening protocol in their oncology clinic should consider reviewing the barriers to domestic violence screening an documentation and the potential solutions identified in this study. C1 [Owen-Smith, Ashli] Emory Univ, Dept Behav Sci & Hlth Educ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Hathaway, Jeanne] Harvard Univ, Sch Publ Hlth, Div Publ Hlth Practice, Boston, MA 02115 USA. [Roche, Maria; Whall-Strojwas, Denise] Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. [Gioiella, Marie Elena] Massachusetts Gen Hosp, Social Serv Dept, Boston, MA 02114 USA. [Silverman, Jay] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Cambridge, MA 02138 USA. RP Owen-Smith, A (reprint author), Emory Univ, Dept Behav Sci & Hlth Educ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. EM aowensm@emory.edu NR 38 TC 13 Z9 13 U1 3 U2 9 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD JUL PY 2008 VL 35 IS 4 BP 625 EP 633 DI 10.1188/08.ONF.625-633 PG 9 WC Oncology; Nursing SC Oncology; Nursing GA 328ES UT WOS:000257781200005 PM 18591166 ER PT J AU Litsas, G AF Litsas, Georgia TI Sequential therapy with tamoxifen and aromatase inhibitors in early-stage postmenopausal breast cancer: A review of the evidence SO ONCOLOGY NURSING FORUM LA English DT Review ID QUALITY-OF-LIFE; BONE-MINERAL DENSITY; SURGICAL ADJUVANT BREAST; RANDOMIZED-TRIAL; HORMONAL-THERAPY; INTERGROUP EXEMESTANE; COMBINATION TRIAL; ENDOCRINE THERAPY; AMERICAN-SOCIETY; ATAC ARIMIDEX AB Purpose/Objectives: To review the available evidence for the emerging role of aromatase inhibitors (AIs) in postmenopausal women with hormone-sensitive early-stage breast cancer. Data Sources: Studies published in journals indexed in PubMede and abstracts and presentations from international conferences. Data Synthesis: Switching to an AI improves survival and reduces cancer recurrence in postmenopausal women who have received two or three years of adjuvant tamoxifen treatment but presents challenges with regard to patient selection, cost, and management of treatment-related adverse events such as bone loss and arthralgia. Conclusions: Third-generation AIs have the potential to significantly improve clinical outcomes in postmenopausal women with early-stage breast cancer, although the optimal treatment regimen for individual patients has yet to be determined. Implications for Nursing: Oncology nurses play a vital role in identifying patients suitable for Al therapy, educating patients about their treatment, and preventing and managing treatment-related adverse events. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Litsas, G (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM georgia_litsas@dfci.harvard.edu NR 71 TC 2 Z9 2 U1 0 U2 2 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD JUL PY 2008 VL 35 IS 4 BP 714 EP 721 DI 10.1188/08.ONF.714-721 PG 8 WC Oncology; Nursing SC Oncology; Nursing GA 328ES UT WOS:000257781200015 PM 18591176 ER PT J AU Savar, A Kirszrot, J Rubin, PAD AF Savar, Aaron Kirszrot, James Rubin, Peter A. D. TI Canalicular involvement in dog bite related eyelid lacerations SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 30-MAY 04, 2006 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol ID INJURIES AB Purpose: To evaluate the incidence of canalicular involvement in periocular dog bite injuries. The majority of eyelid injuries do not involve the canaliculi. It has been our observation that periocular dog bite injuries involve the canaliculi more frequently than lacerations due to other mechanisms. Methods: In this retrospective case series, the records of all patients referred to the oculoplastics service at the Massachusetts Eye and Ear Infirmary with a dog bite injury between 1995 and 2005 were reviewed. Sixty-eight cases of eyelid lacerations due to dog bites were identified. A control group was constructed consisting of 92 patients referred for management of periocular eyelid lacerations not due to dog bite. Variables assessed included canalicular involvement, age, sex, associated injuries, and surgical repair. Results: Canalicular injuries were present in 45 patients (66%) in the dog bite group and 34 patients (37%) in the control group (p < 0.01). In the dog bite group, 7 injuries (16%) involved only the superior canaliculus, 33 (73%) only the inferior canaliculus, and 5 (11%) involved both. In the control group, 12 injuries (35%) involved only the superior canaliculus, 18 (53%) only the inferior canaliculus, and 4 (12%) involved both. The average time from presentation to repair was 0.53 days (range, 0-3 days). Four patients had extensive tissue loss that prevented stenting. Conclusions: Periocular dog bites have a propensity for involvement of the lacrimal canaliculus. We present the largest series to date of periocular dog bite injuries. The index of suspicion for canalicular lacerations should be raised when evaluating patients with dog bite injuries. C1 [Rubin, Peter A. D.] Univ Tennessee, Hlth Sci Ctr, Dept Ophthalmol, Memphis, TN 38105 USA. [Savar, Aaron; Kirszrot, James] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Savar, Aaron; Kirszrot, James] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Rubin, PAD (reprint author), Univ Tennessee, Hlth Sci Ctr, Dept Ophthalmol, Memphis, TN 38105 USA. EM padrmd@aol.com NR 19 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD JUL-AUG PY 2008 VL 24 IS 4 BP 296 EP 298 DI 10.1097/IOP.0b013e318177e21f PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 331HU UT WOS:000258004100011 PM 18645435 ER PT J AU Filippopoulos, T Paula, JS Torun, N Hatton, MP Pasquale, LR Grosskreutz, CL AF Filippopoulos, Theodoros Paula, Jayter S. Torun, Nurhan Hatton, Mark P. Pasquale, Louis R. Grosskreutz, Cynthia L. TI Periorbital changes associated with topical bimatoprost SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the American-Glaucoma-Society CY MAR, 2006 CL Charleston, SC SP Amer Glaucoma Soc ID ELEVATED INTRAOCULAR-PRESSURE; PROSTAGLANDIN ANALOGS; OCULAR HYPERTENSION; FP; LATANOPROST; RECEPTORS; DIFFERENTIATION; DECOMPRESSION; 0.03-PERCENT; TRAVOPROST AB Purpose: To describe periorbital changes induced by chronic topical therapy with daily bimatoprost 0.03% (Lumigan, Allergan Inc., Irvine, CA, U.S.A.). Methods: A clinical investigation of 5 nonconsecutive patients with unilateral glaucoma treated daily with topical bimatoprost 0.03% for up to 4 years prior to presentation. Results: In eyes treated with bimatoprost 0.03% the authors noted periorbital fat atrophy, deepening of the upper eyelid sulcus, relative enophthalmos, loss of the lower eyelid fullness, and involution of dermatochalasis compared with the fellow untreated eye. By inspecting old photographs the authors confirmed that these unilateral changes were not present prior to starting bimatoprost. In addition, these changes were partially reversible after discontinuation of the medication, whenever that was possible. In 2 cases imaging studies confirmed the clinical impression that these findings were not related to primary orbital pathology. Conclusions: Physicians and patients should be aware of the potential of bimatoprost 0.03% to produce periorbital changes. C1 [Filippopoulos, Theodoros; Pasquale, Louis R.; Grosskreutz, Cynthia L.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Glaucoma Consultat Serv, Boston, MA 02114 USA. [Paula, Jayter S.] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Ophthalmol Otorhinolaryngol & Head & Neck Su, BR-14049 Ribeirao Preto, Brazil. [Torun, Nurhan] Beth Israel Deaconess Med Ctr, Div Ophthalmol, Neuroophthalmol Serv, Boston, MA 02215 USA. [Hatton, Mark P.] Ophthalm Consultants Boston, Boston, MA USA. RP Grosskreutz, CL (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Glaucoma Consultat Serv, 243 Charles St, Boston, MA 02114 USA. EM cynthia_grosskreutz@meei.harvard.edu RI PAULA, JAYTER/D-1249-2013 OI PAULA, JAYTER/0000-0002-8111-3810 NR 31 TC 43 Z9 46 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD JUL-AUG PY 2008 VL 24 IS 4 BP 302 EP 307 DI 10.1097/IOP.0b013e31817d81df PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 331HU UT WOS:000258004100013 PM 18645437 ER PT J AU Esmaili, DD Chang, EL O'Hearn, TM Smith, RE Rao, NA AF Esmaili, Daniel D. Chang, Eli L. O'Hearn, Thomas M. Smith, Ronald E. Rao, Narsing A. TI Simultaneous presentation of Kimura disease and angiolymphoid hyperplasia with eosinophilia SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID ENTITIES AB Kimura disease and angiolymphoid hyperplasia with eosinophilia are rare disease entities that can manifest as subcutaneous nodules, plaques, or papules of the head and neck, and less commonly the orbit and ocular adnexa. The merits of each entity have been debated with regard to whether they are truly individual or are separate points on a single spectrum. Current opinion favors the former. This clinicopathologic report of a patient who presented with a right lower eyelid mass with pathologic features consistent with Kimura disease and a left conjunctival mass with features consistent with angiolymphoid hyperplasia with eosinophilia poses a challenge to the notion that these are distinct conditions. C1 [Esmaili, Daniel D.; Chang, Eli L.; O'Hearn, Thomas M.; Smith, Ronald E.; Rao, Narsing A.] Univ So Calif, Keck Sch Med, Doheny Eye Inst, Los Angeles, CA 90033 USA. RP Esmaili, DD (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St,12th Floor Retina Serv, Boston, MA 02114 USA. EM daniel_esmaili@meei.harvard.edu FU NEI NIH HHS [EY03040] NR 6 TC 7 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD JUL-AUG PY 2008 VL 24 IS 4 BP 310 EP 311 DI 10.1097/IOP.0b013e31817e9bba PG 2 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 331HU UT WOS:000258004100015 PM 18645439 ER PT J AU Hatton, MP Durand, ML AF Hatton, Mark P. Durand, Marlene L. TI Orbital cellulitis with abscess formation following surgical treatment of canaliculitis SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID EIKENELLA-CORRODENS; SECONDARY AB The authors report a case of orbital cellulitis with abscess formation that developed after surgical management of canaliculitis. The patient developed pain, erythema, proptosis, and limited eye movements 3 days after canalicular debridement. She required urgent drainage of an orbital abscess and was treated with intravenous antibiotics for 2 weeks. Complications from surgical management of canaliculitis are unusual. Clinicians should be aware of the rare but serious risk of spread of the infection to the orbit. C1 [Hatton, Mark P.] Ophthalm Consultants Boston, Boston, MA 02114 USA. [Durand, Marlene L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Durand, Marlene L.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Hatton, MP (reprint author), Ophthalm Consultants Boston, 50 Staniford St, Boston, MA 02114 USA. EM mphatton@eyeboston.com RI Lambrecht, Bart/M-4734-2015 NR 5 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD JUL-AUG PY 2008 VL 24 IS 4 BP 314 EP 316 DI 10.1097/IOP.0b013e31817e9be7 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 331HU UT WOS:000258004100018 PM 18645442 ER PT J AU DeAngelis, MM Ji, F Adams, S Morrison, MA Harring, AJ Sweeney, MO Capone, A Miller, JW Dryja, TP Ott, J Kim, IK AF DeAngelis, Margaret M. Ji, Fei Adams, Scott Morrison, Margaux A. Harring, Amanda J. Sweeney, Meredith O. Capone, Antonio, Jr. Miller, Joan W. Dryja, Thaddeus P. Ott, Jurg Kim, Ivana K. TI Alleles in the HtrA serine peptidase 1 gene alter the risk of neovascular age-related macular degeneration SO OPHTHALMOLOGY LA English DT Article ID COMPLEMENT FACTOR-H; QUANTITATIVE TRAIT LOCI; DISCORDANT SIB PAIRS; CIGARETTE-SMOKING; HUMAN GENOME; SUSCEPTIBILITY; ASSOCIATION; POLYMORPHISM; LOC387715; VARIANT AB Objective: To examine if the genes encoding the pleckstrin homology domain-containing protein gene (PLE-KHA1), hypothetical LOC387715/ARMS2 gene, and HtrA serine peptidase 1 gene (HTRA1) located on the long arm of chromosome 10 (10q26 region) confer risk for neovascular age-related macular degeneration (AMD) in an independent or interactive manner when controlling for complement factor H gene (CFH) genotype and smoking exposure. Design: Retrospective matched-pair case-control study. Participants: Hospital clinic-based sample of 134 unrelated patients with neovascular AMD who have a sibling with normal maculae (268 subjects). Methods: Disease status was ascertained by at least 2 investigators by review of fundus photographs and/or fluorescein angiography according to the Age-Related Eye Disease Study grading scale. If necessary, a home retinal examination was performed (n = 6). A combination of direct sequencing and analysis of 8 highly polymorphic microsatellite markers was used to genotype 33 megabases of the 10q26 region on leukocyte DNA. Smoking history was obtained via a standardized questionnaire and measured in pack-years. The family-based association test, haplotype analysis, multiple conditional logistic regression, and linkage analysis were used to determine significant associations. Main Outcome Measure: Neovascular AMD status. Results: Of the 23 variants we identified in the 10q26 region, 6 were significant. Four of the 6 were novel and included 2 genotypes that reduced risk of AMD. Many single-nucleotide polymorphisms (SNPs), including the previously reported variants rs-10490924 (hypothetical LOC387715/ARMS2) and rs1 1200638 (HTRA1), defined 2 significant haplotypes associated with increased risk of neovascular AMD. The coding HTRA1 SNP rs2293870, not part of the significant haplotypes containing rs10490924 and rs11200638, showed as strong an association with increased susceptibility to neovascular AMD. Linkage 'analysis supported our findings of SNP association (p<10(-15)). No significant interactions were found between any of the SNPs in the 10q26 and smoking or between these SNPs and CFH genotype. Conclusions: Independent of CFH genotype or smoking history, an individual's risk of AMD could be increased or decreased, depending on their genotype or haplotype in the 10q26region. C1 [DeAngelis, Margaret M.; Adams, Scott; Morrison, Margaux A.; Harring, Amanda J.; Sweeney, Meredith O.; Miller, Joan W.; Dryja, Thaddeus P.; Kim, Ivana K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Ji, Fei; Ott, Jurg] Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA. [Capone, Antonio, Jr.] William Beaumont Hosp, Associated Retinal Consultants PC, Royal Oak, MI 48072 USA. [Ott, Jurg] Chinese Acad Sci, Beijing Inst Genom, Beijing, Peoples R China. RP DeAngelis, MM (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM margaret_deangelis@hms.harvard.edu RI DeAngelis, e/J-7863-2015 FU NEI NIH HHS [P30 EY014104, EY14104, R01 EY014458, EY014458]; NIMH NIH HHS [MH44292, R01 MH044292, R37 MH044292] NR 32 TC 43 Z9 45 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUL PY 2008 VL 115 IS 7 BP 1209 EP 1215 DI 10.1016/j.ophtha.2007.10.032 PG 7 WC Ophthalmology SC Ophthalmology GA 320CK UT WOS:000257211100017 PM 18164066 ER PT J AU Dobscha, SK Corson, K Flores, JA Tansill, EC Gerrity, MS AF Dobscha, Steven K. Corson, Kathryn Flores, Jennifer A. Tansill, Erin C. Gerrity, Martha S. TI Veterans affairs primary care clinicians' attitudes toward chronic pain and correlates of opioid prescribing rates SO PAIN MEDICINE LA English DT Editorial Material DE addiction; chronic pain; narcotics; pain management; primary care; satisfaction ID PHYSICIAN JOB-SATISFACTION; CHRONIC NONMALIGNANT PAIN; DISORDERS; HEALTH; ANALGESICS; MANAGEMENT; KNOWLEDGE; THERAPY; ABUSE AB Objectives. The primary objective of this study was to identify veterans affairs (VA) primary care clinicians' attitudes regarding chronic pain treatment. A secondary objective was to explore relationships between clinician and practice characteristics and an objective measure of opioid prescribing rates. Design. Cross-sectional study of clinician survey and pharmacy data. Participants. Forty-five VA clinicians from five primary care clinics of one VA medical center. Measures. Survey of pain-related attitudes and behaviors, satisfaction with treatment resources, and job satisfaction; percentage of patients in clinicians' panels prescribed opioids (PCPO). Results. Seventy-one percent of clinicians felt moderately or strongly confident in their ability to treat chronic pain, and 77% moderately or strongly agreed that skilled pain management is a high priority. However, 73% moderately or strongly agreed that patients with chronic pain are a major source of frustration and 38% reported moderate or greater dissatisfaction with their ability to provide optimal pain treatment. Fifty-two percent moderately or strongly agreed that their management is influenced by previous experiences with patients addicted to drugs. The mean PCPO was 16.5% (SD = 6.7). In bivariate comparisons, clinician panel size, job and resource satisfaction, and professional training were associated with opioid prescribing rates. Conclusion. High clinician confidence and interest in treating chronic pain concurrent with low satisfaction with ability to provide optimal treatment suggests a need for more system support. VA primary care clinicians are frequently influenced by fears of contributing to dependence or addiction. The relationships among panel size, job satisfaction, and opioid prescribing rates merit additional investigation. C1 [Dobscha, Steven K.; Corson, Kathryn; Flores, Jennifer A.; Tansill, Erin C.; Gerrity, Martha S.] Portland VA Med Ctr, Columbia Ctr Study Chron, Portland, OR 97207 USA. [Dobscha, Steven K.; Corson, Kathryn] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Gerrity, Martha S.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Gerrity, Martha S.] Portland VA Med Ctr, Div Hosp & Specialty Med, Portland, OR 97207 USA. RP Dobscha, SK (reprint author), Portland VA Med Ctr, Columbia Ctr Study Chron, POB 1034 R&D 66, Portland, OR 97207 USA. EM steven.dobscha@va.gov NR 31 TC 60 Z9 60 U1 1 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1526-2375 J9 PAIN MED JI Pain Med. PD JUL-AUG PY 2008 VL 9 IS 5 BP 564 EP 571 DI 10.1111/j.1526-4637.2007.00330.x PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 334MD UT WOS:000258225000009 PM 18777608 ER PT J AU Meghani, SH Gallagher, RM AF Meghani, Salimah H. Gallagher, Rollin M. TI Disparity vs inequity: Toward reconceptualization of pain treatment disparities SO PAIN MEDICINE LA English DT Article DE disparities; inequities; pain; pain treatment; race; ethnicity; minorities ID LOW-BACK-PAIN; COOPERATIVE-ONCOLOGY-GROUP; HEALTH-CARE; CANCER PAIN; EMERGENCY-DEPARTMENT; POSTOPERATIVE PAIN; ETHNIC DISPARITIES; RACIAL-DIFFERENCES; AFRICAN-AMERICANS; OPIOID ANALGESICS AB Context. "Disparity" and "inequity" are two interdependent, yet distinct concepts that inform our discourse on ethics and morals in pain medicine practice and in health policy. Disparity implies a difference of some kind, whereas inequity implies unfairness and injustice. An overwhelming body of literature documents racial/ethnic disparities in health. The debate on health disparities is generally formulated using the principle of "horizontal equity," which requires that individuals having the same needs be treated equally. While some types of health treatments are amenable to the principle of horizontal equity, others may not be appropriately studied in this way. The existing research surrounding racial/ethnic disparities in pain treatment presents a conceptual predicament when placed within the framework of horizontal equity. Objective. Using pain treatment as a prototype, we advance the conceptual debate about racial/ ethnic disparities in health. More specifically, we ask three questions: (1) When may disparities be considered inequities? (2) When may disparities not be considered inequities? (3) What are the uncertainties in the disparity-inequity discourse? Discussion. Significant policy implications may result from the manner in which health disparities are conceptualized. Increasingly, researchers and policy makers use the term disparity interchangeably with inequity. This usage confuses the meaning and application of these distinct concepts. In a given health care setting, different types of disparities may operate simultaneously, each requiring serious scrutiny to avoid categorical interpretation leading to misguided practice and policy. While the science of pain treatment disparities is still emerging, the authors present one perspective toward the conceptualization of racial/ethnic disparities in pain treatment. C1 [Meghani, Salimah H.] Univ Penn, Ctr Hlth Dispar Res, Sch Nursing, Philadelphia, PA 19104 USA. [Gallagher, Rollin M.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Gallagher, Rollin M.] Univ Penn, Ctr Pain Med Res & Policy, Philadelphia, PA 19104 USA. [Gallagher, Rollin M.] Philadelphia Vet Affairs Med Ctr, Pain Med Serv, Philadelphia, PA USA. RP Meghani, SH (reprint author), Univ Penn, Ctr Hlth Dispar Res, Sch Nursing, Claire M Fagin Hall 418 Curie Blvd, Philadelphia, PA 19104 USA. EM meghanis@nursing.upenn.edu NR 73 TC 6 Z9 6 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1526-2375 J9 PAIN MED JI Pain Med. PD JUL-AUG PY 2008 VL 9 IS 5 BP 613 EP 623 DI 10.1111/j.1526-4637.2007.00344.x PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 334MD UT WOS:000258225000014 PM 18777609 ER PT J AU Gallagher, RM AF Gallagher, Rollin M. TI Opioid analgesia: Managing risks and obtaining benefits SO PAIN MEDICINE LA English DT Editorial Material ID CHRONIC NONCANCER PAIN; PRIMARY-CARE; MANAGEMENT C1 Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Gallagher, RM (reprint author), Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. NR 10 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1526-2375 J9 PAIN MED JI Pain Med. PD JUL-AUG PY 2008 VL 9 SU 2 BP S143 EP S144 DI 10.1111/j.1526-4637.2008.00485.x PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 335JP UT WOS:000258287200001 ER PT J AU Manchikanti, L Singh, V Derby, R Schultz, DM Benyamin, RM Prager, JP Hirsch, JA AF Manchikanti, Laxmaiah Singh, Vijay Derby, Richard Schultz, David M. Benyamin, Ramsin M. Prager, Joshua P. Hirsch, Joshua A. TI Reassessment of Evidence Synthesis of Occupational Medicine Practice Guidelines for Interventional Pain Management SO PAIN PHYSICIAN LA English DT Review DE Guidelines; evidence-based medicine; systematic reviews; ACOEM; interventional pain management; interventional techniques; guideline development; workers' compensation; chronic pain guidelines; low back pain guidelines ID LOW-BACK-PAIN; SPINAL-CORD STIMULATION; LUMBAR FACET JOINTS; RANDOMIZED CONTROLLED-TRIAL; EPIDURAL STEROID INJECTIONS; REFLEX SYMPATHETIC DYSTROPHY; GENE-RELATED PEPTIDE; LOCAL-ANESTHETIC BLOCKS; MEDIAL BRANCH BLOCKS; DOUBLE-BLIND TRIAL AB Background: Appropriately developed practice guidelines present statements of best practice based on a thorough evaluation of the evidence from published studies on the outcomes of treatments, which include the application of multiple methods for collecting and evaluating evidence for a wide range of clinical interventions and disciplines. However, the guidelines are neither infallible nor a sub, stitute for clinical judgment. While the guideline development process is a complex phenomenon, conflict of interest in guideline development and inappropriate methodologies must be avoided. It has been alleged that the guidelines by the American College of Occupational and Environmental Medicine (ACOEM) p,event injured workers from receiving the majority of medically necessary and appropriate interventional pain management services, An independent critical appraisal of both chapters of the ACOEM guidelines showed startling finding,; with a conclusion that these guidelines may not be applied in patient care as they scored below 30% in the majority of evaluations utilizing multiple standardized criteria. Objective: To reassess the evidence synthesis for the ACOEM guidelines for the low back pain and chronic pain chapters utilizing an expanded methodology, which includes the criteria included in the ACOEM guidelines with the addition of omitted literature and application of appropriate criteria. Methods: For reassessment, randomized trials were utilized as it was in the preparation of the guidelines. In this process, quality of evidence was assessed and recommendations were made based on grading recommendations of Guyatt et al. The level of evidence was determined utilizing the quality of evidence criteria developed by the U.S. Preventive Services Task Force (USPSTF) as well, as the outdated quality of evidence criteria utilized by ACOEM in the guideline preparation. Methodologic quality of each individual article was assessed utilizing the Agency for Healthcare Research and Quality (AHRQ) methodologic assessment criteria for diagnostic interventions and Cochrane methodologic quality assessment criteria for therapeutic interventions. Results: The results of reassessment are vastly different from the conclusions derived by the ACOEM guidelines. The differences in strength of rating for the diagnosis of discogenic pain by provocation discography and facet joint pain by diagnostic facet joint nerve blocks is established with strong evidence. Therapeutic cervical and lumbar medial branch blocks and radiofrequency neurolysis, therapeutic thoracic medial branch blocks, cervical interlaminar epidural steroid injections, caudal epidural steroid injections, lumbar transforaminal epidural injections, percutaneous and endoscopic adhesiolysis, and spinal cord stimulation qualified for moderate to strong evidence. Additional insight is also provided for evidence rating for intradiscal electrothermal therapy (IDET), automated percutaneous disc decompression, and intrathecal implantables. Conclusion: The reassessment and reevaluation of the low back and chronic pain chapters of the ACOEM guidelines present results that are vastly different from the published and proposed guidelines. Contrary to ACOEM's conclusions of insufficient evidence for most interventional techniques, the results illustrate moderate to strong evidence for most diagnostic and therapeutic interventional techniques. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Singh, Vijay] Pain Diagnost Associates, Niagara, WI USA. [Derby, Richard] Spinal Diagnost & Treatment Ctr, Daly City, CA USA. [Schultz, David M.] Med Adv Pain Specialists, Minneapolis, MN USA. [Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA. [Prager, Joshua P.] Ctr Rehabil Pain Syndromes, Los Angeles, CA USA. [Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Derby, Richard] Stanford Univ, Dept Phys Med & Rehabil, Stanford, CA 94305 USA. [Benyamin, Ramsin M.] Univ Illinois, Coll Med, Dept Surg, Urbana, IL 61801 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42001 USA. EM drlm@thepainmd.com NR 513 TC 107 Z9 109 U1 0 U2 4 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD JUL-AUG PY 2008 VL 11 IS 4 BP 393 EP 482 PG 90 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 375GR UT WOS:000261102600002 PM 18690276 ER PT J AU Irani, K Rodriguez, L Doody, DP Goldstein, AM AF Irani, Katy Rodriguez, Leonel Doody, Daniel P. Goldstein, Allan M. TI Botulinum toxin for the treatment of chronic constipation in children with internal anal sphincter dysfunction SO PEDIATRIC SURGERY INTERNATIONAL LA English DT Article DE constipation; anal achalasia; internal anal sphincter; botulinum toxin; anorectal manometry ID HIRSCHSPRUNGS-DISEASE; RANDOMIZED-TRIAL; ACHALASIA; MYECTOMY AB Internal anal sphincter (IAS) dysfunction is a cause of refractory constipation in children. The goal of this study was to determine whether intrasphincteric injection of botulinum toxin is effective in the treatment of constipation in pediatric patients with IAS dysfunction. A retrospective review was performed of 24 pediatric patients with intractable constipation. All patients had abnormal anorectal manometry, with either elevated IAS resting pressure (>= 100 mm Hg) or an absent or diminished rectoanal inhibitory reflex. Patients with Hirschsprung's disease were excluded. All patients underwent botox injection into the IAS and were followed for a minimum of 6 months. Of 24 patients, 22 experienced significant improvement in their constipation lasting greater than 2 weeks. The duration of effect was variable, with 12 patients demonstrating benefit lasting at least 6 months. Transient postoperative incontinence occurred in five patients. Intrasphincteric injection of botox is a safe and effective treatment for intractable constipation in children with IAS dysfunction. C1 [Irani, Katy; Doody, Daniel P.; Goldstein, Allan M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Intestinal Rehabil Program,Dept Pediat Sur, Boston, MA 02114 USA. [Irani, Katy] NYU, Dept Surg, New York, NY 10016 USA. [Rodriguez, Leonel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Intestinal Rehabil Program,Div Pediat Gast, Boston, MA 02114 USA. RP Goldstein, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Intestinal Rehabil Program,Dept Pediat Sur, Warren 1153, Boston, MA 02114 USA. EM agoldstein@partners.org NR 19 TC 19 Z9 20 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0179-0358 J9 PEDIATR SURG INT JI Pediatr. Surg. Int. PD JUL PY 2008 VL 24 IS 7 BP 779 EP 783 DI 10.1007/s00383-008-2171-3 PG 5 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 313RJ UT WOS:000256757400005 PM 18443801 ER PT J AU Mansbach, JM Camargo, CA AF Mansbach, Jonathan M. Camargo, Carlos A., Jr. TI Bronchiolitis: Lingering questions about its definition and the potential role of vitamin D SO PEDIATRICS LA English DT Editorial Material ID RESPIRATORY SYNCYTIAL VIRUS; D DEFICIENCY; CONTROLLED-TRIAL; NUTRITIONAL RICKETS; TRACT INFECTIONS; VIRAL ETIOLOGY; CHILDREN; INFANTS; MULTICENTER; RHINOVIRUS C1 [Mansbach, Jonathan M.] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Mansbach, JM (reprint author), Childrens Hosp, Dept Med, Main Clinical Bldg 9 S 9157, Boston, MA 02115 USA. EM jonathan.mansbach@childrens.harvard.edu NR 37 TC 18 Z9 22 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 2008 VL 122 IS 1 BP 177 EP 179 DI 10.1542/peds.2007-3323 PG 3 WC Pediatrics SC Pediatrics GA 320YN UT WOS:000257271200022 PM 18596000 ER PT J AU Becker, ML Aarnoudse, AJLHJ Newton-Cheh, C Hofman, A Witteman, JCM Uitterlinden, AG Visser, LE Stricker, BHC AF Becker, Matthijs L. Aarnoudse, Albert-Jan L. H. J. Newton-Cheh, Christopher Hofman, Albert Witteman, Jacqueline C. M. Uitterlinden, Andre G. Visser, Loes E. Stricker, Bruno H. Ch. TI Common variation in the NOS1AP gene is associated with reduced glucose-lowering effect and with increased mortality in users of sulfonylurea SO PHARMACOGENETICS AND GENOMICS LA English DT Article DE diabetes mellitus; nitric oxide synthase; sulfonylurea compounds; type 2 ID GROUP DIABETES PROGRAM; PANCREATIC BETA-CELLS; VASCULAR SMOOTH-MUSCLE; SENSITIVE K+ CHANNELS; NITRIC-OXIDE SYNTHASE; CARDIAC REPOLARIZATION; MYOCARDIAL PROTECTION; INSULIN-SECRETION; ATP CHANNELS; ROTTERDAM AB Objective The single nucleotide polymorphism rs10494366 in the nitric oxide synthase 1 adaptor protein (NOS1AP) gene is associated with QTc prolongation, through an effect on the intracellular Ca(2+) levels. As sulfonylurea stimulate insulin secretion by an increased 21 influx of Ca(2+) we hypothesized that this polymorphism is associated with the glucose-lowering effect and mortality risk in sulfonylurea users. Methods Associations between the NOS1AP polymorphism, prescribed doses, and mortality rates in sulfonylurea, metformin, and insulin users were assessed in the Rotterdam Study, a population-based cohort study of 7983 elderly people. Results We identified 619 participants who were prescribed oral antidiabetic drugs during follow-up. In glibenclamide users carrying the TG genotype, the prescribed doses were higher compared with the glibenclamide users carrying the TT genotype [0.38 defined daily dose units, 95% confidence interval (Cl) 0.14-0.63]. Glibenclamide users with the TG or GG genotype had an increased mortality risk compared with glibenclamide users with the TT genotype [hazard ratio (H R) 2.80, 95% Cl: 1.09-722]. Tolbutamide users with the TG or GG genotype HR: 0.30, 95% Cl: 0.14-0.63) and glimepiride users with the TG or GG genotype (H R: 0.18, 95% Cl: 0.04-0.74) had a decreased mortality risk compared with tolbutamide and glimepiride users with the TT genotype. Conclusion In participants with the TG or GG genotype at rs10494366 in the NOS1AP gene, glibenclamide is less effective in reducing glucose levels and mortality rates were higher compared with glibenclamide users with the TT genotype. In tolbutamide and glimepiride users, the TG and GG genotype were associated with a reduced mortality rate. Pharmacogenetics and Genomics 18:591-597 (c) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Becker, Matthijs L.; Aarnoudse, Albert-Jan L. H. J.; Hofman, Albert; Witteman, Jacqueline C. M.; Uitterlinden, Andre G.; Visser, Loes E.; Stricker, Bruno H. Ch.] Erasmus MC, Dept Epidemiol & Biostat, NL-3000 CA Rotterdam, Netherlands. [Becker, Matthijs L.; Visser, Loes E.] Erasmus MC, Dept Hosp Pharm, NL-3000 CA Rotterdam, Netherlands. [Uitterlinden, Andre G.; Stricker, Bruno H. Ch.] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. [Aarnoudse, Albert-Jan L. H. J.; Stricker, Bruno H. Ch.] Drug Safety Unit, The Hague, Netherlands. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Newton-Cheh, Christopher] MIT, Cambridge, MA 02139 USA. RP Stricker, BHC (reprint author), Erasmus MC, Dept Epidemiol & Biostat, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM b.stricker@erasmusmc.nl RI Becker, Matthijs/A-6437-2012 NR 37 TC 21 Z9 24 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1744-6872 J9 PHARMACOGENET GENOM JI Pharmacogenet. Genomics PD JUL PY 2008 VL 18 IS 7 BP 591 EP 597 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 320GV UT WOS:000257222600005 PM 18551039 ER PT J AU Lehmann, S Schwartz, M Hansen, LK AF Lehmann, Sune Schwartz, Martin Hansen, Lars Kai TI Biclique communities SO PHYSICAL REVIEW E LA English DT Article ID NETWORKS; EVOLUTION AB We present a method for detecting communities in bipartite networks. Based on an extension of the k-clique community detection algorithm, we demonstrate how modular structure in bipartite networks presents itself as overlapping bicliques. If bipartite information is available, the biclique community detection algorithm retains all of the advantages of the k-clique algorithm, but avoids discarding important structural information when performing a one-mode projection of the network. Further, the biclique community detection algorithm provides a level of flexibility by incorporating independent clique thresholds for each of the nonoverlapping node sets in the bipartite network. C1 [Lehmann, Sune] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. [Lehmann, Sune] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Lehmann, Sune] Harvard Univ, Ctr Canc Syst Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Lehmann, Sune; Schwartz, Martin; Hansen, Lars Kai] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Schwartz, Martin] IT Univ Copenhagen, DK-2300 Copenhagen, Denmark. RP Lehmann, S (reprint author), Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. RI Hansen, Lars/E-3174-2013; OI Lehmann, Sune/0000-0001-6099-2345 NR 31 TC 38 Z9 45 U1 0 U2 9 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 2470-0045 EI 2470-0053 J9 PHYS REV E JI Phys. Rev. E PD JUL PY 2008 VL 78 IS 1 AR 016108 DI 10.1103/PhysRevE.78.016108 PN 2 PG 9 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 333UV UT WOS:000258179000016 PM 18764021 ER PT J AU Adonizio, A Dawlaty, J Ausubel, FM Clardy, J Mathee, K AF Adonizio, A. Dawlaty, J. Ausubel, F. M. Clardy, J. Mathee, K. TI Ellagitannins from Conocarpus erectus exhibit anti-quorum sensing activity against Pseudomonas aeruginosa SO PLANTA MEDICA LA English DT Meeting Abstract CT 7th Joint Meeting of the Association-Francophone-pour-l'Enselgnement-et-la-Recherche-en-Pharmacog nosie/American-Society-of-Pharmacognosy/Society-for-Medicinal-Plant-Rese arch/Phytochem-Society-of-Europe/Societa-Italiana-di-Fitochimica CY AUG 03-08, 2008 CL Athens, GREECE SP Assoc Francophone Enseignement Rech Pharmacognosie, Amer Soc Pharmacognosy, Soc Medicinal Plant Res, Phytochem Soc Europe, Soc Italiana Fitochim C1 [Adonizio, A.; Mathee, K.] Florida Int Univ, Miami, FL 33199 USA. [Dawlaty, J.; Clardy, J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ausubel, F. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 3 Z9 4 U1 0 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD JUL PY 2008 VL 74 IS 9 BP 1035 EP 1035 PG 1 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 334ZY UT WOS:000258261800530 ER PT J AU Georgantea, P Vagias, C Tegos, G Moreau, D Roussakis, C Roussis, V AF Georgantea, P. Vagias, C. Tegos, G. Moreau, D. Roussakis, C. Roussis, V TI New sesquiterpenoid metabolites from the tropical coral Pseudopterogorgia rigida SO PLANTA MEDICA LA English DT Meeting Abstract CT 7th Joint Meeting of the Association-Francophone-pour-l'Enselgnement-et-la-Recherche-en-Pharmacog nosie/American-Society-of-Pharmacognosy/Society-for-Medicinal-Plant-Rese arch/Phytochem-Society-of-Europe/Societa-Italiana-di-Fitochimica CY AUG 03-08, 2008 CL Athens, GREECE SP Assoc Francophone Enseignement Rech Pharmacognosie, Amer Soc Pharmacognosy, Soc Medicinal Plant Res, Phytochem Soc Europe, Soc Italiana Fitochim C1 [Georgantea, P.; Vagias, C.; Roussis, V] Univ Athens, Sch Pharm, Dept Pharmacognosy & Chem Nat Prod, GR-15771 Athens, Greece. [Tegos, G.] Harvard Univ, Sch Med, Bartlett Hall Wellman Ctr Photomed 406, Boston, MA 02114 USA. [Tegos, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Moreau, D.; Roussakis, C.] Fac Pharm, Lab Pharmacogen Marine, ISOMer, F-44035 Nantes, France. RI Tegos, George/C-8830-2011; Moreau, Dimitri/E-5092-2012; Moreau, Dimitri/A-7503-2017 OI Moreau, Dimitri/0000-0002-9282-3324; Moreau, Dimitri/0000-0002-9282-3324 NR 2 TC 0 Z9 0 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD JUL PY 2008 VL 74 IS 9 BP 1051 EP 1051 PG 1 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 334ZY UT WOS:000258261800579 ER PT J AU Parrett, BM Winograd, JM Garfein, ES Lee, WPA Hornicek, FJ Austen, WG AF Parrett, Brian M. Winograd, Jonathan M. Garfein, Evan S. Lee, W. P. Andrew Hornicek, Francis J. Austen, William G., Jr. TI The vertical and extended rectus abdominis myocutaneous flap for irradiated thigh and groin defects SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID SOFT-TISSUE SARCOMA; LOWER-EXTREMITY RECONSTRUCTION; INFERIOR EPIGASTRIC FLAP; CLINICAL-APPLICATIONS; RADIATION-THERAPY; SURGERY; COMPLICATIONS; RESECTION; RADIOTHERAPY AB Background: Thigh and groin tumors are often treated with limb-sparing surgery and adjuvant preoperative irradiation, frequently resulting in complex soft-tissue defects and wounds. The authors evaluated outcomes after reconstruction of these difficult wounds with the vertical and extended rectus abdominis myocutaneous (RAM) flap. Methods: A retrospective chart review was performed of 50 consecutive patients who underwent inferiorly based RAM pedicle flaps to reconstruct thigh and groin defects after preoperative irradiation and oncologic resection. Timing of reconstruction, flap design, complications, metastasis/recurrence, and ambulation status were analyzed. Results: Fifty patients (mean age, 56 years; range, 10 to 83 years) underwent 51 RAM flaps. Sixty-three percent of flaps were for immediate reconstruction and the remaining flaps were for secondary coverage after failure of initial closure. There were no perioperative deaths. The median length of hospital stay was 9 days. All flaps survived. The vertical RAM flap was used in 63 percent of cases; the extended RAM flap was used in 37 percent and permitted closure of larger, contralateral, and more distal defects. With a mean follow-up of 28 months, complications included partial flap necrosis [n = 2 (4 percent)], infection [n = 8 (16 percent)], seroma [n = 2 (4 percent)], dehiscence [n = 2 (4 percent)], and donor-site bulge[ n = 6 (12 percent)]. Postoperative wound complications were significantly higher in patients who underwent delayed or secondary (47 percent) versus immediate reconstruction (9.4 percent, 0.005). Three patients required additional coverage. There was no significant difference in flap complications between the extended and non-extended flap designs. Independent ambulation was achieved in 82 percent of patients. Conclusions: The vertical and extended RAM flaps provide reliable coverage of irradiated thigh and groin oncologic wounds, with significantly improved results obtained with immediate versus delayed reconstruction. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Oncol Serv, Boston, MA 02115 USA. RP Austen, WG (reprint author), Massachusetts Gen Hosp, Wang Bldg,ACC-435 15 Parkman St, Boston, MA 02114 USA. EM wausten@partners.org NR 23 TC 11 Z9 12 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JUL PY 2008 VL 122 IS 1 BP 171 EP 177 DI 10.1097/PRS.0b013e3181774330 PG 7 WC Surgery SC Surgery GA 318PO UT WOS:000257104300021 PM 18594402 ER PT J AU Hagmann, P Cammoun, L Gigandet, X Meuli, R Honey, CJ Wedeen, V Sporns, O AF Hagmann, Patric Cammoun, Leila Gigandet, Xavier Meuli, Reto Honey, Christopher J. Wedeen, Van J. Sporns, Olaf TI Mapping the structural core of human cerebral cortex SO PLOS BIOLOGY LA English DT Article ID DIFFUSION-WEIGHTED MRI; SURFACE-BASED ANALYSIS; HUMAN BRAIN; FUNCTIONAL CONNECTIVITY; ALZHEIMERS-DISEASE; FIBER PATHWAYS; DEFAULT MODE; GRAPH-THEORY; NETWORKS; ORGANIZATION AB Structurally segregated and functionally specialized regions of the human cerebral cortex are interconnected by a dense network of cortico-cortical axonal pathways. By using diffusion spectrum imaging, we noninvasively mapped these pathways within and across cortical hemispheres in individual human participants. An analysis of the resulting large-scale structural brain networks reveals a structural core within posterior medial and parietal cerebral cortex, as well as several distinct temporal and frontal modules. Brain regions within the structural core share high degree, strength, and betweenness centrality, and they constitute connector hubs that link all major structural modules. The structural core contains brain regions that form the posterior components of the human default network. Looking both within and outside of core regions, we observed a substantial correspondence between structural connectivity and resting-state functional connectivity measured in the same participants. The spatial and topological centrality of the core within cortex suggests an important role in functional integration. C1 [Honey, Christopher J.; Sporns, Olaf] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA. [Hagmann, Patric; Meuli, Reto] Univ Hosp Ctr, Dept Radiol, Lausanne, Switzerland. [Hagmann, Patric; Meuli, Reto] Univ Lausanne, Lausanne, Switzerland. [Hagmann, Patric; Cammoun, Leila; Gigandet, Xavier] Ecole Polytech Fed Lausanne, Signal Proc Lab LTS5, Lausanne, Switzerland. [Wedeen, Van J.] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Wedeen, Van J.] Harvard Univ, Sch Med, Boston, MA USA. RP Sporns, O (reprint author), Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA. EM osporns@indiana.edu RI Sporns, Olaf/A-1667-2010; Centre d'imagerie Biomedicale, CIBM/B-5740-2012; Honey, Christopher/C-3105-2015 OI Sporns, Olaf/0000-0001-7265-4036; Honey, Christopher/0000-0002-0745-5089 FU NIMH NIH HHS [1R01-MH64-44] NR 55 TC 1455 Z9 1487 U1 16 U2 183 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD JUL PY 2008 VL 6 IS 7 BP 1479 EP 1493 AR e159 DI 10.1371/journal.pbio.0060159 PG 15 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 330VO UT WOS:000257971100019 PM 18597554 ER PT J AU Chenine, AL Shai-Kobiler, E Steele, LN Ong, H Augostini, P Song, RJ Lee, SJ Autissier, P Ruprecht, RM Secor, WE AF Chenine, Agnes-Laurence Shai-Kobiler, Ela Steele, Lisa N. Ong, Helena Augostini, Peter Song, Ruijiang Lee, Sandra J. Autissier, Patrick Ruprecht, Ruth M. Secor, W. Evan TI Acute Schistosoma mansoni Infection Increases Susceptibility to Systemic SHIV Clade C Infection in Rhesus Macaques after Mucosal Virus Exposure SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID POLYMERASE CHAIN-REACTION; BLOOD MONONUCLEAR-CELLS; HIV-1 INFECTION; CYTOKINE RESPONSES; HELMINTH INFECTION; MALE CIRCUMCISION; IMMUNE-RESPONSES; UGANDAN ADULTS; RNA LOAD; T-CELL AB Background: Individuals living in sub-Saharan Africa represent 10% of the world's population but almost 2/3 of all HIV-1/AIDS cases. The disproportionate HIV-1 infection rates in this region may be linked to helminthic parasite infections that affect many individuals in the developing world. However, the hypothesis that parasite infection increases an individual's susceptibility to HIV-1 has never been prospectively tested in a relevant in vivo model. Methodology/Principal Findings: We measured whether pre-existing infection of rhesus monkeys with a parasitic worm would facilitate systemic infection after mucosal AIDS virus exposure. Two groups of animals, one consisting of normal monkeys and the other harboring Schistosoma mansoni, were challenged intrarectally with decreasing doses of R5-tropic clade C simian-human immunodeficiency virus (SHIV-C). Systemic infection occurred in parasitized monkeys at viral doses that remained sub-infectious in normal hosts. In fact, the 50% animal infectious (AID(50)) SHIV-C dose was 17-fold lower in parasitized animals compared to controls (P < 0.001). Coinfected animals also had significantly higher peak viral RNA loads than controls (P < 0.001), as well as increased viral replication in CD4(+) central memory cells (P=0.03). Conclusions/Significance: Our data provide the first direct evidence that acute schistosomiasis significantly increases the risk of de novo AIDS virus acquisition, and the magnitude of the effect suggests that control of helminth infections may be a useful public health intervention to help decrease the spread of HIV-1. C1 [Chenine, Agnes-Laurence; Shai-Kobiler, Ela; Ong, Helena; Song, Ruijiang; Ruprecht, Ruth M.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Chenine, Agnes-Laurence; Shai-Kobiler, Ela; Song, Ruijiang; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA USA. [Steele, Lisa N.; Augostini, Peter; Secor, W. Evan] Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Parasit Dis, Atlanta, GA USA. [Lee, Sandra J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Autissier, Patrick] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. RP Chenine, AL (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM ruth_ruprecht@dfci.harvard.edu; was4@cdc.gov RI Greenberg, Robert/D-1091-2009 FU National Institutes of Health [R56 A1062515, P01 A1348240] FX This study was supported in part by National Institutes of Health grants R56 A1062515 and P01 A1348240 to RMR. LNS was an Emerging Infectious Diseases Research Fellow sponsored by the Association of Public Health Laboratories and the CDC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 31 TC 40 Z9 40 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JUL PY 2008 VL 2 IS 7 AR e265 DI 10.1371/journal.pntd.0000265 PG 7 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 385IE UT WOS:000261807100006 PM 18648516 ER PT J AU Pastor, R McKinnon, CS Scibelli, AC Burkhart-Kasch, S Reed, C Ryabinin, AE Coste, SC Stenzel-Poore, MP Phillips, TJ AF Pastor, Raul McKinnon, Carrie S. Scibelli, Angela C. Burkhart-Kasch, Sue Reed, Cheryl Ryabinin, Andrey E. Coste, Sarah C. Stenzel-Poore, Mary P. Phillips, Tamara J. TI Corticotropin-releasing factor-1 receptor involvement in behavioral neuroadaptation to ethanol: A urocortin(1)-independent mechanism SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE addiction; CP-154,526; HPA axis; knockout mice; psychomotor sensitization ID PITUITARY-ADRENAL AXIS; ANXIETY-LIKE BEHAVIOR; PSYCHOMOTOR-STIMULANT SENSITIZATION; STRESS-INDUCED SENSITIZATION; MESSENGER-RNA EXPRESSION; LONG-TERM EXPRESSION; FACTOR CRF; UNITARY PHENOMENON; MOTOR-ACTIVITY; ANIMAL-MODELS AB A common expression of neuroadaptations induced by repeated exposure to addictive drugs is a persistent sensitized behavioral response to their stimulant properties. Neuroplasticity underlying drug-induced sensitization has been proposed to explain compulsive drug pursuit and consumption characteristic of addiction. The hypothalamic-pituitary-adrenal (HPA) axis-activating neuropeptide, corticotropin-releasing factor (CRF), may be the keystone in drug-induced neuroadaptation. Corticosterone-activated glucocorticoid receptors (GRs) mediate the development of sensitization to ethanol (EtOH), implicating the HPA axis in this process. EtOH-induced increases in corticosterone require CRF activation of CRF, receptors. We posited that CRF, signaling pathways are crucial for EtOH-induced sensitization. We demonstrate that mice lacking CRF, receptors do not show psychomotor sensitization to ROH, a phenomenon that was also absent in CRF1 + 2 receptor double-knockout mice. Deletion of CRF2 receptors alone did not prevent sensitization. A blunted endocrine response to EtOH was found only in the genotypes showing no sensitization. The CRF, receptor antagonist CP-154,526 attenuated the acquisition and prevented the expression of EtOH-induced psychomotor sensitization. Because CRF, receptors are also activated by urocortin-1 (Ucn(1)), we tested Ucn(1) knockout mice for EtOH sensitization and found normal sensitization in this genotype. Finally, we show that the GR antagonist mifepristone does not block the expression of EtOH sensitization. CRF and CRF, receptors, therefore, are involved in the neurobiological adaptations that underlie the development and expression of psychomotor sensitization to EtOH. A CRF/CRF,mediated mechanism involving the HPA axis is proposed for acquisition, whereas an extrahypothalamic CRF/CRF, participation is suggested for expression of sensitization to EtOH. C1 [Pastor, Raul; McKinnon, Carrie S.; Scibelli, Angela C.; Burkhart-Kasch, Sue; Reed, Cheryl; Ryabinin, Andrey E.; Phillips, Tamara J.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. [Coste, Sarah C.; Stenzel-Poore, Mary P.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. [Pastor, Raul; McKinnon, Carrie S.; Scibelli, Angela C.; Burkhart-Kasch, Sue; Reed, Cheryl; Ryabinin, Andrey E.; Phillips, Tamara J.] Oregon Hlth & Sci Univ, Portland Alcohol Res Ctr, Portland, OR 97239 USA. [Phillips, Tamara J.] Portland VA Med Ctr, Res Serv, Portland, OR 97239 USA. [Pastor, Raul] Univ Jaume 1, Area Psicobiol, Castellon de La Plana 12071, Spain. RP Phillips, TJ (reprint author), Oregon Hlth & Sci Univ, Dept Behav Neurosci, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM phillipt@ohsu.edu FU NIAAA NIH HHS [R01 AA013331, P60AA010760, R01 AA013738, R01AA013738, R01AA13331, P60 AA010760]; NIMH NIH HHS [R01 MH065689, R01MH65689]; PHS HHS [UO1016647] NR 74 TC 43 Z9 43 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 JUL 1 PY 2008 VL 105 IS 26 BP 9070 EP 9075 DI 10.1073/pnas.0710181105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 322DC UT WOS:000257354400049 PM 18591672 ER PT J AU Sajatovic, M Biswas, K Kilbourne, AK Fenn, H Williford, W Bauer, MS AF Sajatovic, Martha Biswas, Kousick Kilbourne, Amy K. Fenn, Howard Williford, William Bauer, Mark S. TI Factors associated with prospective long-term treatment adherence among individuals with bipolar disorder SO PSYCHIATRIC SERVICES LA English DT Article ID SERIOUS MENTAL-ILLNESS; HEALTH BELIEF MODEL; LITHIUM TREATMENT; COLLABORATIVE CARE; DOUBLE-BLIND; NONADHERENCE; MEDICATION; PREDICTORS; RISK; PROPHYLAXIS AB Objective: Clinical characteristics, adverse effects of medication, and treatment attitudes have been associated with adherence in bipolar populations in cross-sectional studies. The aim of this secondary analysis from a larger study was to identify the association between baseline variables and average treatment adherence over a subsequent three-year period. Methods: Veterans with bipolar disorder were evaluated on self-reported adherence status at baseline and every six months over a three-year period. The sample was dichotomized into two clinically relevant categories: those who were primarily adherent and those who were primarily nonadherent. Demographic and clinical variables were examined for the two groups of patients in relation to their average adherence over the three-year period. Results: The study recruited a sample of 306 persons with severe bipolar disorder. The sample was predominantly male ( 278 men, or 91%), with a mean +/- SD age of 46.6 +/- 10.1 years. A total of 240 individuals ( 78%) were largely adherent to treatment, and 37 individuals ( 12%) were largely nonadherent to treatment. Nonadherent individuals were less likely to be on intensive somatotherapy regimens ( p=. 001); experienced more barriers to care, including lack of telephone access ( p <. 05) and life obligations and commitments ( p <. 05); and had more prior suicide attempts ( p=. 003). Conclusions: Nonadherent individuals with bipolar disorder received less intensive pharmacologic treatments, had more suicide attempts, and experienced more barriers to care than adherent individuals. Nonadherence may have system as well as patient components. Consideration of nonadherence as a function of both patient factors and system factors will enhance our ability to understand nonadherence and intervene more effectively. C1 [Sajatovic, Martha] Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. [Biswas, Kousick] Dept VA Cooperat Studies Program Coordinating Ctr, Perry Point, MD USA. [Kilbourne, Amy K.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Fenn, Howard] Stanford Univ, Palo Alto, CA 94304 USA. [Bauer, Mark S.] VA Boston Healthcare Syst, Boston, MA USA. RP Sajatovic, M (reprint author), Case Western Reserve Univ, Dept Psychiat, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM martha.sajatovic@uhhs.com RI Sajatovic, Martha/I-8001-2014 FU NCRR NIH HHS [UL1 RR024989]; NIMH NIH HHS [K23 MH 065599-01A] NR 51 TC 37 Z9 37 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JUL PY 2008 VL 59 IS 7 BP 753 EP 759 DI 10.1176/appi.ps.59.7.753 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 319YV UT WOS:000257201800010 PM 18586992 ER PT J AU Kilbourne, AM Post, EP Nossek, A Drill, L Cooley, S Bauer, MS AF Kilbourne, Amy M. Post, Edward P. Nossek, Agnes Drill, Larry Cooley, Susan Bauer, Mark S. TI Improving medical and psychiatric outcomes among individuals with bipolar disorder: A Randomized controlled trial SO PSYCHIATRIC SERVICES LA English DT Article ID QUALITY-OF-LIFE; DISEASE MANAGEMENT PROGRAMS; HEALTH-CARE UTILIZATION; SERIOUS MENTAL-ILLNESS; CARDIOVASCULAR-DISEASE; DIABETES-MELLITUS; OLDER PATIENTS; GLOBAL BURDEN; RISK-FACTORS; FOLLOW-UP AB Objectives: Comorbid medical conditions, notably cardiovascular disease, occur disproportionately among persons with bipolar disorder; yet the quality and outcomes of medical care for these individuals are suboptimal. This pilot study examined a bipolar disorder medical care model ( BCM) and determined whether, compared with usual care, individuals randomly assigned to receive BCM care had improved medical and psychiatric outcomes. Methods: Persons with bipolar disorder and cardiovascular disease-related risk factors were recruited from a large Department of Veterans Affairs mental health facility and randomly assigned to receive BCM or usual care. BCM care consisted of four self-management sessions on bipolar disorder symptom control strategies, education and behavioral change related to cardiovascular disease risk factors, and promotion of provider engagement. Primary outcomes were physical and mental health-related quality of life; secondary outcomes included functioning and bipolar symptoms. Results: Fifty-eight persons participated. Twentyseven received BCM care, and 31 received usual care. The mean +/- SD age was 55 +/- 8 years, 9% were female, 90% were white, and 10% were African American. Repeated-measures analysis was used, and significant differences were observed between the two groups in change in scores from baseline to six months for the 12-Item Short-Form Health Survey ( SF-12) subscale for physical health ( t=2.01, df= 173, p=. 04), indicating that the usual care group experienced a decline in physical health over the study period. Change in SF- 12 scores also indicated that compared with the usual care group, the BCM group showed improvements in mental health - related quality of life over the six-month study period; however, this finding was not significant. Conclusions: Compared with usual care, BCM care may have slowed the decline in physical health - related quality of life. Further studies are needed to determine whether BCM care leads to longterm positive changes in physical and mental health - related quality of life and reduced risk of cardiovascular disease among persons with bipolar disorder. C1 [Kilbourne, Amy M.; Post, Edward P.] Dept Vet Affairs, Hlth Serv Res & Dev, Serious Mental Illness Treatment Res & Educ Ctr, Ann Arbor, MI 48105 USA. [Nossek, Agnes; Drill, Larry; Cooley, Susan] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Bauer, Mark S.] VA Boston Healthcare Syst, Cambridge, MA USA. [Bauer, Mark S.] Harvard Univ, Dept Psychiat, Cambridge, MA 02138 USA. RP Kilbourne, AM (reprint author), Dept Vet Affairs, Hlth Serv Res & Dev, Serious Mental Illness Treatment Res & Educ Ctr, 2215 Fuller Rd, Ann Arbor, MI 48105 USA. EM amykilbo@umich.edu NR 52 TC 72 Z9 72 U1 4 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JUL PY 2008 VL 59 IS 7 BP 760 EP 768 DI 10.1176/appi.ps.59.7.760 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 319YV UT WOS:000257201800011 PM 18586993 ER PT J AU Zanjani, F Miller, B Turiano, N Ross, J Oslin, D AF Zanjani, Faika Miller, Bree Turiano, Nicholas Ross, Jennifer Oslin, David TI Effectiveness of telephone-based referral care management, a brief intervention to improve psychiatric treatment engagement SO PSYCHIATRIC SERVICES LA English DT Article ID BRIEF PHYSICIAN ADVICE; ALCOHOL-PROBLEMS; UNITED-STATES; USE DISORDERS; AT-RISK; DSM-IV; DEPRESSION; DRINKERS; COMORBIDITY; POPULATION AB Objective: This study examined the effectiveness of a telephone-based referral care management (TBR-CM) intervention for improving engagement in psychiatric treatment. Methods: From September 2005 to May 2006, 169 primary care patients at the Philadelphia Veterans Affairs Medical Center completed a psychiatric diagnostic interview and were identified as needing psychiatric care. From this total of eligible patients, 113 ( 67%) gave informed consent and were randomly assigned to receive either usual care or the intervention. Usual care consisted of participants' being schedule for a behavioral health care appointment, followed by a letter and reminder by telephone. The intervention group received the same, plus one or two brief motivational telephone sessions. Participant interviews and medical records provided study data. Results: Research participants were primarily African American and 22-83 years old. In the sample, 40 patients (39%) had severe depression, 40 ( 39%) had substance use problems, and 33 ( 22%) had co-occurring severe depression and substance abuse. Overall, 40 participants (70%) in the intervention group compared with 18 ( 32%) in the usual care group engaged in at least one psychiatric treatment appointment ( p <. 001). Analyses also indicated that on average the intervention group attended more appointments ( more than three) compared with the usual care group ( less than two) ( p=. 008). Conclusions: The TBR-CM intervention program was effective at improving psychiatric treatment engagement. Future research is necessary to examine effectiveness of TBR-CM in more heterogeneous and larger samples and to evaluate economic benefits versus costs of intervention delivery. C1 [Zanjani, Faika] Univ Kentucky, Dept Gerontol, Lexington, KY 40536 USA. [Miller, Bree; Ross, Jennifer; Oslin, David] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. [Turiano, Nicholas] Purdue Univ, Dept Child Dev & Family Studies, W Lafayette, IN 47907 USA. RP Zanjani, F (reprint author), Univ Kentucky, Dept Gerontol, 900 S Limestone,306B Wethington Bldg, Lexington, KY 40536 USA. EM f.zanjani@uky.edu FU NIMH NIH HHS [5 T32 MH 19931] NR 30 TC 31 Z9 31 U1 2 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JUL PY 2008 VL 59 IS 7 BP 776 EP 781 DI 10.1176/appi.ps.59.7.776 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 319YV UT WOS:000257201800013 PM 18586995 ER PT J AU Stoddard, FJ AF Stoddard, Frederick J., Jr. TI Methods for disaster mental health research SO PSYCHIATRIC SERVICES LA English DT Book Review C1 [Stoddard, Frederick J., Jr.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Stoddard, Frederick J., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Stoddard, FJ (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 1 TC 1 Z9 1 U1 2 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JUL PY 2008 VL 59 IS 7 BP 815 EP 816 DI 10.1176/appi.ps.59.7.815 PG 2 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 319YV UT WOS:000257201800025 ER PT J AU Biederman, J Petty, CR Dolan, C Hughes, S Mick, E Monuteaux, MC Faraone, SV AF Biederman, J. Petty, C. R. Dolan, C. Hughes, S. Mick, E. Monuteaux, M. C. Faraone, S. V. TI The long-term longitudinal course of oppositional defiant disorder and conduct disorder in ADHD boys: findings from a controlled 10-year prospective longitudinal follow-up study SO PSYCHOLOGICAL MEDICINE LA English DT Article DE adults; ADHD; conduct; children; oppositional ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY DISORDER; LARGE-SAMPLE; CHILDREN; CHILDHOOD; PREVALENCE; ADOLESCENCE; PREDICTORS; GENDER; AGE AB Background. A better understanding of the long-term scope and impact of the co-morbidity with oppositional defiant disorder (ODD) and conduct disorder (CD) in attention deficit hyperactivity disorder (ADHD) youth has important clinical and public health implications. Method. Subjects were assessed blindly at baseline (mean age = 10.7 years), 1-year (mean age = 11.9 years), 4-year (mean age = 14.7 years) and 10-year follow-up (mean age = 21.7 years). The subjects' lifetime diagnostic status of ADHD, ODD and CD by the 4-year follow-up were used to define four groups (Controls, ADHD, ADHD plus ODD, and ADHD plus ODD and CD). Diagnostic outcomes at the 10-year follow-up were considered positive if full criteria were met any time after the 4-year assessment (interval diagnosis). Outcomes were examined using a Kaplan-Meier survival function (persistence of ODD), logistic regression (for binary outcomes) and negative binomial regression (for count outcomes) controlling for age. Results. ODD persisted in a substantial minority of subjects at the 10-year follow-up. Independent of co-morbid CD, ODD was associated with major depression in the interval between the 4-year and the 10-year follow-up. Although ODD significantly increased the risk for CD and antisocial personality disorder, CD conferred a much larger risk for these outcomes. Furthermore, only CD was associated with significantly increased risk for psychoactive substance use disorders, smoking, and bipolar disorder. Conclusions. These longitudinal findings support and extend previously reported findings from this sample at the 4-year follow-up indicating that ODD and CD follow a divergent course. They also support previous findings that ODD heralds a compromised outcome for ADHD youth grown up independently of the co-morbidity with CD. C1 [Biederman, J.] Massachusetts Gen Hosp, Pediatr Psychopharmacol Unit, Dept Psychiat, Clin & Res Programs Pediatr Psychopharmacol & Adu, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediatr Psychopharmacol Unit, Dept Psychiat, Clin & Res Programs Pediatr Psychopharmacol & Adu, 55 Fruit St,YAW 6A-6900, Boston, MA 02114 USA. EM jbiederman@partners.org OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH 41314-07] NR 40 TC 93 Z9 97 U1 3 U2 26 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JUL PY 2008 VL 38 IS 7 BP 1027 EP 1036 DI 10.1017/S0033291707002668 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 324GP UT WOS:000257506100013 PM 18205967 ER PT J AU Biederman, J Makris, N Valera, EM Monuteaux, MC Goldstein, JM Buka, S Boriel, DL Bandyopadhyay, S Kennedy, DN Caviness, VS Bush, G Aleardi, M Hammerness, P Faraone, SV Seidman, LJ AF Biederman, J. Makris, N. Valera, E. M. Monuteaux, M. C. Goldstein, J. M. Buka, S. Boriel, D. L. Bandyopadhyay, S. Kennedy, D. N. Caviness, V. S. Bush, G. Aleardi, M. Hammerness, P. Faraone, S. V. Seidman, L. J. TI Towards further understanding of the co-morbidity between attention deficit hyperactivity disorder and bipolar disorder: a MRI study of brain volumes SO PSYCHOLOGICAL MEDICINE LA English DT Article DE ADHD; bipolar disorder; co-morbidity; MRI ID CEREBRAL WHITE-MATTER; DEFICIT/HYPERACTIVITY DISORDER; TOPOGRAPHIC PARCELLATION; FUNCTIONAL NEUROANATOMY; CORTICAL ABNORMALITIES; MORPHOMETRIC-ANALYSIS; PREFRONTAL CORTEX; FAMILIAL SUBTYPE; MOOD DISORDERS; RESONANCE AB Background. Although attention deficit hyperactivity disorder (ADHD) and bipolar disorder (BPD) co-occur frequently and represent a particularly morbid clinical form of both disorders, neuroimaging research addressing this co-morbidity is scarce. Our aim was to evaluate the morphometric magnetic resonance imaging (MRI) underpinnings of the co-morbidity of ADHD with BPD, testing the hypothesis that subjects with this co-morbidity would have neuro-anatomical correlates of both disorders. Method. Morphometric MRI findings were compared between 31 adults with ADHD and BPD and with those of 18 with BPD, 26 with ADHD, and 23 healthy controls. The volumes (cm(3)) of our regions of interest (ROIs) were estimated as a function of ADHD status, BPD status, age, sex, and omnibus brain volume using linear regression models. Results. When BPD was associated with a significantly smaller orbital prefrontal cortex and larger right thalamus, this pattern was found in co-morbid subjects with ADHD plus BPD. Likewise, when ADHD was associated with significantly less neocortical gray matter, less overall frontal lobe and superior prefrontal cortex volumes, a smaller right anterior cingulate cortex and less cerebellar gray matter, so did co-morbid ADHD plus BPD subjects. Conclusions. Our results support the hypothesis that ADHD and BPD independently contribute to volumetric alterations of selective and distinct brain structures. In the co-morbid state of ADHD plus BPD, the profile of brain volumetric abnormalities consists of structures that are altered in both disorders individually. Attention to co-morbidity is necessary to help clarify the heterogeneous neuroanatomy of both BPD and ADHD. C1 [Biederman, J.; Makris, N.; Valera, E. M.; Monuteaux, M. C.; Goldstein, J. M.; Buka, S.; Boriel, D. L.; Bandyopadhyay, S.; Kennedy, D. N.; Caviness, V. S.; Bush, G.; Aleardi, M.; Hammerness, P.; Faraone, S. V.; Seidman, L. J.] Massachusetts Gen Hosp, Dept Psychiat, Clin & Res Program Pediatr Psychopharmacol, Boston, MA 02114 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Clin & Res Program Pediatr Psychopharmacol, Fruit St,Warren 7, Boston, MA 02114 USA. EM jbiederman@partners.org RI Kennedy, David/H-3627-2012; Buka, Stephen/H-7335-2014; OI Buka, Stephen/0000-0002-8578-9308; Faraone, Stephen/0000-0002-9217-3982 FU NCRR NIH HHS [P41 RR 14075]; NICHD NIH HHS [MH/HD 62152]; NIMH NIH HHS [F32 MH 065040-01A1, MH 16259, MH 56956, MH 57934, MH 63951] NR 56 TC 50 Z9 52 U1 2 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JUL PY 2008 VL 38 IS 7 BP 1045 EP 1056 DI 10.1017/S0033291707001791 PG 12 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 324GP UT WOS:000257506100015 PM 17935640 ER PT J AU Jubelt, LE Barr, RS Goff, DC Logvinenko, T Weiss, AP Evins, AE AF Jubelt, Lindsay E. Barr, Ruth S. Goff, Donald C. Logvinenko, Tanya Weiss, Anthony P. Evins, A. Eden TI Effects of transdermal nicotine on episodic memory in non-smokers with and without schizophrenia SO PSYCHOPHARMACOLOGY LA English DT Article DE nicotine; memory; inhibitory control; novelty detection; false alarm; impulsivity; schizophrenia; acetylcholine ID COGNITIVE FUNCTION; CIGARETTE-SMOKING; DISCRIMINATION ACCURACY; NONPSYCHIATRIC CONTROLS; ATTENTIONAL DEFICITS; PREPULSE INHIBITION; RETRIEVAL-PROCESSES; DIVIDED ATTENTION; ACOUSTIC STARTLE; WORKING-MEMORY AB Rationale Nicotinic agonists may improve attention and memory in humans and may ameliorate some cognitive deficits associated with neuropsychiatric disorders such as schizophrenia. Materials and methods We investigated the effects of a single dose of nicotine on episodic memory performance in 10 adults with schizophrenia and 12 healthy controls. Participants were nonsmokers in order to avoid confounding effects of nicotine withdrawal and reinstatement on memory. At each of two study visits, participants performed a test of episodic memory before and 4 h after application of a 14-mg transdermal nicotine ( or identical placebo) patch in counterbalanced order. Results Compared with placebo, nicotine treatment was associated with more rapid and accurate recognition of novel items. There was a trend for a treatment by diagnosis interaction, such that the effect of nicotine to reduce false alarms was stronger in the schizophrenia than the control group. There was no effect of nicotine on accuracy or reaction time for identification of previously viewed items. Conclusions These data suggest that nicotine improves novelty detection in non-smokers, an effect that may be more pronounced in non-smokers with schizophrenia. Because memory deficits are associated with functional impairment in schizophrenia and because impaired novelty detection has been linked to the positive symptoms of schizophrenia, study of the effects of chronic nicotinic agonist treatment on novelty detection may be warranted. C1 [Evins, A. Eden] MGH Ctr Addict Med, Boston, MA 02114 USA. [Jubelt, Lindsay E.; Barr, Ruth S.; Goff, Donald C.; Weiss, Anthony P.; Evins, A. Eden] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Logvinenko, Tanya] Massachusetts Gen Hosp, Div Biostat, Boston, MA 02114 USA. [Barr, Ruth S.; Goff, Donald C.; Logvinenko, Tanya; Weiss, Anthony P.; Evins, A. Eden] Harvard Univ, Sch Med, Boston, MA USA. RP Evins, AE (reprint author), MGH Ctr Addict Med, 60 Staniford St, Boston, MA 02114 USA. EM a_eden_evins@hms.harvard.edu FU NIDA NIH HHS [1K23DA00510-01, K23 DA000510, K24 DA030443, U01 DA019378]; NIMH NIH HHS [K23 MH06019] NR 79 TC 50 Z9 50 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 2008 VL 199 IS 1 BP 89 EP 98 DI 10.1007/s00213-008-1133-8 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 322NQ UT WOS:000257383000009 PM 18548234 ER PT J AU Repper-DeLisi, J Stern, TA Mitchell, M Lussier-Cushing, M Lakatos, B Fricchione, GL Quinlan, J Kane, M Berube, R Blais, M Capasso, V Pathan, F Karson, A Bierer, M AF Repper-DeLisi, Jennifer Stern, Theodore A. Mitchell, Monique Lussier-Cushing, Mary Lakatos, Barbara Fricchione, Gregory L. Quinlan, Joan Kane, Martha Berube, Rhodes Blais, Mark Capasso, Virginia Pathan, Firdosh Karson, Andrew Bierer, Michael TI Successful implementation of an alcohol-withdrawal pathway in a general hospital SO PSYCHOSOMATICS LA English DT Article ID CARE; INTERVENTION; MANAGEMENT; INPATIENTS; PATIENT; TRIAL AB Background: Although alcohol use and abuse are common among general-hospital inpatients, many patients are inadequately assessed and treated for alcohol withdrawal. Objective: The purpose of this study was to determine whether the implementation of a clinical pathway for the treatment of alcohol withdrawal in medical inpatients would result in improvements in clinical practice and patient outcomes. Method: Authors retrospectively reviewed 80 patient records (including 40 of those treated before the implementation of a pathway and 40 of those treated after pathway implementation). Results: Assessment procedures and ordering patterns of physicians (medical house staff and staff physicians) shifted in a fashion consistent with the new treatment guidelines. Patient outcomes (e.g., length of stay and the incidence of delirium) improved for those patients who received benzodiazepines within the range of the pathway guidelines. Conclusions: Timely assessment and staff education can shift prescription patterns, increase patient monitoring, and reduce costs associated with alcohol withdrawal. C1 [Repper-DeLisi, Jennifer] Massachusetts Gen Hosp, Dept Nursing, Boston, MA 02114 USA. RP Repper-DeLisi, J (reprint author), Massachusetts Gen Hosp, Dept Nursing, Blake 11, Boston, MA 02114 USA. EM jrepperdelisi@partners.org NR 22 TC 10 Z9 10 U1 0 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JUL PY 2008 VL 49 IS 4 BP 292 EP 299 DI 10.1176/appi.psy.49.4.292 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 353TD UT WOS:000259590200003 PM 18621934 ER PT J AU Huffman, JC Smith, FA Blais, MA Taylor, AM Januzzi, JL Fricchione, GL AF Huffman, Jeff C. Smith, Felicia A. Blais, Mark A. Taylor, Amy M. Januzzi, James L. Fricchione, Gregory L. TI Pre-existing major depression predicts in-hospital cardiac complications after acute myocardial infarction SO PSYCHOSOMATICS LA English DT Article ID ISCHEMIC-HEART-DISEASE; SOCIAL SUPPORT; ANXIETY; MORTALITY; SYMPTOMS; EVENTS; RISK; ANTIDEPRESSANT; ASSOCIATION; PERSISTENCE AB Background: Depression (MDD) and anxiety have been associated with negative long-term outcomes among patients with acute myocardial infarction (MI). Objective: The objective of the study was to determine whether MDD and anxiety preceding MI were associated with in-hospital post-MI cardiac complications. Method: Subjects (N = 129) underwent psychiatric interviews within 72 hours of MI and were evaluated for five in-hospital cardiac complications (recurrent ischemia, ventricular arrhythmia, ventricular arrhythmia requiring intervention, congestive heart failure, and reinfarction). Results: Current (pre-MI) MDD was a significant and independent predictor of all complications except recurrent ischemia on multivariate regression analysis. In contrast, pre-MI anxiety was not associated with complications. Conclusion: These findings underscore the importance of identifying and treating MDD in post-MI patients and those at risk for MI. C1 [Huffman, Jeff C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St Warren 1220C, Boston, MA 02114 USA. EM jhuffman@partners.org FU Kaplen Fellowship Award Grant; Livingston Fellowship Award Grant FX This study was supported by the Kaplen Fellowship Award Grant and the Livingston Fellowship Award Grant, both through Harvard Medical School, Boston, MA. NR 39 TC 22 Z9 22 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JUL PY 2008 VL 49 IS 4 BP 309 EP 316 DI 10.1176/appi.psy.49.4.309 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 353TD UT WOS:000259590200005 PM 18621936 ER PT J AU Eneli, IU Keast, DR Rappley, MD Camargo, CA AF Eneli, Ihuoma U. Keast, Debra R. Rappley, Marsha D. Camargo, Carlos A., Jr. TI Adequacy of two ambulatory care surveillance systems for tracking childhood obesity practice patterns SO PUBLIC HEALTH LA English DT Article DE obesity; children; surveillance; treatment ID ADOLESCENT OBESITY; NATIONAL-HEALTH; UNITED-STATES; RISK-FACTORS; CHILDREN; OVERWEIGHT; PREVALENCE; MANAGEMENT; PRACTITIONERS; PROFESSIONALS AB Background: The National Ambulatory Medical Care Surveys (NAMCS) and National Hospital Ambulatory Medical Care Surveys (NHAMCS) are surveillance systems in the USA that track provider practice patterns at ambulatory care visits. This study investigated the adequacy of the NAMCS/NHAMCS for surveillance of childhood obesity practice patterns. Methods: The frequency of obesity visits in the 1997-2000 NAMCS/NHAMCS (outpatient component) was compared with obesity prevalence among children who reported a physician visit in the preceding 12 months in the National Health and Nutrition Examination Survey (NHANES) 1999-2000. Obesity was identified using the International Classification of Diseases 9th revision clinical modification code ICD-9-278.0 in the NAMCS/NHAMCS. For the NHANES, age- and gender-specific body mass index >95th percentile was used. Results: Between 1997 and 2000, obesity was identified in 4.1 million (0.8%) of 516 million ambulatory care visits. With an obesity prevalence of 14.2% from the NHANES survey, NAMCS/NHAMCS only identified 5.6% of all children aged 2-17 years >95th percentile. Of those identified, the rate of obesity visits in the NAMCS/NHAMCS was lowest for non-Hispanic Whites (3.9%) compared with non-Hispanic Blacks (6.9%) and Hispanics (10.2%). Conclusion: The very infrequent reporting of obesity in the NAMCS/NHAMCS suggests that these surveillance systems do not reflect how healthcare providers identify and care for overweight children. Collecting weight and height measures would improve their utility in tracking identification and management of overweight children. (C) 2007 The Royal Institute of Public Health. Published by Elsevier Ltd. All rights reserved. C1 [Eneli, Ihuoma U.] Ohio State Univ, Columbus Childrens Hosp, Dept Pediat, Ctr Healthy Weight & Nutr, Columbus, OH 43205 USA. [Keast, Debra R.] Food & Nutr Database Res Consulting, Okemos, MI 48864 USA. [Rappley, Marsha D.] Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Eneli, IU (reprint author), Ohio State Univ, Columbus Childrens Hosp, Dept Pediat, Ctr Healthy Weight & Nutr, 700 Columbus Childrens Dr, Columbus, OH 43205 USA. EM enelii@pediatrics-ohio.state.edu RI Eneli, Ihuoma/E-3031-2011 FU NIDDK NIH HHS [P30 DK040561-13, P30 DK040561] NR 35 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0033-3506 J9 PUBLIC HEALTH JI Public Health PD JUL PY 2008 VL 122 IS 7 BP 700 EP 707 DI 10.1016/j.puhe.2007.10.001 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 325YU UT WOS:000257625900012 PM 18313702 ER PT J AU Bogart, LM Howerton, D Lange, J Becker, K Setodji, CM Asch, SM AF Bogart, Laura M. Howerton, Devery Lange, James Becker, Kirsten Setodji, Claude Mfssan Asch, Steven M. TI Scope of in rapid HIV testing in urban US hospitals SO PUBLIC HEALTH REPORTS LA English DT Article ID NATIONAL PROBABILITY SAMPLES; HUMAN-IMMUNODEFICIENCY-VIRUS; LOW-PREVALENCE DISEASES; HEALTH-CARE SETTINGS; EMERGENCY-DEPARTMENT; REVISED RECOMMENDATIONS; SERVICES UTILIZATION; RANDOMIZED-TRIAL; EXPERIENCE; ROUTINE AB Objective. The present study examined the scope of rapid human immunodeficiency virus (HIV) testing in urban U.S. hospitals. Methods. In a multistage national probability sample, 12 primary metropolitan statistical areas (three per region) were sampled randomly, with weights proportionate to acquired immunodeficiency syndrome (AIDS) populations. All 671 eligible hospitals within areas were selected. Laboratory staff from 584 hospitals (87%) were interviewed by telephone in 2005. Results. About 52% reported rapid HIV test availability (50% in occupational health, 29% in labor and delivery, and 13% in emergency department/urgent care), and 86% of hospitals offering rapid tests processed them in the laboratory. In multivariate models, rapid test availability was more likely in hospitals serving more patients, and located in high-poverty, high-AIDS prevalence areas, and in the South or Midwest vs. West. It was less likely in hospitals serving areas with large percentages of people who were black/African American or Hispanic/Latino (p<0.05). Conclusions. Rapid HIV testing is increasing across urban U.S. hospitals, primarily for occupational exposure and in hospitals with greater resources and need. To achieve routine HIV screening, policies should encourage greater breadth of diffusion of rapid testing at the point of care, especially in smaller facilities, the West, and communities with racial/ethnic diversity. C1 [Bogart, Laura M.; Becker, Kirsten; Setodji, Claude Mfssan; Asch, Steven M.] RAND Corp, Santa Monica, CA 90407 USA. [Howerton, Devery; Lange, James] Ctr Dis Control & Prevent, Lab Practice Evaluat & Genom Branch, Atlanta, GA USA. [Asch, Steven M.] Vet Affairs Greater Los Angeles Healthcare, Los Angeles, CA USA. [Asch, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Bogart, LM (reprint author), RAND Corp, 1776 Main St,POB 2138, Santa Monica, CA 90407 USA. EM lbogart@rand.org FU NCCDPHP CDC HHS [U48 DP000056, U48/DP000056]; ODCDC CDC HHS [U65/CCU924523-01] NR 52 TC 11 Z9 11 U1 3 U2 4 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1101 15TH ST NW, STE 910, WASHINGTON, DC 20005 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JUL-AUG PY 2008 VL 123 IS 4 BP 494 EP 503 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 310ZX UT WOS:000256570700013 PM 18763412 ER PT J AU Ellis, C Egede, LE AF Ellis, Charles Egede, Leonard E. TI Ethnic disparities in stroke recognition in individuals with prior stroke SO PUBLIC HEALTH REPORTS LA English DT Article ID AMERICAN-HEART-ASSOCIATION; RISK-FACTOR SURVEY; WARNING SIGNS; HEALTH-CARE; EMERGENCY-DEPARTMENT; KNOWLEDGE; AWARENESS; DELAY; SYMPTOMS; TIME AB Objective. Studies of stroke awareness suggest that knowledge of early warning signs of stroke is low in high-risk groups. However, little is known about stroke knowledge among individuals with a history of prior stroke who are at significant risk for recurrent stroke. Methods. Data from 2,970 adults with a history of prior stroke from the 2003 Behavioral Risk Factor Surveillance System were examined. Recognition of the five warning signs of stroke and appropriate action to call 911 was compared across three racial/ethnic groups: non-Hispanic white, non-Hispanic black, and Hispanic/other. Multiple logistic regression analyses were used to: (1) determine the association between race/ethnicity and recognition of multiple stroke signs and appropriate first action and (2) identify independent correlates of recognition of multiple stroke signs and taking appropriate action to seek treatment among individuals with prior stroke. Results. Recognition of all five signs of stroke and taking appropriate action to call 911 was lowest among the non-Hispanic black group (22.3%) and Hispanic/other group (16.7%). In multivariate models, Hispanic/other (odds ratio [OR) 0.42 [0.25, 0.71]), age 50-64 (OR 0.64 [0.43, 0.971), age >= 65 (OR 0.36 [0.23, 0.551), and >high school education (OR 1.79 [1.22, 2.63]) emerged as independent correlates of recognition of all five signs of stroke and first action to call 911. Conclusions. Less than 35% of people with prior stroke can distinguish the complex symptom profile of a stroke and take appropriate action to call 911. Targeted educational activities that are sensitive to differences in race/ethnicity, age, and education levels are needed for individuals with prior stroke. C1 [Egede, Leonard E.] Med Univ S Carolina, Dept Med, Ctr Hlth Disparities Res, Charleston, SC 29425 USA. [Ellis, Charles] Med Univ S Carolina, Dept Rehabil Sci, Charleston, SC 29425 USA. [Egede, Leonard E.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Egede, LE (reprint author), Med Univ S Carolina, Dept Med, Ctr Hlth Disparities Res, 135 Rutledge Ave,Rm 280H, Charleston, SC 29425 USA. EM egedel@musc.edu NR 33 TC 11 Z9 12 U1 0 U2 0 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1101 15TH ST NW, STE 910, WASHINGTON, DC 20005 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JUL-AUG PY 2008 VL 123 IS 4 BP 514 EP 522 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 310ZX UT WOS:000256570700015 PM 18763414 ER PT J AU Kiger, JL Kiger, WS Riley, KJ Binns, PJ Patel, H Hopewell, JW Harling, OK Busse, PM Coderre, JA AF Kiger, Jingli Liu Kiger, W. S., III Riley, Kent J. Binns, Peter J. Patel, Hemant Hopewell, John W. Harling, Otto K. Busse, Paul M. Coderre, Jeffrey A. TI Functional and histological changes in rat lung after boron neutron capture therapy SO RADIATION RESEARCH LA English DT Article ID I CLINICAL-TRIAL; RADIATION-THERAPY; MOUSE LUNG; X-RAYS; P-BORONOPHENYLALANINE; IRRADIATION; BEAM; REPAIR; PNEUMONITIS; TOLERANCE AB The motivation for this work was an unexpected occurrence of lung side effects in two human subjects undergoing cranial boron neutron capture therapy (BNCT). The objectives were to determine experimentally the biological weighting factors in rat lung for the high-LET dose components for a retrospective assessment of the dose to human lung during cranial BNCT. Lung damage after whole-thorax irradiation was assessed by serial measurement of breathing rate and evaluation of terminal lung histology. A positive response was defined as a breathing rate 20% above the control group mean and categorized as occurring either early (<110 days) or late (>110 days). The ED50 values derived from probit analyses of the early breathing rate dose-response data for X rays and neutrons were 11.4 +/- 0.4 and 9.2 +/- 0.6 Gy, respectively, and were similar for the other end points. The ED50 values for irradiation with neutrons plus p-boronophenylalanine were 8.7 +/- 1.0 and 6.7 +/- 0.4 for the early and late breathing rate responses, respectively, and 7.0 +/- 0.5 Gy for the histological response. The RBEs for thermal neutrons ranged between 2.9 +/- 0.7 and 3.1 +/- 1.2 for all end points. The weighting factors for the boron component of the dose differed significantly between the early (1.4 +/- 0.3) and late (2.3 +/- 0.3) breathing rate end points. A reassessment of doses in patients during cranial BNCT confirmed that the maximum weighted doses were well below the threshold for the onset of pneumonitis in healthy human lung. (C) 2008 by Radiation Research Society. C1 [Kiger, Jingli Liu; Harling, Otto K.; Coderre, Jeffrey A.] Harvard Univ, MIT, Dept Nucl Sci & Engn, Cambridge, MA 02139 USA. [Riley, Kent J.; Binns, Peter J.] Harvard Univ, MIT, Nucl Reactor Lab, Cambridge, MA 02139 USA. [Kiger, W. S., III] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02115 USA. [Hopewell, John W.] Churchill Hosp, Dept Clin Oncol, Oxford OX3 7LJ, England. [Busse, Paul M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Coderre, JA (reprint author), Harvard Univ, MIT, Dept Nucl Sci & Engn, Cambridge, MA 02139 USA. EM coderre@mit.edu NR 43 TC 12 Z9 13 U1 0 U2 1 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUL PY 2008 VL 170 IS 1 BP 60 EP 69 DI 10.1667/RR1266.1 PG 10 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 321IN UT WOS:000257298100007 PM 18582158 ER PT J AU Kalva, SP Mueller, PR AF Kalva, Sanjeeva P. Mueller, Peter R. TI Vascular Imaging in the Elderly SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Geriatrics; Atherosclerosis; Peripheral arterial disease; Renovascular disease; Carotid artery stenosis; Venous thromboembolism; Segmental arterial mediolysis; Giant cell arteritis; Varicose veins ID RENAL-ARTERY STENOSIS; DIGITAL-SUBTRACTION-ANGIOGRAPHY; MAGNETIC-RESONANCE ANGIOGRAPHY; ROW CT ANGIOGRAPHY; COMPUTED-TOMOGRAPHY ANGIOGRAPHY; SYMPTOMATIC CAROTID STENOSIS; COLOR DUPLEX ULTRASONOGRAPHY; ENHANCED MR-ANGIOGRAPHY; RENOVASCULAR HYPERTENSION; LOWER-EXTREMITY AB Though a myriad of vascular conditions affect the elderly, atherosclerosis remains the most common vascular disorder, followed by venous thromboembolism and varicose veins. In this article, the authors discuss the imaging of atherosclerosis affecting various vascular territories and pay special attention to the elderly population. The authors also discuss imaging findings of segmental arterial mediolysis, giant cell arteritis, and venous thromboembolism. C1 [Kalva, Sanjeeva P.] Massachusetts Gen Hosp, Dept Radiol, Div Cardiovasc Imaging & Intervent, Boston, MA 02114 USA. [Kalva, Sanjeeva P.; Mueller, Peter R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Mueller, Peter R.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Kalva, SP (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Cardiovasc Imaging & Intervent, GRB 290,MGH,55 Fruit St, Boston, MA 02114 USA. EM skalva@partners.org NR 73 TC 1 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JUL PY 2008 VL 46 IS 4 BP 663 EP + DI 10.1016/j.rcl.2008.04.009 PG 22 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 366BU UT WOS:000260455900004 PM 18922287 ER PT J AU Pomerantz, SR AF Pomerantz, Stuart R. TI Net assets: RSS to the rescue SO RADIOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dept Neuroradiol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Pomerantz, SR (reprint author), Harvard Univ, Sch Med, Dept Neuroradiol, Massachusetts Gen Hosp, 55 Fruit St,Gray 2-B285, Boston, MA 02114 USA. EM spomerantz@partners.org NR 1 TC 4 Z9 4 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 2008 VL 248 IS 1 BP 16 EP 19 DI 10.1148/radiol.2481080709 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 316VX UT WOS:000256978900005 PM 18566167 ER PT J AU Pandharipande, PV Gervais, DA Mueller, PR Hur, C Gazelle, GS AF Pandharipande, Pari V. Gervais, Debra A. Mueller, Peter R. Hur, Chin Gazelle, G. Scott TI Radiofrequency ablation versus nephron-sparing surgery for small unilateral renal cell carcinoma: Cost-effectiveness analysis SO RADIOLOGY LA English DT Article ID WILLINGNESS-TO-PAY; RADIO-FREQUENCY ABLATION; ADJUSTED LIFE YEAR; PARTIAL NEPHRECTOMY; CONVENIENT APPROXIMATION; RISING INCIDENCE; UNITED-STATES; 100 TUMORS; FOLLOW-UP; HEALTH AB Purpose: To evaluate the relative cost-effectiveness of percutaneous radiofrequency (RF) ablation versus nephron-sparing surgery (NSS) in patients with small (<= 4-cm) renal cell carcinoma (RCC), given a commonly accepted level of societal willingness to pay. Materials and Methods: A decision-analytic Markov model was developed to estimate life expectancy and lifetime costs for 65-year-old patients with a small RCC treated with RF ablation or NSS. The model incorporated RCC presence, treatment effectiveness and costs, and short- and long-term outcomes. An incremental cost-effectiveness analysis was performed to identify treatment preference under an assumed $75 000 per quality-adjusted life-year (QALY) societal willingness-to-pay threshold level, within proposed ranges for guiding implementation of new health care interventions. The effect of changes in key parameters on strategy preference was addressed in sensitivity analysis. Results: By using base-case assumptions, NSS yielded a minimally greater average quality-adjusted life expectancy than did RF ablation (2.5 days) but was more expensive. NSS had an incremental cost-effectiveness ratio of $1 152 529 per QALY relative to RF ablation, greatly exceeding $75 000 per QALY. Therefore, RF ablation was considered preferred and remained so if the annual probability of post-RF ablation local recurrence was up to 48% higher relative to that post-NSS. NSS preference required an estimated NSS cost reduction of $7500 or RF ablation cost increase of $6229. Results were robust to changes in most model parameters, but treatment preference was dependent on the relative probabilities of local recurrence after RF ablation and NSS, the short- term costs of both, and quality of life after NSS. Conclusion: RF ablation was preferred over NSS for small RCC treatment at a societal willingness-to-pay threshold level of $75 000 per QALY. This result was robust to changes in most model parameters, but somewhat dependent on the relative probabilities of post-RF ablation and post-NSS local recurrence, NSS and RF ablation short- term costs, and post-NSS quality of life, factors which merit further primary investigation. (c) RSNA, 2008. C1 [Pandharipande, Pari V.; Gervais, Debra A.; Mueller, Peter R.; Hur, Chin; Gazelle, G. Scott] Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Boston, MA 02114 USA. RP Pandharipande, PV (reprint author), Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM pari@mgh-ita.org FU NCI NIH HHS [R25 CA 92203, R25 CA092203] NR 50 TC 30 Z9 31 U1 1 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 2008 VL 248 IS 1 BP 169 EP 178 DI 10.1148/radiol.2481071448 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 316VX UT WOS:000256978900019 PM 18458248 ER PT J AU McMahon, PM Kong, CY Johnson, BE Weinstein, MC Weeks, JC Kuntz, KM Shepard, JAO Swensen, SJ Gazelle, GS AF McMahon, Pamela M. Kong, Chung Yin Johnson, Bruce E. Weinstein, Milton C. Weeks, Jane C. Kuntz, Karen M. Shepard, Jo-Anne O. Swensen, Stephen J. Gazelle, G. Scott TI Estimating long-term effectiveness of lung cancer screening in the Mayo CT screening study SO RADIOLOGY LA English DT Article ID COST-EFFECTIVENESS ANALYSIS; SPIRAL COMPUTED-TOMOGRAPHY; FOLLOW-UP; DECISION-ANALYSIS; ACTION PROJECT; ADULT SMOKERS; SMOKING; MORTALITY; OVERDIAGNOSIS; EXPERIENCE AB Purpose: To use individual-level data provided from the single-arm study of helical computed tomographic (CT) screening at the Mayo Clinic (Rochester, Minn) to estimate the long-term effectiveness of screening in Mayo study participants and to compare estimates from an existing lung cancer simulation model with estimates from a different modeling approach that used the same data. Materials and Methods: The study was approved by institutional review boards and was HIPAA compliant. Deidentified individual-level data from participants (1520 current or former smokers aged 50-85 years) in the Mayo Clinic helical CT screening study were used to populate the Lung Cancer Policy Model, a comprehensive microsimulation model of lung cancer development, screening findings, treatment results, and long-term outcomes. The model predicted diagnosed cases of lung cancer and deaths per simulated study arm (five annual screening examinations vs no screening). Main outcome measures were predicted changes in lung cancer specific and all-cause mortality as functions of follow-up time after simulated enrollment and randomization. Results: At 6-year follow-up, the screening arm had an estimated 37% relative increase in lung cancer detection, compared with the control arm. At 15-year follow-up, five annual screening examinations yielded a 9% relative increase in lung cancer detection. The relative reduction in cumulative lung cancer-specific mortality from five annual screening examinations was 28% at 6-year follow-up (15% at 15 years). The relative reduction in cumulative all-cause mortality from five annual screening examinations was 4% at 6-year follow-up (2% at 15 years). Conclusion: Screening may reduce lung cancer-specific mortality but may offer a smaller reduction in overall mortality because of increased competing mortality risks associated with smoking. C1 [McMahon, Pamela M.; Kong, Chung Yin; Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [McMahon, Pamela M.; Kong, Chung Yin; Shepard, Jo-Anne O.; Gazelle, G. Scott] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Johnson, Bruce E.; Weinstein, Milton C.; Weeks, Jane C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Johnson, Bruce E.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Weeks, Jane C.] Dana Farber Canc Inst, Dept Med Oncol Populat Sci, Boston, MA 02115 USA. [Weinstein, Milton C.; Kuntz, Karen M.; Gazelle, G. Scott] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Univ Minnesota, Sch Publ Hlth, Dept Hlth Policy & Management, Minneapolis, MN USA. [Swensen, Stephen J.] Mayo Clin, Dept Radiol, Rochester, MN USA. RP McMahon, PM (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM pamela@mgh-ita.org FU NCI NIH HHS [K99 CA126147, R01 CA97337] NR 57 TC 58 Z9 63 U1 0 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 2008 VL 248 IS 1 BP 278 EP 287 DI 10.1148/radiol.2481071446 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 316VX UT WOS:000256978900032 PM 18458247 ER PT J AU Carnargo, CA Tsai, CL Clark, S Kenney, PA Radeos, MS AF Carnargo, Carlos A., Jr. Tsai, Chu-Lin Clark, Sunday Kenney, Patrick A. Radeos, Michael S. TI Spirometric correlates of dyspnea improvement among emergency department patients with chronic obstructive pulmonary disease exacerbation SO RESPIRATORY CARE LA English DT Article DE chronic obstructive pulmonary disease; COPD; dyspnea; emergency department; exacerbation; slow vital capacity; spirometry ID QUALITY-OF-LIFE; EXERCISE PERFORMANCE; HYPERINFLATION; BREATHLESSNESS; INTOLERANCE; RECOVERY AB OBJECTIVE: To examine whether change in slow vital capacity (SVC) correlates to dyspnea improvement during emergency department (ED) treatment of chronic obstructive pulmonary disease (COPD) exacerbation. METHODS: We performed a prospective cohort study and enrolled consecutive patients during a 3-week period. ED patients : 55 years old with COPD exacerbation were asked to perform bedside spirometry shortly after ED arrival and again at discharge. SVC was measured first, then forced expiratory volume in the first second (FEVj), peak expiratory flow (PEF), and forced vital capacity (FVC). Concurrent with spirometry, patients rated their dyspnea on a 10-cm visual analogue scale. RESULTS: Thirty-six patients were enrolled. The median ED stay was 271 min (interquartile range 219-370 min). Seventy-one percent of the patients reported dyspnea improvement during their ED stay. Change in SVC was significantly higher among the patients whose dyspnea improved than among those whose did not (median increase of 0.15 L vs median decrease of 0.25 L, respectively, p < 0.01). By contrast, the change in spirometry values were similar for FEV1, PEF, and FVC (all p > 0.30). Spearman correlation supported these findings: SVC r = 0.45 (p = 0.02) versus nonsignificant correlation with FEV, (r = 0.33), PEF (r = -0.22), and FVC (r = 0.35). CONCLUSIONS: Increase in SVC significantly correlated with dyspnea improvement among ED patients with moderate-to-severe COPD exacerbation. Change in SVC merits consideration when evaluating therapeutic response during COPD exacerbation. C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Carnargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org OI TSAI, CHU-LIN/0000-0003-4639-1513 NR 27 TC 0 Z9 0 U1 1 U2 1 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD JUL PY 2008 VL 53 IS 7 BP 892 EP 896 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 327LB UT WOS:000257729500007 ER PT J AU Cruz-Gonzalez, I Solis, J Inglessis-Azuaje, I Palacios, IF AF Cruz-Gonzalez, Ignacio Solis, Jorge Inglessis-Azuaje, Ignacio Palacios, Igor F. TI Patent foramen ovale: current state of the art SO REVISTA ESPANOLA DE CARDIOLOGIA LA Spanish DT Review DE patent foramen ovale; treatment; cryptogenic stroke; migraine ID ATRIAL SEPTAL ANEURYSM; TO-LEFT SHUNT; CEREBRAL ISCHEMIC EVENTS; TRANSCATHETER CLOSURE; PARADOXICAL EMBOLISM; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; CRYPTOGENIC STROKE; TRANSTHORACIC ECHOCARDIOGRAPHY; PLATYPNEA-ORTHODEOXIA; TRANSCRANIAL DOPPLER AB Patent foramen ovale is a congenital cardiac lesion that persists into adulthood and which is present in over 25% of the adult population. Its diagnosis, evaluation and treatment have attracted increasing interest as it has been suggested that it may be associated with various pathologic conditions, such as cryptogenic stroke, platypnea-orthodeoxia syndrome, decompression sickness and migraine. However, data on these associations are contradictory. Similarly, the optimum treatment of patients with patent foramen ovale is still debated. This article contains a review of the anatomy, embryology and epidemiology of the condition, its association with other clinical disorders, and current therapeutic options. C1 [Cruz-Gonzalez, Ignacio; Solis, Jorge; Inglessis-Azuaje, Ignacio; Palacios, Igor F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Cruz-Gonzalez, I (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Gray Bigelow 800,55 Fruit St, Boston, MA 02114 USA. EM i-cruz@secardiologia.es RI 2008, Ibsal/A-1268-2012 NR 97 TC 21 Z9 29 U1 0 U2 4 PU EDICIONES DOYMA S A PI BARCELONA PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN SN 0300-8932 J9 REV ESP CARDIOL JI Rev. Esp. Cardiol. PD JUL PY 2008 VL 61 IS 7 BP 738 EP 751 DI 10.1016/S1885-5857(08)60211-X PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 320FJ UT WOS:000257218800010 PM 18590647 ER PT J AU Wynn, JK Lee, J Horan, WP Green, MF AF Wynn, Jonathan K. Lee, Junghee Horan, William P. Green, Michael F. TI Using event related potentials to explore stages of facial affect recognition deficits in schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Article DE face processing; emotion identification; ERP ID VISUAL-EVOKED-POTENTIALS; SOCIAL COGNITION INFLUENCE; NEUROCOGNITIVE DEFICITS; EMOTION RECOGNITION; BIPOLAR DISORDER; FACE PERCEPTION; N170; BRAIN; LOCALIZATION; IMPAIRMENTS AB Schizophrenia patients show impairments in identifying facial affect; however, it is not known at what stage facial affect processing is impaired. We evaluated 3 event-related potentials (ERPs) to explore stages of facial affect processing in schizophrenia patients. Twenty-six schizophrenia patients and 27 normal controls participated. In separate blocks, subjects identified the gender of a face, the emotion of a face, or if a building had 1 or 2 stories. Three ERPs were examined: (1) P100 to examine basic visual processing, (2) N170 to examine facial feature encoding, and (3) N250 to examine affect decoding. Behavioral performance on each task was also measured. Results showed that schizophrenia patients' P100 was comparable to the controls during all 3 identification tasks. Both patients and controls exhibited a comparable N170 that was largest during processing of faces and smallest during processing of buildings. For both groups, the N250 was largest during the emotion identification task and smallest for the building identification task. However, the patients produced a smaller N250 compared with the controls across the 3 tasks. The groups did not differ in behavioral performance in any of the 3 identification tasks. The pattern of intact P100 and N170 suggest that patients maintain basic visual processing and facial feature encoding abilities. The abnormal N250 suggests that schizophrenia patients are less efficient at decoding facial affect features. Our results imply that abnormalities in the later stage of feature decoding could potentially underlie emotion identification deficits in schizophrenia. C1 [Wynn, Jonathan K.; Lee, Junghee; Horan, William P.; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, MIRECC, Los Angeles, CA 90073 USA. [Lee, Junghee; Horan, William P.; Green, Michael F.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. RP Wynn, JK (reprint author), VA Greater Los Angeles Healthcare Syst, MIRECC, Bldg 210, Los Angeles, CA 90073 USA. EM jkwynn@ucla.edu RI Lee, Junghee/C-5226-2014; Wynn, Jonathan/H-3749-2014 OI Lee, Junghee/0000-0001-9567-8700; Wynn, Jonathan/0000-0002-1763-8540 FU NIMH NIH HHS [MH-43292, MH-65707] NR 49 TC 48 Z9 53 U1 6 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JUL PY 2008 VL 34 IS 4 BP 679 EP 687 DI 10.1093/schbul/sbn047 PG 9 WC Psychiatry SC Psychiatry GA 323AV UT WOS:000257417300014 PM 18499704 ER PT J AU Dyer, MA Freudenreich, O Culhane, MA Pacha, GN Deckersbach, T Murphy, E Goff, DC Evins, AE AF Dyer, Michael A. Freudenreich, Oliver Culhane, Melissa A. Pacha, Gladys N. Deckersbach, Thilo Murphy, Erin Goff, Donald C. Evins, A. Eden TI High-dose galantamine augmentation inferior to placebo on attention, inhibitory control and working memory performance in nonsmokers with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE galantamine; schizophrenia; attention; nicotine; acetylcholine ID NICOTINIC ACETYLCHOLINE-RECEPTORS; DOUBLE-BLIND; CIGARETTE-SMOKING; CONTROLLED TRIAL; ALLOSTERIC POTENTIATION; COGNITIVE IMPAIRMENTS; ADJUNCTIVE DONEPEZIL; STABLE SCHIZOPHRENIA; ALZHEIMERS-DISEASE; SMOOTH-PURSUIT AB Dysfunction in the neuronal nicotinic acetylcholine receptor (nAChR) system has been implicated in the pathophysiology of schizophrenia, and it has been postulated that treatments that increase nAChR activity may improve symptoms of the disorder. We investigated the effects of the acetylcholinesterase inhibitor and allosteric nAChR modulator, galantamine, on cognitive performance and clinical symptoms when added to a stable antipsychotic medication regimen in nonsmoking outpatients with schizophrenia in a double-blind, placebo-controlled, parallel-group design. Participants were randomized to receive either galantamine (n = 10) up to 32 mg/day or identical placebo (n = 10) for 8 weeks and completed a cognitive battery at baseline and week 8 and clinical scales at baseline, week 4 and week 8. The primary outcome measure was attentional performance as measured by the d' measure in the Continuous Performance Test - Identical Pairs (CPT-IP) Version. Contrary to our hypothesis, galantamine treatment was associated with inferior performance on the CPT-IP, on the three-card Stroop task, and on the Letter-Number Span task without reordering. Galantamine had no effect on clinical symptoms. In summary, galantamine treatment, at a dose of 32 mg/day, was well tolerated but was not effective as an adjunctive treatment for cognitive deficits in stable nonsmokers with schizophrenia. (c) 2008 Elsevier B.V. All rights reserved. C1 [Dyer, Michael A.; Freudenreich, Oliver; Culhane, Melissa A.; Pacha, Gladys N.; Deckersbach, Thilo; Goff, Donald C.; Evins, A. Eden] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Dyer, Michael A.; Freudenreich, Oliver; Culhane, Melissa A.; Pacha, Gladys N.; Deckersbach, Thilo; Murphy, Erin; Goff, Donald C.; Evins, A. Eden] Harvard Univ, Sch Med, Boston, MA USA. [Murphy, Erin] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Evins, AE (reprint author), 60 Staniford St, Boston, MA 02114 USA. EM a_eden_evins@hms.harvard.edu FU NIDA NIH HHS [K23 DA000510, K23 DA000510-01, K23 DA000510-02, K23 DA000510-03, K23 DA000510-04, K23 DA000510-05, K23 DA00510] NR 57 TC 44 Z9 45 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JUL PY 2008 VL 102 IS 1-3 BP 88 EP 95 DI 10.1016/j.schres.2007.12.491 PG 8 WC Psychiatry SC Psychiatry GA 328ZW UT WOS:000257837700011 PM 18325740 ER PT J AU Atfi, A Baron, R AF Atfi, Azeddine Baron, Roland TI p53 Brings a New Twist to the Smad Signaling Network SO SCIENCE SIGNALING LA English DT Article AB Transforming growth factor beta (TGF-beta) signaling regulates a plethora of cellular responses, including specification of developmental fate during embryogenesis, cell proliferation, differentiation, and apoptosis. Components of this pathway are often mutated in cancers and other human disorders. TGF-beta signaling involves activation of transcriptional regulators of the Smad family. The tumor suppressor p53 is an essential partner of Smads, affecting TGF-beta signaling at various points in the pathway. Inactivation of p53 may contribute to the aberrant behavior of cancer cells that escape the cytostatic action of TGF-beta despite the apparent integrity of the TGF-beta receptor or Smads. Thus, the discovery that p53 and TGF-beta cooperate in cell-fate decisions and cellular homeostatic mechanisms has important pathophysiological implications. C1 [Atfi, Azeddine] Hop St Antoine, INSERM, U893, F-75571 Paris, France. [Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immunol, Boston, MA 02115 USA. [Baron, Roland] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Baron, Roland] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02115 USA. RP Atfi, A (reprint author), Hop St Antoine, INSERM, U893, 184 Rue Faubourg St Antoine, F-75571 Paris, France. EM azeddine.atfi@inserm.fr NR 25 TC 12 Z9 12 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD JUL 1 PY 2008 VL 1 IS 26 AR pe33 DI 10.1126/scisignal.126pe33 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA V10WF UT WOS:000207493400001 PM 18594115 ER PT J AU Jetter, GM Cavazos, JE AF Jetter, Gina Mapes Cavazos, Jose E. TI Epilepsy in the elderly SO SEMINARS IN NEUROLOGY LA English DT Article DE epilepsy; geriatrics; antiepileptic drugs ID NONCONVULSIVE STATUS EPILEPTICUS; NURSING-HOME RESIDENTS; ANTIEPILEPTIC DRUG-USE; TONIC CLONIC SEIZURES; VITAMIN-D LEVELS; SERUM CONCENTRATIONS; BONE TURNOVER; CARBAMAZEPINE; PHENYTOIN; AGE AB There are many unique characteristics in elderly patients with epilepsy. The incidence of seizures in this age group is the highest of any age group and continues to increase as people live longer. Etiology of seizures is different than for adults and includes cerebrovascular disease, dementia, closed head injury, and metabolic encephalopathies. The elderly patient with epilepsy most often presents with complex partial seizures that have a higher recurrence rate than the younger population. The seizures are often difficult to diagnose since they present with atypical symptoms, particularly prolonged postictal symptoms, including memory lapses, confusion, altered mental status, and inattention. There are also therapeutic challenges due to age-related changes in pharmacokinetics, including variations in absorption, distribution, metabolism, and excretion. These must be considered when selecting antiepileptic drug (AED) therapy to avoid harmful side effects. In addition, several of the AEDs have drug-drug interactions, a problem potentially exacerbated in this population of patients due to the use of medications for comorbid conditions. C1 [Jetter, Gina Mapes; Cavazos, Jose E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurol, San Antonio, TX 78229 USA. [Cavazos, Jose E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Cavazos, Jose E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Cavazos, Jose E.] Univ Texas Hlth Sci Ctr San Antonio, S Texas Comprehens Epilepsy Ctr, San Antonio, TX 78229 USA. [Cavazos, Jose E.] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP Cavazos, JE (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Neurol, 7703 Floyd Curl Dr,MC7883, San Antonio, TX 78229 USA. EM cavazosj@uthscsa.edu RI Cavazos, Jose/J-4122-2016; OI Cavazos, Jose/0000-0001-5777-2608 NR 41 TC 17 Z9 18 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0271-8235 J9 SEMIN NEUROL JI Semin. Neurol. PD JUL PY 2008 VL 28 IS 3 BP 336 EP 341 DI 10.1055/s-2008-1079338 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 336OL UT WOS:000258374400008 PM 18777480 ER PT J AU Zietman, A AF Zietman, Anthony TI The future of radiation oncology: The evolution, diversification, and survival of the specialty SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID LOCALIZED PROSTATE-CANCER; BRACHYTHERAPY; THERAPY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Zietman, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. EM azietman@partners.org NR 11 TC 11 Z9 12 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 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD JUL PY 2008 VL 18 IS 3 BP 207 EP 213 DI 10.1016/j.semradonc.2008.01.009 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 310UD UT WOS:000256555100009 PM 18513631 ER PT J AU Sarwar, A Shapiro, MD Abbara, S Cury, RC AF Sarwar, Ammar Shapiro, Michael D. Abbara, Suhny Cury, Ricardo C. TI Cardiac magnetic resonance imaging for the evaluation of ventricular function SO SEMINARS IN ROENTGENOLOGY LA English DT Article ID CONGENITAL HEART-DISEASE; STEADY-STATE PRECESSION; THROUGH-PLANE MOTION; ENCODED CINE MRI; DIASTOLIC FUNCTION; BREATH-HOLD; DILATED CARDIOMYOPATHY; EJECTION FRACTION; MYOCARDIAL MASS; HYPERTROPHIC CARDIOMYOPATHY C1 [Cury, Ricardo C.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Cury, RC (reprint author), Massachusetts Gen Hosp, Dept Radiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM rcury@partners.org NR 72 TC 8 Z9 8 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 0037-198X J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD JUL PY 2008 VL 43 IS 3 BP 183 EP 192 DI 10.1053/j.ro.2008.02.004 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 308GJ UT WOS:000256376000005 PM 18486680 ER PT J AU Song, X Zhou, XH AF Song, Xiao Zhou, Xiao-Hua TI A semiparametric approach for the covariate specific ROC curve with survival outcome SO STATISTICA SINICA LA English DT Article DE location model; proportional hazards model; receiver operating characteristic curve; survival analysis ID MODEL AB The receiver operating characteristic (ROC) curve has been extended to survival data recently, including the nonparametric approach by Heagerty, Lumley and Pepe (2000) and the semiparametric approach by Heagerty and Zheng (2005) using standard survival analysis techniques based on two different time-dependent ROC curve definitions. However, both approaches do not involve covariates other than the biomarker and cannot be used to estimate the ROC curve adjusted for covariates. To account for the covariate effect, we propose a joint model approach which assumes that the hazard of failure depends on the biomarker and the covariates through a proportional hazards model and that the biomarker depends the covariates through a semiparametric location model. We propose semiparametric estimators for covariate-specific ROC curves corresponding to the two time-dependent ROC curve definitions, respectively. We show that the estimators are consistent and converge to Gaussian processes. In the case of no covariates., the estimators are demonstrated to be more efficient than the Heagerty-Lumley-Pepe estimator and the Heagerty-Zheng estimator via simulation studies. In addition. the estimators can be easily extended to other survival models. We apply these estimators to an HIV dataset. C1 [Song, Xiao] Univ Georgia, Dept Epidemiol & Biostat, Coll Publ Hlth, Athens, GA 30602 USA. [Zhou, Xiao-Hua] Univ Washington, Dept Biostat, Seattle, WA 98101 USA. [Zhou, Xiao-Hua] VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98101 USA. RP Song, X (reprint author), Univ Georgia, Dept Epidemiol & Biostat, Coll Publ Hlth, Athens, GA 30602 USA. EM xsong@uga.edu; azhou@u.washington.edu NR 11 TC 20 Z9 20 U1 0 U2 3 PU STATISTICA SINICA PI TAIPEI PA C/O DR H C HO, INST STATISTICAL SCIENCE, ACADEMIA SINICA, TAIPEI 115, TAIWAN SN 1017-0405 J9 STAT SINICA JI Stat. Sin. PD JUL PY 2008 VL 18 IS 3 BP 947 EP 965 PG 19 WC Statistics & Probability SC Mathematics GA 337UA UT WOS:000258459800010 ER PT J AU Viswanathan, A Patel, P Rahman, R Nandigam, RNK Kinnecom, C Bracoud, L Rosand, J Chabriat, H Greenberg, SM Smith, EE AF Viswanathan, Anand Patel, Pratik Rahman, Rosanna Nandigam, R. N. Kaveer Kinnecom, Catherine Bracoud, Luc Rosand, Jonathan Chabriat, Hugues Greenberg, Steven M. Smith, Eric E. TI Tissue microstructural changes are independently associated with cognitive impairment in cerebral amyloid angiopathy SO STROKE LA English DT Article DE cerebral amyloid angiopathy; cerebral microhemorrhage; cognitive impairment; dementia; diffusion; microbleeds; white matter disease ID WHITE-MATTER LESIONS; DIFFUSION TENSOR MRI; LOBAR INTRACEREBRAL HEMORRHAGE; INFORMANT QUESTIONNAIRE; ELDERLY IQCODE; ISCHEMIC LEUKOARAIOSIS; INTRACRANIAL VOLUME; CADASIL; DECLINE; PROGRESSION AB Background and Purpose - Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage and cognitive impairment and is associated with white matter hyperintensities and cerebral microbleeds. MRI diffusion tensor imaging detects microstructural tissue damage in advanced CAA even in areas that appear normal on conventional MRI. We hypothesized that higher global mean apparent diffusion coefficient (mean ADC), reflecting a higher amount of chronic tissue disruption caused by CAA, would be independently associated with CAA-related cognitive impairment. Methods - Preintracerebral hemorrhage cognitive impairment was systematically assessed using a standardized questionnaire (IQCODE) in 49 patients. Volume of white matter hyperintensities, number of microbleeds, and mean ADC were determined from MRIs obtained within 14.0 +/- 22.5 days of intracerebral hemorrhage cognitive impairment. White matter hyperintensities and mean ADC were measured in the hemisphere uninvolved by intracerebral hemorrhage to avoid confounding. Results - Preintracerebral hemorrhage cognitive impairment was identified in 10 of 49 subjects. Mean ADC was the only variable associated with preintracerebral hemorrhage cognitive impairment and was elevated in those with preintracerebral hemorrhage cognitive impairment compared with those without (12.4 x 10(-4) versus 11.7 x 10(-4) mm(2)/s; P = 0.03). Mean ADC positively correlated with age but not white matter hyperintensities or number of microbleeds. In logistic regression controlling for age and visible cerebral atrophy, mean ADC was independently associated with preintracerebral hemorrhage cognitive impairment (OR per 1 x 10(-4) mm(2)/s increase = 2.45, 95% CI 1.11 to 5.40, P = 0.04). Conclusions - Mean ADC is independently associated with preintracerebral hemorrhage cognitive impairment in CAA. The lack of correlation with other MRI markers of CAA suggests that mean ADC may be sensitive to distinct aspects of CAA pathology and its tissue consequences. These results suggest that global MRI diffusion changes are sensitive to clinically relevant microstructural alterations and may be useful markers of CAA-related tissue damage. C1 [Viswanathan, Anand] Massachusetts Gen Hosp, Hemorrhag Stroke Res Program, Ctr Stroke Res, Boston, MA 02114 USA. [Viswanathan, Anand; Patel, Pratik; Rahman, Rosanna; Nandigam, R. N. Kaveer; Kinnecom, Catherine; Rosand, Jonathan; Greenberg, Steven M.; Smith, Eric E.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Chabriat, Hugues] CHU Lariboisiere, AP HP, Dept Neurol, Paris, France. [Bracoud, Luc] Bioimaging Technol SAS, Lyon, France. RP Viswanathan, A (reprint author), Massachusetts Gen Hosp, Hemorrhag Stroke Res Program, Ctr Stroke Res, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM aviswanathan1@partners.org RI Smith, Eric/C-5443-2012; Chabriat, Hugues/G-5699-2010 OI Smith, Eric/0000-0003-3956-1668; Chabriat, Hugues/0000-0001-8436-6074 FU NIA NIH HHS [5R01AG026484-02, R01 AG026484, R01 AG026484-05]; NINDS NIH HHS [5K23NS046327-04, K23 NS046327] NR 37 TC 33 Z9 36 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 JUL PY 2008 VL 39 IS 7 BP 1988 EP 1992 DI 10.1161/STROKEAHA.107.509091 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 317KP UT WOS:000257019400010 PM 18436874 ER PT J AU FitzMaurice, E Wendell, L Snider, R Schwab, K Chanderraj, R Kinnecom, C Nandigam, K Rost, NS Viswanathan, A Rosand, J Greenberg, SM Smith, EE AF FitzMaurice, Emilie Wendell, Lauren Snider, Ryan Schwab, Kristin Chanderraj, Rishi Kinnecom, Cathrine Nandigam, Kaveer Rost, Natalia S. Viswanathan, Anand Rosand, Jonathan Greenberg, Steven M. Smith, Eric E. TI Effect of statins on intracerebral hemorrhage outcome and recurrence SO STROKE LA English DT Article DE intracerebral hemorrhage; outcome; statins ID COA REDUCTASE INHIBITOR; ISCHEMIC-STROKE; ATORVASTATIN; RATS AB Background and Purpose - 3-hydroxy-3- methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, have been associated with improved outcome after ischemic stroke and subarachnoid hemorrhage but an increased risk of incident intracerebral hemorrhage (ICH). We investigated (1) whether statin use before ICH was associated with functional independence at 90 days, and (2) whether survivors exposed to statins after ICH had an increased risk of recurrence. Methods - We analyzed 629 consecutive ICH patients with 90-day outcome data enrolled in a prospective cohort study between 1998 to 2005. Statin use was determined by patient interview at the time of ICH and supplemented by medical record review. Independent status was defined as Glasgow Outcome Scale 4 or 5. ICH survivors were followed by telephone interview every 6 months. Results - Statins were used by 149/629 ( 24%) before ICH. There was no effect of pre-ICH statin use on the rates of functional independence (28% versus 29%, P = 0.84) or mortality (46% versus 45%, P = 0.93). Medical comorbidities and warfarin use were more common in statin users. Hematoma volumes were similar (median 28 cm(3) in pre-ICH statin users compared to 22 cm3 in nonusers, P = 0.18). The multivariable-adjusted odds ratio for independent status in pre-ICH statin users was 1.16 ( 95% CI 0.65 to 2.10, P = 0.62). ICH survivors treated with statins after discharge did not have a higher risk of recurrence ( adjusted HR 0.82, 95% CI 0.34 to 1.99, P = 0.66). Conclusions - Pre-ICH statin use is not associated with improved ICH functional outcome or mortality. Post-ICH statin use is not associated with an increased risk of ICH recurrence. C1 [FitzMaurice, Emilie; Wendell, Lauren; Snider, Ryan; Schwab, Kristin; Chanderraj, Rishi; Kinnecom, Cathrine; Nandigam, Kaveer; Rost, Natalia S.; Viswanathan, Anand; Rosand, Jonathan; Greenberg, Steven M.; Smith, Eric E.] Massachusetts Gen Hosp, Hemorrhag Stroke Res Program, Dept Neurol, Boston, MA 02114 USA. [Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Smith, EE (reprint author), Mass Gen Hosp, Acute Stroke Serv, CPZ 300,55 Fruit St, Boston, MA 02114 USA. EM eesmith@partners.org OI Smith, Eric/0000-0003-3956-1668 FU NINDS NIH HHS [K23 NS046327] NR 15 TC 44 Z9 44 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUL PY 2008 VL 39 IS 7 BP 2151 EP 2154 DI 10.1161/STROKEAHA.107.508861 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 317KP UT WOS:000257019400036 PM 18436876 ER PT J AU Rost, NS Greenberg, SM Rosand, J AF Rost, Natalia S. Greenberg, Steven M. Rosand, Jonathan TI The genetic architecture of intracerebral Hemorrhage SO STROKE LA English DT Review DE genetics; association; intracerebral hemorrhage; stroke prevention; review ID CEREBRAL AMYLOID ANGIOPATHY; MATTER HYPERINTENSITY VOLUME; GENOME-WIDE ASSOCIATION; ATRIAL-FIBRILLATION; ISCHEMIC-STROKE; RISK-FACTORS; VKORC1 HAPLOTYPES; CROHN-DISEASE; POPULATION; WARFARIN AB Background and Purpose - Intracerebral hemorrhage (ICH), the acute manifestation of a common progressive cerebrovascular disease of the elderly, is the most fatal and least treatable form of stroke. There is a desperate need for ICH-specific therapeutics and effective primary prevention strategies, a need that is certain to grow with the aging of the population. Data point to a sizable genetic component to ICH susceptibility. Identification of ICH-related genes therefore holds promise for identifying novel biological targets for ICH prevention. This review focuses on evidence for a genetic contribution to ICH, delineates approaches to genetic studies of ICH, and explores foundations for their future applications. Summary of Review - ICH occurs both sporadically and as part of familial syndromes. Monogenic disorders associated with ICH or microscopic bleeding, such as hereditary cerebral amyloid angiopathy, CADASIL, and collagen type IV A1-associated vasculopathy, demonstrate the potent effect of rare mutations. Dissecting the more complex genetics of sporadic ICH, however, will likely require defining multiple common DNA variants with weaker effects. Advances in high-throughput genotyping technology, computational and analytic methodologies, and large-scale collaborative efforts have already led to the identification of new genetic risk factors for dozens of common diseases. Such whole-genome association studies are being undertaken in sporadic ICH. Conclusions - Investigations of genetic risk factors for sporadic ICH have thus far been limited to candidate gene polymorphisms. Genome-wide association studies currently hold the greatest hope for robust discovery of ICH genes, which can generate novel insights into ICH biology and strategies for prevention. C1 [Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Rost, Natalia S.; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Rost, Natalia S.; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Hemorrhag Stroke Res Program, Boston, MA 02114 USA. [Rost, Natalia S.; Rosand, Jonathan] MIT & Harvard, Broad Inst, Cambridge, MA USA. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 6818, Boston, MA 02114 USA. EM jrosand@partners.org FU NINDS NIH HHS [K23 NS42695, R01 NS04217] NR 51 TC 43 Z9 43 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD JUL PY 2008 VL 39 IS 7 BP 2166 EP 2173 DI 10.1161/STROKEAHA.107.501650 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 317KP UT WOS:000257019400039 PM 18467649 ER PT J AU Califano, R Blackhall, FH Finocchiaro, G Toschi, L Thatcher, N Cappuzzo, F Crino, L AF Califano, Raffaele Blackhall, Fiona H. Finocchiaro, Giovanna Toschi, Luca Thatcher, Nicholas Cappuzzo, Federico Crino, Lucio TI EGFR tyrosine kinase inhibitors in non-small cell lung cancer patients: how do we interpret the clinical and biomarker data? SO TARGETED ONCOLOGY LA English DT Review DE EGFR; Tyrosine kinase inhibitors; Erlotinib; Gefitinib; Non-small cell lung cancer ID GROWTH-FACTOR-RECEPTOR; CHEMOTHERAPY-NAIVE PATIENTS; PREVIOUSLY TREATED PATIENTS; SOUTHWEST-ONCOLOGY-GROUP; RANDOMIZED PHASE-II; GENE COPY NUMBER; K-RAS MUTATIONS; ACTIVATING MUTATIONS; PREDICTIVE FACTORS; BRONCHIOLOALVEOLAR-CARCINOMA AB The clinical development of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for treatment of non-small cell lung cancer (NSCLC) is a major breakthrough in the field. Erlotinib is the first of this class of drug demonstrated in a placebo-controlled trial to prolong survival of patients with previously treated NSCLC. The challenge now is how best to select patients for this treatment. Clinical factors including female gender, East Asian ethnic origin, adenocarcinoma histology, and a history of never-smoking are associated with better response rates, but response to erlotinib is not exclusive to these populations or essential for a survival benefit. Molecular factors such as EGFR mutation and increased EGFR gene copy number provide objective tests that may be superior to clinical factors for patient selection, but assay for these factors is crucially dependent on available tumor tissue and to date, there are no published data from randomized trials where tumor tissue is available from all patients. Here we review the clinical and biological factors that may be applied to select patients for treatment with EGFR-TKIs and conclude that the available data are premature for definitive guidelines to select against an EGFR-TKI. C1 [Califano, Raffaele; Blackhall, Fiona H.; Thatcher, Nicholas] Christie Hosp NHS Fdn Trust, Dept Med Oncol, Manchester M20 4BX, Lancs, England. [Califano, Raffaele; Crino, Lucio] Osped Santa Maria Misericordia, Perugia, Italy. [Finocchiaro, Giovanna; Cappuzzo, Federico] Ist Clin Humanitas IRCCS, Div Hematol Oncol, Rozzano, Italy. [Toschi, Luca] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Califano, R (reprint author), Christie Hosp NHS Fdn Trust, Dept Med Oncol, Wilmslow Rd, Manchester M20 4BX, Lancs, England. EM raffaele.califano@poste.it RI Blackhall, Fiona/N-2186-2015; Califano, Raffaele/C-4055-2013; OI Blackhall, Fiona/0000-0001-8716-3395; Califano, Raffaele/0000-0003-2611-5319; Cappuzzo, Federico/0000-0002-6295-6767 NR 88 TC 2 Z9 2 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1776-2596 EI 1776-260X J9 TARGET ONCOL JI Target. Oncol. PD JUL PY 2008 VL 3 IS 3 BP 173 EP 186 DI 10.1007/s11523-008-0084-7 PG 14 WC Oncology SC Oncology GA 451RF UT WOS:000266486900005 ER PT J AU Kelley, L Chou, CL Dibble, SL Robertson, PA AF Kelley, Leah Chou, Calvin L. Dibble, Suzanne L. Robertson, Patricia A. TI A critical intervention in lesbian, gay, bisexual, and transgender health: Knowledge and attitude outcomes among second-year medical students SO TEACHING AND LEARNING IN MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-of-Professors-of-Gynecology-and-Obstetrics/Council-on-Reside nt-Education-in-Obstetrics-and-Gynecology CY MAR 02-06, 2005 CL Salt Lake City, UT SP Assoc Professors Gynecol & Obstet, Council Resident Educ Obstet & Gynecol ID HOMOSEXUALITY; CARE; SCHOOLS; ISSUES; PANEL; MEN AB Background: Lesbian, gay, bisexual, and transgender (LGBT) persons represent an underserved population susceptible to health care disparities. Description: In February 2004, we implemented an LGBT health curriculum for students at the University of California at San Francisco. Confidential matched questionnaires elicited students' knowledge, attitudes, and beliefs about LGBT health issues before and after the intervention. Evaluation: The surveyed population (52% response rate) was demographically similar to the entire class. There was statistically significant change in the responses to 4 of 16 questionnaire items (p <= .001; largest absolute change was 0.57 on a 5-point scale). Students demonstrate increased knowledge about access to health care and LGBT relationships, increased willingness to treat patients with gender identity issues, and enhanced awareness that sexual identity and practices are clinically relevant. Conclusions: Our simple curricular intervention led to significant short-term changes in a small number of survey items assessing students' knowledge and beliefs about LGBT persons. C1 [Kelley, Leah; Robertson, Patricia A.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. [Chou, Calvin L.] Univ Calif San Francisco, Dept Med, Sch Med, San Francisco, CA 94143 USA. [Dibble, Suzanne L.] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. RP Chou, CL (reprint author), San Francisco VA Med Ctr, 4150 Clement St 111, San Francisco, CA 94121 USA. EM calvin.chou@ucsf.edu NR 19 TC 40 Z9 41 U1 4 U2 16 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1040-1334 J9 TEACH LEARN MED JI Teach. Learn. Med. PD JUL-SEP PY 2008 VL 20 IS 3 BP 248 EP 253 DI 10.1080/10401330802199567 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 340AE UT WOS:000258617600008 PM 18615300 ER PT J AU Peden-Adams, MM Keller, JM EuDaly, JG Berger, J Gilkeson, GS Keil, DE AF Peden-Adams, Margie M. Keller, Jennifer M. EuDaly, Jackie G. Berger, Jennifer Gilkeson, Gary S. Keil, Deborah E. TI Suppression of humoral immunity in mice following exposure to perfluorooctane sulfonate SO TOXICOLOGICAL SCIENCES LA English DT Article DE PFOS; immunotoxicity; immune; humoral immunity; PFC assay; TNP-LPS; serum levels ID PROLIFERATOR-ACTIVATED RECEPTOR; NF-KAPPA-B; PEROXISOME PROLIFERATOR; AMMONIUM PERFLUOROOCTANOATE; PERFLUORINATED COMPOUNDS; PPAR-ALPHA; IN-VIVO; IMMUNOGLOBULIN PRODUCTION; DEVELOPMENTAL TOXICITY; PERFLUORODECANOIC ACID AB Adult male and female B6C3F1 mice were exposed to perfluorooctane sulfonate (PFOS) daily via gavage for 28 days (0, 0.005, 0.05, 0.1, 0.5, 1, or 5 mg/kg total administered dose [TAD]). Following exposure, various immune parameters were assessed and serum PFOS concentrations were determined. Lymphocyte proliferation was not altered in either gender. Natural killer cell activity was increased compared with control at 0.5, 1, and 5 mg/kg TAD in male mice but was not altered in female mice. At these treatment levels, splenic T-cell immunophenotypes were minimally altered in females, but all T-cell subpopulations were significantly modulated in males beginning at 0.1 mg/kg TAD. The sheep red blood cell (SRBC) plaque-forming cell (PFC) response was suppressed in male mice beginning at 0.05 mg/kg TAD and in females at 0.5 mg/kg TAD. Serum trinitrophenyl (TNP)-specific IgM titers were also decreased by PFOS after TNP-LPS (TNP conjugated to lipopolysacharide) challenge suggesting that the humoral immune effects may be attributed to the B-cell rather than T-cell because both T-dependent (SRBC) and T-independent (TI) (TNP-LPS) antigens result in suppressed IgM production. Based on the PFC response, the low observed effect level (LOEL) for males was 0.05 mg/kg TAD (ED50 = 0.021 mg/kg TAD) and for females was 0.5 mg/kg TAD (ED50 = 0.59 mg/kg TAD). Measured PFOS serum concentrations at these dose levels were 91.5 +/- 22.2 ng/g and 666 +/-+/- 108 ng/g (mean +/- SD), respectively. The male LOEL serum level was approximately 14-fold lower than reported mean blood levels from occupationally exposed humans and fell in the upper range of concentrations reported for the general population. Overall, this study provides a profile of PFOS immunotoxicity showing effects at levels reported in humans and identifies the B-cells as a potential target. C1 [Peden-Adams, Margie M.] MUSC, Dept Pediat, Charleston, SC 29412 USA. [Peden-Adams, Margie M.; EuDaly, Jackie G.; Gilkeson, Gary S.] MUSC, Dept Med Rheumatol & Immunol, Charleston, SC 29412 USA. [Peden-Adams, Margie M.; EuDaly, Jackie G.] MUSC, Marine Biomed & Environm Sci Ctr, Charleston, SC 29412 USA. [Keller, Jennifer M.] Natl Inst Stand & Technol, Hollings Marine Lab, Charleston, SC 29412 USA. [Berger, Jennifer; Keil, Deborah E.] Univ Nevada, Clin Sci Lab, Las Vegas, NV 89154 USA. [Gilkeson, Gary S.] Ralph Johnson VAMC, Med Res Serv, Charleston, SC 29403 USA. RP Peden-Adams, MM (reprint author), MUSC, Dept Pediat, 221 Ft Johnson Rd, Charleston, SC 29412 USA. EM pedenada@musc.edu NR 62 TC 98 Z9 100 U1 5 U2 23 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUL PY 2008 VL 104 IS 1 BP 144 EP 154 DI 10.1093/toxsci/kfn059 PG 11 WC Toxicology SC Toxicology GA 313UY UT WOS:000256766700014 PM 18359764 ER PT J AU Khor, B Makar, RS AF Khor, Bernard Makar, Robert S. TI Toward a molecular explanation for cross-presentation of antigens to the immune system SO TRANSFUSION MEDICINE REVIEWS LA English DT Review ID MHC CLASS-I; CD8(+) T-CELLS; HEAT-SHOCK PROTEINS; CD8-ALPHA(+) DENDRITIC CELLS; BONE-MARROW-TRANSPLANTATION; PRESENT EXOGENOUS ANTIGENS; YEAST-BASED IMMUNOTHERAPY; MINOR H-ANTIGENS; ENDOPLASMIC-RETICULUM; CUTTING EDGE AB Cross-presentation is increasingly recognized as a key mechanism by which specific antigen-presenting cells (APCs) activate the cellular immune system against virally infected or neoplastic cells. These APCs have the capacity to acquire exogenous proteins by phagocytosis or endocytosis, derive antigenic peptides, and then cross-present them in the context of class I major histocompatibility complex molecules. Because APCs provide both an antigenic stimulus and costimulatory signals, they can effectively activate naive CD8(+) T lymphocytes, resulting in a brisk cellular immune response. The precise cellular pathways that permit an exogenous antigen to be presented in the context of class I major histocompatibility complex is the focus of intense investigation that has illuminated our understanding of the cell biology of APCs. This article reviews our understanding of how APCs cross-present antigen, illustrating how this process differs from the canonical pathways of antigen presentation. We define the central players required for cross-presentation and then focus on recent studies that reveal the molecular mechanisms underlying this phenomenon. Understanding these mechanisms will likely inform the development of effective cell-based vaccines and other cellular immunotherapies and is therefore of interest to practitioners of transfusion medicine. (c) 2008 ElsevierInc. All rights reserved. C1 [Khor, Bernard; Makar, Robert S.] Massachusetts Gen Hosp, Dept Pathol, Blood Transfus Serv, Boston, MA 02114 USA. RP Makar, RS (reprint author), Massachusetts Gen Hosp, Dept Pathol, Blood Transfus Serv, 55 Fruit St,GRJ2-206C, Boston, MA 02114 USA. EM rmakar@partners.org OI Khor, Bernard/0000-0003-4689-5092 NR 122 TC 5 Z9 5 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 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD JUL PY 2008 VL 22 IS 3 BP 188 EP 201 DI 10.1016/j.tmrv.2008.02.002 PG 14 WC Hematology SC Hematology GA 323NC UT WOS:000257451800002 PM 18572095 ER PT J AU Berk, M Ng, F Dean, O Dodd, S Bush, AI AF Berk, Michael Ng, Felicity Dean, Olivia Dodd, Seetal Bush, Ashley I. TI Glutathione: a novel treatment target in psychiatry SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID ANTIOXIDANT ENZYME LEVELS; N-ACETYL CYSTEINE; OXIDATIVE STRESS; LIPID-PEROXIDATION; BIPOLAR DISORDER; THERAPEUTIC IMPLICATIONS; SCHIZOPHRENIC-PATIENTS; SUPEROXIDE-DISMUTASE; MITOCHONDRIAL DYSFUNCTION; MAJOR DEPRESSION AB There is accumulating evidence for oxidative stress mechanisms as common pathophysiological pathways in diverse psychiatric disorders, which offers novel treatment targets in oxidation biology systems. Of these the glutathione system has the most favourable theoretical foundation, given its dominance as the most generic of cellular antioxidants. Clinically, this hypothesis has been supported by several recently published studies that have reported on the efficacy of N-acetylcysteine, a glutathione precursor, in the treatment of various psychiatric disorders. This article outlines the multidimensional evidence that currently exists for oxidative stress mechanisms in psychiatric disorders and specifically discusses glutathione as a promising novel therapeutic target. C1 [Berk, Michael; Ng, Felicity; Dodd, Seetal] Univ Melbourne, Dept Clin & Biomed Sci, Barwon Hlth, Geelong, Vic 3220, Australia. [Berk, Michael] Orygen Res Ctr, Parkville, Vic 3052, Australia. [Berk, Michael; Dean, Olivia; Bush, Ashley I.] Mental Hlth Res Inst Victoria, Parkville, Vic 3052, Australia. [Bush, Ashley I.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. RP Berk, M (reprint author), Univ Melbourne, Dept Clin & Biomed Sci, Barwon Hlth, 265 Ryrie St, Geelong, Vic 3220, Australia. EM mikebe@barwonhealth.org.au RI Berk, Michael/M-7891-2013; Bush, Ashley/A-1186-2007 OI Berk, Michael/0000-0002-5554-6946; Bush, Ashley/0000-0001-8259-9069 NR 62 TC 112 Z9 112 U1 1 U2 5 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD JUL PY 2008 VL 29 IS 7 BP 346 EP 351 DI 10.1016/j.tips.2008.05.001 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 328RE UT WOS:000257814700004 PM 18538422 ER PT J AU Ruvkun, G AF Ruvkun, Gary TI Tiny RNA: Where do we come from? What are we? Where are we going? SO TRENDS IN PLANT SCIENCE LA English DT Review ID CRYSTAL-STRUCTURE; SLICER ACTIVITY; C-ELEGANS; MECHANISMS; ARGONAUTE; MAIZE; MIRNA; GENE C1 [Ruvkun, Gary] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Ruvkun, G (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu NR 18 TC 2 Z9 4 U1 0 U2 5 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1360-1385 J9 TRENDS PLANT SCI JI Trends Plant Sci. PD JUL PY 2008 VL 13 IS 7 BP 313 EP 316 DI 10.1016/j.tplants.2008.05.005 PG 4 WC Plant Sciences SC Plant Sciences GA 331VU UT WOS:000258041500002 PM 18562240 ER PT J AU Ernst, JD Lewinsohn, DM Behar, S Blythe, M Schlesinger, LS Kornfeld, H Sette, A AF Ernst, Joel D. Lewinsohn, David M. Behar, Samuel Blythe, Martin Schlesinger, Larry S. Kornfeld, Hardy Sette, Alessandro TI Meeting report: NIH workshop on the tuberculosis immune epitope database SO TUBERCULOSIS LA English DT Article DE tuberculosis; immunity; epitope; lymphocyte; HLA; antibody ID CD8(+) T-CELLS; MYCOBACTERIUM-TUBERCULOSIS; INFECTION; MOUSE; RECOGNITION; PERSISTENCE; DIVERSITY; INSIGHTS; STRAINS; PEPTIDE AB The Immune Epitope Database (IEDB), an online resource available at http://immuneepitope.org/, contains data on T cell and B cells epitopes of multiple pathogens, including M. tuberculosis. A workshop held in June, 2007 reviewed the existing database, discussed the utility of reference sets of epitopes, and identified knowledge gaps pertaining to epitopes and immune responses in tuberculosis. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Ernst, Joel D.] NYU, Sch Med, Div Infect Dis, New York, NY 10016 USA. [Lewinsohn, David M.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97239 USA. [Behar, Samuel] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Blythe, Martin; Sette, Alessandro] La Jolla Inst Allergy & Immunol, Dept Vaccine Discovery, La Jolla, CA 92037 USA. [Schlesinger, Larry S.] Ohio State Univ, Med Ctr, Div Infect Dis, Columbus, OH 43210 USA. [Schlesinger, Larry S.] Ohio State Univ, Med Ctr, Ctr Microbial Interface Biol, Columbus, OH 43210 USA. [Kornfeld, Hardy] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01655 USA. RP Ernst, JD (reprint author), NYU, Sch Med, Div Infect Dis, 522 1st Ave,Smilow 901, New York, NY 10016 USA. EM joel.ernst@med.nyu.edu; lewinsod@ohsu.edu; sbehar@rics.bwh.harvard.edu; mblythe@liai.org; larry.schlesinger@osumc.edu; hardy.kornfetd@umassmed.edu; alex@liai.org RI Lewinsohn, David/I-4936-2013; OI Lewinsohn, David/0000-0001-9906-9494; Behar, Samuel/0000-0002-3374-6699; Ernst, Joel/0000-0001-9951-6207 FU NIAID NIH HHS [R01 AI051242-06, R01 AI046097, R01 AI046097-09, R01 AI051242, R01 AI059667, R01 AI059667-04, R01 AI067731] NR 22 TC 18 Z9 19 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1472-9792 J9 TUBERCULOSIS JI Tuberculosis PD JUL PY 2008 VL 88 IS 4 BP 366 EP 370 DI 10.1016/j.tube.2007.11.002 PG 5 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA 331JG UT WOS:000258007900010 PM 18068490 ER PT J AU Petit, JH Gluck, C Kiger, WS Henry, DL Karasiewicz, C Talcott, J Berg, S Holupka, E Kaplan, I AF Petit, Joshua H. Gluck, Clifford Kiger, W. S., III Henry, D. Laury Karasiewicz, Carol Talcott, James Berg, Solomon Holupka, Edward Kaplan, Irving TI Bicalutamide alone prior to brachytherapy achieves cytoreduction that is similar to luteinizing hormone-releasing hormone analogues with less patient-reported morbidity SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE bicalutamide; brachytherapy; prostate cancer; volume reduction ID BENIGN PROSTATIC HYPERPLASIA; ANDROGEN DEPRIVATION THERAPY; BONE-MINERAL DENSITY; AGONIST LEUPROLIDE; SEED IMPLANTATION; URINARY RETENTION; VOLUME REDUCTION; CANCER PATIENTS; CASODEX; FLUTAMIDE AB Objectives: To compare the impact of bicalutamide (B) vs. luteinizing hormone-releasing hormone analogues (LHRHa) on prostate volume, patient-reported side effects, and postimplant urinary toxicity in the setting of interstitial brachytherapy for early-stage prostate cancer. Methods: Between May 1998 and January 2004, 81 patients received androgen-deprivation therapy (ADT) for cytoreduction prior to interstitial brachytherapy alone. Fifty-six patients received LHRHa and 25 patients received B. Prostate volumes were measured prospectively prior to initiating therapy, and then intraoperatively at the time of implant by a single, blinded ultrasonographer. Patient-reported quality of life data were obtained prospectively, and postimplant urinary toxicity (catheter dependency and need for surgical intervention) was recorded during follow-up. Median follow-up was 53 (range 23-78) months. Results: The median percentage prostate volume reductions of 26% for Band 32% for LHRHa were not statistically different (P = 0.61). Decrements in libido (92% vs. 44%, P < 0.001) and erectile function (79% vs. 20%) were reported in more respondents treated with LHRHa than B. The incidence of recatheterization (28% vs. 24%, P = 0.34), and the need for subsequent surgical intervention (11% vs. 4%, P 0.16) were similar for patients treated with LHRHa and B. Conclusions: The degree of prostate downsizing with B is similar to that achieved with LHRHa. B was associated with fewer patient-reported sexual side effects and similar urinary morbidity. A randomized trial is needed to establish whether LHRHa or B should be the standard of care for prostate downsizing before interstitial brachytherapy. (C) 2008 Elsevier Inc. All rights reserved. C1 [Petit, Joshua H.; Kiger, W. S., III; Henry, D. Laury; Karasiewicz, Carol; Holupka, Edward; Kaplan, Irving] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. [Gluck, Clifford; Berg, Solomon] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Urol, Boston, MA 02215 USA. [Talcott, James] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Boston, MA 02214 USA. RP Petit, JH (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. EM jpetit@partners.org NR 29 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD JUL-AUG PY 2008 VL 26 IS 4 BP 372 EP 377 DI 10.1016/j.urolonc.2007.05.014 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 326HP UT WOS:000257649500009 PM 18367113 ER PT J AU Smith, MR AF Smith, Matthew R. TI Osteoclast targeted therapy for prostate cancer: Bisphosphonates and beyond SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE prostate cancer; bone metastases; osteoclast; bisphosphonate; denosumab ID ZOLEDRONIC ACID; MULTIPLE-MYELOMA; BREAST-CANCER; DOUBLE-BLIND; SKELETAL COMPLICATIONS; POSTMENOPAUSAL WOMEN; AVASCULAR NECROSIS; AMERICAN-SOCIETY; RANDOMIZED-TRIAL; BONE METASTASES AB Bone metastases are a major cause of morbidity for men with prostate cancer. Although typical bone metastases from prostate cancer appear osteoblastic by radiographic imaging, excess number and activity of both osteoblasts and osteoclasts characterize most "osteoblastic" bone metastases. Additionally, pathological osteoclast activation is associated with increased risk of skeletal complications, disease progression, and death. Zoledronic acid, a potent intravenous bisphosphonate, reduces markers of osteoclast activity and significantly decreases the risk of skeletal complications in men with androgen-independent prostate cancer and bone metastases. Additional studies are needed to determine the optimal timing, schedule, and duration of bisphosphonate treatment in men with bone metastases as well as the potential role of bisphosphonates in other settings, including the prevention of bone metastases. Denosumab is a human monoclonal antibody that binds and neutralizes human receptor activator of NF-kappa B ligand (RANKL), a critical mediator of osteoclast activation, differentiation, and survival. Three ongoing pivotal studies involving more than 4,500 subjects will evaluate the role of denosumab for prevention of treatment-related fractures, bone metastases, and disease-related skeletal complications in men with prostate cancer. (C) 2008 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu FU NCI NIH HHS [1K24CA121990-01A1, K24 CA121990, K24 CA121990-02, K24 CA121990-03] NR 27 TC 29 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD JUL-AUG PY 2008 VL 26 IS 4 BP 420 EP 425 DI 10.1016/j.urolonc.2007.11.004 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 326HP UT WOS:000257649500017 PM 18593621 ER PT J AU Anger, JT Saigal, CS Wang, MM Yano, EM AF Anger, Jennifer T. Saigal, Christopher S. Wang, MingMing Yano, Elizabeth M. CA Urologic Dis Amer Project TI Urologic disease burden in the United States: Veteran users of Department of Veterans Affairs healthcare SO UROLOGY LA English DT Article ID NUTRITION EXAMINATION SURVEY; URINARY-INCONTINENCE; NATIONAL-HEALTH; PREVALENCE; MEN AB OBJECTIVES To determine the disease burden, measured by resource utilization, of four Urologic conditions among veteran users of U.S. Department of Veterans Affairs (VA) healthcare services and to assess variations by selected sociodemographic characteristics. METHODS We applied expert-derived diagnosis clusters to establish four patient cohorts from a population of U.S. veterans aged 18 years and older with at least one Outpatient visit in a VA healthcare facility in fiscal year 2001 (n = 3,691,519): (1) benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS), (2) kidney stones (KS), (3) urinary tract infections (UTI), and (4) urinary incontinence (UI). We identified patients with qualifying diagnosis codes associated with Outpatient visits in the national VA Outpatient Clinic file, thereby generating case Counts for each diagnostic category. RESULTS Among veteran users of VA healthcare services, when defined as the primary reason for the visit, the prevalence of BPH/LUTS was 4811 per 100,000 veterans (4.8%); the prevalence of KS was 597 per 100,000 (0.6%); the prevalence of UTI was 4265 and 1719 per 100,000 female and male veterans, respectively (4.3%) and 1.7%); and the prevalence of UI was 2161 and 515 per 100,000 female and male veterans, respectively (2.2% and 0.5%). Prevalence of these conditions when ascertained by capturing diagnoses appearing as secondary reasons for a physician visit was much higher. CONCLUSIONS Although we expected the prevalence of urologic conditions to be high among veterans who use the VA system for care, We found the burden Of Urologic disease among veterans to be comparable to other national data sets. Prevalence estimates based on primary diagnosis, rather than secondary or "any" diagnosis, significantly underestimated the disease burden among veterans. C1 [Anger, Jennifer T.] Univ Calif Los Angeles, Dept Urol, Sch Med, Santa Monica, CA 90404 USA. Univ Calif Los Angeles, RAND Hlth, Santa Monica, CA 90404 USA. Univ Calif Los Angeles, VA Greater Los Angeles HSR&D Ctr Excellence, Study Healthcare Provider Behav, Sepulveda, CA USA. Calif State Univ Los Angeles, Dept Hlth Serv, Sch Publ Hlth, Los Angeles, CA 90032 USA. RP Anger, JT (reprint author), Univ Calif Los Angeles, Dept Urol, Sch Med, 1260 15th St,Suite 1200, Santa Monica, CA 90404 USA. EM janger@mednet.ucla.edu FU NIDDK NIH HHS [N01 DK012460] NR 18 TC 7 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD JUL PY 2008 VL 72 IS 1 BP 37 EP 41 DI 10.1016/j.urology.2007.11.163 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 329QZ UT WOS:000257887000011 PM 18342928 ER PT J AU Florsheim, A Dramard, V Bottiglieri, T Mischoulon, D AF Florsheim, Amanda Dramard, Valerie Bottiglieri, Teodoro Mischoulon, David TI S-adenosylmethionine SO VETERINARY MEDICINE LA English DT Editorial Material ID ADENOSYL-L-METHIONINE; AGE; DOGS; IMPAIRMENT; FOLATE; MODEL C1 [Florsheim, Amanda] Pk Cities Anim Hosp, University Pk, PA USA. [Dramard, Valerie] Vet Behav Referrals Clin, Lyon, France. [Bottiglieri, Teodoro] Baylor Inst Metab Dis, Dallas, TX USA. [Mischoulon, David] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Florsheim, A (reprint author), Pk Cities Anim Hosp, University Pk, PA USA. NR 13 TC 0 Z9 0 U1 0 U2 1 PU VETERINARY MEDICINE PUBL CO PI LENEXA PA 15333 W 95TH STREET, LENEXA, KS 66219 USA SN 8750-7943 J9 VET MED-US JI Vet. Med. PD JUL PY 2008 VL 103 IS 7 BP A1 EP A8 PG 8 WC Veterinary Sciences SC Veterinary Sciences GA 331JO UT WOS:000258008700008 ER PT J AU Reheman, A Yang, H Spring, C Zhu, G Chen, P Wagner, D Fassler, R Freedman, J Ni, H AF Reheman, A. Yang, H. Spring, C. Zhu, G. Chen, P. Wagner, D. Fassler, R. Freedman, J. Ni, H. TI Roles of plasma fibronectin in thrombosis and hemostasis: A lesson from fibrinogen/VWF/and plasma finronectin triple knockout mice SO VOX SANGUINIS LA English DT Meeting Abstract C1 [Yang, H.; Chen, P.; Ni, H.] Univ Toronto, St Michaels Hosp, Canadian Blood Serv, Toronto, ON M5B 1W8, Canada. [Spring, C.; Zhu, G.; Freedman, J.] Univ Toronto, St Michaels Hosp, Toronto Platelet Immunobiol Grp, Toronto, ON M5B 1W8, Canada. [Wagner, D.] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. [Fassler, R.] Max Planck Inst Biochem, Dept Mol Med, D-82152 Martinsried, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0042-9007 J9 VOX SANG JI Vox Sang. PD JUL PY 2008 VL 95 SU 1 BP 35 EP 35 PG 1 WC Hematology SC Hematology GA 298DD UT WOS:000255665700066 ER PT J AU Spaniolas, K Velmahos, GC Kwolek, C Gervasini, A De Moya, M Alam, HB AF Spaniolas, Konstantinos Velmahos, George C. Kwolek, Christopher Gervasini, Alice De Moya, Marc Alam, Hasan B. TI Bedside placement of removable vena cava filters guided by intravascular ultrasound in the critically injured SO WORLD JOURNAL OF SURGERY LA English DT Article ID RISK TRAUMA PATIENTS; INTENSIVE-CARE-UNIT; INTERMITTENT PNEUMATIC COMPRESSION; EARLY CLINICAL-EXPERIENCE; PULMONARY-EMBOLISM; FOLLOW-UP; VENOUS THROMBOEMBOLISM; MULTICENTER; INSERTION; COMPLICATIONS AB Background Bedside placement of removable inferior vena cava filters (RVCF) is increasingly used in critically injured patients. The need for fluoroscopic equipment and specialized intensive care unit beds presents major challenges. Intravascular ultrasound (IVUS) eliminates such problems. The objective of the present study was to analyze the safety and feasibility of IVUS-guided bedside RVCF placement in critically injured patients. Methods Between October 2004 and July 2006 47 IVUS-guided RVCF were placed at the bedside. Medical and trauma registry records were reviewed. Primary outcome was RVCF-related complications. Results The mean patient age was 41 +/- 19 years, and the mean Injury Severity Score was 30 +/- 12. The right common femoral vein was chosen as the site of access in 40 patients, and the left common femoral vein was the access site in 7 patients. The insertion was performed 3.7 +/- 2.5 days after admission. Four patients (8.5%) developed common femoral deep vein thrombosis (DVT) and three (6%) developed a peripheral pulmonary embolism (PE). Complications related to technique were recorded in two patients (4%) and included one misplacement and one access site bleeding with no further associated morbidity. Five patients died during the hospital stay from issues unrelated to RVCF. Forty-one patients were eligible for follow-up. Removal of RVCF was offered only to 8 patients and was performed successfully in 4 (10%) at a mean of 130 days (range: 44-183 days). Conclusions In this study IVUS-guided bedside placement of RVCF was feasible but was also associated with complications. Follow-up was poor, and the rate of removal disappointingly low, underscoring the need for further exploration of the role of RVCF. C1 [Spaniolas, Konstantinos; Velmahos, George C.; Gervasini, Alice; De Moya, Marc; Alam, Hasan B.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Spaniolas, Konstantinos; Velmahos, George C.; Gervasini, Alice; De Moya, Marc; Alam, Hasan B.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kwolek, Christopher] Massachusetts Gen Hosp, Dept Surg, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM gvelmahos@partners.org NR 49 TC 3 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD JUL PY 2008 VL 32 IS 7 BP 1438 EP 1443 DI 10.1007/s00268-008-9523-y PG 6 WC Surgery SC Surgery GA 314RN UT WOS:000256826600028 PM 18330626 ER PT J AU Hermsen, JL Ibele, AR Faucher, LD Nale, JK Schurr, MJ Kudsk, KA AF Hermsen, Joshua L. Ibele, Anna R. Faucher, Lee D. Nale, Jennifer K. Schurr, Michael J. Kudsk, Kenneth A. TI Retrievable inferior vena cava filters in high-risk trauma and surgical patients: Factors influencing successful removal SO WORLD JOURNAL OF SURGERY LA English DT Article ID INTRAVASCULAR ULTRASOUND; VENOUS THROMBOEMBOLISM; SAFETY AB Background An Inferior vena cava filter (IVCF) provides prophylaxis against pulmonary embolism in patients that cannot be anticoagulated. A removable IVCF (R-IVCF) provides prophylaxis during a high-risk period while potentially eliminating long-term complications associated with a permanent IVCF. Factors influencing success of R-IVCF removal are ill-defined. Methods The study was a retrospective review of a prospectively maintained patient registry comprising patients who received an R-IVCF (Bard Recovery (TM) and G2 (TM)) at an academic level 1 trauma center. The influence of time in vivo, filter design, and filter head position on computed abdominal tomographic (CAT) scan (touching caval wall vs. free) on removal success was examined. Results Ninety-two patients each received an R-IVCF. Thirty-nine patients underwent removal attempt and 30 R-IVCFs were removed. Time in vivo did not affect removal success (success: 228 +/- 104 days versus unsuccessful: 289 +/- 158 days, p = 0.18). Filter design impacted filter head position (Recovery: 43% touching versus G2: 6% touching, p = 0.023). Position of the filter head influenced removal success (touching: 50% success versus free: 88% success, p = 0.021). Conclusions Position of the filter head is the key determinant of removal success. Specific device designs may impact filter head position as was the case with the two designs in this analysis. Time in vivo does not affect removal success. C1 [Hermsen, Joshua L.; Ibele, Anna R.; Faucher, Lee D.; Nale, Jennifer K.; Schurr, Michael J.; Kudsk, Kenneth A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI 53792 USA. [Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI 53705 USA. RP Kudsk, KA (reprint author), 600 Highland Ave,H4-736 CSC, Madison, WI 53792 USA. EM KUDSK@surgery.wisc.edu FU NIGMS NIH HHS [R01 GM53439] NR 13 TC 14 Z9 16 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD JUL PY 2008 VL 32 IS 7 BP 1444 EP 1449 DI 10.1007/s00268-007-9462-z PG 6 WC Surgery SC Surgery GA 314RN UT WOS:000256826600029 PM 18264826 ER PT J AU Shao, CL Folkard, M Held, KD Prise, KM AF Shao, Chunlin Folkard, Melvyn Held, Kathryn D. Prise, Kevin M. TI Estrogen enhanced cell-cell signalling in breast cancer cells exposed to targeted irradiation SO BMC CANCER LA English DT Article ID CHARGED-PARTICLE MICROBEAM; MEDIATED INTERCELLULAR COMMUNICATION; SISTER-CHROMATID EXCHANGES; ALPHA-PARTICLES; HUMAN FIBROBLASTS; GLIOMA-CELLS; BYSTANDER RESPONSES; IONIZING-RADIATION; NITRIC-OXIDE; IN-VITRO AB Background: Radiation-induced bystander responses, where cells respond to their neighbours being irradiated are being extensively studied. Although evidence shows that bystander responses can be induced in many types of cells, it is not known whether there is a radiation-induced bystander effect in breast cancer cells, where the radiosensitivity may be dependent on the role of the cellular estrogen receptor ( ER). This study investigated radiation-induced bystander responses in estrogen receptor-positive MCF-7 and estrogen receptor-negative MDA-MB-231 breast cancer cells. Methods: The influence of estrogen and anti-estrogen treatments on the bystander response was determined by individually irradiating a fraction of cells within the population with a precise number of helium-3 using a charged particle microbeam. Damage was scored as chromosomal damage measured as micronucleus formation. Results: A bystander response measured as increased yield of micronucleated cells was triggered in both MCF-7 and MDA-MB-231 cells. The contribution of the bystander response to total cell damage in MCF-7 cells was higher than that in MDA-MB-231 cells although the radiosensitivity of MDA-MB-231 was higher than MCF-7. Treatment of cells with 17 beta-estradiol (E2) increased the radiosensitivity and the bystander response in MCF-7 cells, and the effect was diminished by antiestrogen tamoxifen (TAM). E2 also increased the level of intracellular reactive oxygen species (ROS) in MCF-7 cells in the absence of radiation. In contrast, E2 and TAM had no influence on the bystander response and ROS levels in MDA-MB-231 cells. Moreover, the treatment of MCF-7 cells with antioxidants eliminated both the E2-induced ROS increase and E2-enhanced bystander response triggered by the microbeam irradiation, which indicates that ROS are involved in the E2-enhanced bystander micronuclei formation after microbeam irradiation. Conclusion: The observation of bystander responses in breast tumour cells may offer new potential targets for radiation-based therapies in the treatment of breast cancer. C1 [Prise, Kevin M.] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Belfast BT9 7AB, Antrim, North Ireland. [Shao, Chunlin] Fudan Univ, Inst Radiat Med, Shanghai 200032, Peoples R China. [Folkard, Melvyn] Mt Vernon Hosp, Grey Canc Inst, Northwood HA6 2JR, Middx, England. [Held, Kathryn D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Prise, KM (reprint author), Queens Univ Belfast, Ctr Canc Res & Cell Biol, 97 Lisburn Rd, Belfast BT9 7AB, Antrim, North Ireland. EM clshao@shmu.edu.cn; folkard@gci.ac.uk; kheld@partners.org; k.prise@qub.ac.uk RI Prise, Kevin/N-7872-2015 OI Prise, Kevin/0000-0001-6134-7946 FU Cancer Research UK [A7047, C1513/A7047] NR 56 TC 17 Z9 17 U1 0 U2 9 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 JUN 30 PY 2008 VL 8 AR 184 DI 10.1186/1471-2407-8-184 PG 9 WC Oncology SC Oncology GA 326VS UT WOS:000257687800001 PM 18590532 ER PT J AU Watanabe, N Bodin, L Pandey, M Krause, M Coughlin, S Boussiotis, VA Ginsberg, MH Shattil, SJ AF Watanabe, Naohide Bodin, Laurent Pandey, Manjula Krause, Matthias Coughlin, Shaun Boussiotis, Vassiliki A. Ginsberg, Mark H. Shattil, Sanford J. TI Mechanisms and consequences of agonist-induced talin recruitment to platelet integrin alpha IIb beta 3 SO JOURNAL OF CELL BIOLOGY LA English DT Article ID PROTEASE-ACTIVATED RECEPTORS; GLYCOPROTEIN-IIB-IIIA; EMBRYONIC STEM-CELLS; CYTOPLASMIC DOMAIN; CALDAG-GEFI; GPIIB-IIIA; GLANZMANN THROMBASTHENIA; FLUORESCENT PROTEIN; THROMBUS FORMATION; STRUCTURAL BASIS AB Platelet aggregation requires agonist-induced alpha IIb beta 3 activation, a process mediated by Rap1 and talin. To study mechanisms, we engineered alpha IIb beta 3 Chinese hamster ovary (CHO) cells to conditionally express talin and protease-activated receptor ( PAR) thrombin receptors. Human PAR1 or murine PAR4 stimulation activates alpha IIb beta 3, which was measured with antibody PAC-1, indicating complete pathway reconstitution. Knockdown of Rap1 guanosine triphosphate-interacting adaptor molecule (RIAM), a Rap1 effector, blocks this response. In living cells, RIAM overexpression stimulates and RIAM knockdown blocks talin recruitment to alpha IIb beta 3,which is monitored by bimolecular fluorescence complementation. Mutations in talin or beta 3 that disrupt their mutual interaction block both talin recruitment and alpha IIb beta 3 activation. However, one talin mutant (L325R) is recruited to alpha IIb beta 3 but cannot activate it. In platelets, RIAM localizes to filopodia and lamellipodia, and, in megakaryocytes, RIAM knockdown blocks PAR4-mediated alpha IIb beta 3 activation. The RIAM-related protein lamellipodin promotes talin recruitment and alpha IIb beta 3 activity in CHO cells but is not expressed in megakaryocytes or platelets. Thus, talin recruitment to alpha IIb beta 3 by RIAM mediates agonist-induced alpha IIb beta 3 activation, with implications for hemostasis and thrombosis. C1 [Watanabe, Naohide; Bodin, Laurent; Pandey, Manjula; Ginsberg, Mark H.; Shattil, Sanford J.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Krause, Matthias] Kings Coll London, Randall Div Cell & Mol Biophys, London SE1 1UL, England. [Coughlin, Shaun] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Coughlin, Shaun] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Boussiotis, Vassiliki A.] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. [Boussiotis, Vassiliki A.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02115 USA. RP Shattil, SJ (reprint author), Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. EM sshattil@ucsd.edu RI Krause, Matthias/D-9814-2013 OI Krause, Matthias/0000-0002-3200-3199 FU NHLBI NIH HHS [HL56595, HL57900, P01 HL057900, R01 HL056595]; Wellcome Trust [077429] NR 68 TC 92 Z9 94 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUN 30 PY 2008 VL 181 IS 7 BP 1211 EP 1222 DI 10.1083/jcb.200803094 PG 12 WC Cell Biology SC Cell Biology GA 324VJ UT WOS:000257547200016 PM 18573917 ER PT J AU Heaton, JT Kowaleski, JM Bermejo, R Zeigler, HP Ahlgren, DJ Hadlock, TA AF Heaton, James T. Kowaleski, Jeffrey M. Bermejo, Roberto Zeigler, H. Philip Ahlgren, David J. Hadlock, Tessa A. TI A system for studying facial nerve function in rats through simultaneous bilateral monitoring of eyelid and whisker movements SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE barrel cortex; denervation; facial nerve; palsy; paralysis; regeneration; reinnervation; synkinesis; vibrissae; whisking ID MYSTACIAL VIBRISSAE; ALERT CAT; RESPONSES; TRANSECTION; RETRACTION; SYNKINESIS; RECOVERY; REFLEX; RECTUS; RABBIT AB The occurrence of inappropriate co-contraction (synkinesis) of facially innervated muscles in humans is a common sequela of facial nerve injury and recovery. We have developed a system for studying facial nerve function and synkinesis in restrained rats using non-contact opto-electronic techniques that enable simultaneous bilateral monitoring of eyelid and whisker movements. Whisking is monitored in high spatio-temporal resolution using laser micrometers, and eyelid movements are detected using infrared diode and phototransistor pairs that respond to the increased reflection when the eyelids cover the cornea. To validate the system, 8 rats were tested with multiple 5-min sessions that included corneal air puffs to elicit blink and scented air flows to elicit robust whisking. Four rats then received unilateral facial nerve section and were tested at weeks 3-6. Whisking and eye blink behavior occurred both spontaneously and under stimulus control, with no detectable difference from published whisking data. Proximal facial nerve section caused an immediate ipsilateral loss of whisking and eye blink response, but some ocular closures emerged due to retractor bulbi muscle function. The independence observed between whisker and eyelid control indicates that this system may provide a powerful tool for identifying abnormal co-activation of facial zones resulting from aberrant axonal regeneration. (c) 2008 Elsevier B.V. All rights reserved. C1 [Heaton, James T.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Kowaleski, Jeffrey M.; Hadlock, Tessa A.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Bermejo, Roberto; Zeigler, H. Philip] CUNY Hunter Coll, Biopsychol Program, New York, NY 10065 USA. [Ahlgren, David J.] Trinity Coll, Dept Engn, Hartford, CT 06106 USA. RP Heaton, JT (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM james.heaton@mgh.harvard.edu FU NIDCR NIH HHS [K08 DE015665-02, K08 DE015665, K-08 DE015665-01A2, K08 DE015665-03, K08 DE015665-01A2]; NINDS NIH HHS [NS048937, R01 NS048937-04, R01 NS048937-03, R01 NS048937] NR 23 TC 29 Z9 29 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD JUN 30 PY 2008 VL 171 IS 2 BP 197 EP 206 DI 10.1016/j.jneumeth.2008.02.023 PG 10 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 315EC UT WOS:000256859800003 PM 18442856 ER PT J AU de Crespigny, A Bou-Reslan, H Nishimura, MC Phillips, H Carano, RAD D'Arceuil, HE AF de Crespigny, Alex Bou-Reslan, Hani Nishimura, Merry C. Phillips, Heidi Carano, Richard A. D. D'Arceuil, Helen E. TI 3D micro-CT imaging of the postmortem brain SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE brain; micro-CT; magnetic resonance microscopy; postmortem; pathology; tumor ID MAGNETIC-RESONANCE MICROSCOPY; COMPUTED-TOMOGRAPHY; MR MICROSCOPY; ANGIOGENESIS; TRACTOGRAPHY; SPECIMENS; HISTOLOGY; REPAIR; MOUSE; T1 AB Magnetic resonance microscopy (mu MRI) is becoming an important tool for non-destructive analysis of fixed brain tissue. However, unlike MRI, X-ray computed tomography (CT) scans show little native soft tissue contrast. In this paper, we explored the use of contrast enhanced (brains immersion stained in iodinated CT contrast media) micro-CT (mu CT) for high resolution 3D imaging of fixed normal and pathological brains, compared to mu MRI and standard histopathology. An optimum iodine concentration of 0.27 M resulted in excellent contrast between gray and white matter in normal brain and a wide range of anatomical structures were identified. In glioma bearing mouse brains, there was clear deliniation of tumor margin which closely matched that seen on histopathology sections. mu CT tumor volume was strongly correlated with histopathology volume. Our data suggests that mu CT image contrast in the immersion-stained brains is related to axonal density and myelin content. Compared to traditional histopathology, our mu CT approach is relatively rapid and less labor intensive. In addition, compared to mu MRI, mu CT is robust and requires much lower equipment and maintenance costs. For simple measurements, such as tumor volume and non-destructive postmortem brain screening, mu CT may prove to be a valuable alternative to standard histopathology or mu MRI. 2008 Elsevier B.V. All rights reserved. C1 [de Crespigny, Alex; D'Arceuil, Helen E.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Bou-Reslan, Hani; Nishimura, Merry C.; Phillips, Heidi; Carano, Richard A. D.] Genentech Inc, Tumor Biol & Angiogenesis, San Francisco, CA 94080 USA. RP D'Arceuil, HE (reprint author), MGH NMR Ctr, Room 2301,Bldg 149 13th St, Boston, MA 02129 USA. EM helen@nmr.mgh.harvard.edu FU NCRR NIH HHS [1S10RR016811, P41 RR014075, P41 RR014075-03, P41RR14075, S10 RR016811, S10 RR016811-01]; NIBIB NIH HHS [R01 EB000790-01A2, EB00790, R01 EB000790] NR 27 TC 42 Z9 43 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD JUN 30 PY 2008 VL 171 IS 2 BP 207 EP 213 DI 10.1016/j.jneumeth.2008.03.006 PG 7 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 315EC UT WOS:000256859800004 PM 18462802 ER PT J AU Falke, KJ Busch, T Hoffmann, O Liggins, GC Liggins, J Mohnhaupt, R Roberts, JD Stanek, K Zapol, WM AF Falke, K. J. Busch, T. Hoffmann, O. Liggins, G. C. Liggins, J. Mohnhaupt, R. Roberts, J. D., Jr. Stanek, K. Zapol, W. M. TI Breathing pattern, CO(2) elimination and the absence of exhaled NO in freely diving Weddell seals SO RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY LA English DT Article DE marine mammals; respiratory function; lung volume; lung collapse; apnea; NO ID ENDOGENOUS NITRIC-OXIDE; LEPTONYCHOTES-WEDDELLI; PULMONARY-FUNCTION; NITROGEN TENSIONS; PARANASAL SINUSES; METABOLIC RATES; OXYGEN STORES; HUMANS; GAS; MAMMALS AB Weddell seals undergo lung collapse during dives below 50 m depth. In order to explore the physiological mechanisms contributing to restoring lung volume and gas exchange after surfacing, we studied ventilatory parameters in three Weddell seals between dives from an isolated ice hole on McMurdo Sound, Antarctica. Methods: Lung volumes and CO(2) elimination were investigated using a pneumotachograph, infrared gas analysis, and nitrogen washout. Thoracic circumference was determined with a strain gauge. Exhaled nitric oxide was measured using chemiluminescence. Results: Breathing of Weddell seals was characterized by an apneustic pattern with end-inspiratory pauses with functional residual capacity at the end of inspiration. Respiratory flow rate and tidal volume peaked within the first 3 min after surfacing. Lung volume reductions before and increases after diving were approximately 20% of the lung volume at rest. Thoracic circumference changed by less than 2% during diving. The excess CO(2) eliminated after dives correlated closely with the duration of the preceding dive. Nitric oxide was not present in the expired gas. Conclusion: Our data suggest that most of the changes in lung volume during diving result from compression and decompression of the gas remaining in the respiratory tract. Cranial shifts of the diaphragm and translocation of blood into the thorax rather than a reduction of thoracic circumference appear to compensate for lung collapse. The time to normalise gas exchange after surfacing was mainly determined by the accumulation of CO(2) during the dive. These findings underline the remarkable adaptations of the Weddell seal for restoring lung volume and gas exchange after diving. (c) 2008 Elsevier B.V. All rights reserved. C1 [Falke, K. J.] Univ Med Berlin, Charite Campus Virchow Klinikum, Klin Anaesthesiol & Operat lntensivmed, D-13353 Berlin, Germany. [Busch, T.] Univ Klinikum Leipzig, Klin & Poliklin Anaesthesiol & lntensivtherapie, D-04103 Leipzig, Germany. [Hoffmann, O.] Univ Med Berlin, Klin & Poliklin Neurol, D-10098 Berlin, Germany. [Liggins, G. C.; Liggins, J.] Univ Auckland, Dept Obstet & Gynaecol, Res Ctr Reprod Med, Auckland 1142, New Zealand. [Roberts, J. D., Jr.; Stanek, K.; Zapol, W. M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Falke, KJ (reprint author), Neuen Garten 41, D-14469 Potsdam, Germany. EM Konradj.Falke@charite.de RI Busch, Thilo/J-8258-2015 NR 40 TC 11 Z9 11 U1 0 U2 32 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-9048 J9 RESP PHYSIOL NEUROBI JI Respir. Physiol. Neuro. PD JUN 30 PY 2008 VL 162 IS 1 BP 85 EP 92 DI 10.1016/j.resp.2008.04.007 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 326HW UT WOS:000257650200012 PM 18534926 ER PT J AU Tetzlaff, JE Putcha, P Outeiro, TF Ivanov, A Berezovska, O Hyman, BT McLean, PJ AF Tetzlaff, Julie E. Putcha, Preeti Outeiro, Tiago F. Ivanov, Alexander Berezovska, Oksana Hyman, Bradley T. McLean, Pamela J. TI CHIP targets toxic alpha-synuclein oligomers for degradation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEAT-SHOCK PROTEINS; PARKINSONS-DISEASE; IN-VITRO; CHAPERONE FUNCTIONS; CARBOXYL-TERMINUS; AGGREGATION; TAU; HSP70; UBIQUITINATION; NEUROTOXICITY AB alpha-Synuclein (alpha Syn) can self-associate, forming oligomers, fibrils, and Lewy bodies, the pathological hallmark of Parkinson disease. Current dogma suggests that oligomeric alpha Syn intermediates may represent the most toxic alpha Syn species. Here, we studied the effect of a potent molecular chaperone, CHIP ( carboxyl terminus of Hsp70- interacting protein), on alpha Syn oligomerization using a novel bimolecular fluorescence complementation assay. CHIP is a multidomain chaperone, utilizing both a tetratricopeptide/Hsp70 binding domain and a U-box/ubiquitin ligase domain to differentially impact the fate of misfolded proteins. In the current study, we found that co-expression of CHIP selectively reduced alpha Syn oligomerization and toxicity in a tetratricopeptide domain-dependent, U-box-independent manner by specifically degrading toxic alpha Syn oligomers. We conclude that CHIP preferentially recognizes and mediates degradation of toxic, oligomeric forms of alpha Syn. Further elucidation of the mechanisms of CHIP-induced degradation of oligomeric alpha Syn may contribute to the successful development of drug therapies that target oligomeric alpha Syn by mimicking or enhancing the powerful effects of CHIP. C1 [Tetzlaff, Julie E.; Putcha, Preeti; Outeiro, Tiago F.; Ivanov, Alexander; Berezovska, Oksana; Hyman, Bradley T.; McLean, Pamela J.] Massachusetts Gen Hosp, Alzheimer Dis Res Unit, Dept Neurol, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. RP McLean, PJ (reprint author), Massachusetts Gen Hosp, Alzheimer Dis Res Unit, Dept Neurol, MassGen Inst Neurodegenerat Dis, 114 16th St, Charlestown, MA 02129 USA. EM pmclean@partners.org RI Outeiro, Tiago/C-1067-2008 OI Outeiro, Tiago/0000-0003-1679-1727 FU NIA NIH HHS [P50 AG005134]; NINDS NIH HHS [P50 NS038372, P50 NS038372-030001, P50 NS038372-080001, R01 NS063963, R01 NS063963-01A1] NR 30 TC 79 Z9 80 U1 2 U2 11 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 JUN 27 PY 2008 VL 283 IS 26 BP 17962 EP 17968 DI 10.1074/jbc.M802283200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 316KU UT WOS:000256949200025 PM 18436529 ER PT J AU Reese, PP Sonawane, SB Thomasson, A Yeh, HD Markmann, JF AF Reese, Peter P. Sonawane, Samsher B. Thomasson, Arwin Yeh, Heidi Markmann, James F. TI Donor age and cold ischemia interact to produce inferior 90-day liver allograft survival SO TRANSPLANTATION LA English DT Article DE liver transplantation; donor age; ischemia ID CARDIAC DEATH DONORS; GRAFT-SURVIVAL; ORGAN ALLOCATION; TRANSPLANT RECIPIENTS; WAITING-LIST; IMPACT; CRITERIA; PATIENT; DISEASE; MODEL AB Background. Expanded regional sharing of liver allografts may increase cold ischemia and allograft failure, particularly with livers from older donors. The aim of this study was to examine whether older donor age and cold ischemic time interact to produce inferior allograft survival. Methods. We undertook a retrospective cohort study of adult liver transplants in the United States performed between December 1, 1995 and December 31, 2005, using data from the Organ Procurement and Transplantation Network. The primary outcome was allograft failure within 90 days. Results. Forty-four thousand seven hundred fifty-six liver transplant recipients were analyzed. Older age was defined as 45 years or more, and prolonged cold ischemia was defined as 12 hours or more. Using data from the pre-Model for End Stage Liver Disease (MELD), post-MELD and combined eras, three separate analyses of the interaction between older donor age and prolonged cold ischemia were performed. In multivariable logistic regression, the interaction of age 45 years or more and cold ischemia more than or equal to 12 hr reached statistical significance in the combined (OR 1.24, CI 1.08-1.42, P<0.01) and pre-MELD (OR 1.26, CI 1.08-1.46, P<0.01) datasets, but not in the smaller post-MELD dataset (OR 1.18, CI 0.81-1.72, P=0.38). In the combined dataset, recipients of livers from donors aged 45 years or more and cold ischemia more than or equal to 12 hr showed an adjusted absolute risk of allograft failure at 90 days of 17.3% (odds ratio 1.84), compared with 11.1% for recipients of livers from donors older than 45 years and cold ischemia less than 12 hr. Conclusions. These findings suggest that older donor age and prolonged cold ischemia interact to increase liver allograft failure at 90 days. Proposals to expand regional sharing of older livers should be regarded with caution. C1 [Reese, Peter P.; Sonawane, Samsher B.] Univ Penn, Renal Hypertens & Electrolyte Div, Philadelphia, PA 19104 USA. [Thomasson, Arwin] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Yeh, Heidi; Markmann, James F.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Reese, PP (reprint author), Univ Penn, Sch Med, Div Renal, 3400 Spruce St,1 Founders, Philadelphia, PA 19104 USA. EM peter.reese@uphs.upenn.edu NR 30 TC 28 Z9 29 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 JUN 27 PY 2008 VL 85 IS 12 BP 1737 EP 1744 DI 10.1097/TP.0b013e3181722f75 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 321CP UT WOS:000257282200010 PM 18580465 ER PT J AU Camirand, G Stephan, L Rousseau, J Sackett, MK Caron, NJ Mills, P Kurtz, J Sykes, M Rothstein, DM Tremblay, JP AF Camirand, Geoffrey Stephan, Lionel Rousseau, Joel Sackett, Melanie K. Caron, Nicolas J. Mills, Philippe Kurtz, Josef Sykes, Megan Rothstein, David M. Tremblay, Jacques P. TI Central tolerance to myogenic cell transplants does not include muscle neoantigens SO TRANSPLANTATION LA English DT Article DE transplantation; tolerance; dystrophin; Foxp3 ID REGULATORY T-CELLS; DUCHENNE MUSCULAR-DYSTROPHY; BONE-MARROW-TRANSPLANTATION; IMMUNOLOGICAL SELF-TOLERANCE; STAGE RENAL-DISEASE; MYOBLAST TRANSPLANTATION; IN-VIVO; ALLOGRAFT TOLERANCE; LYMPHOHEMATOPOIETIC CHIMERISM; ANTI-CD154 ANTIBODY AB Background. Duchenne muscular dystrophy is a fatal genetic disease caused by lack of dystrophin. Myogenic cell transplantation (MT), a potential therapy for Duchenne muscular dystrophy, can restore dystrophin expression in muscles. Because allogeneic MT is highly resistant to peripheral tolerance, we proposed to induce central tolerance. However, given its immunogenicity, we asked whether central tolerance to donor major histocompatibility complex would allow long-term expression of dystrophin, a tissue-specific neoantigen in dystrophic recipients. Methods. Central tolerance was induced in C57BL/10J mdx (dystrophic) mice by allogeneic bone marrow transplantation (BMT) after conditioning with either lethal total body irradiation (TBI) or an established nonmyeloablative protocol (anti-CD 154, anti-CD8 mAbs, and low-dose TBI). Recipients subsequently received donor-strain MT or skin grafts. Results. Long-term hematopoietic chimeras generated using either lethal TBI or the nonmyeloablative regimen were tolerant to donor skin grafts and both primary and secondary donor MT (>90 days). Myogenic cell transplantation survival was decreased when chimerism was transient, which was most common with nonmyeloablative conditioning and fully rather than haplo-mismatched donors. Interestingly, regardless of conditioning, MT was associated with localized muscle infiltration with Foxp3(+) CD4(+), CD25(+)CD4(+), and Perforin(+) CD8(+) cells, whereas skin grafts lacked infiltration. Conclusions. Central tolerance achieved using regimens that eliminate nearly all endogenous peripheral lymphocytes (i.e., lethal irradiation) or a nonmyeloablative protocol that depleted peripheral CD8 cells, results in lymphocytic infiltration in muscles that received MT but not in skin allografts. This suggests that muscle-specific infiltration may result from lack of negative selection for peripheral neoantigens in the thymus after BMT and that tolerance after MT may rely on peripheral regulatory mechanisms. C1 [Camirand, Geoffrey; Rothstein, David M.] Yale Univ, Sch Med, New Haven, CT USA. [Stephan, Lionel; Rousseau, Joel; Sackett, Melanie K.; Caron, Nicolas J.; Mills, Philippe; Tremblay, Jacques P.] Univ Laval, CHUL, Unite Genet Humaine, Ctr Rech, Quebec City, PQ, Canada. [Kurtz, Josef; Sykes, Megan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplantat Sect,Transplantat Biol R, Boston, MA USA. RP Tremblay, JP (reprint author), Univ Laval, CHU Laval, Unite Genet Humaine, 2705 Blvd Laurier,RC-9300, Ste Foy, PQ G1V 4G2, Canada. EM jacques-p.tremblay@crchul.ulaval.ca RI Camirand, Geoffrey/I-9921-2012 FU NIAMS NIH HHS [AR053242, R01 AR053242] NR 52 TC 8 Z9 9 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 JUN 27 PY 2008 VL 85 IS 12 BP 1791 EP 1801 DI 10.1097/TP.0b013e31817726bc PG 11 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 321CP UT WOS:000257282200018 PM 18580473 ER PT J AU Stiles, CD Rowitch, DH AF Stiles, Charles D. Rowitch, David H. TI Glioma stem cells: A midterm exam SO NEURON LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; GROWTH-FACTOR RECEPTOR; LOW-GRADE GLIOMAS; OLIGODENDROCYTE PRECURSOR CELLS; ADULT OLFACTORY-BULB; OLIG GENE-FUNCTION; PROGENITOR CELLS; SELF-RENEWAL; GLIOBLASTOMA-MULTIFORME; SUBVENTRICULAR ZONE C1 [Stiles, Charles D.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Stiles, Charles D.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Rowitch, David H.] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Pediat, San Francisco, CA 94143 USA. [Rowitch, David H.] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Neurol Surg, San Francisco, CA 94143 USA. [Rowitch, David H.] Univ Calif San Francisco, Inst Regenerat Med, San Francisco, CA 94143 USA. RP Stiles, CD (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM charles.stiles@dfci.harvard.edu; rowitchd@peds.ucsf.edu FU NINDS NIH HHS [P01 NS047572, P01NS047572, R01NS057727] NR 157 TC 191 Z9 200 U1 2 U2 19 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD JUN 26 PY 2008 VL 58 IS 6 BP 832 EP 846 DI 10.1016/j.neuron.2008.05.031 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 319NW UT WOS:000257171700005 PM 18579075 ER PT J AU Wang, Q Zengin, A Ying, W Newell, KA Wang, P Yeo, W Wong, PTH Yenari, MA Huang, XF AF Wang, Q. Zengin, A. Ying, W. Newell, K. A. Wang, P. Yeo, W. Wong, P. T. -H. Yenari, M. A. Huang, X. -F. TI Chronic treatment with simvastatin upregulates muscarinic M1/4 receptor binding in the rat brain SO NEUROSCIENCE LA English DT Article DE statins; muscarinic receptors; hydroxymethylglutaryl-coenzyme; reductase inhibitors; upregulation; Alzheimer's disease ID STRIATAL DOPAMINE RELEASE; AMYLOID PRECURSOR PROTEIN; CENTRAL-NERVOUS-SYSTEM; IN-VIVO MICRODIALYSIS; ALZHEIMERS-DISEASE; M2-MUSCARINIC DRUGS; PREFRONTAL CORTEX; TRANSGENIC MICE; ALPHA-FORM; STATINS AB Statins are increasingly being used for the treatment of a variety of conditions beyond their original indication for cholesterol lowering. We previously reported that simvastatin affected the dopaminergic system in the rat brain. This study aims to investigate regional changes of muscarinic M1/4 receptors in the rat brain after 4-week administration of simvastatin (1 or 10 mg/kg/day). M1/4 receptor distribution and alterations in the post-mortem rat brain were detected by [H-3]pirenzepine binding autoradiography. Simvastatin (1 mg/kg/day) increased [H-3]pirenzepine binding, predominantly in the prefrontal cortex (171%, P<0.001), primary motor cortex (153%, P=0.001), cingulate cortex (109%, P<0.001), hippocampus (138%, P<0.001), caudate putamen (122%, P=0.002) and nucleus accumbens (170%, P<0.001) compared with controls; while lower but still significant increases of [H-3]pirenzepine binding were observed in the examined regions following simvastatin (10 mg/kg/day) treatment. Our results also provide strong evidence that chronic simvastatin administration, especially at a low dosage, up-regulates M1/4 receptor binding, which is likely to be independent of its muscarinic agonist-like effect. Alterations in [H-3]pirenzepine binding in the examined brain areas may represent the specific regions that mediate the clinical effects of simvastatin treatment on cognition and memory via the muscarinic cholinergic system. These findings contribute to a better understanding of the critical roles of simvastatin in treating neurodegenerative disorders, via muscarinic receptors. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Wang, Q.; Zengin, A.; Newell, K. A.; Yeo, W.; Huang, X. -F.] Univ Wollongong, Neurobiol Res Ctr, Sch Hlth Sci, Wollongong, NSW 2522, Australia. [Wang, Q.; Zengin, A.; Newell, K. A.; Yeo, W.; Huang, X. -F.] Univ Wollongong, Grad Sch Med, Wollongong, NSW 2522, Australia. [Ying, W.; Yenari, M. A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Ying, W.; Yenari, M. A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Wong, P. T. -H.] Natl Univ Singapore, Dept Pharmacol, Yong Loo Lin Sch Med, Singapore 117597, Singapore. [Wang, P.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. RP Wang, Q (reprint author), Univ Wollongong, Neurobiol Res Ctr, Sch Hlth Sci, Wollongong, NSW 2522, Australia. EM denniswq@yahoo.com RI Huang, Xu-Feng/D-6053-2013; Newell, Kelly/K-5550-2014; Huang, Xu-Feng/H-7408-2015; OI Newell, Kelly/0000-0002-1245-5585; Huang, Xu-Feng/0000-0002-5895-2253; Zengin, Ayse/0000-0001-6428-6165 NR 53 TC 12 Z9 13 U1 0 U2 5 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 JUN 26 PY 2008 VL 154 IS 3 BP 1100 EP 1106 DI 10.1016/j.neuroscience.2008.04.026 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 319OE UT WOS:000257172500024 PM 18501522 ER PT J AU Hunter, DJ Altshuler, D Rader, DJ AF Hunter, David J. Altshuler, David Rader, Daniel J. TI From Darwin's finches to canaries in the coal mine - Mining the genome for new biology SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID LOCI C1 [Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Altshuler, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rader, Daniel J.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. RP Hunter, DJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 5 TC 52 Z9 55 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 26 PY 2008 VL 358 IS 26 BP 2760 EP 2763 DI 10.1056/NEJMp0804318 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 317UO UT WOS:000257045900002 PM 18579810 ER PT J AU Bonkovsky, HL Siao, P Roig, Z Hedley-Whyte, ET Flotte, TJ Bloom, AK Harris, NL Buonanno, FS Gonzalez, E AF Bonkovsky, Herbert L. Siao, Peter Roig, Zulmarie Hedley-Whyte, E. Tessa Flotte, Thomas J. Bloom, Allyson K. Harris, Nancy Lee Buonanno, Ferdinando S. Gonzalez, Ernesto TI A woman with abdominal pain and weakness after gastric bypass surgery - Acute porphyria (variegate porphyria) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE INTERMITTENT PORPHYRIA; SYNTHASE; REPRESSION; HEMATIN; GENE C1 [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT 06030 USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Mol Microbial & Struct Biol, Farmington, CT USA. [Bonkovsky, Herbert L.] Carolinas Med Ctr, Dept Med, Charlotte, NC 28203 USA. [Bonkovsky, Herbert L.] Univ N Carolina, Chapel Hill, NC USA. [Bonkovsky, Herbert L.] Univ N Carolina, Dept Biol, Charlotte, NC 28223 USA. [Siao, Peter] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Roig, Zulmarie] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hedley-Whyte, E. Tessa; Flotte, Thomas J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Siao, Peter] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Roig, Zulmarie] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Hedley-Whyte, E. Tessa; Flotte, Thomas J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Bonkovsky, HL (reprint author), Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT 06030 USA. NR 25 TC 12 Z9 12 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 JUN 26 PY 2008 VL 358 IS 26 BP 2813 EP 2825 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 317UO UT WOS:000257045900011 PM 18579817 ER PT J AU Rahilly-Tierney, CR Nash, IS AF Rahilly-Tierney, Catherine R. Nash, Ira S. TI Decision-making in percutaneous coronary intervention: a survey SO BMC MEDICAL INFORMATICS AND DECISION MAKING LA English DT Article ID BYPASS-SURGERY; APPROPRIATENESS; DISEASE; REVASCULARIZATION; CONSISTENCY; GENERALISTS; SPECIALTY AB Background: Few researchers have examined the perceptions of physicians referring cases for angiography regarding the degree to which collaboration occurs during percutaneous coronary intervention (PCI) decision-making. We sought to determine perceptions of physicians concerning their involvement in PCI decisions in cases they had referred to the cardiac catheterization laboratory at a major academic medical center. Methods: An anonymous survey was mailed to internal medicine faculty members at a major academic medical center. The survey elicited whether responders perceived that they were included in decision-making regarding PCI, and whether they considered such collaboration to be the best process of decision-making. Results: Of the 378 surveys mailed, 35% (133) were returned. Among responding non-cardiologists, 89% indicated that in most cases, PCI decisions were made solely by the interventionalist at the time of the angiogram. Among cardiologists, 92% indicated that they discussed the findings with the interventionalist prior to any PCI decisions. When asked what they considered the best process by which PCI decisions are made, 66% of non-cardiologists answered that they would prefer collaboration between either themselves or a non-interventional cardiologist and the interventionalist. Among cardiologists, 95% agreed that a collaborative approach is best. Conclusion: Both non-cardiologists and cardiologists felt that involving another decision-maker, either the referring physician or a non-interventional cardiologist, would be the best way to make PCI decisions. Among cardiologists, there was more concordance between what they believed was the best process for making decisions regarding PCI and what they perceived to be the actual process. C1 [Rahilly-Tierney, Catherine R.] MAVERIC, Boston VA Healthcare Syst, Boston, MA USA. [Rahilly-Tierney, Catherine R.] Harvard Univ, Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Nash, Ira S.] Mt Sinai Med Ctr, Zena & Michael A Wiener Cardiovasc Inst, New York, NY 10029 USA. RP Rahilly-Tierney, CR (reprint author), MAVERIC, Boston VA Healthcare Syst, Boston, MA USA. EM Catherine.Rahilly@va.gov; ira.nash@msnyuhealth.org NR 10 TC 2 Z9 2 U1 0 U2 2 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 JUN 25 PY 2008 VL 8 AR 28 DI 10.1186/1472-6947-8-28 PG 4 WC Medical Informatics SC Medical Informatics GA 323JW UT WOS:000257443400002 PM 18578880 ER PT J AU Winton, MJ Van Deerlin, VM Kwong, LK Yuan, W Wood, EM Yu, CE Schellenberg, GD Rademakers, R Caselli, R Karydas, A Trojanowski, JQ Miller, BL Lee, VMY AF Winton, Matthew J. Van Deerlin, Vivianna M. Kwong, Linda K. Yuan, Wuxing Wood, Elisabeth McCarty Yu, Chang-En Schellenberg, Gerard D. Rademakers, Rosa Caselli, Richard Karydas, Anna Trojanowski, John Q. Miller, Bruce L. Lee, Virginia M. -Y. TI A90V TDP-43 variant results in the aberrant localization of TDP-43 in vitro SO FEBS LETTERS LA English DT Article DE TDP-43; FTLD-U; ALS; TARDBP mutations; A90V ID FRONTOTEMPORAL LOBAR DEGENERATION; AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DISEASE; DNA-BINDING PROTEIN; DEMENTIA; INCLUSIONS; MUTATIONS AB TAR DNA-binding protein-43 (TDP-43) is a highly conserved, ubiquitously expressed nuclear protein that was recently identified as the disease protein in frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS). Pathogenic TDP-43 gene (TARDBP) mutations have been identified in familial ALS kindreds, and here we report a TARDBP variant (A90V) in a FTLD/ALS patient with a family history of dementia. Significantly, A90V is located between the bipartite nuclear localization signal sequence of TDP-43 and the in vitro expression of TDP-43-A90V led to its sequestration with endogenous TDP-43 as insoluble cytoplasmic aggregates. Thus, A90V may be a genetic risk factor for FTLD/ALS because it predisposes nuclear TDP-43 to redistribute to the cytoplasm and form pathological aggregates. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 [Winton, Matthew J.; Van Deerlin, Vivianna M.; Kwong, Linda K.; Yuan, Wuxing; Wood, Elisabeth McCarty; Trojanowski, John Q.; Lee, Virginia M. -Y.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. [Van Deerlin, Vivianna M.; Trojanowski, John Q.; Lee, Virginia M. -Y.] Univ Penn, Sch Med, Alzheimers Dis Core Ctr, Philadelphia, PA 19104 USA. [Van Deerlin, Vivianna M.; Trojanowski, John Q.; Lee, Virginia M. -Y.] Univ Penn, Sch Med, Inst Aging, Philadelphia, PA 19104 USA. [Yu, Chang-En; Schellenberg, Gerard D.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle Div, Seattle, WA 98108 USA. [Yu, Chang-En; Schellenberg, Gerard D.] Univ Washington, Div Gerontol & Geriatr Med, Dept Med, Seattle, WA 98108 USA. [Rademakers, Rosa] Mayo Clin, Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA. [Caselli, Richard] Mayo Clin, Dept Neurosci, Scottsdale, AZ 85259 USA. [Caselli, Richard] Arizona Alzheimers Dis Ctr, Scottsdale, AZ 85259 USA. [Karydas, Anna; Miller, Bruce L.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94117 USA. RP Lee, VMY (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. EM vmylee@mail.med.upenn.edu FU NIA NIH HHS [AG 16574, P01 AG017586-089002, P30 AG010124, P50 AG016574, P01 AG019724, P50 AG005136, AG 10124, P30 AG010124-09, P30 AG010129, AG 05142, P01 AG017586-09, AG 10129, P50 AG005142, AG 17586, P01 AG017586, P50 AG005136-25]; NIMH NIH HHS [R01 MH057899, MH 57899] NR 19 TC 47 Z9 49 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 25 PY 2008 VL 582 IS 15 BP 2252 EP 2256 DI 10.1016/j.febslet.2008.05.024 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 326PI UT WOS:000257671000018 PM 18505686 ER PT J AU Ancuta, P Kamat, A Kunstman, KJ Kim, EY Autissier, P Wurcel, A Zaman, T Stone, D Mefford, M Morgello, S Singer, EJ Wolinsky, SM Gabuzda, D AF Ancuta, Petronela Kamat, Anupa Kunstman, Kevin J. Kim, Eun-Young Autissier, Patrick Wurcel, Alysse Zaman, Tauheed Stone, David Mefford, Megan Morgello, Susan Singer, Elyse J. Wolinsky, Steven M. Gabuzda, Dana TI Microbial Translocation Is Associated with Increased Monocyte Activation and Dementia in AIDS Patients SO PLOS ONE LA English DT Article AB Elevated plasma lipopolysaccharide (LPS), an indicator of microbial translocation from the gut, is a likely cause of systemic immune activation in chronic HIV infection. LPS induces monocyte activation and trafficking into brain, which are key mechanisms in the pathogenesis of HIV-associated dementia (HAD). To determine whether high LPS levels are associated with increased monocyte activation and HAD, we obtained peripheral blood samples from AIDS patients and examined plasma LPS by Limulus amebocyte lysate (LAL) assay, peripheral blood monocytes by FACS, and soluble markers of monocyte activation by ELISA. Purified monocytes were isolated by FACS sorting, and HIV DNA and RNA levels were quantified by real time PCR. Circulating monocytes expressed high levels of the activation markers CD69 and HLA-DR, and harbored low levels of HIV compared to CD4(+) T-cells. High plasma LPS levels were associated with increased plasma sCD14 and LPS-binding protein (LBP) levels, and low endotoxin core antibody levels. LPS levels were higher in HAD patients compared to control groups, and were associated with HAD independently of plasma viral load and CD4 counts. LPS levels were higher in AIDS patients using intravenous heroin and/or ethanol, or with Hepatitis C virus (HCV) co-infection, compared to control groups. These results suggest a role for elevated LPS levels in driving monocyte activation in AIDS, thereby contributing to the pathogenesis of HAD, and provide evidence that cofactors linked to substance abuse and HCV co-infection influence these processes. C1 [Ancuta, Petronela; Kamat, Anupa; Mefford, Megan; Gabuzda, Dana] Harvard Univ, Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. [Kunstman, Kevin J.; Kim, Eun-Young; Wolinsky, Steven M.] Northwestern Univ, Med Sch, Chicago, IL USA. [Autissier, Patrick] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Wurcel, Alysse; Zaman, Tauheed; Stone, David] Lemuel Shattuck Hosp, Jamaica Plain, MA USA. [Morgello, Susan] Mount Sinai Med Ctr, New York, NY USA. [Singer, Elyse J.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA USA. RP Ancuta, P (reprint author), Harvard Univ, Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. EM dana_gabuzda@dfci.harvard.edu RI Wolinsky, Steven/B-2893-2012; OI Wolinsky, Steven/0000-0002-9625-6697 FU NIH [DA016549, MH083588]; Fonds de la Recherche en Sante Quebec (FRSQ); French National Institute of Health and Medical Research (INSERM); Harvard Center for AIDS Research; DFCI/Harvard Center for Cancer Research; NNTC [MH 59745, NS38841, MH59656, NS54591, MH59724]; [NS060611] FX This work was supported by NIH DA016549 and MH083588. P.A. was supported in part by Fonds de la Recherche en Sante Quebec (FRSQ) and the French National Institute of Health and Medical Research (INSERM). M.M. was supported in part by NS060611. Core facilities were supported by the Harvard Center for AIDS Research and DFCI/Harvard Center for Cancer Research grants. NNTC sites were supported by MH 59745, NS38841, MH59656, NS54591, and MH59724. NR 64 TC 236 Z9 243 U1 2 U2 22 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 JUN 25 PY 2008 VL 3 IS 6 AR e2516 DI 10.1371/journal.pone.0002516 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 406IK UT WOS:000263288000033 PM 18575590 ER PT J AU Stahl, JE Kreke, JE Malek, FAA Schaefer, AJ Vacanti, J AF Stahl, James E. Kreke, Jennifer E. Malek, Fawaz Ali Abdul Schaefer, Andrew J. Vacanti, Joseph TI Consequences of Cold-Ischemia Time on Primary Nonfunction and Patient and Graft Survival in Liver Transplantation: A Meta-Analysis SO PLOS ONE LA English DT Article AB Introduction: The ability to preserve organs prior to transplant is essential to the organ allocation process. Objective: The purpose of this study is to describe the functional relationship between cold-ischemia time (CIT) and primary nonfunction (PNF), patient and graft survival in liver transplant. Methods: To identify relevant articles Medline, EMBASE and the Cochrane database, including the non-English literature identified in these databases, was searched from 1966 to April 2008. Two independent reviewers screened and extracted the data. CIT was analyzed both as a continuous variable and stratified by clinically relevant intervals. Nondichotomous variables were weighted by sample size. Percent variables were weighted by the inverse of the binomial variance. Results: Twenty-six studies met criteria. Functionally, PNF% = -6.678281+ 0.9134701*CIT Mean+0.1250879*(CIT Mean -9.89535)(Lambda)2-0.0067663*(CIT Mean -9.89535)(Lambda)3, r2 = .625,, p < .0001. Mean patient survival: 93% (1 month), 88% (3 months), 83% (6 months) and 83% (12 months). Mean graft survival: 85.9% (1 month), 80.5% (3 months), 78.1% (6 months) and 76.8% (12 months). Maximum patient and graft survival occurred with CITs between 7.5-12.5 hrs at each survival interval. PNF was also significantly correlated with ICU time, % first time grafts and % immunologic mismatches. Conclusion: The results of this work imply that CIT may be the most important pre-transplant information needed in the decision to accept an organ. C1 [Stahl, James E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Inst Technol Assessment, Boston, MA 02115 USA. [Stahl, James E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Stahl, James E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Kreke, Jennifer E.; Schaefer, Andrew J.] Univ Pittsburgh, Dept Industrial Engn, Pittsburgh, PA USA. [Schaefer, Andrew J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Malek, Fawaz Ali Abdul] Univ Kuwait, Industrial & Management Syst Engn Dept, Kuwait, Kuwait. [Vacanti, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA USA. RP Stahl, JE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Inst Technol Assessment, Boston, MA 02115 USA. EM Jstahl@partners.org FU National Science Foundation [DMI-0223084]; National Institutes of Health [R01-HS09694, 1K08HS011637-01A1] FX The authors of this paper did not receive any commercial funding for this project. Supported by grant DMI-0223084 from the National Science Foundation and partially by grants R01-HS09694 and 1K08HS011637-01A1 from the National Institutes of Health. NR 59 TC 37 Z9 39 U1 1 U2 5 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 JUN 25 PY 2008 VL 3 IS 6 AR e2468 DI 10.1371/journal.pone.0002468 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 406IK UT WOS:000263288000001 PM 18575623 ER PT J AU Libby, P Nahrendorf, M Pittet, MJ Swirski, FK AF Libby, Peter Nahrendorf, Matthias Pittet, Mikael J. Swirski, Filip K. TI Diversity of denizens of the atherosclerotic plaque - Not all monocytes are created equal SO CIRCULATION LA English DT Editorial Material DE editorials; endothelium; atherosclerosis; plaque ID MACROPHAGE HETEROGENEITY; PROGENITOR CELLS; TISSUE FACTOR; P-SELECTIN; MICE; CD40; SUBSETS; INHIBITION; ACTIVATION; ATHEROMA C1 [Libby, Peter; Swirski, Filip K.] Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Med,Cardiovasc Div, Donald W Reynolds Cardiovasc Clin Res Ctr, Boston, MA 02115 USA. [Nahrendorf, Matthias; Pittet, Mikael J.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Nahrendorf, Matthias; Pittet, Mikael J.] Harvard Univ, Sch Med, Boston, MA USA. [Nahrendorf, Matthias; Pittet, Mikael J.; Swirski, Filip K.] Harvard Univ, Sch Med, Charlestown, MA USA. [Nahrendorf, Matthias; Pittet, Mikael J.; Swirski, Filip K.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. RP Libby, P (reprint author), 77 Ave Louis Pasteur NRB7, Boston, MA 02115 USA. EM plibby@rics.bwh.harvard.edu FU NHLBI NIH HHS [HL-34636, R01 HL034636] NR 25 TC 40 Z9 42 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 JUN 24 PY 2008 VL 117 IS 25 BP 3168 EP 3170 DI 10.1161/CIRCULATIONAHA.108.783068 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 318DV UT WOS:000257072700003 PM 18574058 ER PT J AU Stadtfeld, M Brennand, K Hochedlinger, K AF Stadtfeld, Matthias Brennand, Kristen Hochedlinger, Konrad TI Reprogramming of pancreatic beta cells into induced pluripotent stem cells SO CURRENT BIOLOGY LA English DT Article ID ADULT-MOUSE PANCREAS; HUMAN SOMATIC-CELLS; DEFINED FACTORS; FIBROBLASTS; EXPRESSION; INDUCTION AB Induced pluripotent stem (iPS) cells have been derived from fibroblast, stomach, and liver cultures at extremely low frequencies by ectopic expression of the transcription factors Oct4, Sox2, c-myc, and KIM, a process coined direct or in vitro reprogramming [1-8]. iPS cells are molecularly and functionally highly similar to embryonic stem cells (ESCs), including their ability to contribute to all tissues as well as the germline in mice. The heterogeneity of the starting cell populations and the low efficiency of reprogramming suggested that a rare cell type, such as an adult stem cell, might be the cell of origin for iPS cells and that differentiated cells are refractory to reprogramming. Here, we used inducible lentiviruses [9] to express Oct4, Sox2, c-myc, and KIM in pancreatic beta cells to assess whether a defined terminally differentiated cell type remains amenable to reprogramming. Genetically marked beta cells gave rise to iPS cells that expressed pluripotency markers, formed teratomas, and contributed to cell types of all germ layers in chimeric animals. Our results provide genetic proof that terminally differentiated cells can be reprogrammed into pluripotent cells, suggesting that in vitro reprogramming is not restricted to certain cell types or differentiation stages. C1 [Stadtfeld, Matthias; Hochedlinger, Konrad] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Stadtfeld, Matthias; Hochedlinger, Konrad] Harvard Univ, Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Stadtfeld, Matthias; Brennand, Kristen; Hochedlinger, Konrad] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Brennand, Kristen] Harvard Univ, Dept Mol & Cell Biol, Cambridge, MA 02138 USA. [Brennand, Kristen] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Hochedlinger, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, 185 Cambridge St, Boston, MA 02114 USA. EM khochedlinger@helix.mgh.harvard.edu RI Brennand, Kristen/J-8704-2012; OI Brennand, Kristen/0000-0003-0993-5956; Stadtfeld, Matthias/0000-0002-5852-9906 FU Howard Hughes Medical Institute; NIH HHS [DP2 OD003266, DP2 OD003266-01] NR 22 TC 267 Z9 304 U1 3 U2 42 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 JUN 24 PY 2008 VL 18 IS 12 BP 890 EP 894 DI 10.1016/j.cub.2008.05.010 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 319GK UT WOS:000257151900027 PM 18501604 ER PT J AU Saliba, W Reddy, VY Wazni, O Cummings, JE Burkhardt, JD Haissaguerre, M Kautzner, J Peichl, P Neuzil, P Schibgilla, V Noelker, G Brachmann, J Di Biase, L Barrett, C Jais, P Natale, A AF Saliba, Walid Reddy, Vivek Y. Wazni, Oussama Cummings, Jennifer E. Burkhardt, J. David Haissaguerre, Michel Kautzner, Josef Peichl, Petr Neuzil, Petr Schibgilla, Volker Noelker, Georg Brachmann, Johannes Di Biase, Luigi Barrett, Conor Jais, Pierre Natale, Andrea TI Atrial fibrillation ablation using a robotic catheter remote control system - Initial human experience and long-term follow-up results SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID MAGNETIC NAVIGATION; RADIOFREQUENCY ABLATION; CARDIAC-ARRHYTHMIAS; PULMONARY VEIN; EFFICACY; THERAPY; SAFETY AB Objectives We present the initial clinical human experience with the use of a robotic remote navigation system (Hansen Medical, Mountain View, California), to perform left and right atrial mapping and radiofrequency ablation of atrial fibrillation (AF) and atrial flutter (AFL). Background Catheter ablation is an established curative modality for various arrhythmias. A robotic steerable sheath system (SSS) (Hansen Medical) allows better catheter stability and greater degrees of freedom of catheter movement. Methods A total of 40 patients (mean age 57 years) with antiarrhythmic drug (AAD)-refractory AF (23 had also concomitant documented typical AFL) were studied. Three-dimensional reconstruction of the corresponding atrial chamber anatomy was performed with the CARTO electroanatomic mapping system (Biosense Webster, Diamond Bar, California or the EnSite NavX system (St. Jude Medical, Minneapolis, Minnesota) in combination with the Artisan catheter (Hansen Medical). In patients undergoing AF ablation, 2 transseptal punctures were performed under intracardiac ultrasound (ICE) guidance, with one of the punctures being performed using SSS. Pulmonary vein antrum isolation was performed with a 3.5-mm thermocool catheter manipulated with the use of the SSS and was verified by circular mapping. Patients were followed clinically for recurrence of arrhythmia with an event transmitter and ambulatory holter monitoring. Clinical recurrence of AF/AFL was defined as AF/AFL episodes >1 min in duration. Results Pulmonary vein antrum isolation was performed in 40 patients, including 23 with concomitant typical AFL ablation. All pulmonary veins, including the superior vena cava, were successfully isolated. In 23 of 40 patients, cavotricuspid ablation was also performed with bidirectional block obtained. At 1-year follow-up, 34 patients (86%) and 5 patients were free from atrial arrhythmia off AADs and on AADs, respectively. Conclusions This preliminary human experience suggests that mapping and ablation of AFL and AF using this novel robotic catheter with remote control system is feasible with similar results to conventional approach. C1 [Saliba, Walid; Wazni, Oussama; Cummings, Jennifer E.; Burkhardt, J. David; Di Biase, Luigi; Barrett, Conor] Cleveland Clin Fdn, Dept Cardiovasc Med, Sect Cardiac Electrophysiol & Pacing, Cleveland, OH 44195 USA. [Reddy, Vivek Y.] Massachusetts Gen Hosp, Dept Med, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Reddy, Vivek Y.] Harvard Univ, Sch Med, Boston, MA USA. [Haissaguerre, Michel; Jais, Pierre] Hop Cardiol Haut Leveque, Bordeaux, France. [Haissaguerre, Michel; Jais, Pierre] Univ Bordeaux 2, F-33076 Bordeaux, France. [Peichl, Petr] Inst Clin & Expt Med, IKEM, Dept Cardiol, Prague, Czech Republic. [Schibgilla, Volker; Noelker, Georg; Brachmann, Johannes] Klinikum Coburg 2, Dept Cardiol, Med Klin, Coburg, Germany. [Di Biase, Luigi] Univ Foggia, Dept Cardiol, Foggia, Italy. [Neuzil, Petr] Na Homolce Hosp, Dept Cardiol, Prague, Czech Republic. [Natale, Andrea] St Davids Med Ctr, Texas Cardiac Arrhythmia Inst, Austin, TX 78705 USA. [Natale, Andrea] Stanford Univ, Div Cardiol, Palo Alto, CA 94304 USA. [Natale, Andrea] Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Natale, A (reprint author), St Davids Med Ctr, Texas Cardiac Arrhythmia Inst, Suite 516,1015 E 32nd St, Austin, TX 78705 USA. EM nataleam@roadrunner.com OI Di Biase, Luigi/0000-0001-6508-4047 NR 14 TC 120 Z9 124 U1 0 U2 12 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 JUN 24 PY 2008 VL 51 IS 25 BP 2407 EP 2411 DI 10.1016/j.jacc.2008.03.027 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 316EW UT WOS:000256932800005 PM 18565397 ER PT J AU Mega, JL Morrow, DA de Lemos, JA Mohanavelu, S Cannon, CP Sabatine, MS AF Mega, Jessica L. Morrow, David A. de Lemos, James A. Mohanavelu, Satishkumar Cannon, Christopher P. Sabatine, Marc S. TI Thrombus precursor protein and clinical outcomes in patients with acute coronary syndromes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID FACTOR XA INHIBITOR; MYOCARDIAL-INFARCTION; SOLUBLE FIBRIN; ARTERY-DISEASE; NATRIURETIC PEPTIDE; FIBRINOPEPTIDE-A; ANGINA-PECTORIS; RISK-ASSESSMENT; EARLY-DIAGNOSIS; HEART-DISEASE AB Objectives We sought to test the prognostic performance of thrombus precursor protein (TpP) in patients presenting with an acute coronary syndrome (ACS). Background Because thrombus formation is a critical step in the development of ACS, a measurement of activated coagulation could yield important information. Thrombus precursor protein is a biomarker that is used to measure soluble fibrin polymers, which are the penultimate products in fibrin formation. Methods We measured the levels of TpP in 284 healthy volunteers and in 2,349 patients with ACS. Results Median TpP concentrations were 3.6 mu g/ml (interquartile range 2.6 to 5.5) in the volunteers and 8.9 mu g/ml (interquartile range 4.9 to 15.9) in the ACS patients (p < 0.001). Patients with ACS who had elevated TpP were older, more likely to be women, and more likely to have diabetes and pre-existing CAD (p < 0.02 for each). Thrombus precursor protein levels greater than the median were associated with a significantly increased risk for the composite of death, myocardial infarction (MI), or recurrent ischemia leading to rehospitalization or urgent revascularization through 10 months (hazard ratio [HR] 1.45, p < 0.001), as well as death or MI (HR 1.42, p = 0.02). We found that TpP correlated only weakly with cardiac troponin I, B-type natriuretic peptide, and high-sensitivity C-reactive protein (vertical bar r vertical bar < 0.15 for each). After adjusting for clinical characteristics, cardiac troponin I, high-sensitivity C-reactive protein, and B-type natriuretic peptide, we found that patients with TpP levels greater than the median remained at significantly increased risk for the composite outcome (adjusted HR 1.51, p = 0.001) and death or MI (adjusted HR 1.58, p = 0.02). Conclusions In patients with ACS, increased levels of TpP are associated with an increased risk of death or ischemic complications. The incorporation of a marker of activated coagulation, such as TpP, with established cardiovascular risk factors may offer valuable complementary insight into risk assessment in ACS. C1 [Mega, Jessica L.; Morrow, David A.; Mohanavelu, Satishkumar; Cannon, Christopher P.; Sabatine, Marc S.] Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. [Mega, Jessica L.; Morrow, David A.; Mohanavelu, Satishkumar; Cannon, Christopher P.; Sabatine, Marc S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [de Lemos, James A.] Univ Texas Dallas, Med Ctr, Dept Med, Div Cardiol, Dallas, TX 75230 USA. RP Mega, JL (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM jmega@partners.org FU NHLBI NIH HHS [U01 HL083-1341] NR 35 TC 9 Z9 12 U1 0 U2 2 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 JUN 24 PY 2008 VL 51 IS 25 BP 2422 EP 2429 DI 10.1016/j.jacc.2008.01.069 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 316EW UT WOS:000256932800008 PM 18565400 ER PT J AU Bourgeois, C Hao, ZY Rajewsky, K Potocnik, AJ Stockinger, B AF Bourgeois, Christine Hao, Zhenyue Rajewsky, Klaus Potocnik, Alexandre J. Stockinger, Brigitta TI Ablation of thymic export causes accelerated decay of naive CD4 T cells in the periphery because of activation by environmental antigen SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE homeostasis; thymus; lymphopenia; CD4 depletion; T cell life span ID LIPOPOLYSACCHARIDE-BINDING-PROTEIN; HIV-INFECTION; IN-VIVO; BONE-MARROW; HOMEOSTASIS; DEPLETION; MICE; PROLIFERATION; REPERTOIRE; AGE AB A model of chemical thymectomy by inducible Rag ablation was used to study peripheral T cell homeostasis. Induction of Rag ablation was efficient and complete, leading to cessation of thymic T cell production within 3-4 weeks. The decay of peripheral T cells became apparent with a delay of an additional 2-3 weeks and was entirely accounted for by loss of naive T cells, whereas numbers of memory phenotype and regulatory T cells were not decreased. Naive CD4 T cells decayed with an average half-life of 50 days, whereas naive CD8 T cells exhibited a considerably longer half-life. The rapid decay of naive CD4 T cells was not caused by intrinsic survival differences compared with naive CD8 T cells, but was caused by changes in the lymphopenic environment resulting in higher microbial load and consequential activation. This finding suggests that in lymphopenic conditions involving compromised thymic function replenishment and survival of a naive CD4 T cell repertoire may be severely curtailed because of chronic activation. Such a scenario might play a role in the aging immune system and chronic viral infection, such as HIV infection, and contribute to loss of CD4 T cells and impaired immune function. As our data show, continued replenishment with cells from the thymus seems to be required to maintain efficient gut mucosal defense. C1 [Rajewsky, Klaus] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Bourgeois, Christine; Potocnik, Alexandre J.; Stockinger, Brigitta] Natl Inst Med Res, Div Mol Immunol, London NW7 1AA, England. [Hao, Zhenyue] Ontario Canc Res Inst, Campbell Family Inst Breast Canc Res, Toronto, ON, Canada. RP Rajewsky, K (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 200 Longwood Ave, Boston, MA 02115 USA. EM rajewsky@cbr.med.harvard.edu; bstocki@nimr.mrc.ac.uk FU Medical Research Council [MC_U117565359, ] NR 39 TC 43 Z9 46 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 24 PY 2008 VL 105 IS 25 BP 8691 EP 8696 DI 10.1073/pnas.0803732105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 319TA UT WOS:000257185700038 PM 18562288 ER PT J AU Dutt, A Salvesen, HB Chent, TH Ramos, AH Onofrio, RC Hatton, C Nicoletti, R Winckler, W Grewal, R Hanna, M Wyhs, N Ziaugra, L Richter, DJ Trovik, J Engelsen, IB Stefansson, IM Fennell, T Cibulskis, K Zody, MC Akslen, LA Gabriel, S Wong, KK Sellers, WR Meyerson, M Greulich, H AF Dutt, Amit Salvesen, Helga B. Chent, Tzu-Hsiu Ramos, Alex H. Onofrio, Robert C. Hatton, Charlie Nicoletti, Richard Winckler, Wendy Grewal, Rupinder Hanna, Megan Wyhs, Nicolas Ziaugra, Liuda Richter, Daniel J. Trovik, Jone Engelsen, Ingeborg B. Stefansson, Ingunn M. Fennell, Tim Cibulskis, Kristian Zody, Michael C. Akslen, Lars A. Gabriel, Stacey Wong, Kwok-Kin Sellers, William R. Meyerson, Matthew Greulich, Heidi TI Drug-sensitive FGFR2 mutations in endometrial carcinoma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE endometrial cancer; fibroblast growth factor receptor 2; oncogene; targeted therapy; tyrosine kinase ID GROWTH-FACTOR RECEPTOR-3; LIGAND-BINDING SPECIFICITY; GENOME-WIDE ASSOCIATION; APERT-SYNDROME; BREAST-CANCER; LUNG-CANCER; ACTIVATING MUTATIONS; MULTIPLE-MYELOMA; TYROSINE KINASE; FACTOR FAMILY AB Oncogenic activation of tyrosine kinases is a common mechainism of carcinogenesis and, given the druggable nature of these enzymes, an attractive target for anticancer therapy. Here, we show that somatic mutations of the fibroblast growth factor receptor 2 (FGFR2) tyrosine kinase gene, FGFR2, are present in 12% of endometrial carcinomas, with additional instances found in lung squamous cell carcinoma and cervical carcinoma. These FGFR2 mutations, many of which are identical to mutations associated with congenital craniofacial developmental disorders, are constitutively activated and oncogenic when ectopically expressed in NIH 3T3 cells. Inhibition of FGFR2 kinase activity in endometrial carcinoma cell lines bearing such FGFR2 mutations inhibits transformation and survival, implicating FGFR2 as a novel therapeutic target in endometrial carcinoma. C1 [Dutt, Amit; Chent, Tzu-Hsiu; Ramos, Alex H.; Nicoletti, Richard; Wong, Kwok-Kin; Sellers, William R.; Meyerson, Matthew; Greulich, Heidi] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hatton, Charlie; Nicoletti, Richard; Winckler, Wendy; Grewal, Rupinder; Hanna, Megan; Wyhs, Nicolas; Ziaugra, Liuda; Richter, Daniel J.; Fennell, Tim; Cibulskis, Kristian; Zody, Michael C.; Gabriel, Stacey; Meyerson, Matthew; Greulich, Heidi] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Wong, Kwok-Kin; Greulich, Heidi] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Dutt, Amit; Chent, Tzu-Hsiu; Ramos, Alex H.; Onofrio, Robert C.; Hatton, Charlie; Nicoletti, Richard; Winckler, Wendy; Grewal, Rupinder; Hanna, Megan; Wyhs, Nicolas; Ziaugra, Liuda; Richter, Daniel J.; Trovik, Jone; Fennell, Tim; Cibulskis, Kristian; Zody, Michael C.; Gabriel, Stacey; Meyerson, Matthew; Greulich, Heidi] MIT & Harvard, Broad Inst, Cambridge, MA 02142 USA. [Salvesen, Helga B.; Trovik, Jone; Engelsen, Ingeborg B.] Univ Bergen, Dept Clin Med, N-5020 Bergen, Norway. [Stefansson, Ingunn M.; Akslen, Lars A.] Univ Bergen, Gade Inst, Sect Pathol, N-5020 Bergen, Norway. [Stefansson, Ingunn M.; Akslen, Lars A.] Haukeland Hosp, Dept Pathol, N-5020 Bergen, Norway. [Salvesen, Helga B.; Engelsen, Ingeborg B.] Haukeland Hosp, Dept Obstet & Gynecol, N-5020 Bergen, Norway. [Sellers, William R.] Novartis Inst Biomed Res, Cambridge, MA 02139 USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu; heidig@broad.mit.edu RI Meyerson, Matthew/E-7123-2012; Dutt, Amit/I-1911-2013; Akslen, Lars /C-1202-2017; salvesen, Helga/C-1187-2017; OI Dutt, Amit/0000-0002-1119-4774; Akslen, Lars /0000-0003-2710-9543; salvesen, Helga/0000-0002-4438-8831; wong, kwok kin/0000-0001-6323-235X FU NCI NIH HHS [U24 CA126546] NR 41 TC 198 Z9 200 U1 2 U2 12 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 JUN 24 PY 2008 VL 105 IS 25 BP 8713 EP 8717 DI 10.1073/pnas.0803379105 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 319TA UT WOS:000257185700042 PM 18552176 ER PT J AU Cameron, DE Urbach, JM Mekalanos, JJ AF Cameron, D. Ewen Urbach, Jonathan M. Mekalanos, John J. TI A defined transposon mutant library and its use in identifying motility genes in Vibrio cholerae SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cholera; flagella; flgT; mariner ID N-TERMINAL DOMAIN; PSEUDOMONAS-AERUGINOSA; HIMAR1-MARINER TRANSPOSON; TRANSCRIPTION HIERARCHY; BACTERIAL VIRULENCE; COLONIZATION; CHEMOTAXIS; VACCINE; EXPRESSION; FLAGELLUM AB Defined mutant libraries allow for efficient genome-scale screening and provide a convenient collection of mutations in almost any nonessential gene of interest. Here, we present a near-saturating transposon insertion library in Vibrio cholerae strain C6706, a clinical isolate belonging to the 01 El Tor biotype responsible for the current cholera pandemic. Automated sequencing analysis of 23,312 mutants allowed us to build a 3,156-member subset library containing a representative insertion in every disrupted ORF. Because uncharacterized mutations that affect motility have shown utility in attenuating V. cholerae live vaccines, we used this genome-wide subset library to define all genes required for motility and to further assess the accuracy and purity of the library. In this screen, we identified the hypothetical gene VC2208 (flgT) as essential for motility. Flagellated cells were very rare in a flgT mutant, and transcriptional analysis showed it was specifically stalled at the class III/IV assembly checkpoint of the V. cholerae flagellar regulatory system. Because FlgT is predicted to have structural homology to TolB, a protein involved in determining outer membrane architecture, and the sheath of the V. cholerae flagellum appears to be derived from the cell's outer membrane, FlgT may play a direct role in flagellar sheath formation. C1 [Cameron, D. Ewen; Mekalanos, John J.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Urbach, Jonathan M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Mekalanos, JJ (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, 200 Longwood Ave, Boston, MA 02115 USA. EM john_mekalanos@hms.harvard.edu FU NIAID NIH HHS [AI-064332, AI-18045, AI-26289, R01 AI018045, R01 AI026289, R01 AI064332, R37 AI018045]; NIDDK NIH HHS [DK-040561, P30 DK040561] NR 53 TC 86 Z9 3807 U1 3 U2 33 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 JUN 24 PY 2008 VL 105 IS 25 BP 8736 EP 8741 DI 10.1073/pnas.0803281105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 319TA UT WOS:000257185700046 PM 18574146 ER PT J AU Maddox, TM Reid, KJ Spertus, JA Mittleman, M Krumholz, HM Parashar, S Ho, PM Rumsfeld, JS AF Maddox, Thomas M. Reid, Kimberly J. Spertus, John A. Mittleman, Murray Krumholz, Harlan M. Parashar, Susmita Ho, P. Michael Rumsfeld, John S. TI Angina at 1 year after myocardial infarction - Prevalence and associated findings SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc ID QUALITY-OF-LIFE; CORONARY-ARTERY-DISEASE; 3-YEAR FOLLOW-UP; SMOKING-CESSATION; BYPASS-SURGERY; HEALTH-STATUS; HEART-DISEASE; MAJOR DEPRESSION; RANDOMIZED-TRIAL; UNSTABLE ANGINA AB Background: Eradication of angina is a primary goal of care after myocardial infarction (MI). However, the prevalence of angina 1 year after MI and factors associated with it are unknown. Methods: From January 1, 2003, through June 28, 2004, 2498 patients with acute MI were recruited from 9 hospitals in the United States. Among this multicenter cohort of patients, angina was measured by the Seattle Angina Questionnaire 1 year after hospitalization for MI. Multivariate regression modeling identified the sociodemographic factors, clinical history, MI presentation, inpatient treatments, and outpatient treatments associated with 1-year angina, adjusted for site. Results: Of 1957 patients in the cohort, 389 (19.9%) reported angina 1 year after MI. After multivariate analysis, patients with 1-year angina were more likely to be younger (relative risk [RR] per 10-year decrease, 1.19; 95% confidence interval [ CI],1.09-1.30), to be nonwhite males (RR, 1.50; 95% CI, 1.16-1.96), to have had prior angina (RR, 1.78; 95% CI, 1.54-2.06), to have undergone prior coronary artery bypass graft surgery (RR, 1.92; 95% CI, 1.512.44), and to experience recurrent rest angina during their hospitalization (RR, 1.54; 95% CI, 1.22-1.93). Among the outpatient variables, patients with 1-year angina were more likely to continue smoking (RR, 1.23; 95% CI, 1.02-1.48), to undergo revascularization after index hospitalization (percutaneous coronary intervention or coronary artery bypass graft) (RR, 1.37; 95% CI, 1.09-1.73), and to have significant new (RR, 1.96; 95% CI, 1.34-2.87), persistent (RR, 1.88; 95% CI, 1.29-2.75), or transient (RR, 1.77; 95% CI, 1.49-2.11) depressive symptoms. Conclusions: Angina occurs in nearly 1 of 5 patients 1 year after MI. It is associated with several modifiable factors, including persistent smoking and depressive symptoms. C1 [Maddox, Thomas M.; Ho, P. Michael; Rumsfeld, John S.] Univ Colorado, Cardiol Sect, Denver Vet Affairs Med Ctr, Dept Med, Denver, CO 80209 USA. [Reid, Kimberly J.; Spertus, John A.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Mittleman, Murray] Beth Israel Deaconess Med Ctr, Cardiovasc Epidemiol Res Unit, Boston, MA 02215 USA. [Krumholz, Harlan M.] Yale Univ, Sch Publ Hlth, Sect Cardiovasc Med, New Haven, CT USA. [Krumholz, Harlan M.] Yale Univ, Sch Publ Hlth, Robert Wood Johnson Clin Scholars Program, Dept Med, New Haven, CT USA. [Krumholz, Harlan M.] Yale Univ, Sch Publ Hlth, Sect Hlth Policy & Adm, New Haven, CT USA. [Krumholz, Harlan M.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. [Parashar, Susmita] Emory Univ, Sch Med, Dept Med, Div Gen Internal Med, Atlanta, GA USA. RP Maddox, TM (reprint author), Univ Colorado, Cardiol Sect, Denver Vet Affairs Med Ctr, Dept Med, 111B,1055 Clermont St, Denver, CO 80209 USA. EM thomas.maddox@va.gov FU NHLBI NIH HHS [P50 HL077113] NR 44 TC 41 Z9 42 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 23 PY 2008 VL 168 IS 12 BP 1310 EP 1316 DI 10.1001/archinte.168.12.1310 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 315YR UT WOS:000256916600015 PM 18574088 ER PT J AU Weisbord, SD Mor, MK Resnick, AL Hartwig, KC Sonel, AF Fine, MJ Palevsky, PM AF Weisbord, Steven D. Mor, Maria K. Resnick, Abby L. Hartwig, Kathryn C. Sonel, Ali F. Fine, Michael J. Palevsky, Paul M. TI Prevention, incidence, and outcomes of contrast-induced acute kidney injury SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HIGH-RISK PATIENTS; INDUCED NEPHROPATHY; RENAL-FUNCTION; CORONARY-ANGIOGRAPHY; N-ACETYLCYSTEINE; INSUFFICIENCY; INTERVENTION; STRATEGIES; HYDRATION AB Background: Little is known about whether health care providers (physicians) implement preventive care for contrast-induced acute kidney injury (CIAKI). The objectives of our prospective cohort study were (1) to assess provider use of preventive strategies for CIAKI, (2) to determine the incidence of CIAKI, and (3) to examine the association of CIAKI with adverse outcomes at 30 days, including death, need for dialysis, and hospital admission. Methods: We prospectively identified patients with estimated glomerular filtration rates less than 60 mL/min/ 1.73 m(2) undergoing procedures with intravascular radiocontrast agents and recorded the use of intravenous fluids and N-acetylcysteine and the discontinuation of nonsteroidal anti-inflammatory medications. We measured postprocedure serum creatinine levels to quantify the incidence of CIAKI and tracked 30-day mortality and need for dialysis or hospitalization to evaluate the association of CIAKI with these outcomes. Results: Preprocedure and postprocedure intravenous fluids were administered to 264 of 660 study patients (40.0%), more commonly with coronary angiography than with computed tomography (91.2% vs 16.6%, P <.001). N-acetylcysteine was administered to 39.2% of patients, while only 6.8% of patients using nonsteroidal anti-inflammatory drugs were instructed to discontinue the medication. In a propensity analysis, the use of intravenous fluids was associated with a reduced rate of CIAKI. The incidence of CIAKI was lowest following computed tomography (range, 0.0%-10.9%) and was highest following noncoronary angiography (range, 1.9%-34.0%). Eleven patients (1.7%) died, l patient (0.2%) required dialysis, and 83 patients (12.6%) were hospitalized; however, CIAKI was not independently associated with hospital admission or death. Conclusions: Strategies to prevent CIAKI are implemented nonuniformly. Although biochemical evidence of CIAKI is relatively common, clinically significant CIAKI is rare. These findings should help health care providers focus the use of preventive care on the highest-risk patients and have important implications for future clinical trials. C1 [Weisbord, Steven D.; Mor, Maria K.; Resnick, Abby L.; Hartwig, Kathryn C.; Sonel, Ali F.; Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.; Hartwig, Kathryn C.; Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Renal Sect, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.; Palevsky, Paul M.] Univ Pittsburgh, Renal Electrolyte Div, Pittsburgh, PA USA. [Fine, Michael J.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. [Mor, Maria K.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. [Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Mail Stop 111F-U,7E Room 120, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu FU NIAID NIH HHS [K24 AI001769] NR 26 TC 57 Z9 59 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 23 PY 2008 VL 168 IS 12 BP 1325 EP 1332 DI 10.1001/archinte.168.12.1325 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 315YR UT WOS:000256916600017 PM 18574090 ER PT J AU Lai, YY Hsieh, KC Nguyen, D Peever, J Siegel, JM AF Lai, Y. -Y. Hsieh, K. -C. Nguyen, D. Peever, J. Siegel, J. M. TI Neurotoxic lesions at the ventral mesopontine junction change sleep time and muscle activity during sleep: An animal model of motor disorders in sleep SO NEUROSCIENCE LA English DT Article DE periodic leg movements; REM sleep behavior disorder; Parkinsonism; pons; retrorubral nucleus; substantia nigra ID RESTLESS-LEGS-SYNDROME; IN-VIVO MICRODIALYSIS; MEDULLARY RETICULAR-FORMATION; STEM-MEDIATED LOCOMOTION; PARADOXICAL REM SLEEP; CHOLINERGIC CELL AREA; LEWY BODY DISEASE; BEHAVIOR DISORDER; LOCUS-COERULEUS; PARKINSONS-DISEASE AB There is no adequate animal model of restless legs syndrome (RLS) and periodic leg movements disorder (PLMD), disorders affecting 10% of the population. Similarly, there is no model of rapid eye movement (REM) sleep behavior disorder (RBD) that explains its symptoms and its link to Parkinsonism. We previously reported that the motor inhibitory system in the brainstem extends from the medulla to the ventral mesopontine junction (VMPJ). We now examine the effects of damage to the VMPJ in the cat. Based on the lesion sites and the changes in sleep pattern and behavior, we saw three distinct syndromes resulting from such lesions; the rostrolateral, rostromedial and caudal VMPJ syndromes. The change in sleep pattern was dependent on the lesion site, but was not significantly correlated with the number of dopaminergic neurons lost. An increase in wakefulness and a decrease in slow wave sleep (SWS) and REM sleep were seen in the rostrolateral VMPJ-Iesioned animals. In contrast, the sleep pattern was not significantly changed in the rostromedial and caudal VMPJ-Iesioned animals. All three groups of animals showed a significant increase in periodic and isolated leg movements in SWS and increased tonic muscle activity in REM sleep. Beyond these common symptoms, an increase in phasic motor activity in REM sleep, resembling that seen in human RBD, was found in the caudal VMPJ-lesioned animals. In contrast, the increase in motor activity in SWS in rostral VMPJ-Iesioned animals is similar to that seen in human RLS/PLMD patients. The proximity of the VMPJ region to the substantia nigra suggests that the link between RLS/PLMD and Parkinsonism, as well as the progression from RBD to Parkinsonism may be mediated by the spread of damage from the regions identified here into the substantia nigra. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Lai, Y. -Y.; Hsieh, K. -C.; Nguyen, D.; Siegel, J. M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Neurobiol Res 151A3, North Hills, CA 91343 USA. [Lai, Y. -Y.; Hsieh, K. -C.; Nguyen, D.; Siegel, J. M.] Vet Adm Greater Los Angeles Healthcare Syst Sepul, North Hills, CA 91343 USA. [Peever, J.] Univ Toronto, Dept Physiol, Syst Neurobiol Lab, Toronto, ON M5S 3G5, Canada. [Peever, J.] Univ Toronto, Dept Cell & Syst Biol, Syst Neurobiol Lab, Toronto, ON M5S 3G5, Canada. RP Lai, YY (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Neurobiol Res 151A3, 16111 Plummer St, North Hills, CA 91343 USA. EM yylai@ucia.edu FU BLRD VA [I01 BX001753]; NHLBI NIH HHS [R37 HL041370, HL041370, R01 HL041370, R01 HL041370-16A2]; NIDA NIH HHS [R01 DA034748]; NIMH NIH HHS [R01 MH064109]; NINDS NIH HHS [R01 NS069640, R01 NS014610, R01 NS042566-02, R01 NS042566, NS042566, R01 NS042566-01A2, R01 NS042566-04, R01 NS042566-03] NR 87 TC 33 Z9 33 U1 0 U2 0 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 JUN 23 PY 2008 VL 154 IS 2 BP 431 EP 443 DI 10.1016/j.neuroscience.2008.03.085 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 319OB UT WOS:000257172200004 PM 18487021 ER PT J AU Tang, XN Cairns, B Cairns, N Yenari, MA AF Tang, X. N. Cairns, B. Cairns, N. Yenari, M. A. TI Apocynin improves outcome in experimental stroke with a narrow dose range SO NEUROSCIENCE LA English DT Article DE apocynin; superoxide; NADPH oxidase; stroke; brain hemorrhage ID FUNCTIONAL NADPH OXIDASE; MILD HYPOTHERMIA; CEREBRAL-ISCHEMIA; REACTIVE OXYGEN; HEMORRHAGIC TRANSFORMATION; EMBOLIC STROKE; BRAIN; EXPRESSION; MECHANISMS; PROTEIN AB Inflammation following ischemic stroke is known to contribute to injury. NADPH oxidase (NOX) is a major enzyme system originally studied in immune cells that leads to superoxide (O center dot(-)) generation. Apocynin is a NOX inhibitor that has been studied as a potential treatment in experimental stroke. Here we explored the effect of different doses of apocynin in a mouse model of 2 h transient middle cerebral artery occlusion (tMCAO) followed by 22 h reperfusion. Apocynin, given i.v. at a dose of 2.5 mg/kg 30 min before reperfusion, improved neurological function (P<0.01), reduced infarct volume (P<0.05), and reduced the incidence of cerebral hemorrhage (P<0.05), but not at higher doses of 3.75 and 5 mg/kg, where it actually increased brain hemorrhage. Apocynin also tended to reduce mortality at the lower dose, but not at higher doses. Using hydroethine fluorescence to delineate O center dot(-) in the brain, neurons and some microglia/macrophages, but not vascular endothelial cells were found to contain O center dot(-). Apocynin at protective doses markedly prevented ischemia-induced increases in O center dot(-). Our data suggested that apocynin can protect against experimental stroke, but with a narrow therapeutic window. Published by Elsevier Ltd on behalf of IBRO. C1 [Tang, X. N.; Yenari, M. A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Tang, X. N.; Yenari, M. A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Tang, X. N.] Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA. [Cairns, B.; Cairns, N.] Combinix Inc, Mountain View, CA USA. RP Yenari, MA (reprint author), Univ Calif San Francisco, Dept Neurol, 4150 Clement St, San Francisco, CA 94121 USA. EM yenari@alum.mit.edu FU NINDS NIH HHS [P01 NS037520-100004, P01 NS014543, P01 NS014543-300002, P01 NS037520, P01 NS037520-060004, P01NS37520, P50 NS014543, P50 NS014543-290002, R01 NS040516, R01 NS040516-09, R01 NS40516] NR 33 TC 91 Z9 93 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD JUN 23 PY 2008 VL 154 IS 2 BP 556 EP 562 DI 10.1016/j.neuroscience.2008.03.090 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 319OB UT WOS:000257172200016 PM 18511205 ER PT J AU Edderkaoui, M Odinokova, I Ohno, I Gukovsky, I Go, VLW Pandol, SJ Gukovskaya, AS AF Edderkaoui, Mouad Odinokova, Irina Ohno, Izumi Gukovsky, Ilya Go, Vay Liang W. Pandol, Stephen J. Gukovskaya, Anna S. TI Ellagic acid induces apoptosis through inhibition of nuclear factor kappa B in pancreatic cancer cells SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE ellagic acid; nuclear factor-kappa B; apoptosis; pancreatic cancer ID IN-VITRO; DEATH; MITOCHONDRIAL; PROLIFERATION; QUERCETIN; PATHWAYS; SURVIVAL; OXIDASE; PROTECT; GROWTH AB AIM: To determine the effect of ellagic acid on apoptosis and proliferation in pancreatic cancer cells and to determine the mechanism of the pro-survival effects of ellagic acid. METHODS: The effect of ellagic acid on apoptosis was assessed by measuring Phosphatidylserine externalization, caspase activity, mitochondrial membrane potential and DNA fragmentation; and proliferation by measuring DNA thymidine incorporation. Mitochondrial membrane potential was measured in permeabilized cells, and in isolated mitochondria. Nuclear factor kappa B (NF-kappa B) activity was measured by electromobility shift assay (EMSA). RESULTS: We show that ellagic acid, a polyphenolic compound in fruits and berries, at concentrations 10 to 50 mmol/L stimulates apoptosis in human pancreatic adenocarcinoma cells. Further, ellagic acid decreases proliferation by up to 20-fold at 50 mmol/L. Ellagic acid stimulates the mitochondrial pathway of apoptosis associated with mitochondrial depolarization, cytochrome C release, and the downstream caspase activation. Ellagic acid does not directly affect mitochondria. Ellagic acid dose-dependently decreased NF-kappa B binding activity. Furthermore, inhibition of NF-kappa B activity using IkB wild type plasmid prevented the effect of ellagic acid on apoptosis. CONCLUSION: Our data indicate that ellagic acid stimulates apoptosis through inhibition of the prosurvival transcription factor NF-kappa B. (C) 2008 The WJG Press. All rights reserved. C1 [Gukovskaya, Anna S.] W Los Angeles VA Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. [Edderkaoui, Mouad; Odinokova, Irina; Ohno, Izumi; Gukovsky, Ilya; Go, Vay Liang W.; Pandol, Stephen J.; Gukovskaya, Anna S.] Univ Calif Los Angeles, Los Angeles, CA 90073 USA. [Odinokova, Irina] Russian Acad Sci, Inst Theoret & Expt Biophys, Moscow 142290, Russia. RP Gukovskaya, AS (reprint author), W Los Angeles VA Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Dept Med, 11301 Wilshire Blvd,Blg 258,Rm 340, Los Angeles, CA 90073 USA. EM agukovsk@ucla.edu FU NCCIH NIH HHS [P01 AT003960, 1P01AT003960-01] NR 29 TC 63 Z9 72 U1 0 U2 10 PU W J G PRESS PI BEIJING PA APT 1066, YISHOU GARDEN, NO 58, NORTH LANGXINZHUANG RD, PO BOX 2345, BEIJING 100023, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD JUN 21 PY 2008 VL 14 IS 23 BP 3672 EP 3680 DI 10.3748/wjg.14.3672 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 325HS UT WOS:000257580600009 PM 18595134 ER PT J AU Smith, MR AF Smith, Matthew R. TI Rapid testosterone cycling and chemotherapy for prostate cancer: A way forward or return to the past? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID BREAST-CANCER; ADJUVANT CHEMOTHERAPY; ANDROGEN DEPRIVATION; RANDOMIZED-TRIAL; TMPRSS2; FUSION; HETEROGENEITY; MITOXANTRONE; PREDNISONE; DOCETAXEL C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA. RP Smith, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA. FU NCI NIH HHS [K24 CA121990-03] NR 21 TC 0 Z9 0 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 JUN 20 PY 2008 VL 26 IS 18 BP 2932 EP 2933 DI 10.1200/JCO.2008.16.0788 PG 2 WC Oncology SC Oncology GA 315KU UT WOS:000256879700003 PM 18565878 ER PT J AU D'Amico, AV Chen, MH Renshaw, AA Loffredo, B Kantoff, PW AF D'Amico, Anthony V. Chen, Ming-Hui Renshaw, Andrew A. Loffredo, Brittany Kantoff, Philip W. TI Risk of prostate cancer recurrence in men treated with radiation alone or in conjunction with combined or less than combined androgen suppression therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; SURROGATE END-POINT; DEFINITIVE RADIOTHERAPY; RADICAL PROSTATECTOMY; DEPRIVATION; CARCINOMA; ADJUVANT AB Purpose We determined the risk of recurrence in men enrolled on a randomized trial for prostate cancer who were treated with radiation therapy (RT) alone or in conjunction with combined or less than combined androgen suppression therapy (AST). Patients and Methods Between 1995 and 2001, 206 men with localized but unfavorable-risk adenocarcinoma of the prostate were randomly assigned to receive RT or RT and AST, which was defined as 6 months of both a luteinizing hormone-releasing hormone agonist and an antiandrogen. A post -random assignment hypothesis that was generated by multivariable Cox regression analyses was used to evaluate whether the risk of prostate-specific antigen (PSA) recurrence was significantly associated with months of antiandrogen use; regression analysis adjusted for known prognostic factors, comorbidity score, and medications that can elevate liver function tests sufficiently to necessitate discontinuation of the antiandrogen. Results After a median follow-up of 8.2 years (interquartile range, 7.0 to 9.5 years), 81 men sustained PSA recurrence. An increasing PSA level (P < .001); Gleason score of 8, 9, or 10 (P < .001); and clinical category T2 disease (P = .005) were significantly associated with an increased risk of recurrence. However, recurrence risk was significantly decreased (adjusted hazard ratio, 0.81; 95% CI, 0.72 to 0.92; P = .001) with each additional month of antiandrogen use after analysis was adjusted for these known prognostic factors. Conclusion Men with localized but unfavorable-risk prostate cancer who were treated with RT and 6 months of planned combined AST appear to have an increased risk of recurrence when treated with less than as compared with 6 months of the antiandrogen. C1 [D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Pathol & Med Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. 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 02215 USA. EM adamico@partners.org NR 18 TC 35 Z9 35 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 JUN 20 PY 2008 VL 26 IS 18 BP 2979 EP 2983 DI 10.1200/JCO.2007.15.9699 PG 5 WC Oncology SC Oncology GA 315KU UT WOS:000256879700012 PM 18565884 ER PT J AU Ng, K Meyerhardt, JA Wu, K Feskanich, D Hollis, BW Giovannucci, EL Fuchs, CS AF Ng, Kimmie Meyerhardt, Jeffrey A. Wu, Kana Feskanich, Diane Hollis, Bruce W. Giovannucci, Edward L. Fuchs, Charles S. TI Circulating 25-hydroxyvitamin D levels and survival in patients with colorectal cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NATIONAL DEATH INDEX; VITAMIN-D-RECEPTOR; COLON-CANCER; 1,25-DIHYDROXYVITAMIN D-3; PHYSICAL-ACTIVITY; CARCINOMA-CELLS; PROSTATE-CANCER; SUBSEQUENT RISK; NURSES HEALTH; CALCIUM AB Purpose Higher plasma 25-hydroxyvitamin D(3) (25(OH) D) levels are associated with a decreased incidence of colorectal cancer, but the influence of plasma 25(OH) D on the outcome of patients with established colorectal cancer is unknown. Patients and Methods We prospectively examined the association between prediagnosis 25(OH) D levels and mortality among 304 participants in the Nurses' Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS) who were diagnosed with colorectal cancer from 1991 to 2002. Participants diagnosed within 2 years of blood collection were excluded. Patients were observed until death, June 2005 (NHS), or January 2005 (HPFS), whichever came first. The primary end point was overall mortality. Cox proportional hazards models were used to calculate hazard ratios (HR) adjusted for other risk factors for cancer survival. Results Higher plasma 25(OH) D levels were associated with a significant reduction in overall mortality (P for trend = .02). Compared with the lowest quartile, participants in the highest quartile had an adjusted HR of 0.52 (95% CI, 0.29 to 0.94) for overall mortality. A trend toward improved colorectal cancer -specific mortality was also seen (HR = 0.61; 95% CI, 0.31 to 1.19). The results remained unchanged after excluding patients diagnosed within 5 years of blood collection (P for trend = .04); the multivariate HR for overall mortality comparing extreme quartiles was 0.45 (95% CI, 0.19 to 1.09). Conclusion Among patients with colorectal cancer, higher prediagnosis plasma 25(OH) D levels were associated with a significant improvement in overall survival. Further study of the vitamin D pathway and its influence on colorectal carcinogenesis and cancer progression is warranted. C1 [Ng, Kimmie] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Med Univ S Carolina, Div Pediat, Charleston, SC 29425 USA. RP Ng, K (reprint author), Dana Farber Canc Inst, Div Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM kng4@partners.org FU NCI NIH HHS [CA108341, CA118553, CA87969, R01 CA118553, T32 CA009172] NR 44 TC 156 Z9 158 U1 2 U2 9 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 JUN 20 PY 2008 VL 26 IS 18 BP 2984 EP 2991 DI 10.1200/JCO.2007.15.1027 PG 8 WC Oncology SC Oncology GA 315KU UT WOS:000256879700013 PM 18565885 ER PT J AU Pestalozzi, BC Zahrieh, D Mallon, E Gusterson, BA Price, KN Gelber, RD Holmberg, SB Lindtner, J Snyder, R Thuerlimann, B Murray, E Viale, G Castiglione-Gertsch, M Coates, AS Goldhirsch, A AF Pestalozzi, Bernhard C. Zahrieh, David Mallon, Elizabeth Gusterson, Barry A. Price, Karen N. Gelber, Richard D. Holmberg, Stig B. Lindtner, Jurij Snyder, Raymond Thuerlimann, Beat Murray, Elizabeth Viale, Giuseppe Castiglione-Gertsch, Monica Coates, Alan S. Goldhirsch, Aron TI Distinct clinical and prognostic features of infiltrating lobular carcinoma of the breast: Combined results of 15 International Breast Cancer Study Group clinical trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIAL; FAILURE PROBABILITIES; COMPETING RISK; FOLLOW-UP; TAMOXIFEN; THERAPY; COMBINATION; PATTERNS; SURVIVAL AB Purpose To determine how patients with infiltrating lobular carcinoma (ILC) differ from patients with the more common infiltrating ductal carcinoma (IDC) with regard to patient and tumor factors, local treatment, and patterns of recurrence. Patients and Methods Twelve thousand two hundred six breast cancer patients entered onto 15 International Breast Cancer Study Group trials between 1978 and 2002 were categorized as having ILC, IDC, or other/ mixed types. Results Seven hundred sixty-seven tumors (6.2%) were classified as ILC, 8,607 (70.5%) were classified as IDC, and 2,832 (23.2%) were classified as other. The analysis is limited to the 9,374 patients categorized as either pure IDC or ILC. The median follow-up time was 13 years. Compared with IDC, ILC was associated with older age; larger, better differentiated, and estrogen receptor (ER) -positive tumors; and less vessel invasion. Mastectomy was used more frequently for ILC (P < .01). There was a significant (P < .01) early advantage in disease-free survival and overall survival for the ILC cohort followed by a significant (P < .01) late advantage for the IDC cohort after 6 and 10 years, respectively. Similar patterns were observed in cohorts defined by ER status. ILC was associated with an increased incidence of bone events but a decrease in regional and lung events (all P < .01). Conclusion ILC is more than a histologic variant of breast cancer. The diagnosis of ILC carries distinct prognostic and biologic implications. C1 [Pestalozzi, Bernhard C.] Univ Zurich Hosp, Dept Oncol, CH-8091 Zurich, Switzerland. Int Breast Canc Study Grp IBCSG Coordinating Ctr, Bern, Switzerland. Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. Kantonsspital, Senol Ctr Eastern Switzerland, St Gallen, Switzerland. Oncol Inst So Switzerland, Bellinzona, Switzerland. IBCSG Stat Ctr, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Glasgow, Fac Med, Div Canc Sci & Mol Pathol, Glasgow G12 8QQ, Lanark, Scotland. Sahlgrens Univ Hosp, Dept Surg, Gothenburg, Sweden. Inst Oncol, Ljubljana, Slovenia. St Vincents Hosp, Dept Oncol, Melbourne, Vic, Australia. Univ Sydney, Sydney, NSW 2006, Australia. Univ Cape Town, ZA-7925 Cape Town, South Africa. Groote Shuur Hosp, Cape Town, South Africa. Univ Milan, Div Pathol & Lab Med, European Inst Oncol, Milan, Italy. Univ Milan, Dept Med, European Inst Oncol, Milan, Italy. RP Pestalozzi, BC (reprint author), Univ Zurich Hosp, Dept Oncol, Raemistr 100, CH-8091 Zurich, Switzerland. EM bernhard.pestalozzi@usz.ch RI gusterson, barry/D-3752-2009 FU NCI NIH HHS [CA-75362, U24 CA075362] NR 33 TC 112 Z9 118 U1 1 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 JUN 20 PY 2008 VL 26 IS 18 BP 3006 EP 3014 DI 10.1200/JCO.2007.14.9336 PG 9 WC Oncology SC Oncology GA 315KU UT WOS:000256879700016 PM 18458044 ER PT J AU Chi, LY Yu, J Zhu, H Li, XG Zhu, SG Kindy, MS AF Chi, Ling-Yi Yu, Jin Zhu, Hong Li, Xin-Gang Zhu, Shu-Gan Kindy, Mark S. TI The dual role of tumor necrosis factor-alpha in the pathophysiology of spinal cord injury SO NEUROSCIENCE LETTERS LA English DT Article DE spinal cord injury; tumor necrosis factor-alpha; apoptosis; astrocytes ID TRANSGENIC MICE; FUNCTIONAL RECOVERY; ASTROCYTES; EXPRESSION; RATS; ACTIVATION; APOPTOSIS; NGF AB Recent studies have demonstrated that tumor necrosis factor-alpha (TNF-alpha) is one of the most important mediators in spinal cord injury (SCI). However, the role of TNF-alpha in this process is still under debate due to conflicting evidence. Here, we utilized TNF-alpha transgenic (tg) rats and wild-type (wt) littermates to further investigate the role of TNF-alpha in SCI. We observed that, in the acute phase post-SCI (<= 3 days), TNF-alpha tg rats showed higher expression of TNF-alpha protein and more apoptotic cells in the spinal cord than wt rats, while in the chronic period (>= 7 days), TNF-alpha tg rats exhibited persistent baseline level of TNF-alpha protein, better tissue healing, and more activated astrocytes in the border of the lesion than wt rats. These data further demonstrate that TNF-alpha plays a dual role in SCI and its role probably depends on when it is released after SCI and on which cellular population it acts on. Published by Elsevier Ireland Ltd. C1 [Chi, Ling-Yi; Li, Xin-Gang; Zhu, Shu-Gan] Shandong Univ, Qilu Hosp, Dept Neurosurg, Jinan 250012, Shandong, Peoples R China. [Chi, Ling-Yi; Yu, Jin; Zhu, Hong; Kindy, Mark S.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Kindy, Mark S.] Shandong Univ, Sch Med, Dept Anat, Jinan 250012, Shandong, Peoples R China. [Kindy, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Li, XG (reprint author), Shandong Univ, Qilu Hosp, Dept Neurosurg, 107 Wenhua Xi Rd, Jinan 250012, Shandong, Peoples R China. EM drlixingangneurosurgery@yahoo.com.cn; drkms2000@yahoo.com.cn NR 21 TC 11 Z9 13 U1 1 U2 2 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 JUN 20 PY 2008 VL 438 IS 2 BP 174 EP 179 DI 10.1016/j.neulet.2008.04.043 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 321AQ UT WOS:000257276900010 PM 18468795 ER PT J AU Parekkadan, B Berdichevsky, Y Irimia, D Leeder, A Yarmush, G Toner, M Levine, JB Yarmush, ML AF Parekkadan, Biju Berdichevsky, Yevgeny Irimia, Daniel Leeder, Avrum Yarmush, Gabriel Toner, Mehmet Levine, John B. Yarmush, Martin L. TI Cell-cell interaction modulates neuroectodermal specification of embryonic stem cells SO NEUROSCIENCE LETTERS LA English DT Article DE embryonic stem cell; microfabricated cell pairs; neuroectodermal differentiation; connexin-43 ID DIFFERENTIATION; DERIVATION; COMMUNICATION; PRECURSORS; EXPRESSION; PLATFORM; CONTACT AB The controlled differentiation of embryonic stem (ES) cells is of utmost interest to their clinical, biotechnological, and basic science use. Many investigators have combinatorially assessed the role of specific soluble factors and extracellular matrices in guiding ES cell fate, yet the interaction between neighboring cells in these heterogeneous cultures has been poorly defined due to a lack of conventional tools to specifically uncouple these variables. Herein, we explored the role of cell-cell interactions during neuroectodermal specification of ES cells using a microfabricated cell pair array. We tracked differentiation events in situ, using an ES cell line expressing green fluorescent protein (GFP) under the regulation of the Sox1 gene promoter, an early marker of neuroectodermal germ cell commitment in the adult forebrain. We observed that a previously specified Sox1-GFP+ cell could induce the specification of an undifferentiated ES cell. This induction was modulated by the two cells being in contact and was dependent on the age of previously specified cell prior to coculture. A screen of candidate cell adhesion molecules revealed that the expression of connexin (Cx)-43 correlated with the age-dependent effect of cell contact in cell pair experiments. ES cells deficient in Cx-43 showed aberrant neuroectodermal specification and lineage commitment, highlighting the importance of gap junctional signaling in the development of this germ layer. Moreover, this study demonstrates the integration of microscale culture techniques to explore the biology of ES cells and gain insight into relevant developmental processes otherwise undefined due to bulk culture methods. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Parekkadan, Biju; Berdichevsky, Yevgeny; Irimia, Daniel; Leeder, Avrum; Yarmush, Gabriel; Toner, Mehmet; Levine, John B.; Yarmush, Martin L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA USA. [Parekkadan, Biju; Berdichevsky, Yevgeny; Irimia, Daniel; Leeder, Avrum; Yarmush, Gabriel; Toner, Mehmet; Levine, John B.; Yarmush, Martin L.] Shriners Hosp Children, Boston, MA USA. [Parekkadan, Biju; Toner, Mehmet; Yarmush, Martin L.] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. [Parekkadan, Biju; Irimia, Daniel; Toner, Mehmet; Yarmush, Martin L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, BioMEMS Resource Ctr, Boston, MA USA. [Levine, John B.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Levine, John B.] Massachusetts Gen Hosp, Benson Henry Inst, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org RI Levine, John/G-6221-2015; OI Irimia, Daniel/0000-0001-7347-2082 FU NIBIB NIH HHS [P41 EB-002503, P41 EB002503]; NIDDK NIH HHS [R01 DK43371, K18 DK076819, K18 DK076819-01, R01 DK043371, R01 DK043371-13] NR 23 TC 31 Z9 32 U1 1 U2 7 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 JUN 20 PY 2008 VL 438 IS 2 BP 190 EP 195 DI 10.1016/j.neulet.2008.03.094 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 321AQ UT WOS:000257276900013 PM 18467031 ER PT J AU Muller, B Sheen, J AF Muller, Bruno Sheen, Jen TI Cytokinin and auxin interaction in root stem-cell specification during early embryogenesis SO NATURE LA English DT Article ID ARABIDOPSIS RESPONSE REGULATORS; TOBACCO BY-2 CELLS; SIGNAL-TRANSDUCTION; DNA-BINDING; GENE; THALIANA; FAMILY; SHOOT; SCARECROW; MERISTEM AB Plant stem-cell pools, the source for all organs, are first established during embryogenesis. It has been known for decades that cytokinin and auxin interact to control organ regeneration in cultured tissue(1). Auxin has a critical role in root stem-cell specification in zygotic embryogenesis(2,3), but the early embryonic function of cytokinin is obscure(4-6). Here, we introduce a synthetic reporter to visualize universally cytokinin output in vivo. Notably, the first embryonic signal is detected in the hypophysis, the founder cell of the root stem-cell system. Its apical daughter cell, the precursor of the quiescent centre, maintains phosphorelay activity, whereas the basal daughter cell represses signalling output. Auxin activity levels, however, exhibit the inverse profile. Furthermore, we show that auxin antagonizes cytokinin output in the basal cell lineage by direct transcriptional activation of ARABIDOPSIS RESPONSE REGULATOR genes, ARR7 and ARR15, feedback repressors of cytokinin signalling. Loss of ARR7 and ARR15 function or ectopic cytokinin signalling in the basal cell during early embryogenesis results in a defective root stem-cell system. These results provide a molecular model of transient and antagonistic interaction between auxin and cytokinin critical for specifying the first root stem-cell niche. C1 [Muller, Bruno; Sheen, Jen] Harvard Univ, Sch Med, Dept Mol Biol, Massachusetts Gen Hosp,Dept Genet, Boston, MA 02114 USA. RP Sheen, J (reprint author), Harvard Univ, Sch Med, Dept Mol Biol, Massachusetts Gen Hosp,Dept Genet, Boston, MA 02114 USA. EM mueller@molbio.mgh.harvard.edu; sheen@molbio.mgh.harvard.edu RI Mueller, Bruno/E-9888-2017 OI Mueller, Bruno/0000-0003-2664-7219 FU NIGMS NIH HHS [R01 GM060493, R01 GM060493-08, R01 GM070567, R01 GM070567-04] NR 36 TC 267 Z9 280 U1 13 U2 83 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 19 PY 2008 VL 453 IS 7198 BP 1094 EP U7 DI 10.1038/nature06943 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 314WM UT WOS:000256839900055 PM 18463635 ER PT J AU Roy, D Talajic, M Nattel, S Wyse, DG Dorian, P Lee, KL Bourassa, MG Arnold, JMO Buxton, AE Camm, AJ Connolly, SJ Dubuc, M Ducharme, A Guerra, PG Hohnloser, SH Lambert, J Le Heuzey, JY O'Hara, G Pedersen, OD Rouleau, JL Singh, BN Stevenson, LW Stevenson, WG Thibault, B Waldo, AL AF Roy, Denis Talajic, Mario Nattel, Stanley Wyse, D. George Dorian, Paul Lee, Kerry L. Bourassa, Martial G. Arnold, J. Malcolm O. Buxton, Alfred E. Camm, A. John Connolly, Stuart J. Dubuc, Marc Ducharme, Anique Guerra, Peter G. Hohnloser, Stefan H. Lambert, Jean Le Heuzey, Jean-Yves O'Hara, Gilles Pedersen, Ole Dyg Rouleau, Jean-Lucien Singh, Bramah N. Stevenson, Lynne Warner Stevenson, William G. Thibault, Bernard Waldo, Albert L. CA Atrial Fibrillation & Congestive H TI Rhythm control versus rate control for atrial fibrillation and heart failure SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; VENTRICULAR SYSTOLIC DYSFUNCTION; ANTIARRHYTHMIC DRUG-THERAPY; SINUS RHYTHM; PROGNOSTIC-SIGNIFICANCE; RANDOMIZED-TRIAL; MORTALITY; RISK; MAINTENANCE; AMIODARONE AB Background It is common practice to restore and maintain sinus rhythm in patients with atrial fibrillation and heart failure. This approach is based in part on data indicating that atrial fibrillation is a predictor of death in patients with heart failure and suggesting that the suppression of atrial fibrillation may favorably affect the outcome. However, the benefits and risks of this approach have not been adequately studied. Methods We conducted a multicenter, randomized trial comparing the maintenance of sinus rhythm (rhythm control) with control of the ventricular rate (rate control) in patients with a left ventricular ejection fraction of 35% or less, symptoms of congestive heart failure, and a history of atrial fibrillation. The primary outcome was the time to death from cardiovascular causes. Results A total of 1376 patients were enrolled (682 in the rhythm-control group and 694 in the rate-control group) and were followed for a mean of 37 months. Of these patients, 182 (27%) in the rhythm-control group died from cardiovascular causes, as compared with 175 (25%) in the rate-control group (hazard ratio in the rhythm-control group, 1.06; 95% confidence interval, 0.86 to 1.30; P=0.59 by the log-rank test). Secondary outcomes were similar in the two groups, including death from any cause (32% in the rhythm-control group and 33% in the rate-control group), stroke (3% and 4%, respectively), worsening heart failure (28% and 31%), and the composite of death from cardiovascular causes, stroke, or worsening heart failure (43% and 46%). There were also no significant differences favoring either strategy in any predefined subgroup. Conclusions In patients with atrial fibrillation and congestive heart failure, a routine strategy of rhythm control does not reduce the rate of death from cardiovascular causes, as compared with a rate-control strategy. C1 [Roy, Denis; Talajic, Mario; Nattel, Stanley; Bourassa, Martial G.; Dubuc, Marc; Ducharme, Anique; Guerra, Peter G.; Lambert, Jean; Rouleau, Jean-Lucien; Thibault, Bernard] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Roy, Denis; Talajic, Mario; Nattel, Stanley; Bourassa, Martial G.; Dubuc, Marc; Ducharme, Anique; Guerra, Peter G.; Lambert, Jean; Rouleau, Jean-Lucien; Thibault, Bernard] Univ Montreal, Montreal, PQ, Canada. [Wyse, D. George] Libin Cardiovasc Inst, Calgary, AB, Canada. [Dorian, Paul] St Michaels Hosp, Toronto, ON M5B 1W8, Canada. [Lee, Kerry L.] Duke Univ, Med Ctr, Durham, NC USA. [Arnold, J. Malcolm O.] London Hlth Sci Ctr, London, ON, Canada. [Buxton, Alfred E.] Rhode Isl Hosp, Lifespan Acad Ctr, Providence, RI USA. [Camm, A. John] Univ London St Georges Hosp, Med Ctr, London, England. [Connolly, Stuart J.] Populat Hlth Res Inst, Hamilton, ON, Canada. [Hohnloser, Stefan H.] Goethe Univ Frankfurt, Frankfurt, Germany. [Le Heuzey, Jean-Yves] Hop Europeen Georges Pompidou, Paris, France. [O'Hara, Gilles] Inst Cardiol Quebec, Quebec City, PQ, Canada. [Pedersen, Ole Dyg] Bispebjerg Hosp, Copenhagen, Denmark. [Singh, Bramah N.] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. [Stevenson, Lynne Warner; Stevenson, William G.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Waldo, Albert L.] Case Western Reserve Univ Hosp, Med Ctr, Cleveland, OH 44106 USA. RP Roy, D (reprint author), Montreal Heart Inst, 5000 Belanger St, Montreal, PQ H1T 1C8, Canada. EM d_roy@icm-mhi.com OI Bourassa, Martial G./0000-0002-4439-8650 NR 44 TC 612 Z9 646 U1 5 U2 28 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 19 PY 2008 VL 358 IS 25 BP 2667 EP 2677 DI 10.1056/NEJMoa0708789 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 314NC UT WOS:000256815100003 PM 18565859 ER PT J AU Busse, PM Clark, JR Muse, VV Liu, V Robbins, GK AF Busse, Paul M. Clark, John R. Muse, Victorine V. Liu, Vincent Robbins, Gregory K. TI Case 19-2008: A 63-year-old HIV-positive man with cutaneous Merkel-cell carcinoma - Merkel-cell carcinoma, stage III SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LUNG-CANCER; CASE SERIES; SKIN; CHEMOTHERAPY; RADIOTHERAPY; METAANALYSIS; INFECTION; RADIATION; SURVIVAL C1 [Busse, Paul M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Busse, Paul M.; Clark, John R.; Muse, Victorine V.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Clark, John R.] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. [Muse, Victorine V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Liu, Vincent] Univ Iowa, Carver Coll Med, Dept Dermatol, Iowa City, IA USA. [Liu, Vincent] Univ Iowa, Carver Coll Med, Dept Pathol, Iowa City, IA USA. RP Busse, PM (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 23 TC 12 Z9 12 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 19 PY 2008 VL 358 IS 25 BP 2717 EP 2723 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 314NC UT WOS:000256815100010 PM 18565865 ER PT J AU Grady, WM Parkin, RK Mitchell, PS Lee, JH Kim, YH Tsuchiya, KD Washington, MK Paraskeva, C Willson, JKV Kaz, AM Kroh, EM Allen, A Fritz, BR Markowitz, SD Tewari, M AF Grady, W. M. Parkin, R. K. Mitchell, P. S. Lee, J. H. Kim, Y-H Tsuchiya, K. D. Washington, M. K. Paraskeva, C. Willson, J. K. V. Kaz, A. M. Kroh, E. M. Allen, A. Fritz, B. R. Markowitz, S. D. Tewari, M. TI Epigenetic silencing of the intronic microRNA hsa-miR-342 and its host gene EVL in colorectal cancer SO ONCOGENE LA English DT Article DE microRNA; epigenetic; colorectal cancer; colon cancer; methylation; apoptosis ID OLIGONUCLEOTIDE ARRAYS; EXPRESSION PROFILES; COLON-CANCER; IDENTIFICATION; TARGETS; TUMOR; HYPERMETHYLATION; SIGNATURE; NEOPLASIA; MECHANISM AB MicroRNAs are small, non-coding RNAs that influence gene regulatory networks by post-transcriptional regulation of specific messenger RNA targets. MicroRNA expression is dysregulated in human malignancies, frequently leading to loss of expression of certain microRNAs. We report that expression of hsa-miR-342, a microRNA encoded in an intron of the gene EVL, is commonly suppressed in human colorectal cancer. The expression of hsa-miR- 342 is coordinated with that of EVL and our results indicate that the mechanism of silencing is CpG island methylation upstream of EVL. We found methylation at the EVL/hsa-miR-342 locus in 86% of colorectal adenocarcinomas and in 67% of adenomas, indicating that it is an early event in colorectal carcinogenesis. In addition, we observed a higher frequency of methylation ( 56%) in histologically normal colorectal mucosa from individuals with concurrent cancer compared to mucosa from individuals without colorectal cancer ( 12%), suggesting the existence of a 'field defect' involving methylated EVL/hsa-miR-342. Furthermore, reconstitution of hsa-miR- 342 in the colorectal cancer cell line HT-29 induced apoptosis, suggesting that this microRNA could function as a proapoptotic tumor suppressor. In aggregate, these results support a novel mechanism for silencing intronic microRNAs in cancer by epigenetic alterations of cognate host genes. C1 [Grady, W. M.; Lee, J. H.; Kim, Y-H; Tsuchiya, K. D.; Kaz, A. M.; Tewari, M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Grady, W. M.; Kaz, A. M.] Univ Washington, Sch Med, Div Gastroenterol, Seattle, WA USA. [Grady, W. M.; Kaz, A. M.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Parkin, R. K.; Mitchell, P. S.; Kroh, E. M.; Fritz, B. R.; Tewari, M.] Fred Hutchinson Canc Res Ctr, Human Biol Div, Seattle, WA 98109 USA. [Lee, J. H.; Kim, Y-H] Sungkyunkwan Univ, Samsung Med Ctr, Dept Med, Seoul, South Korea. [Tsuchiya, K. D.] Seattle Childrens Hosp & Reg Med Ctr, Seattle, WA USA. [Washington, M. K.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Paraskeva, C.] Univ Bristol, Bristol, Avon, England. [Willson, J. K. V.] Univ Texas SW, Sch Med, Dallas, TX USA. [Allen, A.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Markowitz, S. D.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Markowitz, S. D.] Univ Hosp Cleveland, Cleveland, OH 44106 USA. [Markowitz, S. D.] Howard Hughes Med Inst, Cleveland, OH USA. RP Tewari, M (reprint author), Fred Hutchinson Canc Res Ctr, Human Biol & Clin Res Div, 1100 Fairview Ave N,Mailstop D4-100, Seattle, WA 98109 USA. EM mtewari@fhcrc.org NR 29 TC 167 Z9 180 U1 2 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 19 PY 2008 VL 27 IS 27 BP 3880 EP 3888 DI 10.1038/onc.2008.10 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 315UC UT WOS:000256904700013 PM 18264139 ER PT J AU Maier, M Peng, Y Jiang, LY Seabrook, TJ Carroll, MC Lemere, CA AF Maier, Marcel Peng, Ying Jiang, Liying Seabrook, Timothy J. Carroll, Michael C. Lemere, Cynthia A. TI Complement C3 deficiency leads to accelerated amyloid beta plaque deposition and neurodegeneration and modulation of the microglia/macrophage phenotype in amyloid precursor protein transgenic mice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Alzheimer's disease; amyloid beta; A beta peptide; complement; C3; neurodegeneration ID CELLULAR IMMUNE-RESPONSE; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; MOUSE MODEL; PERIPHERAL CLEARANCE; NEURONAL EXPRESSION; ACTIVATION; PATHWAY; CELLS; BRAIN AB Complement factor C3 is the central component of the complement system and a key inflammatory protein activated in Alzheimer's disease (AD). Previous studies demonstrated that inhibition of C3 by overexpression of soluble complement receptor-related protein y in an AD mouse model led to reduced microgliosis, increased amyloid beta(A beta) plaque burden, and neurodegeneration. To further address the role of C3 in AD pathology, we generated a complement C3-deficient amyloid precursor protein (APP) transgenic AD mouse model (APP; C3(-/-)). Brains were analyzed at 8, 12, and 17 months of age by immunohistochemical and biochemical methods and compared with age-matched APP transgenic mice. At younger ages (8-12 months), no significant neuropathological differences were observed between the two transgenic lines. In contrast, at 17 months of age, APP; C3(-/-) mice showed significant changes of up to twofold increased total A beta and fibrillar amyloid plaque burden in midfrontal cortex and hippocampus, which correlated with (1) significantly increased Tris-buffered saline (TBS)-insoluble A beta(42) levels and reduced TBS-soluble A beta(42) and A beta(40) levels in brain homogenates, (2) a trend for increased A beta levels in the plasma, (3) a significant loss of neuronal-specific nuclear protein-positive neurons in the hippocampus, and (4) differential activation of microglia toward a more alternative phenotype (e. g., significantly increased CD45-positive microglia, increased brain levels of interleukins 4 and 10, and reduced levels of CD68, F4/80, inducible nitric oxide synthase, and tumor necrosis factor). Our results suggest a beneficial role for complement C3 in plaque clearance and neuronal health as well as in modulation of the microglia phenotype. C1 [Maier, Marcel; Peng, Ying; Jiang, Liying; Lemere, Cynthia A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. [Carroll, Michael C.] Harvard Univ, Sch Med, Inst Biomed Res, Ctr Blood Res, Boston, MA 02115 USA. [Carroll, Michael C.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Lemere, CA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Harvard New Res Bldg,Room 636F,77 Ave Louis Paste, Boston, MA 02115 USA. EM clemere@rics.bwh.harvard.edu FU NIA NIH HHS [AG20159, R01 AG020159, R01 AG020159-07, R01 AG020159-08] NR 44 TC 128 Z9 130 U1 0 U2 13 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 JUN 18 PY 2008 VL 28 IS 25 BP 6333 EP 6341 DI 10.1523/JNEUROSCI.0829-08.2008 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 315OT UT WOS:000256890000006 PM 18562603 ER PT J AU Wang, J Ho, L Zhao, W Ono, K Rosensweig, C Chen, LH Humala, N Teplow, DB Pasinetti, GM AF Wang, Jun Ho, Lap Zhao, Wei Ono, Kenjiro Rosensweig, Clark Chen, Linghong Humala, Nelson Teplow, David B. Pasinetti, Giulio M. TI Grape-derived polyphenolics prevent A beta oligomerization and attenuate cognitive deterioration in a mouse model of Alzheimer's disease SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Alzheimer's disease; A beta peptide; amyloid beta; cognitive; dementia; Morris water maze; spatial memory ID TRANSGENIC MICE; PROTEIN; DEMENTIA; WINE; NEUROPATHOLOGY; A-BETA(1-42); AGGREGATION; CONSUMPTION; AMYLOIDOSIS; TOXICITY AB Alzheimer's disease ( AD) is a neurodegenerative disorder characterized by progressive impairments in memory and cognition. Extracellular accumulation of soluble high-molecular-weight (HMW) A beta oligomers has been proposed to be largely responsible for AD dementia and memory deficits in the Tg2576 mice, a model of AD. In this study, we found that a naturally derived grape seed polyphenolic extract can significantly inhibit amyloid beta-protein aggregation into high-molecular-weight oligomers in vitro. When orally administered to Tg2576 mice, this polyphenolic preparation significantly attenuates AD-type cognitive deterioration coincidentally with reduced HMW soluble oligomeric A beta in the brain. Our study suggests that grape seed-derived polyphenolics may be useful agents to prevent or treat AD. C1 [Pasinetti, Giulio M.] Mt Sinai Sch Med, Icahn Res Inst, Dept Psychiat, New York, NY 10029 USA. [Pasinetti, Giulio M.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. [Ono, Kenjiro; Rosensweig, Clark; Teplow, David B.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Dept Neurol, Los Angeles, CA 90095 USA. [Ono, Kenjiro; Rosensweig, Clark; Teplow, David B.] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. [Pasinetti, Giulio M.] James J Peters Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY 10468 USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Icahn Res Inst, Dept Psychiat, 1425 Madison Ave,Box 1230, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu RI Zhao, Wei/B-3220-2010; Zhao, Wei/A-2206-2010; OI Rosensweig, Clark/0000-0001-6364-2025 FU NCCIH NIH HHS [P01 AT004511, P01 AT004511-01, P01 AT004511-020001, P01 AT004511-020003]; NIA NIH HHS [AG027818, P01 AG027818] NR 33 TC 177 Z9 184 U1 2 U2 13 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 JUN 18 PY 2008 VL 28 IS 25 BP 6388 EP 6392 DI 10.1523/JNEUROSCI.0364-08.2008 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 315OT UT WOS:000256890000012 PM 18562609 ER PT J AU Grady, D Cauley, JA Geiger, MJ Kornitzer, M Mosca, L Collins, P Wenger, NK Song, J Mershon, J Barrett-Connor, E AF Grady, Deborah Cauley, Jane A. Geiger, Mary Jane Kornitzer, Marcel Mosca, Lori Collins, Peter Wenger, Nanette K. Song, Jingli Mershon, John Barrett-Connor, Elizabeth CA Raloxifene Use Heart Trial Investi TI Reduced incidence of invasive breast cancer with raloxifene among women at increased coronary risk SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ESTROGEN-RECEPTOR-BETA; SURGICAL ADJUVANT BREAST; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; ER-ALPHA; TAMOXIFEN; REDUCTION; NUTRITION; OUTCOMES; DISEASE AB Background In the Raloxifene Use for The Heart trial, 10 101 postmenopausal women with coronary heart disease (CHD) or multiple CHD risk factors were randomly assigned to 60 mg/d raloxifene or to placebo and followed for a median of 5.6 years. Raloxifene, a selective estrogen receptor modulator, was found to reduce the risk of invasive breast cancer and vertebral fractures but not the risk of cardiovascular events. Here, we provide further details about breast cancer incidence by tumor characteristics, duration of treatment, and subgroup. Methods Reported breast cancer was adjudicated by an independent committee based on medical records and pathology reports. The primary analyses used Cox proportional hazards models with time to first breast cancer as the outcome. Subgroup effects were analyzed using similar models with terms for treatment by subgroup. All statistical tests were two-sided. Results As previously reported, raloxifene reduced the incidence of invasive breast cancer by 44% (hazard ratio [HR] = 0.56; 95% confidence interval [CI] = 0.38 to 0.83; absolute risk reduction = 1.2 invasive breast cancers per 1000 women treated for 1 year). The lower incidence of invasive breast cancer reflected a 55% lower incidence of invasive estrogen receptor (ER)-positive tumors (HR = 0.45; 95% CI = 0.28 to 0.72). However, raloxifene treatment did not reduce the incidence of noninvasive breast cancer or of invasive ER-negative breast cancer. The reduced incidence of invasive breast cancer was similar across subgroups, including those defined by age, body mass index, family history of breast cancer, prior use of postmenopausal hormones, and 5-year estimated risk of invasive breast cancer. Conclusion Raloxifene reduces risk of invasive ER-positive breast cancer regardless of a woman's baseline breast cancer risk but does not reduce risk of noninvasive or ER-negative breast cancers. These results confirm those of the Multiple Outcomes of Raloxifene Evaluation, a previous randomized trial among women with osteoporosis. C1 [Grady, Deborah] Univ Calif San Francisco, San Francisco, CA 94115 USA. [Grady, Deborah] San Francisco VA Med Ctr, San Francisco, CA USA. [Cauley, Jane A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Geiger, Mary Jane; Song, Jingli; Mershon, John] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. [Kornitzer, Marcel] Free Univ Brussels, Sch Publ Hlth, Dept Epidemiol & Hlth Promot, Brussels, Belgium. [Mosca, Lori] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. [Collins, Peter] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Royal Brompton Hosp, Dept Cardiac Med, London, England. [Wenger, Nanette K.] Emory Univ, Sch Med, Atlanta, GA USA. [Barrett-Connor, Elizabeth] Univ Calif San Diego, Dept Family & Prevent Med & Med, La Jolla, CA 92093 USA. RP Grady, D (reprint author), Univ Calif San Francisco, 1635 Divisadero St,Ste 600, San Francisco, CA 94115 USA. EM deborah.grady@ucsf.edu RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU NHLBI NIH HHS [K24 HL076346] NR 27 TC 27 Z9 27 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 JUN 18 PY 2008 VL 100 IS 12 BP 854 EP 861 DI 10.1093/jnci/djn153 PG 8 WC Oncology SC Oncology GA 316VY UT WOS:000256979000009 PM 18544744 ER PT J AU Warren, JL Yabroff, KR Meekins, A Topor, M Lamont, EB Brown, ML AF Warren, Joan L. Yabroff, K. Robin Meekins, Angela Topor, Marie Lamont, Elizabeth B. Brown, Martin L. TI Evaluation of trends in the cost of initial cancer treatment SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CELL LUNG-CANCER; STAGE BREAST-CANCER; SEER-MEDICARE DATA; HEALTH-CARE COSTS; ADJUVANT CHEMOTHERAPY; CLAIMS; METAANALYSIS; POPULATION; RADIATION; ACCURACY AB Background Despite reports of increases in the cost of cancer treatment, little is known about how costs of cancer treatment have changed over time and what services have contributed to the increases. Methods We used data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database for 306 709 persons aged 65 and older and diagnosed with breast, lung, colorectal, or prostate cancer between 1991 and 2002 to assess the number of patients assigned to initial cancer care, from 2 months before diagnosis to 12 months after diagnosis, and mean annual Medicare payments for this care according to cancer type and type of treatment. Mutually exclusive treatment categories were cancer-related surgery, chemotherapy, radiation therapy, and other hospitalizations during the period of initial cancer care. Linear regression models were used to assess temporal trends in the percentage of patients receiving treatment and costs for those treated. We extrapolated our results based on the SEER data to the US Medicare population to estimate national Medicare payments by cancer site and treatment category. All statistical tests were two-sided. Results For patients diagnosed in 2002, Medicare paid an average of $39 891 for initial care for each lung cancer patient, $41 134 for each colorectal cancer patient, and $20 964 for each breast cancer patient, corresponding to inflation-adjusted increases from 1991 of $7139, $5345, and $4189, respectively. During the same interval, the mean Medicare payment for initial care for prostate cancer declined by $196 to $18261 in 2002. Costs for any hospitalization accounted for the largest portion of payments for all cancers. Chemotherapy use increased markedly for all cancers between 1991 and 2002, as did radiation therapy use (except for colorectal cancers). Total 2002 Medicare payments for initial care for these four cancers exceeded $6.7 billion, with colorectal and lung cancers being the most costly overall. Conclusions The statistically significant increase in costs of initial cancer treatment reflects more patients receiving surgery and adjuvant therapy and rising prices for these treatments. These trends are likely to continue in the near future, although more efficient targeting of costly therapies could mitigate the overall economic impact of this trend. C1 [Warren, Joan L.; Yabroff, K. Robin; Brown, Martin L.] NCI, Div Canc Control & Populat Sci, Appl Res Program, Hlth Serv & Econ Branch, Bethesda, MD 20892 USA. [Meekins, Angela; Topor, Marie] Management Informat Serv, Silver Spring, MD USA. [Lamont, Elizabeth B.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Lamont, Elizabeth B.] Harvard Univ, Sch Med, Boston, MA USA. RP Warren, JL (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, Hlth Serv & Econ Branch, Execut Plaza N,Rm 4005,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. EM joan_warren@nih.gov OI Yabroff, K. Robin/0000-0003-0644-5572 NR 39 TC 170 Z9 173 U1 2 U2 14 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 JUN 18 PY 2008 VL 100 IS 12 BP 888 EP 897 DI 10.1093/jnci/djn175 PG 10 WC Oncology SC Oncology GA 316VY UT WOS:000256979000012 PM 18544740 ER PT J AU Lockhart, PB Brennan, MT Sasser, HC Fox, PC Paster, BJ Bahrani-Mougeot, FK AF Lockhart, Peter B. Brennan, Michael T. Sasser, Howell C. Fox, Philip C. Paster, Bruce J. Bahrani-Mougeot, Farah K. TI Bacteremia associated with toothbrushing and dental extraction SO CIRCULATION LA English DT Article DE bacteremia; bacteria; infective endocarditis; valves; risk factors ID INFECTIVE ENDOCARDITIS; ANTIMICROBIAL PROPHYLAXIS; ANTIBIOTIC-PROPHYLAXIS; BACTERIAL DIVERSITY; EFFICACY; CHLORHEXIDINE; INFLAMMATION; PREVENTION; PLAQUE AB Background-Antibiotic prophylaxis recommendations for the prevention of infective endocarditis are based in part on studies of bacteremia from dental procedures, but toothbrushing may pose a greater threat. The purpose of this study was to compare the incidence, duration, nature, and magnitude of endocarditis-related bacteremia from single-tooth extraction and toothbrushing and to determine the impact of amoxicillin prophylaxis on single-tooth extraction. Methods and Results-In this double-blind, placebo-controlled study, 290 subjects were randomized to (1) toothbrushing, (2) single-tooth extraction with amoxicillin prophylaxis, or (3) single-tooth extraction with identical placebo. Blood was drawn for bacterial culturing and identification at 6 time points before, during, and after these interventions. The focus of our analysis was on bacterial species reported to cause infective endocarditis. We identified 98 bacterial species, 32 of which are reported to cause endocarditis. Cumulative incidence of endocarditis-related bacteria from all 6 blood draws was 23%, 33%, and 60% for the toothbrushing, extraction-amoxicillin, and extraction-placebo groups, respectively (P < 0.0001). Significant differences were identified among the 3 groups at draws 2, 3, 4, and 5 (all P < 0.05). Amoxicillin resulted in a significant decrease in positive cultures (P < 0.0001). Conclusions-Although amoxicillin has a significant impact on bacteremia resulting from a single-tooth extraction, given the greater frequency for oral hygiene, toothbrushing may be a greater threat for individuals at risk for infective endocarditis. C1 [Lockhart, Peter B.; Brennan, Michael T.; Fox, Philip C.; Bahrani-Mougeot, Farah K.] Carolinas Med Ctr, Dept Oral Med, Charlotte, NC 28232 USA. [Sasser, Howell C.] Carolinas Med Ctr, Dickson Inst Hlth Studies, Charlotte, NC 28232 USA. [Paster, Bruce J.] Forsyth Inst, Boston, MA USA. RP Lockhart, PB (reprint author), Carolinas Med Ctr, Dept Oral Med, POB 32861, Charlotte, NC 28232 USA. EM Peter.Lockhart@carolinashealthcare.org FU NIDCR NIH HHS [R01 DE013559, R01 DE013559-01A2, R01 DE013559-02, R01 DE013559-03, R01 DE13559-01] NR 36 TC 196 Z9 201 U1 3 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 17 PY 2008 VL 117 IS 24 BP 3118 EP 3125 DI 10.1161/CIRCULATIONAHA.107.758524 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 314KX UT WOS:000256809400009 PM 18541739 ER PT J AU Leadbetter, EA Brigl, M Illarionovt, P Cohen, N Luteran, MC Pillai, S Besra, GS Brenner, MB AF Leadbetter, Elizabeth A. Brigl, Manfred Illarionovt, Petr Cohen, Nadia Luteran, Megan C. Pillai, Shiv Besra, Gurdyal S. Brenner, Michael B. TI NK T cells provide lipid antigen-specific cognate help for B cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE antibodies; CD1d; T cell helper; iNK T cell; alpha-galactosylceramide ID ANTIBODY-PRODUCTION; IN-VIVO; RESPONSES; IMMUNITY; CD1D; THIOGLYCOSIDES; INTERLEUKIN-4; ACTIVATION; CONTRIBUTE AB The mechanisms of T cell help for production of antilipid antibodies are largely unknown. This study shows that invariant Nk T cells (INK T cells) and B cells cooperate in a model of antilipid antigen-specific antibody responses. We use a model haptenated lipid molecule, 4-hydroxy-3-nitrophenyl-alpha GalactosylCeramide (NP-alpha GalCer), to demonstrate that INK T cells provide cognate help to lipid-antigen-presenting B cells. B cells proliferate and IgG anti-NP is produced from in vivo-immunized mice and in vitro cocultures of B and iNK T cells after exposure to NP-alpha GalCer, but not closely related control glycolipids. This B cell response is absent in CD1d(-/-) and J alpha 18(-/-) mice but not CD4(-/-) mice. The antibody response to NP-alpha GalCer is dominated by the IgM, IgG3, and IgG2c isotypes, and marginal zone B cells stimulate better in vitro lipid antigen-driven proliferation than follicular B cells, suggesting an important role for this B cell subset. INK T cell help for 8 cells is shown to involve cognate help from CD1d-instructed lipid-specific INK T cells, with help provided via CD40L, B7-1/B7-2, and IFN-gamma, but not IL-4. This model provides evidence of INK T cell help for antilipid antibody production, an important aspect of infections, autoimmune diseases, and vaccine development. Our findings also now allow prediction of those microbial antigens that would be expected to elicit cognate iNKT cell help for antibody production, namely those that can stimulate iNKT cells and at the same time have a polar moiety that can be recognized by antibodies. C1 [Leadbetter, Elizabeth A.; Brigl, Manfred; Cohen, Nadia; Luteran, Megan C.; Brenner, Michael B.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Illarionovt, Petr; Besra, Gurdyal S.] Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England. [Pillai, Shiv] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02115 USA. RP Brenner, MB (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM mbrenner@rics.bwh.harvard.edu OI Besra, Gurdyal/0000-0002-5605-0395 FU Medical Research Council [G0400421]; NIAMS NIH HHS [T32 AR007530, T32 AR007530-21] NR 31 TC 113 Z9 116 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 17 PY 2008 VL 105 IS 24 BP 8339 EP 8344 DI 10.1073/pnas.0801375105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 317HR UT WOS:000257011200032 PM 18550809 ER PT J AU Ghuman, AS Bar, M Dobbins, IG Schnyeri, DM AF Ghuman, Avniel S. Bar, Moshe Dobbins, Ian G. Schnyeri, David M. TI The effects of priming on frontal-temporal communication SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE functional communication; learning; magnetoencepholography; synchrony memory ID PREFRONTAL CORTEX; NEURAL MECHANISMS; CORTICAL ACTIVITY; FUSIFORM CORTEX; HUMAN BRAIN; REPETITION; SYNCHRONIZATION; OSCILLATIONS; SPECIFICITY; PREDICTIONS AB Repeated exposure to a stimulus facilitates its processing. This is reflected in faster and more accurate identification, reduced perceptual identification thresholds, and more efficient classifications for repeated compared with novel items. Here, we test a hypothesis that this experience-based behavioral facilitation is a result of enhanced communication between distinct cortical regions, which reduces local processing demands. A magnetoencephalographic investigation revealed that repeated object classification led to decreased neural responses in the prefrontal cortex and temporal cortex. Critically, this decrease in absolute activity was accompanied by greater neural synchrony (a measure of functional connectivity) between these regions with repetition. Additionally, the onset of the enhanced interregional synchrony predicted the degree of behavioral facilitation. These findings suggest that object repetition results in enhanced interactions between brain regions, which facilitates performance and reduces processing demands on the regions involved. C1 [Ghuman, Avniel S.; Bar, Moshe; Schnyeri, David M.] Harvard Univ, Sch Med, MIT,Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. [Dobbins, Ian G.] Duke Univ, Dept Psychol & Neurosci, Durham, NC 27708 USA. [Ghuman, Avniel S.] Harvard Univ, Program Biophys, Cambridge, MA 02138 USA. [Schnyeri, David M.] Boston Vet Adm Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02215 USA. [Schnyeri, David M.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Ghuman, AS (reprint author), NIMH, Lab Brain & Cognit, 10 Ctr Dr,Room 4C116,MSC 1366, Bethesda, MD 20892 USA. EM ghumana@mail.nih.gov OI Ghuman, Avniel/0000-0003-1746-4656 FU NCRR NIH HHS [P41 RR014075, P41RR14075]; NIMH NIH HHS [K23 MH064004, K23MH64004, R01 MH073982, R01 MH073982-01A1]; NINDS NIH HHS [R01 NS044319, R01 NS050615, R01 NS44319-01] NR 44 TC 63 Z9 67 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 JUN 17 PY 2008 VL 105 IS 24 BP 8405 EP 8409 DI 10.1073/pnas.0710674105 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 317HR UT WOS:000257011200043 PM 18541919 ER PT J AU Ponce-Coria, J San-Cristobal, P Kahle, KT Vazquez, N Pacheco-Alvarez, D de los Heros, P Juarez, P Munoz, E Michel, G Bobadilla, NA Gimenez, I Lifton, RP Hebert, SC Gamba, G AF Ponce-Coria, Jose San-Cristobal, Pedro Kahle, Kristopher T. Vazquez, Norma Pacheco-Alvarez, Diana de los Heros, Paola Juarez, Patricia Munoz, Eva Michel, Gabriela Bobadilla, Norma A. Gimenez, Ignacio Lifton, Richard P. Hebert, Steven C. Gamba, Gerardo TI Regulation of NKCC2 by a chloride-sensing mechanism involving the WNK3 and SPAK kinases SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ion transport; loop of Henle; protein serine-threonine kinases; hypertension; diuretics ID K-CL COTRANSPORTER; ALANINE-RICH KINASE; NA+-K+-2CL(-) COTRANSPORTER; NA-K-2CL COTRANSPORTER; CELL-VOLUME; PHOSPHORYLATION; PROTEIN; TRANSPORT; OSR1; MODULATION AB The Na+:K+:2Cl(-) cotransporter (NKCC2) is the target of loop diuretics and is mutated in Bartter's syndrome, a heterogeneous autosomal recessive disease that impairs salt reabsorption in the kidney's thick ascending limb (TAL). Despite the importance of this cation/chloride cotransporter (CCC), the mechanisms that underlie its regulation are largely unknown. Here, we show that intracellular chloride depletion in Xenopus laevis oocytes, achieved by either coexpression of the K-Cl cotransporter KCC2 or low-chloride hypotonic stress, activates NKCC2 by promoting the phosphorylation of three highly conserved threonines (96, 101, and 111) in the amino terminus. Elimination of these residues renders NKCC2 unresponsive to reductions of [Cl-](i). The chloride-sensitive activation of NKCC2 requires the interaction of two serine-threonine kinases, WNK3 (related to WNK1 and WNK4, genes mutated in a Mendelian form of hypertension) and SPAK (a Ste20-type kinase known to interact with and phosphorylate other CCCs). WNK3 is positioned upstream of SPAK and appears to be the chloride-sensitive kinase. Elimination of WNK3's unique SPAK-binding motif prevents its activation of NKCC2, as does the mutation of threonines 96, 101, and 111. A catalytically inactive WNK3 mutant also completely prevents NKCC2 activation by intracellular chloride depletion. Together these data reveal a chloride-sensing mechanism that regulates NKCC2 and provide insight into how increases in the level of intracellular chloride in TAIL cells, as seen in certain pathological states, could drastically impair renal salt reabsorption. C1 [Ponce-Coria, Jose; San-Cristobal, Pedro; Vazquez, Norma; Pacheco-Alvarez, Diana; de los Heros, Paola; Juarez, Patricia; Michel, Gabriela; Bobadilla, Norma A.; Gamba, Gerardo] Univ Nacl Autonoma Mexico, Inst Nacl Ciencias Med & Nutr Salvador Zubrian, Mol Physiol Unit, Mexico City 14000, DF, Mexico. [Kahle, Kristopher T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. [Pacheco-Alvarez, Diana] Univ Panamer, Escuela Med, Mexico City 03920, DF, Mexico. [Munoz, Eva; Gimenez, Ignacio] Univ Zaragoza, Dept Physiol & Pharmacol, Sch Med, E-50009 Zaragoza, Spain. [Lifton, Richard P.] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, New Haven, CT 06510 USA. [Hebert, Steven C.] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Mol & Cellular Physiol, New Haven, CT 06510 USA. RP Gamba, G (reprint author), Univ Nacl Autonoma Mexico, Inst Nacl Ciencias Med & Nutr Salvador Zubrian, Mol Physiol Unit, Mexico City 14000, DF, Mexico. EM gamba@biomedicas.unam.mx RI Gimenez, Ignacio/B-6322-2013; Ponce-Coria, Jose/D-4866-2016 OI Gimenez, Ignacio/0000-0002-6043-4869; Ponce-Coria, Jose/0000-0002-3345-0206 FU NIDDK NIH HHS [DK-64635, R01 DK064635] NR 41 TC 113 Z9 113 U1 0 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 JUN 17 PY 2008 VL 105 IS 24 BP 8458 EP 8463 DI 10.1073/pnas.0802966105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 317HR UT WOS:000257011200052 PM 18550832 ER PT J AU Bass, MD Morgan, MR Roach, KA Settleman, J Goryachev, AB Humphries, MJ AF Bass, Mark D. Morgan, Mark R. Roach, Kirsty A. Settleman, Jeffrey Goryachev, Andrew B. Humphries, Martin J. TI p190RhoGAP is the convergence point of adhesion signals from alpha(5)beta(1) integrin and syndecan-4 SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CELL-ADHESION; DIRECTIONAL MIGRATION; CYTOPLASMIC DOMAIN; BINDING DOMAIN; RHOA ACTIVITY; WOUND REPAIR; SRC KINASE; PKC-ALPHA; C-SRC; FIBRONECTIN AB The fibronectin receptors alpha(5)beta(1) integrin and syndecan-4 cocluster in focal adhesions and coordinate cell migration by making individual contributions to the suppression of RhoA activity during matrix engagement. p190Rho-guanosine triphosphatase-activating protein (GAP) is known to inhibit RhoA during the early stages of cell spreading in an Src-dependent manner. This paper dissects the mechanisms of p190RhoGAP regulation and distinguishes the contributions of alpha(5)beta(1) integrin and syndecan-4. Matrix-induced tyrosine phosphorylation of p190RhoGAP is stimulated solely by engagement of alpha(5)beta(1) integrin and is independent of syndecan-4. Parallel engagement of syndecan-4 causes redistribution of the tyrosine-phosphorylated pool of p190RhoGAP between membrane and cytosolic fractions by a mechanism that requires direct activation of protein kinase C alpha by syndecan-4. Activation of both pathways is necessary for the efficient regulation of RhoA and, as a consequence, focal adhesion formation. Accordingly, we identify p190RhoGAP as the convergence point for adhesive signals mediated by alpha(5)beta(1) integrin and syndecan-4. This molecular mechanism explains the cooperation between extracellular matrix receptors during cell adhesion. C1 [Bass, Mark D.; Morgan, Mark R.; Roach, Kirsty A.; Humphries, Martin J.] Univ Manchester, Fac Life Sci, Wellcome Trust Ctr Cell Matrix Res, Manchester M13 9PT, England. [Settleman, Jeffrey] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Goryachev, Andrew B.] Univ Edinburgh, Sch Biol Sci, Ctr Syst Biol, Edinburgh EH9 3JR, Midlothian, Scotland. RP Humphries, MJ (reprint author), Univ Manchester, Fac Life Sci, Wellcome Trust Ctr Cell Matrix Res, Manchester M13 9PT, England. EM martin.humphries@manchester.ac.uk RI Goryachev, Andrew/A-6553-2013; OI Goryachev, Andrew/0000-0002-1332-4819; Humphries, Martin/0000-0002-4331-6967 FU Wellcome Trust [045225, 074941] NR 48 TC 72 Z9 72 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUN 16 PY 2008 VL 181 IS 6 BP 1013 EP 1026 DI 10.1083/jcb.200711129 PG 14 WC Cell Biology SC Cell Biology GA 317ZH UT WOS:000257058500014 PM 18541700 ER PT J AU Ha, JH Lo, KWH Myers, KR Carr, TM Humsi, MK Rasoul, BA Segal, RA Pfister, KK AF Ha, Junghoon Lo, Kevin W. -H. Myers, Kenneth R. Carr, Tiffany M. Humsi, Michael K. Rasoul, Bareza A. Segal, Rosalind A. Pfister, K. Kevin TI A neuron-specific cytoplasmic dynein isoform preferentially transports TrkB signaling endosomes SO JOURNAL OF CELL BIOLOGY LA English DT Article ID INTERMEDIATE CHAIN SUBUNIT; FLUORESCENT PROTEIN; AXONAL-TRANSPORT; POSTTRANSLATIONAL MODIFICATION; CULTURED NEURONS; BETA-TUBULIN; IDENTIFICATION; DYNACTIN; GROWTH; MOTOR AB Cytoplasmic dynein is the multisubunit motor protein for retrograde movement of diverse cargoes to microtubule minus ends. Here, we investigate the function of dynein variants, defined by different intermediate chain (IC) isoforms, by expressing fluorescent ICs in neuronal cells. Green fluorescent protein (GFP)-IC incorporates into functional dynein complexes that copurify with membranous organelles. In living PC12 cell neurites, GFP-dynein puncta travel in both the anterograde and retrograde directions. In cultured hippocampal neurons, neurotrophin receptor tyrosine kinase B (TrkB) signaling endosomes are transported by cytoplasmic dynein containing the neuron-specific IC-1B isoform and not by dynein containing the ubiquitous IC-2C isoform. Similarly, organelles containing TrkB isolated from brain by immuno-affinity puri. cation also contain dynein with IC-1 but not IC-2 isoforms. These data demonstrate that the IC isoforms de. ne dynein populations that are selectively recruited to transport distinct cargoes. C1 [Ha, Junghoon; Lo, Kevin W. -H.; Myers, Kenneth R.; Carr, Tiffany M.; Humsi, Michael K.; Rasoul, Bareza A.; Pfister, K. Kevin] Univ Virginia, Sch Med, Dept Cell Biol, Charlottesville, VA 22908 USA. [Segal, Rosalind A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Neurobiol, Boston, MA 02115 USA. [Segal, Rosalind A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Pfister, KK (reprint author), Univ Virginia, Sch Med, Dept Cell Biol, Charlottesville, VA 22908 USA. EM kkp9w@virginia.edu FU NINDS NIH HHS [NS050674, NS29996, R01 NS029996, R01 NS050674] NR 51 TC 67 Z9 72 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUN 16 PY 2008 VL 181 IS 6 BP 1027 EP 1039 DI 10.1083/jcb.200803150 PG 13 WC Cell Biology SC Cell Biology GA 317ZH UT WOS:000257058500015 PM 18559670 ER PT J AU El-Serag, HB Wieman, M Richardson, P AF El-Serag, H. B. Wieman, M. Richardson, P. TI The use of acid-decreasing medication in veteran patients with gastro-oesophageal reflux disorder with and without Barrett's oesophagus SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID PROTON-PUMP INHIBITOR; THERAPY; RISK; ADENOCARCINOMA; DYSPLASIA AB Aim To examine use of acid-decreasing medications, especially proton pump inhibitors (PPIs), in patients with gastro-oesophageal reflux disorder (GERD) with and without Barrett's oesophagus (BO) in a large-scale study. Methods We conducted a retrospective cohort study of patients with newly diagnosed BO (ICD-9 code 5302) and patients with GERD and no BO (ICD-9 53081, 5301) in Department of Veterans Affairs (VA) databases. Filled prescriptions for oral PPI and histamine2-receptor antagonists (H2RA) were identified in the VA Pharmacy Benefit Management database during 365 days following diagnosis. Groups with or without PPI or H2RA were compared in unadjusted and adjusted regression analyses. Chart review was used to validate diagnoses in a subset of patients with and without BO. Results We evaluated 7732 patients with BO and 13 457 with GERD and no BO diagnosed between 1/2000 and 12/2002. At least one PPI prescription was filled during the first year following diagnosis in 91.5% of BO and 61.4% of non-BO patients (P < 0.0001), and one H2RA in 31.7% of BO and 59.4% of non-BO patients (P < 0.0001), respectively. However, 6.1% of BO patients were prescribed neither. Median duration for PPI filled prescriptions was twice as long for BO (221.7 vs. 106.9 days) compared with non-BO patients. The ratio of PPI or H2RA filled prescription days to available follow-up days among BO subjects was 0.66 (122.8 days were not covered with prescription for either), and 0.55 in GERD patients with no BO (165.0 days on neither). Conclusions Veterans Affairs patients with BO are 50% more likely to be prescribed a PPI than patients with GERD and no BO. However, on average, PPI prescriptions cover only 60% of follow-up time for BO patients. C1 [El-Serag, H. B.; Wieman, M.; Richardson, P.] Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Sect Gastroenterol & Hlth Serv Res, Houston, TX USA. [El-Serag, H. B.; Wieman, M.; Richardson, P.] Baylor Coll Med, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu NR 13 TC 7 Z9 7 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD JUN 15 PY 2008 VL 27 IS 12 BP 1293 EP 1299 DI 10.1111/j.1365-2036.2008.03690.x PG 7 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 301XZ UT WOS:000255931100014 PM 18363892 ER PT J AU Yan, BP Duffy, SJ Clark, DJ Lefkovits, J Warren, R Gurvitch, R Lew, R Sebastian, M Brennan, A Andrianopoulos, N Reid, CM Ajani, AE AF Yan, Bryan P. Duffy, Stephen J. Clark, David J. Lefkovits, Jeffery Warren, Roderic Gurvitch, Ronen Lew, Robert Sebastian, Martin Brennan, Angela Andrianopoulos, Nick Reid, Christopher M. Ajani, Andrew E. CA Melbourne Interventional Grp TI Rates of stent thrombosis in bare-metal versus drug-eluting stents (from a large Australian multicenter registry) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LONG-TERM OUTCOMES; PREMATURE DISCONTINUATION; MYOCARDIAL-INFARCTION; CLINICAL-PRACTICE; IMPLANTATION; INTERVENTIONS; CLOPIDOGREL; RESTENOSIS; PREVENTION; PREDICTORS AB Recent reports suggest that drug-eluting stents (DESs) may increase the risk of stent thrombosis (ST) relative to bare-metal stents (BMSs). Therefore, the aim of this study was to compare DES and BMS outcomes with a specific focus on ST. We analyzed 30-day and 1-year outcomes of 2,919 patients who underwent percutaneous coronary intervention with stent implantation from the Melbourne Interventional Group registry. Academic Research Consortium definitions of ST were used: (1) definite ST (confirmed using angiography in patients with an acute coronary syndrome), (2) probable ST (unexplained death < 30 days or target-vessel myocardial infarction without angiographic confirmation), and (3) possible ST (unexplained death > 30 days). Multivariate analysis was performed to identify predictors of ST. The incidence of ST (early or late) was similar between BMSs and DESs (1.6% vs 1.4%; p = 0.66), and DES use was not predictive of ST. Independent predictors of ST included the absence of clopidogrel,therapy at 30 days (odds ratio [OR] 2.58, 95% confidence interval [CI] 1.29 to 5.29, p < 0.01), renal failure (OR 3.30, 95% CI 1.43 to 7.59, p < 0.01), index procedure presentation with an acute coronary syndrome (OR 2.59, 95% CI 1.14 to 5.87, p = 0.02), diabetes mellitus (OR 2.25, 95% CI 1.19 to 4.23, p = 0.01), and total stent length >= 20 min (OR 1.85, 95% CI 1.00 to 3.42, p = 0.04). In conclusion, DESs were not Associated with increased risk of ST compared with BMSs at 12 months in this large Australian registry that selectively used DESs for patients at high risk of restenosis. (c) 2008 Elsevier Inc. All rights reserved. C1 [Lefkovits, Jeffery; Warren, Roderic; Gurvitch, Ronen; Ajani, Andrew E.] Royal Melbourne Hosp, Dept Cardiol, Melbourne, Vic, Australia. [Lew, Robert] Frankston Hosp, Dept Cardiol, Melbourne, Vic, Australia. [Yan, Bryan P.] Harvard Univ, Sch Med, Boston, MA USA. [Yan, Bryan P.] Massachusetts Gen Hosp, Div Cardiol, Sect Vasc Med, Boston, MA 02114 USA. [Duffy, Stephen J.] Alfred Hosp, Dept Cardiol, Sydney, NSW, Australia. [Clark, David J.] Austin Hosp, Dept Cardiol, Austin, TX USA. [Sebastian, Martin] Geelong Hosp, Dept Cardiol, Geelong, Vic, Australia. [Brennan, Angela; Andrianopoulos, Nick; Reid, Christopher M.; Ajani, Andrew E.] Monash Univ, Dept Epidemiol & Prevent Med, Natl Hlth & Med Res Council, Ctr Clin Res Excellence Therapeut, Clayton, Vic 3800, Australia. [Ajani, Andrew E.] Univ Melbourne, Melbourne, Vic, Australia. RP Ajani, AE (reprint author), Royal Melbourne Hosp, Dept Cardiol, Melbourne, Vic, Australia. EM andrew.ajani@mh.org.au RI Yan, Bryan/P-5928-2015; Yan, Bryan/C-3390-2008; Shaw, James/F-1522-2010 NR 21 TC 19 Z9 19 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 JUN 15 PY 2008 VL 101 IS 12 BP 1716 EP 1722 DI 10.1016/j.amjcard.2008.02.058 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 314OO UT WOS:000256818900007 PM 18549846 ER PT J AU Friedewald, VE Burnett, JC Januzzi, JL Roberts, WC Yancy, CW AF Friedewald, Vincent E., Jr. Burnett, John C., Jr. Januzzi, James L., Jr. Roberts, William C. Yancy, Clyde W. TI The editor's roundtable: B-type natriuretic peptide SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID HEART-FAILURE; DIAGNOSIS; PROGNOSIS; DISEASE; BRAIN C1 [Friedewald, Vincent E., Jr.] Univ Texas Houston, Sch Med, Dept Internal Med, Houston, TX 77030 USA. [Friedewald, Vincent E., Jr.] Univ Notre Dame, Coll Sci, Notre Dame, IN 46556 USA. [Burnett, John C., Jr.] Mayo Clin, Cardiorenal Res Lab, Rochester, MN USA. [Januzzi, James L., Jr.] Harvard Univ, Sch Med, Boston, MA USA. [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Cardiovasc Execut Hlth Program, Boston, MA 02114 USA. [Roberts, William C.] Baylor Univ, Med Ctr, Baylor Heart & Vasc Inst, Waco, TX 76798 USA. [Roberts, William C.] Dean A Webb Roberts Ctr Continuing Med Educ Baylo, Dallas, TX USA. [Yancy, Clyde W.] Baylor Univ, Med Ctr, Baylor Heart & Vasc Inst, Dallas, TX USA. RP Friedewald, VE (reprint author), Univ Texas Houston, Sch Med, Dept Internal Med, Houston, TX 77030 USA. EM vfriedew@nd.edu NR 12 TC 4 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 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 15 PY 2008 VL 101 IS 12 BP 1733 EP 1740 DI 10.1016/j.amjcard.2008.03.017 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 314OO UT WOS:000256818900010 PM 18549849 ER PT J AU Cohen, T Colijn, C Wright, A Zignol, M Pym, A Murray, M AF Cohen, Ted Colijn, Caroline Wright, Abigail Zignol, Matteo Pym, Alexander Murray, Megan TI Challenges in estimating the total burden of drug-resistant tuberculosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE public health surveillance; drug resistance; epidemiology; bias (epidemiology); HIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; AFRICAN GOLD MINERS; MYCOBACTERIUM-TUBERCULOSIS; UNDIAGNOSED TUBERCULOSIS; PRIVATE PRACTITIONERS; HIV-INFECTION; PREVALENCE; TRANSMISSION; EPIDEMICS; TRENDS AB The International Union Against Tuberculosis and Lung Disease/ World Health Organization Global Project on Anti-Tuberculosis Drug Resistance Surveillance recently released the fourth global survey, which documents the highest burden of multidrug-resistant tuberculosis (TB) yet reported. The best estimate of the number of new cases of multidrug-resistant disease occurring in 2006 is close to half a million and the recent recognition of extensively drug-resistant TB underscores the need for expanded surveillance, especially in areas in which TB control programs have been compromised by an escalating burden of TB and HIV. We review current methods used for drug resistance surveillance and describe methodologic obstacles for estimating the true extent of the problem, particularly in settings where HIV/TB coinfection is common or where a substantial portion of TB cases are treated in the private sector. We highlight practical challenges to the validity of surveillance studies and discuss how additional investment in laboratory capacity, diagnostic technologies, and sentinel site surveillance can improve our ability to estimate of the burden of drug-resistant TB. C1 [Cohen, Ted; Colijn, Caroline; Murray, Megan] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Cohen, Ted; Murray, Megan] Brigham & Womens Hosp, Div Social Med & Hlth Inequal, Boston, MA 02115 USA. [Wright, Abigail; Zignol, Matteo] WHO, Stop TB Dept, CH-1211 Geneva, Switzerland. [Pym, Alexander] S African MRC, Clin & Biomed TB Res Unit, Durban, South Africa. [Murray, Megan] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Cohen, T (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM tcohen@hsph.harvard.edu RI Cohen, Ted/G-8101-2011; OI Pym, Alexander/0000-0002-6260-8180 FU NIAID NIH HHS [K08 AI055985-06, 5K08AI055985-05, K08 AI055985] NR 28 TC 40 Z9 42 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUN 15 PY 2008 VL 177 IS 12 BP 1302 EP 1306 DI 10.1164/rccm.200801-175PP PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 310SE UT WOS:000256549700003 PM 18369201 ER PT J AU Ficarro, SB Parikh, JR Blank, NC Marto, JA AF Ficarro, Scott B. Parikh, Jignesh R. Blank, Nathaniel C. Marto, Jarrod A. TI Niobium(V) oxide (Nb2O5): Application to phosphoproteomics SO ANALYTICAL CHEMISTRY LA English DT Article ID MASS-SPECTROMETRY; PHOSPHOPEPTIDE ENRICHMENT; PHOSPHORYLATED PEPTIDES; AFFINITY-CHROMATOGRAPHY; SIGNALING NETWORKS; LC-MS/MS; PROTEOMICS; MIXTURES; PROTEINS; TAGS AB Proteomics-based analysis of signaling cascades relies on a growing suite of affinity resins and methods aimed at efficient enrichment of phosphorylated peptides from complex biological mixtures. Given the heterogeneity of phosphopeptides and the overlap in chemical properties between phospho- and unmodified peptides, it is likely that the use of multiple resins will provide the best combination of specificity, yield, and coverage for large-scale proteomics studies. Recently titanium and zirconium dioxides have been used successfully for enrichment of phosphopeptides. Here we report the first demonstration that niobium pentoxide (Nb2O5) provides for efficient enrichment and recovery (similar to 50-100%) of phosphopeptides from simple mixtures and facilitates identification of several hundred putative sites of phosphorylation from cell lysate. Comparison of phosphorylated peptides identified from Nb2O5 and TiO2 With sequences in the PhosphoELM database suggests a useful degree of divergence in the selectivity of these metal oxide resins. Collectively our data indicate that Nb2O5 provides efficient enrichment for phosphopeptides and offers a complementary approach for large-scale phosphoproteomics studies. C1 [Marto, Jarrod A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Ficarro, Scott B.; Parikh, Jignesh R.; Blank, Nathaniel C.; Marto, Jarrod A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol,Blais Proteom Ctr, Boston, MA 02115 USA. [Parikh, Jignesh R.] Boston Univ, Bioinformat Program, Boston, MA 02115 USA. RP Marto, JA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St,Smith 1158A, Boston, MA 02115 USA. EM jarrod_marto@dfci.harvard.edu NR 26 TC 94 Z9 100 U1 6 U2 47 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JUN 15 PY 2008 VL 80 IS 12 BP 4606 EP 4613 DI 10.1021/ac800564h PG 8 WC Chemistry, Analytical SC Chemistry GA 313TR UT WOS:000256763400022 PM 18491922 ER PT J AU Saag, KG Teng, GG Patkar, NM Anuntiyo, J Finney, C Curtis, JR Paulus, HE Mudano, A Pisu, M Elkins-Melton, M Outman, R Allison, JJ Almazor, MS Bridges, SL Chatham, WW Hochberg, M Maclean, C Mikuls, T Moreland, LW O'Dell, J Turkiewicz, AM Furst, DE AF Saag, Kenneth G. Teng, Gim Gee Patkar, Nivedita M. Anuntiyo, Jeremy Finney, Catherine Curtis, Jeffrey R. Paulus, Harold E. Mudano, Amy Pisu, Maria Elkins-Melton, Mary Outman, Ryan Allison, Jeroan J. Almazor, Maria Suarez Bridges, S. Louis, Jr. Chatham, W. Winn Hochberg, Marc Maclean, Catherine Mikuls, Ted Moreland, Larry W. O'Dell, James Turkiewicz, Anthony M. Furst, Daniel E. TI American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Review ID ANTITUMOR-NECROSIS-FACTOR; PLACEBO-CONTROLLED TRIAL; LOW-DOSE METHOTREXATE; GOLD SODIUM THIOMALATE; ALPHA MONOCLONAL-ANTIBODY; RECEIVING CONCOMITANT METHOTREXATE; ELECTIVE ORTHOPEDIC-SURGERY; RANDOMIZED CONTROLLED-TRIAL; HEPATITIS-C-VIRUS; ADALIMUMAB PLUS METHOTREXATE AB Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient. The ACR considers adherence to these guidelines and recommendations to be voluntary, with the ultimate determination regarding their application to be made by the physician in light of each patient's individual circumstances. Guidelines and recommendations are intended to promote beneficial or desirable outcomes but cannot guarantee any specific outcome. Guidelines and recommendations developed or endorsed by the ACR are subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice. C1 [Anuntiyo, Jeremy; Finney, Catherine; Paulus, Harold E.; Maclean, Catherine; O'Dell, James; Furst, Daniel E.] Univ Calif Los Angeles, Los Angeles, CA 90095 USA. [Saag, Kenneth G.; Teng, Gim Gee; Patkar, Nivedita M.; Curtis, Jeffrey R.; Mudano, Amy; Pisu, Maria; Elkins-Melton, Mary; Outman, Ryan; Allison, Jeroan J.; Bridges, S. Louis, Jr.; Chatham, W. Winn; Turkiewicz, Anthony M.] Univ Alabama, Tuscaloosa, AL 35487 USA. [Almazor, Maria Suarez] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Hochberg, Marc] Univ Maryland, Baltimore, MD 21201 USA. [Maclean, Catherine; O'Dell, James] RAND Corp, Santa Monica, CA USA. [Finney, Catherine; O'Dell, James] W Los Angeles VAMC, Los Angeles, CA USA. [Mikuls, Ted] Univ Nebraska, Omaha, NE 68182 USA. [Moreland, Larry W.] Univ Pittsburgh, Pittsburgh, PA USA. RP Furst, DE (reprint author), Univ Calif Los Angeles, Los Angeles, CA 90095 USA. EM furst@mednet.ucla.edu OI Allison, Jeroan/0000-0003-4472-2112 FU NIAMS NIH HHS [K23 AR053351, K24 AR052361]; PHS HHS [U18-H510389] NR 258 TC 744 Z9 806 U1 4 U2 36 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD JUN 15 PY 2008 VL 59 IS 6 BP 762 EP 784 DI 10.1002/art.23721 PG 23 WC Rheumatology SC Rheumatology GA 312TA UT WOS:000256692500003 PM 18512708 ER PT J AU Iosifescu, DV Bolo, NR Nierenberg, AA Jensen, JE Fava, M Renshaw, PF AF Iosifescu, Dan V. Bolo, Nicolas R. Nierenberg, Andrew A. Jensen, J. Eric Fava, Maurizio Renshaw, Perry F. TI Brain bioenergetics and response to triiodothyronine augmentation in major depressive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE bioenergetic metabolism; magnetic resonance spectroscopy; major depressive disorder; treatment response; triiodothyronine; T3 ID MAGNETIC-RESONANCE-SPECTROSCOPY; SEROTONIN REUPTAKE INHIBITORS; HIGH-ENERGY PHOSPHATE; ADENOSYL-L-METHIONINE; P-31 MR SPECTROSCOPY; IN-VIVO ASSESSMENT; REFRACTORY DEPRESSION; FREE MAGNESIUM; TRICYCLIC ANTIDEPRESSANTS; INTRACELLULAR PH AB Background: Low cerebral bioenergetic metabolism has been reported in subjects with major depressive disorder (MDD). Thyroid hormones have been shown to increase brain bioenergetic metabolism. We assessed whether changes in brain bioenergetics measured with phosphorus magnetic resonance spectroscopy (P-31 MRS) correlate with treatment outcome during augmentation treatment with triiodothyronine (T3) in MDD. Methods: Nineteen subjects meeting DSM-IV criteria for MDD who had previously failed to respond to selective serotonin reuptake inhibitor (SSRI) antidepressant drugs received open label and prospective augmentation treatment with T3 for 4 weeks. We obtained P-31 MRS spectra before and after treatment from all MDD subjects and baseline P-31 MRS from nine normal control subjects matched forage and gender. Results: At baseline, depressed subjects had lower intracellular Mg2+ compared with control subjects. Seven MDD subjects (38.9%) were treatment responders (>= 50% improvement). Total nucleoside triphosphate (NTP), which primarily represents adenosine triphosphate (ATP), increased significantly in MDD subjects responding to T3 augmentation compared with treatment nonresponders. Phosphocreatine, which has a buffer role for ATP, decreased in treatment responders compared with nonresponders. Conclusions: The antidepressant effect of thyroid hormone (T3) augmentation of SSRIs is correlated with significant changes in the brain bioenergetic metabolism. This seems to be a re-normalization of brain bioenergetics in treatment responders. Further studies will determine whether these findings can be generalized to other antidepressant treatments. C1 [Iosifescu, Dan V.; Nierenberg, Andrew A.; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Bolo, Nicolas R.; Jensen, J. Eric; Renshaw, Perry F.] Harvard Univ, Sch Med, McLean Hosp, Brain Imaging Ctr, Boston, MA USA. RP Iosifescu, DV (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 50 Staniford St,Suite 401, Boston, MA 02114 USA. EM diosifescu@partners.org FU NIDA NIH HHS [DA15116]; NIMH NIH HHS [MH58681] NR 45 TC 50 Z9 50 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 15 PY 2008 VL 63 IS 12 BP 1127 EP 1134 DI 10.1016/j.biopsych.2007.11.020 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 309WU UT WOS:000256491700005 PM 18206856 ER PT J AU Weinstock, DM Case, C Bader, JL Chao, NJ Coleman, CN Hatchett, RJ Weisdorf, DJ Confer, DL AF Weinstock, David M. Case, Cullen, Jr. Bader, Judith L. Chao, Nelson J. Coleman, C. Norman Hatchett, Richard J. Weisdorf, Daniel J. Confer, Dennis L. TI Radiologic and nuclear events: contingency planning for hematologists/oncologists SO BLOOD LA English DT Article ID MEDICAL-MANAGEMENT; RADIATION ACCIDENTS; CARE; TRANSPLANTATION; CASUALTIES; INJURY AB Untoward events involving radioactive material, either accidental or intentional, are potentially devastating. Hematologists and oncologists are uniquely suited to help manage radiation victims, as myelosuppression is a frequent complication of radiation exposure. In the aftermath of a large event, such as a nuclear detonation, there may be a national call for surge capacity that involves hematologists/oncologists across the country in the disaster response. In preparation, the National Marrow Donor Program and American Society for Blood and Marrow Transplantation have established the Radiation Injury Treatment Network (RITN), a voluntary consortium of transplant centers, donor centers, and umbilical cord blood banks. RITN is partnered with the Office of the Assistant Secretary for Preparedness and Response in the United States Department of Health and Human Services to develop treatment guidelines, educate healthcare professionals, coordinate situation response, and provide comprehensive evaluation and care for radiation injury victims. We outline the current plans for event response and describe scenarios, including catastrophic events that would require extensive support from hematologists/oncologists across the country. In addition, we highlight important reference resources and discuss current efforts to develop medical countermeasures against radiation toxicity. Practitioners and institutions across the country are encouraged to become involved and participate in the planning. C1 [Weinstock, David M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Case, Cullen, Jr.; Confer, Dennis L.] Natl Marrow Donor Program, Minneapolis, MN USA. Office Assistant Secretary Preparedness & Respons, Dept Hlth & Human Serv, Washington, DC USA. RP Weinstock, DM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, D510B, Boston, MA 02115 USA. EM DavidM_Weinstock@dfci.harvard.edu FU NIAID NIH HHS [U19 AI 067798, U19 AI067798] NR 21 TC 30 Z9 35 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 2008 VL 111 IS 12 BP 5440 EP 5445 DI 10.1182/blood-2008-01-134817 PG 6 WC Hematology SC Hematology GA 314CN UT WOS:000256786500013 PM 18287516 ER PT J AU Savage, KJ Harris, NL Vose, JM Ullrich, F Jaffe, ES Connors, JM Rimsza, L Pileri, SA Chhanabhai, M Gascoyne, RD Armitage, JO Weisenburger, DD AF Savage, Kerry J. Harris, Nancy Lee Vose, Julie M. Ullrich, Fred Jaffe, Elaine S. Connors, Joseph M. Rimsza, Lisa Pileri, Stefano A. Chhanabhai, Mukesh Gascoyne, Randy D. Armitage, James O. Weisenburger, Dennis D. CA Int Peripheral T Cell Lymphoma Pro TI ALK-anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK(+) ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMA; EXPRESSION; DISEASE; PROGNOSIS; MODEL AB The International Peripheral T-Cell Lymphoma Project is a collaborative effort designed to gain better understanding of peripheral T-cell and natural killer (NK)/T-cell lymphomas (PTCLs). A total of 22 institutions in North America, Europe, and Asia submitted clinical and pathologic information on PTCLs diagnosed and treated at their respective centers. Of the 1314 eligible patients, 181 had anaplastic large-cell lymphoma (ALCL; 13.8%) on consensus review: One hundred fifty-nine had systemic ALCL (12.1%) and 22 had primary cutaneous ALCL (1.7%). Patients with anaplastic lymphoma kinase-positive (ALK(+)) ALCL had a superior outcome compared with those with ALK(-)ALCL (5-year failure-free survival [FFS], 60% vs 36%; P =.015; 5-year overall survival [OS], 70% vs 49%; P =.016). However, contrary to prior reports, the 5-year FFS (36% vs 20%; P =.012) and OS (49% vs 32%; P =.032) were superior for ALK(-)ALCL compared with PTCL, not otherwise specified (PTCL-NOS). Patients with primary cutaneous ALCL had a very favorable 5-year OS (90%), but with a propensity to relapse (5-year FFS, 55%). In summary, ALK(-)ALCL should continue to be separated from both ALK(+) ALCL and PTCL-NOS. Although the prognosis of ALK(-) ALCL appears to be better than that for PTCL-NOS, it is still unsatisfactory and better therapies are needed. Primary cutaneous ALCL is associated with an indolent course. C1 [Savage, Kerry J.; Connors, Joseph M.] British Columbia Canc Agcy, Dept Med Oncol, Vancouver, BC V5Z 4E6, Canada. [Harris, Nancy Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Vose, Julie M.] Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE USA. [Ullrich, Fred] Univ Nebraska Med Ctr, Dept Prevent & Societal Med, Omaha, NE USA. [Jaffe, Elaine S.] NCI, Dept Hematopathol, Bethesda, MD 20892 USA. [Rimsza, Lisa] Univ Arizona, Dept Pathol, Tucson, AZ USA. [Pileri, Stefano A.] Univ Bologna, Sch Med, Dept Pathol, Bologna, Italy. [Chhanabhai, Mukesh; Gascoyne, Randy D.] British Columbia Canc Agcy, Dept Pathol, Vancouver, BC V5Z 4E6, Canada. [Weisenburger, Dennis D.] Univ Nebraska Med Ctr, Dept Pathol, Omaha, NE USA. RP Savage, KJ (reprint author), British Columbia Canc Agcy, Dept Med Oncol, 600 W 10th Ave, Vancouver, BC V5Z 4E6, Canada. EM ksavage@bccancer.bc.ca RI Cuadros, Marta/K-1576-2014; Zinzani, Pier Luigi/J-9182-2016; OI Cuadros, Marta/0000-0002-8329-4854; Zinzani, Pier Luigi/0000-0002-2112-2651; Campo, elias/0000-0001-9850-9793 NR 25 TC 332 Z9 360 U1 2 U2 9 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 JUN 15 PY 2008 VL 111 IS 12 BP 5496 EP 5504 DI 10.1182/blood-2008-01-134270 PG 9 WC Hematology SC Hematology GA 314CN UT WOS:000256786500019 PM 18385450 ER PT J AU Mody, R Li, S Dover, DC Sallan, S Leisenring, W Oeffinger, KC Yasui, Y Robison, LL Neglia, JP AF Mody, Rajen Li, Suwen Dover, Douglas C. Sallan, Stephen Leisenring, Wendy Oeffinger, Kevin C. Yasui, Yutaka Robison, Leslie L. Neglia, Joseph P. TI Twenty-five-year follow-up among survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study SO BLOOD LA English DT Article ID LONG-TERM SURVIVORS; 2ND MALIGNANT NEOPLASMS; ADULT SURVIVORS; 5-YEAR SURVIVORS; CRANIAL RADIOTHERAPY; ADOLESCENT CANCER; GROWTH-HORMONE; LATE MORTALITY; EDUCATIONAL-ATTAINMENT; NORDIC COUNTRIES AB Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for late effects of cancer therapy. Five-year ALL survivors (< 21 years at diagnosis; n = 5760 eligible, 4151 participants), diagnosed from 1970 to 1986 were compared with the general population and a sibling cohort (n = 3899). Cumulative mortality of 5760 5-year survivors was 13% at 25 years from diagnosis. Recurrent ALL (n = 483) and second neoplasms (SNs; n = 89) were the major causes of death. Among 185 survivors, 199 SNs occurred, 53% in the CNS. Survivors reported more multiple chronic medical conditions (CMCs; odds ratio [OR], 2.8; 95% CI, 2.4-3.2) and severe or life-threatening CMCs (OR, 3.6; 95% CI, 3.0-4.5) than siblings. Cumulative incidence of severe CMCs, including death, 25 years from diagnosis was 21.3% (95% CI, 18.2-24.4; 23.3% [95% CI, 19.4-27.2] and 13.4% [95% CI, 8.4-18.4] for irradiated and nonirradiated survivors, respectively). Survivors reported more adverse general and mental health, functional impairment, and activity limitations compared with siblings (P < .001). Rates of marriage, college graduation, employment, and health insurance were all lower compared with sibling controls (P < .001). Long-term survivors of childhood ALL exhibit excess mortality and morbidity. Survivors who received radiation therapy as part of their treatment or had a leukemia relapse are at greatest risk for adverse outcomes. C1 [Neglia, Joseph P.] Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA. [Mody, Rajen] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. [Li, Suwen; Dover, Douglas C.; Yasui, Yutaka] Univ Alberta, Sch Publ Hlth, Edmonton, AB, Canada. [Sallan, Stephen] Fred Hutchinson Canc Res Ctr, Dept Biostat, Seattle, WA 98104 USA. [Leisenring, Wendy] Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. [Oeffinger, Kevin C.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Robison, Leslie L.] St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. RP Neglia, JP (reprint author), Univ Minnesota, Sch Med, Dept Pediat, 420 Delaware St Se, Minneapolis, MN 55455 USA. EM jneglia@umn.edu RI Yasui, Yutaka/E-2564-2015 OI Yasui, Yutaka/0000-0002-7717-8638 FU Intramural NIH HHS; PHS HHS [U24 55727] NR 66 TC 150 Z9 155 U1 1 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JUN 15 PY 2008 VL 111 IS 12 BP 5515 EP 5523 DI 10.1182/blood-2007-10-117150 PG 9 WC Hematology SC Hematology GA 314CN UT WOS:000256786500022 PM 18334672 ER PT J AU Dreicer, R Li, HL Cooney, MM Wilding, G Roth, BJ AF Dreicer, Robert Li, Hailun Cooney, Matthew M. Wilding, George Roth, Bruce J. TI Phase 2 trial of pemetrexed disodium and gemcitabine in advanced urothelial cancer (E4802) - A trial of the Eastern Cooperative Oncology Group SO CANCER LA English DT Article DE gemcitabine; pemetrexed disodium; bladder cancer; urothelial cancer ID TRANSITIONAL-CELL CARCINOMA; LONG-TERM-SURVIVAL; II TRIAL; BLADDER-CANCER; PACLITAXEL; CISPLATIN; THERAPY; AGENT; METHOTREXATE; VINBLASTINE AB BACKGROUND. There is a need to identify active new regimens in patients with advanced urothelial cancer. Pemetrexed and gemcitabine are active agents in advanced urothelial cancer. A phase 2 trial of the combination of these 2 agents was performed in patients with advanced urothelial cancer who were previously untreated for metastatic disease. METHODS. Forty-six patients with advanced urothelial carcinoma received pemetrexed disodium 500 mg/m(2) and gemcitabine 1000 mg/m(2) intravenously on Day 1, with gemcitabine repeated on Day 8. Cycles were repeated every 3 weeks for a maximum of 6 cycles. RESULTS. Two patients attained a complete response, and 12 patients attained a partial response for an overall response rate of 31.8% (90% confidence interval, 20.4%-45.2%). The median time to disease progression was 5.8 months, and the median overall survival was 13.4 months. Thirty-three patients (75%) experienced grade >= 3 neutropenia, and 5 patients (11%) had febrile neutropenia. There were 2 therapy-related deaths. CONCLUSIONS. The combination of pemetrexed and gemcitabine had moderate antitumor activity in previously untreated patients with advanced urothelial cancer at the expense of significant myelo suppression. C1 [Dreicer, Robert] Cleveland Clin, Dept Solid Tumor Oncol, Taussig Canc Inst, Cleveland, OH 44195 USA. [Li, Hailun] Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. [Cooney, Matthew M.] Univ Hosp Cleveland, Div Hematol Oncol, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Wilding, George] Univ Wisconsin, Ctr Clin Canc, Div Med Oncol, Madison, WI USA. [Roth, Bruce J.] Vanderbilt Ingram Canc Ctr, Div Hematol Oncol, Nashville, TN USA. RP Dreicer, R (reprint author), Cleveland Clin, Dept Solid Tumor Oncol, Taussig Canc Inst, 9500 Euclid Ave R35, Cleveland, OH 44195 USA. EM dreicer@ccf.org FU NCI NIH HHS [U10 CA021115-25, U10 CA023318-23, CA14548, CA21076, U10 CA049957, CA21115, U10 CA049957-11, CA49957, U10 CA014548, U10 CA014548-25, U10 CA066636-06, U10 CA021076, U10 CA021115, CA66636, U10 CA021076-24, U10 CA066636, U10 CA023318, CA23318] NR 19 TC 18 Z9 18 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 15 PY 2008 VL 112 IS 12 BP 2671 EP 2675 DI 10.1002/cncr23503 PG 5 WC Oncology SC Oncology GA 311DJ UT WOS:000256580200007 PM 18459175 ER PT J AU Jiang, Z Lohse, CM Chu, PG Wu, CL Woda, BA Rock, KL Kwon, ED AF Jiang, Zhong Lohse, Christine M. Chu, Peigou G. Wu, Chin-Lee Woda, Bruce A. Rock, Kenneth L. Kwon, Eugene D. TI Oncofetal protein IMP3 - A novel molecular marker that predicts metastasis of papillary and chromophobe renal cell carcinomas SO CANCER LA English DT Article DE IMP3; oncofetal protein; mRNA binding protein; prognostic biomarker; papillary renal cell carcinoma; chromophobe renal cell carcinoma ID RNA-BINDING PROTEIN; HEIDELBERG CLASSIFICATION; PROGNOSTIC FEATURES; INTERFERON-ALPHA; MESSENGER-RNA; CANCER; TUMORS; NEPHRECTOMY; SUNITINIB; SURVIVAL AB BACKGROUND. Whether an oncofetal protein, IMP3, can serve as a prognostic biomarker to predict metastasis for patients with localized papillary and chromophobe subtypes of renal cell carcinomas (RCCs) was investigated. METHODS. The expression of IMP3 in 334 patients with primary papillary and chromophobe RCC from multiple medical centers was evaluated by immunohistochemistry. The 317 patients with localized papillary and chromophobe RCCs were further evaluated for outcome analyses. RESULTS. IMP3 was significantly increased in a subset of localized papillary and chromophobe RCCs that subsequently metastasized. Patients with localized IMP3-positive tumors (n = 33; 10%) were over 10 times more likely to metastasize (risk ratio [RR], 11.38; 95% confidence interval [CI], 5.40-23.96; P < .001) and were nearly twice as likely to die (RR, 1.91; 95% CI, 1.13-3.22; P = .016) compared with patients with localized IMP3 negative tumors. The 5-year metastasis-free and overall survival rates were 64% and 58% for patients with IMP3-positive localized papillary and chromophobe RCCs compared with 98% and 85% for patients with IMP3 negative tumors, respectively In multivariable analysis adjusting for the TNM stage and nuclear grade, patients with IMP3-positive tumors were still over 10 times more likely to progress to distant metastasis (RR, 13.45; 95% CI, 6.00-30.14; P < .001) and were still nearly twice as likely die (RR, 1.95; 95% CI, 1.15-3.31; P = .013) compared with patients with IMP3-negative tumors. CONCLUSIONS. IMP3 is an independent prognostic biomarker that can be used to identify a subgroup of patients with localized papillary and chromophobe RCC who are at high risk for developing distant metastasis. C1 [Jiang, Zhong; Woda, Bruce A.; Rock, Kenneth L.] Univ Massachusetts, Dept Pathol, Med Ctr, Worcester, MA 01605 USA. [Lohse, Christine M.] Mayo Clin, Div Biostat, Rochester, MI USA. [Chu, Peigou G.] City Hope Natl Med Ctr, Div Pathol, Los Angeles, CA USA. [Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kwon, Eugene D.] Mayo Clin, Dept Urol, Rochester, MI USA. RP Jiang, Z (reprint author), Univ Massachusetts, Dept Pathol, Med Ctr, 3 Biotech,1 Innovat Dr, Worcester, MA 01605 USA. EM jiangz@ummhc.org; kwon.eugene@mayo.edu FU NCI NIH HHS [R01 CA134345, R01 CA134345-01A1] NR 34 TC 48 Z9 49 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 15 PY 2008 VL 112 IS 12 BP 2676 EP 2682 DI 10.1002/cncr.23484 PG 7 WC Oncology SC Oncology GA 311DJ UT WOS:000256580200008 PM 18412154 ER PT J AU Galiegue-Zouitina, S Delestre, L Dupont, C Troussard, X Shelley, CS AF Galiegue-Zouitina, Sylvie Delestre, Laure Dupont, Caroline Troussard, Xavier Shelley, Carl Simon TI Underexpression of RhoH in hairy cell leukemia SO CANCER RESEARCH LA English DT Article ID DNA-BINDING ACTIVITY; GENE-EXPRESSION; LEUKOCYTE ADHESION; ACID-PHOSPHATASE; NUCLEAR-PROTEIN; C-FOS; JUN; LINE; INDUCTION; ONCOGENE AB The cause of hairy cell leukemia (HCL) is unknown. Current treatments seem effective only for a limited period of time. In addition, a significant proportion of patients remain refractive to ail treatment options. These considerations indicate the need to develop alternative therapeutic strategies for HCL. Here, we report that HCL is characterized by underexpression of RhoH. In vitro reconstitution of RhoH expression inhibits the aberrant adhesion and transendothelial migration that drives disease pathogenesis. In an in vivo model of HCL, RhoH reconstitution limits malignant progression and protects against mortality. These findings provide the proof of principle that RhoH reconstitution represents a potential new approach to the treatment of HCL. C1 [Shelley, Carl Simon] La Crosse Med Hlth Sci Ctr, Gundersen Lutheran Med Fdn, La Crosse, WI 54601 USA. [Galiegue-Zouitina, Sylvie; Delestre, Laure; Dupont, Caroline; Shelley, Carl Simon] Inst Rech Canc Lille, Ctr Jean Pierre Aubert, U 837, Inst Natl Sante & Rech Med, Lille, France. [Troussard, Xavier] Univ Caen, Ctr Hosp, Hematol Lab, F-14032 Caen, France. [Shelley, Carl Simon] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit, Boston, MA USA. RP Shelley, CS (reprint author), La Crosse Med Hlth Sci Ctr, Gundersen Lutheran Med Fdn, 1300 Badger St, La Crosse, WI 54601 USA. EM carlsimonshelley@yahoo.com NR 49 TC 15 Z9 15 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 JUN 15 PY 2008 VL 68 IS 12 BP 4531 EP 4540 DI 10.1158/0008-5472.CAN-07-5661 PG 10 WC Oncology SC Oncology GA 315CO UT WOS:000256855700009 PM 18559497 ER PT J AU Montagut, C Sharma, SV Shioda, T McDermott, U Ulman, M Ulkus, LE Dias-Santagata, D Stubbs, H Lee, DY Singh, A Drew, L Haber, DA Settleman, J AF Montagut, Clara Sharma, Sreenath V. Shioda, Toshi McDermott, Ultan Ulman, Matthew Ulkus, Lindsey E. Dias-Santagata, Dora Stubbs, Hannah Lee, Diana Y. Singh, Anurag Drew, Lisa Haber, Daniel A. Settleman, Jeffrey TI Elevated CRAF as a potential mechanism of acquired resistance to BRAF inhibition in melanoma SO CANCER RESEARCH LA English DT Article ID GASTROINTESTINAL STROMAL TUMORS; B-RAF; LUNG-CANCER; BCR-ABL; CLINICAL RESISTANCE; ONCOGENE ADDICTION; KINASE INHIBITORS; RECEPTOR GENE; PHASE-I; MUTATIONS AB Activating BRAF kinase mutations arise in similar to 7% of all human tumors, and preclinical studies have validated the RAF-mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase-ERK signaling cascade as a potentially important therapeutic target in this setting. Selective RAF kinase inhibitors are currently undergoing clinical development, and based on the experience with other kinase-targeted therapeutics, it is expected that clinical responses to these agents, if observed, will lead to the eventual emergence of drug resistance in most cases. Thus, it is important to establish molecular mechanisms underlying such resistance to develop effective therapeutic strategies to overcome or prevent drug resistance. To anticipate potential mechanisms of acquired resistance to RAF inhibitors during the course of treatment, we established drug-resistant clones from a human melanoma-derived cell line harboring the recurrent V600E activating BRAF mutation, which exhibits exquisite sensitivity to AZ628, a selective RAF kinase inhibitor. We determined that elevated CRAF protein levels account for the acquisition of resistance to AZ628 in these cells, associated with a switch from BRAF to CRAF dependency in tumor cells. We also found that elevated CRAF protein levels may similarly contribute to primary insensitivity to RAF inhibition in a subset of BRAF mutant tumor cells. Interestingly, AZ628-resistant cells demonstrating either primary drug insensitivity or acquired drug resistance exhibit exquisite sensitivity to the HSP90 inhibitor geldanamycin. Geldanamycin effectively promotes the degradation of CRAF, thereby revealing a potential therapeutic strategy to overcome resistance to RAF inhibition in a subset of BRAF mutant tumors. C1 [Montagut, Clara; Sharma, Sreenath V.; Shioda, Toshi; McDermott, Ultan; Ulman, Matthew; Ulkus, Lindsey E.; Dias-Santagata, Dora; Stubbs, Hannah; Lee, Diana Y.; Singh, Anurag; Haber, Daniel A.; Settleman, Jeffrey] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc,Ctr Mol Therapeut, Charlestown, MA 02129 USA. [Drew, Lisa] AstraZeneca R&D Boston, Waltham, MA USA. RP Settleman, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc,Ctr Mol Therapeut, 149 13th St, Charlestown, MA 02129 USA. EM Settleman@helix.mgh.harvard.edu RI Singh, Anurag/C-7347-2014; OI Singh, Anurag/0000-0003-4705-8683; McDermott, Ultan/0000-0001-9032-4700 FU NCI NIH HHS [R01 CA109447-04, R01 CA115830, R01CA115830, T32 CA009216, T32 CA009216-28] NR 42 TC 290 Z9 295 U1 1 U2 25 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 JUN 15 PY 2008 VL 68 IS 12 BP 4853 EP 4861 DI 10.1158/0008-5472.CAN-07-6787 PG 9 WC Oncology SC Oncology GA 315CO UT WOS:000256855700045 PM 18559533 ER PT J AU Young, AP Kaelin, WG AF Young, Arthur P. Kaelin, William G., Jr. TI Senescence triggered by the loss of the VHL tumor suppressor SO CELL CYCLE LA English DT Article DE VHL; senescence; Hif; Rb; p27; p400; tumor suppression ID ONCOGENE-INDUCED SENESCENCE; CONDITIONAL INACTIVATION; VASCULAR TUMORS; CELL-CYCLE; CANCER; MICE; PROTEIN; HIF; CARCINOGENESIS; INHIBITORS C1 [Young, Arthur P.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Dev & Stem Cell Biol, Boston, MA 02215 USA. [Kaelin, William G., Jr.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kaelin, William G., Jr.] Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. [Kaelin, William G., Jr.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Kaelin, William G., Jr.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Young, AP (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Dev & Stem Cell Biol, 1 Joslin Pl,Rm 630, Boston, MA 02215 USA. EM arthur.young@joslin.harvard.edu NR 37 TC 7 Z9 7 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUN 15 PY 2008 VL 7 IS 12 BP 1709 EP 1712 DI 10.4161/cc.7.12.6124 PG 4 WC Cell Biology SC Cell Biology GA 320QE UT WOS:000257249300004 PM 18583945 ER PT J AU Signoretti, S Bratslavsky, G Waldman, FM Reuter, VE Haaga, J Merino, M Thomas, GV Pins, MR Libermann, T Gillespie, J Tomaszewski, JE Compton, CC Hruszkewycz, A Linehan, WM Atkins, MB AF Signoretti, Sabina Bratslavsky, Gennady Waldman, Frederick M. Reuter, Victor E. Haaga, John Merino, Maria Thomas, George V. Pins, Michael R. Libermann, Towia Gillespie, John Tomaszewski, Joseph E. Compton, Carolyn C. Hruszkewycz, Andrew Linehan, W. Marston Atkins, Michael B. TI Tissue-based research in kidney cancer: Current challenges and future directions SO CLINICAL CANCER RESEARCH LA English DT Review ID RENAL-CELL CARCINOMA; MICROARRAY TECHNOLOGY; PERCUTANEOUS BIOPSY; MASSES; TEMSIROLIMUS; SENSITIVITY; THERAPIES; TUMORS AB The past several years have seen unprecedented advances in the application of various therapeutic strategies for the treatment of patients with renal cancer. The availability of active immunotherapy, antiangiogenic therapy, and targeted therapy for this disease has brought front and center issues related to choosing the appropriate treatment for particular patient populations. It is increasingly evident that the most promising treatment selection strategies will incorporate identifying specific features of the tumor itself. To facilitate this move toward personalized medicine, it is critically important to establish some standard principles for renal cancer tissue collection, preparation, and analysis for translational research studies. In this article, we identify and discuss some critical issues related to tissue-based kidney cancer research. We focus on five major areas as follows: (a) surgical and image-guided techniques for tissue collection; (b) quality control of specimen collection, processing, storage, and review; (c) issues related to analysis of paraffin embedded tissues; (d) genomic studies; and (e) assessment of reproducibility of assays across institutions. In addition, some practical implementation strategies are proposed. Although many of the topics discussed are specific for renal cancer, several are also relevant to tissue based biomarker investigations in a broad array of malignancies. C1 [Signoretti, Sabina] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Signoretti, Sabina] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Libermann, Towia] BIDMC Genom Ctr, Boston, MA USA. [Atkins, Michael B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol, Boston, MA 02215 USA. [Bratslavsky, Gennady; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Merino, Maria] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Compton, Carolyn C.] NCI, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA. [Waldman, Frederick M.] Univ Calif San Francisco, Dept Lab Med, Ctr Comprehens Canc, San Francisco, CA 94143 USA. [Waldman, Frederick M.] Univ Calif San Francisco, Dept Urol, Ctr Comprehens Canc, San Francisco, CA 94143 USA. [Reuter, Victor E.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Haaga, John] Univ Hosp Cleveland, Dept Radiol, Cleveland, OH 44106 USA. [Haaga, John] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Thomas, George V.] Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90024 USA. [Pins, Michael R.] Advocate Lutheran Gen Hosp, Dept Pathol, Park Ridge, IL USA. [Gillespie, John] NCI, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA. [Tomaszewski, Joseph E.] NCI, Div Canc Treatment & Diag, Rockville, MD USA. [Hruszkewycz, Andrew] NCI, Organ Syst Branch, Rockville, MD USA. RP Signoretti, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, 75 Francis St, Boston, MA 02115 USA. EM ssignoretti@partners.org RI Libermann, Towia/F-9866-2010; OI Libermann, Towia/0000-0002-4006-8179 FU Intramural NIH HHS [Z01 SC006659-25]; NCI NIH HHS [N01 CO012400] NR 28 TC 18 Z9 19 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2008 VL 14 IS 12 BP 3699 EP 3705 DI 10.1158/1078-0432.CCR-07-4733 PG 7 WC Oncology SC Oncology GA 313ZS UT WOS:000256779100012 PM 18559586 ER PT J AU Ahn, MJ Park, BB Ahn, JS Kim, SW Kim, HT Lee, JS Kang, JH Cho, JY Song, HS Park, SH Sohn, CH Shin, SW Choi, JH Ki, CS Park, CK Holmes, AJ Janne, PA Park, K AF Ahn, Myung-Ju Park, Byeong-Bae Ahn, Jin Seok Kim, Sang We Kim, Heung-Tae Lee, Jong Seog Kang, Jin Hyung Cho, Jae Yong Song, Hong Suk Park, Se Hoon Sohn, Chang Hak Shin, Sang Won Choi, Jin Hyuck Ki, Chang-Seok Park, Chan Keum Holmes, Alison J. Janne, Pasi A. Park, Keunchil TI Are there any ethnic differences in molecular predictors of erlotinib efficacy in advanced non-small cell lung cancer? SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 01-05, 2007 CL Chicago, IL SP Amer Soc Clin Oncol ID FACTOR-RECEPTOR GENE; GEFITINIB SENSITIVITY; EGFR MUTATIONS; SURVIVAL AB Purpose: This study investigated possible molecular predictors of outcome in Korean patients with advanced non-small cell lung cancer treated with erlotinib. Experimental Design: One hundred and twenty patients received erlotinib and were followed prospectively. Ninety-two tissue samples were analyzed for epidermal growth factor receptor (EGFR) gene mutations (exons 18, 19, and 21), 88 for EGFR gene amplification by real-time PCR, and 75 for EGFR protein expression by immunohistochemistry. Results: The overall tumor response rate was 24.2% (complete response, 4; partial response, 25) with 56.7% of disease control rate. With a median follow-up of 23.6 months, the median time to progression (TTP) was 2.7 months and the median overall survival was 12.9 months. EGFR gene mutations were found in 26.1% (24 of 92), EGFR gene amplification in 40.9% (36 of 88), and EGFR protein expression in 72% (54 of 75). There was a strong association between EGFR gene mutations and gene amplification (gamma = 0.241). Patients with EGFR gene mutations or gene amplification showed both better response rate (58.3% versus 16.2%, P < 0.001; 41.7% versus 17.3%, P = 0.012) and TTP (8.6 versus 2.5 months, P = 0.003; 5.8 versus 1.8 months, P < 0.001) and overall survival (not reached versus 10.8 months, P = 0.023; not reached versus 10.1 months, P = 0.033). By multivariate analysis, EGFR gene mutation was the only significant molecular predictor for TTP (hazard ratio, 0.47; 95% confidence interval, 0.25-0.89). Conclusions: Our findings indicate that EGFR gene mutation is a more predictive marker for improved TTP than EGFR gene amplification in erlotinib-treated Korean non-small cell lung cancer patients. Prospective studies from diverse ethnic backgrounds are required to determine the exact role of these molecular markers. C1 [Ahn, Myung-Ju; Ahn, Jin Seok; Park, Keunchil] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Internal Med,Div Hematol Oncol, Seoul, South Korea. [Ki, Chang-Seok] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Lab Med & Genet, Seoul, South Korea. [Park, Byeong-Bae] Hanyang Univ, Coll Med, Div Hematol Oncol, Dept Internal Med, Seoul, South Korea. [Park, Chan Keum] Hanyang Univ, Coll Med, Dept Pathol, Seoul, South Korea. [Kim, Sang We] Univ Ulsan, Coll Med, Div Oncol, Dept Internal Med,Asan Med Ctr, Ulsan, South Korea. [Kang, Jin Hyung] Catholic Univ, Kang Nam St Marys Hosp, Dept Internal Med, Seoul, South Korea. [Cho, Jae Yong] Yonsei Univ, Coll Med, Dept Internal Med, Yongdong Severance Hosp, Seoul 120749, South Korea. [Shin, Sang Won] Korea Univ, Ctr Med, Anam Hosp, Div Hematol Oncol,Dept Internal Med, Seoul, South Korea. [Kim, Heung-Tae] Natl Canc Ctr, Res Inst Hosp, Goyang 411769, Gyeonggi, South Korea. [Lee, Jong Seog] Seoul Natl Univ, Dept Internal Med, Bundang, South Korea. [Song, Hong Suk] Keimyung Univ, Sch Med, Dept Internal Med, Taegu, South Korea. [Park, Se Hoon] Gil Med Ctr, Gachun Med Sch, Dept Hematol Oncol, Inchon, South Korea. [Sohn, Chang Hak] Inje Univ Coll Med, Dept Internal Med, Pusan, South Korea. [Choi, Jin Hyuck] Ajou Univ, Sch Med, Dept Hematol Oncol, Suwon 441749, South Korea. [Holmes, Alison J.; Janne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Park, K (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Internal Med,Div Hematol Oncol, Seoul, South Korea. EM kpark@smc.samsung.co.kr RI Ki, Chang Seok/C-9599-2011; ki, cs/O-5931-2014; Park, Byeong-Bae/D-2137-2015; OI Ki, Chang-Seok/0000-0001-7679-8731 NR 21 TC 38 Z9 42 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2008 VL 14 IS 12 BP 3860 EP 3866 DI 10.1158/1078-0432.CCR-07-4608 PG 7 WC Oncology SC Oncology GA 313ZS UT WOS:000256779100032 PM 18559606 ER PT J AU Sittler, T Zhou, J Park, J Yuen, NK Sarantopoulos, S Mollick, J Salgia, R Giobbie-Hurder, A Dranoff, G Hodi, FS AF Sittler, Taylor Zhou, Jun Park, Joosang Yuen, Noah K. Sarantopoulos, Stefanie Mollick, Joseph Salgia, Ravi Giobbie-Hurder, Anita Dranoff, Glenn Hodi, F. Stephen TI Concerted potent humoral immune responses to autoantigens are associated with tumor destruction and favorable clinical outcomes without autoimmunity SO CLINICAL CANCER RESEARCH LA English DT Article ID COLONY-STIMULATING FACTOR; UPSTREAM BINDING-FACTOR; AUGMENTS ANTITUMOR IMMUNITY; T-LYMPHOCYTE ANTIGEN-4; FOCAL ADHESION KINASE; HEPATOCELLULAR-CARCINOMA; METASTATIC MELANOMA; PROGNOSTIC-SIGNIFICANCE; SEROLOGICAL ANALYSIS; CANCER-CELLS AB Purpose: The therapeutic importance of immune responses against single versus multiple antigens is poorly understood. There also remains insufficient understanding whether responses to one subset of antigens are more significant than another. Autoantibodies are frequent in cancer patients. They can pose no biological significance or lead to debilitating paraneoplastic syndromes. Autoreactivity has been associated with clinical benefits, but the magnitude necessary for meaningful results is unknown. Autologous tumor cells engineered to secrete granulocyte macrophage colony-stimulating factor generate immune infiltrates in preexisting metastases with associated tumor destruction. We sought to identify targets of responses from this vaccination strategy. Experimental Design: Postvaccination sera used in screening a cDNA expression library prepared from a densely infiltrated metastasis of a long-term surviving melanoma patient identified several autoantigens. Additional autoantigens were identified through similar screenings in non - small cell lung cancer and murine models, and proteins implicated in cancer propagation. ELISAs for several targets were established using recombinant proteins, whereas others were evaluated by petit serologies. Results: Eleven gene products were identified through serologic screening from two patients showing highly favorable clinical outcomes. A subset of antigens revealed significant changes in antibody titers compared with weak responses to other proteins. Time course analyses showed coordinated enhanced titers against several targets as a function of vaccination in responding patients. Conclusions: This study shows the range of biologically significant antigens resulting from a whole-cell vaccine. Targets include autoantigens that are components of cell cycle regulation. Potent antibody responses against multiple autoantigens are associated with effective tumor destruction without clinical autoimmunity. C1 [Zhou, Jun; Park, Joosang; Sarantopoulos, Stefanie; Dranoff, Glenn; Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sittler, Taylor] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. [Sittler, Taylor; Zhou, Jun; Sarantopoulos, Stefanie; Dranoff, Glenn; Hodi, F. Stephen] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Giobbie-Hurder, Anita] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Dranoff, Glenn; Hodi, F. Stephen] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Dranoff, Glenn; Hodi, F. Stephen] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Yuen, Noah K.] Univ Hawaii Manoa, John A Burns Sch Med, Honolulu, HI 96822 USA. [Mollick, Joseph] Stanford Univ, Div Hematol Oncol, Dept Med, Stanford, CA 94305 USA. [Salgia, Ravi] Univ Chicago, Div Hematol Oncol, Dept Med, Chicago, IL 60637 USA. RP Hodi, FS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM stephen.hodi@dfci.harvard.edu FU NCI NIH HHS [CA78880, T32 CA009172] NR 47 TC 18 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2008 VL 14 IS 12 BP 3896 EP 3905 DI 10.1158/1078-0432.CCR-07-4782 PG 10 WC Oncology SC Oncology GA 313ZS UT WOS:000256779100037 PM 18559611 ER PT J AU Asomaning, K Reid, AE Zhou, W Heist, RS Zhai, R Su, L Kwak, EL Blaszkowsky, L Zhu, AX Ryan, DP Christiani, DC Liu, G AF Asomaning, Kofi Reid, Amy E. Zhou, Wei Heist, Rebecca S. Zhai, Rihong Su, Li Kwak, Eunice L. Blaszkowsky, Lawrence Zhu, Andrew X. Ryan, David P. Christiani, David C. Liu, Geoffrey TI MDM2 promoter polymorphism and pancreatic cancer risk and prognosis SO CLINICAL CANCER RESEARCH LA English DT Article ID REPAIR GENE POLYMORPHISMS; CELL LUNG-CANCER; PROSTATE CARCINOMA; POOR-PROGNOSIS; ONCOLOGY-GROUP; P53; SURVIVAL; SUSCEPTIBILITY; TRENDS; OVEREXPRESSION AB Purpose: The mouse double minute 2 homologue (MDM2) -309T/G promoter polymorphism has been associated recently with the development and prognosis of a variety of tumors. The G allele is associated with increased affinity for Sp1 binding and higher MDM2 mRNA and protein levels, leading to diminished tumor suppressor activity of the p53 pathway. We hypothesized that the G allele is also associated with increased risk and worse outcome in pancreatic cancer. Experimental Design: We evaluated the association between MDM2 309T/G and the risk of histologically confirmed pancreatic adenocarcinoma at Massachusetts General Hospital using unconditional logistic regression (123 cases and 372 controls). Complete overall survival and progression-free survival data were also available for 109 newly diagnosed patients. Results: The adjusted odds ratios (95% confidence intervals) of pancreatic cancer associated with the MDM2 T/G and G/G genotypes compared with TT were 1.89 (1.20-2.99) and 2.07 (1.03-4.16), respectively (adjusting forage, gender, smoking status, and pack-years of smoking). In Cox proportional hazards model with the wild-type T/T genotype as the reference category and adjusting for stage, treatment, and performance status, both the heterozygous T/G and the homozygous G/G genotypes were associated with decreased progression-free survival [adjusted hazard ratio (95% confidence interval), 1.67 (0.98-2.84) for T/G and 2.28 (1.11-4.71) for G/G] and overall survival [2.64 (1.23-5.67) for T/G and 3.12 (1.22-7.91) for G/G]. Conclusions: The G allele of the MDM2 -309T/G polymorphism is associated with 2- to 3-fold increase risk and progression of pancreatic adenocarcinoma and a corresponding decrease in survival. C1 [Asomaning, Kofi; Zhou, Wei; Zhai, Rihong; Su, Li; Christiani, David C.; Liu, Geoffrey] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Cambridge, MA 02138 USA. [Reid, Amy E.; Heist, Rebecca S.; Kwak, Eunice L.; Blaszkowsky, Lawrence; Zhu, Andrew X.; Ryan, David P.; Liu, Geoffrey] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Liu, Geoffrey] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. RP Liu, G (reprint author), 610 Univ Ave,Room 7-124, Toronto, ON M5G 2M9, Canada. EM Geoffrey.Liu@uhn.on.ca RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [R01CA074386, R01CA092824, R01CA109193, R03CA110822] NR 30 TC 25 Z9 26 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2008 VL 14 IS 12 BP 4010 EP 4015 DI 10.1158/1078-0432.CCR-07-4187 PG 6 WC Oncology SC Oncology GA 313ZS UT WOS:000256779100050 PM 18559624 ER PT J AU Walkley, CR Qudsi, R Sankaran, VG Perry, JA Gostissa, M Roth, SI Rodda, SJ Snay, E Dunning, P Fahey, FH Alt, FW McMahon, AP Orkin, SH AF Walkley, Carl R. Qudsi, Rameez Sankaran, Vijay G. Perry, Jennifer A. Gostissa, Monica Roth, Sanford I. Rodda, Stephen J. Snay, Erin Dunning, Patricia Fahey, Frederic H. Alt, Frederick W. McMahon, Andrew P. Orkin, Stuart H. TI Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease SO GENES & DEVELOPMENT LA English DT Article DE cancer; mouse model; osteocarcinoma ID RADIATION-INDUCED SARCOMAS; LI-FRAUMENI-SYNDROME; STEM-CELLS; TUMOR-SUPPRESSOR; C-FOS; OSTEOBLAST DIFFERENTIATION; TRANSGENIC MICE; BREAST-CANCER; BONE-MARROW; RETINOBLASTOMA PROTEIN AB Osteosarcoma is the most common primary malignant tumor of bone. Analysis of familial cancer syndromes and sporadic cases has strongly implicated both p53 and pRb in its pathogenesis; however, the relative contribution of these mutations to the initiation of osteosarcoma is unclear. We describe here the generation and characterization of a genetically engineered mouse model in which all animals develop short latency malignant osteosarcoma. The genetically engineered mouse model is based on osteoblast-restricted deletion of p53 and pRb. Osteosarcoma development is dependent on loss of p53 and potentiated by loss of pRb, revealing a dominance of p53 mutation in the development of osteosarcoma. The model reproduces many of the defining features of human osteosarcoma including cytogenetic complexity and comparable gene expression signatures, histology, and metastatic behavior. Using a novel in silico methodology termed cytogenetic region enrichment analysis, we demonstrate high conservation of gene expression changes between murine osteosarcoma and known cytogentically rearranged loci from human osteosarcoma. Due to the strong similarity between murine osteosarcoma and human osteosarcoma in this model, this should provide a valuable platform for addressing the molecular genetics of osteosarcoma and for developing novel therapeutic strategies. C1 [Walkley, Carl R.; Qudsi, Rameez; Sankaran, Vijay G.; Perry, Jennifer A.; Orkin, Stuart H.] Harvard Univ, Sch Med,Harvard Stem Cell Inst, Dept Pediat Oncol,Childrens Hosp, Dana Farber Canc Inst,Div Hematol Oncol, Boston, MA 02115 USA. [Walkley, Carl R.; Qudsi, Rameez; Sankaran, Vijay G.; Perry, Jennifer A.; Orkin, Stuart H.] Harvard Univ, Sch Med, Stem Cell Program, Childrens Hosp,Harvard Stem Cell Inst, Boston, MA 02115 USA. [Gostissa, Monica; Alt, Frederick W.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,Dept Genet, Boston, MA 02115 USA. [Gostissa, Monica; Alt, Frederick W.] Immune Dis Inst, Boston, MA 02115 USA. [Roth, Sanford I.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rodda, Stephen J.; McMahon, Andrew P.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Snay, Erin; Fahey, Frederic H.] Harvard Univ, Sch Med, Div Nucl Med, Childrens Hosp, Boston, MA 02115 USA. [Dunning, Patricia] Harvard Univ, Sch Med, Dept Radiol, 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,Harvard Stem Cell Inst, Dept Pediat Oncol,Childrens Hosp, Dana Farber Canc Inst,Div Hematol Oncol, Boston, MA 02115 USA. EM Orkin@dfci.harvard.edu OI Walkley, Carl/0000-0002-4784-9031 FU Howard Hughes Medical Institute; PHS HHS [P01 056246] NR 80 TC 148 Z9 161 U1 1 U2 13 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 JUN 15 PY 2008 VL 22 IS 12 BP 1662 EP 1676 DI 10.1101/gad.1656808 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 314GG UT WOS:000256797300011 PM 18559481 ER PT J AU Lee, J Hagerty, S Cormier, KA Kim, J Kung, AL Ferrante, RJ Ryu, H AF Lee, Junghee Hagerty, Sean Cormier, Kerry A. Kim, Jinho Kung, Andrew L. Ferrante, Robert J. Ryu, Hoon TI Monoallele deletion of CBP leads to pericentromeric heterochromatin condensation through ESET expression and histone H3 (K9) methylation SO HUMAN MOLECULAR GENETICS LA English DT Article ID CREB-BINDING PROTEIN; HUNTINGTONS-DISEASE; DROSOPHILA MODEL; MOUSE MODEL; TRANSCRIPTION; GENE; METHYLTRANSFERASE; DOMAIN; ETS-2; ACETYLATION AB Chromatin remodeling is tightly controlled under physiological conditions. Alterations in chromatin structure are involved in the pathogenesis of neuronal systems. We found that the monoallelic deletion of CREB binding protein (CBP) results in the induction of ERG-associated protein with SET domain (ESET) and increases trimethylation of histone H3 (K9) and condensation of pericentromeric heterochromatin structure in neurons. Nested deletion and mutational analysis of the ESET promoter further demonstrated that the Ets-2 transcription factor regulates transcriptional activity of the ESET gene. In CBP(+/-) mice, Ets-2 occupancy in the ESET promoter DNA was markedly elevated. Our results suggest that CBP is a transcriptional repressor of ESET gene expression by limiting Ets-2 transcriptional activity, while CBP siRNA enhances basal and Ets-2-dependent ESET transcriptional activity. Altered expression of the ESET gene and hypertrimethylation of H3 (K9) correlate with striatal neuron atrophy and dysfunction in CBP(+/-) mice. These results establish an alternative pathway that loss of CBP leads to the pericentric heterochromatin condensation through ESET expression and trimethylation of H3 (K9). C1 [Lee, Junghee; Hagerty, Sean; Cormier, Kerry A.; Kim, Jinho; Ferrante, Robert J.; Ryu, Hoon] Boston Univ, Sch Med, Dept Neurol, Bedford, MA 01730 USA. [Ferrante, Robert J.] Boston Univ, Sch Med, Dept Pathol, Bedford, MA 01730 USA. [Ferrante, Robert J.] Boston Univ, Sch Med, Dept Psychiat, Bedford, MA 01730 USA. [Lee, Junghee; Hagerty, Sean; Cormier, Kerry A.; Kim, Jinho; Ferrante, Robert J.; Ryu, Hoon] Bedford Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Bedford, MA 01730 USA. [Kung, Andrew L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Ryu, H (reprint author), Boston Univ, Sch Med, Dept Neurol, 200 Springs Rd, Bedford, MA 01730 USA. EM hoonryu@bu.edu RI Hartman, Jessica/N-3210-2016; OI Kung, Andrew/0000-0002-9091-488X FU NIA NIH HHS [P30 AG13846]; NINDS NIH HHS [NS045806, NS04524] NR 32 TC 26 Z9 28 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN 15 PY 2008 VL 17 IS 12 BP 1774 EP 1782 DI 10.1093/hmg/ddn067 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 306VJ UT WOS:000256275600007 PM 18319327 ER PT J AU Ogino, S Kawasaki, T Nosho, K Ohnishi, M Suemoto, Y Kirkner, GJ Fuchs, CS AF Ogino, Shuji Kawasaki, Takako Nosho, Katsuhiko Ohnishi, Mutsuko Suemoto, Yuko Kirkner, Gregory J. Fuchs, Charles S. TI LINE-1 hypomethylation is inversely associated with microsatellite instability and CpG island methylator phenotype in colorectal cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE colon cancer; methylation; epigenomics; CIMP; LINE-1 ID POPULATION-BASED SAMPLE; DNA METHYLATION; CHROMOSOMAL INSTABILITY; COLON-CANCER; BRAF MUTATION; LIFE-STYLE; CIMP-LOW; HYPERMETHYLATION; DEMETHYLATION; FEATURES AB The CpG island methylator phenotype (CIMP) with widespread promoter CpG island methylation is a phenotype in colorectal cancer, associated with microsatellite instability (MSI) and BRAF mutation. Genome-wide hypomethylation may also play an important role in genomic instability. However, the relation between global DNA methylation level and methylation in individual CpG islands remains uncertain. Utilizing 869 population-based colorectal cancers, we measured long interspersed nucleotide element-1 (LINE-1) methylation level by Pyrosequencing, which correlates with global DNA methylation level. We quantified DNA methylation in 8 CIMP-specific promoters (CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1) by real-time PCR (MethyLight technology). LINE-1 methylation levels in tumors were approximately normally distributed (mean, 61.4%; median, 62.3%; standard deviation, 9.6%). Among the 869 tumors, 128 (15%) were classified as CIMP-high (>= 6/8 methylated promoters). The mean LINE-1 methylation level was higher in CIMP-high tumors (65.1%, p < 0.0001) than non-CIMP-high tumors (60.7%), and higher in MSI-high tumors (64.7%, p < 0.0001) than non-MSI-high tumors (60.7%). When tumors were stratified by MSI/CIMP status, compared to non-MSI-high non-CIMP-high tumors (mean LINE-1 methylation level, 60.4%), the mean LINE-1 methylation level was higher in MSI-high CIMP-high (64.8%, p < 0.0001), MSI-high non-CIMP-high (64.6%, p = 0.03) and non-MSI-high CIMP-high tumors (66.1%, p = 0.0003). In addition, 18q loss of heterozygosity in non-MSI-high tumors was correlated with LINE-1 hypomethylation (p = 0.004). In conclusion, both CIMP-high and MSI-high are inversely associated with LINE-1 hypomethylation, suggesting that CIMP/MSI and genomic hypomethylation may represent different pathways to colorectal cancer. Our data also support a possible link between global hypomethylation and chromosomal instability. (C) 2008 Wiley-Liss, Inc. C1 [Ogino, Shuji] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kirkner, Gregory J.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Room JF-215C, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU NCI NIH HHS [P01 CA087969-09, K07 CA122826, K07 CA122826-02, P01 CA055075, P01 CA055075-17, P01 CA087969, P01 CA55075, P01 CA87969] NR 48 TC 151 Z9 152 U1 1 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 15 PY 2008 VL 122 IS 12 BP 2767 EP 2773 DI 10.1002/ijc.23470 PG 7 WC Oncology SC Oncology GA 313AP UT WOS:000256713800015 PM 18366060 ER PT J AU Werneck, MBF Lugo-Villarino, G Hwang, ES Cantor, H Glimcher, LH AF Werneck, Miriam B. F. Lugo-Villarino, Geanncarlo Hwang, Eun Sook Cantor, Harvey Glimcher, Laurie H. TI T-bet plays a key role in NK-Mediated control of melanoma metastatic disease SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACTIVATED KILLER-CELLS; DENDRITIC CELLS; IFN-GAMMA; INTERFERON-GAMMA; TUMOR REJECTION; IN-VIVO; TRANSCRIPTION FACTOR; LINEAGE COMMITMENT; LUNG-CANCER; EFFECTOR AB Antitumor responses depend on type I immunity, which is severely impaired in mice deficient for the T-box expressed in T cells (T-bet) transcription factor. Both T-bet-deficient (T-bet(-/-)) NK and CTL show defective function, which can be overcome by strong stimuli due to the expression of eomesodermin, another member of the T-box family. The effective response from T-bet-mice to viral infection and tumor initiation corroborates with these findings. However, T-bet(-/-) animals fail to control cancer metastasis and are, therefore, highly susceptible to tumor spread. The mechanism of T-bet-dependent resistance to metastatic disease is not known. In this study, we show that T-bet plays a role in inhibiting cancer metastasis by regulating the longevity and function of NK cells. Our data demonstrate that the absence of a proper innate immune response driven by NK cells in T-bet(-/-) mice precludes the initiation of a potent adaptive response to tumors. Adoptive transfer of wild-type activated NK cells protects T-bet(-/-) animals after melanoma challenge showing that reconstitution of the NK compartment in these mice is sufficient to mediate a significant reduction in tumor burden. Transfer of T-bet(-/-) A-NK cells fails to do so, due to their reduced in vivo survival, inefficient lysis of cancer cells, and poor IFN-gamma production. Taken together, these results show for the first time an irreplaceable role for T-bet in the NK-mediated cross-talk between innate and adaptive immune responses to metastatic disease. C1 [Werneck, Miriam B. F.; Cantor, Harvey] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Werneck, Miriam B. F.; Cantor, Harvey] Harvard Univ, Dept Pathol, Sch Med, Boston, MA 02115 USA. [Lugo-Villarino, Geanncarlo; Glimcher, Laurie H.] Harvard Univ, Dept Med, Sch Med, Boston, MA 02115 USA. [Glimcher, Laurie H.] Harvard Univ, Dept Immunol & Infect Dis, Sch Publ Hlth, Boston, MA 02115 USA. [Hwang, Eun Sook] Ewha Womans Univ, Coll Pharm, Seoul, South Korea. [Hwang, Eun Sook] Ewha Womans Univ, Div Life & Pharmaceut Sci, Seoul, South Korea. [Hwang, Eun Sook] Ewha Womans Univ, Ctr Cell Signaling & Drug Discovery Res, Seoul, South Korea. RP Cantor, H (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM Harvey_Cantor@dfci.harvard.edu RI Werneck, Miriam/H-5802-2012; OI Lugo, Geanncarlo/0000-0003-4620-8491 FU NCI NIH HHS [CA 112663, R01 CA112663]; NIAID NIH HHS [AI 12184, AI 31541, AI 46125, P01 AI031541, R37 AI012184, U19 AI031541] NR 54 TC 42 Z9 46 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 JUN 15 PY 2008 VL 180 IS 12 BP 8004 EP 8010 PG 7 WC Immunology SC Immunology GA 322VY UT WOS:000257404600024 PM 18523263 ER PT J AU Sabbagh, L Pulle, G Liu, Y Tsitsikov, EN Watts, TH AF Sabbagh, Laurent Pulle, Gayle Liu, Yuanqing Tsitsikov, Erdyni N. Watts, Tania H. TI ERK-dependent Bim modulation downstream of the 4-1BB-TRAF1 signaling axis is a critical mediator of CD8 T cell survival in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NECROSIS-FACTOR RECEPTOR; NF-KAPPA-B; FAMILY-MEMBER BIM; 4-1BB LIGAND; TRANSCRIPTION FACTOR; FACTOR (TRAF)-1; ACTIVATION; COSTIMULATION; MEMORY; RESPONSES AB During an acute immune response, CD8 T cells undergo rapid expansion followed by a contraction phase during which the majority of activated T cells die, leaving a few survivors to persist as memory cells. The regulation of T cell survival is critical at each stage of this response. 4-1BB, a TNFR family member, has been implicated in prolonging the survival of activated and memory CD8 T cells; however, the precise mechanisms by which 4-1BB sustains T cell survival are incompletely understood. Upon aggregation on T cells, 4-1BB associates with two TNFR-associated factors (TRAF), TRAF1 and TRAF2. TRAF2 is essential for downstream signaling from 4-1BB; however, the role of TRAF1 in 4-1BB signaling has not been elucidated and there have been conflicting data as to whether TRAF1 provides a positive or a negative signal in T cells. In this study, we report that TRAF1 plays a critical role in survival signaling downstream of 4-1BB during CD8 T cell expansion in response to viral infection in vivo. Further analysis reveals that TRAF1-deficient cells are impaired in their ability to up-regulate the prosurvival Bcl-2 family member Bcl-x(L), and show increased levels of the proapoptotic Bcl-2 family member Bim following 4-1BB signaling. TRAF1-deficient CD8 T cells fail to activate ERK in response to 4-1BB ligation and inhibition of ERK signaling downstream of 4-1BB in wild-type cells leads to increased Bim levels. Thus, TRAF1 has a prosurvival effect in CD8 T cells via the 4-1BB-mediated up-regulation of Bcl-x(L) and ERK-dependent Bim down-modulation. C1 [Sabbagh, Laurent; Pulle, Gayle; Liu, Yuanqing; Watts, Tania H.] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada. [Tsitsikov, Erdyni N.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. RP Watts, TH (reprint author), Univ Toronto, Dept Immunol, Room 5263 Med Sci Bldg, Toronto, ON M5S 1A8, Canada. EM tania.watts@utoronto.ca NR 47 TC 65 Z9 65 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 JUN 15 PY 2008 VL 180 IS 12 BP 8093 EP 8101 PG 9 WC Immunology SC Immunology GA 322VY UT WOS:000257404600034 PM 18523273 ER PT J AU Sakai, K Kita, M Sawai, N Shiomi, S Sumida, Y Kanemasa, K Mitsufuji, S Imanishi, J Yamaoka, Y AF Sakai, Kyoko Kita, Masakazu Sawai, Naoki Shiomi, Satoshi Sumida, Yoshio Kanemasa, Kazuyuki Mitsufuji, Shoji Imanishi, Jiro Yamaoka, Yoshio TI Levels of interleukin-18 are markedly increased in Helicobacter pylori-Infected gastric mucosa among patients with specific IL18 genotypes SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 20th International Workshop on Helicobacter and Related Bacteria in Chronic Digestive Inflammation CY SEP 20-22, 2007 CL Istanbul, TURKEY SP European Helicobacter Study Grp ID IFN-GAMMA PRODUCTION; MESSENGER-RNA; INTERFERON-GAMMA; T-CELLS; SERUM INTERLEUKIN-18; EXPRESSION; CYTOKINE; POLYMORPHISMS; IL-18; PROMOTER AB Background. The cellular immune response in gastric mucosa infected with Helicobacter pylori is proposed to be predominantly of the T helper cell type 1 type. Methods. Interleukin (IL)-18, IL-12, and interferon (IFN)-gamma levels were measured in gastric mucosal biopsy specimens by reverse-transcription polymerase chain reaction (PCR) and by enzyme-linked immunosorbent assay; IL18 polymorphisms were determined by PCR. Results. Biopsy specimens from 128 patients (56 with nonulcer dyspepsia, 28 with gastric ulcers, 28 with duodenal ulcers, and 16 with gastric cancer) were examined; 96 patients had H. pylori infection. IL-18 levels were markedly up-regulated in mucosa infected with H. pylori (P < .001), whereas IL-12 and IFN-gamma levels were independent of H. pylori status. IL-18 levels correlated with IFN-gamma levels only in infected patients (R = 0.31 to R = 0.51). IL-18 levels were the determining factor for monocyte infiltration in H. pylori-infected mucosa (P = .001). H. pylori-infected patients displaying IL18-607C/C and-137G/G had higher IL-18 levels than did those with other genotypes and were more likely to experience treatment failure. Conclusion. H. pylori infection induces IL-18 in the gastric mucosa. H. pylori-infected patients with IL18-607C/C and -137G/G have higher IL-18 levels, which causes severe gastric inflammation. IL18 genotype might be a marker for predicting the effects of eradication therapy. C1 [Yamaoka, Yoshio] Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Gastroenterol Sect, Houston, TX USA. [Sakai, Kyoko; Sumida, Yoshio; Kanemasa, Kazuyuki] Nara City Hosp, Dept Gastroenterol & Hepatol, Nara, Japan. [Sakai, Kyoko; Sawai, Naoki; Shiomi, Satoshi; Mitsufuji, Shoji] Kyoto Prefectural Univ Med, Dept Gastroenterol, Kyoto, Japan. [Kita, Masakazu; Imanishi, Jiro] Kyoto Prefectural Univ Med, Dept Microbiol, Kyoto, Japan. [Yamaoka, Yoshio] Baylor Coll Med, Houston, TX 77030 USA. RP Yamaoka, Y (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Gastroenterol Sect, 2002 Holcombe Blvd 111D,Rm 3A-320, Houston, TX USA. EM yyamaoka@bcm.tmc.edu FU NIDDK NIH HHS [DK 62813, R01 DK062813-04, R01 DK062813] NR 38 TC 16 Z9 18 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 15 PY 2008 VL 197 IS 12 BP 1752 EP 1761 DI 10.1086/588196 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 307JN UT WOS:000256315300017 PM 18442334 ER PT J AU Chan, AW Liebsch, NJ AF Chan, Annie W. Liebsch, Norbert J. TI Proton radiation therapy for head and neck cancer SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Review DE proton radiation therapy; head and neck cancer; skull base tumor; paranasal sinus cancer; intensity-modulated radiation therapy; intensity-modulated proton therapy; sinus cancer; nasopharyngeal carcinoma ID ADENOID-CYSTIC CARCINOMA; PARANASAL SINUS CANCER; NASAL CAVITY; OROPHARYNGEAL CARCINOMA; NASOPHARYNGEAL CARCINOMA; RADIOTHERAPY; MALIGNANCIES; EXPERIENCE; PHOTON; IRRADIATION AB Due to the close spatial relationship of head and neck and skull base tumors to numerous normal anatomical structures, conventional photon radiation therapy can be associated with significant acute and long-term treatment-related toxicities. Superior dose localization properties of proton radiation therapy allow smaller volumes of normal tissues to be irradiated than is feasible with any photon technique. Intensity-modulated proton therapy (IMPT) is a powerful delivery technique which results in improved dose distribution as compared to that of intensity-modulated radiation therapy (IMRT). Initial clinical experience with proton radiation therapy in treatment of head and neck and skull base tumors is promising. Prospective multi-institutional trials are underway to define the role of proton radiation therapy, particularly IMPT, in the treatment of head and neck and skull base tumors. C1 [Chan, Annie W.; Liebsch, Norbert J.] Harvard Univ, Sch Med, Francis H Burr Proton Therapy Ctr, Massachusetts Gen Hosp,Dept Radiat Oncol, Boston, MA 02114 USA. RP Chan, AW (reprint author), Harvard Univ, Sch Med, Francis H Burr Proton Therapy Ctr, Massachusetts Gen Hosp,Dept Radiat Oncol, 55 Fruit St,Cox 3, Boston, MA 02114 USA. EM awchan@partners.org NR 30 TC 24 Z9 25 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD JUN 15 PY 2008 VL 97 IS 8 BP 697 EP 700 DI 10.1002/jso.21013 PG 4 WC Oncology; Surgery SC Oncology; Surgery GA 312DG UT WOS:000256648700014 PM 18493920 ER PT J AU Antonacci, AC Lam, S Lavarias, V Homel, P Eavey, RD AF Antonacci, Anthony C. Lam, Steven Lavarias, Valentina Homel, Peter Eavey, Roland D. TI A morbidity and mortality conference-based classification system for adverse events: Surgical outcome analysis: Part I SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE morbidity; mortality; adverse events ID TRANSFUSION MEDICINE; REPORTING SYSTEM; GENERAL-SURGERY; RISK-FACTORS; COMPLICATIONS; QUALITY; IDENTIFICATION; INCIDENTS; AMERICAN; PROPOSAL AB Background. We hypothesized that an archive database in conjunction with Morbidity and Mortality (M&M) review could be used to define a systematic list of post-surgical adverse events and identify areas for performance improvement. Study design. Adverse event data following surgery were prospectively collected at the Beth Israel Medical Center in NYC from academic, specialty, community hospital, and ambulatory care settings over a 5-year period from September 2000 through April 2005. A classification system and analysis methodology was developed to guide and maximize the effectiveness of M&M review. Results. A total of 1618 adverse events, including 219 deaths, were analyzed following 29,237 operative procedures according to the analysis method described. A list of 245 adverse events was classified among 15 groups, and a subgroup of 25 adverse events accounted for over 80% of total adverse events. Five categories of adverse events were associated with death in surgical patients and 4 of 5 categories were postoperative events. Used in conjunction with M&M review, data derived from this analysis highlighted those adverse events with the greatest clinical frequency to the department's quality profile. Conclusions. We present a classification system for surgical adverse events and propose a specific analysis method which may be used in conjunction with Morbidity and Mortality Conference to standardize the profiling of surgical performance. (C) 2008 Elsevier Inc. All rights reserved. C1 [Antonacci, Anthony C.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Antonacci, Anthony C.] Christ Hosp, Jersey City, NJ USA. [Antonacci, Anthony C.; Lam, Steven; Lavarias, Valentina] Lenox Hill Hosp, New York, NY 10021 USA. [Antonacci, Anthony C.; Homel, Peter] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. [Eavey, Roland D.] Harvard Univ, Sch Med, Dept Otol & Laryngol,Pediat Otolaryngol Serv, Massachusetts Eye & Ear Infirm,Dept Otolaryngol, Boston, MA 02115 USA. RP Antonacci, AC (reprint author), Cornell Univ, Weill Med Coll, Dept Surg, 55 North St, Greenwich, CT 06830 USA. EM aantonacci@gmail.com NR 28 TC 14 Z9 14 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUN 15 PY 2008 VL 147 IS 2 BP 172 EP 177 DI 10.1016/j.jss.2008.02.054 PG 6 WC Surgery SC Surgery GA 306JP UT WOS:000256244500003 PM 18498865 ER PT J AU Abbruzzese, TA Albadawi, H Kang, J Patel, VI Yoo, JH LaMuraglia, GM Watkins, MT AF Abbruzzese, Thomas A. Albadawi, Hassan Kang, Jeanwan Patel, Virendra I. Yoo, Jin-Hyung LaMuraglia, Glenn M. Watkins, Michael T. TI Enoxaparin does not ameliorate limb ischemia-reperfusion injury SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE heparin; ischemia; reperfusion; skeletal muscle; cytokines ID MOLECULAR-WEIGHT HEPARIN; SKELETAL-MUSCLE; UNFRACTIONATED HEPARIN; HINDLIMB ISCHEMIA; MURINE MODEL; ISCHEMIA/REPERFUSION; HEMODIALYSIS; METAANALYSIS; COAGULATION; INHIBITOR AB Objective. Since low molecular weight heparin has greater bioavailability and sustained serum levels in vivo than unfractionated heparin, it has been used to supplant unfractionated heparin to achieve therapeutic anticoagulation in humans. These studies were designed to determine whether treatment with enoxaparin could protect murine skeletal muscle from ischemia reperfusion injury. Methods. C57BL6 mice were divided into four groups. Sham control animals underwent 90 min of anesthesia alone. All other groups underwent 90 min of unilateral hindlimb ischemia. At the onset of reperfusion, animals received either normal saline (control and saline) or 4 mg/kg of enoxaparin subcutaneously twice daily. Groups were followed for 24 or 48 h reperfusion. Hindlimb skeletal muscle blood flow was measured by laser Doppler, and muscle was removed for histological and protein analysis. Tissue thrombosis was evaluated by thrombin antithrombin III (TAT III), local inflammation by measurement of proinflammatory cytokines (macrophage inflammatory protein-2: MIP-2, monocyte chemoattractant protein-1: MCP-1), and neutrophil infiltration by myeloperoxidase (MPO) using enzyme-linked immunosorbent assay. Plasma levels of Factor Xa were measured during reperfusion to confirm therapeutic levels of anticoagulation. Comparisons were calculated using analysis of variance. Results. At 24 h reperfusion, there was increased expression of MIP-2, MCP-1, MPO, and TAT III in saline and enoxaparin treated mice compared with control (*P < 0.05). By 48 h reperfusion, all parameters measured remained greater than control except for the enoxaparin treated mice whose TAT III levels were significantly less than untreated mice (P < 0.05). Despite documented therapeutic anticoagulation and decreased levels of markers of thrombosis in enoxaparin treated mice, there was no difference in tissue cytokines, inflammatory markers, degree of muscle fiber injury (31% +/- 8% versus 30% +/- 5%) or muscle flow between ischemia-reperfusion groups (2447 +/- 141 versus 2475 +/- 74 flux units) at 48 h reperfusion. Conclusions. Post hoe administration of enoxaparin did not affect local tissue thrombosis, inflammatory markers, or muscle necrosis. This suggests that despite its potent in vivo activity, enoxaparin did not modulate skeletal muscle injury, thrombosis, or inflammatory following ischemia reperfusion. enoxaparin may not be useful in mediating skeletal muscle injury when administered in a clinically relevant scenario. (C) 2008 Elsevier Inc. All rights reserved. C1 [Abbruzzese, Thomas A.; Albadawi, Hassan; Kang, Jeanwan; Patel, Virendra I.; Yoo, Jin-Hyung; LaMuraglia, Glenn M.; Watkins, Michael T.] Massachusetts Gen Hosp, Dept Surg, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. RP Watkins, MT (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Vasc & Endovasc Surg, 15 Parkman St,Suite 458, Boston, MA 02114 USA. EM mtwatkins@partners.org NR 37 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 EI 1095-8673 J9 J SURG RES JI J. Surg. Res. PD JUN 15 PY 2008 VL 147 IS 2 BP 260 EP 266 DI 10.1016/j.jss.2008.03.024 PG 7 WC Surgery SC Surgery GA 306JP UT WOS:000256244500019 PM 18498878 ER PT J AU Oh, WY Vakoc, BJ Yun, SH Tearney, GJ Bouma, BE AF Oh, W. Y. Vakoc, B. J. Yun, S. H. Tearney, G. J. Bouma, B. E. TI Single-detector polarization-sensitive optical frequency domain imaging using high-speed intra A-line polarization modulation SO OPTICS LETTERS LA English DT Article ID COHERENCE TOMOGRAPHY; IN-VIVO AB We demonstrate a novel high-speed polarization-sensitive optical frequency domain imaging system employing high-speed polarization modulation. Rapid and continuous polarization modulation of light prior to illumination of the sample is accomplished by shifting the frequency of one polarization eigenstate by an amount equal to one quarter of the digitization sampling frequency. This approach enables polarization-sensitive imaging with a single detection channel and overcomes artifacts that may arise from temporal variations of the birefringence in fiber-optic imaging probes and spatial variation of birefringence in the sample. (C) 2008 Optical Society of America. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. 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 FU NHLBI NIH HHS [R01 HL 076398, R01 HL076398, R01 HL076398-04] NR 15 TC 18 Z9 20 U1 1 U2 5 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 JUN 15 PY 2008 VL 33 IS 12 BP 1330 EP 1332 DI 10.1364/OL.33.001330 PG 3 WC Optics SC Optics GA 323ED UT WOS:000257425900016 PM 18552948 ER PT J AU Dhond, RP Yeh, C Park, K Kettner, N Napadow, V AF Dhond, Rupali P. Yeh, Calvin Park, Kyungmo Kettner, Norman Napadow, Vitaly TI Acupuncture modulates resting state connectivity in default and sensorimotor brain networks SO PAIN LA English DT Article DE pain; functional magnetic resonance imaging; limbic; alternative; complementary medicine ID INDEPENDENT COMPONENT ANALYSIS; HUMAN CINGULATE CORTEX; FUNCTIONAL CONNECTIVITY; BASE-LINE; PAIN; FMRI; FLUCTUATIONS; MRI; STIMULATION; SINGLE AB Previous studies have defined low-frequency, spatially consistent networks in resting fMRI data which may reflect functional connectivity. We sought to explore how a complex somatosensory stimulation, acupuncture, influences intrinsic connectivity in two of these networks: the default mode network (DMN) and sensorimotor network (SMN). We analyzed resting fMRI data taken before and after verum and sham acupuncture. Electrocardiography data were used to infer autonomic modulation through measures of heart rate variability (HRV). Probabilistic independent component analysis was used to separate resting fMRI data into DMN and SMN components. Following verum, but not sham, acupuncture there was increased DMN connectivity with pain (anterior cingulate cortex (ACC), periaqueductal gray), affective (amygdala, ACC), and memory (hippocampal formation, middle temporal gyrus) related brain regions. Furthermore, increased DMN connectivity with the hippocampal formation, a region known to support memory and interconnected with autonomic brain regions, was negatively correlated with acupuncture-induced increase in a sympathetic related HRV metric (LFu), and positively correlated with a parasympathetic related metric (HFu). Following verum, but not sham, acupuncture there was also increased SMN connectivity with pain-related brain regions (ACC, cerebellum). We attribute differences between verum and sham acupuncture to more varied and stronger sensations evoked by verum acupuncture. Our results demonstrate for the first time that acupuncture can enhance the post-stimulation spatial extent of resting brain networks to include anti-nociceptive, memory, and affective brain regions. This modulation and sympathovagal response may relate to acupuncture analgesia and other potential therapeutic effects. (C) 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Dhond, Rupali P.; Yeh, Calvin; Park, Kyungmo; Napadow, Vitaly] Massachusetts Gen Hosp, MGH MIT HMS Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Dhond, Rupali P.; Kettner, Norman; Napadow, Vitaly] Logan Coll Chiropract, Dept Radiol, Chesterfield, MO USA. [Park, Kyungmo] Kyung Hee Univ, Dept Biomed Engn, Yongin, South Korea. RP Napadow, V (reprint author), Massachusetts Gen Hosp, MGH MIT HMS Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. EM vitaly@nmr.mgh.harvard.edu FU NCCIH NIH HHS [K01 AT002166-03, F05 AT003770, F05 AT003770-01, F05 AT003770-02, F05-AT003770, K01 AT002166, K01 AT002166-04, K01 AT004481, K01-AT002166, P01 AT002048, P01 AT002048-04, P01 AT002048-05, P01-AT002048] NR 63 TC 147 Z9 162 U1 1 U2 23 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD JUN 15 PY 2008 VL 136 IS 3 BP 407 EP 418 DI 10.1016/j.pain.2008.01.011 PG 12 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 318PX UT WOS:000257105200023 PM 18337009 ER PT J AU Ho, KJ Owens, CD Johnson, SR Khwaja, K Curry, MP Pavlakis, M Mandelbrot, D Pomposelli, JJ Shah, SA Saidi, RF Ko, DSC Malek, S Belcher, J Hull, D Tullius, SG Freeman, RB Pomfret, EA Whiting, JF Hanto, DW Karp, SJ AF Ho, Karen J. Owens, Christopher D. Johnson, Scott R. Khwaja, Khalid Curry, Michael P. Pavlakis, Martha Mandelbrot, Didier Pomposelli, James J. Shah, Shimul A. Saidi, Reza F. Ko, Dicken S. C. Malek, Sayeed Belcher, John Hull, David Tullius, Stefan G. Freeman, Richard B. Pomfret, Elizabeth A. Whiting, James F. Hanto, Douglas W. Karp, Seth J. TI Donor postextubation hypotension and age correlate with outcome after donation after cardiac death transplantation SO TRANSPLANTATION LA English DT Article DE liver; kidney; DCD; hemodynamic instability ID HEART-BEATING DONORS; OF-WISCONSIN EXPERIENCE; LIVER-TRANSPLANTATION; KIDNEY-TRANSPLANTATION; RENAL-TRANSPLANTATION; NONHEARTBEATING DONORS; GRAFT FUNCTION; RISK-FACTORS; NONFUNCTION; PROCUREMENT AB Background. Compared with standard donors, kidneys recovered from donors after cardiac death (DCD) exhibit higher rates of delayed graft function (DGF), and DCD livers demonstrate higher rates of biliary ischemia, graft loss, and worse patient survival. Current practice limits the use of these organs based on time from donor extubation to asystole, but data to support this is incomplete. We hypothesized that donor postextubation parameters, including duration and severity of hemodynamic instability or hypoxia might be a better predictor of subsequent graft function. Methods. We performed a retrospective examination of the New England Organ Bank DCD database, concentrating on donor factors including vital signs after withdrawal of support. Results. Prolonged, severe hypotension in the postextubation period was a better predictor of subsequent organ function that time from extubation to asystole. For DCD kidneys, this manifested as a trend toward increased DGF. For DCD livers, this manifested as increased rates of poor outcomes. Maximizing the predictive value of this test in the liver cohort suggested that greater than 15 min between the time when the donor systolic blood pressure drops below 50 rum Hg and flush correlates with increased rates of diffuse biliary ischemia, graft loss, or death. Donor age also correlated with worse outcome. Conclusions. Time between profound instability and cold perfusion is a better predictor of outcome than time from extubation to asystole. If validated, this information could be used to predict DGF after DCD renal transplant and improve outcomes after DCD liver transplant. C1 [Ho, Karen J.; Johnson, Scott R.; Khwaja, Khalid; Hanto, Douglas W.; Karp, Seth J.] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. [Ho, Karen J.; Owens, Christopher D.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Curry, Michael P.; Pavlakis, Martha; Mandelbrot, Didier] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Pomposelli, James J.; Pomfret, Elizabeth A.] Lahey Clin Fdn, Dept Surg, Burlington, MA USA. [Shah, Shimul A.] UMass Mem Med Ctr, Dept Surg, Worcester, MA USA. [Saidi, Reza F.; Ko, Dicken S. C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Malek, Sayeed; Tullius, Stefan G.] Brigham & Womens Hosp, Div Transplant Surg, Boston, MA 02115 USA. [Belcher, John] One Gateway Ctr, New England Organ Bank, Newton, MA USA. [Hull, David] Hartford Hosp, Dept Surg, Hartford, CT 06115 USA. [Freeman, Richard B.] Tufts Med Ctr, Dept Surg, Boston, MA USA. [Whiting, James F.] Maine Med Ctr, Dept Surg, Portland, ME 04102 USA. RP Karp, SJ (reprint author), Beth Israel Deaconess Med Ctr, Dept Surg, 110 Francis St,7th Floor, Boston, MA 02215 USA. EM skarp@bidmc.harvard.edu NR 30 TC 48 Z9 55 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUN 15 PY 2008 VL 85 IS 11 BP 1588 EP 1594 DI 10.1097/TP.0b013e318170b6bb PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 313AG UT WOS:000256712900011 PM 18551064 ER PT J AU Wilens, TE Klint, T Adler, L West, S Wesnes, K Graff, O Mikkelsen, B AF Wilens, Timothy E. Klint, Thorsten Adler, Lenard West, Scott Wesnes, Keith Graff, Ole Mikkelsen, Birgit TI A randomized controlled trial of a novel mixed monoamine reuptake inhibitor in adults with ADHD SO BEHAVIORAL AND BRAIN FUNCTIONS LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; DOPAMINE TRANSPORTER; COGNITIVE FUNCTION; CLINICAL-TRIAL; METHYLPHENIDATE; COMORBIDITY; ADOLESCENTS; CHILDREN; SMOKING AB Background: NS2359 is a potent reuptake blocker of noradrenalin, dopamine, and serotonin. The aim of the study was to investigate the efficacy, safety and cognitive function of NS2359 in adults with a DSM IV diagnosis of ADHD. Methods: The study was a multi-centre, double-blind, randomized placebo-controlled, parallel group design in outpatient adults (18 - 55 years) testing 0.5 mg NS2359 vs. placebo for 8 weeks. Multiple assessments including computerized neuropsychological evaluation were performed. Results: There was no significant difference between NS2359 (n = 63) versus placebo (n = 63) on the primary outcome measure reduction in investigator rated ADHD-RS total score (7.8 versus 6.4; p < 0.45). However, in subjects with the inattentive subtype, there were significantly more responders in the NS2359 group compared to placebo (41% versus 7%; p < 0.01). For all secondary variables (ADHD-RS patient rated; The Conners Adult ADHD Scale; The Brown Adult Scale, and CGI-improvement scale) there were no significant differences between the two groups; however, in the inattentive subgroup, the response to treatment was significantly larger than to placebo. NS2359 improved composite factor scores of attention, episodic- and working memory. No serious adverse events were reported with insomnia, headaches and loss of appetite most commonly reported as side effects. Conclusion: No overall effect of NS2359 was found on overall symptoms of ADHD. There was also a modest signal of improvement in the inattentive adults with ADHD and cognition warranting further exploration using differing doses. C1 [Wilens, Timothy E.] Massachusetts Gen Hosp, Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Wilens, Timothy E.] Harvard Univ, Sch Med, Boston, MA USA. [Adler, Lenard] NYU Med Ctr, Fac Practice Off, New York, NY 10016 USA. [West, Scott] CNS Healthcare, Orlando, FL USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. EM twilens@partners.org; TKLINT@PRDBE.JNJ.COM; lenard.adler@med.nyu.edu; scott@cnshealthcare.com; keithw@cognitivedrugresearch.com; ole.x.graff@gsk.com; BOM@Neurosearch.dk OI Adler, Len/0000-0002-9812-8234 NR 35 TC 15 Z9 16 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1744-9081 J9 BEHAV BRAIN FUNCT JI Behav. Brain Funct. PD JUN 13 PY 2008 VL 4 AR 24 DI 10.1186/1744-9081-4-24 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 328NL UT WOS:000257805000001 PM 18554401 ER PT J AU Cichowski, K Hahn, WC AF Cichowski, Karen Hahn, William C. TI Unexpected pieces to the senescence puzzle SO CELL LA English DT Review ID ONCOGENE-INDUCED SENESCENCE; BREAST-CANCER CELLS; CELLULAR SENESCENCE; TUMORIGENESIS; FIBROBLASTS; BARRIER; GROWTH AB Although initially described as the end state of cells after extended rounds of division in culture, it is now clear that cellular senescence induced by different stimuli plays an important role in tumor suppression in vivo. Three recent studies in Cell report that secreted proteins play an important role in enforcing the senescence response (Acosta et al., 2008; Kuilman et al., 2008; Wajapeyee et al., 2008). These new studies identify unanticipated contributors to this tumor-suppressing cell state. C1 [Cichowski, Karen] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Hahn, William C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Cichowski, Karen; Hahn, William C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hahn, William C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hahn, William C.] Broad Inst Harvard, Cambridge, MA 02142 USA. [Hahn, William C.] MIT, Cambridge, MA 02142 USA. RP Cichowski, K (reprint author), Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA. EM kcichowski@rics.bwh.harvard.edu; william_hahn@dfci.harvard.edu FU NIA NIH HHS [R01 AG023145-05, R01 AG023145] NR 18 TC 48 Z9 51 U1 2 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JUN 13 PY 2008 VL 133 IS 6 BP 958 EP 961 DI 10.1016/j.cell.2008.05.027 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 312TJ UT WOS:000256693400012 PM 18555773 ER PT J AU Housley, MP Rodgers, JT Udeshi, ND Kelly, TJ Shabanowitz, J Hunt, DF Puigserver, P Hart, GW AF Housley, Michael P. Rodgers, Joseph T. Udeshi, Namrata D. Kelly, Timothy J. Shabanowitz, Jeffrey Hunt, Donald F. Puigserver, Pere Hart, Gerald W. TI O-GlcNAc regulates FoxO activation in response to glucose SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FORKHEAD TRANSCRIPTION FACTOR; LINKED N-ACETYLGLUCOSAMINE; INSULIN-RESISTANCE; MASS-SPECTROMETRY; SEQUENCE-ANALYSIS; NUCLEOCYTOPLASMIC GLYCOSYLATION; HEPATIC GLUCONEOGENESIS; HEXOSAMINE BIOSYNTHESIS; OXIDATIVE-STRESS; AKT ACTIVATION AB FoxO proteins are key transcriptional regulators of nutrient homeostasis and stress response. The transcription factor FoxO1 activates expression of gluconeogenic, including phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, and also activates the expression of the oxidative stress response enzymes catalase and manganese superoxide dismutase. Hormonal and stress-dependent regulation of FoxO1 via acetylation, ubiquitination, and phosphorylation, are well established, but FoxOs have not been studied in the context of the glucose-derived O-linked beta-N-acetylglucosamine (O-GlcNAc) modification. Here we show that O-GlcNAc on hepatic FoxO1 is increased in diabetes. Furthermore, O-GlcNAc regulates FoxO1 activation in response to glucose, resulting in the paradoxically increased expression of gluconeogenic genes while concomitantly inducing expression of genes encoding enzymes that detoxify reactive oxygen species. GlcNAcylation of FoxO provides a new mechanism for direct nutrient control of transcription to regulate metabolism and stress response through control of FoxO1 activity. C1 [Housley, Michael P.; Hart, Gerald W.] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA. [Rodgers, Joseph T.; Kelly, Timothy J.; Puigserver, Pere] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Rodgers, Joseph T.; Kelly, Timothy J.; Puigserver, Pere] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Udeshi, Namrata D.; Shabanowitz, Jeffrey; Hunt, Donald F.] Univ Virginia, Dept Chem, Charlottesville, VA 22904 USA. [Hunt, Donald F.] Univ Virginia, Dept Pathol, Charlottesville, VA 22904 USA. RP Hart, GW (reprint author), Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA. EM gwhart@jhmi.edu RI Hunt, Donald/I-6936-2012 OI Hunt, Donald/0000-0003-2815-6368 FU NICHD NIH HHS [HD13563, R37 HD013563]; NIDDK NIH HHS [DK61671, R01 DK061671]; NIGMS NIH HHS [GM37537] NR 56 TC 150 Z9 155 U1 5 U2 20 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 JUN 13 PY 2008 VL 283 IS 24 BP 16283 EP 16292 DI 10.1074/jbc.M802240200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 309YW UT WOS:000256497100004 PM 18420577 ER PT J AU Boedigheimer, MJ Wolfinger, RD Bass, MB Bushel, PR Chou, JW Cooper, M Corton, JC Fostel, J Hester, S Lee, JS Liu, FL Liu, J Qian, HR Quackenbush, J Pettit, S Thompson, KL AF Boedigheimer, Michael J. Wolfinger, Russell D. Bass, Michael B. Bushel, Pierre R. Chou, Jeff W. Cooper, Matthew Corton, J. Christopher Fostel, Jennifer Hester, Susan Lee, Janice S. Liu, Fenglong Liu, Jie Qian, Hui-Rong Quackenbush, John Pettit, Syril Thompson, Karol L. TI Sources of variation in baseline gene expression levels from toxicogenomics study control animals across multiple laboratories SO BMC GENOMICS LA English DT Article ID RAT-LIVER; KIDNEY; TRANSCRIPTOME; PROFILES; PATTERNS; ARRAYS; BLOOD; MODEL AB Background: The use of gene expression profiling in both clinical and laboratory settings would be enhanced by better characterization of variance due to individual, environmental, and technical factors. Meta-analysis of microarray data from untreated or vehicle-treated animals within the control arm of toxicogenomics studies could yield useful information on baseline fluctuations in gene expression, although control animal data has not been available on a scale and in a form best served for data-mining. Results: A dataset of control animal microarray expression data was assembled by a working group of the Health and Environmental Sciences Institute's Technical Committee on the Application of Genomics in Mechanism Based Risk Assessment in order to provide a public resource for assessments of variability in baseline gene expression. Data from over 500 Affymetrix microarrays from control rat liver and kidney were collected from 16 different institutions. Thirty-five biological and technical factors were obtained for each animal, describing a wide range of study characteristics, and a subset were evaluated in detail for their contribution to total variability using multivariate statistical and graphical techniques. Conclusion: The study factors that emerged as key sources of variability included gender, organ section, strain, and fasting state. These and other study factors were identified as key descriptors that should be included in the minimal information about a toxicogenomics study needed for interpretation of results by an independent source. Genes that are the most and least variable, gender-selective, or altered by fasting were also identified and functionally categorized. Better characterization of gene expression variability in control animals will aid in the design of toxicogenomics studies and in the interpretation of their results. C1 [Thompson, Karol L.] US FDA, CDER, Silver Spring, MD 20993 USA. [Boedigheimer, Michael J.; Bass, Michael B.] Amgen Inc, Thousand Oaks, CA 91320 USA. [Wolfinger, Russell D.] SAS Inst Inc, Cary, NC 27513 USA. [Bushel, Pierre R.; Chou, Jeff W.; Fostel, Jennifer] NIEHS, Res Triangle Pk, NC 27709 USA. [Cooper, Matthew] Roche Palo Alto LLC, Palo Alto, CA 94304 USA. [Corton, J. Christopher; Hester, Susan; Lee, Janice S.] US EPA, Res Triangle Pk, NC 27711 USA. [Liu, Fenglong; Quackenbush, John] Dana Farber Canc Inst, Boston, MA 02115 USA. [Liu, Jie] NIEHS, NCI, ICS, Res Triangle Pk, NC 27709 USA. [Qian, Hui-Rong] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Quackenbush, John] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Pettit, Syril] ILSI HESI, Washington, DC 20005 USA. RP Thompson, KL (reprint author), US FDA, CDER, Silver Spring, MD 20993 USA. EM mboedigh@amgen.com; Russ.Wolfinger@jmp.com; mbass@amgen.com; bushel@niehs.nih.gov; chou@niehs.nih.gov; matthew.cooper.mc1@roche.com; Corton.Chris@epamail.epa.gov; fostel@niehs.nih.gov; hester.susan@epa.gov; lee.janices@epa.gov; fliu@jimmy.harvard.edu; liu6@niehs.nih.gov; QIAN_HUI-RONG@LILLY.COM; johnq@jimmy.harvard.edu; spettit@ilsi.org; karol.thompson@fda.hhs.gov NR 32 TC 32 Z9 32 U1 0 U2 4 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 JUN 12 PY 2008 VL 9 AR 285 DI 10.1186/1471-2164-9-285 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 327PR UT WOS:000257741500001 PM 18549499 ER PT J AU Brown, MC Levine, JL AF Brown, M. C. Levine, J. L. TI Dendrites of medial olivocochlear neurons in mouse SO NEUROSCIENCE LA English DT Article DE superior olive; cochlear nucleus; efferent; descending pathway; auditory reflex ID SUPERIOR OLIVARY COMPLEX; VENTRAL COCHLEAR NUCLEUS; GUINEA-PIG COCHLEA; BRAIN-STEM; INFERIOR COLLICULUS; CHOLERA-TOXIN; HORSERADISH-PEROXIDASE; EFFERENT INNERVATION; RESPONSE PROPERTIES; ALBINO-RAT AB Stains for acetylcholinesterase (ACNE) and retrograde labeling with Fluorogold (FG) were used to study olivocochlear neurons and their dendritic patterns in mice. The two methods gave similar results for location and number of somata. The total number of medial olivocochlear (MOC) neurons in the ventral nucleus of the trapezoid body (VNTB) is about 170 per side. An additional dozen large olivocochlear neurons are located in the dorsal periolivary nucleus (DPO). Dendrites of all of these neurons are long and extend in all directions from the cell bodies, a pattern that contrasts with the sharp frequency tuning of their responses. For VNTB neurons, there were greater numbers of dendrites directed medially than laterally and those directed medially were longer (on average, 25-50% longer). Dendrite extensions were most pronounced for neurons located in the rostral portion of the VNTB. When each dendrite from a single neuron was represented as a vector, and all the vectors summed, the result was also skewed toward the medial direction. DPO neurons, however, had more symmetric dendrites that projected into more dorsal parts of the trapezoid body, suggesting that this small group of olivocochlear neurons has very different physiological properties. Dendrites of both types of neurons were somewhat elongated rostrally, about 20% longer than those directed caudally. These results can be interpreted as extensions of dendrites of olivocochlear neurons toward their synaptic inputs: medially to meet crossing fibers from the cochlear nucleus that are part of the MOC reflex pathway, and rostrally to meet descending inputs from higher centers. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Brown, M. C.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Brown, M. C.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Brown, M. C.; Levine, J. L.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Brown, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM Chris_Brown@meei.harvard.edu FU NIDCD NIH HHS [R01 DC001089, R01 DC001089-17]; PHS HHS [DCD 01089] NR 66 TC 19 Z9 19 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD JUN 12 PY 2008 VL 154 IS 1 BP 147 EP 159 DI 10.1016/j.neuroscience.2007.12.045 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 315IP UT WOS:000256872300013 PM 18313859 ER PT J AU Brent, GA AF Brent, Gregory A. TI Graves' disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ANTITHYROID DRUGS; RADIOIODINE TREATMENT; THYROID-HORMONE; PAINLESS THYROIDITIS; CONSENSUS STATEMENT; I-131 THERAPY; BLOOD-FLOW; HYPERTHYROIDISM; MANAGEMENT; OPHTHALMOPATHY AB A 23- year- old woman presents with palpitations. Over the past 6 months, she has reported loose stools, a 10- lb ( 4.5- kg) weight loss despite a good appetite and food intake, and increased irritability. She appears to be anxious and has a pulse of 119 beats per minute and a blood pressure of 137/ 80 mm Hg. Her thyroid gland is diffusely and symmetrically enlarged to twice the normal size, and it is firm and non-tender; a thyroid bruit is audible. She has an eyelid lag, but no proptosis or periorbital edema. The serum thyrotropin level is 0.02 mu U per milliliter ( normal range, 0.35 to 4.50) and the level of free thyroxine is 4.10 ng per deciliter ( normal range, 0.89 to 1.76). How should she be further evaluated and treated? C1 Vet Affairs Greater Los Angeles Healthcare Syst, Endocrinol & Diabet Div, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. RP Brent, GA (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Endocrinol & Diabet Div, 111D,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM gbrent@ucla.edu FU NIDDK NIH HHS [R01 DK 67233] NR 56 TC 182 Z9 209 U1 2 U2 29 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 JUN 12 PY 2008 VL 358 IS 24 BP 2594 EP 2605 DI 10.1056/NEJMcp0801880 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 311IJ UT WOS:000256593600007 PM 18550875 ER PT J AU Seton, M Pless, M Fishman, JA Caruso, PA Hedley-Whyte, ET Steere, AC AF Seton, Margaret Pless, Misha Fishman, Jay A. Caruso, Paul A. Hedley-Whyte, E. Tessa Steere, Allen C. TI A man with headache and visual changes after liver transplantation - Ruptured mycotic aneurysm of the basilar artery due to invasive aspergillosis of the ethmoid and sphenoid sinuses, resulting from infection with Aspergillus fumigatus. - Infarction of the right optic nerve and pons. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GIANT-CELL ARTERITIS; PLACEBO-CONTROLLED TRIAL; FUNGAL-INFECTIONS; POLYMYALGIA-RHEUMATICA; MEDICAL PROGRESS; RANDOMIZED-TRIAL; DOUBLE-BLIND; RECIPIENTS; VASCULITIS; METHOTREXATE C1 [Seton, Margaret] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Seton, Margaret] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. [Pless, Misha] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Fishman, Jay A.] Massachusetts Gen Hosp, Dept Infect Dis, Boston, MA 02114 USA. [Caruso, Paul A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hedley-Whyte, E. Tessa] Massachusetts Gen Hosp, Div Neuropathol, Dept Pathol, Boston, MA 02114 USA. [Seton, Margaret; Fishman, Jay A.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Pless, Misha] Harvard Univ, Sch Med, Dept Neurol, Cambridge, MA 02138 USA. [Hedley-Whyte, E. Tessa] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. [Caruso, Paul A.] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Caruso, Paul A.] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. RP Seton, M (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. NR 32 TC 11 Z9 12 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 JUN 12 PY 2008 VL 358 IS 24 BP 2619 EP 2628 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 311IJ UT WOS:000256593600011 PM 18550878 ER PT J AU Han, ES Muller, FL Perez, VI Qi, WB Liang, HY Xi, L Fu, CX Doyle, E Hickey, M Cornell, J Epstein, CJ Roberts, LJ Van Remmen, H Richardson, A AF Han, Eun-Soo Muller, Florian L. Perez, Viviana I. Qi, Wenbo Liang, Huiyun Xi, Liang Fu, Chunxiao Doyle, Erin Hickey, Morgen Cornell, John Epstein, Charles J. Roberts, L. Jackson Van Remmen, Holly Richardson, Arlan TI The in vivo gene expression signature of oxidative stress SO PHYSIOLOGICAL GENOMICS LA English DT Article DE oxidative stress; gene expression; p53 target genes; Sod1; Gpx1 ID MITOCHONDRIAL SUPEROXIDE DISMUTASE; LIFE-SPAN; CU,ZN-SUPEROXIDE DISMUTASE; P53-DEPENDENT APOPTOSIS; LIPID-PEROXIDATION; HYDROGEN-PEROXIDE; CELLULAR-RESPONSE; MOUSE DEVELOPMENT; MOLECULAR-WEIGHT; SELENOPROTEIN-W AB How higher organisms respond to elevated oxidative stress in vivo is poorly understood. Therefore, we measured oxidative stress parameters and gene expression alterations (Affymetrix arrays) in the liver caused by elevated reactive oxygen species induced in vivo by diquat or by genetic ablation of the major antioxidant enzymes CuZn-superoxide dismutase (Sod1) and glutathione peroxidase-1 (Gpx1). Diquat (50 mg/kg) treatment resulted in a significant increase in oxidative damage within 3-6 h in wild-type mice without any lethality. In contrast, treatment of Sod1(-/-) or Gpx1(-/-) mice with a similar concentration of diquat resulted in a significant increase in oxidative damage within an hour of treatment and was lethal, i.e., these mice are extremely sensitive to the oxidative stress generated by diquat. The expression response to elevated oxidative stress in vivo does not involve an upregulation of classic antioxidant genes, although long-term oxidative stress in Sod1(-/-) mice leads to a significant upregulation of thiol antioxidants (e.g., Mt1, Srxn1, Gclc, Txnrd1), which appears to be mediated by the redox-sensitive transcription factor Nrf2. The main finding of our study is that the common response to elevated oxidative stress with diquat treatment in wild-type, Gpx1(-/-), and Sod1(-/-) mice and in untreated Sod1(-/-) mice is an upregulation of p53 target genes (p21, Gdf15, Plk3, Atf3, Trp53inp1, Ddit4, Gadd45a, Btg2, Ndrg1). A retrospective comparison with previous studies shows that induction of these p53 target genes is a conserved expression response to oxidative stress, in vivo and in vitro, in different species and different cells/organs. C1 [Cornell, John; Van Remmen, Holly; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Han, Eun-Soo; Xi, Liang; Fu, Chunxiao; Doyle, Erin; Hickey, Morgen] Univ Tulsa, Dept Biol Sci, Tulsa, OK 74104 USA. [Muller, Florian L.; Perez, Viviana I.; Qi, Wenbo; Liang, Huiyun; Van Remmen, Holly; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78245 USA. [Cornell, John] Univ Texas Hlth Sci Ctr San Antonio, Ctr Biostat & Epidemiol, San Antonio, TX 78245 USA. [Cornell, John; Van Remmen, Holly; Richardson, Arlan] S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. [Epstein, Charles J.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. [Roberts, L. Jackson] Vanderbilt Univ, Dept Pharmacol, Nashville, TN USA. [Roberts, L. Jackson] Vanderbilt Univ, Dept Med, Nashville, TN USA. RP Richardson, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, Texas Res Pk Campus,15355 Lambda Dr, San Antonio, TX 78245 USA. EM richardsona@uthscsa.edu FU NIA NIH HHS [1P30-AG-13319, 5T3-AG021890-02, AG-14674-04S1, P01 AG019316, P01 AG019316-010003, P01 AG020591, P01 AG020591-019002, P01-AG-020591, P01-AG-19316, P30 AG013319, P30 AG013319-10, P30 AG013319-119009, R01 AG023843, R01 AG023843-01, R01-AG-23843, R37 AG026557, R37 AG026557-01, R37-AG026557, T32 AG021890]; NIGMS NIH HHS [R37 GM042056-19, R37 GM042056, R37-GM-42056] NR 94 TC 112 Z9 114 U1 1 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD JUN 12 PY 2008 VL 34 IS 1 BP 112 EP 126 DI 10.1152/physiolgenomics.00239.2007 PG 15 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 314OT UT WOS:000256819400013 PM 18445702 ER PT J AU Weber, W Vander Stoep, A McCarty, RL Weiss, NS Biederman, J McClellan, J AF Weber, Wendy Vander Stoep, Ann McCarty, Rachelle L. Weiss, Noel S. Biederman, Joseph McClellan, Jon TI Hypericum perforatum (St John's Wort) for attention-deficit/hyperactivity disorder in children and adolescents - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID DEFICIT-HYPERACTIVITY DISORDER; DAILY ATOMOXETINE TREATMENT; DOUBLE-BLIND; OPEN-LABEL; ALTERNATIVE THERAPIES; CHILDHOOD ATTENTION; US CHILDREN; DEPRESSION; METHYLPHENIDATE; COMPLEMENTARY AB Context Stimulant medication can effectively treat 60% to 70% of youth with attention-deficit/ hyperactivity disorder ( ADHD). Yet many parents seek alternative therapies, and Hypericum perforatum ( St John's wort) is 1 of the top 3 botanicals used. Objective To determine the efficacy and safety of H perforatum for the treatment of ADHD in children. Design, Setting, and Participants Randomized, double- blind, placebo-controlled trial conducted between March 2005 and August 2006 at Bastyr University, Kenmore, Washington, among a volunteer sample of 54 children aged 6 to 17 years who met Diagnostic and Statistical Manual of Mental Disorders ( Fourth Edition) criteria for ADHD by structured interview. Intervention After a placebo run- in phase of 1 week, participants were randomly assigned to receive 300 mg of H perforatum standardized to 0.3% hypericin ( n= 27) or a matched placebo ( n= 27) 3 times daily for 8 weeks. Other medications for ADHD were not allowed during the trial. Main Outcome Measures Performance on the ADHD Rating Scale - IV ( range, 0- 54) and Clinical Global Impression Improvement Scale ( range, 0- 7), and adverse events. Results One patient in the placebo group withdrew because of an adverse event. No significant difference was found in the change in ADHD Rating Scale - IV scores from baseline to week 8 between the treatment and placebo groups: inattentiveness improved 2.6 points ( 95% confidence interval [ CI], - 4.6 to - 0.6 points) with H perforatum vs 3.2 points ( 95% CI, - 5.7 to - 0.8 points) with placebo ( P=. 68) and hyperactivity improved 1.8 points ( 95% CI, - 3.7 to 0.1 points) with H perforatum vs 2.0 points ( 95% CI, - 4.1 to 0.1 points) with placebo ( P=. 89). There was also no significant difference between the 2 groups in the percentage of participants who met criteria for improvement ( score <= 2) on the Clinical Global Impression Improvement Scale ( H perforatum, 44.4%; 95% CI, 25.5%- 64.7% vs placebo, 51.9%; 95% CI, 31.9%- 71.3%; P=. 59). No difference between groups was found in the number of participants who experienced adverse effects during the study period ( H perforatum, 40.7%; 95% CI, 22.4%- 61.2% vs placebo, 44.4%; 95% CI, 25.5%- 64.7%; P=. 78). Conclusion In this study, use of H perforatum for treatment of ADHD over the course of 8 weeks did not improve symptoms. Trial Registration clinicaltrials. gov Identifier: NCT00100295. C1 [Weber, Wendy; McCarty, Rachelle L.] Bastyr Univ, Sch Naturopath Med, Kenmore, WA USA. [Vander Stoep, Ann] Univ Washington, Dept Psychiat & Behav Sci, Childrens Hosp & Reg Med Ctr, Seattle, WA 98195 USA. [Vander Stoep, Ann; Weiss, Noel S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [McClellan, Jon] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Biederman, Joseph] Massachusetts Gen Hosp, Dept Pediat Psychopharmacol, Boston, MA 02114 USA. [Biederman, Joseph] Harvard Univ, Dept Psychiat, Boston, MA 02115 USA. RP Weber, W (reprint author), 14500 Juanita Dr NE, Kenmore, WA USA. EM wendyw@bastyr.edu FU NCCIH NIH HHS [T32AT00815, K23AT000929, T32 AT000815, T32 AT000815-05, K23 AT000929, K23 AT000929-05] NR 41 TC 31 Z9 32 U1 3 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 11 PY 2008 VL 299 IS 22 BP 2633 EP 2641 DI 10.1001/jama.299.22.2633 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 311FN UT WOS:000256586200020 PM 18544723 ER PT J AU Zhang, L Kanda, Y Roberts, DJ Ecker, JL Losel, R Wehling, M Peluso, JJ Pru, JK AF Zhang, Ling Kanda, Yoshiaki Roberts, Drucilla J. Ecker, Jeffrey L. Losel, Ralf Wehling, Martin Peluso, John J. Pru, James K. TI Expression of progesterone receptor membrane component 1 and its partner serpine 1 mRNA binding protein in uterine and placental tissues of the mouse and human SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE membrane progesterone receptor; PGRMC1; placenta; pregnancy; progesterone; SERBP1; uterus ID CELL VIABILITY; ANTIAPOPTOTIC ACTION; RAPID PROGESTERONE; GENE-EXPRESSION; INDIAN HEDGEHOG; SMOOTH-MUSCLE; MECHANISM; INHIBITION; GRANULOSA; UTERUS AB Although activation of the nuclear progesterone (P(4)) receptor (PGR) is required for uterine function, some of the actions Of P(4) are mediated through a PGR-independent mechanism. The receptors that account for the PGR-independent actions have not been identified with certainty. The purpose of this study was to assess the expression, localization and hormonal regulation of two novel P(4) receptor candidates, P(4) receptor membrane component (PGRMC) 1 and PGRMC2, as well as the PGRMC1 partner Serpine1 mRNA binding protein (SERBP1). Unlike Pgrmc1 and Serbp 1, which remained unchanged throughout the estrous cycle, Pgrmc2 was highly up-regulated during proestrus and metestrus. Immunohistochemical analyses suggest that PGRMC1 and SERBP1 promote differentiation, since the expression of these proteins increased in endometrial cells undergoing steroid-depended terminal differentiation. Progesterone rather than estrogen appears to be primarily responsible for up-regulating the expression of PGRMCs. PGRMC1 and SERBP1 also showed overlapping patterns of expression in the human placenta and associated membranes with the most abundant expression in smooth muscle of the placental vasculature, villous capillaries and the syncytiotrophoblast. Based on these findings, it is proposed that PGRMC1:SERBP1 protein complex functions in events important to early pregnancy including cellular differentiation, modulation of apoptosis and steroidogenesis. These studies provide a platform from which to build a clearer understanding Of P(4) actions in the female reproductive tract and placental tissues that are mediated by non-classical mechanisms. (c) 2008 Published by Elsevier Ireland Ltd. C1 [Zhang, Ling; Kanda, Yoshiaki; Ecker, Jeffrey L.; Pru, James K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv,Vincent Ctr Reprod, Boston, MA 02114 USA. [Roberts, Drucilla J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Losel, Ralf; Wehling, Martin] Univ Heidelberg, Fac Clin Med, Clin Pharmacol Mannheim, D-68135 Mannheim, Germany. [Peluso, John J.] Univ Connecticut, Ctr Hlth, Dept Cell Biol, Farmington, CT 06030 USA. [Peluso, John J.] Univ Connecticut, Ctr Hlth, Dept Obstet, Farmington, CT 06030 USA. [Peluso, John J.] Univ Connecticut, Ctr Hlth, Dept Gynecol, Farmington, CT 06030 USA. RP Pru, JK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv,Vincent Ctr Reprod, Thier Res Bldg,Room 931,55 Fruit St, Boston, MA 02114 USA. EM jpru@parterns.org FU NICHD NIH HHS [HD047205]; NIEHS NIH HHS [ES012070] NR 50 TC 51 Z9 52 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JUN 11 PY 2008 VL 287 IS 1-2 BP 81 EP 89 DI 10.1016/j.mce.2008.02.012 PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 316XD UT WOS:000256982100010 PM 18440126 ER PT J AU Parodi, K Bortfeld, T Enghardt, W Fiedler, F Knopf, A Paganetti, H Pawelke, J Shakirin, G Shih, H AF Parodi, Katia Bortfeld, Thomas Enghardt, Wolfgang Fiedler, Fine Knopf, Antje Paganetti, Harald Pawelke, Joerg Shakirin, Georgy Shih, Helen TI PET imaging for treatment verification of ion therapy: Implementation and experience at GSI Darmstadt and MGH Boston SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT LA English DT Article; Proceedings Paper CT 9th International Workshop on Radiation Imaging Detectors CY JUL 22-26, 2007 CL Univ Erlangen, Nuremberg, GERMANY HO Univ Erlangen DE positron emission tomography; proton therapy; carbon ion therapy ID IN-BEAM PET; POSITRON-EMISSION-TOMOGRAPHY; PROTON THERAPY; TUMOR-THERAPY; FEASIBILITY; RANGE AB Ion beams offer the possibility of improved conformation of the dose delivered to the tumor with better sparing of surrounding tissue and critical structures in comparison to conventional photon and electron external radiation treatment modalities. Full clinical exploitation of this advantage can benefit from in vivo confirmation of the actual beam delivery and, in particular, of the ion range in the patient. During irradiation, positron emitters like (15)O (half-life T(1/2) approximate to 2 min) and (11)C (T(1/2) approximate to 20 min) are formed in nuclear interactions between the ions and the tissue. Detection of this transient radioactivity via positron emission tomography (PET) and comparison with the expectation based on the prescribed beam application may serve as an in vivo, non-invasive range validation method of the whole treatment planning and delivery chain. For technical implementation, PET imaging during irradiation (in-beam) requires the development of customized, limited angle detectors with data acquisition synchronized with the beam delivery. Alternatively, commercial PET or PET/CT scanners in close proximity to the treatment site enable detection of the residual activation from long-lived emitters shortly after treatment (offline). This paper reviews two clinical examples using a dedicated in-beam PET scanner for verification of carbon ion therapy at GSI Darmstadt, Germany, as well as a commercial offline PET/CT tomograph for post-radiation imaging of proton treatments at Massachusetts General Hospital, Boston, USA. Challenges as well as pros and cons of the two imaging approaches in dependence of the different ion type and beam delivery system are discussed. (C) 2008 Elsevier B.V. All rights reserved. C1 [Parodi, Katia] Heidelberg Ion Beam Therapy Ctr, D-69120 Heidelberg, Germany. [Bortfeld, Thomas; Knopf, Antje; Paganetti, Harald; Shih, Helen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Enghardt, Wolfgang; Fiedler, Fine; Pawelke, Joerg; Shakirin, Georgy] Forschungszentrum Dresden Rossendorf, D-01314 Dresden, Germany. [Enghardt, Wolfgang] Tech Univ Dresden, D-01307 Dresden, Germany. RP Parodi, K (reprint author), Heidelberg Ion Beam Therapy Ctr, D-69120 Heidelberg, Germany. EM Katia.Parodi@med.uni-heidelberg.de RI Fiedler, Fine/B-7165-2014 OI Fiedler, Fine/0000-0002-2352-2042 NR 17 TC 38 Z9 39 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-9002 J9 NUCL INSTRUM METH A JI Nucl. Instrum. Methods Phys. Res. Sect. A-Accel. Spectrom. Dect. Assoc. Equip. PD JUN 11 PY 2008 VL 591 IS 1 BP 282 EP 286 DI 10.1016/j.nima.2008.03.075 PG 5 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Nuclear; Physics, Particles & Fields SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA 324PA UT WOS:000257529300071 ER PT J AU Tamehiro, N Zhou, S Okuhira, K Benita, Y Brown, CE Zhuang, DZ Latz, E Hornemann, T von Eckardstein, A Xavier, RJ Freeman, MW Fitzgerald, ML AF Tamehiro, Norimasa Zhou, Suiping Okuhira, Keiichiro Benita, Yair Brown, Cari E. Zhuang, Debbie Z. Latz, Eicke Hornemann, Thorsten von Eckardstein, Arnold Xavier, Ramnik J. Freeman, Mason W. Fitzgerald, Michael L. TI SPTLC1 binds ABCA1 to negatively regulate trafficking and cholesterol efflux activity of the transporter SO BIOCHEMISTRY LA English DT Article ID APOE-KNOCKOUT MICE; TANGIER-DISEASE; SERINE PALMITOYLTRANSFERASE; PHOSPHOLIPID BIOSYNTHESIS; SPHINGOLIPID METABOLISM; SPHINGOMYELIN SYNTHESIS; PLASMA SPHINGOMYELIN; ATHEROSCLEROSIS; MUTATIONS; MACROPHAGES AB ABCA1 transport of cholesterol and phospholipids to nascent HDL particles plays a central role in lipoprotein metabolism and macrophage cholesterol homeostasis. ABCA1 activity is regulated both at the transcriptional level and at the post-translational level. To explore mechanisms involved in the post-translational regulation of the transporter, we have used affinity purification and mass spectrometry to identify proteins that bind ABCA1 and influence its activity. Previously, we demonstrated that an interaction between beta 1-syntrophin stimulated ABCA1 activity, at least in part, be slowing the degradation of the transporter. This work demonstrates that one subunit of the serine palmitoyltransferase enzyme, SPTLC1, but not subunit 2 (SPTLC2), is copurified with ABCA1 and negatively regulates its function. In human THP-I macrophages and in mouse liver, the ABCA1-SPTLC1 complex was detected by co-immunoprecipitation, demonstrating that the interaction occurs in cellular settings where ABCA1 activity is critical for HDL genesis. Pharmacologic inhibition of SPTLC1 with myriocin, which resulted in the disruption of the SPTLC1ABCA1 complex, and siRNA knockdown of SPTLC1 expression both stimulated ABCA1 efflux by nearly 60% (p < 0.05). In contrast, dominant-negative mutants of SPTLC1 inhibited ABCA1 efflux, indicating that a reduced level of sphingomyelin synthesis could not explain the effect of myriocin on ABCA1 activity. In 293 cells, the SPTLC1 inhibition of ABCA1 activity led to the blockade of the exit of ABCA1 from the endoplasmic reticulum. In contrast, myriocin treatment of macrophages increased the level of cell surface ABCA1. In composite, these results indicate that the physical interaction of ABCA1 and SPTLC1 results in reduction of ABCA1 activity and that inhibition of this interaction produces enhanced cholesterol efflux. C1 [Fitzgerald, Michael L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol,Lipid Metab Unit, Boston, MA 02114 USA. [Okuhira, Keiichiro] Natl Inst Hlth Sci, Setagaya Ku, Tokyo 1588501, Japan. [Latz, Eicke] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. [Hornemann, Thorsten; von Eckardstein, Arnold] Univ Zurich Hosp, Inst Clin Chem, CH-8091 Zurich, Switzerland. RP Fitzgerald, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol,Lipid Metab Unit, 185 Cambridge St, Boston, MA 02114 USA. EM mfitzgerald@ccib.mgh.harvard.edu RI Benita, Yair/E-3094-2012; Latz, Eicke/H-3951-2014 OI Latz, Eicke/0000-0003-1488-5666 FU NCRR NIH HHS [R24 RR020345, R24RR020345]; NHLBI NIH HHS [R01 HL074136-03, HL074136, R01 HL074136]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-13] NR 37 TC 28 Z9 28 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 10 PY 2008 VL 47 IS 23 BP 6138 EP 6147 DI 10.1021/bi800182t PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 308QT UT WOS:000256405800006 PM 18484747 ER PT J AU Crimi, E Baggish, A Leffert, L Pian-Smith, MCM Januzzi, JL Jiang, YD AF Crimi, Ettore Baggish, Aaron Leffert, Lisa Pian-Smith, May C. M. Januzzi, James L. Jiang, Yandong TI Acute reversible stress-induced cardiomyopathy associated with cesarean delivery under spinal anesthesia SO CIRCULATION LA English DT Editorial Material C1 [Crimi, Ettore; Leffert, Lisa; Pian-Smith, May C. M.; Jiang, Yandong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Baggish, Aaron; Januzzi, James L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. RP Jiang, YD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 55 Fruit St,Jackson 422, Boston, MA 02114 USA. EM yjiang@partners.org NR 4 TC 20 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 10 PY 2008 VL 117 IS 23 BP 3052 EP 3053 DI 10.1161/CIRCULATIONAHA.107.744102 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 311CB UT WOS:000256576600012 PM 18541755 ER PT J AU Ilhan, SO Sarioglu, Y Vural, IM Dilekoz, E Ozturk, GS Ercan, ZS AF Ilhan, Sevil Oezger Sarioglu, Yusuf Vural, Ismail Mert Dilekoez, Ergin Oeztuerk, Goekce Sevim Ercan, Zeynep Sevim TI Hydrogen peroxide and antioxidizing enzymes involved in modulation of transient facilitatory effects of nicotine on neurogenic contractile responses in rat gastric fundus SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE nicotine; rabbit gastric fundus; cholinergic neurotransmission; nicotinic acetylcholine receptor; hydrogen peroxide (H2O2); catalase; superoxide dismutase (SOD) ID ACETYLCHOLINE-RECEPTORS; NORADRENALINE RELEASE; CIRCULAR MUSCLE; NITRIC-OXIDE; VAS-DEFERENS; GUINEA-PIG; CALCIUM; ACTIVATION; STOMACH; TRANSMISSION AB Nicotine acts as an agonist of nicotinic acetylcholine receptors. Nicotinic acetylcholine receptors play a role in the modulation of neurotransmitter release in both the central and the peripheral nervous system. Moderate reactive oxygen species levels modulate the regulation of physiological functions e.g. neurotransmitter release. Previously in rabbit gastric fundus we demonstrated that nicotine transiently increased neurogenic contraction induced by electrical field stimulation (EFS). In this study we aimed to investigate the effects of hydrogen peroxide (H2O2), antioxidizing enzymes catalase and superoxide dismutase (SOD) on nicotine induced increases at cholinergic neurotransmission in rabbit gastric fundus. Although H2O2 did not alter nicotine induced transient neurogenic contractions at concentrations of 10(-6) and 10(-5) M, at high concentration (10(-4) M) H2O2 inhibited nicotine induced increases. Catalase (500 units/ml), enhanced the effect of nicotine but did not alter nicotine induced transient neurogenic contractions at the concentrations of 100 and 250 units/ml. SOD (75,150 and 225 units/ml) did not alter nicotine induced transient neurogenic contractions. In conclusion, at high concentration H2O2 (10(-4) M) inhibited nicotine's transient ability to augment neurogenic contractions and catalase (500 units/ml) enhanced the effect of nicotine. (C) 2008 Elsevier B.V. All rights reserved. C1 [Sarioglu, Yusuf; Vural, Ismail Mert; Oeztuerk, Goekce Sevim; Ercan, Zeynep Sevim] Gazi Univ, Fac Med, Dept Pharmacol, Sch Med, TR-06510 Ankara, Turkey. [Ilhan, Sevil Oezger] Ufuk Univ, Sch Med, Dept Pharmacol, Ankara, Turkey. [Dilekoez, Ergin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. RP Vural, IM (reprint author), Gazi Univ, Fac Med, Dept Pharmacol, Sch Med, TR-06510 Ankara, Turkey. EM imvural@yahoo.com NR 36 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JUN 10 PY 2008 VL 587 IS 1-3 BP 267 EP 272 DI 10.1016/j.ejphar.2008.03.029 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 314PR UT WOS:000256821800040 ER PT J AU Ezzell, RM Goldmann, WH Wang, N Parashurama, N Ingber, DE AF Ezzell, Robert M. Goldmann, Wolfgang H. Wang, Ning Parashurama, Natesh Ingber, Donald E. TI Vinculin promotes cell spreading by mechanically coupling integrins to the cytoskeleton (vol 231, pg 14, 1997) SO EXPERIMENTAL CELL RESEARCH LA English DT Correction C1 [Ezzell, Robert M.; Goldmann, Wolfgang H.; Parashurama, Natesh] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Res Labs, Charlestown, MA 02129 USA. [Wang, Ning] Harvard Univ, Sch Publ Hlth, Physiol Program, Boston, MA 02115 USA. [Ingber, Donald E.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ingber, Donald E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ingber, Donald E.] Childrens Hosp, Dept Surg, Boston, MA 02115 USA. RP Parashurama, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Res Labs, Charlestown, MA 02129 USA. EM nateshp@stanford.edu RI Goldmann, Wolfgang/H-5572-2013 NR 1 TC 0 Z9 0 U1 0 U2 9 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUN 10 PY 2008 VL 314 IS 10 BP 2163 EP 2163 DI 10.1016/j.yexcr.2008.02.017 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 312AI UT WOS:000256641100017 ER PT J AU Meliga, E Garcia-Garcia, HM Valgimigli, M Chieffo, A Biondi-Zoccai, G Maree, AO Cook, S Reardon, L Moretti, C De Servi, S Palacios, IF Windecker, S Colombo, A van Domburg, R Sheiban, I Serruys, PW AF Meliga, Emanuele Garcia-Garcia, Hector Manuel Valgimigli, Marco Chieffo, Alaide Biondi-Zoccai, Giuseppe Maree, Andrew O. Cook, Stephen Reardon, Lindsay Moretti, Claudio De Servi, Stefano Palacios, Igor F. Windecker, Stephen Colombo, Antonio van Domburg, Ron Sheiban, Imad Serruys, Patrick W. TI Longest available clinical outcomes after drug-eluting stent implantation for unprotected left main coronary artery disease - The DELFT (Drug Eluting stent for LeFT main) registry SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; PERCUTANEOUS TREATMENT; THROMBOSIS LAST; BYPASS-SURGERY; DOUBLE-BLIND; T-SEARCH; STENOSIS; TERM; INSIGHTS; LESIONS AB Objectives The purpose of this study was to investigate the long-term safety and efficacy of percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation for unprotected left main coronary artery (ULMCA) disease. Background Long-term clinical outcomes after DES implantation for ULMCA disease have not yet been ascertained. Methods From April 2002 to April 2004, 358 consecutive patients who underwent PCI with DES implantation for de novo lesions on ULMCA were retrospectively selected and analyzed in 7 European and U. S. tertiary care centers. No patients were excluded from the analysis, and all patients had a minimum follow-up of 3 years. Results Technical success rate was 100%. Procedural success rate was 89.6%. After 3 years, major adverse cardiovascular events (MACE)-free survival in the whole population was 73.5%. According to the Academic Research Consortium definitions, cardiac death occurred in 9.2% of patients, and reinfarction, target lesion revascularization (TLR), and target vessel revascularization (TVR) occurred in 8.6%, 5.8%, and 14.2% of patients, respectively. Definite stent thrombosis occurred in 2 patients (specifically at 0 and 439 days). In elective patients, the 3-year MACE-free survival was 74.2%, with mortality, reinfarction, TLR, and TVR rates of 6.2%, 8.3%, 6.6%, and 16%, respectively. In the emergent group the 3-year MACE-free survival was 68.2%, with mortality, reinfarction, TLR, and TVR rates of 21.4%, 10%, 2.8%, and 7.1%, respectively. Conclusions Routine DES implantation in ULMCA disease seems encouraging, with favorable long-term clinical results. C1 [Serruys, Patrick W.] Erasmus Univ, Dept Intervent Cardiol, Thoraxctr, Erasmus Med Ctr, NL-3015 GD Rotterdam, Netherlands. [Meliga, Emanuele; Biondi-Zoccai, Giuseppe; Moretti, Claudio; Sheiban, Imad] Univ Turin, S Giovanni Battista Hosp, Dept Intervent Cardiol, Turin, Italy. [Valgimigli, Marco] Univ Ferrara, S Anna Hosp, Dept Intervent Cardiol, I-44100 Ferrara, Italy. [Chieffo, Alaide; Colombo, Antonio] Hosp San Raffaele, Dept Intervent Cardiol, I-20132 Milan, Italy. [Maree, Andrew O.; Reardon, Lindsay; Palacios, Igor F.] Massachusetts Gen Hosp, Dept Intervent Cardiol, Boston, MA 02114 USA. [Cook, Stephen; Windecker, Stephen] Univ Hosp Bern, Dept Intervent Cardiol, CH-3010 Bern, Switzerland. [De Servi, Stefano] Osped Civile Legnano, Dept Cardiovasc Dis, Milan, Italy. RP Serruys, PW (reprint author), Erasmus Univ, Dept Intervent Cardiol, Thoraxctr, Erasmus Med Ctr, Dr Molewaterpl 40, NL-3015 GD Rotterdam, Netherlands. EM p.w.j.c.serruys@erasmusmc.nl RI MORETTI, CLAUDIO/G-4396-2012; OI MORETTI, CLAUDIO/0000-0002-4475-7289 NR 29 TC 110 Z9 114 U1 2 U2 2 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 JUN 10 PY 2008 VL 51 IS 23 BP 2212 EP 2219 DI 10.1016/j.jacc.2008.03.020 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 309BG UT WOS:000256434200002 PM 18534266 ER PT J AU Dec, GW AF Dec, G. William TI Istaroxime in heart failure - New hope or more hype SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID IN-HOSPITAL MORTALITY AB Acute decompensated heart failure (ADHF) remains the most common indication for hospitalization in the U. S., accounting for nearly 1 million admissions annually (1). A small minority of patients (approximately 10%) present with a systolic blood pressure below 120 mm Hg on admission (2). These individuals often have evidence of end-organ dysfunction, particularly prerenal azotemia, and generally have progressive heart failure refractory to outpatient therapy. In-hospital mortality averages 7%, whereas 90-day readmission rates approximate 30%. Data from the Acute Decompensated Heart Failure National Registry (ADHERE), identified elevated blood urea nitrogen (>= 43 mg/dl) as the best single predictor of in-hospital mortality, followed by low systolic blood pressure (< 115 mm Hg) and elevated serum creatinine (>= 2.5 mg/dl) (3). Further, the combination of elevated B-type natriuretic peptide and troponin-I can identify patients with a 12-fold increased risk of death during hospitalization (2). Thus, standard measures readily available at the time of hospital admission or shortly thereafter (e. g., vital signs, laboratory values) can provide an important method for assessing in-hospital mortality risk and for basing decisions on the use of hemodynamic monitoring and intravenous vasoactive therapy. C1 Massachusetts Gen Hosp, Div Cardiol, Heart Failure & Transplantat Unit, Boston, MA 02114 USA. RP Dec, GW (reprint author), Massachusetts Gen Hosp, Div Cardiol, Heart Failure & Transplantat Unit, Bigelow 800,Mailstop 817,55 Fruit St, Boston, MA 02114 USA. EM gdec@partners.org NR 14 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN 10 PY 2008 VL 51 IS 23 BP 2286 EP 2288 DI 10.1016/j.jacc.2008.04.005 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 309BG UT WOS:000256434200013 PM 18534277 ER PT J AU Jacobs, BS Greenberg, SM AF Jacobs, Bradley S. Greenberg, Steven M. TI Statins, low cholesterol, and hemorrhagic stroke - An uncertain triangle SO NEUROLOGY LA English DT Editorial Material ID INTRACEREBRAL HEMORRHAGE; DOSE ATORVASTATIN; RISK-FACTORS; POPULATION C1 [Jacobs, Bradley S.] Wright State Univ, Boonshoft Sch Med, Dept Internal Med, Div Neurol, Dayton, OH 45435 USA. [Greenberg, Steven M.] Massachusetts Gen Hosp, Ctr Stroke Res, Boston, MA 02114 USA. RP Jacobs, BS (reprint author), Dept Med Educ, 2200 Bldg,3rd Floor,2222 Philadelphia Dr, Dayton, OH 45406 USA. EM bradley.jacobs@wright.edu NR 9 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN 10 PY 2008 VL 70 IS 24 BP 2355 EP 2356 DI 10.1212/01.wnl.0000314696.61422.12 PN 2 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 317ZT UT WOS:000257060100002 PM 18541869 ER PT J AU Mejia, NI Park, S Ning, MM Buonanno, FS AF Mejia, Nicte I. Park, Soojin Ning, MingMing Buonanno, Ferdinando S. TI Pearls and Oy-sters: Reversible iatrogenic Balint syndrome SO NEUROLOGY LA English DT Article ID ANGIOPLASTY C1 [Mejia, Nicte I.; Park, Soojin; Ning, MingMing; Buonanno, Ferdinando S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Buonanno, FS (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM fbuonanno@partners.org NR 11 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN 10 PY 2008 VL 70 IS 24 BP E97 EP E989 DI 10.1212/01.wnl.0000314730.64232.5a PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 317ZS UT WOS:000257060000019 PM 18541879 ER PT J AU Zhang, H Morrison, MA DeWan, A Adams, S Andreoli, M Huynh, N Regan, M Brown, A Miller, JW Kim, IK Hoh, J DeAngelis, MM AF Zhang, Hong Morrison, Margaux A. DeWan, Andy Adams, Scott Andreoli, Michael Huynh, Nancy Regan, Maureen Brown, Alison Miller, Joan W. Kim, Ivana K. Hoh, Josephine DeAngelis, Margaret M. TI The NEI/NCBI dbGAP database: Genotypes and haplotypes that may specifically predispose to risk of neovascular age-related macular degeneration SO BMC MEDICAL GENETICS LA English DT Article ID COMPLEMENT FACTOR-H; DISCORDANT SIB PAIRS; QUANTITATIVE TRAIT LOCI; FACTOR-XIII; B-SUBUNIT; POLYMORPHISM; PREVALENCE; GENE; MACULOPATHY; VARIANT AB Background: To examine if the significantly associated SNPs derived from the genome wide allelic association study on the AREDS cohort at the NEI (dbGAP) specifically confer risk for neovascular age-related macular degeneration (AMD). We ascertained 134 unrelated patients with AMD who had one sibling with an AREDS classification 1 or less and was past the age at which the affected sibling was diagnosed (268 subjects). Genotyping was performed by both direct sequencing and Sequenom iPLEX system technology. Single SNP analyses were conducted with McNemar's Test (both 2 x 2 and 3 x 3 tests) and likelihood ratio tests (LRT). Conditional logistic regression was used to determine significant gene-gene interactions. LRT was used to determine the best fit for each genotypic model tested (additive, dominant or recessive). Results: Before release of individual data, p-value information was obtained directly from the AREDS dbGAP website. Of the 35 variants with P < 10(-6) examined, 23 significantly modified risk of neovascular AMD. Many variants located in tandem on 1q32q22 including those in CFH, CFHR4, CFHR2, CFHR5, F13B, ASPM and ZBTB were significantly associated with AMD risk. Of these variants, single SNP analysis revealed that CFH rs572515 was the most significantly associated with AMD risk (P < 10(-6)). Haplotype analysis supported our findings of single SNP association, demonstrating that the most significant haplotype, GATAGTTCTC, spanning CFH, CFHR4, and CFHR2 was associated with the greatest risk of developing neovascular AMD ( P < 10(-6)). Other than variants on 1q32-q22, only two SNPs, rs9288410 ( MAP2)on 2q34-q35 and rs2014307 (PLEKHA1/HTRA1) on 10q26 were significantly associated with AMD status (P =.03 and P < 10(-6) respectively). After controlling for smoking history, gender and age, the most significant gene-gene interaction appears to be between rs10801575 (CFH) and rs2014307 (PLEKHA1/HTRA1) (P < 10(-11)). The best genotypic fit for rs10801575 and rs2014307 was an additive model based on LRT. After applying a Bonferonni correction, no other significant interactions were identified between any other SNPs. Conclusion: This is the first replication study on the NEI dbGAP SNPs, demonstrating that alleles on 1q, 2q and 10q may predispose an individual to AMD. C1 [Zhang, Hong; DeWan, Andy; Hoh, Josephine] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Morrison, Margaux A.; Adams, Scott; Andreoli, Michael; Huynh, Nancy; Miller, Joan W.; Kim, Ivana K.; DeAngelis, Margaret M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Ophthalmol, Boston, MA USA. [Regan, Maureen; Brown, Alison] Harvard Univ, Sch Med, Partners Healthcare Ctr Genet & Genom, Cambridge, MA 02138 USA. RP Hoh, J (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. EM hong.zhang@yale.edu; margaux_morrison@meei.harvard.edu; andrew.dewan@yale.edu; scott_adams@meei.harvard.edu; michael_andreoli@meei.harvard.edu; nancy_huynh@meei.harvard.edu; MEREGAN@PARTNERS.ORG; ABROWN13@PARTNERS.ORG; joan_miller@meei.harvard.edu; ivana_kim@meei.harvard.edu; josephine.hoh@yale.edu RI DeAngelis, e/J-7863-2015 FU NEI NIH HHS [EY014458, P30 EY014104, EY14104, R01 EY014458] NR 36 TC 47 Z9 50 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD JUN 9 PY 2008 VL 9 AR 51 DI 10.1186/1471-2350-9-51 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 322ZR UT WOS:000257414300001 PM 18541031 ER PT J AU Homig-Holzel, C Hojer, C Rastelli, J Casola, S Strobl, LJ Muller, W Quintanilla-Martinez, L Gewies, A Ruland, J Rajewsky, K Zimber-Strobl, U AF Hoemig-Hoelzel, Cornelia Hojer, Caroline Rastelli, Julia Casola, Stefano Strobl, Lothar J. Mueller, Werner Quintanilla-Martinez, Leticia Gewies, Andreas Ruland, Juergen Rajewsky, Klaus Zimber-Strobl, Ursula TI Constitutive CD40 signaling in B cells selectively activates the noncanonical NF-kappa B pathway and promotes lymphomagenesis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID X-LINKED IMMUNODEFICIENCY; T-CELL; ANTIGEN RECEPTOR; GENE-EXPRESSION; PROTEIN-KINASE; IN-VIVO; MULTIPLE-MYELOMA; IMMUNE-RESPONSES; HYPER-IGM; LIGAND AB CD40, a member of the tumor necrosis factor (TNF) receptor family, plays an essential role in T cell-dependent immune responses. Because CD40 is widely expressed on the surface of tumor cells in various B cell malignancies, deregulated CD40 signaling has been suggested to contribute to lymphomagenesis. In this study, we show that B cell-specific expression of a constitutively active CD40 receptor, in the form of a latent membrane protein 1 (LMP1)/CD40 chimeric protein, promoted an increase in the number of follicular and marginal zone B cells in secondary lymphoid organs in transgenic mice. The B cells displayed an activated phenotype, prolonged survival and increased proliferation, but were significantly impaired in T cell-dependent immune responses. Constitutive CD40 signaling in B cells induced selective and constitutive activation of the noncanonical NF-kappa B pathway and the mitogen-activated protein kinases Jnk and extracellular signal-regulated kinase. LMP1/CD40-expressing mice older than 12 mo developed B cell lymphomas of mono- or oligoclonal origin at high incidence, thus showing that the interplay of the signaling pathways induced by constitutive CD40 signaling is sufficient to initiate a tumorigenic process, ultimately leading to the development of B cell lymphomas. C1 [Hoemig-Hoelzel, Cornelia; Hojer, Caroline; Rastelli, Julia; Strobl, Lothar J.; Zimber-Strobl, Ursula] German Res Ctr Environm & Hlth, Helmholtz Ctr Munich, Inst Clin Mol Biol & Tumor Genet, D-81377 Munich, Germany. [Casola, Stefano; Rajewsky, Klaus] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Mueller, Werner] Helmholtz Ctr Infect Res, Dept Expt Immunol, D-38124 Braunschweig, Germany. [Quintanilla-Martinez, Leticia] German Res Ctr Environm & Hlth, Helmholtz Ctr Munich, Inst Pathol, D-85764 Neuherberg, Germany. [Gewies, Andreas; Ruland, Juergen] Tech Univ Munich, Dept Med 3, Klinikum Rechts Isar, D-81675 Munich, Germany. RP Zimber-Strobl, U (reprint author), German Res Ctr Environm & Hlth, Helmholtz Ctr Munich, Inst Clin Mol Biol & Tumor Genet, D-81377 Munich, Germany. EM strobl@helmholtz-muenchen.de RI Muller, Werner/B-9044-2008; OI Muller, Werner/0000-0002-1297-9725; Gewies, Andreas/0000-0002-7606-6482 NR 48 TC 59 Z9 60 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 9 PY 2008 VL 205 IS 6 BP 1317 EP 1329 DI 10.1084/jem.20080238 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 317EG UT WOS:000257002000010 PM 18490492 ER PT J AU Shimomura, Y Ogawa, A Kawada, M Sugimoto, K Mizoguchi, E Shi, HN Pillai, S Bhan, AK Mizoguchi, A AF Shimomura, Yasuyo Ogawa, Atsuhiro Kawada, Mayumi Sugimoto, Ken Mizoguchi, Emiko Shi, Hai-Ning Pillai, Shiv Bhan, Atul K. Mizoguchi, Atsushi TI A unique B2B cell subset in the intestine SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID GUT LAMINA PROPRIA; MATURE B-CELLS; RECEPTOR-ALPHA; BONE-MARROW; T-CELLS; BAFF; LYMPHOCYTES; SURVIVAL; MICE; INFLAMMATION AB Over 80% of the body's activated B cells are located in mucosal sites, including the intestine. The intestine contains IgM(+) B cells, but these cells have not been characterized phenotypically or in terms of their developmental origins. We describe a previously unidentified and unique subset of immunoglobulin M+ B cells that present with an AA4.1(-)CD21(-)CD23(-) major histocompatibility complex class IIbright surface phenotype and are characterized by a low frequency of somatic hypermutation and the potential ability to produce interleukin-12p70. This B cell subset resides within the normal mucosa of the large intestine and expands in response to inflammation. Some of these intestinal B cells originate from the AA4.1(+) immature B2 cell pool in the steady state and are also recruited from the recirculating naive B cell pool in the context of intestinal inflammation. They develop in an antigen-independent and BAFF-dependent manner in the absence of T cell help. Expansion of these cells can be induced in the absence of the spleen and gut-associated lymphoid tissues. These results describe the existence of an alternative pathway of B cell maturation in the periphery that gives rise to a tissue-specific B cell subset. C1 [Shimomura, Yasuyo; Ogawa, Atsuhiro; Sugimoto, Ken; Bhan, Atul K.; Mizoguchi, Atsushi] Massachusetts Gen Hosp, Expt Pathol Unit, Boston, MA 02114 USA. [Shimomura, Yasuyo; Sugimoto, Ken; Bhan, Atul K.; Mizoguchi, Atsushi] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Kawada, Mayumi; Mizoguchi, Emiko] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Mizoguchi, Emiko; Shi, Hai-Ning; Pillai, Shiv; Bhan, Atul K.; Mizoguchi, Atsushi] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Shi, Hai-Ning] Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA 02129 USA. [Pillai, Shiv] Massachusetts Gen Hosp, MGH Canc Ctr, Charlestown, MA 02129 USA. [Shimomura, Yasuyo; Ogawa, Atsuhiro; Kawada, Mayumi; Sugimoto, Ken; Mizoguchi, Emiko; Shi, Hai-Ning; Pillai, Shiv; Bhan, Atul K.; Mizoguchi, Atsushi] Harvard Univ, Sch Med, Boston, MA 02116 USA. RP Mizoguchi, A (reprint author), Massachusetts Gen Hosp, Expt Pathol Unit, Boston, MA 02114 USA. EM amizoguchi@partners.org FU NIDDK NIH HHS [K08 DK064289, DK47677, R01 DK064351, R01 DK047677, DK64289, DK64351] NR 68 TC 25 Z9 27 U1 0 U2 2 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 JUN 9 PY 2008 VL 205 IS 6 BP 1343 EP 1355 DI 10.1084/jem.20071572 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 317EG UT WOS:000257002000012 PM 18519649 ER PT J AU Crump, B Landefeld, CS Shojania, KG Auerbach, AD AF Crump, Bernard Landefeld, C. Seth Shojania, Kaveh G. Auerbach, Andrew D. TI Should we use large scale healthcare interventions without clear evidence that benefits outweigh costs and harms? SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material C1 [Crump, Bernard] NHS Inst Innovat & Improvement, Coventry CV4 7AL, W Midlands, England. [Landefeld, C. Seth; Auerbach, Andrew D.] Univ Calif San Francisco, San Francisco, CA 94118 USA. [Landefeld, C. Seth] San Francisco VA Med Ctr, San Francisco, CA USA. [Shojania, Kaveh G.] Ottawa Hlth Res Inst, Ottawa, ON, Canada. RP Crump, B (reprint author), NHS Inst Innovat & Improvement, Coventry CV4 7AL, W Midlands, England. EM bernard.crump@institute.nhs.uk; sethl@medicine.ucsf.edu NR 0 TC 5 Z9 5 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD JUN 7 PY 2008 VL 336 IS 7656 BP 1276 EP 1277 DI 10.1136/bmj.a145 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 312XO UT WOS:000256705900028 PM 18535068 ER PT J AU Craft, D Bortfeld, T AF Craft, David Bortfeld, Thomas TI How many plans are needed in an IMRT multi-objective plan database? SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID MODULATED RADIATION-THERAPY; OPTIMIZATION; RADIOTHERAPY AB In multi-objective radiotherapy planning, we are interested in Pareto surfaces of dimensions 2 up to about 10 (for head and neck cases, the number of structures to trade off can be this large). A key question that has not been answered yet is: how many plans does it take to sufficiently represent a high-dimensional Pareto surface? In this paper, we present a method to answer this question, and we show that the number of points needed is modest: 75 plans always controlled the error to within 5%, and in all cases but one, N + 1 plans, where N is the number of objectives, was enough for < 15% error. We introduce objective correlation matrices and principal component analysis (PCA) of the beamlet solutions as two methods to understand this. PCA reveals that the feasible beamlet solutions of a Pareto database lie in a narrow, small dimensional subregion of the full beamlet space, which helps explain why the number of plans needed to characterize the database is small. C1 [Craft, David; Bortfeld, Thomas] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Craft, David; Bortfeld, Thomas] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Craft, D (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM dcraft@partners.org FU NCI NIH HHS [1 R01 CA103904-01A1] NR 14 TC 41 Z9 42 U1 0 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JUN 7 PY 2008 VL 53 IS 11 BP 2785 EP 2796 DI 10.1088/0031-9155/53/11/002 PG 12 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 307XD UT WOS:000256352000003 PM 18451463 ER PT J AU Salomatina, E Yaroslavsky, AN AF Salomatina, E. Yaroslavsky, A. N. TI Evaluation of the in vivo and ex vivo optical properties in a mouse ear model SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID HUMAN SKIN; TISSUE; BLOOD; REFLECTANCE; LASER; WATER AB Determination of in vivo optical properties is a challenging problem. Absorption and scattering measured ex vivo are often used for in vivo applications. To investigate the validity of this approach, we have obtained and compared the optical properties of mouse ears in vivo and ex vivo in the spectral range from 370 to 1650 nm. Integrating sphere spectrophotometry in combination with the inverse Monte Carlo technique was employed to determine absorption coefficients, mu(a), scattering coefficients, mu(s), and anisotropy factors, g. Two groups of mice were used for the study. The first group was measured in vivo and ex vivo within 5-10 min post mortem. The second group was measured in vivo and ex vivo every 24 h for up to 72 h after sacrifice. Between the measurements the tissues were kept at 4 degrees C wrapped in a gauze moistened with saline solution. Then the specimens were frozen at -25 degrees C for 40 min, thawed and measured again. The results indicate that the absorption coefficients determined in vivo and ex vivo within 5-10 min post mortem differed considerably only in the spectral range dominated by hemoglobin. These changes can be attributed to rapid deoxygenation of tissue and blood post mortem. Absorption coefficients determined ex vivo up to 72 h post mortem decreased gradually with time in the spectral regions dominated by hemoglobin and water, which can be explained by the continuing loss of blood. Absorption properties of the frozen-thawed ex vivo tissues showed increase in oxygenation, which is likely caused by the release of hemoglobin from hemolyzed erythrocytes. Scattering of the ex vivo tissues decreased gradually with time in the entire spectral range due to the continuing loss of blood and partial cell damage. Anisotropy factors did not change considerably. C1 [Salomatina, E.; Yaroslavsky, A. N.] Wellman Ctr Photomed, Boston, MA 02114 USA. [Salomatina, E.; Yaroslavsky, A. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yaroslavsky, A. N.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Salomatina, E (reprint author), Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM Yaroslav@helix.mgh.harvard.edu NR 22 TC 32 Z9 32 U1 0 U2 4 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JUN 7 PY 2008 VL 53 IS 11 BP 2797 EP 2807 DI 10.1088/0031-9155/53/11/003 PG 11 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 307XD UT WOS:000256352000004 PM 18451462 ER PT J AU Poh, KK Ton-Nu, TT Neilan, TG Tournoux, FB Picard, MH Wood, MJ AF Poh, Kian-Keong Ton-Nu, Thanh-Thao Neilan, Tomas G. Tournoux, Francois B. Picard, Michael H. Wood, Malissa J. TI Myocardial adaptation and efficiency in response to intensive physical training in elite speedskaters SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE athletes; echocardiography; adaptive changes; ventricular function ID LEFT-VENTRICULAR HYPERTROPHY; ATHLETES HEART; EXERCISE; SPORTS; DYSFUNCTION; ECHOCARDIOGRAPHY; MARATHON; FEATURES; LIMITS; MASS AB Background: Physiological cardiac adaptations to exercise training resulting in the 'athlete's heart' are well known. Most of these studies, however, were included either those who exercise to exhaustion, non-elite athletes or those who participate primarily in sports requiring extensive weight training. Studies utilizing conventional and tissue Doppler echocardiographic studies in highly competitive elite athletes whose training includes both aerobic and weight training are limited. Aims and methods: 1) To identify baseline cardiovascular structural and physiologic adaptations present in elite athletes who participate in both endurance aerobic and weight training programs and to compare them to similarly aged sedentary controls. The population includes 24 speedskaters participating in the 2006 Olympic Games and 15 sedentary young subjects. 2) To evaluate possible structural and physiologic cardiac changes following short duration, vigorous exercise. We repeated the baseline echocardiographic protocol in the athletes following a 3000 m sprint conducted at race pace. Results: Compared to non-athletes, the atrial and left ventricular (LV) volumes at rest were larger in elite athletes. There was enhanced LV diastolic function as manifested by higher early annular (septal and lateral) tissue Doppler velocities (E'): 12.7 +/- 2.3 vs 11.3 +/- 1.1 cm/s and 17.4 +/- 4.7 vs 14.4 +/- 1.2 cm/s, P=0.025 and 0.020 respectively. Evidence of right ventricular (RV) remodeling included larger basal RV dimensions (38 +/- 5 vs 32 +/- 4 mm, P=0.001), attenuated RV systolic function at rest (RV area change 35 +/- 13% in athletes vs 47 +/- 11% in controls, P=0.006) and lower RV systolic strain rate (SSR) 1.9 +/- 0.5 vs 2.9 +/- 1.1/s, P<0.001). However, there was better right ventricular (RV) diastolic function at rest, E': 13.5 +/- 3.6 vs 11.1 +/- 1.5 cm/s (P=0.016). Following exercise, the athletes exhibited augmentation of RV systolic function with increased RV fractional area change (increasing to 43 +/- 10%, P=0.007) and SSR (2.5 +/- 1.2/s post-exercise, P=0.038). Conclusion: Participation by world-class speedskaters in a vigorous training regimen results in cardiovascular anatomic and physiologic adaptations. These changes, including cardiac chamber dilatation, enhanced ventricular diastolic function and attenuated resting RV systolic function, are likely adaptive and allow for more efficient energy use at rest and a robust response to demands of exercise. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wood, MJ (reprint author), Cardiac Ultrasound Lab, 55 Fruit St,Blake 256, Boston, MA 02115 USA. EM mjwood@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 29 TC 22 Z9 22 U1 0 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD JUN 6 PY 2008 VL 126 IS 3 BP 346 EP 351 DI 10.1016/j.ijcard.2007.04.051 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 301WS UT WOS:000255927500008 PM 17602763 ER PT J AU Resto, VA Burdick, MM Dagia, NM McCammon, SD Fennewald, SM Sackstein, R AF Resto, Vicente A. Burdick, Monica M. Dagia, Nilesh M. McCammon, Susan D. Fennewald, Susan M. Sackstein, Robert TI L-selectin-mediated lymphocyte-cancer cell interactions under low fluid shear conditions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIGH ENDOTHELIAL VENULES; COLON-CARCINOMA CELLS; TUMOR LYMPHANGIOGENESIS; HOMING RECEPTORS; BINDING-ACTIVITY; ADHESION; LIGAND; METASTASIS; PSGL-1; FLOW AB Cell migration in blood flow is mediated by engagement of specialized adhesion molecules that function under hemodynamic shear conditions, and many of the effectors of these adhesive interactions, such as the selectins and their ligands, are well defined. However, in contrast, our knowledge of the adhesion molecules operant under lymphatic flow conditions is incomplete. Among human malignancies, head and neck squamous cell cancer displays a marked predilection for locoregional lymph node metastasis. Based on this distinct tropism, we hypothesized that these cells express adhesion molecules that promote their binding to lymphoid tissue under lymphatic fluid shear stress. Accordingly, we investigated adhesive interactions between these and other cancer cells and the principal resident cells of lymphoid organs, lymphocytes. Parallel plate flow chamber studies under defined shear conditions, together with biochemical analyses, showed that human head and neck squamous cell cancer cells express heretofore unrecognized L-selectin ligand(s) that mediate binding to lymphocyte L-selectin at conspicuously low shear stress levels of 0.07-0.08 dynes/cm(2), consistent with lymphatic flow. The binding of head and neck squamous cancer cells to L-selectin displays canonical biochemical features, such as requirements for sialylation, sulfation, and N-glycosylation, but displays a novel operational shear threshold differing from all other L-selectin ligands, including those expressed on colon cancer and leukemic cells (e. g. HCELL). These data define a novel class of L-selectin ligands and expand the scope of function for L-selectin within circulatory systems to now include a novel activity within shear stresses characteristic of lymphatic flow. C1 [Resto, Vicente A.; Burdick, Monica M.; Dagia, Nilesh M.; Sackstein, Robert] Harvard Univ, Brigham & Womens Hosp, Skin Dis Res Ctr, Dept Dermatol, Boston, MA 02115 USA. [Sackstein, Robert] Harvard Univ, Brigham & Womens Hosp, Skin Dis Res Ctr, Dept Med, Boston, MA 02115 USA. [Sackstein, Robert] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Resto, Vicente A.; McCammon, Susan D.; Fennewald, Susan M.] Univ Texas Galveston, Med Branch, Dept Otolaryngol, Galveston, TX 77555 USA. [Resto, Vicente A.; Fennewald, Susan M.] Univ Texas Galveston, Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA. [Resto, Vicente A.; Fennewald, Susan M.] Univ Texas Galveston, Med Branch, Sealy Ctr Canc Cell Biol, Galveston, TX 77555 USA. RP Sackstein, R (reprint author), Harvard Univ, Skin Dis Res Ctr, 77 Ave Louis Pasteur,Rm 671, Boston, MA 02115 USA. EM rsackstein@rics.bwh.harvard.edu RI Resto, Vicente/D-9891-2014 FU NCI NIH HHS [R01 CA121335, K08 CA132988]; NHLBI NIH HHS [R01 HL073714, R01 HL060528] NR 36 TC 20 Z9 23 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 6 PY 2008 VL 283 IS 23 BP 15816 EP 15824 DI 10.1074/jbc.M708899200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 307QD UT WOS:000256332500039 PM 18385135 ER PT J AU Cao, XH Antonyuk, SV Seetharaman, SV Whitson, LJ Taylor, AB Holloway, SP Strange, RW Doucette, PA Valentine, JS Tiwari, A Hayward, LJ Padua, S Cohlberg, JA Hasnain, SS Hart, PJ AF Cao, Xiaohang Antonyuk, Svetlana V. Seetharaman, Sai V. Whitson, Lisa J. Taylor, Alexander B. Holloway, Stephen P. Strange, Richard W. Doucette, Peter A. Valentine, Joan Selverstone Tiwari, Ashutosh Hayward, Lawrence J. Padua, Shelby Cohlberg, Jeffrey A. Hasnain, S. Samar Hart, P. John TI Structures of the G85R variant of SOD1 in familial amyotrophic lateral sclerosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ZINC SUPEROXIDE-DISMUTASE; COPPER CHAPERONE CCS; ALS-LINKED SOD1; CU,ZN-SUPEROXIDE DISMUTASE; DIMER STABILITY; MOTOR-NEURONS; MOUSE MODEL; HUMAN CU; AGGREGATION; MUTATIONS AB Mutations in the gene encoding human copper-zinc superoxide dismutase (SOD1) cause a dominant form of the progressive neurodegenerative disease amyotrophic lateral sclerosis. Transgenic mice expressing the human G85R SOD1 variant develop paralytic symptoms concomitant with the appearance of SOD1-enriched proteinaceous inclusions in their neural tissues. The process(es) through which misfolding or aggregation of G85R SOD1 induces motor neuron toxicity is not understood. Here we present structures of the human G85R SOD1 variant determined by single crystal x-ray diffraction. Alterations in structure of the metal-binding loop elements relative to the wild type enzyme suggest a molecular basis for the metal ion deficiency of the G85R SOD1 protein observed in the central nervous system of transgenic mice and in purified recombinant G85R SOD1. These findings support the notion that metal-deficient and/or disulfide-reduced mutant SOD1 species contribute to toxicity in SOD1-linked amyotrophic lateral sclerosis. C1 [Cao, Xiaohang; Seetharaman, Sai V.; Whitson, Lisa J.; Taylor, Alexander B.; Holloway, Stephen P.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Cao, Xiaohang; Seetharaman, Sai V.; Whitson, Lisa J.; Taylor, Alexander B.; Holloway, Stephen P.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Xray Crystallog Core Lab, San Antonio, TX 78229 USA. [Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Ctr Geriatr Res Educ & Clin, Dept Vet Affairs, San Antonio, TX 78229 USA. [Antonyuk, Svetlana V.; Strange, Richard W.; Hasnain, S. Samar] SERC, Daresbury Lab, Mol Biophys Grp, Sci & Technol Facil Council, Warrington WA4 4AD, Cheshire, England. [Doucette, Peter A.; Valentine, Joan Selverstone] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. [Tiwari, Ashutosh; Hayward, Lawrence J.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA. [Padua, Shelby; Cohlberg, Jeffrey A.] Calif State Univ Long Beach, Dept Chem & Biochem, Long Beach, CA 90840 USA. RP Hart, PJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. EM pjhart@biochem.uthscsa.edu RI Tiwari, Ashutosh/A-7458-2008; Antonyuk, Svetlana/B-6002-2013; OI Tiwari, Ashutosh/0000-0001-7373-349X; Antonyuk, Svetlana/0000-0002-2779-9946 FU NIGMS NIH HHS [GM28222]; NINDS NIH HHS [NS44170, NS049134, R01 NS039112-08, NS39112, R01 NS044170, R01 NS039112] NR 59 TC 41 Z9 43 U1 2 U2 11 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 JUN 6 PY 2008 VL 283 IS 23 BP 16169 EP 16177 DI 10.1074/jbc.M801522200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 307QD UT WOS:000256332500075 PM 18378676 ER PT J AU Nogueira, E Fidalgo, M Molnar, A Kyriakis, J Force, T Zalvide, J Pombo, CM AF Nogueira, Emilio Fidalgo, Miguel Molnar, Arpad Kyriakis, John Force, Thomas Zalvide, Juan Pombo, Celia M. TI SOK1 translocates from the Golgi to the nucleus upon chemical anoxia and induces apoptotic cell death SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GERMINAL CENTER KINASE; MAMMALIAN STE20-LIKE PROTEIN-KINASE-3; PROTEIN-KINASE; PROMOTES APOPTOSIS; OXIDATIVE-STRESS; STE20-RELATED KINASE; CASPASE ACTIVATION; TUMOR-SUPPRESSOR; OXIDANT STRESS; MAP KINASE AB SOK1 is a Ste20 protein kinase of the germinal center kinase (GCK) family that has been shown to be activated by oxidant stress and chemical anoxia, a cell culture model of ischemia. More recently, it has been shown to be localized to the Golgi apparatus, where it functions in a signaling pathway required for cell migration and polarization. Herein, we demonstrate that SOK1 regulates cell death after chemical anoxia, as its down-regulation by RNA interference enhances cell survival. Furthermore, expression of SOK1 elicits apoptotic cell death by activating the intrinsic pathway. We also find that a cleaved form of SOK1 translocates from the Golgi to the nucleus after chemical anoxia and that this translocation is dependent on both caspase activity and on amino acids 275-292, located immediately C-terminal to the SOK1 kinase domain. Furthermore, SOK1 entry into the nucleus is important for the cell death response since SOK1 mutants unable to enter the nucleus do not induce cell death. In summary, SOK1 is necessary to induce cell death and can induce death when over-expressed. Furthermore, SOK1 appears to play distinctly different roles in stressed versus non-stressed cells, regulating cell death in the former. C1 [Nogueira, Emilio; Fidalgo, Miguel; Zalvide, Juan; Pombo, Celia M.] Univ Santiago de Compostela, Sch Med, Dept Physiol, Lab Cell Signaling & Canc Res, Santiago De Compostela 15705, Spain. [Molnar, Arpad] Massachusetts Gen Hosp, Diabet Res Lab, Charlestown, MA 02129 USA. [Kyriakis, John] Tufts Univ, Sch Med, Tufts New England Med Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA. [Force, Thomas] Thomas Jefferson Univ, Ctr Translat Med, Philadelphia, PA 19107 USA. RP Pombo, CM (reprint author), Univ Santiago de Compostela, Sch Med, Dept Physiol, Lab Cell Signaling & Canc Res, San Francisco S-N, Santiago De Compostela 15705, Spain. EM fspombo@usc.es OI Force, Thomas/0000-0002-0450-8659; Fidalgo, Miguel/0000-0003-1134-2674 FU NHLBI NIH HHS [HL67371] NR 46 TC 27 Z9 29 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 6 PY 2008 VL 283 IS 23 BP 16248 EP 16258 DI 10.1074/jbc.M709724200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 307QD UT WOS:000256332500083 PM 18364353 ER PT J AU Ogawa, Y Sun, BK Lee, JT AF Ogawa, Yuya Sun, Bryan K. Lee, Jeannie T. TI Intersection of the RNA interference and X-inactivation pathways SO SCIENCE LA English DT Article ID EMBRYONIC STEM-CELLS; CHROMOSOME INACTIVATION; XIST RNA; CHOICE; TSIX; GENE; DIFFERENTIATION; TRANSCRIPTION; DICER; XITE AB In mammals, dosage compensation is achieved by X- chromosome inactivation ( XCI) in the female. The noncoding Xist gene initiates silencing of the X chromosome, whereas its antisense partner Tsix blocks silencing. The complementarity of Xist and Tsix RNAs has long suggested a role for RNA interference ( RNAi). Here, we report that murine Xist and Tsix form duplexes in vivo. During XCI, the duplexes are processed to small RNAs ( sRNAs), most likely on the active X ( Xa) in a Dicer- dependent manner. Deleting Dicer compromises sRNA production and derepresses Xist. Furthermore, without Dicer, Xist RNA cannot accumulate and histone 3 lysine 27 trimethylation is blocked on the inactive X ( Xi). The defects are partially rescued by truncating Tsix. Thus, XCI and RNAi intersect, down- regulating Xist on Xa and spreading silencing on Xi. C1 [Ogawa, Yuya; Sun, Bryan K.; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Ogawa, Yuya; Sun, Bryan K.; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Ogawa, Yuya; Sun, Bryan K.; Lee, Jeannie T.] Howard Hughes Med Inst, Boston, MA 02114 USA. RP Lee, JT (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu OI Sun, Bryan/0000-0002-0740-0125 FU Howard Hughes Medical Institute; NIGMS NIH HHS [R01 GM058839, R01 GM058839-10] NR 21 TC 177 Z9 197 U1 2 U2 22 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 JUN 6 PY 2008 VL 320 IS 5881 BP 1336 EP 1341 DI 10.1126/science.1157676 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 309DO UT WOS:000256441100044 PM 18535243 ER PT J AU Smith, B Chu, LK Smith, TC Amoroso, PJ Boyko, EJ Hooper, TI Gackstetter, GD Ryan, MAK AF Smith, Besa Chu, Laura K. Smith, Tyler C. Amoroso, Paul J. Boyko, Edward J. Hooper, Tomoko I. Gackstetter, Gary D. Ryan, Margaret A. K. CA Millennium Cohort Study Team TI Challenges of self-reported medical conditions and electronic medical records among members of a large military cohort SO BMC MEDICAL RESEARCH METHODOLOGY LA English DT Article ID MILLENNIUM COHORT; HEART-ATTACK; RISK-FACTORS; US MILITARY; HEALTH; VALIDATION; AGREEMENT; QUESTIONNAIRE; VALIDITY; STROKE AB Background: Self- reported medical history data are frequently used in epidemiological studies. Self- reported diagnoses may differ from medical record diagnoses due to poor patient- clinician communication, self- diagnosis in the absence of a satisfactory explanation for symptoms, or the " health literacy" of the patient. Methods: The US Department of Defense military health system offers a unique opportunity to evaluate electronic medical records with near complete ascertainment while on active duty. This study compared 38 self- reported medical conditions to electronic medical record data in a large population- based US military cohort. The objective of this study was to better understand challenges and strengths in self- reporting of medical conditions. Results: Using positive and negative agreement statistics for less- prevalent conditions, nearperfect negative agreement and moderate positive agreement were found for the 38 diagnoses. Conclusion: This report highlights the challenges of using self- reported medical data and electronic medical records data, but illustrates that agreement between the two data sources increases with increased surveillance period of medical records. Self- reported medical data may be sufficient for ruling out history of a particular condition whereas prevalence studies may be best served by using an objective measure of medical conditions found in electronic healthcare records. Defining medical conditions from multiple sources in large, long- term prospective cohorts will reinforce the value of the study, particularly during the initial years when prevalence for many conditions may still be low. C1 [Smith, Besa; Chu, Laura K.; Smith, Tyler C.; Ryan, Margaret A. K.] USN, Hlth Res Ctr, Dept Def Ctr Deployment Hlth Res, Washington, DC 20375 USA. [Amoroso, Paul J.] Madigan Army Med Ctr, Tacoma, WA 98431 USA. [Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Gackstetter, Gary D.] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. [Hooper, Tomoko I.; Gackstetter, Gary D.] Analyt Serv Inc ANSER, Arlington, VA USA. RP Smith, B (reprint author), USN, Hlth Res Ctr, Dept Def Ctr Deployment Hlth Res, Washington, DC 20375 USA. EM besa.smith@med.navy.mil; laurakaychu@yahoo.com; tyler.smith2@med.navy.mil; paul.amoroso@us.army.mil; eboyko@u.washington.edu; thooper@usuhs.mil; gary.gackstetter@anser.org; margaret.ryan@med.navy.mil NR 28 TC 36 Z9 36 U1 2 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2288 J9 BMC MED RES METHODOL JI BMC Med. Res. Methodol. PD JUN 5 PY 2008 VL 8 AR 37 DI 10.1186/1471-2288-8-37 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 335PE UT WOS:000258301700001 PM 18644098 ER PT J AU Gonzalez, MC Hidalgo, CA Barabasi, AL AF Gonzalez, Marta C. Hidalgo, Cesar A. Barabasi, Albert-Laszlo TI Understanding individual human mobility patterns SO NATURE LA English DT Article ID FLIGHT SEARCH PATTERNS; LEVY FLIGHT; WANDERING ALBATROSSES; COMPLEX NETWORKS; SCALING LAWS; TRAVEL; DYNAMICS; BEHAVIOR; MEDIA AB Despite their importance for urban planning(1), traffic forecasting(2) and the spread of biological(3-5) and mobile viruses(6), our understanding of the basic laws governing human motion remains limited owing to the lack of tools to monitor the time- resolved location of individuals. Here we study the trajectory of 100,000 anonymized mobile phone users whose position is tracked for a six- month period. We find that, in contrast with the random trajectories predicted by the prevailing Levy flight and random walk models(7), human trajectories show a high degree of temporal and spatial regularity, each individual being characterized by a time-independent characteristic travel distance and a significant probability to return to a few highly frequented locations. After correcting for differences in travel distances and the inherent anisotropy of each trajectory, the individual travel patterns collapse into a single spatial probability distribution, indicating that, despite the diversity of their travel history, humans follow simple reproducible patterns. This inherent similarity in travel patterns could impact all phenomena driven by human mobility, from epidemic prevention to emergency response, urban planning and agent- based modelling. C1 [Gonzalez, Marta C.; Hidalgo, Cesar A.; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. [Gonzalez, Marta C.; Hidalgo, Cesar A.; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys Biol & Comp Sci, Boston, MA 02115 USA. [Hidalgo, Cesar A.; Barabasi, Albert-Laszlo] Univ Notre Dame, Ctr Complex Network Res, Notre Dame, IN 46556 USA. [Hidalgo, Cesar A.; Barabasi, Albert-Laszlo] Univ Notre Dame, Dept Phys & Comp Sci, Notre Dame, IN 46556 USA. [Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. RP Barabasi, AL (reprint author), Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. EM alb@neu.edu RI Hidalgo, Cesar/B-5155-2009; Gonzalez, Marta/E-9456-2011; OI Gonzalez, Marta/0000-0002-8482-0318; , /0000-0002-6031-5982 NR 30 TC 1538 Z9 1614 U1 56 U2 391 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 5 PY 2008 VL 453 IS 7196 BP 779 EP 782 DI 10.1038/nature06958 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 308UK UT WOS:000256415300043 PM 18528393 ER PT J AU Schwarzberg, AB Alexander, CB DeAngelo, DJ Helfgott, SM AF Schwarzberg, Abraham B. Alexander, Cristina B. DeAngelo, Daniel J. Helfgott, Simon M. TI A joint venture SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE MYELOID-LEUKEMIA; ADULT ACUTE-LEUKEMIA; MYELODYSPLASTIC SYNDROMES; MULTIVARIATE-ANALYSIS; GROUP-B; CANCER; MANIFESTATIONS C1 [Schwarzberg, Abraham B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Schwarzberg, Abraham B.; Alexander, Cristina B.; DeAngelo, Daniel J.; Helfgott, Simon M.] Harvard Univ, Sch Med, Boston, MA USA. [Schwarzberg, Abraham B.; DeAngelo, Daniel J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Alexander, Cristina B.; Helfgott, Simon M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Schwarzberg, AB (reprint author), Massachusetts Gen Hosp, Dept Med, 10 N Grove St,POB 221, Boston, MA 02114 USA. EM aschwarzberg@partners.org FU NCI NIH HHS [2P01CA 066996-11A1, P01CA68484] NR 14 TC 1 Z9 1 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 JUN 5 PY 2008 VL 358 IS 23 BP 2496 EP 2501 DI 10.1056/NEJMcps070565 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 308HY UT WOS:000256380700010 PM 18525046 ER PT J AU Polonis, VR Brown, BK Borges, AR Zolla-Pazner, S Dimitrov, DS Zhang, MY Barnett, SW Ruprecht, RM Scarlatti, G Fenyo, EM Montefiori, DC McCutchan, FE Michael, NL AF Polonis, Victoria R. Brown, Bruce K. Borges, Andrew Rosa Zolla-Pazner, Susan Dimitrov, Dimiter S. Zhang, Mei-Yun Barnett, Susan W. Ruprecht, Ruth M. Scarlatti, Gabriella Fenyoe, Eva-Maria Montefiori, David C. McCutchan, Francine E. Michael, Nelson L. TI Recent advances in the characterization of HIV-1 neutralization assays for standardized evaluation of the antibody response to infection and vaccination SO VIROLOGY LA English DT Review DE human immunodeficiency virus type I (HIV-1); antibodies; neutralization assays; pseudovirus; vaccine immune assessment; standardization ID IMMUNODEFICIENCY-VIRUS TYPE-1; MONOCLONAL-ANTIBODIES; ENVELOPE GLYCOPROTEIN; VACCINES; EPITOPES; BINDING; FUSION; PANEL AB In AIDS vaccine development the pendulum has swung towards a renewed emphasis on the potential role for neutralizing antibodies in a successful global vaccine. It is recognized that vaccine-induced antibody performance, as assessed in the available neutralization assays, may well serve as a "gatekeeper" for HIV-1 subunit vaccine prioritization and advancement. As a result, development of a standardized platform for reproducible measurement of neutralizing antibodies has received considerable attention. Here we review current advancements in our knowledge of the performance of different types of antibodies in a traditional primary cell neutralization assay and the newer, more standardized TZM-bl reporter cell line assay. In light of recently revealed differences (see accompanying article) in the results obtained in these two neutralization formats, parallel evaluation with both platforms should be contemplated as an interim solution until a better understanding of immune correlates of protection is achieved. Published by Elsevier Inc. C1 [Polonis, Victoria R.; Michael, Nelson L.] Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Washington, DC 20307 USA. [Brown, Bruce K.; Borges, Andrew Rosa; McCutchan, Francine E.] Henry M Jackson Fdn, Rockville, MD USA. [Zolla-Pazner, Susan] NYU, Sch Med, New York, NY USA. [Zolla-Pazner, Susan] VA Hosp, New York, NY USA. [Dimitrov, Dimiter S.; Zhang, Mei-Yun] NCI, US NIH, Frederick, MD 21701 USA. [Barnett, Susan W.] Novartis Vaccines & Diagnost Inc, Emeryville, CA USA. [Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Scarlatti, Gabriella] Ist Sci San Raffaele, I-20132 Milan, IT, Italy. [Fenyoe, Eva-Maria] Lund Univ, Lund, Sweden. [Montefiori, David C.] Duke Univ, Durham, NC USA. RP Polonis, VR (reprint author), WRAIR, 13 Taft Court, Rockville, MD 20850 USA. EM vpolonis@hivresearch.org FU Intramural NIH HHS; NCI NIH HHS [N01 CO 12400] NR 21 TC 84 Z9 86 U1 0 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 5 PY 2008 VL 375 IS 2 BP 315 EP 320 DI 10.1016/j.virol.2008.02.007 PG 6 WC Virology SC Virology GA 304JQ UT WOS:000256106200001 PM 18367229 ER PT J AU Chan, JA Meyerhardt, JA Niedzwiecki, D Hollis, D Saltz, LB Mayer, RJ Thomas, J Schaefer, P Whittom, R Hantel, A Goldberg, RM Warren, RS Bertagnolli, M Fuchs, CS AF Chan, Jennifer A. Meyerhardt, Jeffrey A. Niedzwiecki, Donna Hollis, Donna Saltz, Leonard B. Mayer, Robert J. Thomas, James Schaefer, Paul Whittom, Renaud Hantel, Alexander Goldberg, Richard M. Warren, Robert S. Bertagnolli, Monica Fuchs, Charles S. TI Association of family history with cancer recurrence and survival among patients with stage III colon cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MICROSATELLITE INSTABILITY; COLORECTAL-CANCER; ADENOMATOUS POLYPS; FOLLOW-UP; PROGNOSIS; IMPACT; RISK; COMPLETENESS; CALGB-89803; DATABASE AB Context A family history of colorectal cancer in a first- degree relative increases the risk of developing colorectal cancer. However, the influence of family history on cancer recurrence and survival among patients with established disease remains uncertain. Objective To examine the association of family history of colorectal cancer with cancer recurrence and survival of patients with colon cancer. Design, Setting, and Participants Prospective observational study of 1087 patients with stage III colon cancer enrolled in a randomized adjuvant chemotherapy trial ( CALGB 89803) between April 1999 and May 2001. Patients provided data on family history at baseline and were followed up until March 2007 for disease recurrence and death ( median follow- up, 5.6 years). In a subset of patients, we assessed microsatellite instability ( MSI) and expression of the mismatch repair ( MMR) proteins MLH1 and MSH2 in tumor specimens. Main Outcome Measures Disease- free survival, recurrence- free survival, and overall survival according to the presence or absence of a family history of colorectal cancer. Results Among 1087 eligible patients, 195 ( 17.9%) reported a family history of colorectal cancer in a first- degree relative. Cancer recurrence or death occurred in 57 of 195 patients ( 29%; 95% confidence interval [ CI], 23%- 36%) with a family history of colorectal cancer and 343 of 892 patients ( 38%; 95% CI, 35%- 42%) without a family history. Compared with patients without a family history, the adjusted hazard ratios ( HRs) among those with 1 or more affected first- degree relatives were 0.72 ( 95% CI, 0.54- 0.96) for disease- free survival, 0.74 ( 95% CI, 0.55- 0.99) for recurrence- free survival, and 0.75 ( 95% CI, 0.54- 1.05) for overall survival. This reduction in risk of cancer recurrence or death associated with a family history became stronger with an increasing number of affected first- degree relatives. Compared with participants without a family history of colorectal cancer, those with 1 affected relative had a multivariate HR of 0.77 ( 95% CI, 0.57- 1.04) for disease- free survival. For participants with 2 or more affected relatives, we observed a greater reduction in risk ( multivariate HR for disease- free survival, 0.49; 95% CI, 0.23- 1.04; P for trend with increasing number of affected relatives=. 01). The improved disease- free survival associated with a family history was independent of tumoral MSI or MMR status. Conclusion Among patients with stage III colon cancer receiving adjuvant chemotherapy, a family history of colorectal cancer is associated with a significant reduction in cancer recurrence and death. C1 [Chan, Jennifer A.; Meyerhardt, Jeffrey A.; Mayer, Robert J.; Fuchs, Charles S.] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. [Niedzwiecki, Donna; Hollis, Donna] Duke Univ, Med Ctr, CALGB Stat Ctr, Durham, NC USA. [Saltz, Leonard B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Thomas, James] Ohio State Univ, Columbus, OH 43210 USA. [Schaefer, Paul] Toledo Community Hosp Oncol Program, Community Clin Oncol Program, Toledo, OH USA. [Whittom, Renaud] Hop Sacre Coeur, Montreal, PQ H4J 1C5, Canada. [Hantel, Alexander] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. [Goldberg, Richard M.] Univ N Carolina, Dept Hematol Oncol, Chapel Hill, NC USA. [Warren, Robert S.] Univ Calif San Francisco, Div Surg Oncol, San Francisco, CA 94143 USA. [Bertagnolli, Monica] Brigham & Womens Hosp, Div Surg Oncol, Boston, MA 02115 USA. RP Chan, JA (reprint author), Dana Farber Canc Inst, Div Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM jang@partners.org RI Goldberg , Richard/M-1311-2013; OI Saltz, Leonard/0000-0001-8353-4670 FU NCI NIH HHS [CA31946, CA02599, CA03927, CA04326, CA04457, CA07968, CA08025, CA11028, CA11789, CA118553, CA12046, CA12449, CA16450, CA21076, CA21115, CA23318, CA26806, CA29165, CA31983, CA32102, CA32291, CA33601, CA35279, CA35415, CA35421, CA37135, CA38926, CA41287, CA45389, CA45418, CA45564, CA45808, CA46282, CA47555, CA47559, CA47577, CA47642, CA60138, CA66636, CA71323, CA74811, CA77298, CA77406, CA77440, CA77597, CA77651, CA77658, R01 CA118553, R01 CA118553-01A2, T32 CA009001, T32 CA009001-26, T32 CA009172, T32-CA009001, U10 CA003927, U10 CA031946, U10 CA031946-25, U10 CA032291, U10 CA032291-18, U10 CA033601, U10 CA033601-20, U10 CA035279, U10 CA035421, U10 CA041287, U10 CA045389, U10 CA045418, U10 CA045564, U10 CA045808, U10 CA047559, U10 CA047577, U10 CA047642, U10 CA071323, U10 CA074811, U10 CA077440, U10 CA077597, U10 CA077651, U10 CA077658, U10 CA077658-02] NR 28 TC 42 Z9 44 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 4 PY 2008 VL 299 IS 21 BP 2515 EP 2523 DI 10.1001/jama.299.21.2515 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 308AR UT WOS:000256361200023 PM 18523220 ER PT J AU de la Iglesia, N Konopka, G Lim, KL Nutt, CL Bromberg, JF Frank, DA Mischel, PS Louis, DN Bonni, A AF de la Iglesia, Nuria Konopka, Genevieve Lim, Kah-Leong Nutt, Catherine L. Bromberg, Jacqueline F. Frank, David A. Mischel, Paul S. Louis, David N. Bonni, Azad TI Deregulation of a STAT3-interleukin 8 signaling pathway promotes human glioblastoma cell proliferation and invasiveness SO JOURNAL OF NEUROSCIENCE LA English DT Article DE STAT3; IL8; astrocyte; astroglia; gliogenesis; glioma; tumor ID FACTOR-KAPPA-B; CENTRAL-NERVOUS-SYSTEM; STAT3; GLIOMA; GENE; INTERLEUKIN-8; ACTIVATION; DIFFERENTIATION; GLIOMAGENESIS; GROWTH AB Inactivation of the tumor suppressor phosphatase and tensin homolog (mutated in multiple advanced cancers 1) (PTEN) is recognized as a major event in the pathogenesis of the brain tumor glioblastoma. However, the mechanisms by which PTEN loss specifically impacts the malignant behavior of glioblastoma cells, including their proliferation and propensity for invasiveness, remain poorly understood. Genetic studies suggest that the transcription factor signal transducers and activators of transcription 3 (STAT3) harbors a PTEN-regulated tumor suppressive function in mouse astrocytes. Here, we report that STAT3 plays a critical tumor suppressive role in PTEN-deficient human glioblastoma cells. Endogenous STAT3 signaling is specifically inhibited in PTEN-deficient glioblastoma cells. Strikingly, reactivation of STAT3 in PTEN-deficient glioblastoma cells inhibits their proliferation, invasiveness, and ability to spread on myelin. We also identify the chemokine interleukin 8 (IL8) as a novel target gene of STAT3 in human glioblastoma cells. Activated STAT3 occupies the endogenous IL8 promoter and directly represses IL8 transcription. Consistent with these results, IL8 is upregulated in PTEN-deficient human glioblastoma tumors. Importantly, IL8 repression mediates STAT3 inhibition of glioblastoma cell proliferation, invasiveness, and spreading on myelin. Collectively, our findings uncover a novel link between STAT3 and IL8, the deregulation of which plays a key role in the malignant behavior of PTEN-deficient glioblastoma cells. These studies suggest that STAT3 activation or IL8 inhibition may have potential in patient-tailored treatment of PTEN-deficient brain tumors. C1 [de la Iglesia, Nuria; Konopka, Genevieve; Lim, Kah-Leong; Bonni, Azad] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. [Konopka, Genevieve; Bonni, Azad] Harvard Univ, Sch Med, Dana Farber Canc Inst, Program Neurosci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Bromberg, Jacqueline F.; Frank, David A.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Mischel, Paul S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol & Med, Los Angeles, CA 90095 USA. RP Bonni, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, 44 Binney St, Boston, MA 02115 USA. EM azad_bonni@hms.harvard.edu RI Nutt, Catherine/K-8794-2012; de la Iglesia, Nuria/E-1420-2015 OI de la Iglesia, Nuria/0000-0002-1083-7715 FU NCI NIH HHS [R01 CA57683]; NINDS NIH HHS [NS047188, NS051255, NS41021, R01 NS041021, R01 NS041021-08, R01 NS047188, R01 NS047188-02, R01 NS051255, R01 NS051255-04] NR 37 TC 80 Z9 80 U1 0 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 4 PY 2008 VL 28 IS 23 BP 5870 EP 5878 DI 10.1523/JNEUROSCI.5385-07.2008 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 308QF UT WOS:000256404400001 PM 18524891 ER PT J AU Setlur, SR Mertz, KD Hoshida, Y Demichelis, F Lupien, M Perner, S Sboner, A Pawitan, Y Andren, O Johnson, LA Tang, J Adami, HO Calza, S Chinnaiyan, AM Rhodes, D Tomlins, S Fall, K Mucci, LA Kantoff, PW Stampfer, MJ Andersson, SO Varenhorst, E Johansson, JE Brown, M Golub, TR Rubin, MA AF Setlur, Sunita R. Mertz, Kirsten D. Hoshida, Yujin Demichelis, Francesca Lupien, Mathieu Perner, Sven Sboner, Andrea Pawitan, Yudi Andren, Ove Johnson, Laura A. Tang, Jeff Adami, Hans-Olov Calza, Stefano Chinnaiyan, Arul M. Rhodes, Daniel Tomlins, Scott Fall, Katja Mucci, Lorelei A. Kantoff, Philip W. Stampfer, Meir J. Andersson, Swen-Olof Varenhorst, Eberhard Johansson, Jan-Erik Brown, Myles Golub, Todd R. Rubin, Mark A. TI Estrogen-dependent signaling in a molecularly distinct subclass of aggressive prostate cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RECEPTOR-BETA; ER-BETA; EXPRESSION; SURVIVAL; TMPRSS2; FUSION; SWEDEN; CELLS; PROLIFERATION; TISSUES AB Background The majority of prostate cancers harbor gene fusions of the 5'-untranslated region of the androgen-regulated transmembrane protease serine 2 (TMPRSS2) promoter with erythroblast transformation-specific transcription factor family members. The common fusion between TMPRESS2 and v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) is associated with a more aggressive clinical phenotype, implying the existence of a distinct subclass of prostate cancer defined by this fusion. Methods We used complementary DNA-mediated annealing, selection, ligation, and extension to determine the expression profiles of 6144 transcriptionally informative genes in archived biopsy samples from 455 prostate cancer patients in the Swedish Watchful Waiting cohort (1987-1999) and the United States-based Physicians(') Health Study cohort (1983-2003). A gene expression signature for prostate cancers with the TMPRSS2-ERG fusion was determined using partitioning and classification models and used in computational functional analysis. Cell proliferation and TMPRSS2-ERG expression in androgen receptor-negative (NCI-H660) prostate cancer cells after treatment with vehicle or estrogenic compounds were assessed by viability assays and quantitative polymerase chain reaction, respectively. All statistical tests were two-sided. Results We identified an 87-gene expression signature that distinguishes TMPRSS2-ERG fusion prostate cancer as a discrete molecular entity (area under the curve = 0.80, 95% confidence interval [CI] = 0.792 to 0.81; P < .001). Computational analysis suggested that this fusion signature was associated with estrogen receptor (ER) signaling. Viability of NCI-H660 cells decreased after treatment with estrogen (viability normalized to day 0, estrogen vs vehicle at day 8, mean = 2.04 vs 3.40, difference = 1.36, 95% CI = 1.12 to 1.62) or ER beta agonist (ER beta agonist vs vehicle at day 8, mean = 1.86 vs 3.40, difference = 1.54, 95% CI = 1.39 to 1.69) but increased after ER alpha agonist treatment (ER alpha agonist vs vehicle at day 8, mean = 4.36 vs 3.40, difference = 0.96, 95% CI = 0.68 to 1.23). Similarly, expression of TMPRSS2-ERG decreased after ER beta agonist treatment (fold change over internal control, ER beta agonist vs vehicle at 24 hours, NCI-H660, mean = 0.57- vs 1.0-fold, difference = 0.43-fold, 95% CI = 0.29- to 0.57-fold) and increased after ER alpha agonist treatment (ER alpha agonist vs vehicle at 24 hours, mean = 5.63- vs 1.0-fold, difference = 4.63-fold, 95% CI = 4.34- to 4.92-fold). Conclusions TMPRSS2-ERG fusion prostate cancer is a distinct molecular subclass. TMPRSS2-ERG expression is regulated by a novel ER-dependent mechanism. C1 [Setlur, Sunita R.; Mertz, Kirsten D.; Demichelis, Francesca; Perner, Sven; Johnson, Laura A.; Tang, Jeff; Rubin, Mark A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Stampfer, Meir J.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Setlur, Sunita R.; Mertz, Kirsten D.; Demichelis, Francesca; Perner, Sven; Johnson, Laura A.; Kantoff, Philip W.; Stampfer, Meir J.; Rubin, Mark A.] Harvard Univ, Sch Med, Boston, MA USA. [Hoshida, Yujin; Golub, Todd R.; Rubin, Mark A.] MIT & Harvard, Canc Program, Broad Inst, Cambridge, MA USA. [Hoshida, Yujin; Lupien, Mathieu; Kantoff, Philip W.; Brown, Myles; Golub, Todd R.; Rubin, Mark A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Perner, Sven] Univ Hosp Ulm, Inst Pathol, Ulm, Germany. [Sboner, Andrea] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT USA. [Pawitan, Yudi; Adami, Hans-Olov; Calza, Stefano; Fall, Katja] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Andren, Ove; Andersson, Swen-Olof] Orebro Univ Hosp, Dept Urol, Orebro, Sweden. [Adami, Hans-Olov; Mucci, Lorelei A.; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Calza, Stefano] Univ Brescia, Dept Biomed Sci & Biotechnol, Brescia, Italy. [Chinnaiyan, Arul M.; Rhodes, Daniel; Tomlins, Scott] Univ Michigan, Dept Pathol, Sch Med, Ann Arbor, MI 48109 USA. [Varenhorst, Eberhard] Linkoping Univ Hosp, Dept Urol, S-58185 Linkoping, Sweden. RP Rubin, MA (reprint author), Weill Cornell Med Coll, Dept Pathol & Lab Med, 1300 York Ave,Rm C 410-A,Box 69, New York, NY 10021 USA. EM rubinma@med.cornell.edu RI Sboner, Andrea/C-6487-2008; Fall, Katja/A-9186-2012; Calza, Stefano/B-1915-2010; OI Sboner, Andrea/0000-0001-6915-3070; Calza, Stefano/0000-0003-4996-7995; Brown, Myles/0000-0002-8213-1658; Rubin, Mark/0000-0002-8321-9950; Demichelis, Francesca/0000-0002-8266-8631; Fall, Katja/0000-0002-3649-2639 FU NCI NIH HHS [P50 CA090381, P50 CA090381-10]; NIA NIH HHS [R01 AG021404-05, R01 AG021404, R01AG21404] NR 32 TC 178 Z9 184 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 4 PY 2008 VL 100 IS 11 BP 815 EP 825 DI 10.1093/jnci/djn150 PG 11 WC Oncology SC Oncology GA 310IU UT WOS:000256522900012 PM 18505969 ER PT J AU Cohen, T Colijn, C Finklea, B Wright, A Zignol, M Pym, A Murray, M AF Cohen, Ted Colijn, Caroline Finklea, Bryson Wright, Abigail Zignol, Matteo Pym, Alexander Murray, Megan TI Are Survey-Based Estimates of the Burden of Drug Resistant TB Too Low? Insight from a Simulation Study SO PLOS ONE LA English DT Article AB Background: The emergence of tuberculosis resistant to multiple first- and second-line antibiotics poses challenges to a global control strategy that relies on standard drug treatment regimens. Highly drug-resistant strains of Mycobacterium tuberculosis have been implicated in outbreaks and have been found throughout the world; a comprehensive understanding the magnitude of this threat requires an accurate assessment of the worldwide burden of resistance. Unfortunately, in many settings where resistance is emerging, laboratory capacity is limited and estimates of the burden of resistance are obtained by performing drug sensitivity testing on a sample of incident cases rather than through the use of routine surveillance. Methodology/Principal Findings: Using an individual-based dynamic tuberculosis model to simulate surveillance strategies for drug resistance, we found that current surveys may underestimate the total burden of resistant tuberculosis because cases of acquired resistance are undercounted and resistance among prevalent cases is not assessed. We explored how this bias is affected by the maturity of the epidemic and by the introduction of interventions that target the emergence and spread of resistant tuberculosis. Conclusions: Estimates of drug resistant tuberculosis based on samples of incident cases should be viewed as a lower bound of the total burden of resistance. C1 [Cohen, Ted; Murray, Megan] Brigham & Womens Hosp, Div Social Med & Hlth Inequal, Boston, MA 02115 USA. [Cohen, Ted; Colijn, Caroline; Finklea, Bryson; Murray, Megan] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Wright, Abigail; Zignol, Matteo] WHO, STOP TB Dept, Geneva, Switzerland. [Pym, Alexander] S African MRC, Clin & Biomed TB Res Unit, Durban, South Africa. [Murray, Megan] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA USA. RP Cohen, T (reprint author), Brigham & Womens Hosp, Div Social Med & Hlth Inequal, 75 Francis St, Boston, MA 02115 USA. EM tcohen@hsph.harvard.edu RI Cohen, Ted/G-8101-2011; OI Pym, Alexander/0000-0002-6260-8180 FU NIH [5K08AI055985-05] FX TC is supported by an NIH grant (5K08AI055985-05). The funding source had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 36 TC 11 Z9 11 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 4 PY 2008 VL 3 IS 6 AR e2363 DI 10.1371/journal.pone.0002363 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 396TO UT WOS:000262614300050 PM 18523659 ER PT J AU Li, HJ Smolen, GA Beers, LF Xia, L Gerald, W Wang, J Haber, DA Lee, SB AF Li, Hongjie Smolen, Gromoslaw A. Beers, Lisa F. Xia, Li Gerald, William Wang, Joanne Haber, Daniel A. Lee, Sean Bong TI Adenosine Transporter ENT4 Is a Direct Target of EWS/WT1 Translocation Product and Is Highly Expressed in Desmoplastic Small Round Cell Tumor SO PLOS ONE LA English DT Article AB Background: Desmoplastic Small Round Cell Tumor (DSRCT) is a highly aggressive malignancy that affects mainly adolescents and young adults. A defining characteristic of DSRCT is a specific chromosomal translocation, t(11;22)(p13;q12), that fuses EWS with WT1, leading to a production of two isoforms of chimeric transcription factor, EWS/WT1(-KTS) and EWS/WT1(+KTS). The chimeric proteins are thought to play critical roles in various stages of oncogenesis through aberrant transcription of different genes, but only a few of these genes have been identified. Methodology/Principal Findings: We report the identification of a new target of EWS/WT1, ENT4 (equilibrative nucleoside transporter 4) which encodes a pH-dependent adenosine transporter. ENT4 is transcriptionally activated by both isoforms of EWS/WT1 as evidenced by promoter-reporter and chromatin immunoprecipitation (ChIP) analyses. Furthermore, ENT4 is highly and specifically expressed in primary tumors of DSRCT as well as in a DSRCT cell line, JN-DSRCT-1. Treatment of JN-DSRCT1 cells with adenosine analogs, such as 2-chloro-2'-deoxyadenosine (2-CdA), resulted in an increased cytotoxic response in dose- and pH-dependent manner. Conclusions/Significance: Our detailed analyses of a novel target of EWS/WT1 in DSRCT reveal an insight into the oncogenic mechanism of EWS-fusion chromosomal translocation gene products and provide a new marker for DSRCT. Furthermore, identification of ENT4 as a highly expressed transcript in DSRCT may represent an attractive pathway for targeting chemotherapeutic drugs into DSRCT. C1 [Li, Hongjie; Beers, Lisa F.; Lee, Sean Bong] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20824 USA. [Smolen, Gromoslaw A.; Haber, Daniel A.] Massachusetts Gen Hosp Canc Ctr, Harvard Med Sch, Charlestown, MA USA. [Xia, Li; Wang, Joanne] Univ Washington, Dept Pharmaceut, Seattle, WA USA. [Gerald, William] Memorial Sloan Kettering Canc Ctr, Dept Pathol, New York, NY USA. RP Li, HJ (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20824 USA. EM seanL@intra.niddk.nih.gov FU Intramural Research Program of the NIH, NIDDK FX This research was supported by the Intramural Research Program of the NIH, NIDDK (S.B.L.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript NR 45 TC 21 Z9 21 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 4 PY 2008 VL 3 IS 6 AR e2353 DI 10.1371/journal.pone.0002353 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 396TO UT WOS:000262614300041 PM 18523561 ER PT J AU Ngumbela, KC Ryan, KP Sivamurthy, R Brockman, MA Gandhi, RT Bhardwaj, N Kavanagh, DG AF Ngumbela, Kholiswa C. Ryan, Kieran P. Sivamurthy, Rohini Brockman, Mark A. Gandhi, Rajesh T. Bhardwaj, Nina Kavanagh, Daniel G. TI Quantitative Effect of Suboptimal Codon Usage on Translational Efficiency of mRNA Encoding HIV-1 gag in Intact T Cells SO PLOS ONE LA English DT Article AB Background: The sequences of wild-isolate strains of Human Immunodeficiency Virus-1 (HIV-1) are characterized by low GC content and suboptimal codon usage. Codon optimization of DNA vectors can enhance protein expression both by enhancing translational efficiency, and by altering RNA stability and export. Although gag codon optimization is widely used in DNA vectors and experimental vaccines, the actual effect of altered codon usage on gag translational efficiency has not been quantified. Methodology and Principal Findings: To quantify translational efficiency of gag mRNA in live T cells, we transfected Jurkat cells with increasing doses of capped, polyadenylated synthetic mRNA corresponding to wildtype or codon-optimized gag sequences, measured Gag production by quantitative ELISA and flow cytometry, and estimated the translational efficiency of each transcript as mu g of Gag antigen produced per mg of input mRNA. We found that codon optimization yielded a small increase in gag translational efficiency (approximately 1.6 fold). In contrast when cells were transfected with DNA vectors requiring nuclear transcription and processing of gag mRNA, codon optimization resulted in a very large enhancement of Gag production. Conclusions: We conclude that suboptimal codon usage by HIV-1 results in only a slight loss of gag translational efficiency per se, with the vast majority of enhancement in protein expression from DNA vectors due to altered processing and export of nuclear RNA. C1 [Ngumbela, Kholiswa C.] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. [Ryan, Kieran P.; Sivamurthy, Rohini; Brockman, Mark A.; Gandhi, Rajesh T.; Bhardwaj, Nina; Kavanagh, Daniel G.] Harvard Med Sch, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Div AIDS, Boston, MA USA. [Bhardwaj, Nina] NYU, Sch Med, New York, NY USA. RP Ngumbela, KC (reprint author), Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. EM dkavanagh@partners.org OI Brockman, Mark/0000-0001-6432-1426 FU Emerald Foundation, NY; NIH [R01AI0571278-03, R01AI066992]; [R37AI044628-08]; [F32AI058457] FX This research was supported by the Emerald Foundation, NY and NIH grants R37AI044628-08 (NB), R01AI0571278-03 (NB), and by R01AI066992 (RTG) and F32AI058457 (DGK). The funders did not particiapate in collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript. NR 22 TC 22 Z9 22 U1 0 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 JUN 4 PY 2008 VL 3 IS 6 AR e2356 DI 10.1371/journal.pone.0002356 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 396TO UT WOS:000262614300043 PM 18523584 ER PT J AU Sullivan, G Blevins, D Kauth, MR AF Sullivan, Greer Blevins, Dean Kauth, Michael R. TI Translating clinical training into practice in complex mental health systems: Toward opening the 'Black Box' of implementation SO IMPLEMENTATION SCIENCE LA English DT Article ID FACILITATION AB Background: Implementing clinical training in a complex health care system is challenging. This report describes two successive trainings programs in one Veterans Affairs healthcare network and the lessons we drew from their success and failures. The first training experience led us to appreciate the value of careful implementation planning while the second suggested that use of an external facilitator might be an especially effective implementation component. We also describe a third training intervention in which we expect to more rigorously test our hypothesis regarding the value of external facilitation. Results: Our experiences appear to be consonant with the implementation model proposed by Fixsen. In this paper we offer a modified version of the Fixsen model with separate components related to training and implementation. Conclusion: This report further reinforces what others have noted, namely that educational interventions intended to change clinical practice should employ a multilevel approach if patients are to truly benefit from new skills gained by clinicians. We utilize an implementation research model to illustrate how the aims of the second intervention were realized and sustained over the 12-month follow-up period, and to suggest directions for future implementation research. The present report attests to the validity of, and contributes to, the emerging literature on implementation research. C1 [Sullivan, Greer; Blevins, Dean; Kauth, Michael R.] Cent Arkansas Vet Healthcare Syst, SC MIRECC, N Little Rock, AR USA. [Sullivan, Greer; Blevins, Dean] Cent Arkansas Vet Healthcare Syst, HSR&D, CeMHOR, N Little Rock, AR USA. [Sullivan, Greer; Blevins, Dean] Univ Arkansas Med Sci, Dept Psychiat, Div Hlth Serv Res, Little Rock, AR 72205 USA. [Kauth, Michael R.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Kauth, Michael R.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP Sullivan, G (reprint author), Cent Arkansas Vet Healthcare Syst, SC MIRECC, N Little Rock, AR USA. EM gsullivan@uams.edu; blevinsdean@uams.edu; michael.kauth@va.gov FU VA South Central MIRECC FX This work was supported by the VA South Central MIRECC. The VA played no direct role in decisions related to the study design, data analysis or interpretation, manuscript preparation or decision to submit this paper. The authors thank Snigdha Mukherjee, Kathy Henderson, Joann Kirchner, Marisue Cody, Debra Hollis, Becky Lancaster, Donna Lipin, and Butch Fort for their assistance in the design of the programs and the evaluation and in securing the data reported in this manuscript. The authors thank Lisa Martone for her assistance in coordinating the trainers in one intervention. We also thank the University of Arkansas for Medical Sciences Office of Grants and Scientific Publications and Susan Moore and Carrie Edlund for their editorial assistance. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the U. S. Department of Veterans Affairs. NR 18 TC 17 Z9 17 U1 1 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 JUN 3 PY 2008 VL 3 AR 33 DI 10.1186/1748-5908-3-33 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 432RJ UT WOS:000265151500001 PM 18522742 ER PT J AU Henkes, LE Sullivan, BT Lynch, MP Kolesnick, R Arsenault, D Pudert, M Davis, JS Rueda, BR AF Henkes, Luiz E. Sullivan, Brian T. Lynch, Maureen P. Kolesnick, Richard Arsenault, Danielle Pudert, Mark Davis, John S. Rueda, Bo R. TI Acid sphingomyelinase involvement in tumor necrosis factor alpha-regulated vascular and steroid disruption during luteolysis in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE corpus luteum; cytokines; endothelial cells; ovary; progesterone ID BOVINE CORPUS-LUTEUM; MONOCYTE CHEMOATTRACTANT PROTEIN-1; CELL SYNTHETIC CAPACITY; ENDOTHELIAL-CELLS; TNF-ALPHA; INTERFERON-GAMMA; KNOCKOUT MICE; LIFE-SPAN; APOPTOSIS; CERAMIDE AB TNF is well known for its role in inflammation, including direct effects on the vasculature. TNF also is implicated in the regulation of reproduction by its actions to affect ovarian steroidogenic cells and to induce apoptosis of corpus luteum (CL)-derived endothelial cells in vitro. We hypothesized that the disruption of TNF signaling would postpone the regression of the highly vascularized CL in vivo, and this effect could be replicated in mutant mouse models lacking TNF receptor (TNFRI(-/-)) and/or a critical enzyme of TNF signaling, acid sphingomyelinase (ASMase(-/-)). In the current study, the treatment of pseudopregnant mice with the luteolytic mediator prostaglandin F2-alpha (PGF) significantly increased TNF in the ovaries when compared with saline-treated controls. Treatment with PGF also reduced serum progesterone (P4) concentrations and caused involution of the CL. However, pretreatment of pseudopregnant mice with Etanercept (ETA), a TNF-neutralizing antibody, inhibited the PGF-induced decrease in P4 and delayed luteal regression. A similar outcome was evident in pseudopregnant TNFRI(-/-) animals. Treatment of luteal microvascular endothelial cells (MVECs) with TNF provoked a significant increase in ASMase activity when compared with the corresponding controls. Furthermore, TNF-induced MVEC death was inhibited in the ASMase(-/-) mice. The ASMase(-/-) mice displayed no obvious evidence of luteal regression 24 h after treatment with PGF and were resistant to the PGF-induced decrease in P4. Together these data provide evidence that TNF plays an active role in luteolysis. Further studies are required to determine the deleterious effects of anti-inflammatory agents on basic ovarian processes. C1 [Henkes, Luiz E.; Sullivan, Brian T.; Lynch, Maureen P.; Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Henkes, Luiz E.; Lynch, Maureen P.; Pudert, Mark; Rueda, Bo R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Davis, John S.] Univ Nebraska, Med Ctr, Olson Ctr Womens Hlth, VA Med Ctr, Omaha, NE 68198 USA. [Kolesnick, Richard] Mem Sloan Kettering Canc Ctr, Lab Signal Transduct, New York, NY 10021 USA. [Arsenault, Danielle; Pudert, Mark] Childrens Hosp, Dept Surg, Boston, MA 02115 USA. [Arsenault, Danielle; Pudert, Mark] Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. RP Rueda, BR (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. EM brueda@partners.org FU NCI NIH HHS [R01 CA085704, CA085704]; NICHD NIH HHS [HD35934, R01 HD035934, HD38813, R01 HD038813] NR 56 TC 16 Z9 17 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 3 PY 2008 VL 105 IS 22 BP 7670 EP 7675 DI 10.1073/pnas.0712260105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 312DF UT WOS:000256648600010 PM 18505843 ER PT J AU Nosek, K Dennis, K Andrus, BM Ahmadiyeh, N Baum, AE Woods, LCS Redei, EE AF Nosek, Katarzyna Dennis, Kristen Andrus, Brian M. Ahmadiyeh, Nasim Baum, Amber E. Woods, Leah C. Solberg Redei, Eva E. TI Context and strain-dependent behavioral response to stress SO BEHAVIORAL AND BRAIN FUNCTIONS LA English DT Article ID ELEVATED PLUS-MAZE; WISTAR-KYOTO WKY; INBRED RAT STRAINS; OPEN-FIELD; PLASMA-CORTICOSTERONE; GENETIC-ANALYSIS; ANXIETY; MICE; CHLORDIAZEPOXIDE; EMOTIONALITY AB Background: This study posed the question whether strain differences in stress-reactivity lead to differential behavioral responses in two different tests of anxiety. Strain differences in anxiety-measures are known, but strain differences in the behavioral responses to acute prior stress are not well characterized. Methods: We studied male Fisher 344 (F344) and Wistar Kyoto (WKY) rats basally and immediately after one hour restraint stress. To distinguish between the effects of novelty and prior stress, we also investigated behavior after repeated exposure to the test chamber. Two behavioral tests were explored; the elevated plus maze (EPM) and the open field (OFT), both of which are thought to measure activity, exploration and anxiety-like behaviors. Additionally, rearing, a voluntary behavior, and grooming, a relatively automatic, stress-responsive stereotyped behavior were measured in both tests. Results: Prior exposure to the test environment increased anxiety-related measures regardless of prior stress, reflecting context-dependent learning process in both tests and strains. Activity decreased in response to repeated testing in both tests and both strains, but prior stress decreased activity only in the OFT which was reversed by repeated testing. Prior stress decreased anxiety-related measures in the EPM, only in F344s, while in the OFT, stress led to increased freezing mainly in WKYs. Conclusion: Data suggest that differences in stressfulness of these tests predict the behavior of the two strains of animals according to their stress-reactivity and coping style, but that repeated testing can overcome some of these differences. C1 [Nosek, Katarzyna; Dennis, Kristen; Andrus, Brian M.; Ahmadiyeh, Nasim; Baum, Amber E.; Woods, Leah C. Solberg; Redei, Eva E.] Northwestern Univ, Feinberg Sch Med, Asher Ctr, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Ahmadiyeh, Nasim] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ahmadiyeh, Nasim] Dana Farber Canc Inst, Boston, MA 02115 USA. [Baum, Amber E.] NIH, Bethesda, MD 20892 USA. [Woods, Leah C. Solberg] Med Coll Wisconsin, Milwaukee, WI 53226 USA. RP Redei, EE (reprint author), Northwestern Univ, Feinberg Sch Med, Asher Ctr, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. EM kmn@uchicago.edu; k-dennis@northwestern.edu; b-andrus@northwestern.edu; nahmadiyeh@partners.org; bauma@mail.nih.gov; lsolberg@mcw.edu; e-redei@northwestern.edu FU NIMH NIH HHS [R21 MH077234] NR 49 TC 29 Z9 30 U1 2 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1744-9081 J9 BEHAV BRAIN FUNCT JI Behav. Brain Funct. PD JUN 2 PY 2008 VL 4 AR 23 DI 10.1186/1744-9081-4-23 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 314SB UT WOS:000256828000001 PM 18518967 ER PT J AU Tsifansky, MD Yeo, Y Evgenov, OV Bellas, E Benjamin, J Kohane, DS AF Tsifansky, Michael D. Yeo, Yoon Evgenov, Oleg V. Bellas, Evangelia Benjamin, John Kohane, Daniel S. TI Microparticles for inhalational delivery of antipseudomonal antibiotics SO AAPS JOURNAL LA English DT Article DE co-encapsulation; cystic fibrosis; dry-powder; inhalational delivery of antibiotics; microparticles ID RESISTANT STAPHYLOCOCCUS-AUREUS; DURATION LOCAL-ANESTHESIA; PROTEIN-SUGAR PARTICLES; SCIATIC-NERVE BLOCKADE; CYSTIC-FIBROSIS; PSEUDOMONAS-AERUGINOSA; AEROSOLIZED VANCOMYCIN; INHALED TOBRAMYCIN; DRY POWDER; CIPROFLOXACIN AB Chronic pseudomonal bronchopulmonary infections in cystic fibrosis patients are frequently controlled with inhaled antibiotics. Dry-powder inhalable antibiotics are an attractive alternative to nebulized medications. We produced and evaluated microparticles composed of dipalmitoylphosphatidylcholine, albumin, and lactose as a model system for intrapulmonary delivery of ceftazidime, ciprofloxacin, and several combinations of the two, none of which is presently available for inhalation. Microparticles containing one or both antibiotics were prepared by spray-drying. Their Anderson cascade impactor deposition profiles showed 10-30% fine particle fractions of the nominal dose. Microparticles containing varying amounts of each antibiotic showed statistically different deposition profiles. Aerodynamics and deposition of microparticles co-encapsulating both antibiotics were similar to those of single-drug microparticles with the same proportion of ciprofloxacin alone. The antipseudomonal activities of microparticles co-encapsulating half of the 50% effective concentration (EC50) of both ceftazidime and ciprofloxacin (5 mg of particles containing 5% ceftazidime and 10% ciprofloxacin) were at least additive compared to particles containing the EC50 of each antibiotic separately (5 mg of particles containing 10% ceftazidime or 5 mg of particles containing 20% ciprofloxacin). Co-encapsulation of the antibiotics in microparticles ensures co-deposition at desired ratios, improves the particles' aerodynamics and fine particle fraction, as compared to microparticles with equivalent amounts of ceftazidime alone, and achieves additive antipseudomonal activity. C1 [Kohane, Daniel S.] Harvard Univ, Sch Med, Childrens Hosp, Lab Biomat & Drug Delivery,Dept Anesthesiol, Boston, MA 02115 USA. [Tsifansky, Michael D.] Lutheran Gen Childrens Hosp, Dept Pediat, Div Pediat Intens Care Med, Park Ridge, IL 60068 USA. [Yeo, Yoon] Purdue Univ, W Lafayette, IN 47907 USA. [Evgenov, Oleg V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care Med, Boston, MA 02114 USA. [Bellas, Evangelia] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Benjamin, John] Shriners Hosp Children, Boston, MA 02114 USA. RP Kohane, DS (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Lab Biomat & Drug Delivery,Dept Anesthesiol, 300 Longwood Ave, Boston, MA 02115 USA. EM daniel.kohane@childrens.harvard.edu FU Cystic Fibrosis Foundation Research; Clinical Fellowship [TSIFAN02B0]; NIH [GM073626] FX We would like to express our gratitude to Henry Dorkin, MD for helpful insights. This work was supported by Cystic Fibrosis Foundation Research and Clinical Fellowship grant (TSIFAN02B0) to MDT and NIH GM073626 to DSK. NR 37 TC 22 Z9 22 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J PD JUN PY 2008 VL 10 IS 2 BP 254 EP 260 DI 10.1208/s12248-008-9033-8 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 347IK UT WOS:000259133600003 PM 18454321 ER PT J AU Schrader, C Barsan, WG Gordon, JA Hollander, J King, BR Lewis, R Richardson, LD Sklar, D AF Schrader, Chet Barsan, William G. Gordon, James A. Hollander, Judd King, Brent R. Lewis, Roger Richardson, Lynne D. Sklar, David TI Scholarship in emergency medicine in an environment of increasing clinical demand: Proceedings from the 2007 Association of American Medical Colleges annual meeting SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE scholarship; emergency medicine ID PROGRAMS AB Academic emergency medicine can benefit by broadening the way in which scholarship is defined to include teaching, integration of knowledge, application of knowledge to practical clinical problems and as discovery of new knowledge. A broad view of scholarship will help foster innovation and may lead to new areas of expertise. The creation of a scholarly environment in emergency medicine faces the continued challenge of an increasing clinical demand. The solution to this dilemma will likely require a mix of clinical staff physicians and academic faculty who are appreciated, nurtured and rewarded in different ways, for the unique contributions they make to the overall success of the academic program. C1 [Schrader, Chet] Washington Univ, Dept Emergency Med, St Louis, MO 63130 USA. [Barsan, William G.] Univ Michigan, Ann Arbor, MI 48109 USA. [Gordon, James A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hollander, Judd] Univ Penn, Philadelphia, PA 19104 USA. [King, Brent R.] Texas Med Ctr, Houston, TX USA. [Lewis, Roger] Univ Calif Los Angeles, Harbor Med Ctr, Torrance, CA 90509 USA. [Richardson, Lynne D.] Mt Sinai Sch Med, New York, NY USA. [Sklar, David] Univ New Mexico, Albuquerque, NM 87131 USA. RP Sklar, D (reprint author), Washington Univ, Dept Emergency Med, St Louis, MO 63130 USA. EM dsklar@salud.unm.edu OI Hollander, Judd/0000-0002-1318-2785 NR 10 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD JUN PY 2008 VL 15 IS 6 BP 567 EP 572 DI 10.1111/j.1553-2712.2008.00118.x PG 6 WC Emergency Medicine SC Emergency Medicine GA 306FM UT WOS:000256233700013 PM 18616446 ER PT J AU Ginde, AA Weiner, SG Pallin, DJ Camargo, CA AF Ginde, Adit A. Weiner, Scott G. Pallin, Daniel J. Camargo, Carlos A., Jr. TI Multicenter study of limited health literacy in emergency department patients SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE literacy; disparities; emergency medicine; public health; communication AB Objectives: The objective was to evaluate the prevalence of limited health literacy and its association with sociodemographic variables in emergency department (ED) patients. Methods: This was a cross-sectional survey in three Boston EDs. The authors enrolled consecutive adult patients during two 24-hour periods at each site. They measured health literacy by the short version of the Test of Functional Health Literacy in Adults (S-TOFHLA). Using multivariate logistic regression, the authors evaluated associations between sociodemographic variables and limited health literacy, as classified by S-TOFHLA scores. Results: The authors enrolled 300 patients (77% of eligible). Overall, 75 (25%; 95% confidence interval [CI] = 20% to 30%) of participants had limited health literacy. Limited health literacy was independently associated with older age (compared to 18-44 years, odds ratio [OR] 4.3 [95% CI = 2.0 to 9.2] for 45-64 years and OR 3.4 [95% CI = 1.4 to 8.5] for >= 65 years), less education (compared to high school graduates, OR 2.7 [95% CI = 1.1 to 7.3] for some high school or lower and OR 0.43 [95% CI = 0.21 to 0.88] for some college or higher), and lower income (OR 2.8 [95% CI = 1.2 to 6.6] for <=$40,000 compared to >$40,000). Although ethnicity, race, and language were associated with limited health literacy in unadjusted analyses, the associations were not significant on multivariate analysis. Conclusions: In this sample, one-quarter of ED patients would be expected to have difficulty understanding health materials and following prescribed treatment regimens. Advanced age and low socioeconomic status were independently associated with limited health literacy. The ability of a significant subgroup of ED patients to understand health information, especially during illness or injury, requires further study. C1 [Ginde, Adit A.] Univ Colorado Denver, Sch Med, Dept Emergency Med, Aurora, CO USA. [Ginde, Adit A.] Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. [Weiner, Scott G.] Tufts Univ New England Med Ctr, Dept Emergency Med, Boston, MA USA. [Pallin, Daniel J.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Ginde, AA (reprint author), Univ Colorado Denver, Sch Med, Dept Emergency Med, Aurora, CO USA. EM adit.ginde@uchsc.edu RI Pallin, Daniel/H-6382-2013; Siry, Bonnie/D-7189-2017 OI Pallin, Daniel/0000-0002-8517-9702; NR 10 TC 27 Z9 27 U1 2 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD JUN PY 2008 VL 15 IS 6 BP 577 EP 580 DI 10.1111/j.1553-2712.2008.00116.x PG 4 WC Emergency Medicine SC Emergency Medicine GA 306FM UT WOS:000256233700015 PM 18616448 ER PT J AU Schroeder, T Melo, MFV Musch, G Harris, RS Venegas, JG Winkler, T AF Schroeder, Tobias Melo, Marcos F. Vidal Musch, Guido Harris, R. Scott Venegas, Jose G. Winkler, Tilo TI Modeling pulmonary kinetics of 2-deoxy-2-[F-18]fluoro-D-glucose during acute lung injury SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT International Workshop on Functional Lung Imaging CY 2006 CL Univ Penn, Philadelphia, PA HO Univ Penn DE radionuclide imaging; F-18-FDG; positron emission tomography ID POSITRON-EMISSION-TOMOGRAPHY; BRAIN TRANSFER CONSTANTS; TIME UPTAKE DATA; REGIONAL VENTILATION; GRAPHICAL EVALUATION; METABOLIC-ACTIVITY; SMOKE INHALATION; F-18-FDG UPTAKE; GLUCOSE; PET AB Rationale and Objectives. Dynamic positron emission tomographic imaging of the radiotracer 2-deoxy-2-[F-18]fluoro-D-glucose (F-18-FDG) is increasingly used to assess metabolic activity of lung inflammatory cells. To analyze the kinetics of F-18-FDG in brain and tumor tissues, the Sokoloff model has been typically used. In the lungs, however, a high blood-to-parenchymal volume ratio and F-18-FDG distribution in edematous injured tissue could require a modified model to properly describe F-18-FDG kinetics. Materials and Methods. We developed and validated a new model of lung F-18-FDG kinetics that includes an extravascular/noncellular compartment in addition to blood and F-18-FDG precursor pools for phosphorylation. Parameters obtained from this model were compared with those obtained using the Sokoloff model. We analyzed dynamic PET data from 15 sheep with smoke or ventilator-induced lung injury. Results. In the majority of injured lungs, the new model provided better fit to the data. than the Sokoloff model. Rate of pulmonary F-18-FDG net uptake and distribution volume in the precursor pool for phosphorylation correlated between the two models (R-2 = 0.98, 0.78), but were overestimated with the Sokoloff model by 17% (P <.05) and 16% (P <.0005) compared to the new one. The range of the extravascular/noncellular F-18-FDG distribution Volumes was up to 13% and 49% of lung tissue volume in smoke- and ventilator-induced lung injury, respectively. Conclusion. The lung-specific model predicted F-18-FDG kinetics during acute lung injury more accurately than the Sokoloff model and may provide new insights in the pathophysiology of lung injury. C1 [Schroeder, Tobias; Melo, Marcos F. Vidal; Musch, Guido; Venegas, Jose G.; Winkler, Tilo] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Harris, R. Scott] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Schroeder, T (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM tobias.schroeder@vgpet.mgh.harvard.edu RI Winkler, Tilo/B-5337-2009; OI Winkler, Tilo/0000-0002-7276-5550; Schroeder, Tobias/0000-0002-4439-8060 FU NHLBI NIH HHS [R01 HL068011, HL-056879, R01 HL086827, R01-HL-086827, R01 HL086827-02, HL-068011, K08 HL076464, R01 HL068011-05A2, K08 HL076464-03, HL-076464] NR 36 TC 30 Z9 30 U1 1 U2 2 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 JUN PY 2008 VL 15 IS 6 BP 763 EP 775 DI 10.1016/j.acra.2007.12.016 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 306RW UT WOS:000256266500010 PM 18486012 ER PT J AU Suter, MJ Reinhardt, JM McLennan, G AF Suter, Melissa J. Reinhardt, Joseph M. McLennan, Geoffrey TI Integrated CT/bronchoscopy in the central airways: Preliminary results SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT International Workshop on Functional Lung Imaging CY 2006 CL Univ Penn, Philadelphia, PA HO Univ Penn DE eidomics; digital bronchoscopy; computed tomography; virtual bronchoscopy; fusion of 2D and 3D medical image datasets ID COMPUTED-TOMOGRAPHY; LUNG-CANCER; FLUORESCENCE BRONCHOSCOPY; IN-VIVO; IMAGES; MICROSCOPY; CT AB Rationale and Objectives. Many imaging modalities and methodologies exist for evaluating the pulmonary airways. Individually, each modality provides insight to the state of the airways; however, alone they do not necessarily provide a comprehensive description. The goal of this work is to integrate complementary medical imaging datasets to form a synergistic description of the airways. Materials and Methods. Two digital bronchoscopic techniques were used to evaluate the pulmonary mucosa. A digital color bronchoscopic system was used to detect mucosal color alterations, and a fluorescence detection system was used to assess the microvasculature of the bronchial mucosa. Study participants were also imaged with a multidetector row computed tomographic (MDCT) scanner. Virtual bronchoscopic and image registration techniques were exploited to combine three-dimensional surface renderings, extracted from the MDCT data, together with the two-dimensional digital bronchoscopic images. Validation of the fusion process was performed on a rubber phantom of an adult airway with 4 embedded metal beads. Results. The fusion of the MDCT extracted airway tree and the digital bronchoscopic datasets were presented for three study participants. In addition, the detected accuracy of the registration method to reliably align the MDCT and bronchoscopic image datasets was determined to be 1.98 mm in the phantom airway model. Conclusion. We have demonstrated that merging of three distinct digital datasets to provide a single synergistic description of the air-ways is possible. This is a pilot project in the field of eidomics, the process of combining digital image datasets and image-based processes together. We anticipate that in the future eidomics will provide a universal and predictive imaging language that will change health care delivery. C1 [McLennan, Geoffrey] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. [McLennan, Geoffrey] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Radiol, Iowa City, IA 52242 USA. [Reinhardt, Joseph M.; McLennan, Geoffrey] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Biomed Engn, Iowa City, IA 52242 USA. [Suter, Melissa J.] Harvard Univ, Sch Med, Boston, MA USA. [Suter, Melissa J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP McLennan, G (reprint author), Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Internal Med, 200 Hawkins Dr,C325-GH, Iowa City, IA 52242 USA. EM Geoffrey-mclennan@uiowa.edu FU NCI NIH HHS [CA094310, R21 CA094310-02, R21 CA094310] NR 29 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JUN PY 2008 VL 15 IS 6 BP 786 EP 798 DI 10.1016/j.acra.2008.03.001 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 306RW UT WOS:000256266500012 PM 18486014 ER PT J AU Denmark, DL Buck, KJ AF Denmark, D. L. Buck, K. J. TI Identification of potential candidate genes and testing for a role in susceptibility to ethanol dependence and associated withdrawal SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism/International-Society-for-Biomedical-Rese arch-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Portland Alcohol Res Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Portland Alcohol Res Ctr, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 11A EP 11A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200004 ER PT J AU Kozell, LB Milner, LC Wickman, K Buck, KJ AF Kozell, L. B. Milner, L. C. Wickman, K. Buck, K. J. TI Delineation of a role for KIR3.3 (GIRK3) in sedative-hypnotic drug physiological dependence using a novel KCNJ9 null mutant mouse SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland Alcohol Res Cntr, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. Univ Minnesota, Dept Pharmacol, Minneapolis, MN 55455 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 12A EP 12A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200008 ER PT J AU Buck, KJ AF Buck, K. J. TI QTG identification for alcohol physiological dependence and associated withdrawal in mice SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Buck, K. J.] Oregon Hlth & Sci Univ, Portland Alcohol Res Ctr, Portland, OR 97239 USA. [Buck, K. J.] Portland VA Med Ctr, Portland, OR 97239 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 13A EP 13A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200010 ER PT J AU Lieber, CS Leo, MA Wang, X DeCarli, LM AF Lieber, C. S. Leo, M. A. Wang, X. DeCarli, L. M. TI Chronic alcohol consumption interferes with gene regulators of mitochondrial biogenesis in rats SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 James J Peters VA Med Ctr, Sect Liver Dis & Nutr, Bronx, NY 10468 USA. Mt Sinai Sch Med, Bronx, NY 10468 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 41A EP 41A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200124 ER PT J AU Marinkovic, K AF Marinkovic, K. TI Effects of alcohol on the neural dynamics of cognitive control SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Marinkovic, K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging,Radiol Dept, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 51A EP 51A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200164 ER PT J AU Meyerhoff, DJ Gazdzinski, S Yeh, PH Durazzo, TC AF Meyerhoff, D. J. Gazdzinski, S. Yeh, P. -H. Durazzo, T. C. TI Microstructural abnormalities in alcoholics are related to cognitive test performance and recover in non-smoking alcoholics during abstinence SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Meyerhoff, D. J.; Gazdzinski, S.; Yeh, P. -H.; Durazzo, T. C.] Univ Calif San Francisco, San Francisco VA Med Ctr, CIND, San Francisco, CA 94121 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 101A EP 101A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200363 ER PT J AU Durazzo, TC Gazdzinski, S Meyerhoff, DJ AF Durazzo, T. C. Gazdzinski, S. Meyerhoff, D. J. TI Magnetic resonance derived and neuropsychological predictors of relapse in treatment seeking alcoholics SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Durazzo, T. C.; Gazdzinski, S.; Meyerhoff, D. J.] Univ Calif San Francisco, San Francisco VA Med Ctr, Ctr Neuroimaging Neurodegenerat Dis, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 103A EP 103A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200370 ER PT J AU LoCastro, JS Larson, M Amodeo, M Muroff, J Gerstenberger, E AF LoCastro, J. S. Larson, M. Amodeo, M. Muroff, J. Gerstenberger, E. TI Web-delivered CBT training and dissemination for community based counselors: The TEACH-CBT project SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 New England Res Inst, Watertown, MA 02172 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 140A EP 140A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200519 ER PT J AU Chen, G Kozell, LB Hitzemann, R Buck, KJ AF Chen, Gang Kozell, Laura B. Hitzemann, Robert Buck, Kari J. TI Involvement of the limbic basal ganglia in ethanol withdrawaly SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Portland Alcohol Res Ctr, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 146A EP 146A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200544 ER PT J AU Durazzo, TC Rothlind, JC Gazdzinski, S Mon, A Meyerhoff, DJ AF Durazzo, T. C. Rothlind, J. C. Gazdzinski, S. Mon, A. Meyerhoff, D. J. TI Neurocognition in short-term abstinent treatment-seeking alcoholics: The influence of common comorbidities and sociodemograhic factors SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Durazzo, T. C.; Rothlind, J. C.; Gazdzinski, S.; Mon, A.; Meyerhoff, D. J.] Univ Calif San Francisco, San Francisco VA Med Ctr, Ctr Neuroimaging Neurodegenerat Dis, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 175A EP 175A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200658 ER PT J AU Leontieva, L Dimmock, JA Carey, KB Ploutz-Snyder, RJ Cavallerano, M DeRycke, SB Meszaros, Z Batki, SL AF Leontieva, L. Dimmock, J. A. Carey, K. B. Ploutz-Snyder, R. J. Cavallerano, M. DeRycke, S. B. Meszaros, Z. Batki, S. L. TI Monitored naltrexone treatment of alcohol dependence in schizophrenia: Patient and provider attitudes SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. UCSF, Dept Psychiat, San Francisco, CA USA. VA Ctr Integrated Healthcare, Syracuse, NY USA. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 248A EP 248A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200950 ER PT J AU Mckay, JR Lynch, KG Van Horn, D Ward, K Oslin, D AF McKay, J. R. Lynch, K. G. Van Horn, D. Ward, K. Oslin, D. TI Effectiveness of extended telephone continuing care SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 249A EP 249A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200956 ER PT J AU Prause, N O'Farrell, TJ AF Prause, N. O'Farrell, T. J. TI Sexual satisfaction and sexual functioning over time in male alcoholics engaged in couples' alcoholism treatment SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 Idaho State Univ, Dept Psychol, Pocatello, ID 83209 USA. Harvard Univ, Sch Med, ID & Families & Addict Program, Brockton, MA 02401 USA. VA Boston Healthcare System, Brockton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 251A EP 251A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200961 ER PT J AU Ostacher, MJ Nierenberg, AA Ametrano, RM Bhagat, SM Desrosiers, A Salloum, IM Sachs, GS Weiss, RD AF Ostacher, M. J. Nierenberg, A. A. Ametrano, R. M. Bhagat, S. M. Desrosiers, A. Salloum, I. M. Sachs, G. S. Weiss, R. D. TI Re-evaluating DSM-IV criteria for alcohol dependence in bipolar disorder SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Ostacher, M. J.; Nierenberg, A. A.; Ametrano, R. M.; Bhagat, S. M.; Desrosiers, A.; Salloum, I. M.; Sachs, G. S.; Weiss, R. D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Clin & Res Program, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 263A EP 263A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201008 ER PT J AU Williams, EC Bryson, CL Sun, H Frey, MS Bradley, KA AF Williams, E. C. Bryson, C. L. Sun, H. Frey, M. S. Bradley, K. A. TI Association between anginal symptoms and alcohol screening scores in va outpatients SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 VA Puget Sound, NW Ctr Excellence Hlth Serv, Res & Dev, Seattle, WA 98101 USA. Univ Washington, Seattle, WA 98101 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 265A EP 265A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201017 ER PT J AU Pandol, SJ Gukovskaya, A Go, VLW AF Pandol, S. J. Gukovskaya, A. Go, V. L. W. TI Alcohol abuse, pancreatitis and pancreatic cancer SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Pandol, S. J.; Gukovskaya, A.; Go, V. L. W.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Hlth Care Syst, Dept Med, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 297A EP 297A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201137 ER PT J AU Chen, S Charness, ME AF Chen, S. Charness, M. E. TI Ethanol inhibits neuronal differentiation by disrupting signalling between astrocytes and neurons SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02132 USA. VA Boston Hlth Care Syst, Boston, MA 02132 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 298A EP 298A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201144 ER PT J AU Kelly, JF Brown, SA Abrantes, AM Kahler, CW Myers, MG AF Kelly, John F. Brown, Sandra A. Abrantes, Ana M. Kahler, Christopher W. Myers, Mark G. TI Social recovery model - The influence of 12-step mutual-help participation on the course of youth recovery over 8-years following inpatient treatment SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. VA San Diego Hlth Care Syst, San Diego, CA 92616 USA. Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 302A EP 302A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201157 ER PT J AU Myrick, H AF Myrick, Hugh TI FMRI studies of craving SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Myrick, Hugh] Med Univ S Carolina, Charleston Alcohol Res Ctr, Ralph H Johnson VAMC, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 331A EP 331A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201276 ER PT J AU Bradley, KA Williams, EC Greiner, G Achtmeyer, CE Volpp, B Frey, MS Hawkins, E Harris, A Kivlahan, DR AF Bradley, K. A. Williams, E. C. Greiner, G. Achtmeyer, C. E. Volpp, B. Frey, M. S. Hawkins, E. Harris, A. Kivlahan, D. R. TI Use of electronic reminders and a performance measure to increase brief alcohol counseling by primary care providers in VA SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Bradley, K. A.; Williams, E. C.; Greiner, G.; Achtmeyer, C. E.; Volpp, B.; Frey, M. S.; Hawkins, E.; Harris, A.; Kivlahan, D. R.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98101 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 337A EP 337A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201298 ER PT J AU Harris, GJ Jaffin, SK Hodge, SM Kennedy, D Caviness, VS Marinkovic, K Papadimitriou, GM Makris, N Oscar-Berman, M AF Harris, Gordon J. Jaffin, Sharon Kim Hodge, Steven M. Kennedy, David Caviness, Verne S. Marinkovic, Ksenija Papadimitriou, George M. Makris, Nikos Oscar-Berman, Marlene TI Frontal white matter and cingulum diffusion tensor imaging deficits in alcoholism SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Review DE alcoholism; diffusion tensor magnetic resonance imaging; white matter; reward system; right hemisphere ID WHOLE-HEMISPHERE AUTORADIOGRAPHY; SPATIAL WORKING-MEMORY; DOPAMINE-D-2 RECEPTORS; CORPUS-CALLOSUM; TOPOGRAPHIC PARCELLATION; ABSTINENT ALCOHOLICS; PREFRONTAL CORTEX; SOCIAL DRINKERS; GENE-EXPRESSION; DRUG-ADDICTION AB Background: Alcoholism-related deficits in cognition and emotion point toward frontal and limbic dysfunction, particularly in the right hemisphere. Prefrontal and anterior cingulate cortices are involved in cognitive and emotional functions and play critical roles in the oversight of the limbic reward system. In the present study, we examined the integrity of white matter tracts that are critical to frontal and limbic connectivity. Methods: Diffusion tensor magnetic resonance imaging (DT-MRI) was used to assess functional anisotropy (FA), a measure of white matter integrity, in 15 abstinent long-term chronic alcoholic and 15 demographically equivalent control men. Voxel-based and region-based analyses of group FA differences were applied to these scans. Results: Alcoholic subjects had diminished frontal lobe FA in the right superior longitudinal fascicles II and III, orbitofrontal cortex white matter, and cingulum bundle, but not in corresponding left hemisphere regions. These right frontal and cingulum white matter regional FA measures provided 97% correct group discrimination. Working Memory scores positively correlated with superior longitudinal fascicle III FA measures in control subjects only. Conclusions: The findings demonstrate white matter microstructure deficits in abstinent alcoholic men in several right hemisphere tracts connecting prefrontal and limbic systems. These white matter deficits may contribute to underlying dysfunction in memory, emotion, and reward response in alcoholism. C1 [Harris, Gordon J.; Jaffin, Sharon Kim; Hodge, Steven M.] Massachusetts Gen Hosp, Dept Radiol, Radiol Comp Aided Diagnost Lab, Boston, MA 02114 USA. [Jaffin, Sharon Kim; Hodge, Steven M.; Kennedy, David; Caviness, Verne S.; Marinkovic, Ksenija; Papadimitriou, George M.; Makris, Nikos] Harvard Univ, Sch Med,Psychiat & Radiol Serv, Ctr Morphometr Anal,Athinoula A Martinos Ctr, Dept Nerol,Massachusetts Gen Hosp, Boston, MA USA. [Makris, Nikos; Oscar-Berman, Marlene] VA Healthcare Syst, Dept Psychiat, Boston, MA USA. [Makris, Nikos; Oscar-Berman, Marlene] VA Healthcare Syst, Dept Neurol, Boston, MA USA. [Makris, Nikos; Oscar-Berman, Marlene] VA Healthcare Syst, Dept Anat & Neurobiol, Boston, MA USA. [Makris, Nikos; Oscar-Berman, Marlene] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Harris, GJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Radiol Comp Aided Diagnost Lab, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. EM gjharris@partners.org FU NCRR NIH HHS [P41 RR014075, P41RR14075]; NIAAA NIH HHS [K01 AA013402, K05 AA000219, K05-AA00219, R01 AA007112, R01-AA07112, K01-AA13402] NR 107 TC 73 Z9 74 U1 3 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 BP 1001 EP 1013 DI 10.1111/j.1530-0277.2008.00661.x PG 13 WC Substance Abuse SC Substance Abuse GA 304NQ UT WOS:000256116600012 PM 18422840 ER PT J AU Lieber, CS Weiss, DG Paronetto, F AF Lieber, Charles S. Weiss, David G. Paronetto, Fiorenzo CA Vet Affairs Cooperative Study 391 TI Value of fibrosis markers for staging liver fibrosis in patients with precirrhotic alcoholic liver disease SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcoholic liver disease; fibrosis markers; fibrosis score ID CHRONIC HEPATITIS-C; SERUM MARKERS; PERIVENULAR FIBROSIS; TISSUE INHIBITOR; HYALURONIC-ACID; BIOPSY; PROGRESSION; CIRRHOSIS; POLYENYLPHOSPHATIDYLCHOLINE; METALLOPROTEINASE AB Background: Our aim was to identify markers predictive of fibrosis in alcoholic liver disease (ALD). Percutaneous liver biopsy is the recommended standard for histologic assessment of liver fibrosis. Seven serum markers (tissue inhibitor of matrix metalloproteinase 1 {TIMP1}, tenascin, collagen VI, amino-terminal propeptide of type III collagen {PIIINP}, matrix metalloproteinases {MMP2}, laminin, and hyaluronic acid {HA}) representing various aspects of collagen and extracellular matrix deposition and degradation, have been proposed as noninvasive surrogates for liver biopsy. Moreover, a diagnostic algorithm including 3 serum markers (TIMP1, PIIINP, HA) and age has been proposed to accurately detect fibrosis with acceptable levels of sensitivity/specificity in a chronic hepatitis C subgroup. Methods: To determine variability of these markers in liver fibrosis with different etiologies, we conducted an evaluation of their correlative properties in a subgroup of patients (n = 247) with biopsy confirmed liver fibrosis resulting from long-term heavy alcohol consumption. Patients were participants in a recently completed VA multicenter clinical trial followed over 2 years with liver biopsy at baseline and 24 months, and with markers assessed every 3 months. Results: Among the markers measured in this alcoholic subgroup all except collagen VI displayed significant correlation with degrees of fibrosis. Three markers, TIMP1, PIIINP and HA adjusted for age, emerged as the most promising predictors of the degree of fibrosis in a population of alcoholics. However, there was little change over time as related to change in fibrosis. The lower than expected accuracy of these markers based on receiver operating curves (ROC) also showed their limited use in this etiologic subgroup. Conclusion: In alcoholic patients, various markers have limited value in predicting and diagnosing the stages of fibrosis compared to liver biopsy. Thus, further prospective studies are required to better define the usefulness of each marker or their combination which are possibly affected by alcohol metabolism. C1 [Lieber, Charles S.; Paronetto, Fiorenzo] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. [Weiss, David G.] Vet Affairs Med Ctr, Perry Point, MD USA. RP Lieber, CS (reprint author), James J Peters Vet Affairs Med Ctr, 130 W Kingsbridge Rd 151-2, Bronx, NY 10468 USA. EM liebercs@aol.com FU NIAAA NIH HHS [AA014326] NR 48 TC 28 Z9 33 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 BP 1031 EP 1039 DI 10.1111/j.1530-0277.2008.00664.x PG 9 WC Substance Abuse SC Substance Abuse GA 304NQ UT WOS:000256116600015 PM 18422837 ER PT J AU Groeneveld, PW Matta, MA Greenhut, AP Yang, FF AF Groeneveld, Peter W. Matta, Mary Anne Greenhut, Alexis P. Yang, Feifei TI The costs of drug-eluting coronary stents among Medicare beneficiaries SO AMERICAN HEART JOURNAL LA English DT Article ID TRIAL; LESIONS; SIRIUS; MODELS; ARTERY; RISK; LOG AB Background Clinical trials predict the higher initial costs of drug-eluting coronary stents (DES) compared to bare metal stents (BMS) would be partially offset by decreased costs during the first year after percutaneous coronary intervention (PCI). However, the costs of DES in nonexperimental settings are not well understood. Methods We used a random, nationwide sample of Medicare beneficiaries who had received either DES from April through December 2003 or BMS from July 2002 through December 2003. Propensity score methods separately matched DES recipients (n = 4,375) to historical and contemporary BMS controls. Costs were estimated for each patient based on all physician and institutional claims beginning with the PCI hospitalization through the subsequent year, with institutional charges converted to costs via cost center-specific cost-to-charge ratios, as reported to Medicare by each institution. Results Drug-eluting stent patients had higher 30-day costs compared to both historical controls (mean difference $2,131, 95% CI $1,726 to $2,516) and contemporary controls ($1,882, 95% CI $1,480 to $2,322), but at 1 year, the DES-BMS mean cost differences had diminished substantially ($647, 95% CI $-385 to $1,664 compared to historical controls; $-84, 95% CI $-1,202 to $1,018 compared to contemporary controls) and were no longer statistically significant. Conclusions Despite higher initial costs of DES, the lower follow-up costs during the first year resulted in relatively small cumulative cost differences between DES and BMS recipients. These differences are comparable to those modeled in economic studies predicting acceptable cost-effectiveness for drug-eluting stents. C1 [Groeneveld, Peter W.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Groeneveld, Peter W.; Matta, Mary Anne; Greenhut, Alexis P.; Yang, Feifei] Univ Penn, Sch Med, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Groeneveld, Peter W.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Groeneveld, PW (reprint author), VA Med Ctr, 9 E 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM pefer.groeneveld@va.gov NR 22 TC 7 Z9 7 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2008 VL 155 IS 6 BP 1097 EP 1105 DI 10.1016/j.ahj.2008.01.012 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 309WM UT WOS:000256490900021 PM 18513525 ER PT J AU Mendez, MF Licht, EA Shapira, JS AF Mendez, Mario F. Licht, Eliot A. Shapira, Jill S. TI Changes in dietary or eating behavior in frontotemporal dementia versus Alzheimer's disease SO AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS LA English DT Article DE dietary or eating behaviors; frontotemporal dementia ID FRONTAL-LOBE DEGENERATION; KLUVER-BUCY-SYNDROME; VASCULAR DEMENTIA; TEMPORAL VARIANTS; SEMANTIC DEMENTIA; DISORDERS; ATROPHY; COMPULSIONS; DIAGNOSIS; CONSENSUS AB Background: Changes in dietary or eating behavior are common in dementia and may help distinguish between different dementing illnesses. Objective: To evaluate and characterize differences in dietary and eating behavior among patients with early frontotemporal dementia (FTD) versus Alzheimer's disease (AD). Methods: This study administered the Food-Related Problems Questionnaire (FRPQ) to caregivers of 16 patients with FTD and 16 comparable patients with AD. The FRPQ was evaluated at initial presentation when patients presented for a diagnostic evaluation. Results: Compared with the AD patients, the FTD patients had significantly more changes on the FRPQ. Subscale analysis indicated that the FTD patients showed impairment of observed satiety, improper taking of food, and inappropriate responses when food was not available. Conclusions: The use of food-related questionnaires, such as the FRPQ, can help distinguish FTD patients, early in their course, from those with AD and can further characterize the altered dietary and eating behavior. C1 [Mendez, Mario F.; Licht, Eliot A.; Shapira, Jill S.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Mendez, Mario F.] Univ Calif Los Angeles, Dept Psychiat & Biobehavicating Sci, Los Angeles, CA 90024 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles, Neurobehav Unit AF116, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Mmendez@UCLA.edu NR 38 TC 15 Z9 15 U1 0 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1533-3175 J9 AM J ALZHEIMERS DIS JI Am. J. Alzheimers Dis. Other Dement. PD JUN-JUL PY 2008 VL 23 IS 3 BP 280 EP 285 DI 10.1177/1533317507313140 PG 6 WC Geriatrics & Gerontology; Clinical Neurology SC Geriatrics & Gerontology; Neurosciences & Neurology GA 344WE UT WOS:000258957200010 PM 18198236 ER PT J AU Lewis, GD Gona, P Larson, MG Plehn, JF Benjamin, EJ O'Donnell, CJ Levy, D Vasan, RS Wang, TJ AF Lewis, Gregory D. Gona, Philimon Larson, Martin G. Plehn, Jonathan F. Benjamin, Emelia J. O'Donnell, Christopher J. Levy, Daniel Vasan, Ramachandran S. Wang, Thomas J. TI Exercise blood pressure and the risk of incident cardiovascular disease (from the Framingham Heart Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY-DISEASE; MIDDLE-AGED MEN; PROGNOSTIC-SIGNIFICANCE; RATE RECOVERY; HEALTHY-SUBJECTS; GRADED-EXERCISE; MORTALITY; HYPERTENSION AB Exaggerated systolic blood pressure (BP) augmentation with exercise has been associated with impaired endothelial function and cardiovascular risk. However, previous studies were largely restricted to men, did not evaluate diastolic BP, and focused on peak exercise measures, which are influenced by effort and fitness level. The aim of this study was to determine the association of exercise BP responses with risk of incident cardiovascular disease (CVD). BP was assessed during stage 2 of the Bruce protocol and during recovery in 3,045 Framingham Study subjects (mean age 43 years; 53% women). The association between exercise BP and CVD events during 20 years of follow-up was examined using Cox proportional hazards models. In age- and sex-adjusted analyses, exercise systolic and diastolic BP were associated with incident CVD (adjusted hazard ratios [HRs] for top quintile 1.55, 95% confidence interval [CI] 1.18 to 2.04; and 1.77, 95% CI 1.35 to 2.31, respectively, relative to the lower 4 quintiles; p < 0.005). After adjustment for BP at rest and conventional risk factors, exercise diastolic BP (HR 1.41, 95% CI 1.01 to 1.95, p = 0.04), but not exercise systolic BP (HR 0.97, 95% CI 0.68 to 1.38, p = 0.86), remained a significant predictor of CVD. Similarly, in recovery responses after exercise, only diastolic BP (HR 1.53, 95% CI 1.08 to 2.18, p = 0.02) predicted incident CVD in multivariable models. In conclusion, in middle-aged adults, diastolic BP during low-intensity exercise and recovery predicted incident CVD. Our findings support the concept that dynamic BP provides incremental information to BP at rest and suggest that exercise diastolic BP may be a better predictor than exercise systolic BP in this age group. (c) 2008 Elsevier Inc. All rights reserved. C1 [Lewis, Gregory D.; O'Donnell, Christopher J.; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA 02115 USA. [Gona, Philimon; Larson, Martin G.; Benjamin, Emelia J.; O'Donnell, Christopher J.; Levy, Daniel; Vasan, Ramachandran S.; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Gona, Philimon; Larson, Martin G.] Boston Univ, Sch Med, Dept Math & Stat, Boston, MA 02118 USA. [Benjamin, Emelia J.; Levy, Daniel; Vasan, Ramachandran S.] Boston Univ, Sch Med, Epidemiol Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.; Levy, Daniel; Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Plehn, Jonathan F.; O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Bethesda, MD 20892 USA. RP Wang, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA 02115 USA. EM tjwang@partners.org OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [K24 HL004334-08, K23 HL074077, K23 HL074077-05, K23-HL074077, K24 HL004334, K24-HL-04334, N01-HC-25195, N01HC25195, R01-HC-25195] NR 30 TC 45 Z9 47 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 JUN 1 PY 2008 VL 101 IS 11 BP 1614 EP 1620 DI 10.1016/j.amjcard.2008.01.046 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 309HG UT WOS:000256450700013 PM 18489939 ER PT J AU Leaf, A AF Leaf, Alexander TI Historical overview of n-3 fatty acids and coronary heart disease SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Beyond Cholesterol - Prevention and Treatment of Coronary Heart Disease with n-3 Fatty Acids CY JUN 09, 2007 CL New York, NY ID PREVENTION AB The first evidence that fish oil fatty acids might have a beneficial effect on coronary heart disease came from the discovery that Greenland Eskimos, who have a diet high in n-3 fatty acids, have a lower mortality from coronary heart disease than do Danes and Americans. Long-chain polyunsaturated fatty acids are essential in our diets and can be classified in 2 groups: n-6 fatty acids found in plant seeds and n-3 fatty acids found in marine vertebrates. Further evidence of n-3 benefits to human health include a 1989 study demonstrating a 29% reduction in fatal cardiac arrhythmias among subjects with a recent myocardial infarction who had been advised to consume fish oil. The GISSI-Prevenzione Trial found a significant reduction in relative reduction of death, cardiac death, nonfatal myocardial infarction, and stroke in subjects consuming n-3 fatty acids. In a recent study, subjects with implanted cardiac defibrillators (ICDs) at high risk for fatal ventricular arrhythmias were randomly assigned to four 1-g capsules of either an ethyl ester concentrate of n-3 fatty acids or olive oil daily for 12 mo. Subjects receiving n-3 who thus had significantly higher levels of eicosapentaenoic acid and docosahexaenoic acid in their red blood cell membranes showed a longer time to first ICD events and had a significantly lower relative risk of having an ICD event or probable event (P = 0.033). These studies demonstrate that fish oil fatty acids have beneficial effects on coronary heart disease. C1 [Leaf, Alexander] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Leaf, Alexander] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Leaf, A (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 5 TC 12 Z9 13 U1 1 U2 7 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 2008 VL 87 IS 6 BP 1978S EP 1980S PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 313ET UT WOS:000256724600064 PM 18541598 ER PT J AU Deckelbaum, RJ Leaf, A Mozaffarian, D Jacobson, TA Harris, WS Akabas, SR AF Deckelbaum, Richard J. Leaf, Alexander Mozaffarian, Dariush Jacobson, Terry A. Harris, William S. Akabas, Sharon R. TI Conclusions and recommendations from the symposium, Beyond Cholesterol: Prevention and Treatment of Coronary Heart Disease with n-3 Fatty Acids SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Beyond Cholesterol - Prevention and Treatment of Coronary Heart Disease with n-3 Fatty Acids CY JUN 09, 2007 CL New York, NY ID CARDIOVASCULAR-DISEASE; FISH AB After the symposium "Beyond Cholesterol: Prevention and Treatment of Coronary Heart Disease with n-3 Fatty Acids," faculty who presented at the conference submitted manuscripts relating to their conference topics, and these are presented in this supplement. The content of these manuscripts was reviewed, and 2 conference calls were convened. The objective was to summarize existing evidence, gaps in evidence, and future research needed to strengthen recommendations for specific intakes of n-3 fatty acids for different conditions relating to cardiovascular disease. The following 2 questions were the main items discussed. What are the roles of n-3 fatty acids in primary versus secondary prevention of coronary heart disease? What are the roles of n-3 fatty acids in hypertriglyceridemia, in the metabolic syndrome and type 2 diabetes, and in sudden cardiac death, cardiac arrhythmias, and vulnerable plaque? Each area was summarized by using 2 general categories: 1) current knowledge for which general consensus exists, and 2) recommendations for research and policy. Additional references for these conclusions can be found in the articles included in the supplement. C1 [Deckelbaum, Richard J.; Akabas, Sharon R.] Columbia Univ, Inst Human Nutr, Med Ctr, New York, NY 10032 USA. [Deckelbaum, Richard J.; Akabas, Sharon R.] Columbia Univ, Dept Pediat, Med Ctr, New York, NY 10032 USA. [Leaf, Alexander] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Leaf, Alexander; Mozaffarian, Dariush] Harvard Univ, Sch Med, Boston, MA USA. [Mozaffarian, Dariush] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Mozaffarian, Dariush] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mozaffarian, Dariush] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Jacobson, Terry A.] Emory Univ, Dept Med, Off Hlth Promot & Dis Prevent, Atlanta, GA 30322 USA. [Harris, William S.] Univ S Dakota, Sanford Sch med, Sioux City, SD USA. [Harris, William S.] Sanford Res USD, Nutr & Metab Dis Res Ctr, Sioux City, SD USA. RP Akabas, SR (reprint author), Columbia Univ, Inst Human Nutr, Med Ctr, 630 W 168th St,PH 15-1512, New York, NY 10032 USA. EM sa109@columbia.edu RI Mozaffarian, Dariush/B-2276-2008 NR 12 TC 17 Z9 19 U1 0 U2 3 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 2008 VL 87 IS 6 BP 2010S EP 2012S PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 313ET UT WOS:000256724600069 PM 18541603 ER PT J AU Siegel, AJ Januzzi, J Sluss, P Lee-Lewandrowski, E Wood, M Shirey, T Lewandrowski, KB AF Siegel, Arthur J. Januzzi, James Sluss, Patrick Lee-Lewandrowski, Elizabeth Wood, Malissa Shirey, Terry Lewandrowski, Kent B. TI Cardiac biomarkers, electrolytes, and other analytes in collapsed marathon runners: implications for the evaluation of runners following competition SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE cardiac troponin T; B-type natriuretic peptide; N-terminal pro-B-type natriuretic peptide; lactic acidosis; ionized magnesium; acute coronary syndrome; sudden cardiac death; marathon ID BOSTON-MARATHON; EXERCISE; MARKERS; DEATH; STATEMENT; EXERTION; ACIDOSIS AB We measured analytes in collapsed Boston Marathon runners to compare with changes in asymptomatic runners. Of collapsed runners at the 2007 marathon, 18.2% had a measurable cardiac troponin T (cTnT) value with a mean postrace level of 0.017 ng/mL (0.017 mu g/L; SD, 0.02 ng/mL [0.02 mu g/L]). Three subjects had cTnT values above the cutoff (0.10 ng/mL [0.10 mu g/L]) typically used for the diagnosis of acute myocardial infarction. The mean and median N-terminal pro-B-type natriuretic peptide levels were 73 ng/L (SD, 77.3 ng/L) and 54.3 ng/L (interquartile range, 22.8-87.3 ng/L), respectively, in collapsed runners. Only 4.9% had values more than the age-specific normal value (< 125 ng/L for subjects younger than 75 years). In collapsed subjects at the 2006 marathon, 18.0% had an abnormal sodium value, including 18 cases of hypernatremia and 7 cases of hyponatremia. The ionized calcium level was low in 49% of subjects, and the ionized magnesium level was low in 19.5% and elevated in 1 subject. The blood lactate level was elevated in 95% of subjects. The frequency of elevated postrace cTnT levels in collapsed athletes after endurance exercise is similar to that in asymptomatic runners. Other metabolic abnormalities, including hypernatremia, hyponatremia, low ionized calcium and magnesium levels, and lactic acidosis may contribute to muscle fatigue and collapse. C1 [Sluss, Patrick; Lee-Lewandrowski, Elizabeth; Lewandrowski, Kent B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Januzzi, James; Wood, Malissa] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Siegel, Arthur J.] McLean Hosp, Dept Med, Belmont, MA 02178 USA. [Siegel, Arthur J.; Januzzi, James; Sluss, Patrick; Lee-Lewandrowski, Elizabeth; Wood, Malissa; Lewandrowski, Kent B.] Harvard Univ, Sch Med, Boston, MA USA. [Shirey, Terry] Novo Biomed, Waltham, MA USA. RP Lewandrowski, KB (reprint author), Massachusetts Gen Hosp, Dept Pathol, Gray 5,Fruit St, Boston, MA 02114 USA. NR 19 TC 19 Z9 21 U1 0 U2 6 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JUN PY 2008 VL 129 IS 6 BP 948 EP 951 DI 10.1309/4L0M60MGAQBCHMV7 PG 4 WC Pathology SC Pathology GA 302HP UT WOS:000255959700014 PM 18480012 ER PT J AU Kramer, N Lohbauer, U Garcia-Godoy, F Frankenberger, R AF Kraemer, Norbert Lohbauer, Ulrich Garcia-Godoy, Franklin Frankenberger, Roland TI Light curing of resin-based composites in the LED era SO AMERICAN JOURNAL OF DENTISTRY LA English DT Review ID SOFT-START POLYMERIZATION; POST-GEL SHRINKAGE; QUARTZ-TUNGSTEN-HALOGEN; DENTIN BOND STRENGTH; CLASS-V RESTORATIONS; TEMPERATURE RISE; MARGINAL ADAPTATION; EMITTING DIODE; IN-VITRO; CERAMIC INLAYS AB This review thoroughly accumulated information regarding new technologies for state-of-the-art light curing of resin composite materials. Visible light cured resin-based composites allow the dentist to navigate the initiation of the polymerization step for each layer being applied. Curing technology was regularly subjected to changes during the last decades, but meanwhile the LED era is fully established. Today, four main polymerization types are available, i.e. halogen bulbs, plasma are lamps, argon ion lasers, and light emitting diodes. Additionally, different curing protocols should help to improve photopolymerization in terms of less stress being generated. Conclusions were: (1) with high-power LED units of the latest generation, curing time of 2 mm thick increments of resin composite can be reduced to 20 seconds to obtain durable results; (2) curing depth is fundamentally dependent on the distance of the resin composite to the light source, but only decisive when exceeding 6 mm; (3) polymerization kinetics can be modified for better marginal adaptation by softstart polymerization; however, in the majority of cavities this may not be the case; (4) adhesives should be light-cured separately for at least 10 seconds when resin composite is applied directly; (5) photocuring through indirect restorations such as ceramics is still a problem, therefore, both dual-cured adhesives and dual-cured composites and resin coating in any way are recommended; and (6) heat generation with high-power photopolymerization units should not be underestimated as a biological problem for both gingival and pulpal tissues. C1 [Lohbauer, Ulrich; Frankenberger, Roland] Univ Erlangen Nurnberg, Dent Clin Operat Dent & Periodontol 1, Clin Med Ctr, D-91054 Erlangen, Germany. [Kraemer, Norbert] Univ Dresden, Dept Pediat Dent, Dresden, Germany. [Garcia-Godoy, Franklin] Nova SE Univ, Biosci Res Ctr, Coll Dent Med, Ft Lauderdale, FL 33314 USA. [Garcia-Godoy, Franklin] Forsyth Inst, Boston, MA USA. RP Frankenberger, R (reprint author), Univ Erlangen Nurnberg, Dent Clin 1, Univ Med Ctr Erlangen, Gluckstr 11, D-91054 Erlangen, Germany. EM frankbg@dent.uni-erlangen.de NR 105 TC 31 Z9 32 U1 1 U2 11 PU MOSHER & LINDER, INC PI WESTON PA 318 INDIAN TRACE SUITE 500, WESTON, FL 33326 USA SN 0894-8275 J9 AM J DENT JI Am. J. Dent. PD JUN PY 2008 VL 21 IS 3 BP 135 EP 142 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 327YP UT WOS:000257764700001 PM 18686762 ER PT J AU Cagidiaco, MC Garcia-Godoy, F Vichi, A Grandini, S Goracci, C Ferrari, M AF Cagidiaco, Maria Crysanti Garcia-Godoy, Franklin Vichi, Alessandro Grandini, Simone Goracci, Cecilia Ferrari, Marco TI Placement of fiber prefabricated or custom made posts affects the 3-year survival of endodontically treated premolars SO AMERICAN JOURNAL OF DENTISTRY LA English DT Article ID REINFORCED COMPOSITE POST; EPOXY-RESIN POSTS; FRACTURE-RESISTANCE; IN-VITRO; MAXILLARY PREMOLARS; STRUCTURAL CHARACTERISTICS; CLINICAL-PERFORMANCE; BOND STRENGTH; CORE SYSTEMS; TEETH AB Purpose: To assess whether the amount of residual coronal dentin and the placement of a prefabricated (DT Light Post)(LP) or a customized fiber post (Ever Stick Post)(ES) have a significant influence on the 3-year survival of endodontically treated premolars. Methods: A sample of 345 patients provided six groups of 60 premolars in need of endodontic treatment. Groups were defined based on the amount of dentin left at the coronal level after endodontic treatment and before abutment build-up. Within each group teeth were randomly divided into three subgroups (n=20). In Subgroup A, no root canal retention was provided for the coronal restoration. In Subgroups B and C, LP and ES, respectively, were placed inside the root canal. All the teeth were finally restored with a single unit metal-ceramic crown. Results: Data were not affected by any loss to follow-up. The overall 36-month survival rate of crowned endodontically treated premolars was 76.7%. The lowest survival rate was recorded for teeth restored without any root canal retention (62.5%). Teeth restored with LP had a survival rate higher (90.9%) than those restored with ES (76.7%). The Cox regression analysis showed that the presence of root canal retention was a significant factor for survival (P < 0.05). The decrease in failure risk was higher in teeth restored with LP (HR=0.1; 95% CI for HR=0.09 to 0.34; P < 0.001) than when using ES (HR= 0.5; 95% Cl for HR= 0.3 to 0.7; P=0.003). Teeth retaining one (HR= 0.3; 95% CI for HR= 0.2 to 0.7; P=0.003), two (HR= 0.2; 95% Cl for HR= 0.1 to 0.5; P < 0.001), or three coronal walls (HR= 0. 1; 95% CI for HR= 0.05 to 0.3; P < 0.001) had a significantly lower failure risk than teeth deprived even of the ferrule effect. Similar failure risks existed for teeth missing all the coronal walls regardless of the presence or absence of a ferrule effect (P > 0.05). Interaction terms were not significant (P > 0.05). Post placement and the amount of residual coronal dentin affected the 3-year survival of endodontically treated premolars. C1 [Ferrari, Marco] Univ Siena, Dept Oral Sci, Sch Dent Med, Policlin Le Scotte, I-53100 Siena, Italy. [Garcia-Godoy, Franklin] Nova SE Univ, Coll Dent Med, Biosci Res Ctr, Ft Lauderdale, FL 33314 USA. [Garcia-Godoy, Franklin] Forsyth Inst, Boston, MA USA. RP Ferrari, M (reprint author), Univ Siena, Dept Oral Sci, Sch Dent Med, Policlin Le Scotte, Viale Bracci, I-53100 Siena, Italy. EM m.ferrari@mclink.it NR 37 TC 40 Z9 42 U1 2 U2 5 PU MOSHER & LINDER, INC PI WESTON PA 318 INDIAN TRACE SUITE 500, WESTON, FL 33326 USA SN 0894-8275 J9 AM J DENT JI Am. J. Dent. PD JUN PY 2008 VL 21 IS 3 BP 179 EP 184 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 327YP UT WOS:000257764700010 PM 18686771 ER PT J AU Nagurney, JT Huang, C Heredia, O Sane, S Lewis, SC Chang, YC Jang, IK AF Nagurney, John Tobias Huang, Calvin Heredia, Orlando Sane, Swati Lewis, Sarah C. Chang, Yuchiao Jang, Ik-Kyung TI The new and old definitions of acute myocardial infarction: a data-based comparison SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID ACUTE CORONARY SYNDROMES; CARDIAC TROPONIN-T; JOINT EUROPEAN-SOCIETY; CREATINE-KINASE-MB; CHEST-PAIN; CARDIOLOGY/AMERICAN COLLEGE; EMERGENCY-DEPARTMENT; DIAGNOSTIC-CRITERIA; CONSENSUS DOCUMENT; RISK-FACTORS AB Purpose: To measure the agreement between the newer European Society of Cardiology-American College of Cardiology (ESC-ACC) definition of acute myocardial infarction (AMI) and the traditional definition established by the World Health Organization (WHO). Basic Procedures: All adult ED patients admitted to our institution with at least one abnormally elevated cardiac biomarker were determined to have had an AMI by either or both definitions. The degree of agreement and the frequency of the reasons for disagreement between these 2 definitions were measured. Main Findings: A final study population consisted of 339 patients; 196 (58%) had an AMI by one or both definitions. Among them, 126 (64%; 95% confidence interval [CI], 57-71) were discordant for these 2 definitions: 104 (53%; 95% CI, 46-60) met only the ESC-ACC, whereas 22 (11%; 95% CI, 6-16) met only the WHO definition. Among those who met only the ESC-ACC definition, 37 (36%; 95% CI, 27-45) met none of the 3 traditional WHO criteria. Principal Conclusions: More patients are discordant than concordant for the 2 standard definitions of AML Among them, a large majority meet only the new ESC-ACC definition. (C) 2008 Elsevier Inc. All rights reserved. C1 [Nagurney, John Tobias; Heredia, Orlando; Sane, Swati] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Huang, Calvin] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Lewis, Sarah C.] Stanford Univ, Palo Alto, CA 94305 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Jang, Ik-Kyung] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Nagurney, JT (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. EM nagurney.john@mgh.harvard.edu NR 51 TC 2 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD JUN PY 2008 VL 26 IS 5 BP 523 EP 531 DI 10.1016/j.ajem.2007.08.001 PG 9 WC Emergency Medicine SC Emergency Medicine GA 315QG UT WOS:000256893900001 PM 18534279 ER PT J AU Sriwattanakomen, R Ford, AF Thomas, SB Miller, MD Stack, JA Morse, JQ Kasckow, J Brown, C Reynolds, CF AF Sriwattanakomen, Roy Ford, Angela F. Thomas, Stephen B. Miller, Mark D. Stack, Jacqueline A. Morse, Jennifer Q. Kasckow, John Brown, Charlotte Reynolds, Charles F., III TI Preventing depression in later life: Translation from concept to experimental design and implementation SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE depression prevention; indicated preventive intervention; elderly; African American; translation ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY-CARE PATIENTS; MENTAL-HEALTH; MEDICAL ILLNESS; RATING-SCALE; OLDER-ADULTS; EPIDEMIOLOGY; DISORDERS; INVENTORY; DIAGNOSIS AB Objective: The authors detail the public health need for depression prevention research and the decisions made in designing an experiment testing problem solving therapy as "indicated" preventive intervention for high-risk older adults with sub-syndromal depression. Special attention is given to the recruitment of African Americans because of well-documented inequalities in mental health services and depression treatment outcomes between races. Methods: A total of 306 subjects (half white, half African American) with scores of 16 or higher on the Center for Epidemiological Studies of Depression Scale, but with no history of major depressive disorder in the past 12 months, are being recruited and randomly assigned to either problem solving therapy-primary care or to a dietary education control condition. Time to, and rate of, incident episodes of major depressive disorder are to be modeled using survival analysis. Level of depressive symptoms will be analyzed via a mixed models approach. Results: Twenty-two subjects have been recruited into the study, and to date eight have completed the randomly assigned intervention and postintervention assessment. Four of 22 have exited after developing major depressive episodes. None have complained about study procedures or demands. Implementation in a variety of community settings is going well. Conclusion: The data collected to date support the feasibility of translating from epidemiology to RCT design and implementation of empirical depression prevention research in later life. C1 [Sriwattanakomen, Roy; Miller, Mark D.; Stack, Jacqueline A.; Kasckow, John; Brown, Charlotte; Reynolds, Charles F., III] Univ Pittsburgh, Sch Med, Adv Ctr Intervent, Pittsburgh, PA USA. [Sriwattanakomen, Roy; Miller, Mark D.; Stack, Jacqueline A.; Kasckow, John; Brown, Charlotte; Reynolds, Charles F., III] Univ Pittsburgh, Sch Med, Serv Res Late Life Mood Disorders, Pittsburgh, PA USA. [Reynolds, Charles F., III] Univ Pittsburgh, Sch Med, John A Hartford Ctr Excellence Geriat Psychiat, Pittsburgh, PA USA. [Kasckow, John] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Kasckow, John] Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. [Ford, Angela F.; Thomas, Stephen B.] Univ Pittsburgh, Grad Sch Publ Hlth, Ctr Minor Hlth, Pittsburgh, PA USA. [Ford, Angela F.; Thomas, Stephen B.] Univ Pittsburgh, Grad Sch Publ Hlth, Res Ctr Excellence Minor Hlth Dispar, Pittsburgh, PA USA. RP Reynolds, CF (reprint author), Western Psychiat Inst & Clin, 3811 OHara St,E-1135, Pittsburgh, PA 15213 USA. EM reynoldscf@upmc.edu FU NIMH NIH HHS [P30 MH071944-05, T32 MH019986, P30 MH071944, T32 MH19986]; NIMHD NIH HHS [P60 MD000-207, P60 MD000207] NR 37 TC 13 Z9 13 U1 1 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 JUN PY 2008 VL 16 IS 6 BP 460 EP 468 DI 10.1097/JGP.0b013e318165db95 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 307GJ UT WOS:000256307100005 PM 18515690 ER PT J AU Teng, E Ringman, JM Ross, LK Mulnard, RA Dick, MB Bartzokis, G Davies, HD Galasko, D Hewett, L Mungas, D Reed, BR Schneider, LS Segal-Gidan, F Yaffe, K Cummings, JL AF Teng, Edmond Ringman, John M. Ross, Leslie K. Mulnard, Ruth A. Dick, Malcolm B. Bartzokis, George Davies, Helen D. Galasko, Douglas Hewett, Linda Mungas, Dan Reed, Bruce R. Schneider, Lon S. Segal-Gidan, Freddi Yaffe, Kristine Cummings, Jeffrey L. CA Alzheimer's Dis Res Ctr Californi Depression Alzheimer's Dis Investi TI Diagnosing depression in Alzheimer disease with the National Institute of Mental Health provisional criteria SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID CORNELL SCALE; NEUROPSYCHIATRIC INVENTORY; RATING-SCALE; DEMENTIA; SYMPTOMS; VALIDITY; VALIDATION AB Objective: To compare the rates of depression in Alzheimer Disease (AD) determined using National Institute of Mental Health (NIMH) provisional criteria for depression in AD (NIMH-dAD) to those determined using other established depression assessment tools. Design: Descriptive longitudinal cohort study. Setting: The Alzheimer's Disease Research Centers of California. Participants: A cohort of 101 patients meeting NINDS-ADRDA criteria for possible/probable AD, intentionally selected to increase the frequency of depression at baseline. Measurements: Depression was diagnosed at baseline and after 3 months using NIMH-dAD criteria and the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Axis I Disorders. Depressive symptoms also were assessed with the Cornell Scale for Depression in Dementia (CSDD), the Geriatric Depression Scale (GDS), and the Neuropsychiatric Inventory Questionnaire. Results: The baseline frequency of depression using NIMH-dAD criteria (44%) was higher than that obtained using DSM-IV criteria for major depression (14%; Z = -5.50, df = 101, p < 0.001) and major or minor depression (36%; Z = -2.86, df = 101, p = 0.021) or using established cut-offs for the CSDD (30%; Z = -2.86, df = 101, p = 0.004) or GDS (33%; Z = -2.04, df = 101, p = 0.041). The NIMH-dAD criteria correctly identified all patients meeting DSM-IV criteria for major depression, and correlated well with DSM-IV criteria for major or minor depression (kappa = 0.753, p < 0.001), exhibiting 94% sensitivity and 85% specificity. The higher rates of depression found with NIMH-dAD criteria derived primarily from its less stringent requirements for the frequency and duration of symptoms. Remission rates at 3 months were similar across instruments. Conclusions: The NIMH-dAD criteria identify a greater proportion of AD patients as depressed than several other established tools. C1 [Teng, Edmond; Ringman, John M.; Bartzokis, George; Cummings, Jeffrey L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA USA. [Cummings, Jeffrey L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA USA. [Ross, Leslie K.] Univ Calif San Francisco, Sch Nursing, Inst Hlth & Aging, San Francisco, CA 94143 USA. [Mulnard, Ruth A.] Univ Calif Irvine, Program Nursing Sci, Irvine, CA USA. [Dick, Malcolm B.] Univ Calif Irvine, Inst Brain Aging & Dementia, Irvine, CA USA. [Davies, Helen D.] Stanford Univ, Dept Psychiat, Stanford, CA 94305 USA. [Galasko, Douglas] Univ Calif San Diego, Dept Neurosci, San Diego, CA USA. [Galasko, Douglas] VA Med Ctr, San Diego, CA USA. [Hewett, Linda] Calif State Univ Fresno, Alzheimers & Memory Ctr, Fresno, CA 93740 USA. [Mungas, Dan] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA. [Reed, Bruce R.] Univ Calif Davis, Rush Alzheimers Dis Ctr, Davis, CA 95616 USA. [Schneider, Lon S.] USC, Keck Sch Med, Dept Psychiat, Los Angeles, CA USA. [Schneider, Lon S.] USC, Keck Sch Med, Dept Neurol, Los Angeles, CA USA. [Schneider, Lon S.] USC, Keck Sch Med, Dept Gerontol, Los Angeles, CA USA. [Segal-Gidan, Freddi] USC, Keck Sch Med, Rancho Los Amigos Natl Rehabil Ctr, Downey, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Teng, E (reprint author), W Los Angeles VA Healthcare Ctr, Neurobehav Unit 116AF, Bldg 500,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM eteng@ucla.edu RI Mungas, Dan/E-6810-2011; Bartzokis, George/K-2409-2013 FU NIA NIH HHS [P30 AG010129, P30 AG010129-129001, P50 AG 16570, P50 AG016570] NR 37 TC 42 Z9 44 U1 0 U2 6 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 JUN PY 2008 VL 16 IS 6 BP 469 EP 477 DI 10.1097/JGP.0b013e318165dbae PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 307GJ UT WOS:000256307100006 PM 18515691 ER PT J AU Weinick, RM Wilcox, SR Park, ER Griffey, RT Weissman, JS AF Weinick, Robin M. Wilcox, Susan R. Park, Elyse R. Griffey, Richard T. Weissman, Joel S. TI Use of advance directives for nursing home residents in the emergency department SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE LA English DT Article DE advance directives; nursing home patients; emergency departments ID SELF-DETERMINATION ACT AB Documented requests can ensure that patients' end-of-life care preferences are implemented, particularly in emergent circumstances. This study a) compared information on advance directives found in different sources of documentation in the hospital record of nursing home patients admitted through the emergency department and b) assessed emergency department clinicians perceptions of how end-of-life care requests are communicated to them. Seven potential Sources of documentation were reviewed in the medical records of 40 patients, and semistructured interviews were conducted with 10 emergency department clinicians. We found little concordance among sources of advance directive documentation. Our results suggest variability in documentation for nursing home patients on transfer to the emergency department, and that emergency department clinicians experience substantial difficulty in reliably obtaining information about advance directives. As treatment may vary based solely on available documentation, Such information gaps may decrease the likelihood Of adherence in the emergency department to patients' previously expressed care preferences. C1 [Weinick, Robin M.; Weissman, Joel S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy,Dept Med, Boston, MA 02114 USA. [Park, Elyse R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy,Dept Psychiat, Boston, MA 02114 USA. [Wilcox, Susan R.] Harvard Affiliated Emergency Med Residency, Dept Emergency Med, Brigham & Womens Hosp, Boston, MA USA. [Griffey, Richard T.] Washington Univ, Dept Emergency Med, St Louis, MO USA. RP Weinick, RM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy,Dept Med, Boston, MA 02114 USA. EM rweinick@partners.org OI Wilcox, Susan/0000-0001-7477-7531 NR 12 TC 9 Z9 9 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-9091 J9 AM J HOSP PALLIAT ME JI Am. J. Hosp. Palliat. Med. PD JUN-JUL PY 2008 VL 25 IS 3 BP 179 EP 183 DI 10.1177/1049909108315512 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 340SB UT WOS:000258664200002 PM 18403576 ER PT J AU Refaat, M Hyle, E Malhotra, R Seidman, D Dey, B AF Refaat, Marwan Hyle, Emily Malhotra, Rajeev Seidman, Dominika Dey, Bimalangshu TI Linezolid-induced lingua villosa nigra SO AMERICAN JOURNAL OF MEDICINE LA English DT Article C1 [Refaat, Marwan; Hyle, Emily; Malhotra, Rajeev; Seidman, Dominika; Dey, Bimalangshu] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med, Boston, MA 02115 USA. RP Refaat, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med, Boston, MA 02115 USA. OI Malhotra, Rajeev/0000-0003-0120-4630 NR 3 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUN PY 2008 VL 121 IS 6 BP E1 EP E1 DI 10.1016/j.amjmed.2008.02.023 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 303PI UT WOS:000256052300020 PM 18501207 ER PT J AU Wallington, SF AF Wallington, Sherrie Flynt TI The Internet as an Emerging Patient Education Tool Among African American Men With Prostate Cancer: An Exploratory Study SO AMERICAN JOURNAL OF MENS HEALTH LA English DT Article DE African American males; prostate cancer; Internet; health-information seeking ID COMMUNICATION; INFORMATION; STRATEGIES AB The lives of African American men with prostate cancer are greatly influenced by the information available to them, some of which is accessed on the Internet. Research indicates that the Internet can enhance consumer health knowledge but has not reached socioeconomic groups at highest risk for health disparities, such as African American men with prostate cancer. In this study, focus groups were used to explore the perceptions and uses of the Internet as a patient education tool among 39 African American men aged 39 years and older with diverse socioeconomic backgrounds. Nineteen (49%) participants reported using the Internet, 15 (38%) reported no use but indicated it was used on their behalf, and 5 (13%) reported no use and no use on their behalf. The findings revealed varying degrees of Internet use for information and social support. Prostate cancer diagnosis, poor patient-doctor communications, and accessibility influenced Internet use. Accessibility related more to lack of ease and familiarity with Internet use than lack of computer access. With training and awareness, the Internet has potential as a patient education tool among African American men with prostate cancer. C1 [Wallington, Sherrie Flynt] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. EM sherrie_wallington@dfci.harvard.edu NR 58 TC 6 Z9 6 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1557-9883 J9 AM J MENS HEALTH JI Am. J. Mens Health PD JUN PY 2008 VL 2 IS 2 BP 106 EP 121 DI 10.1177/1557988306296156 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 386FT UT WOS:000261868400002 PM 19477775 ER PT J AU Torres-Mozqueda, F He, J Yeh, IB Schwamm, LH Lev, MH Schaefer, PW Gonzalez, RG AF Torres-Mozqueda, F. He, J. Yeh, I. B. Schwamm, L. H. Lev, M. H. Schaefer, P. W. Gonzalez, R. G. TI An acute ischemic stroke classification instrument that includes CT or MR angiography: The Boston Acute Stroke Imaging Scale 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 COMPUTED-TOMOGRAPHY; HYPERACUTE STROKE; NIHSS SCORE; DIFFUSION; THROMBOLYSIS; TRIAL; RELIABILITY; PREDICTION; INFARCTION; OCCLUSION AB BACKGROUND AND PURPOSE: A simple classification instrument based on imaging that predicts outcomes in patients with actute ischemic stroke is lacking. We tested the hypotheses that the Boston Acute Stroke Imaging Scale (BASIS) classification instrument effectively predicts patient outcomes and is superior to the Alberta Stroke Program Early CT Score (ASPECTS) in predicting outcomes in acute ischemic stroke. MATERIALS AND METHODS: Of 230 prospectively screened, consecutive patients with acute ischemic stroke, 87 had noncontrast CT (NCCT)/CT angiography (CTA), and 118 had MR imaging/MR angiography (MRA) at admission and were classified as having major stroke by BASIS criteria if they had a proximal cerebral artery occlusion or, if no occlusion, imaging evidence of significant parenchymal ischemia; all of the others were classified as minor strokes. Outcomes included death, length of hospitalization, and discharge disposition. BASIS was compared with ASPECTS (dichotomized > or <= 7) in 87 patients who had NCCT/CTA. RESULTS: BASIS classification by NCCT/CTA was equivalent to MR imaging/MRA. Fifty-six of 205 patients were classified as having major strokes including all 6 of the deaths. A total of 71.4% and 15.4% of major and minor stroke survivors, respectively, were discharged to a rehabilitation facility, whereas 14.3% and 79.2% of patients with major and minor strokes were discharged to home. The mean length of hospitalization was 12.3 and 3.3 days for the major and minor stroke groups, respectively (all outcomes, P < .0001). In 87 NCCT/CTA patients, BASIS and ASPECTS agreed in 22 major and 44 minor strokes. BASIS classified 21 patients as having major strokes who were classified as having minor strokes by ASPECTS. The BASIS major/ASPECTS minor stroke group had outcomes similar to those classified as major strokes by both instruments. CONCLUSIONS: The BASIS classification instrument is effective and appears superior to ASPECTS in predicting outcomes in acute ischemic stroke. C1 [Torres-Mozqueda, F.; He, J.; Yeh, I. B.; Lev, M. H.; Schaefer, P. W.; Gonzalez, R. G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroradiol Div, Boston, MA 02114 USA. [Schwamm, L. H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke Serv, Boston, MA 02114 USA. RP Gonzalez, RG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroradiol Div, GRB 285,Fruit St, Boston, MA 02114 USA. EM rggonzalez@partners.org OI Schwamm, Lee/0000-0003-0592-9145 FU NINDS NIH HHS [NS50041] NR 27 TC 39 Z9 41 U1 0 U2 4 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 JUN-JUL PY 2008 VL 29 IS 6 BP 1111 EP 1117 DI 10.3174/ajnr.A1000 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 315QI UT WOS:000256894100016 PM 18467521 ER PT J AU Jakobiec, FA AF Jakobiec, Frederick A. TI Ocular adnexal lymphoid tumors: Progress in need of clarification SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID B-CELL LYMPHOMA; MALIGNANT-LYMPHOMA; LYMPHOCYTES-T; HYPERPLASIA; PROGNOSIS; DISEASE; LESIONS; NEOPLASMS; TISSUE AB PURPOSE: To evaluate recent ophthalmic publications on ocular adnexal lymphomas (OALs) according to his, topathologic and immunophenotypic criteria used in the diagnosis of systemic lymphomas (World Health Organization classification). DESIGN: Summary and critical analysis of recent clinical and pathologic studies. METHODS: Literature review and interpretation. RESULTS: In the largest study of 353 cases of OALs published in the pathology literature, extranodal marginal zone lymphoma (EMZL) constituted 52%, follicular lymphoma 23%, mantle cell lymphoma 5%, and small cell lymphocytic and chronic lymphocytic leukemia 4%-plus a residuum of arcane entities. In smaller series of less intensively studied OALs in the ophthalmic literature, EMZLs had a higher preponderance and also were associated with a favorable prognosis. Many EMZLs seemed to arise primarily in the ocular adnexa (mucosa, associated lymphoid tissue [MALT] lymphoma should be restricted for EMZLs involving epithelial tissues). CONCLUSIONS: Rigorous diagnostic criteria and a proposal for a prospective multicenter study may bring further clarification to the emerging order in this set of tumors. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, 243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 37 TC 39 Z9 44 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUN PY 2008 VL 145 IS 6 BP 941 EP 950 DI 10.1016/j.ajo.2008.03.01 PG 10 WC Ophthalmology SC Ophthalmology GA 307PS UT WOS:000256331400001 PM 18405875 ER PT J AU Asbell, PA Colby, KA Deng, S McDonnell, P Meisler, DM Raizman, MB Sheppard, JD Sahm, DF AF Asbell, Penny A. Colby, Kathryn A. Deng, Sophie McDonnell, Peter Meisler, David M. Raizman, Michael B. Sheppard, John D., Jr. Sahm, Daniel F. TI Ocular TRUST: Nationwide antimicrobial susceptibility patterns in ocular isolates SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; STREPTOCOCCUS-PNEUMONIAE; UNITED-STATES; FLUOROQUINOLONE RESISTANCE; BACTERIAL KERATITIS; HAEMOPHILUS-INFLUENZAE; MORAXELLA-CATARRHALIS; SURVEILLANCE; CIPROFLOXACIN; LEVOFLOXACIN AB PURPOSE: Ocular Tracking Resistance in U.S. Today (TRUST) annually evaluates in vitro antimicrobial susceptibility of Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae to ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, penicillin, azithromycin, tobramycin, trimethoprim, and polymyxin B in national samples of ocular isolates. DESIGN: Laboratory investigation. METHODS: Prospectively collected ocular isolates (197 S. aureus, 49 S. pneumoniae, and 32 H. influenzae) from 35 institutions and archived ocular isolates (760 S. pneumoniae and 356 H. influenzae) from 34 institutions were tested by an independent, central laboratory. Mean minimum inhibitory concentrations that would inhibit growth of 90% of the tested isolates (MIC(90)) were interpreted as susceptible, intermediate, or resistant according to standardized breakpoints for systemic treatment. S. aureus isolates were classified as methicillin susceptible (MSSA) or methicillin resistant (MRSA). RESULTS: MSSA or MRSA susceptibility patterns were virtually identical for the fluoroquinolones, that is, MSSA susceptibility was 79.9% to 81.1% and MRSA susceptibility was 15.2%. Trimethoprim was the only agent tested with high activity against MRSA. All S. pneumoniae isolates were susceptible to gatifloxacin, levofloxacin, and moxifloxacin; 89.8% were susceptible to ciprofloxacin. H. influenzae isolates were 100% susceptible to all tested agents but trimethoprim. Ocular TRUST I data were consistent with the eight,year longitudinal sample of archived ocular isolates. CONCLUSIONS: The fluoroquinolones were consistently active in MSSA, S. pneumoniae, and H. influent zae. After more than a decade of intensive ciprofloxacin and levofloxacin use as systemic therapy, 100% of ocular S. pneumoniae isolates were susceptible to gatifloxacin, levofloxacin, and moxifloxacin; nonsusceptibility to ciprofloxacin was less than 15%. High,level in vitro MRSA resistance suggests the need to consider alternative therapy to fluoroquinolones when MRSA is a likely pathogen. C1 [Asbell, Penny A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY 10029 USA. [Colby, Kathryn A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Deng, Sophie] Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. [McDonnell, Peter] Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD USA. [Meisler, David M.] Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA. [Raizman, Michael B.] Tufts Univ, Sch Med & Ophthalm Consultants Boston, New England Eye Ctr, Boston, MA 02111 USA. [Sheppard, John D., Jr.] Virginia Eye Consultants, Norfolk, VA USA. [Sahm, Daniel F.] Eurofins Medinet Inc, Antiinfect Serv, Herndon, VA USA. RP Asbell, PA (reprint author), Mt Sinai Sch Med, Dept Ophthalmol, 1 Gustave L Levy Pl,Box 1183, New York, NY 10029 USA. EM penny.asbell@mssm.edu NR 29 TC 90 Z9 92 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUN PY 2008 VL 145 IS 6 BP 951 EP 958 DI 10.1016/j.ajo.2008.01.025 PG 8 WC Ophthalmology SC Ophthalmology GA 307PS UT WOS:000256331400002 PM 18374299 ER PT J AU Shimizu, A Hisashi, Y Kuwaki, K Tseng, YL Dor, FJMF Houser, SL Robson, SC Schuurman, HJ Cooper, DKC Sachs, DH Yamada, K Colvin, RB AF Shimizu, Akira Hisashi, Yosuke Kuwaki, Kenji Tseng, Yau-Lin Dor, Frank J. M. F. Houser, Stuart L. Robson, Simon C. Schuurman, Henk-Jan Cooper, David K. C. Sachs, David H. Yamada, Kazuhiko Colvin, Robert B. TI Thrombotic microangiopathy associated with humoral rejection of cardiac xenografts from alpha 1, 3-galactosyltransferase gene-knockout pigs in baboons SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ACUTE VASCULAR REJECTION; HEART-TRANSPLANTATION; PORCINE KIDNEY; TISSUE FACTOR; ANTIBODIES; XENOTRANSPLANTATION; ENDOTHELIUM; ACTIVATION; DONORS; GAL AB Heterotopic cardiac xenotransplantation from alpha 1,3-galactosyltransferase gene-knockout (GalT-KO) swine to baboons was performed to characterize immunological reaction to the xenograft in the absence of anti-Gal antibody-mediated rejection. Eight baboons received heterotopic cardiac xenografts from GalT-KO porcine donors. All baboons were treated with chronic immunosuppressive therapy. Both histological and immunohistochemical studies were performed on biopsy and graftectomy samples. No hyperacute rejection was observed. Three baboons were euthanized or died 16 to 56 days after transplantation. The other five grafts ceased beating between days 59 and 179 (median, 78 days). All failing grafts exhibited thrombotic microangiopathy (TM) with platelet-rich fibrin thrombi in the microvasculature, myocardial ischemia and necrosis, and focal interstitial hemorrhage. TM developed in parallel with increases in immunoglobulin (IgM and IgG) and complement (C3, C4d, and C5b-9) deposition, as well as with subsequent increases in both TUNEL+ endothelial cell death and procoagulant activation (increased expression of both tissue factor and von Willebrand factor and decreased expression of CD39). CD3(+) T-cell infiltration occurred in all grafts and weakly correlated with the development of TM. in conclusion, although the use of GalT-KO swine donors prevented hyperacute rejection and prolonged graft survival, slowly progressive humoral rejection-probably associated with non-Gal antibodies to the xenograft-and disordered thromboregulation represent major immunological barriers to long-term xenograft survival. C1 [Shimizu, Akira; Hisashi, Yosuke; Kuwaki, Kenji; Tseng, Yau-Lin; Dor, Frank J. M. F.; Cooper, David K. C.; Sachs, David H.; Yamada, Kazuhiko] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Shimizu, Akira; Houser, Stuart L.; Colvin, Robert B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02129 USA. [Robson, Simon C.] Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Med Ctr,Transplant Ctr, Boston, MA 02129 USA. [Shimizu, Akira; Schuurman, Henk-Jan] Immerge BioTherapeut Inc, Cambridge, MA USA. [Shimizu, Akira] Nippon Med Sch, Dept Pathol, Tokyo 113, Japan. RP Shimizu, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bldg 149-9019,13th St, Boston, MA 02129 USA. EM akirashimizu@tbrc.mgh.harvard.edu RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 FU NHLBI NIH HHS [R01 HL057307]; NIAID NIH HHS [1P01 AI45897, 1U01 AI066331, U01 AI066331, U01 AI066331-03, U01 AI066331-04] NR 39 TC 78 Z9 82 U1 1 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 2008 VL 172 IS 6 BP 1471 EP 1481 DI 10.2353/ajpath.2008.070672 PG 11 WC Pathology SC Pathology GA 307NY UT WOS:000256326800005 PM 18467706 ER PT J AU Rajan, S Hammond, MC Goldstein, B AF Rajan, Suparna Hammond, Margaret C. Goldstein, Barry TI Trends in diabetes mellitus indicators in veterans with spinal cord injury SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE spinal cord injury; diabetes mellitus; chronic disease; veteran ID AFFAIRS HEALTH-CARE; QUALITY IMPROVEMENT; MANAGED CARE; RETINOPATHY; GUIDELINES; DISORDERS; CENTERS; SYSTEM; MODEL AB Objective: Persons with spinal cord injury (SCI) are at increased risk for developing diabetes mellitus (M). However, published data on the care provided to this population are minimal. The purpose of this study was to examine a set of measures of quality of DM care in veterans with SCI. Design: Retrospective analysis of the External Peer Review Program data for veterans with SCI and DM from 2002 to 2004 in the Veterans Healthcare System. Trends in DM measures were examined using generalized estimation equation models. Results: The percentage of veterans who received testing for lipids, retinal, and renal exams significantly increased during this period. This was accompanied by significant improvements in intermediate outcomes, glycemic, lipid, and blood pressure (BP) control. The percentage of veterans with glycosylated hemoglobin (HbA1c) (levels <= 9%; P < 0.001) and those with poorly controlled levels (HbA1c >9.5%; P = 0.022) improved. BP (140/90) rates increased from 59% in fiscal year (FY) 2002 to nearly 70% in 2004 (P < 0.001). The percentage of veterans who received renal screening (anatomical tests, physiologic test, and urine microalbumin) increased significantly (P < 0.001). Retinopathy exam rates also increased from 55.1% in FY 2002 to 70.8% in IFY 2004 (P < 0.001). Conclusions: Significant improvements were made in a set of DM measures used to evaluate care provided to veterans with SCI. The positive trends in DM care seen in the general veteran population were also evident in the SCI population. C1 [Rajan, Suparna; Hammond, Margaret C.; Goldstein, Barry] VA Puget Sound Hlth Care Syst, Spinal Cord Injury Qual Enhancement Res Initiat S, Seattle, WA 98108 USA. [Hammond, Margaret C.; Goldstein, Barry] VA Puget Sound Hlth Care Syst, Spinal Cord Injury Disorders Serv, Seattle, WA 98108 USA. RP Rajan, S (reprint author), VA Puget Sound Hlth Care Syst, Spinal Cord Injury Qual Enhancement Res Initiat S, 1660 S Columbian Way,S-152, Seattle, WA 98108 USA. NR 29 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD JUN PY 2008 VL 87 IS 6 BP 468 EP 474 DI 10.1097/PHM.0b013e318174e66e PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 305EP UT WOS:000256160900007 PM 18496249 ER PT J AU Brown, D AF Brown, Dennis TI "Systems biology" - What's in name? SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Editorial Material C1 [Brown, Dennis] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. [Brown, Dennis] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. RP Brown, D (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUN PY 2008 VL 294 IS 6 BP C1299 EP C1299 DI 10.1152/ajpcell.zh0-5636.2008 PG 1 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 311BL UT WOS:000256574900001 PM 18541925 ER PT J AU Lin, AL Zhu, B Zhang, WK Dang, H Zhang, BX Katz, MS Yeh, CK AF Lin, Alan L. Zhu, Bing Zhang, WanKe Dang, Howard Zhang, Bin-Xian Katz, Michael S. Yeh, Chih-Ko TI Distinct pathways of ERK activation by the muscarinic agonists pilocarpine and carbachol in a human salivary cell line SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE muscarinic receptor; epidermal growth factor receptor; protein kinase C ID GROWTH-FACTOR RECEPTOR; PROTEIN-KINASE-C; SIGNAL-REGULATED KINASE; ACETYLCHOLINE-RECEPTORS; EPITHELIAL-CELLS; PAROTID-GLAND; ADENYLYL-CYCLASE; CANCER CELLS; MAP KINASE; T-84 CELLS AB Cholinergic-muscarinic receptor agonists are used to alleviate mouth dryness, although the cellular signals mediating the actions of these agents on salivary glands have not been identified. We examined the activation of ERK1/2 by two muscarinic agonists, pilocarpine and carbachol, in a human salivary cell line (HSY). Immunoblot analysis revealed that both agonists induced transient activation of ERK1/2. Whereas pilocarpine induced phosphorylation of the epidermal growth factor (EGF) receptor, carbachol did not. Moreover, ERK activation by pilocarpine, but not carbachol, was abolished by the EGF receptor inhibitor AG-1478. Downregulation of PKC by prolonged treatment of cells with the phorbol ester PMA diminished carbachol-induced ERK phosphorylation but had no effect on pilocarpine responsiveness. Depletion of intracellular Ca2+ ([Ca2+](i)) by EGTA did not affect ERK activation by either agent. In contrast to carbachol, pilocarpine did not elicit [Ca2+](i) mobilization in HSY cells. Treatment of cells with the muscarinic receptor subtype 3 (M-3) antagonist N-(3-chloropropyl)-4-piperidnyl diphenylacetate decreased ERK responsiveness to both agents, whereas the subtype 1 (M-1) antagonist pirenzepine reduced only the carbachol response. Stimulation of ERKs by pilocarpine was also decreased by M-3, but not M-1, receptor small interfering RNA. The Src inhibitor PP2 blocked pilocarpine-induced ERK activation and EGF receptor phosphorylation, without affecting ERK activation by carbachol. Our results demonstrate that the actions of pilocarpine and carbachol in salivary cells are mediated through two distinct signaling mechanisms-pilocarpine acting via M-3 receptors and Src-dependent transactivation of EGF receptors, and carbachol via M-1/M-3 receptors and PKC- converging on the ERK pathway. C1 [Zhang, Bin-Xian; Katz, Michael S.; Yeh, Chih-Ko] S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Audie L Murphy Div, San Antonio, TX 78229 USA. [Lin, Alan L.; Zhu, Bing; Yeh, Chih-Ko] Univ Texas Hlth Sci Ctr San Antonio, Dept Dent Diagnost Sci, San Antonio, TX 78229 USA. [Dang, Howard; Yeh, Chih-Ko] Univ Texas Hlth Sci Ctr San Antonio, Dept Community Dent, San Antonio, TX 78229 USA. [Zhang, WanKe; Zhang, Bin-Xian; Katz, Michael S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. RP Yeh, CK (reprint author), S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Audie L Murphy Div, San Antonio, TX 78229 USA. EM yeh@uthscsa.edu FU NHLBI NIH HHS [R01-HL-075011]; NIDCR NIH HHS [R21 DE-15381] NR 47 TC 17 Z9 18 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUN PY 2008 VL 294 IS 6 BP C1454 EP C1464 DI 10.1152/ajpcell.00151.2007 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 311BL UT WOS:000256574900020 PM 18385290 ER PT J AU Hasler, WL Coleski, R Chey, WD Koch, KL McCallum, RW Wo, JM Kuo, B Sitrin, MD Katz, LA Hwang, J Semler, JR Parkman, HP AF Hasler, William L. Coleski, Radoslav Chey, William D. Koch, Kenneth L. McCallum, Richard W. Wo, John M. Kuo, Braden Sitrin, Michael D. Katz, Leonard A. Hwang, Judy Semler, John R. Parkman, Henry P. TI Differences in intragastric pH in diabetic vs. idiopathic gastroparesis: relation to degree of gastric retention SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE gastric emptying; diabetes mellitus; gastric acid ID HELICOBACTER-PYLORI INFECTION; ACID-SECRETION; GASTROINTESTINAL SYMPTOMS; GASTRODUODENAL DISORDERS; CLINICAL CHARACTERISTICS; PATHOLOGICAL FINDINGS; INTERSTITIAL-CELLS; MELLITUS; INSULIN; RATS AB Evidence suggests that distinct mechanisms underlie diabetic and idiopathic gastroparesis. Differences in gastric acid in gastroparesis of different etiologies and varying degrees of gastric stasis are uninvestigated. We tested the hypotheses that 1) gastric pH profiles show differential alteration in diabetic vs. idiopathic gastroparesis and 2) abnormal pH profiles relate to the severity of gastric stasis. Sixty-four healthy control subjects and 44 gastroparesis patients (20 diabetic, 24 idiopathic) swallowed wireless transmitting capsules and then consumed Tc-99m-sulfur colloid-labeled meals for gastric scintigraphy. Gastric pH from the capsule was recorded every 5 s. Basal pH was higher in diabetic (3.64 +/- 0.41) vs. control subjects (1.90 +/- 0.18) and idiopathic subjects (2.41 +/- 0.42; P < 0.05). Meals evoked initial pH increases that were greater in diabetic (4.98 +/- 0.32) than idiopathic patients (3.89 +/- 0.39; P = 0.03) but not control subjects (4.48 +/- 0.14). pH nadirs prior to gastric capsule evacuation were higher in diabetic patients (1.50 +/- 0.23) than control subjects (0.58 +/- 0.11; P = 0.003). Four-hour gastric retention was similar in diabetic (18.3 +/- 0.5%) and idiopathic (19.4 +/- 0.5%) patients but higher than control subjects (2.2 +/- 0.5%; P < 0.001). Compared with control subjects, those with moderate-severe stasis (>20% retention at 4 h) had higher basal (3.91 +/- 0.55) and nadir pH (2.23 +/- 0.42) values (P < 0.05). In subgroup analyses, both diabetic and idiopathic patients with moderate-severe gastroparesis exhibited increased pH parameters vs. those with mild gastroparesis. In conclusion, diabetic patients with gastroparesis exhibit reduced gastric acid, an effect more pronounced in those with severely delayed gastric emptying. Idiopathic gastroparetic subjects exhibit nearly normal acid profiles, although those with severely delayed emptying show reduced acid vs. those with mild delays. Thus both etiology and degree of gastric stasis determine gastric acidity in gastroparesis. C1 [Hasler, William L.; Coleski, Radoslav; Chey, William D.] Univ Michigan Hlth Syst, Div Gastroenterol, Ann Arbor, MI USA. [Koch, Kenneth L.] Wake Forest Baptist Med Ctr, Winston Salem, NC USA. [McCallum, Richard W.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Wo, John M.] Univ Louisville, Med Ctr, Louisville, KY 40292 USA. [Kuo, Braden] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sitrin, Michael D.] Buffalo Vet Adm Hosp, Buffalo, NY USA. [Katz, Leonard A.] SUNY Buffalo, Sch Med, Buffalo, NY 14260 USA. [Hwang, Judy; Semler, John R.] SmartPill Corp, Buffalo, NY USA. [Parkman, Henry P.] Temple Univ, Med Ctr, Philadelphia, PA 19122 USA. RP Hasler, WL (reprint author), Univ Michigan Hosp, Taubman Ctr 3912, Box 0362, Ann Arbor, MI 48109 USA. EM whasler@umich.edu NR 34 TC 21 Z9 22 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUN PY 2008 VL 294 IS 6 BP G1384 EP G1391 DI 10.1152/ajpgi.00023.2008 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 310YU UT WOS:000256567800011 PM 18403619 ER PT J AU Mizumori, M Choi, Y Guth, PH Engel, E Kaunitz, JD Akiba, Y AF Mizumori, Misa Choi, Yuri Guth, Paul H. Engel, Eli Kaunitz, Jonathan D. Akiba, Yasutada TI CFTR inhibition augments NHE3 activity during luminal high CO2 exposure in rat duodenal mucosa SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE CO2 absorption; bicarbonate secretion; portal venous PCO2 ID APICAL CL-/HCO3-EXCHANGER; ACID-BASE-BALANCE; BICARBONATE ABSORPTION; CARBONIC-ANHYDRASES; NA+/H+ EXCHANGERS; PROXIMAL TUBULE; FLUID SECRETION; HCO3-SECRETION; EPITHELIUM; MICE AB We hypothesized that the function of duodenocyte apical membrane acid-base transporters are essential for H+ absorption from the lumen. We thus examined the effect of inhibition of Na+/H+ exchanger-3 (NHE3), cystic fibrosis transmembrane regulator (CFTR), or apical anion exchangers on transmucosal CO2 diffusion and HCO3- secretion in rat duodenum. Duodena were perfused with a pH 6.4 high CO2 solution or pH 2.2 low CO2 solution with the NHE3 inhibitor, S3226, the anion transport inhibitor, DIDS, or pretreatment with the potent CFTR inhibitor, CFTRinh-172, with simultaneous measurements of luminal and portal venous (PV) pH and carbon dioxide concentration ([CO2]). Luminal high CO2 solution increased CO2 absorption and HCO3- secretion, accompanied by PV acidification and PV PCO2 increase. During CO2 challenge, CFTRinh-172 induced HCO3- absorption, while inhibiting PV acidification. S3226 reversed CFTRinh-associated HCO3- absorption. Luminal pH 2.2 challenge increased H+ and CO2 absorption and acidified the PV, inhibited by CFTRinh-172 and DIDS, but not by S3226. CFTR inhibition and DIDS reversed HCO3- secretion to absorption and inhibited PV acidification during CO2 challenge, suggesting that HCO3- secretion helps facilitate CO2/H+ absorption. Furthermore, CFTR inhibition prevented CO2-induced cellular acidification reversed by S3226. Reversal of increased HCO3- loss by NHE3 inhibition and reduced intracellular acidification during CFTR inhibition is consistent with activation or unmasking of NHE3 activity by CFTR inhibition, increasing cell surface H+ available to neutralize luminal HCO3- with consequent CO2 absorption. NHE3, by secreting H+ into the luminal microclimate, facilitates net transmucosal HCO3- absorption with a mechanism similar to proximal tubular HCO3- absorption. C1 [Guth, Paul H.; Kaunitz, Jonathan D.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. [Mizumori, Misa; Kaunitz, Jonathan D.; Akiba, Yasutada] Sch Med, Dept Med, Los Angeles, CA USA. [Engel, Eli] Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA USA. [Mizumori, Misa; Akiba, Yasutada] Brentwood Biomed Res Inst, Los Angeles, CA USA. [Choi, Yuri] Harvard Westlake Sch, Los Angeles, CA USA. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, Bldg 114,Ste 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU NIDDK NIH HHS [P30 DK0413, R01 DK54221, R01 DK054221] NR 41 TC 10 Z9 10 U1 0 U2 1 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 JUN PY 2008 VL 294 IS 6 BP G1318 EP G1327 DI 10.1152/ajpgi.00025.2008 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 310YU UT WOS:000256567800003 PM 18420826 ER PT J AU Siccardi, D Mumy, KL Wall, DM Bien, JD McCormick, BA AF Siccardi, Dario Mumy, Karen L. Wall, Daniel M. Bien, Jeffrey D. McCormick, Beth A. TI Salmonella enterica serovar Typhimurium modulates P-glycoprotein in the intestinal epithelium SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE ATP-binding cassette transporter; inflammation; multidrug resistance 1 ID INFLAMMATORY-BOWEL-DISEASE; TUMOR-NECROSIS-FACTOR; DRUG-RESISTANCE; CACO-2 CELLS; EXPRESSION; GENE; PROTEIN; TRANSPORT; CANCER; EFFLUX AB Studies over the last decade have shown that Salmonella enterica serovar Typhimurium (S. typhimurium) is able to preferentially locate to sites of tumor growth and modulate (shrink) the growth of many cancers. Given this unique association between S. typhimurium and cancer cells, the objective of this study was to investigate the capacity of this microorganism to modulate the plasma membrane multidrug resistance (MDR) protein P-glycoprotein (P-gp), an ATP-binding cassette transporter responsible for effluxing many cancer drugs. Using an in vitro model of S. typhimurium infection of polarized human cancer intestinal cell lines, we have found that this enteric pathogen functionally downregulates the efflux capabilities of P-gp. Specifically, we show that S. typhimurium infection of human intestinal cancer cells results in the enhanced intracellular accumulation of a number of P-gp substrates that corresponds to the posttranscriptional downregulation of P-gp expression. Furthermore, cells expressing small interfering RNAs against MDR1, the gene encoding P-gp, were significantly more susceptible to the cytotoxic effects of bacterial infection. This result is consistent with our observation that S. typhimurium was significantly less able to invade cells overexpressing MDR1. Taken together, these results reveal a novel role for P-gp in the maintenance of homeostasis in the gastrointestinal tract in regard to bacterial infection. Thus the regulation of P-gp by S. typhimurium has important implications not only for the development of new cancer therapeutics aimed at reversing drug resistance but also in the understanding of how microbes have evolved diverse strategies to interact with their host. C1 [McCormick, Beth A.] Massachusetts Gen Hosp, Dept Pediat Gastroenterol & Nutr, Mucosal Immunol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP McCormick, BA (reprint author), Massachusetts Gen Hosp, Dept Pediat Gastroenterol & Nutr, Mucosal Immunol Lab, 114 16th St 114-3503, Charlestown, MA 02129 USA. EM mccormic@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK-56754]; PHS HHS [T32 TRAINING GRANT] NR 37 TC 12 Z9 12 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUN PY 2008 VL 294 IS 6 BP G1392 EP G1400 DI 10.1152/ajpgi.00599.2007 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 310YU UT WOS:000256567800012 PM 18403618 ER PT J AU Thrower, EC Osgood, S Shugrue, CA Kolodecik, TR Chaudhuri, AM Reeve, JR Pandol, SJ Gorelick, FS AF Thrower, Edwin C. Osgood, Sara Shugrue, Christine A. Kolodecik, Thomas R. Chaudhuri, Anamika M. Reeve, Joseph R., Jr. Pandol, Stephen J. Gorelick, Fred S. TI The novel protein kinase C isoforms -delta and -epsilon modulate caerulein-induced zymogen activation in pancreatic acinar cells SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE translocation; PKC activator phorbol ester; PKC inhibitor ID MURINE PERITONEAL-MACROPHAGES; KAPPA-B ACTIVATION; INOSITOL 1,4,5-TRISPHOSPHATE; PKC-DELTA; TRYPSINOGEN ACTIVATION; CATHEPSIN-B; CHOLECYSTOKININ RECEPTOR; PHOSPHORYLATION; CA2+; RELEASE AB Isoforms of protein kinase C (PKC) have been shown to modulate some cellular responses such as pathological secretion and generation of inflammatory mediators during acute pancreatitis (AP). We propose that PKC also participates in premature zymogen activation within the pancreatic acinar cell, a key event in the initiation of AP. This hypothesis was examined in in vivo and cellular models of caerulein-induced AP using PKC activators and inhibitors. Phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA, 200 nM), a known activator of PKC, enhanced zymogen activation at both 0.1 nM and 100 nM caerulein, concentrations which mimic physiological and supraphysiological effects of the hormone cholecystokinin, respectively, in preparations of pancreatic acinar cells. Isoform-specific PKC inhibitors for PKC-delta and PKC-epsilon reduced supraphysiological caerulein-induced zymogen activation. Using a cell-free reconstitution system, we showed that inhibition of PKC-delta and -epsilon, reduced zymogen activation in both zymogen granule-enriched and microsomal fractions. In dispersed acinar cells, 100 nM caerulein stimulation caused PKC-delta and -epsilon isoform translocation to microsomal membranes using cell fractionation and immunoblot analysis. PKC translocation was confirmed with in vivo studies and immunofluorescence microscopy in pancreatic tissues from rats treated with or without 100 nM caerulein. PKC-epsilon redistributed from an apical to a supranuclear region following caerulein administration. The signal for PKC-epsilon overlapped with granule membrane protein, GRAMP-92, an endosomal/lysosomal marker, in a supranuclear region where zymogen activation takes place. These results indicate that PKC-delta and -epsilon isoforms translocate to specific acinar cell compartments and modulate zymogen activation. C1 [Thrower, Edwin C.; Osgood, Sara; Shugrue, Christine A.; Kolodecik, Thomas R.; Chaudhuri, Anamika M.; Gorelick, Fred S.] Dept Internal Med, Sect Digest Dis, New Haven, CT USA. [Gorelick, Fred S.] Vet Affairs Connecticut Healthcare W Haven, Dept Cell Biol, New Haven, CT USA. [Gorelick, Fred S.] Yale Univ, Sch Med, New Haven, CT USA. [Reeve, Joseph R., Jr.; Pandol, Stephen J.] Vet Affairs Greater Los Angeles Hlth Care Syst, Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA USA. [Reeve, Joseph R., Jr.; Pandol, Stephen J.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Thrower, EC (reprint author), Vet Adm Med Ctr, 950 Campbell Ave,Bldg 4, West Haven, CT 06516 USA. EM edwin.thrower@yale.edu FU NIAAA NIH HHS [P50 AA011999, 5 P60 AA-11999]; NIDDK NIH HHS [R21 DK069702-01, R21 DK069702, R01 DK054021-02, DK-54021, R01 DK054021, R01 DK-33850, R21 DK-69702, R01 DK033850] NR 35 TC 20 Z9 20 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUN PY 2008 VL 294 IS 6 BP G1344 EP G1353 DI 10.1152/ajpgi.00020.2008 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 310YU UT WOS:000256567800006 PM 18388183 ER PT J AU Mimiaga, MJ Fair, AD Tetu, AM Novak, DS VanDerwarker, R Bertrand, T Adelson, S Mayer, KH AF Mimiaga, Matthew J. Fair, Andrew D. Tetu, Ashley M. Novak, David S. VanDerwarker, Rodney Bertrand, Thomas Adelson, Stephan Mayer, Kenneth H. TI Acceptability of an Internet-based partner notification system for sexually transmitted infection exposure among men who have sex with men SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID GAY MEN; RISK; SYPHILIS; DISEASES; BEHAVIOR; HIV AB US men who have sex with men (n=1848) completed an online questionnaire about their willingness to use Internet-based partner notification. Eighty-one percent reported that it would be important to them to receive a partner notification e-mail if they had been exposed to a sexually transmitted infection. Seventy percent reported that if infected, they would use a public health specialist to inform partners of possible exposure through Internet notification. There was broad acceptance of Internet partner notification by at-risk US men who have sex with men, including a willingness to receive or initiate a notification e-mail. C1 [Mayer, Kenneth H.] Brown Univ, Sch Med, Miriam Hosp, Providence, RI 02912 USA. [Mimiaga, Matthew J.; Fair, Andrew D.; Tetu, Ashley M.; VanDerwarker, Rodney; Mayer, Kenneth H.] Fenway Community Hlth, Fenway Inst, Boston, MA 02199 USA. [Adelson, Stephan] Online Buddies Inc, Cambridge, MA USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Novak, David S.; Bertrand, Thomas] Massachusetts Dept Publ Hlth, Div STD Prevent, State Lab Inst, Jamaica, NY USA. RP Mimiaga, MJ (reprint author), Fenway Community Hlth, Fenway Inst, Prudential Tower,4th Fl,800 Boylston St, Boston, MA 02199 USA. EM mmimiaga@fenwayhealth.org NR 25 TC 32 Z9 33 U1 0 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 2008 VL 98 IS 6 BP 1009 EP 1011 DI 10.2105/AJPH.2006.098467 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 308BK UT WOS:000256363100013 PM 17901442 ER PT J AU Checkley, W Brower, R Korpak, A Thompson, BT AF Checkley, William Brower, Roy Korpak, Anna Thompson, B. Taylor CA Acute Resp Distress Syndrome Netwo TI Effects of a clinical trial on mechanical ventilation practices in patients with acute lung injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT 103rd International Conference of the American-Thoracic-Society CY MAY 18-23, 2007 CL San Francisco, CA SP Amer Thorac Soc DE acute lung injury; mechanical ventilation; clinician practices ID RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; TIDAL VOLUMES; PROTECTIVE-VENTILATION; MORTALITY; PULMONARY; STRATEGY; OUTCOMES; EDEMA; ARDS AB Rationale: In a clinical trial by the Acute Respiratory Distress Syndrome Network (ARDSNet), mechanical ventilation with tidal volumes of 6 ml/kg decreased mortality from acute lung injury. However, interpretations of these results generated controversy and it was unclear if this trial would change usual-care practices. Objectives: First, to determine if clinical practices at ARDSNet hospitals changed after the tidal volume trial. Second, to determine if tidal volume and plateau pressure (Pplat) within 48 hours before randomization affected hospital mortality in patients subsequently managed with 6 ml/kg predicted body weight (PBW). Methods: We used preenrollment data from 2,451 patients enrolled in six trials (1996-2005) to describe changes in tidal volume over time. We used logistic regression to determine if preenrollment tidal volume or Pplat affected mortality. Measurements and Main Results: Median preenrollment tidal volume decreased from 10.3 ml/kg PBW (range, 4.3-17.1) during the tidal volume trial (1996-1999) to 7.3 ml/kg PBW (range, 3.9-16.2) after its completion (P < 0.001). Preenrollment tidal volume was not associated with mortality (P = 0.566). The odds of death increased multiplicatively with each cm H(2)O of preenrollment Pplat (P< 0.001) (e.g., the odds of death was 1.37 times greater when preenrollment Pplat increased by 10 cm H(2)O). Conclusions: Physicians used lower tidal volumes after publication of the tidal volume trial. Preenrollment Pplat was strongly associated with mortality, and may reflect disease severity independent of tidal volume. Pplat measured early in the course of acute lung injury, after accounting for tidal volume, is a respiratory system-specific value with strong prognostic significance. C1 [Checkley, William; Brower, Roy] Johns Hopkins Univ, Div Pulm & Crit Care, Sch Med, Baltimore, MD 21205 USA. [Korpak, Anna; Thompson, B. Taylor] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Checkley, W (reprint author), Johns Hopkins Univ, Div Pulm & Crit Care, Sch Med, Baltimore, MD 21205 USA. EM wcheckl1@jhmi.edu FU NHLBI NIH HHS [1F32HL090179-01, N01-HR-16146-54, N01-HR-46046-64] NR 39 TC 53 Z9 57 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUN 1 PY 2008 VL 177 IS 11 BP 1215 EP 1222 DI 10.1164/rccm.200709-1424OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 306QM UT WOS:000256262900008 PM 18356562 ER PT J AU Yu, LY Quinn, DA Garg, HG Hales, CA AF Yu, Lunyin Quinn, Deborah A. Garg, Hari G. Hales, Charles A. TI Deficiency of the NHE1 gene prevents hypoxia-induced pulmonary hypertension and vascular remodeling SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE Na(+)/H(+) exchanger isoform 1; pulmonary hypertension; vascular remodeling; hypoxia; mouse ID NA+/H+ EXCHANGER ISOFORM-1; SMOOTH-MUSCLE-CELLS; NA-H EXCHANGE; SIGNAL-TRANSDUCTION; KINASE INHIBITOR; INTRACELLULAR PH; RHOA ACTIVATION; GROWTH-FACTOR; PROLIFERATION; MICE AB Rationale: Our previous studies found that Na(+)/H(+) exchanger (NHE) activity played an essential role in pulmonary artery smooth muscle cell (PASMC) proliferation and in the development of hypoxia-induced pulmonary hypertension and vascular remodeling. Other investigators recently observed increased expression of the NHE isoform 1 (NHE1) gene in rodents with pulmonary hypertension induced by hypoxia. However, a causal role for the NHE1 gene in pulmonary hypertension has not been determined. Objectives: To determine the causal role of the NHE1 gene in pulmonary hypertension and vascular remodeling. Methods: We used NHE1-null mice to define the role of the NHE1 gene in the development of pulmonary hypertension and remodeling induced by hypoxia and to delineate the NHE1 regulatory pathway. Measurements and Main Results: After 2 weeks of exposure to hypoxia, in contrast to wild-type hypoxic littermates, there was no significant increase in right ventricular systolic pressure, in the ratio of right ventricular to left ventricular plus septal weight [RV/(LV + S)], or in medial wall thickness of the pulmonary arterioles in homozygous mice (NHE1(-/-)). There was a significant decrease in Rho kinase (ROCK1 and ROCK2) expression, accompanied by an increase in p27 expression in NHE1(-/-) mice. Conclusions: Our study demonstrated that deficiency of the NHE1 gene prevented the development of hypoxia-induced pulmonary hypertension and vascular remodeling in mice and revealed a novel regulatory pathway associated with NHE1 signaling. C1 [Yu, Lunyin; Quinn, Deborah A.; Garg, Hari G.; Hales, Charles A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Hales, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. EM chales@partners.org FU NHLBI NIH HHS [HL039150] NR 50 TC 43 Z9 43 U1 1 U2 4 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUN 1 PY 2008 VL 177 IS 11 BP 1276 EP 1284 DI 10.1164/rccm.200710-1522OC PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 306QM UT WOS:000256262900016 PM 18310478 ER PT J AU Wang, ZX Beach, D Su, L Zhai, RH Christiani, DC AF Wang, Zhaoxi Beach, Douglas Su, Li Zhai, Rihong Christiani, David C. TI A genome-wide expression analysis in blood identifies pre-elafin as a biomarker in ARDS SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE gene expression profiling; transcriptomics; acute respiratory distress syndrome; elafin; lung disease ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; LEUKOCYTE PROTEINASE-INHIBITOR; INFLAMMATORY CYTOKINES; NEUTROPHIL APOPTOSIS; GENE; TRANSGLUTAMINASE; INTERLEUKIN-8; TRAPPIN-2; RISK AB Previous microarray-based studies of acute respiratory distress syndrome (ARDS) were performed using various models to mimic disease pathogenesis. The complexity of the pathophysiologic response to direct or indirect lung injury in ARDS is difficult to reconstruct in experimental conditions. Thus, direct analysis of ARDS patient blood may provide valuable information. We investigated genome-wide gene expression profiles in paired whole blood samples from patients with ARDS (n = 8) during the acute stage (within 3 d of diagnosis) and recovery stage of ARDS (around ICU discharge). Among 126 differentially expressed genes, peptidase inhibitor 3 (P13, encoding elafin, a potent neutrophil elastase inhibitor) had the largest fold-change (-3-fold changes, acute stage/recovery stage) in expression, indicating down-regulation during the acute stage of ARDS. We further examined plasma P13 levels in 40 patients with ARDS and 23 at-risk control subjects from the same cohort. There was a coincidence of the microarray findings of lower P13 gene expression with the lower plasma P13 during the acute-stage. The plasma P13 levels were statistically significant different among pre-diagnosis, day of diagnosis, and post-diagnosis groups (ANOVA, P = 0.001), with a trend of decreasing from pre- to post-diagnosis group. The time course of plasma P13 decrease is well correlated with the course of early ARDS development (Pearson correlation coefficient: -0.52, P = 0.0006). Considering that P13 can covalently binding to extracellular matrix in lung, circulating P13 may provide a useful clinical marker for monitoring the early development of ARDS and may have implications for ARDS treatment. C1 [Wang, Zhaoxi; Su, Li; Zhai, Rihong; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Beach, Douglas; Christiani, David C.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Christiani, David C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Wang, ZX (reprint author), 665 Huntington Ave,1-1404B, Boston, MA 02115 USA. EM mikewang@hsph.harvard.edu FU NHLBI NIH HHS [HL60710]; NIEHS NIH HHS [ES00002] NR 52 TC 31 Z9 32 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JUN PY 2008 VL 38 IS 6 BP 724 EP 732 DI 10.1165/rcmb.2007-0354OC PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 303NC UT WOS:000256046200012 PM 18203972 ER PT J AU Perez-Rossello, JM Connolly, SA Newton, AW Thomason, M Jenny, C Sugar, NF Kleinman, PK AF Perez-Rossello, Jeannette M. Connolly, Susan A. Newton, Alice W. Thomason, Michael Jenny, Carole Sugar, Naomi F. Kleinman, Paul K. TI Pubic ramus radiolucencies in infants: The good, the bad, and the indeterminate SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE child abuse; fractures; infants; pelvis; pubic bone ID BATTERED-CHILD SYNDROME; ABUSE AB OBJECTIVE. The purpose of this study was to examine imaging findings that differentiate inflicted injuries from developmental variants of the superior pubic ramus in healthy and abused infants. CONCLUSION. A superior pubic ramus fracture and a developmental variant can be difficult to differentiate radiographically. A smoothly marginated vertical radiolucency of the superior pubic ramus detected without other features suggesting infant abuse should not be interpreted as a fracture. C1 [Perez-Rossello, Jeannette M.; Connolly, Susan A.; Newton, Alice W.; Kleinman, Paul K.] Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. [Connolly, Susan A.; Newton, Alice W.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Thomason, Michael] Greenville Mem Med Ctr, Dept Radiol Serv, Greenville, SC USA. [Jenny, Carole] Hasbro Childrens Hosp, Child Protect Program, Providence, RI USA. [Sugar, Naomi F.] Univ Washington, Harborview Med Ctr, Dept Pediat, Seattle, WA 98104 USA. RP Perez-Rossello, JM (reprint author), Childrens Hosp, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. EM jeannette.perez-rossello@childrens.harvard.edu NR 11 TC 3 Z9 3 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 2008 VL 190 IS 6 BP 1481 EP 1486 DI 10.2214/AJR.07.3251 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 303TV UT WOS:000256064700015 PM 18492895 ER PT J AU Liu, CH Yu, CY Catalano, OA Mueller, PR AF Liu, Chang-Hsien Yu, Chih-Yung Catalano, Onofrio A. Mueller, Peter R. TI Radiological reasoning: Imaging differentiation of a solitary hepatic mass SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT; hepatic actinomycosis; MRI ID ACTINOMYCOTIC ABSCESSES; LIVER C1 [Liu, Chang-Hsien; Catalano, Onofrio A.; Mueller, Peter R.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Liu, Chang-Hsien; Yu, Chih-Yung; Catalano, Onofrio A.] Tri Serv Gen Hosp, Dept Radiol, Taipei, Taiwan. Natl Def Med Ctr, Taipei, Taiwan. [Catalano, Onofrio A.] Azienda Osped Benevento G Rummo, Dept Radiol, Beltiglio di Ceppaloni, BN, Italy. RP Liu, CH (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent Radiol, White 270,55 Fruit St, Boston, MA 02114 USA. EM cute610627@gmail.com NR 12 TC 2 Z9 2 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 2008 VL 190 IS 6 SU S BP S57 EP S61 DI 10.2214/AJR.07.7005 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 303ST UT WOS:000256061900005 PM 18492932 ER PT J AU Liu, CH Rivard, DC Silva, AC Burkholz, KJ Beaty, SD AF Liu, Chang-Hsien Rivard, Douglas C. Silva, Alvin C. Burkholz, Kimberly J. Beaty, Sean D. TI Imaging of focal hepatic lesions: Self-assessment module SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE focal hepatic lesions; hemangiomatosis; hepatoblastoma; Staphylococcus aureus ID NON-HODGKINS-LYMPHOMA; MR-IMAGES; HEMANGIOMAS; LIVER; APPEARANCE AB Focal hepatic lesions are one of the diagnostic challenges in daily practice. This article focuses on the imaging features of focal hepatic lesions on different imaging modalities, including sonography, CT, and MRI. C1 [Silva, Alvin C.; Burkholz, Kimberly J.; Beaty, Sean D.] Mayo Clin, Dept Diagnost Radiol, Scottsdale, AZ USA. [Liu, Chang-Hsien] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Missouri, Kansas City, MO 64110 USA. [Rivard, Douglas C.] Childrens Mercy Hosp & Clin, Dept Radiol, Kansas City, MO USA. RP Silva, AC (reprint author), Mayo Clin, Dept Diagnost Radiol, 13400 E Shea Blvd, Scottsdale, AZ USA. EM silva.alvin@mayo.edu NR 15 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 2008 VL 190 IS 6 SU S BP S65 EP S68 DI 10.2214/AJR.07.7076 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 303ST UT WOS:000256061900007 PM 18492934 ER PT J AU Gomoll, AH Pappas, G Forsythe, B Warner, JJP AF Gomoll, Andreas H. Pappas, George Forsythe, Brian Warner, Jon J. P. TI Individual skill progression on a virtual reality simulator for shoulder arthroscopy - A 3-year follow-up study SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE surgical education; shoulder arthroscopy; arthroscopy simulator ID EXPERIENCE; PERFORMANCE; IMPACT; GAMES AB Background: Previous studies have demonstrated a correlation between surgical experience and performance on a virtual reality arthroscopy simulator but only provided single time point evaluations. Additional longitudinal studies are necessary to confirm the validity of virtual reality simulation before these teaching aids can be more fully recommended for surgical education. Hypothesis: Subjects will show improved performance on simulator retesting several years after an initial baseline evaluation, commensurate with their advanced surgical experience. Study Design: Controlled laboratory study. Methods: After gaining further arthroscopic experience, 10 orthopaedic residents underwent retesting 3 years after initial evaluation on a Procedicus virtual reality arthroscopy simulator. Using a paired t test, simulator parameters were compared in each subject before and after additional arthroscopic experience. Subjects were evaluated for time to completion, number of probe collisions with the tissues, average probe velocity, and distance traveled with the tip of the simulated probe compared to an optimal computer-determined distance. In addition, to evaluate consistency of simulator performance, results were compared to historical controls of equal experience. Results: Subjects improved significantly (P < .02 for all) in the 4 simulator parameters: completion time (-51%), probe collisions (-29%),average velocity (+122%), and distance traveled (-32%). With the exception of probe velocity, there were no significant differences between the performance of this group and that of a historical group with equal experience, indicating that groups with similar arthroscopic experience consistently demonstrate equivalent scores on the simulator. Conclusion: Subjects significantly improved their performance on simulator retesting 3 years after initial evaluation. Additionally, across independent groups with equivalent surgical experience, similar performance can be expected on simulator parameters; thus it may eventually be possible to establish simulator benchmarks to indicate likely arthroscopic skill. Clinical Relevance: These results further validate the use of surgical simulation as an important tool for the evaluation of surgical skills. C1 [Gomoll, Andreas H.; Pappas, George; Forsythe, Brian] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Warner, Jon J. P.] Harvard Univ, Shoulder Serv, Boston, MA 02115 USA. [Warner, Jon J. P.] Harvard Univ, Sch Med, Dept Orthoped Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Gomoll, AH (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthoped Surg, 75 Francis St, Boston, MA 02115 USA. EM agomoll@yahoo.com NR 11 TC 43 Z9 43 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD JUN PY 2008 VL 36 IS 6 BP 1139 EP 1142 DI 10.1177/0363546508314406 PG 4 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 303RL UT WOS:000256058100015 PM 18326032 ER PT J AU Van de Velde, SK Gill, TJ DeFrate, LE Papannagari, R Li, G AF Van de Velde, Samuel K. Gill, Thomas J. DeFrate, Louis E. Papannagari, Ramprasad Li, Guoan TI The effect of anterior cruciate ligament deficiency and reconstruction on the patellofemoral joint SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE anterior cruciate ligament (ACL); patellar tracking; patellofemoral joint; knee kinematics; anterior cruciate ligament (ACL) reconstruction ID PATELLAR TENDON-BONE; IN-VIVO ELONGATION; ARTICULAR-CARTILAGE; TIBIOFEMORAL KINEMATICS; KNEE FLEXION; CONTACT; MOTION; WEIGHTBEARING; AUTOGRAFTS; MECHANICS AB Background: Little is known about the effect of anterior cruciate ligament deficiency and reconstruction on the patellofemoral joint. Hypothesis: Anterior cruciate ligament deficiency changes the patellofemoral joint biomechanics. Reconstruction of the ligament does not restore the altered patellofemoral joint function. Study Design: Controlled laboratory study. Methods: Eight patients with an acute anterior cruciate ligament injury in 1 knee and the contralateral side intact were included in the study. Magnetic resonance and dual-orthogonal fluoroscopic imaging techniques were used to compare the patellofemoral joint function during a single-leg lunge between the intact, the anterior cruciate ligament-injured, and the anterior cruciate ligament-reconstructed knee. Data on the patellar tendon apparent elongation and orientation, patellar tracking, and patellofemoral cartilage contact location were collected preoperatively and at 6 months after reconstruction. Results: Anterior cruciate ligament deficiency caused a significant apparent elongation and change in orientation of the patellar tendon. It decreased the flexion and increased the valgus rotation and tilt of the patella. Anterior cruciate ligament injury caused a proximal and lateral shift in patellofemoral cartilage contact location. Anterior cruciate ligament reconstruction reduced the abnormal apparent elongation but not the orientation of the patellar tendon, and it restored the patellar flexion and proximal shift in contact. The abnormal patellar rotation, tilt, and lateral shift in cartilage contact persisted after reconstruction. Conclusion: The altered function of the patellar tendon in anterior cruciate ligament deficiency resulted in an altered patellar tracking and patellofemoral cartilage contact. Persistent changes in patellofemoral joint function after anterior cruciate ligament reconstruction imply that reconstruction of the anterior cruciate ligament does not restore the normal function of the patellofemoral joint, Clinical Relevance: The abnormal kinematics of the patellofemoral joint might predispose the patellofemoral cartilage to degenerative changes associated with anterior cruciate ligament deficiency, even if the ligament is reconstructed in a way that restores anteroposterior knee laxity. C1 [Van de Velde, Samuel K.; Gill, Thomas J.; DeFrate, Louis E.; Papannagari, Ramprasad] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02114 USA. [DeFrate, Louis E.; Li, Guoan] Duke Univ, Med Ctr, Orthopaed Res Labs, Durham, NC USA. RP Li, G (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU NIAMS NIH HHS [R21 AR051078] NR 41 TC 28 Z9 29 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD JUN PY 2008 VL 36 IS 6 BP 1150 EP 1159 DI 10.1177/0363546508314404 PG 10 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 303RL UT WOS:000256058100017 PM 18400949 ER PT J AU Humar, A Fishman, JA AF Humar, A. Fishman, J. A. TI Donor-derived infection: Old problem, new solutions ? SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material ID ORGAN-TRANSPLANTATION; VIRUS C1 [Humar, A.] Univ Alberta, Dept Med, Edmonton, AB, Canada. [Fishman, J. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplant Infect Dis & Compromised Host, MGH Transplantat Ctr,Infect Dis Div, Boston, MA USA. RP Humar, A (reprint author), Univ Alberta, Dept Med, Edmonton, AB, Canada. EM ahumar@ualberta.ca NR 6 TC 9 Z9 9 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2008 VL 8 IS 6 BP 1087 EP 1088 DI 10.1111/j.1600-6143.2008.02246.x PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 307VP UT WOS:000256347100004 PM 18522543 ER PT J AU Firth, PG Pattinson, KTS AF Firth, P. G. Pattinson, K. T. S. TI Anaesthesia and high altitude: a history SO ANAESTHESIA LA English DT Editorial Material ID OPERATION EVEREST-II; 1 MILE; SURGERY; OXYGEN; ANALGESIA AB During an expedition to climb Everest in 1933, expedition doctor Raymond Greene administered an open-drop chloroform anaesthetic to a Tibetan patient at an altitude of more than 14 000 feet. The patient's subsequent apparent cardiopulmonary arrest has long been attributed to the effects of altitude on anaesthetic delivery. However, anaesthetics can be safely administered at a wide variety of altitudes by adequately trained and experienced anaesthetists. The problems may have arisen from an inadequate depth of anaesthesia consequent to decreased chloroform vaporisation in a cold environment, Greene's concern about potential depression of ventilation and the contemporary lack of a precise approach to assessing depth of anaesthesia. C1 [Firth, P. G.] Harvard Univ, Sch Med, Dept Anaesthesia & Crit Care, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pattinson, K. T. S.] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Anaesthet, Oxford OX3 9DU, England. RP Firth, PG (reprint author), Harvard Univ, Sch Med, Dept Anaesthesia & Crit Care, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM pfirth@partners.org NR 53 TC 6 Z9 6 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0003-2409 J9 ANAESTHESIA JI Anaesthesia PD JUN PY 2008 VL 63 IS 6 BP 662 EP 670 DI 10.1111/j.1365-2044.2008.05446.x PG 9 WC Anesthesiology SC Anesthesiology GA 298PK UT WOS:000255699400018 PM 18477281 ER PT J AU Ehrenfeld, JM Walsh, JL Sandberg, WS AF Ehrenfeld, Jesse M. Walsh, John L. Sandberg, Warren S. TI Right- and left-sided Mallinckrodt double-lumen tubes have identical clinical performance SO ANESTHESIA AND ANALGESIA LA English DT Article ID ANESTHESIA RECORDS; THORACIC-SURGERY; ENDOTRACHEAL-TUBES; BLOOD-PRESSURE; HANDWRITTEN; SAFETY; MARGIN AB BACKGROUND: Left-sided double-lumen tubes are perceived to be safer than right-sided tubes, because they may be less prone to malposition. If this is true, then the incidence and severity of hypoxemia, hypercapnea, and high airway pressures should be higher for right-sided tubes during thoracic surgery than for left-sided tubes. METHODS: We retrospectively reviewed thoracic surgical anesthetics between April 15, 2003, and December 31, 2004, using an automated anesthesia information management system. The system automatically records pulse oximetry, end-tidal carbon dioxide, and peak inspiratory pressure data every 30 s. Side of surgery and double-lumen tube placement are also documented. We compared the frequency of right- and left-sided Mallinckrodt tube use by thoracic anesthesiologists. Next, we examined the incidence, duration, and severity of hypoxemia (Spo(2) <90%), hypercapnea (Etco(2) >45 mm Hg) and high airway pressures (peak inspiratory pressure >35 cm H(2)O) for lung and chest wall surgery patients. Group counts and means were compared by standard statistical methods. RESULTS: Right- (n = 241) and left- (n = 450) sided tubes were almost exclusively used on the side contralateral to surgery. There were no differences in the incidence or duration of hypoxemia, hypercarbia, or high airway pressures. There was a small but significant increase in Etco(2) for patients having left lung ventilation. CONCLUSIONS: The supposition that left-sided double-lumen tubes are safer than right-sided tubes when intraoperative hypoxemia, hypercapnea, and high airway pressures are used as criteria for safety is not supported by our data comparing the two types of tubes from one manufacturer. C1 [Ehrenfeld, Jesse M.; Walsh, John L.; Sandberg, Warren S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Sandberg, WS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 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 15 TC 14 Z9 16 U1 0 U2 0 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 JUN PY 2008 VL 106 IS 6 BP 1847 EP 1852 DI 10.1213/ane.0b013e31816f24d5 PG 6 WC Anesthesiology SC Anesthesiology GA 303XU UT WOS:000256075200038 PM 18499621 ER PT J AU Liang, YF Kimball, WR Kacmarek, RM Zapol, WM Jiang, YD AF Liang, Yafen Kimball, William R. Kacmarek, Robert M. Zapol, Warren M. Jiang, Yandong TI Nasal ventilation is more effective than combined oral-nasal ventilation during induction of general anesthesia in adult subjects SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Anesthesiologists CY OCT 14-17, 2007 CL San Francisco, CA SP Amer Soc Anesthesiologists ID POSITIVE AIRWAY PRESSURE; DIFFICULT MASK VENTILATION; OBSTRUCTIVE SLEEP-APNEA; PROPOFOL ANESTHESIA; HUMANS AB Background The authors hypothesized that nasal mask ventilation may be more effective than combined oral-nasal mask ventilation during induction of general anesthesia. They tested this hypothesis by comparing the volume of carbon dioxide removed per breath with nasal versus combined oral-nasal mask ventilation in nonparalyzed, apneic, adult subjects during induction of general anesthesia. Methods: Fifteen adult subjects receiving general anesthesia were ventilated first with a combined oral-nasal mask and then with only a nasal mask. The patient's head was maintained in a neutral position, without head extension or lower jaw thrust. Respiratory parameters were recorded simultaneously from both the nasal and oral masks regardless of ventilation approach. Results: The volume of carbon dioxide removed per breath during nasal mask ventilation (median, 5.0 ml; interquartile range, 3.4-8.8 ml) was significantly larger than that during combined oral-nasal mask ventilation (median, 0.0 ml; interquartile range, 0.0-0.4 nil; P = 0.001); even the peak inspiratory airway pressure during nasal ventilation (16.7 +/- 2.7 cm H2O) was lower than that during combined oral-nasal ventilation (24.5 +/- 4.7 cm H2O; P = 0.002). The expiratory tidal volume during nasal ventilation (259.8 +/- 134.2 ml) was also larger than that during combined oral-nasal ventilation (98.9 +/- 103.4 ml; P = 0.003). Conclusions: Nasal mask ventilation was more effective than combined oral-nasal mask ventilation in apneic, nonparalyzed, adult subjects during induction of general anesthesia. The authors suggest that nasal mask ventilation, rather than full face-mask ventilation, be considered during induction of anesthesia. C1 [Jiang, Yandong] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Jiang, Yandong] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jiang, YD (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Jackson 422, Boston, MA 02114 USA. EM yjiang@partners.org NR 17 TC 22 Z9 22 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUN PY 2008 VL 108 IS 6 BP 998 EP 1003 DI 10.1097/ALN.0b013e318174f027 PG 6 WC Anesthesiology SC Anesthesiology GA 305UL UT WOS:000256203200006 PM 18497599 ER PT J AU Meyer, MA Seim, AR Fairbrother, P Egan, MT Sandberg, WS AF Meyer, Mark A. Seim, Andreas R. Fairbrother, Pamela Egan, Marie T. Sandberg, Warren S. TI Automatic time-motion study of a multistep preoperative process SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Anesthesiologists CY OCT 14-17, 2007 CL San Francisco, CA SP Amer Soc Anesthesiologists ID TRACKING SYSTEM; REAL-TIME AB Background: Hospitals use time-motion studies to monitor process effectiveness and patient waiting. Manual tracking is labor-intensive and potentially influences system performance. New technology known as indoor positioning systems (HIS) may allow automatic monitoring of patient waiting and progress. The authors tested whether an IPS can track patients through a multistep preoperative process. Methods. The authors used an IPS between October 14, 2005, and June 13, 2006, to track patients in a multistep ambulatory preoperative process: needle localization and excisional biopsy of a breast lesion. The process was distributed across the ambulatory surgery and radiology departments of a large academic hospital. Direct observation of the process was used to develop a workflow template. The authors then developed software to convert the IPS data into usable time-motion data suitable for monitoring process efficiency over time. Results: The authors assigned tags to 306 patients during the study period. Eighty patients never underwent the procedure or never had their tag affixed. one hundred seventy-seven (78%) of the remaining 226 patients successfully matched the workflow template. Process time stamps were automatically extracted from the successful matches, measuring time before radiology (mean +/- SD, 77 +/- 35 min), time in radiology (105 +/- 35 min), and time between radiology and operating room (80 +/- 60 min), which summed to total preoperative time (261 +/- 67 min). Conclusions. The authors have demonstrated that it is possible to use a combination of IPS technology and sequence alignment pattern matching software to automate the time-motion study of patients in a multidepartment, multistep process with the only day-of-surgery intervention being the application of a tag when the patient arrives. C1 [Fairbrother, Pamela; Sandberg, Warren S.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Sandberg, WS (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Clin 3, Boston, MA 02114 USA. EM wsandberg@partners.org NR 11 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUN PY 2008 VL 108 IS 6 BP 1109 EP 1116 DI 10.1097/ALN.0b013e31817302ca PG 8 WC Anesthesiology SC Anesthesiology GA 305UL UT WOS:000256203200020 PM 18497613 ER PT J AU Zheng, L Zelen, M AF Zheng, Lu Zelen, Marvin TI MULTI-CENTER CLINICAL TRIALS: RANDOMIZATION AND ANCILLARY STATISTICS SO ANNALS OF APPLIED STATISTICS LA English DT Article DE Multi-center trials; randomization; permuted blocks design; design based analyses ID CANCER; TESTS; MODEL; SURVIVAL AB The purpose of this paper is to investigate and develop methods for analysis of multi-center randomized clinical trials which only rely on the randomization process as a basis of inference. Our motivation is prompted by the fact that most current statistical procedures used in the analysis of randomized multi-center studies are model based. The randomization feature of the trials is usually ignored. An important characteristic of model based analysis is that it is straightforward to model covariates. Nevertheless, in nearly all model based analyses, the effects due to different centers and, in general, the design of the clinical trials are ignored. An alternative to a model based analysis is to have analyses guided by the design of the trial. Our development of design based methods allows the incorporation of centers as well as other features of the trial design. The methods make use of conditioning on the ancillary statistics in the sample space generated by the randomization process. We have investigated the power of the methods and have found that, in the presence of center variation, there is a significant increase in power. The methods have been extended to group sequential trials with similar increases in power. C1 [Zheng, Lu; Zelen, Marvin] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Zelen, Marvin] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zheng, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. EM lzheng@hsph.harvard.edu; zelen@hsph.harvard.edu NR 27 TC 6 Z9 6 U1 0 U2 4 PU INST MATHEMATICAL STATISTICS PI CLEVELAND PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA SN 1932-6157 J9 ANN APPL STAT JI Ann. Appl. Stat. PD JUN PY 2008 VL 2 IS 2 BP 582 EP 600 DI 10.1214/07-AOAS151 PG 19 WC Statistics & Probability SC Mathematics GA 374QC UT WOS:000261057800012 ER PT J AU Mark, EJ Ruangchira-urai, R AF Mark, Eugene J. Ruangchira-urai, Ruchira TI Bronchiolitis interstitial pneumonitis: a pathologic study of 31 lung biopsies with features intermediate between bronchiolitis obliterans organizing pneumonia and usual interstitial pneumonitis, with clinical correlation SO ANNALS OF DIAGNOSTIC PATHOLOGY LA English DT Article DE bronchiolitis; interstitial pneumonitis; cystic fibrosis ID IDIOPATHIC PULMONARY-FIBROSIS; HIGH-RESOLUTION CT; ACUTE EXACERBATION; HYPERSENSITIVITY PNEUMONITIS; HISTOPATHOLOGIC PATTERN; CYSTIC-FIBROSIS; DISEASE; MANAGEMENT; SERIES AB Bronchiolitis combined with interstitial pneumonitis generally has been equated with bronchiolitis obliterans organizing pneumonia(BOOP). We describe our experience with lung biopsies that had both bronchiolar and interstitial diseases. We studied 31 patients who had respiratory difficulty leading to open lung biopsy, which showed a combination of both prominent bronchiolitis and prominent interstitial pneumonitis. We compared these cases clinically and pathologically with 6 other pulmonary diseases, namely, bronchiolitis obliterans, BOOP, nonspecific interstitial pneumonitis, usual interstitial pneumonitis, airway-centered interstitial fibrosis, and idiopathic bronchiolocentric interstitial pneumonia, and with 10 cases of cystic fibrosis, an unrelated disease with both bronchiolar and interstitial pathology. The commonality of our cases was a combination of bronchiolitis and interstitial inflammation and fibrosis but little or no intra-alveolar organizing pneumonia. Bronchiolitis obliterans with organizing pneumonia involved less area than the interstitial pneumonitis in each case. All 19 patients for whom we had follow-up received corticosteroids for their pulmonary diseases. Seven patients had improvement in symptoms and pulmonary function test results and radiographic findings, 5 patients experienced subjective improvement with unchanged results of pulmonary function tests or chest x-ray, 1 patient's condition was unchanged, 6 patients' disease worsened, and 4 of these 6 died. The natural history of these cases, which we have designated bronchiolitis interstitial pneumonitis, seems more sanguine than usual interstitial pneumonitis and worse than BOOP at least in the short term. On the one hand, response to corticosteroids was not as frequent as generally accepted for BOOP. On the other hand, disease did not progress in most patients on corticosteroids. (C) 2008 Elsevier Inc. All rights reserved. C1 [Mark, Eugene J.; Ruangchira-urai, Ruchira] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02214 USA. [Mark, Eugene J.; Ruangchira-urai, Ruchira] Harvard Univ, Sch Med, Boston, MA 02214 USA. [Ruangchira-urai, Ruchira] Mahidol Univ, Siriraj Hosp, Fac Med, Dept Pathol, Bangkok 10700, Thailand. RP Mark, EJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02214 USA. EM emark@partners.org NR 43 TC 13 Z9 15 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1092-9134 J9 ANN DIAGN PATHOL JI Ann. Diagn. Pathol. PD JUN PY 2008 VL 12 IS 3 BP 171 EP 180 DI 10.1016/j.anndiagpath.2007.07.002 PG 10 WC Pathology SC Pathology GA 308KZ UT WOS:000256390200003 PM 18486892 ER PT J AU Eichler, FS Ren, JQ Cossoy, M Rietsch, AM Nagpal, S Moser, AB Frosch, MP Ransohoff, RM AF Eichler, Florian S. Ren, Ja-Qian Cossoy, Michael Rietsch, Anna M. Nagpal, Sameer Moser, Ann B. Frosch, Matthew P. Ransohoff, Richard M. TI Is microglial apoptosis an early pathogenic change in cerebral X-linked adrenoleukodystrophy? SO ANNALS OF NEUROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; CHAIN FATTY-ACIDS; MOTOR-NEURONS; WHITE-MATTER; IN-VIVO; CELLS; DISEASE; BRAIN; LEUKODYSTROPHY; PROTEIN AB Objective: Mutations in the X-linked adrenoleukodystrophy (X-ALD) protein cause accumulation of unbranched saturated very-long-chain fatty acids, particularly in brain and adrenal cortex. In humans, the genetic defect causes progressive inflammatory demyelination in the brain, where very-long-chain fatty acids accumulate within phospholipid fractions such as lysophosphatidylcholine. Methods: To address mechanisms of inflammation, we studied microglial activation in human ALD (10 autopsies) and lysophosphatidylcholine (C24:0) injection into the parietal cortex of mice. Results: Unexpectedly, we found a zone lacking microglia within perilesional white matter, immediately beyond the actively demyelinating lesion edge. Surrounding this zone we observed clusters of activated and apoptotic microglia within subcortical white matter. Lysophosphatidylcholine (C24:0) injection in mice led to widespread microglial activation and apoptosis. Interpretation: Our data suggest that the distinct mononuclear phagocytic cell response seen in cerebral X-ALD results, at least in part, from aberrant signaling to cognate receptors on microglia. Our Findings support a hypothesis that microglial apoptosis in perilesional white matter represents an early stage in lesion evolution and may be an appropriate target for intervention in X-ALD patients with evidence of cerebral demyelination. C1 [Eichler, Florian S.; Ren, Ja-Qian; Nagpal, Sameer; Frosch, Matthew P.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cossoy, Michael; Rietsch, Anna M.; Ransohoff, Richard M.] Neuroinflammapital Res Ctr, Lerner Res Inst, Dept Neurosci, Cleveland Clin, Cleveland, OH USA. [Moser, Ann B.] Kennedy Krieger Inst, Baltimore, MD USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, Dept Pathol, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. RP Eichler, FS (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, 55 Fruit St,VBK 731, Boston, MA 02114 USA. EM feichler@partners.org FU PHS HHS [1K08N552550-01A1] NR 28 TC 61 Z9 62 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 2008 VL 63 IS 6 BP 729 EP 742 DI 10.1002/ana.21391 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 321HA UT WOS:000257294100006 PM 18571777 ER PT J AU Yaffe, K Lindquist, K Shlipak, MG Simonsick, E Fried, L Rosano, C Satterfield, S Atkinson, H Windham, BG Kurella-Tamura, M AF Yaffe, Kristine Lindquist, Karla Shlipak, Michael G. Simonsick, Eleanor Fried, Linda Rosano, Caterina Satterfield, Suzanne Atkinson, Hal Windham, B. Gwen Kurella-Tamura, Manjula CA Hlth ABC Study TI Cystatin C as a marker of cognitive function in elders: Findings from the Health ABC study SO ANNALS OF NEUROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; ONSET ALZHEIMER-DISEASE; OLDER-ADULTS; FOLLOW-UP; IMPAIRMENT; RISK; ASSOCIATION; HEART AB We determined whether serum cystatin C, a novel measure of kidney function that colocalizes with brain P-amyloid, is associated with cognition among 3,030 elders. Those with high cystatin C (n = 445; 15%) had worse baseline scores on Modified Mini-Mental State Examination or Digit Symbol Substitution Test (p <= 0.02) compared with those with intermediate/low level and 7 years greater decline (p <= 0.04). Incident cognitive impairment (decline >= 1.0 standard deviation) was greatest among those with high cystatin C (Modified Mini-Mental State Examination: 38 vs 25%; adjusted odds ratio, 1.92; 95% confidence interval, 1.37-2.69; Digit Symbol Substitution: 38 vs 26%; odds ratio, 1.54; 95% confidence interval, 1.10-2.15). C1 [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yaffe, Kristine; Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Sch Med, San Francisco, CA 94121 USA. [Lindquist, Karla; Shlipak, Michael G.; Kurella-Tamura, Manjula] Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA 94143 USA. [Simonsick, Eleanor; Windham, B. Gwen] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Fried, Linda] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Rosano, Caterina] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA USA. [Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Atkinson, Hal] Wake Forest Univ, Sch Med, Dept Internal Med, Sect Gerontol & Geriatr Med, Winston Salem, NC 27109 USA. [Yaffe, Kristine; Shlipak, Michael G.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, Box 181,4150 Clement St, San Francisco, CA 94121 USA. EM kristine.yaffe@ucsf.edu RI Kurella Tamura, Manjula/C-8284-2014; OI Kurella Tamura, Manjula/0000-0001-5227-2479; Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010 FU Intramural NIH HHS; NIA NIH HHS [N01 AG062103, AG-6-2101, AG-6-2103, AG-6-2106, AG021918, N01 AG062101, N01 AG062106, R01 AG021918, R01 AG021918-01A1]; NIDDK NIH HHS [DK069406, R01 DK069406, R01 DK069406-01A1] NR 20 TC 40 Z9 47 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 2008 VL 63 IS 6 BP 798 EP 802 DI 10.1002/ana.21383 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 321HA UT WOS:000257294100014 PM 18496846 ER PT J AU Letai, A AF Letai, A. TI Restoring apoptosis to lymphoma by targeting BCL-2 SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Letai, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2008 VL 19 SU 4 BP 97 EP 97 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500061 ER PT J AU Shipp, MA AF Shipp, M. A. TI Molecular heterogeneity and rational therapeutic targets in DLBCL SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Shipp, M. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 JUN PY 2008 VL 19 SU 4 BP 97 EP 97 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500063 ER PT J AU Winter, JN Zhang, L Li, S Aurora, V Variakojis, D Nelson, B Krajewska, M Habermann, T Fisher, RI Weller, E Reed, JC Horning, SJ Gascoyne, RD AF Winter, J. N. Zhang, L. Li, S. Aurora, V. Variakojis, D. Nelson, B. Krajewska, M. Habermann, T. Fisher, R. I. Weller, E. Reed, J. C. Horning, S. J. Gascoyne, R. D. TI P21, Bcl-2, and the IPI, but not Bcl-6, predict clinical outcome in DLBCL treated with rituximab(R)-CHOP: Long-term followup from E4494 SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Winter, J. N.; Aurora, V.; Variakojis, D.; Nelson, B.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Zhang, L.; Li, S.; Weller, E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Krajewska, M.; Reed, J. C.] Burnham Inst Med Res, Canc Res Ctr, La Jolla, CA USA. [Habermann, T.] Mayo Clin, Rochester, MN USA. [Fisher, R. I.] Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. [Horning, S. J.] Stanford Univ, Stanford, CA 94305 USA. [Gascoyne, R. D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. NR 0 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2008 VL 19 SU 4 BP 99 EP 99 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500067 ER PT J AU Griffin, T Weitzman, S Weinstein, H Chang, M Hutchison, R AF Griffin, T. Weitzman, S. Weinstein, H. Chang, M. Hutchison, R. TI A study of rituximab and ifosfamide, carboplatin, etoposide (ICE) chemotherapy in children with recurrent/refractory B-cell non-Hodgkin lymphoma (NHL) and mature B-cell acute lymphoblastic leukemia (B-ALL). A children's oncology group report SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Griffin, T.] Mem Hosp, South Bend, IN USA. [Weitzman, S.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Weinstein, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chang, M.] Childrens Oncol Grp, Stat Data Off, Gainesville, FL USA. [Hutchison, R.] SUNY Syracuse, Syracuse, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2008 VL 19 SU 4 BP 109 EP 109 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500100 ER PT J AU Foss, F Shak-Shie, N Goy, A Jacobson, E Avandii, R Komrokji, M Pendergrass, K Bolejack, V Watts, K Acosta, M AF Foss, F. Shak-Shie, N. Goy, A. Jacobson, E. Avandii, R. Komrokji, M. Pendergrass, K. Bolejack, V. Watts, K. Acosta, M. TI Phase II study of denileukin diftitox with chop in PTCL SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Foss, F.] Yale Univ, Ctr Canc, New Haven, CT USA. [Shak-Shie, N.] US Oncol, St Louis, MO USA. [Goy, A.] Hackensack U Med Ctr, Hackensack, NJ USA. [Jacobson, E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Avandii, R.] Stanford Univ, Palo Alto, CA 94304 USA. [Komrokji, M.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Pendergrass, K.] Univ Cincinnati, Cincinnati, OH USA. [Bolejack, V.] Kansas City Canc Ctr, Kansas City, KS USA. [Watts, K.] Canc Res & Biostat, Biostat, Seattle, WA USA. [Acosta, M.] Eisai Inc, San Diego, 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. PD JUN PY 2008 VL 19 SU 4 BP 114 EP 114 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500113 ER PT J AU O'Connor, O Czuczman, MS LaCasce, A Gerecitano, J Leonard, JP Dunleavy, K Krivoshik, A Shovlin, M Narwal, A Xiong, H Chiu, Y Wilson, W AF O'Connor, O. Czuczman, M. S. LaCasce, A. Gerecitano, J. Leonard, J. P. Dunleavy, K. Krivoshik, A. Shovlin, M. Narwal, A. Xiong, H. Chiu, Y. Wilson, W. TI A phase 1 study evaluating the safety, PK & efficacy of ABT-263 in subjects with refractory or relapsed lymphoid malignancies SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [O'Connor, O.; Narwal, A.] Columbia Univ, Irving Canc Res Ctr, New York, NY 10027 USA. [Czuczman, M. S.] Roswell Pk Canc Inst, Lymphoma Myeloma Serv, Buffalo, NY 14263 USA. [LaCasce, A.] Dana Farber Canc Inst, Lymphoma Program, Boston, MA 02115 USA. [Gerecitano, J.] Mem Sloan Kettering Canc Ctr, Lymphoma Serv, New York, NY 10021 USA. [Leonard, J. P.] Cornell Univ, Weill Cornell Med Coll, Ithaca, NY 14853 USA. [Dunleavy, K.; Shovlin, M.; Wilson, W.] NCI, NIH, Bethesda, MD 20892 USA. [Krivoshik, A.; Xiong, H.; Chiu, Y.] Abbott Labs, Abbott Pk, IL 60064 USA. NR 0 TC 1 Z9 1 U1 1 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 JUN PY 2008 VL 19 SU 4 BP 115 EP 116 PG 2 WC Oncology SC Oncology GA 312TK UT WOS:000256693500118 ER PT J AU Xiao, C Rajewsky, K AF Xiao, C. Rajewsky, K. TI MicroRNA control in lymphocyte physiology and pathology SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Xiao, C.; Rajewsky, K.] Immune Dis Inst, Boston, MA USA. [Xiao, C.; Rajewsky, K.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 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 JUN PY 2008 VL 19 SU 4 BP 117 EP 117 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500123 ER PT J AU Shipp, MA AF Shipp, M. A. TI Grey zone lymphomas SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Shipp, M. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 JUN PY 2008 VL 19 SU 4 BP 118 EP 118 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500125 ER PT J AU Harris, NL Swerdlow, S Campo, E Jaffe, ES Stein, H Pileri, S Thiele, J Vardiman, J AF Harris, N. L. Swerdlow, S. Campo, E. Jaffe, E. S. Stein, H. Pileri, S. Thiele, J. Vardiman, J. TI The World Health Organization (WHO) classification of lymphoid neoplasms: What's new? SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Harris, N. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Swerdlow, S.] Univ Pittsburgh, Pittsburgh, PA USA. [Campo, E.] Univ Barcelona, Barcelona, Spain. [Jaffe, E. S.] NCI, Bethesda, MD 20892 USA. [Stein, H.] Free Univ Berlin, D-1000 Berlin, Germany. [Pileri, S.] Univ Bologna, Bologna, Italy. [Thiele, J.] Univ Cologne, Cologne, Germany. [Vardiman, J.] Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 7 Z9 7 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2008 VL 19 SU 4 BP 119 EP 119 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500129 ER PT J AU Spencer, A DeAngelo, DJ Prince, HM Bhalla, KN Fischer, T Liu, A Parker, K Jalaluddin, M Scott, JW Ottmann, OG AF Spencer, A. DeAngelo, D. J. Prince, H. M. Bhalla, K. N. Fischer, T. Liu, A. Parker, K. Jalaluddin, M. Scott, J. W. Ottmann, O. G. TI Oral panobinostat (LBH589), a novel deacetylase inhibitor (DACI), demonstrates clinical activity in relapsed/refractory Hodgkin lymphoma (HL) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Spencer, A.] Alfred Hosp, BMT, Melbourne, Vic, Australia. [DeAngelo, D. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Prince, H. M.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Bhalla, K. N.] Georgia Canc Ctr, Coll Med, Augusta, GA USA. [Fischer, T.] Johannes Gutenberg Univ Mainz, Mainz, Germany. [Liu, A.; Parker, K.; Jalaluddin, M.; Scott, J. W.] Novartis Oncol, Early Clin Dev, Florham Pk, NJ USA. [Ottmann, O. G.] Univ Frankfurt, Frankfurt, Germany. RI Ottmann, Oliver/D-5007-2016 OI Ottmann, Oliver/0000-0001-9559-1330 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2008 VL 19 SU 4 BP 128 EP 128 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500153 ER PT J AU Habermann, TM Hong, F Morrison, VA Gascoyne, RD Cassileth, PA Cohn, JR Dakhil, SR Fisher, RI Peterson, BA Weller, EA Horning, SJ AF Habermann, T. M. Hong, F. Morrison, V. A. Gascoyne, R. D. Cassileth, P. A. Cohn, J. R. Dakhil, S. R. Fisher, R. I. Peterson, B. A. Weller, E. A. Horning, S. J. TI Long-term results from the US intergroup trial of rituximab-chop vs chop followed by maintenance vs observation in DLBCL SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Habermann, T. M.] Mayo Clin, Rochester, MN USA. [Hong, F.; Weller, E. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gascoyne, R. D.] BCCA, Vancouver, BC, Canada. [Cassileth, P. A.] Univ Miami, HO, Miami, FL USA. [Cohn, J. R.] Albert Einstein Med Ctr, HO, Philadelphia, PA 19141 USA. [Dakhil, S. R.] Canc Ctr Kansas, HO, Wichita, KS USA. [Fisher, R. I.] Univ Rochester, HO, Rochester, NY USA. [Morrison, V. A.; Peterson, B. A.] Univ Minnesota, Minneapolis, MN USA. [Horning, S. J.] HO, Stanford, 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. PD JUN PY 2008 VL 19 SU 4 BP 147 EP 147 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500223 ER PT J AU Habermann, T Hong, F Morrison, VA Gascoyne, RD Cassileth, PA Cohn, JR Dahkil, SR Fisher, RI Peterson, BA Weller, EA Horning, SJ AF Habermann, T. Hong, F. Morrison, V. A. Gascoyne, R. D. Cassileth, P. A. Cohn, J. R. Dahkil, S. R. Fisher, R. I. Peterson, B. A. Weller, E. A. Horning, S. J. TI The cause of death in diffuse large B-cell lymphoma (DLBCL): Results from the USA intergroup study SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Habermann, T.] Mayo Clin, DOM, Rochester, MN USA. [Hong, F.; Weller, E. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Morrison, V. A.] VA Med Ctr, HO, Arden Hills, VA USA. [Gascoyne, R. D.] BCCA, Vancouver, BC, Canada. [Cassileth, P. A.] Univ Miami, HO, Miami, FL USA. [Cohn, J. R.] Albert Einstein Med Ctr, HO, Philadelphia, PA 19141 USA. [Dahkil, S. R.] Canc Ctr Kansas, HO, Wichita, KS USA. [Fisher, R. I.] Univ Rochester, HO, Rochester, MN USA. [Peterson, B. A.] Univ Minnesota, HO, Minneapolis, MN USA. [Horning, S. J.] HO, Stanford, CA 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. PD JUN PY 2008 VL 19 SU 4 BP 152 EP 152 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500244 ER PT J AU Foss, F Pohlman, B Jacobsen, E Hymes, K Advani, R Kim, Y Belt, R Lerner, A Ooi, C Buhl-Jensen, P Duvic, M AF Foss, F. Pohlman, B. Jacobsen, E. Hymes, K. Advani, R. Kim, Y. Belt, R. Lerner, A. Ooi, C. Buhl-Jensen, P. Duvic, M. TI Phase II open-label trial of belinostat (PXD101) in patients with recurrent or refractory peripheral or cutaneous T-cell lymphoma SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Foss, F.] Yale Univ, New Haven, CT USA. [Pohlman, B.] Cleveland Clin, Cleveland, OH 44106 USA. [Jacobsen, E.] DFCI, Boston, MA USA. [Hymes, K.] NYU Med Ctr, New York, NY 10016 USA. [Belt, R.] Kansas City CC, Lenexa, KS USA. [Lerner, A.] Boston Med Ctr, Boston, MA USA. [Buhl-Jensen, P.] TopoTarget, Copenhagen, Denmark. [Duvic, M.] MD Anderson, Houston, TX USA. NR 0 TC 1 Z9 1 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 JUN PY 2008 VL 19 SU 4 BP 156 EP 156 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500258 ER PT J AU Adamia, S Xu, L Ioakimidis, L Hunter, Z Manning, R Ciccarelli, B Hatjiharissi, E Patterson, C Treon, S AF Adamia, S. Xu, L. Ioakimidis, L. Hunter, Z. Manning, R. Ciccarelli, B. Hatjiharissi, E. Patterson, C. Treon, S. TI Exonic mutations are commonly found in patients with Waldenstrom's macroglobulinemia and family members of WM patients with hyper-IGM syndrome SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Adamia, S.; Xu, L.; Ioakimidis, L.; Hunter, Z.; Manning, R.; Ciccarelli, B.; Hatjiharissi, E.; Patterson, C.; Treon, S.] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 0 Z9 0 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 JUN PY 2008 VL 19 SU 4 BP 166 EP 166 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500290 ER PT J AU Hatjiharissi, E Ciccarelli, BT Xu, L Ioakimidis, L Soumerai, JD Hunter, ZR Adamia, S Treon, SP Patterson, CJ AF Hatjiharissi, E. Ciccarelli, B. T. Xu, L. Ioakimidis, L. Soumerai, J. D. Hunter, Z. R. Adamia, S. Treon, S. P. Patterson, C. J. TI Soluble CD27 levels are correlated with disease stage and response to treatment in waldenstrom's macroglobulinemia (WM) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Hatjiharissi, E.; Ciccarelli, B. T.; Xu, L.; Ioakimidis, L.; Soumerai, J. D.; Hunter, Z. R.; Adamia, S.; Treon, S. P.; Patterson, C. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 1 Z9 1 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 JUN PY 2008 VL 19 SU 4 BP 177 EP 177 PG 1 WC Oncology SC Oncology GA 312TK UT WOS:000256693500329 ER PT J AU Treon, SP AF Treon, S. P. TI Novel insights into the pathogenesis and treatment of Waldenstrom's macroglobulinemia SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Conference on Malignant Lymphoma CY JUN 04-07, 2008 CL Lugano, SWITZERLAND C1 [Treon, S. P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Treon, S. P.] Bing Ctr WM, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2008 VL 19 SU 4 BP 268 EP 269 PG 2 WC Oncology SC Oncology GA 312TK UT WOS:000256693500632 ER PT J AU Burstein, HJ Storniolo, AM Franco, S Forster, J Stein, S Rubin, S Salazar, VM Blackwell, KL AF Burstein, H. J. Storniolo, A. M. Franco, S. Forster, J. Stein, S. Rubin, S. Salazar, V. M. Blackwell, K. L. TI A phase II study of lapatinib monotherapy in chemotherapy-refractory HER2-positive and HER2-negative advanced or metastatic breast cancer SO ANNALS OF ONCOLOGY LA English DT Article DE breast cancer; EGFR; ErbB2; targeted therapy; tyrosine kinase inhibitor; trastuzumab ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; TRASTUZUMAB RESISTANCE; IN-VITRO; CELLS; GW572016; AMPLIFICATION; CONTRIBUTES; ACTIVATION; THERAPY AB Background: The efficacy and tolerability of the epidermal growth factor receptor/human epidermal growth factor receptor type 2 (HER2) tyrosine kinase inhibitor lapatinib in refractory metastatic breast cancer were assessed. Patients and methods: In a phase II, open-label study, patients with previously treated HER2-positive (n = 140) or HER2-negative (n = 89) metastatic breast cancer received once-daily oral lapatinib 1500 mg/day. Results: Most (76%) patients had received four or more lines of prior therapy. The response rate in the HER2-positive cohort was 4.3% by investigator assessment and 1.4% by independent assessment. Both assessments established that similar to 6% of HER2-positive patients derived clinical benefit from lapatinib, being progression free for >= 6 months. No objective tumor responses occurred in the HER2-negative cohort. Independent review assessments of median time to progression and median progression-free survival were similar in the HER2-positive and HER2-negative cohorts (9.1 and 7.6 weeks, respectively). All responders exhibited HER2 overexpression (3+ by immunohistochemistry), and five of six responders were HER2 amplified by FISH. Lapatinib-related adverse events, including diarrhea (54%), rash (30%), and nausea (24%), were primarily mild to moderate in severity. Conclusions: Lapatinib monotherapy had modest clinical activity in HER2-positive metastatic breast cancer that progressed on prior trastuzumab regimens. No apparent clinical activity was observed in chemotherapy-refractory, HER2-negative disease. C1 [Burstein, H. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Storniolo, A. M.] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. [Franco, S.] Mem Canc Inst, Hollywood, FL USA. [Forster, J.; Stein, S.; Rubin, S.; Salazar, V. M.] GlaxoSmithKline Inc, Med Dev Ctr Oncol, Collegeville, PA USA. [Blackwell, K. L.] Duke Univ, Med Ctr, Durham, NC USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM hburstein@partners.org NR 31 TC 120 Z9 122 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2008 VL 19 IS 6 BP 1068 EP 1074 DI 10.1093/annonc/mdm601 PG 7 WC Oncology SC Oncology GA 306SM UT WOS:000256268100006 PM 18283035 ER PT J AU Untch, M Gelber, RD Jackisch, C Procter, M Baselga, J Bell, R Cameron, D Bari, M Smith, I Leyland-Jones, B de Azambuja, E Wermuth, P Khasanov, R Feng-yi, F Constantin, C Mayordomo, JI Su, CH Yu, SY Lluch, A Senkus-Konefka, E Price, C Haslbauer, F Sahui, TS Srimuninnimit, V Colleoni, M Coates, AS Piccart-Gebhart, MJ Goldhirsch, A AF Untch, M. Gelber, R. D. Jackisch, C. Procter, M. Baselga, J. Bell, R. Cameron, D. Bari, M. Smith, I. Leyland-Jones, B. de Azambuja, E. Wermuth, P. Khasanov, R. Feng-yi, F. Constantin, C. Mayordomo, J. I. Su, C. -H. Yu, S. -Y. Lluch, A. Senkus-Konefka, E. Price, C. Haslbauer, F. Suarez Sahui, T. Srimuninnimit, V. Colleoni, M. Coates, A. S. Piccart-Gebhart, M. J. Goldhirsch, A. CA HERA Study Team TI Estimating the magnitude of trastuzumab effects within patient subgroups in the HERA trial SO ANNALS OF ONCOLOGY LA English DT Article DE adjuvant therapy; breast cancer; disease-free survival; HER2-oncogene; subgroubs; trastuzumab ID HER2-POSITIVE BREAST-CANCER; ADJUVANT CHEMOTHERAPY AB Background: Trastuzumab (Herceptin (R)) improves disease-free survival (DFS) and overall survival for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. We aimed to assess the magnitude of its clinical benefit for subpopulations defined by nodal and steroid hormone receptor status using data from the Herceptin Adjuvant (HERA) study. Patients and methods: HERA is an international multicenter randomized trial comparing 1 or 2 years of trastuzumab treatment with observation after standard chemotherapy in women with HER2-positive breast cancer. In total, 1703 women randomized to 1-year trastuzumab and 1698 women randomized to observation were included in these analyses. Median follow-up was 23.5 months. The primary endpoint was DFS. Results: The overall hazard ratio (HR) for trastuzumab versus observation was 0.64 [95% confidence interval (CI) 0.54-0.76; P < 0.0001], ranging from 0.46 to 0.82 for subgroups. Estimated improvement in 3-year DFS in subgroups ranged from +11.3% to +0.6%. Patients with the best prognosis (those with node-negative disease and tumors 1.1-2.0 cm) had benefit similar to the overall cohort (HR 0.53, 95% CI 0.26-1.07; 3-year DFS improvement +4.6%, 95% CI -4.0% to 13.2%). Conclusions: Adjuvant trastuzumab therapy reduces the risk of relapse similarly across subgroups defined by nodal status and steroid hormone receptor status, even those at relatively low risk for relapse. C1 [Gelber, R. D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. 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[Goldhirsch, A.] Oncol Inst So Switzerland, Bellinzona, Switzerland. RP Gelber, RD (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM gelber@jimmy.harvard.edu RI Mayordomo, Jose/K-3453-2013; OI Senkus, Elzbieta/0000-0001-6855-397X NR 10 TC 104 Z9 110 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2008 VL 19 IS 6 BP 1090 EP 1096 DI 10.1093/annonc/mdn005 PG 7 WC Oncology SC Oncology GA 306SM UT WOS:000256268100009 PM 18296421 ER EF