FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Sabatine, MS Braunwald, E AF Sabatine, MS Braunwald, E TI Editorial comment - Another look at the age-old question - Which came first, the elevated C-reactive protein or the atherothrombosis? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID ACUTE CORONARY SYNDROMES; APPARENTLY HEALTHY-MEN; UNSTABLE ANGINA; ARTERY-DISEASE; INFLAMMATION; RISK; INTERLEUKIN-6; ATORVASTATIN; THERAPY; EVENTS C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Braunwald, E (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 75 Francis St,350 Longwood Ave,Off Level 1, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 20 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 18 PY 2005 VL 45 IS 2 BP 244 EP 245 DI 10.1016/j.jacc.2004.10.021 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 889IY UT WOS:000226437900010 PM 15653022 ER PT J AU Shlipak, MG Sarnak, MJ Katz, R Fried, L Seliger, S Newman, A Siscovick, D Stehman-Breen, C AF Shlipak, MG Sarnak, MJ Katz, R Fried, L Seliger, S Newman, A Siscovick, D Stehman-Breen, C TI Cystatin-C and mortality in elderly persons with heart failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID RENAL-FUNCTION; RISK-FACTORS; MARKER; DYSFUNCTION; CREATININE AB OBJECTIVES We sought to evaluate cystatin-C, a novel measure of renal function, as a predictor of mortality in elderly persons with heart failure (HF) and to compare it with creatinine. BACKGROUND Renal function is an important prognostic factor in patients with HF, but creatinine levels, which partly reflect muscle mass, may be insensitive for detecting renal insufficiency. METHODS A total of 279 Cardiovascular Health Study participants with prevalent HF and measures of serum cystatin-C and creatinine were followed for mortality outcomes over a median of 6.5 years. RESULTS Median creatinine and cystatin-C levels were 1.05 mg/dl and 1.26 mg/l. Each standard deviation increase in cystatin-C (0.35 mg/l) was associated with a 31% greater adjusted mortality risk (95% confidence interval [CI] 20% to 43%, p < 0.001), whereas each standard deviation increase in creatinine (0.39 mg/dl) was associated with a 17% greater adjusted mortality risk (95% CI 1% to 36%, p = 0.04). When both measures were combined in a single adjusted model, cystatin-C remained associated with elevated mortality risk (hazard ratio 1.60, 95% CI 1.32 to 1.94), whereas creatinine levels appeared associated with lower risk (hazard ratio 0.73, 95% CI 0.57 to 0.95). CONCLUSIONS Cystatin-C is a stronger predictor of mortality than creatinine in elderly persons with HF. If confirmed in future studies, this new marker of renal function could improve risk stratification in patients with HF. (C) 2005 by the American College of Cardiology Foundation C1 Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94121 USA. Tufts Univ, New England Med Ctr, Dept Med, Div Nephrol, Boston, MA 02111 USA. Collaborat Hlth Studies Coordinating Ctr, Seattle, WA USA. Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Med Serv, Pittsburgh, PA USA. Univ Washington, Sch Med, Div Nephrol, Seattle, WA 98195 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA 15260 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol & Hlth Serv, Seattle, WA 98195 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. RP Shlipak, MG (reprint author), Vet Affairs Med Ctr, Gen Internal Med Sect, 4150 Clement St, San Francisco, CA 94121 USA. EM shlip@itsa.ucsf.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [N01 HC 85085, N01 HC 15103, N01 HC 35129, N01 HC 85079, N01 HC 85080, N01 HC 85081, N01 HC 85082, N01 HC 85083, N01 HC 85084, N01 HC 85086, R01 HL 073208] NR 14 TC 125 Z9 136 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 18 PY 2005 VL 45 IS 2 BP 268 EP 271 DI 10.1016/j.jacc.2004.09.061 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 889IY UT WOS:000226437900014 PM 15653026 ER PT J AU Milne, TA Hughes, CM Lloyd, R Yang, ZH Rozenblatt-Rosen, O Dou, YL Schnepp, RW Krankel, C LiVolsi, VA Gibbs, D Hua, XX Roeder, RG Meyerson, M Hess, JL AF Milne, TA Hughes, CM Lloyd, R Yang, ZH Rozenblatt-Rosen, O Dou, YL Schnepp, RW Krankel, C LiVolsi, VA Gibbs, D Hua, XX Roeder, RG Meyerson, M Hess, JL TI Menin and MLL cooperatively regulate expression of cyclin-dependent kinase inhibitors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MEN1; methyltransferase; tumor suppressor ID MULTIPLE ENDOCRINE NEOPLASIA; HISTONE METHYLTRANSFERASE COMPLEX; TUMOR SUPPRESSION; GENE-EXPRESSION; BETA-CELL; MICE; P27(KIP1); TRITHORAX; TYPE-1; P18(INK4C) AB Mutations in the MEN1 gene are associated with the multiple endocrine neoplasia syndrome type 1 (MEN1), which is characterized by parathyroid hyperplasia and tumors of the pituitary and pancreatic islets. The mechanism by which MEN1 acts as a tumor suppressor is unclear. We have recently shown that menin, the MEN1 protein product, interacts with mixed lineage leukemia (MILL) family proteins in a histone methyltransferase complex including Ash2, Rbbp5, and WDR5. Here, we show that menin directly regulates expression of the cyclin-dependent kinase inhibitors p27(Kip1) and p18(Ink4c). Menin activates transcription by means of a mechanism involving recruitment of MILL to the p27(Kip1) and p18(Ink4c) promoters and coding regions. Loss of function of either MILL or menin results in down-regulation of p27(KiP1) and p18(Ink4c) expression and deregulated cell growth. These findings suggest that regulation of cyclin-dependent kinase inhibitor transcription by cooperative interaction between menin and MILL plays a central role in menin's activity as a tumor suppressor. C1 Univ Penn, Sch Med, Dept Pathol & Lab Med, Stellar Chance Labs 413B, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Mayo Clin & Mayo Fdn, Coll Med, Dept Pathol, Rochester, MN 55905 USA. Rockefeller Univ, Biochem & Mol Biol Lab, New York, NY 10021 USA. RP Hess, JL (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, Stellar Chance Labs 413B, 422 Curie Blvd, Philadelphia, PA 19104 USA. EM jhess@mail.med.upenn.edu RI Meyerson, Matthew/E-7123-2012; Milne, Tom/E-1872-2016 OI Milne, Tom/0000-0002-0413-4271 NR 43 TC 261 Z9 267 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 JAN 18 PY 2005 VL 102 IS 3 BP 749 EP 754 DI 10.1073/pnas.0408836102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 889IF UT WOS:000226436000042 PM 15640349 ER PT J AU Zhang, XQ Smith, DL Merlin, AB Engemann, S Russel, DE Roark, M Washington, SL Maxwell, MM Marsh, JL Thompson, LM Wanker, EE Young, AB Housman, DE Bates, GP Sherman, MY Kazantsev, AG AF Zhang, XQ Smith, DL Merlin, AB Engemann, S Russel, DE Roark, M Washington, SL Maxwell, MM Marsh, JL Thompson, LM Wanker, EE Young, AB Housman, DE Bates, GP Sherman, MY Kazantsev, AG TI A potent small molecule inhibits polyglutamine aggregation in Huntington's disease neurons and suppresses neurodegeneration in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE high-throughput screen; small-molecule therapeutics; Drosophila; R6/2 brain slices; genetic disease ID INTRANUCLEAR INCLUSIONS; TRANSGENIC MICE; DROSOPHILA; MUTATION; ASSAY; REPEAT; MODEL; DYSFUNCTION; GLUTAMINE; PEPTIDES AB Polyglutamine (polyQ) disorders, including Huntington's disease (HD), are caused by expansion of polyQ-encoding repeats within otherwise unrelated gene products. In polyQ diseases, the pathology and death of affected neurons are associated with the accumulation of mutant proteins in insoluble aggregates. Several studies implicate polyQ-dependent aggregation as a cause of neurodegeneration in HD, suggesting that inhibition of neuronal polyQ aggregation may be therapeutic in HD patients. We have used a yeast-based high-throughput screening assay to identify small-molecule inhibitors of polyQ aggregation. We validated the effects of four hit compounds in mammalian cell-based models of HD, optimized compound structures for potency, and then tested them in vitro in cultured brain slices from HD transgenic mice. These efforts identified a potent compound (IC50 = 10 nM) with long-term inhibitory effects on polyQ aggregation in HD neurons. Testing of this compound in a Drosophila HD model showed that it suppresses neurodegeneration in vivo, strongly suggesting an essential role for polyQ aggregation in HD pathology. The aggregation inhibitors identified in this screen represent four primary chemical scaffolds and are strong lead compounds for the development of therapeutics for human polyQ diseases. C1 Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. Kings Coll London, Guys Hosp, Guys Kings & St Thomas GKT Sch Med, London SE1 9RT, England. Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany. Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA. Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92697 USA. Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA. MIT, Canc Res Ctr, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Kazantsev, AG (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, 114 16th St, Charlestown, MA 02129 USA. EM akazantsev@partners.org RI Bates, Gillian/E-1146-2012; OI Bates, Gillian/0000-0002-4041-6305; Wanker, Erich/0000-0001-8072-1630 FU NICHD NIH HHS [R01 HD036081, HD36081, HD36049] NR 38 TC 155 Z9 168 U1 2 U2 18 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 18 PY 2005 VL 102 IS 3 BP 892 EP 897 DI 10.1073/pnas.0408936102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 889IF UT WOS:000226436000066 PM 15642944 ER PT J AU Stadtman, ER Van Remmen, H Richardson, A Wehr, NB Levine, RL AF Stadtman, ER Van Remmen, H Richardson, A Wehr, NB Levine, RL TI Methionine oxidation and aging SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Review DE methionine sulfoxide; methionine; methionine sulfoxide reductase; aging ID MANGANESE SUPEROXIDE-DISMUTASE; RADICAL-CATION COMPLEXES; SULFOXIDE REDUCTASE GENE; PROTEIN OXIDATION; TRABECULAR MESHWORK; CATARACTOUS LENSES; ESCHERICHIA-COLI; ALPHA-SYNUCLEIN; ENZYME-ACTIVITY; HUMAN-EYE AB It is well established that many amino acid residues of proteins are susceptible to oxidation by various forms of reactive oxygen species (ROS), and that oxidatively modified proteins accumulate during aging, oxidative stress, and in a number of age-related diseases. Methionine residues and cysteine residues of proteins are particularly sensitive to oxidation by ROS. However, unlike oxidation of other amino acid residues, the oxidation of these sulfur amino acids is reversible. Oxidation of methionine residues leads to the formation of both R- and S-stereoisomers of methionine sulfoxide (MetO) and most cells contain stereospecific methionine sulfoxide reductases (Msr's) that catalyze the thioredoxin-dependent reduction of MetO residues back to methionine residues. We summarize here results of studies, by many workers, showing that the MetO content of proteins increases with age in a number of different aging models, including replicative senescence and erythrocyte aging, but not in mouse tissues during aging. The change in levels of MetO may reflect alterations in any one or more of many different mechanisms, including (i) an increase in the rate of ROS generation; (ii) a decrease in the antioxidant capacity; (iii) a decrease in proteolytic activities that preferentially degrade oxidized proteins; or (iv) a decrease in the ability to convert MetO residues back to Met residues, due either to a direct loss of Msr enzyme levels or indirectly to a loss in the availability of the reducing equivalents (thioredoxin, thioredoxin reductase, NADPH generation) involved. The importance of Msr activity is highlighted by the fact that aging is associated with a loss of Msr activities in a number of animal tissues, and mutations in mice leading to a decrease in the Msr levels lead to a decrease in the maximum life span, whereas overexpression of Msr leads to a dramatic increase in the maximum life span. Published by Elsevier B.V. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Barshop Ctr Longev Studies, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. NHLBI, Biochem Lab, Bethesda, MD 20892 USA. RP Stadtman, ER (reprint author), NIH, Bldg 50,Room 2140, Bethesda, MD 20892 USA. EM EarlStadtman@nih.gov RI Levine, Rodney/D-9885-2011 NR 47 TC 210 Z9 217 U1 2 U2 34 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD JAN 17 PY 2005 VL 1703 IS 2 BP 135 EP 140 DI 10.1016/j.bbapap.2004.08.010 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 899GE UT WOS:000227132100005 PM 15680221 ER PT J AU Mora, JR Cheng, GY Picarella, D Briskin, M Buchanan, N von Andrian, U AF Mora, JR Cheng, GY Picarella, D Briskin, M Buchanan, N von Andrian, U TI Reciprocal and dynamic control of CD8 T cell homing by dendritic cells from skin- and gut-associated lymphoid tissues SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ADHESION IN-VIVO; CHEMOKINE RECEPTOR; P-SELECTIN; NONLYMPHOID TISSUES; INFLAMED SKIN; RECRUITMENT; EXPRESSION; SUBSETS; DIFFERENTIATION; LOCALIZATION AB T cell activation by intestinal dendritic cells (DC) induces gut-tropism. We show that, reciprocally, DC from peripheral lymph nodes (PLN-DC) induce homing receptors promoting CD8 T cell accumulation in inflamed skin, particularly ligands for P- and E-selectin. Differential imprinting of tissue-tropism was independent of Th1/Th2 cytokines and not restricted to particular DC subsets. Fixed PLN-DC retained the capacity to induce selectin ligands on T cells, which was suppressed by addition of live intestinal DC. By contrast, fixed intestinal DC failed to promote gut-tropism and instead induced skin-homing receptors. Moreover, the induction of selectin ligands driven by antigen-pulsed PLN-DC could be suppressed "in trans" by adding live intestinal DC, but PLN-DC did not suppress gut-homing receptors induced by intestinal DC. Reactivation of tissue-committed memory cells modified their tissue-tropism according to the last activating DC's origin. Thus, CD8 T cells activated by DC acquire selectin ligands by default unless they encounter fixation-sensitive signal(s) for gut-tropism from intestinal DC. Memory T cells remain responsive to these signals, allowing for dynamic migratory reprogramming by skin- and gut-associated DC. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Millennium Pharmaceut, Cambridge, MA 02139 USA. RP von Andrian, U (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM uva@cbr.med.harvard.edu RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [HL54936, HL56949, HL62524, P01 HL056949, R01 HL054936]; NIAID NIH HHS [AI-061663, R01 AI061663] NR 44 TC 221 Z9 230 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JAN 17 PY 2005 VL 201 IS 2 BP 303 EP 316 DI 10.1084/jem.20041645 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 893NJ UT WOS:000226726200017 PM 15642741 ER PT J AU Kanwal, F Dulai, GS Spiegel, BMR Yee, HF Gralnek, IM AF Kanwal, F Dulai, GS Spiegel, BMR Yee, HF Gralnek, IM TI A comparison of liver transplantation outcomes in the pre- vs. post-MELD eras SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID PROGNOSTIC FACTORS; CIRRHOTIC-PATIENTS; SURVIVAL; ALLOCATION; MORTALITY; MODEL; RECIPIENTS; DISEASE; DONORS; IMPACT AB Background: The model for end stage liver disease (MELD)-based organ allocation system is designed to prioritize orthotopic liver transplantation (OLT) for patients with the most severe liver disease. However, there are no published data to confirm whether this goal has been achieved or whether the policy has affected long-term post-OLT survival. Aim: To compare pre-OLT liver disease severity and long-term (1 year) post-OLT survival between the pre- and post-MELD eras. Methods: Using the United Network of Organ Sharing database, we compared two cohorts of adult patients undergoing cadaveric liver transplant in the pre-MELD (n = 3857) and post-MELD (n = 4245) eras. We created multivariable models to determine differences in: (i) pre-OLT liver disease severity as measured by MELD; and (ii) 1-year post-OLT outcomes. Results: Patients undergoing OLT in the post-MELD era had more severe liver disease at the time of transplantation (mean MELD = 20.5) vs. those in the pre-MELD era (mean MELD = 17.0). There were no differences in the unadjusted patient or graft survival at 1 year post-OLT. This difference remained insignificant after adjusting for a range of prespecified recipient, donor, and transplant centre-related factors in multivariable survival analysis. Conclusions: Although liver disease severity is higher in the post- vs. pre-MELD era, there has been no change in long-term post-OLT patient or graft survival. These results indicate that the MELD era has achieved its primary goals by allocating cadaveric livers to the sickest patients without compromising post-OLT survival. C1 Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. VA Greater Los Angeles Hlth Care Syst, Div Gastroenterol Hepatol, Los Angeles, CA USA. VA Greater Los Angeles Hlth Care Syst, Div Gen Internal Med Hlth Serv Res, Los Angeles, CA USA. CURE Digest Dis Res, Los Angeles, CA USA. Ctr Study Digest Healthcare Qual & Outcomes, Los Angeles, CA USA. Univ Calif Los Angeles, Ctr Hlth Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA USA. RP Gralnek, IM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM igralnek@mednet.ucla.edu FU NCRR NIH HHS [RR0016188] NR 25 TC 47 Z9 56 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD JAN 15 PY 2005 VL 21 IS 2 BP 169 EP 177 DI 10.1111/j.1365-2036.2005.02321.x PG 9 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 892HA UT WOS:000226639700009 PM 15679767 ER PT J AU Kirtane, AJ Weisbord, AN Karmpaliotis, D Murphy, SA Giugliano, RP Cannon, CP Antman, EM Ohman, EM Roe, MT Braunwald, E Gibson, CM AF Kirtane, AJ Weisbord, AN Karmpaliotis, D Murphy, SA Giugliano, RP Cannon, CP Antman, EM Ohman, EM Roe, MT Braunwald, E Gibson, CM CA TIMI Study Grp TI Relation of impaired thrombolysis in myocardial infarction myocardial perfusion grades to residual thrombus following the restoration of epicardial patency in ST-elevation myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID BLOOD-FLOW; TROPONIN-T; TRIAL; THERAPY; EMBOLIZATION; ANGIOPLASTY; COUNT AB Clinical and angiographic data were analyzed from 929 patients who had ST-elevation myocardial infarction and open epicardial arteries after fibrinolytic therapy. Residual angiographically evident thrombus was associated with more frequent Thrombolysis In Myocardial Infarction (TIMI) grade 2 flow (33.6% vs 26.8%, p = 0.03), higher corrected TIMI frame counts (34 vs 31 frames, p = 0.0003), and lower TIMI myocardial perfusion grades (43.0% vs 32.0% TIMI myocardial perfusion grades 0/1, p = 0.001) among all patients and among patients who had TIMI grade 3 flow (33.5% vs 26.0% TIMI myocardial perfusion grades 0/1, p = 0.043). In multivariate analyses, angiographically evident thrombus was associated with higher corrected TIMI frame counts and worsened myocardial perfusion independent of clinical and angiographic covariates, including TIMI grade 3 flow. (C) 2005 by Excerpta Medica Inc. C1 Beth Israel Deaconess Med Ctr, Dept Med, Cambridge, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp, Cambridge, MA USA. Univ N Carolina, Chapel Hill, NC USA. Duke Clin Res Inst, Durham, NC USA. RP Gibson, CM (reprint author), 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM mgibson@.timi.org NR 20 TC 2 Z9 2 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 15 PY 2005 VL 95 IS 2 BP 224 EP 227 DI 10.1016/j.amjcard.2004.09.007 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 889RV UT WOS:000226461000010 PM 15642554 ER PT J AU Kashani, A Gibson, CM Murphy, SA Sabatine, MS Morrow, DA Antman, EM Giugliano, RP AF Kashani, A Gibson, CM Murphy, SA Sabatine, MS Morrow, DA Antman, EM Giugliano, RP TI Angiography and revascularization in patients with heart failure following fibrinalytic therapy for ST-elevation acute myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID FREE-WALL RUPTURE; PRIMARY ANGIOPLASTY; CARDIOGENIC-SHOCK; CLINICAL-OUTCOMES; INTRAVENOUS NPA; THROMBOLYSIS; FIBRINOLYSIS; SURVIVAL; REGISTRY; RISK AB We evaluated the use of coronary angiography and clinical outcomes among patients who had heart failure and were enrolled in the Intravenous Novel Plasminogen Activator (NPA) for the Treatment of Infarcting Myocardium Early study, a large. international trial of fibrinolytic therapy in ST-elevation myocardial infarction. (C) 2005 by Excerpta Medica Inc. C1 Rochester Gen Hosp, Rochester, NY 14621 USA. Brigham & Womens Hosp, TIMI Study Grp, Boston, MA USA. RP Giugliano, RP (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM rgiugliano@partners.org NR 20 TC 1 Z9 1 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 15 PY 2005 VL 95 IS 2 BP 228 EP 233 DI 10.1016/j.amjcard.2004.08.092 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 889RV UT WOS:000226461000011 PM 15642555 ER PT J AU Kleinerman, RA Linet, MS Hatch, EE Tarone, RE Black, PM Selker, RG Shapiro, WR Fine, HA Inskip, PD AF Kleinerman, RA Linet, MS Hatch, EE Tarone, RE Black, PM Selker, RG Shapiro, WR Fine, HA Inskip, PD TI Self-reported electrical appliance use and risk of adult brain tumors SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE adult; brain neoplasms; case-control studies; electromagnetic fields; meningioma; questionnaires; risk ID ELECTROMAGNETIC-FIELD EXPOSURES; NERVOUS-SYSTEM TUMORS; VOLTAGE POWER-LINES; MAGNETIC-FIELDS; CANCER; LEUKEMIA; COHORT; HOME AB Electrical appliances produce the highest intensity exposures to residential extremely low frequency electromagnetic fields. The authors investigated whether appliances may be associated with adult brain tumors in a hospital-based case-control study at three centers in the United States from 1994 to 1998. A total of 410 glioma, 178 meningioma, and 90 acoustic neuroma cases and 686 controls responded to a self-administered questionnaire about 14 electrical appliances. There was little evidence of association between brain tumors and curling iron, heating pad, vibrating massager, electric blanket, heated water bed, sound system, computer, television, humidifier, microwave oven, and electric stove. Ever use of hair dryers was associated with glioma (odds ratio = 1.7, 95% confidence interval: 1.1, 2.5), but there was no evidence of increasing risk with increasing amount of use. In men, meningioma was associated with electric shaver use (odds ratio = 10.9, 95% confidence interval: 2.3, 50), and odds ratios increased with cumulative minutes of use, although they were based on only two nonexposed cases. Recall bias for appliances used regularly near the head or chance may provide an alternative explanation for the observed associations. Overall, results indicate that extremely low frequency electromagnetic fields from commonly used household appliances are unlikely to increase the risk of brain tumors. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Western Penn Hosp, Div Neurosurg, Pittsburgh, PA 15224 USA. St Josephs Hosp, Barrow Neurol Inst, Dept Neurol, Phoenix, AZ USA. NCI, Neurooncol Branch, Bethesda, MD 20892 USA. NINDS, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Kleinerman, RA (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 7044, Rockville, MD 20852 USA. EM kleinerr@mail.nih.gov OI Kleinerman, Ruth/0000-0001-7415-2478; Hatch, Elizabeth/0000-0001-7901-3928 NR 35 TC 11 Z9 13 U1 2 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 15 PY 2005 VL 161 IS 2 BP 136 EP 146 DI 10.1093/aje/kwi013 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 885WZ UT WOS:000226189300006 PM 15632263 ER PT J AU Kilbourne, AA Good, CB Sereika, SA Justice, AC Fine, MJ AF Kilbourne, AA Good, CB Sereika, SA Justice, AC Fine, MJ TI Algorithm for assessing patients' adherence to oral hypoglycemic medication SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article; Proceedings Paper CT Annual Meeting of the Veterans-Health-Administration-Health-Services-Research-and-Development CY FEB, 2002 CL WASHINGTON, D.C. SP Vet Hlth Adm Hlth Serv Res & Dev ID PHARMACY RECORDS; REPORTED ADHERENCE; CLINICAL-TRIALS; CARE; VALIDATION C1 Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity & Promot 151C, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Ctr Res Hlth Care, Core Fac, Dept Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Ctr Res Hlth Care, Core Fac, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Biostat & Epidemiol, Pittsburgh, PA 15260 USA. W Haven Vet Affaires Med Ctr, West Haven, CT USA. Univ Pittsburgh, Dept Med, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. RP Kilbourne, AA (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity & Promot 151C, Univ Dr C, Pittsburgh, PA 15240 USA. EM amy.kilbourne@med.va.gov FU PHS HHS [K24, K23] NR 32 TC 13 Z9 13 U1 5 U2 5 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD JAN 15 PY 2005 VL 62 IS 2 BP 198 EP 204 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 892TF UT WOS:000226672200017 PM 15700895 ER PT J AU Hang, JQ Zhou, W Wang, XR Zhang, HX Sun, BX Dai, HL Su, L Christiani, DC AF Hang, JQ Zhou, W Wang, XR Zhang, HX Sun, BX Dai, HL Su, L Christiani, DC TI Microsomal epoxide hydrolase, endotoxin, and lung function decline in cotton textile workers SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE chronic obstructive pulmonary disease; microsomal epoxide hydrolase; occupational lung disease; polymorphism ID OBSTRUCTIVE PULMONARY-DISEASE; GLUTATHIONE-S-TRANSFERASE; GENETIC SUSCEPTIBILITY; RESPIRATORY SYMPTOMS; LONGITUDINAL CHANGES; INHALED ENDOTOXIN; POLYMORPHISM; DUST; LIPOPOLYSACCHARIDE; EXPRESSION AB Occupational exposure to endotoxin in organic dust may induce lung function decline. Microsomal epoxide hydrolase (mEH) detoxifies reactive oxygen species generated by endotoxin exposure, and polymorphisms of the mEH gene are associated with altered enzyme activity. We investigated the associations between mEH polymorphisms, endotoxin exposure, and lung function decline in a 20-year prospective study of 265 workers exposed to endotoxin and 234 control subjects. mEH Tyr113His and His139Arg polymorphisms were genotyped by the 5' nuclease assay, and data were analyzed using multivariate linear regression models, adjusting for important covariates. Overall, the annual decline rate of FEV1 was 29.47 ml during the 20-year follow-up. Endotoxin exposure was associated with faster lung function decline among genotypes associated with slower enzyme activity: estimates (SE) of annual FEV1 decline rates for endotoxin exposure were -2.33 (2.07), -2.81 (1.66), and -6.73 (2.83) ml for Tyr/Tyr, Tyr/His, and His/His genotype groups, respectively, for the Tyr113His polymorphism; and -1.82 (2.58) and -4.27 (1.33) ml for Arg/Arg + His/Arg and His/His genotypes, respectively, for the His139Arg polymorphism. We conclude that mEH polymorphisms modify the association between occupational endotoxin exposure and longitudinal lung function decline. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Shanghai Putuo Dist Peoples Hosp, Shanghai, Peoples R China. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, 665 Huntington Ave,Bldg I-1407, Boston, MA 02115 USA. EM dchristi@hsph.harvard.edu RI Lin, Sihao/A-8412-2012 FU FIC NIH HHS [TW00828]; NIOSH CDC HHS [R01OH02421] NR 37 TC 24 Z9 24 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 15 PY 2005 VL 171 IS 2 BP 165 EP 170 DI 10.1164/rccm.200407-888OC PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 886UO UT WOS:000226258400013 PM 15531751 ER PT J AU Handschin, C Meyer, UA AF Handschin, C Meyer, UA TI Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article; Proceedings Paper CT 15th International Symposium on Microsomes and Drug Oxidations CY JUL 04-09, 2004 CL Mainz, GERMANY DE nuclear receptors; drug-induction; lipids; bile acids; cholesterol; CAR; PXR; LXR; FXR; cytochrome P450 ID CONSTITUTIVE-ANDROSTANE RECEPTOR; PREGNANE-X-RECEPTOR; PROLIFERATOR-ACTIVATED RECEPTOR; BILE-ACID SYNTHESIS; 7-ALPHA-HYDROXYLASE GENE CYP7A1; PRIMARY CULTURED RAT; COACTIVATOR 1-ALPHA PGC-1-ALPHA; NEGATIVE FEEDBACK-REGULATION; HUMAN LIVER-MICROSOMES; CHICKEN CYP2H1 GENE AB Cloning and characterization of the orphan nuclear receptors Constitutive androstane receptor (CAR, NR1I3) and pregnane X receptor (PXR, NR1I2) led to major breakthroughs in Studying drug-mediated transcriptional induction of drug-metabolizing cytochromes P450 (CYPs). More recently, additional roles for CAR and PXR have been discovered. As examples, these xenosensors are involved in the homeostasis of cholesterol, bile acids, bilirubin, and other endogenous hydrophobic molecules in the liver: CAR and PXR thus form an intricate regulatory network with other members of the nuclear receptor superfamily, foremost the cholesterol-sensing liver X receptor (LXR, NR1H2/3) and the bile-acid-activated farnesoid X receptor (FXR, NR1H4). In this review, functional interactions between these nuclear receptors as well as the consequences on physiology and pathophysiology of the liver are discussed. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02115 USA. Univ Basel, Biozentrum, Div Pharmacol Neurobiol, CH-4056 Basel, Switzerland. RP Handschin, C (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Cell Biol, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM christoph_handschin@dfci.harvard.edu RI Marion-Poll, Frederic/D-8882-2011; Handschin, Christoph/E-6886-2015 OI Marion-Poll, Frederic/0000-0001-6824-0180; Handschin, Christoph/0000-0003-0603-1097 NR 157 TC 119 Z9 129 U1 3 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JAN 15 PY 2005 VL 433 IS 2 BP 387 EP 396 DI 10.1016/j.abb.2004.08.030 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 888SF UT WOS:000226393800007 PM 15581595 ER PT J AU Blitzer, RD Iyengar, R Landau, EM AF Blitzer, RD Iyengar, R Landau, EM TI Postsynaptic signaling networks: Cellular cogwheels underlying long-term plasticity SO BIOLOGICAL PSYCHIATRY LA English DT Article DE dendrites; hippocampus; long-term potentiation; LTP; protein synthesis; RNA granules; tagging ID LOCAL PROTEIN-SYNTHESIS; AMPA RECEPTOR TRAFFICKING; ACTIN MESSENGER-RNA; KINASE-II; SYNAPTIC PLASTICITY; HIPPOCAMPAL-NEURONS; TETANIC STIMULATION; DENDRITIC SPINES; LATE-PHASE; LTP AB Learning depends on positive or negative changes in synaptic transmission that are synapse-specific and sustained. Synaptic signals can be directly measured and respond to certain kinds of stimulation by becoming persistently enhanced (long-term potentiation, LTP) or decreased (long-term depression, LTD). Studying LTP and LTD opens a window on to the molecular mechanisms of memory. Although changes in both pre- and postsynaptic strength have been implicatcd in LTP and LTD, most attention has been focused on changes in postsynaptic glutamate receptor density. This is controlled by intracellular Ca2+ ions via a network of signaling molecules. Changes in postsynaptic Ca2+ concentration depend on the coincidence of appropriate synaptic signals, as is found in learning situations. The long-term persistence of LTP and LTD requires gene transcription and translation. It is posited that local translation at the synapse, in a self-sustaining manner, mediates the persistence of long-term change despite constant turnover of the synaptic components. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Pharmacol & Biol Chem, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, Psychiat Serv, Bronx, NY USA. RP Landau, EM (reprint author), Mt Sinai Sch Med, Dept Psychiat, Box 1215,1 Gustave Levy Pl, New York, NY 10029 USA. EM manny.landau@mssm.edu FU NIDA NIH HHS [DA015863] NR 69 TC 64 Z9 69 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 15 PY 2005 VL 57 IS 2 BP 113 EP 119 DI 10.1016/j.biophsych.2004.02.031 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 888BQ UT WOS:000226349600001 PM 15652868 ER PT J AU Friedberg, JW Kim, H McCauley, M Hessel, EM Sims, P Fisher, DC Nadler, LM Coffman, RL Freedman, AS AF Friedberg, JW Kim, H McCauley, M Hessel, EM Sims, P Fisher, DC Nadler, LM Coffman, RL Freedman, AS TI Combination immunotherapy with a CpG oligonucleotide (1018 ISS) and rituximab in patients with non-Hodgkin lymphoma: increased interferon-alpha/beta-inducible gene expression, without significant toxicity SO BLOOD LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CA SP Amer Soc Hematol ID ANTI-CD20 MONOCLONAL-ANTIBODY; COLONY-STIMULATING FACTOR; HUMAN B-CELLS; DENDRITIC CELLS; IN-VIVO; LOW-GRADE; PHASE-I; OLIGODEOXYNUCLEOTIDES ENHANCE; BIOLOGIC RESPONSE; IMMUNE-RESPONSE AB CpG oligocleoxynucleotides (CpG-ODNs) affect innate and adaptive immune responses, including antigen presentation, costimulatory molecule expression, dendritic cell maturation, and induction of cytokines enhancing antibody-dependent cell-mediated cytotoxicity (ADCC). We conducted a phase 1 study evaluating 4 dose levels of a CpG-ODN (11018 ISS) with rituximab in 20 patients with relapsed non-Hodgkin lymphoma (NHL). Patients received CpG once a week for 4 weeks beginning after the second of 4 rituximab infusions. Adverse events were minimal. Quantitative polymerase chain reaction (PCR) measurements of a panel of genes inducible by CpG-ODN and interferons were performed on blood samples collected before and 24 hours after CpG. A dose-related increase was measured in the expression of several interferon-inducible genes after CpG and correlated with serum levels of 2'-5' oligoadenylate synthetase (OAS), a validated interferon response marker. Genes induced selectively by interferon-gamma (IFN-gamma) were not significantly induced by CpG. In conclusion, we have defined a set of gene expression markers that provide a sensitive measure of biologic responses of patients to CpG therapy in a dose-related manner. Moreover. all the genes significantly induced by this CpG are regulated by type 1 interferons. providing insight into the dominant immune mechanisms in humans. CpG treatment resulted in no significant toxicity, providing ration-ale for further testing of this exciting combination immunotherapy approach to NHL. (C) 2005 by The American Society of Hematology. C1 Univ Rochester, Lymphoma Program, James P Wilmot Canc Ctr, Rochester, NY 14642 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Dynavax Technol, Berkeley, CA USA. RP Friedberg, JW (reprint author), Univ Rochester, Lymphoma Program, James P Wilmot Canc Ctr, 601 Elmwood Ave,Box 704, Rochester, NY 14642 USA. EM jonathan_friedberg@urmc.rochester.edu FU NCI NIH HHS [CA102216] NR 60 TC 102 Z9 109 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 2005 VL 105 IS 2 BP 489 EP 495 DI 10.1182/blood-2004-06-2156 PG 7 WC Hematology SC Hematology GA 885ZX UT WOS:000226197000018 PM 15358617 ER PT J AU Montgomery, RB Makary, E Schiffman, K Goodell, V Disis, ML AF Montgomery, RB Makary, E Schiffman, K Goodell, V Disis, ML TI Endogenous anti-HER2 antibodies block HER2 phosphorylation and signaling through extracellular signal-regulated kinase SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER CELLS; TUMOR-GROWTH; T-CELL; MONOCLONAL-ANTIBODIES; TRASTUZUMAB HERCEPTIN; ANTITUMOR RESPONSES; HER-2/NEU PROTEIN; IMMUNE-RESPONSES; EPITHELIAL-CELLS; ERBB2 RECEPTOR AB Immunologic targeting of the oncoprotein HER2/neu with monoclonal antibodies is an important component of current therapeutic strategies for patients with locally and systemically advanced breast cancer. Engineered antibodies targeting HER2 may have agonist or antagonist effects on HER2, ut little is known about whether endogenous antibodies modulate HER2 activity. Vaccination of patients with HER2 peptides successfully induced antibodies in a minority of patients with HER2-expressing malignancy. A subset of antibodies specifically suppressed phosphorylation of HER2 on tyrosine Y1248, a residue critical for HER2 signaling through extracellular signal-regulated kinase. These antibodies also suppressed extracellular signal-regulated kinase phosphorylation and inhibited colony formation in soft agar. The majority of the antibodies that suppressed HER2 phosphorylation displayed specificity for amino acids 328 to 345 and 369 to 384. The isotype of anti-HER2 antibodies was predominantly IgG3 of low avidity, suggesting a Th1 response to peptide vaccine. Endogenous anti-HER2 antibodies can effectively suppress HER2 kinase activity and downstream signaling to inhibit the transformed phenotype of HER2-expressing tumor cells. C1 Univ Washington, VA Puget Sound HCS, Dept Med, Div Oncol, Seattle, WA 98108 USA. RP Montgomery, RB (reprint author), Univ Washington, VA Puget Sound HCS, Dept Med, Div Oncol, 1660 S Columbian Way,111 ONC, Seattle, WA 98108 USA. EM rbmontgo@u.washington.edu FU NCI NIH HHS [U54 CA090818, CA82661, CA85218, CA7516]; NCRR NIH HHS [M01-RR-00037] NR 35 TC 42 Z9 43 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2005 VL 65 IS 2 BP 650 EP 656 PG 7 WC Oncology SC Oncology GA 887VV UT WOS:000226334500036 PM 15695410 ER PT J AU Doolittle, ND Abrey, LE Bleyer, WA Brem, S Davis, TP Dore-Duffy, P Drewes, LR Hall, WA Hoffman, JM Korfel, A Martuza, R Muldoon, LL Peereboom, D Peterson, DR Rabkin, SD Smith, Q Stevens, GHJ Neuwelt, EA AF Doolittle, ND Abrey, LE Bleyer, WA Brem, S Davis, TP Dore-Duffy, P Drewes, LR Hall, WA Hoffman, JM Korfel, A Martuza, R Muldoon, LL Peereboom, D Peterson, DR Rabkin, SD Smith, Q Stevens, GHJ Neuwelt, EA TI New frontiers in translational research in neuro-oncology and the blood-brain barrier: Report of the Tenth Annual Blood-Brain Barrier Disruption Consortium Meeting SO CLINICAL CANCER RESEARCH LA English DT Article ID NERVOUS-SYSTEM LYMPHOMA; IRON-OXIDE PARTICLES; PRIMARY CNS LYMPHOMA; RAT-BRAIN; N-ACETYLCYSTEINE; GROWTH-FACTOR; TUMOR-MODEL; ANGIOGENESIS; SURVIVAL; METHOTREXATE AB The blood-brain barrier (BBB) presents a major obstacle to the treatment of malignant brain tumors and other central nervous system (CNS) diseases. For this reason, a meeting partially funded by an NIH R13 grant was convened to discuss recent advances and future directions in translational research in neuro-oncology and the BBB. Cell biology and transport across the BBB. delivery of agents to the CNS. neuroimaging, angiogenesis, immunotherapy and gene therapy, as well as glioma, primary CNS lymphoma. and metastases to the CNS were. discussed. Transport across the BBB relates to the neurovascular unit. which consists not only of endothelial cells but also of pericyte. glia. and neuronal elements. C1 Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. MD Anderson Canc Ctr, Div Pediat, Houston, TX USA. MD Anderson Canc Ctr, Div Community Oncol, Houston, TX USA. H Lee Moffitt Canc Ctr, Dept Neurooncol & Neurosurg, Tampa, FL USA. Univ Arizona, Sch Med, Dept Pharmacol, Program Neurosci & Physiol Sci, Tucson, AZ USA. Wayne State Univ, Dept Neurol, Detroit, MI USA. Univ Minnesota, Sch Med, Dept Biochem & Mol Biol, Duluth, MN 55812 USA. Univ Minnesota, Dept Neurosurg, Minneapolis, MN 55455 USA. NCI, Canc Imaging Program, Bethesda, MD 20892 USA. Charite Campus Benjamin Franklin, Dept Hematol Oncol & Transfus Med, Berlin, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. Cleveland Clin Fdn, Dept Hematol & Med Oncol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Adult Neurooncol Brain Tumor Inst, Cleveland, OH 44195 USA. Univ Chicago, Sch Med, Dept Physiol & Biophys, Chicago, IL 60637 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg,E Mol Neurosur Lab, Charlestown, MA USA. Texas Tech Univ, Dept Pharmaceut Sci, Amarillo, TX USA. RP Neuwelt, EA (reprint author), Oregon Hlth Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk,Rd L603, Portland, OR 97201 USA. EM neuwelte@ohsu.edu RI rabkin, samuel/C-2443-2012; davis, thomas/F-3244-2015 OI rabkin, samuel/0000-0003-2344-2795; davis, thomas/0000-0001-8465-4973 FU NCI NIH HHS [4R13 CA 86959-04] NR 48 TC 26 Z9 28 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 JAN 15 PY 2005 VL 11 IS 2 BP 421 EP 428 PG 8 WC Oncology SC Oncology GA 889IZ UT WOS:000226438000003 PM 15701824 ER PT J AU Dobbin, KK Beer, DG Meyerson, M Yeatman, TJ Gerald, WL Jacobson, JW Conley, B Buetow, KH Heiskanen, M Simon, RN Minna, JD Girard, L Misek, DE Taylor, JMG Hanash, S Naoki, K Hayes, DN Ladd-Acosta, C Enkemann, SA Viale, A Giordano, TJ AF Dobbin, KK Beer, DG Meyerson, M Yeatman, TJ Gerald, WL Jacobson, JW Conley, B Buetow, KH Heiskanen, M Simon, RN Minna, JD Girard, L Misek, DE Taylor, JMG Hanash, S Naoki, K Hayes, DN Ladd-Acosta, C Enkemann, SA Viale, A Giordano, TJ TI Interlaboratory comparability study of cancer gene expression analysis using oligonucleotide microarrays SO CLINICAL CANCER RESEARCH LA English DT Article ID B-CELL LYMPHOMA; MOLECULAR CLASSIFICATION; PREDICT SURVIVAL; ADENOCARCINOMA; LUNG; REPRODUCIBILITY AB A key step in bringing gene expression data into clinical practice is the conduct of large studies to confirm preliminary models. The performance of such confirmatory studies and the transition to clinical practice requires that microarray data from different laboratories are comparable and reproducible. We designed a study to assess the comparability of data front four laboratories that will conduct a larger microarray profiling confirmation project in lung adenocarcinomas. To test the feasibility of combining data across laboratories, frozen tumor tissues, cell line pellets, and purified RNA samples were analyzed at each of the four laboratories. Samples of each type and several subsamples from each tumor and each cell line were blinded before being distributed. The laboratories followed a common protocol for all steps of tissue processing, RNA extraction. and microarrav analysis using Affymetrix Human Genome U133A arrays. High within-laboratory and between-laboratory correlations were observed on the purified RNA samples. the cell tines. and the frozen tumor tissues. Intraclass correlation within laboratories was only slightly stronger than between laboratories, and the intraclass correlation tended to be weakest for genes expressed at low levels and showing small variation. Finally, hierarchical cluster analysis revealed that the repeated samples clustered to-ether regardless of the laboratory in which the experiments were done. The findings indicate that under properly controlled conditions it is feasible to perform complete tumor microarray analysis, from tissue processing to hybridization and scanning, at multiple independent laboratories for a single study. C1 NCI, Canc Diag Program, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Bethesda, MD 20892 USA. NCI, Ctr Bioinformat, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI USA. Univ Michigan, Sch Med, Dept Pediat, Ann Arbor, MI USA. Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Dept Surg, Tampa, FL USA. Univ S Florida, Inst Res, Tampa, FL USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Mol Biol, New York, NY 10021 USA. Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX USA. MIT, Ctr Genome, Whitehead Inst, Cambridge, MA 02139 USA. RP Dobbin, KK (reprint author), NCI, Div Canc Treatment & Diag, Rockville, MD 20852 USA. EM dobbinke@mail.nih.gov RI Meyerson, Matthew/E-7123-2012; OI Hayes, D. Neil/0000-0001-6203-7771; Giordano, Thomas/0000-0003-0641-8873 FU NCI NIH HHS [U19 CA 84593, P50 CA 70907, U01 CA 84995, U01 CA 84999, U01 CA 85052] NR 18 TC 120 Z9 127 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2005 VL 11 IS 2 BP 565 EP 572 PG 8 WC Oncology SC Oncology GA 889IZ UT WOS:000226438000021 PM 15701842 ER PT J AU Lau, L Supko, JG Blaney, S Hershon, L Seibel, N Krailo, M Qu, WC Malkin, D Jimeno, J Bernstein, M Baruchel, S AF Lau, L Supko, JG Blaney, S Hershon, L Seibel, N Krailo, M Qu, WC Malkin, D Jimeno, J Bernstein, M Baruchel, S CA Childrens Oncology Grp TI A phase I and pharmacokinetic study of ecteinascidin-743 (Yondelis) in children with refractory solid tumors. A children's oncology group study SO CLINICAL CANCER RESEARCH LA English DT Article ID CONTINUOUS INTRAVENOUS-INFUSION; DRUG ECTEINASCIDIN-743; ANTITUMOR-ACTIVITY; MARINE COMPOUND; ET-743; CELLS; RAT; MALIGNANCIES; XENOGRAFTS; ACTIVATION AB Purpose: To determine the dose-limiting toxicity (DLT) and the maximum tolerated dose of ecteinascidin-743 (ET-743, Yondelis) in children with refractory solid tumors, to establish the recommended dose for pediatric phase 11 trials, and to characterize the pharmacokinetics of ET-743 in children. Experimental Design: ET-743 was administered as a 3-hour i.v. infusion every 21 days. The starting dose was 1,100 mug/m(2) with planned dose escalation of 200 mug/m(2) increments. Pharmacokinetic sampling was done during the first treatment course. Results: Twelve evaluable patients received a total of 29 courses. One grade 4 DLT (prolonged grade 4 neutropenia) was noted at the first dose level. At the second dose level (1,300 mug/m(2)), there were two DLTs (reversible grade 4 elevations of hepatic transaminase); hence the maximum tolerated dose was defined as 1,100 mug/m(2). Overall, reversible hepatic toxicity, manifested as grade 3 or 4 elevations in hepatic transaminase, occurred in more than 50% of the patients. No grade 3 or 4 thrombocytopenia was reported at either dose level and only one episode of isolated creatine phospho kinase grade 4 elevation was observed. One complete response was documented after six courses in a patient with metastatic Ewing sarcoma. The pharmacokinetics of ET-743 in 8 children was characterized by a terminal disposition phase with a mean half-life of 43.8 +/- 18.4 hours, a total body clearance of 28.2 +/- 10.5 L/h/m(2), and a 959 +/- 807 L/m(2) steady-state apparent volume of distribution. Conclusion: ET-743 is safe. The phase II recommended dose of ET-743 administered as a 3-hour i.v. infusion following premedication with dexamethasone is 1,100 mug/m(2). C1 Hosp Sick Children, New Agent & Innovat Therapy Program, Toronto, ON M5G 1X8, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Texas Childrens Canc Ctr, Houston, TX USA. Hop St Justine, Montreal, PQ H3T 1C5, Canada. Univ Washington, Seattle, WA 98195 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. PharmaMar SA, Madrid, Spain. RP Baruchel, S (reprint author), Hosp Sick Children, New Agent & Innovat Therapy Program, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. RI Lau, Loretta/B-1565-2008 NR 32 TC 37 Z9 39 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2005 VL 11 IS 2 BP 672 EP 677 PG 6 WC Oncology SC Oncology GA 889IZ UT WOS:000226438000034 PM 15701855 ER PT J AU Davis, DW Takamori, R Raut, CP Xiong, HQ Herbst, RS Stadler, WM Heymach, JV Demetri, GD Rashid, A Shen, Y Wen, SJ Abbruzzese, JL McConkey, DJ AF Davis, DW Takamori, R Raut, CP Xiong, HQ Herbst, RS Stadler, WM Heymach, JV Demetri, GD Rashid, A Shen, Y Wen, SJ Abbruzzese, JL McConkey, DJ TI Pharmacodynamic analysis of target inhibition and endothelial cell death in tumors treated with the vascular endothelial growth factor receptor antagonists SU5416 or SU6668 SO CLINICAL CANCER RESEARCH LA English DT Article ID TYROSINE KINASE INHIBITOR; ANTIANGIOGENIC AGENT SU5416; HUMAN PANCREATIC-CARCINOMA; CANCER-PATIENTS; PHASE-II; SOLID TUMORS; ANGIOGENESIS; APOPTOSIS; THERAPY; PHOSPHORYLATION AB Purpose: To determine the effects of small molecule inhibitors of vascular endothelial growth factor receptor (VEGFR)-2 (SU5416 and SU6668) on receptor phosphorylation in tumor xenografts and in paired tumor biopsies obtained in three clinical trials in patients with advanced solid malignancies. Experimental Design: The dose-dependent effects of SU6668 on angiogenesis and tumor growth were investigated in orthotopic L3.6pl pancreatic tumors. Excisional or 18G core biopsies were obtained from patients before and after therapy with SU5416 or SU6668. Laser scanning cytometry-mediated analysis was used to quantify levels of phosphorylated and total VEGFRs and platelet-derived growth factor receptors (PDGFR), tumor microvessel densities, vessel sizes, and endothelial and tumor cell apoptosis. Results: Significant inhibition of tumor microvessel density and growth and increased apoptosis were observed at SU6668 maximum tolerated dose.(100 mg/kg) in L3.6pl xenografts. At 6 hours post therapy, SU6668 reduced VEGFR and PDGFR phosphorylation in the tumors by 50% and 92%, respectively, but levels rebounded beyond the baselines by 24 hours. Levels of phosphorylated VEGFR-2 and PDGFR also decreased significantly ( 50%) 6 hours after therapy in 1 of 6 primary human tumors treated with SU6668, but these effects were not associated with increased apoptosis. A significant increase in endothelial cell apoptosis was observed in one tumor exposed to SU5416 and was associated with an increase in vessel size, but these changes occurred without an increase in tumor cell death. Conclusions: SU5416 and SU6668 displayed biological activity in xenografts. However, neither drug produced marked biological activity in primary patient tumors. C1 Univ Texas, MD Anderson Canc Ctr, Dept Canc Biol, Unit 173, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX USA. Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Harvard Univ, Sch Med, Ctr Canc, Boston, MA USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP McConkey, DJ (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Canc Biol, Unit 173, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM dmcconke@mdanderson.org OI Shen, Yu/0000-0002-3899-7868 FU NCI NIH HHS [CA 91846, U01 CA 62461, U54 CA 090810, CA 16672] NR 40 TC 26 Z9 31 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2005 VL 11 IS 2 BP 678 EP 689 PG 12 WC Oncology SC Oncology GA 889IZ UT WOS:000226438000035 PM 15701856 ER PT J AU Cervi, D Klement, G Stempak, D Baruchel, S Koki, A Ben-David, Y AF Cervi, D Klement, G Stempak, D Baruchel, S Koki, A Ben-David, Y TI Targeting cyclooxygenase-2 reduces overt toxicity toward low-dose vinblastine and extends survival of juvenile mice with Friend disease SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR ANGIOGENESIS; ACUTE-LEUKEMIA; ERYTHROLEUKEMIA; CANCER; CELECOXIB; VIRUS; INHIBITORS; GROWTH; CELLS AB Purpose: To test the efficacy of selective therapy against cyclooxygenase-2 in combination with a low-dose regimen of a cytotoxic agent in the treatment of juvenile hematopoietic malignancies in the experimental model, Friend disease. Experimental Design: Juvenile erythroleukemic mice (n = 8) received no treatment, celecoxib (1600 mg/kg/d), vinblastine (0.5 mu/g twice weekly), vehicle controls, or celecoxib + vinblastine combination (n = 9) over a 6-month period from time of tumor induction. Overt toxicity was assessed daily and recorded weekly. Results: Among randomly selected mice from celecoxib treatment groups, plasma concentrations ranged from 2 to 6 mumol/L. As a single agent, celecoxib was not associated with any apparent toxicity. Monotherapy with vinblastine, however, caused early mortality marked by severe diarrhea, lethargy, and weight loss. At the tested doses, neither vinblastine nor celecoxib enhanced survival as monotherapies. Coadministration of these two drugs alleviated the overt toxicity associated with vinblastine and resulted in a significant increase in survival (P < 0.05). Survivors sampled throughout the study showed a trend to decreased weight loss and hematocrit levels among all groups, but significance was evidenced earlier in the vinblastine monotherapy group overall (P < 0.05). Despite similar degree of splenomegaly, histologic analysis revealed preserved splenic mantle architecture from mice given combination therapy compared with those sampled from mice on all other monotherapies, exhibiting a more diffuse burden of blasts and destruction of germinal centers. Conclusion: We propose that addition of a selective cyclooxygenase-2 inhibitor to a modified low-dose conventional chemotherapeutic regimen protects juvenile mice with Friend disease from succumbing to low-dose cytotoxicity, in part, by neutralizing acute inflammatory responses. C1 Sunnybrook & Womens Coll, Hlth Sci Ctr, Div Mol & Cellular Biol, Toronto, ON M4N 3M5, Canada. Sunnybrook & Womens Coll, Hlth Sci Ctr, Dept Med Biophys, Toronto, ON, Canada. Univ Toronto, Toronto Sunnybrook Reg Canc Ctr, Toronto, ON, Canada. Hosp Sick Children, Div Haematol Oncol, Toronto, ON, Canada. Hosp Sick Children, Div Clin Pharmacol, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Div Toxicol, Toronto, ON, Canada. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. Ipsogen, Marseille, France. RP Ben-David, Y (reprint author), Sunnybrook & Womens Coll, Hlth Sci Ctr, Div Mol & Cellular Biol, Res Bldg S-216, Toronto, ON M4N 3M5, Canada. EM bendavid@srcl.sunnybrook.utoronto.ca NR 29 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2005 VL 11 IS 2 BP 712 EP 719 PG 8 WC Oncology SC Oncology GA 889IZ UT WOS:000226438000039 PM 15701860 ER PT J AU Chen, B Pogue, BW Zhou, XD O'Hara, JA Solban, N Demidenko, E Hoopes, PJ Hasan, T AF Chen, B Pogue, BW Zhou, XD O'Hara, JA Solban, N Demidenko, E Hoopes, PJ Hasan, T TI Effect of tumor host microenvironment on photodynamic therapy in a rat prostate tumor model SO CLINICAL CANCER RESEARCH LA English DT Article ID MURINE TUMORS; BLOOD-FLOW; NUDE-MICE; CANCER; ANGIOGENESIS; METASTASIS; CARCINOMA; OXYGEN; IMPLANTATION; VERTEPORFIN AB Purpose: Tumor host microenvironment plays an important role in tumor growth, metastasis, and response to cancer therapy. In this study, the influence of tumor host environment on tumor pathophysiology, photosensitizer distribution, and photodynamic therapy (PDT) treatment effect was examined in the metastatic at lymph node and lung (MatLyLu) rat prostate tumor. Experimental Design: MatLyLu tumors implanted in different host environment [i.e., orthotopically (in the prostate) or s.c.] were compared for difference in vessel density, average vessel size, vascular permeability, tumor vascular endothelial growth factor production, and tumor oxygenation. Uptake of photosensitizer verteporfin in tumors in both sites was determined by fluorescence microscopy. To compare tumor response to PDT, both orthotopic and s.c. MatLyLu tumors were given the same doses of verteporfin and laser light treatment, and PDT-induced tumor necrotic area was measured histologically. Results: Orthotopic MatLyLu tumors were found to grow faster, have higher vessel density and more permeable vasculature, have higher vascular endothelial growth factor protein levels, and have lower tumor hypoxic fraction than the s.c. tumors. Uptake of photosensitizer verteporfin in the orthotopic tumor was higher than in the s.c. tumors at 15 minutes after injection (1 mg/kg, i.v.), and became similar at 3 hours after injection. For the vascular targeting PDT treatment (0.25 mg/kg verteporfin, 50 J/cm(2) at 50 mW/cm(2), 15 minutes drug-light interval), there was no significant difference in PDT-induced tumor necrotic area between the orthotopic and s.c. tumors, with 85% to 90% necrosis in both types of tumors. However, tumor necrosis induced by the cellular targeting PDT (1 mg/kg verteporfin, 50 J/cm(2) at 50 mW/cm(2), 3 hours drug-light interval) was significantly different in the orthotopic (64%) versus the s.c. (29%) tumors. Conclusions: Tumor host environment can significantly affect photosensitizer verteporfin distribution and PDT treatment effect. Verteporfin-PDT regimen targeting tumor cells is more sensitive to such influence than the vascular targeting PDT. Our study showed the importance of tumor host environment in determining tumor physiologic properties and tumor response to PDT. To obtain clinically relevant information, orthotopic tumor model should be used in the experimental studies. C1 Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. Dartmouth Coll Sch Med, Dept Diagnost Radiol, Hanover, NH USA. Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Div Biostat, Lebanon, NH USA. Dartmouth Coll Sch Med, Dept Surg, Lebanon, NH USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed,Dept Dermatol, Boston, MA USA. RP Pogue, BW (reprint author), Dartmouth Coll, Thayer Sch Engn, 8000 Cummings Hall, Hanover, NH 03755 USA. EM bin.chen@dartmouth.edu; pogue@dartmouth.edu FU NCI NIH HHS [P01 CA 84203] NR 40 TC 40 Z9 43 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2005 VL 11 IS 2 BP 720 EP 727 PG 8 WC Oncology SC Oncology GA 889IZ UT WOS:000226438000040 PM 15701861 ER PT J AU Dooley, KA Davidson, AJ Zon, LI AF Dooley, KA Davidson, AJ Zon, LI TI Zebrafish scl functions independently in hematopoietic and endothelial development SO DEVELOPMENTAL BIOLOGY LA English DT Article DE scl; hematopoiesis; vasculogenesis; angiogenesis; zebrafish ID T-CELL LEUKEMIA; GROWTH-FACTOR; STEM-CELLS; VASCULAR DEVELOPMENT; SPADETAIL EMBRYOS; SCL/TAL-1 GENE; PROTEIN LMO2; TARGET GENE; ADULT-MOUSE; DNA-BINDING AB The SCL transcription factor is critically important for vertebrate hematopoiesis and angiogenesis, and has been postulated to induce hemangioblasts, bipotential precursors for blood and endothelial cells. To investigate the function of scl during zebrafish hematopoietic and endothelial development, we utilized site-directed, anti-sense morpholinos to inhibit scl mRNA. Knockdown of scl resulted in a loss of primitive and definitive hematopoietic cell lineages. However, the expression of early hematopoietic genes, gata2 and lmo2, was unaffected, suggesting that hematopoietic cells were present but unable to further differentiate. Using gene expression analysis and Visualization of vessel formation in live animals harboring an lmo2 promoter-green fluorescent protein reporter transgene (Tg(lmo2:EGFP)), we show that angioblasts were specified normally in the absence of scl, but later defects in angiogenesis were evident. While scl was not required for angioblast specification, forced expression of exogenous scl caused ail expansion of both hematopoietic and endothelial gene expression, and a loss of somitic tissue. In cloche and spadetail mutants, forced expression of scl resulted in an expansion of hematopoietic but not endothelial tissue. Surprisingly, in cloche, lmo2 was not induced in response to scl over-expression. Taken together, these findings support distinct roles for scl in hematopoietic and endothelial development, downstream of hemangioblast development. (C) 2004 Elsevier Inc. All rights reserved. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Zon, LI (reprint author), Childrens Hosp, Div Hematol Oncol, 1 Blackfan Circle,Karp Family Res Bldg,7005C, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu NR 71 TC 88 Z9 90 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JAN 15 PY 2005 VL 277 IS 2 BP 522 EP 536 DI 10.1016/j.ydbio.2004.09.004 PG 15 WC Developmental Biology SC Developmental Biology GA 886KI UT WOS:000226225700018 PM 15617691 ER PT J AU Melov, S Wolf, N Strozyk, D Doctrow, SR Bush, AI AF Melov, S Wolf, N Strozyk, D Doctrow, SR Bush, AI TI Mice transgenic for Alzheimer disease beta-amyloid develop lens cataracts that are rescued by antioxidant treatment SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE free radicals ID SUPEROXIDE DISMUTASE/CATALASE MIMETICS; AGE-RELATED CATARACT; SALEN-MANGANESE COMPLEXES; OXIDATIVE STRESS; CATALASE MIMETICS; DEPOSITION; MOUSE; ATTENUATION; PROTECTION; TOXICITY AB Alzheimer disease is characterized by cerebral A deposition, which we have recently discovered occurs also in the lens as cataracts in Alzheimer disease patients. Here we report the presence of significantly increased cataracts in the lenses of an Abeta-transgenic mouse model for Alzheimer disease and their amelioration upon treatment with EUK-189, a synthetic SOD/catalase mimetic. These data support an oxidative etiology for AD-associated lens cataracts and their potential to be treated preventatively with antioxidants. (C) 2004 Elsevier Inc. All rights reserved. C1 Buck Inst Age Res, Novato, CA 94945 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10462 USA. Eukarion, Bedford, MA 01730 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp East, Lab Oxidat Biol,Genet & Aging Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp East, Dept Psychiat, Charlestown, MA 02129 USA. Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. Univ Melbourne, Mental Hlth Res Inst Victoria, Parkville, Vic 3052, Australia. RP Bush, AI (reprint author), Buck Inst Age Res, 8001 Redwood Blvd, Novato, CA 94945 USA. EM smelov@buckinstitute.org; bush@helix.mgh.harvard.edu RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 FU NEI NIH HHS [R01EY11733]; NIA NIH HHS [R01AG12686, R01AG18679] NR 24 TC 48 Z9 49 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JAN 15 PY 2005 VL 38 IS 2 BP 258 EP 261 DI 10.1016/j.freeradbiomed.2004.10.023 PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 886KM UT WOS:000226226100010 PM 15607908 ER PT J AU Chan, HM Narita, M Lowe, SW Livingstone, DM AF Chan, HM Narita, M Lowe, SW Livingstone, DM TI The p400 E1A-associated protein is a novel component of the p53 -> p21 senescence pathway SO GENES & DEVELOPMENT LA English DT Article DE p400; senescence; p53; p21; ElA; myc ID HISTONE ACETYLTRANSFERASE COMPLEX; DNA-BINDING; CELLULAR SENESCENCE; TUMOR SUPPRESSION; ONCOGENIC RAS; HUMAN-CELLS; P53; CHROMATIN; MYC; IDENTIFICATION AB Adenovirus E1A-associated p400 belongs to the SW12/ SNF2 family of chromatin remodeling proteins. Here, we report that p400 is a component of the p53-p21(WAF1/CIP1/sid1) pathway, regulating the p21 transcription and senescence induction program. Acute depletion of p400 expression by shRNA (short hairpin RNA) synthesis led to premature senescence of untransformed human fibroblasts, whose features include G1 arrest, p21 induction, senescence-associated heterochromatic foci (SAHF), and beta-gal staining. Importantly, p400shRNA-induced premature senescence phenotypes were rescued by coexpression of p53-shRNA or p21shRNA. Furthermore, p400 complex colocalized with p53 on the p21 promoter. These data suggest that the p400 complex inhibits p53 --> p21 transcription and the development of premature senescence. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. RP Livingstone, DM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM david_Livingstone@dfci.harvard.edu FU NCI NIH HHS [P30 CA008748] NR 35 TC 97 Z9 99 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JAN 15 PY 2005 VL 19 IS 2 BP 196 EP 201 DI 10.1101/gad.1280205 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 888KN UT WOS:000226372900002 PM 15655109 ER PT J AU Zucker, B Luthi-Carter, R Kama, JA Dunah, AW Stern, EA Fox, JH Standaert, DG Young, AB Augood, SJ AF Zucker, B Luthi-Carter, R Kama, JA Dunah, AW Stern, EA Fox, JH Standaert, DG Young, AB Augood, SJ TI Transcriptional dysregulation in striatal projection- and interneurons in a mouse model of Huntington's disease: neuronal selectivity and potential neuroprotective role of HAP1 SO HUMAN MOLECULAR GENETICS LA English DT Article ID NITRIC-OXIDE SYNTHASE; ASPARTATE RECEPTOR ACTIVATION; MESSENGER-RNA EXPRESSION; DENSITY PROTEIN PSD-95; GENE-EXPRESSION; NMDA RECEPTORS; TRANSGENIC MICE; ENHANCED SENSITIVITY; FUNCTIONAL-ANATOMY; S-NITROSYLATION AB Transcriptional dysregulation has been described as a central mechanism in the pathogenesis of Huntington's disease (HD), in which medium spiny projection neurons (MSN) selectively degenerate whereas neuronal nitric-oxide-synthase-positive interneurons (nNOS-IN) survive. In order to begin to understand this differential vulnerability we compared mRNA levels of selected genes involved in N-methyl-D-aspartate (NMDA) glutamate receptor and calcium (Ca2+) signaling pathways in MSN and nNOS-IN from 12-week-old R6/2 mice, a transgenic mouse model of HD and wild-type littermates. We undertook a laser capture microdissection (LCM) study to examine the contribution of transcriptional dysregulation in candidate genes involved in these two signaling pathways in discrete populations of striatal neurons. The use of LCM in combination with quantitative real-time polymerase chain reaction (Q-PCR) allowed us to quantify the neuronal abundance of candidate mRNAs. We found different transcriptional alterations in R6/2 neurons for both MSN and nNOS-IN, indicating that global transcriptional dysregulation alone does not account for selective vulnerability. Further, we observed a striking enrichment of several mRNAs in the nNOS-IN population, including that for the NMDA receptor subunit NR2D, the postsynaptic density protein 95 (PSD-95) and the huntingtin-associated protein 1 (HAP1) as well as nitric-oxide-synthase (nNOS) mRNA itself. The higher expression levels of these molecules in nNOS-IN when compared with MSN together with an association of nNOS, NR2D and HAP1 in a protein complex with PSD-95 suggest that these proteins may be involved in protective pathways that contribute to the resistance of this interneuron population to neurodegeneration in HD. C1 Massachusetts Gen Hosp, MassGen Inst Neurogenerat Dis, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Zucker, B (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurogenerat Dis, Dept Neurol, Bldg 114 16th St, Charlestown, MA 02129 USA. EM birgit.zucker@gmx.de OI Standaert, David/0000-0003-2921-8348 FU NIA NIH HHS [AG13617]; NINDS NIH HHS [NS045896] NR 78 TC 63 Z9 63 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN 15 PY 2005 VL 14 IS 2 BP 179 EP 189 DI 10.1093/hmg/ddi014 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 886AT UT WOS:000226199400001 PM 15548548 ER PT J AU Weinberg, A Bloch, KC Li, SB Tang, YW Palmer, M Tyler, KL AF Weinberg, A Bloch, KC Li, SB Tang, YW Palmer, M Tyler, KL TI Dual infections of the central nervous system with Epstein-Barr virus SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID POLYMERASE-CHAIN-REACTION; CEREBROSPINAL-FLUID; HERPESVIRUSES; DIAGNOSIS; DNA AB We describe clinical and laboratory characteristics of 16 patients with central nervous system (CNS) infection caused by Epstein-Barr virus (EBV) and another pathogen. Seven of 10 immunocompromised patients had coinfection with viruses (3 with cytomegalovirus, 2 with JC virus, and 2 with varicella zoster virus) and 3 with nonviral pathogens (2 with pneumococcus and 1 with Cryptococcus species). Three of 6 immunocompetent patients had coinfections with viruses (1 each with herpes simplex virus, varicella zoster virus, and West Nile virus), and 3 had coinfections with nonviral pathogens (2 with Ehrlichia chaffeensis and 1 with Mycoplasma pneumoniae). The EBV load was similar in immunocompromised and immunocompetent patients and in patients with viral and nonviral coinfections. EBV lytic-cycle mRNA was detected in the cerebrospinal fluid of 5 of 6 tested samples, indicating EBV replication in the CNS during coinfection. C1 Univ Colorado, Hlth Sci Ctr, Sch Med, Dept Pediat, Denver, CO 80262 USA. Univ Colorado, Sch Med, Dept Med, Denver, CO 80262 USA. Univ Colorado, Sch Med, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Sch Med, Dept Immunol, Denver, CO 80262 USA. Univ Colorado, Sch Med, Dept Microbiol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Vanderbilt Univ, Dept Med, Nashville, TN USA. Vanderbilt Univ, Dept Prevent Med, Nashville, TN USA. Vanderbilt Univ, Dept Pathol, Nashville, TN USA. RP Weinberg, A (reprint author), Univ Colorado, Hlth Sci Ctr, Sch Med, Dept Pediat, Campus Box C227, Denver, CO 80262 USA. EM adriana.weinberg@uchsc.edu OI Tyler, Kenneth/0000-0003-3294-5888 FU ODCDC CDC HHS [U50/CCU416123-04] NR 9 TC 50 Z9 52 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 15 PY 2005 VL 191 IS 2 BP 234 EP 237 DI 10.1086/426402 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 881SK UT WOS:000225889500012 PM 15609233 ER PT J AU Tseng, YL Sachs, DH Cooper, DKC AF Tseng, YL Sachs, DH Cooper, DKC TI Porcine hematopoietic progenitor cell transplantation in nonhuman primates: A review of progress SO TRANSPLANTATION LA English DT Review DE baboon; bone marrow; chimerism; hematopoietic cells; pig; platelets; transplantation ID DONOR-SPECIFIC TOLERANCE; NONLETHAL PREPARATIVE REGIMEN; SIMULTANEOUS ISLET XENOGRAFTS; BONE-MARROW-TRANSPLANTATION; MIXED XENOGENEIC CHIMERISM; STAGE RENAL-DISEASE; PLATELET-AGGREGATION; ALLOGRAFT TOLERANCE; LYMPHOHEMATOPOIETIC CHIMERISM; THROMBOTIC MICROANGIOPATHY AB The critical shortage of human donor organs for transplantation would be overcome if a suitable animal, e.g., the pig, could be used as an organ source. There are, however, several immune barriers that have to date resulted in limited function of pig organs transplanted into nonhuman primates. It would be beneficial, and indeed may be essential, to induce a state of tolerance in the primate recipient to the pig organ. In allotransplantation, the successful transplantation of hematopoietic progenitor cells with the development of mixed chimerism is associated with the induction of tolerance toward a donor-specific organ. For some years, this approach has been explored in the pig-to-nonhuman primate model. This experience is briefly reviewed, The problems of natural and elicited anti-pig antibodies, recipient platelet adhesion to pig hematopietic progenitor cells, and the rapid removal of these cells by the host macrophage-phagocytic system are highlighted. Recent experience with the use of hematopoietic cells from pigs homozygous for alpha1,3-galactosyltransferase gene-knockout is reported. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. EM David.Cooper@tbrc.mgh.harvard.edu FU NIAID NIH HHS [1P01 AI45897] NR 45 TC 38 Z9 42 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 15 PY 2005 VL 79 IS 1 BP 1 EP 9 DI 10.1097/01.TP.0000146504.73727.13 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 889JH UT WOS:000226438800001 PM 15714161 ER PT J AU Omer, A Duvivier-Kali, V Fernandes, J Tchipashvili, V Colton, CK Weir, GC AF Omer, A Duvivier-Kali, V Fernandes, J Tchipashvili, V Colton, CK Weir, GC TI Long-term normoglycemia in rats receiving transplants with encapsulated islets SO TRANSPLANTATION LA English DT Article DE diabetes; islet transplantation; immunoisolation; microencapsulation; alginate ID BIOARTIFICIAL PANCREAS; ARTIFICIAL PANCREAS; PORCINE ISLETS; BOVINE ISLETS; ALGINATE; MICROENCAPSULATION; RESPONSES; MICE; XENOTRANSPLANTATION; IMMUNOSUPPRESSION AB Background. To follow up on previously successful transplantation of encapsulated islets in mice, the present study was performed in rats to determine the effects of several factors, including alginate composition and concentration of cross-linking agent and capsule size on the effectiveness of encapsulated islets. Methods. Highly purified alginate of either high guluronic acid or high mannuronic acid (M) with low endotoxin content was used. Regular-size (0.8-1.1 mm) or small microcapsules (0.5-0.7 mm) were produced by cross-linking with BaCl2 without additional poly-L-lysine coating and were transplanted into abdominal cavity of normoglycemic (empty capsules) or streptozotocin induced diabetic Lewis rats (islet containing capsules). Results. Empty regular-size capsules made of different alginate compositions had similar biocompatibility and stability results. Compared with empty capsules, regular-size capsules made of high-M alginate containing syngeneic islets had inferior stability indicated with lower fractional volume retrieved. Islet-containing smaller-size microcapsules made of high-M alginate were more stable and had less cellular attachment compared with the regular-size capsules, although the normoglycemic period was comparable between two groups of rats receiving transplants with smaller-size microcapsules (48 +/- 8 days, n = 8) or regular-size capsules (59 +/- 11 days, n = 4) in allogeneic experiments. In syngeneic experiments, all of the rats (n = 4) maintained normoglycemia up to 210 days after transplantation. Conclusion. These results indicate that regular-size alginate capsules do less well in rats than in our previous experiments with mice. Smaller capsules made of alginate cross-linked with barium appear to provide better stability and may be a useful strategy for use in larger recipients. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. MIT, Dept Chem Engn, Boston, MA USA. RP Weir, GC (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM gordon.weir@joslin.harvard.edu FU NIDDK NIH HHS [R01 DK 50657, DK 36836] NR 26 TC 48 Z9 50 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 15 PY 2005 VL 79 IS 1 BP 52 EP 58 DI 10.1097/01.TP.0000149340.37865.46 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 889JH UT WOS:000226438800009 PM 15714169 ER PT J AU Louis, K Guerineau, N Fromigue, O Defamie, V Collazos, A Anglard, P Shipp, MA Auberger, P Joubert, D Mari, B AF Louis, K Guerineau, N Fromigue, O Defamie, V Collazos, A Anglard, P Shipp, MA Auberger, P Joubert, D Mari, B TI Tumor cell-mediated induction of the stromal factor stromelysin-3 requires heterotypic cell contact-dependent activation of specific protein kinase C isoforms SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MATRIX-METALLOPROTEINASE; GENE-EXPRESSION; RETINOIC ACID; BREAST-CANCER; STRUCTURAL DETERMINANTS; PROTEOLYTIC ACTIVATION; PULMONARY FIBROBLASTS; PKC-EPSILON; N-CADHERIN; V3 REGION AB Stromelysin-3 (ST3, MMP-11) has been shown to be strongly overexpressed in stromal fibroblasts of most invasive human carcinomas. However, the molecular mechanisms leading to ST3 expression in nonmalignant fibroblasts remain unknown. The aim of the present study was to analyze the signaling pathways activated in normal pulmonary fibroblasts after their interaction with non-small cell lung cancer (NSCLC) cells and leading to ST3 expression. The use of selective signaling pathway inhibitors showed that conventional and novel protein kinase Cs (PKC) were required for ST3 induction, whereas Src kinases exerted a negative control. We observed by both conventional and real time confocal microscopy that green fluorescent protein-tagged PKCalpha and PKCepsilon, but not PKCdelta, transfected in fibroblasts, accumulate selectively at the cell-cell contacts between fibroblasts and tumor cells. In agreement, RNAi-mediated depletion of PKCalpha and PKCepsilon, but not PKCdelta significantly decreased co-culture-dependent ST3 production. Finally, a tetracycline-inducible expression model allowed us to confirm the central role of these PKC isoforms and the negative regulatory function of c-Src in the control of ST3 expression. Altogether, our data emphasize signaling changes occurring in the tumor microenvironment that may define new stromal targets for therapeutic intervention. C1 Fac Med Pasteur, INSERM, U526, IFR50, F-06107 Nice, France. CNRS, INSERM, U469, CCIPE, F-34094 Montpellier, France. Univ Strasbourg 1, INSERM, U575, F-67084 Strasbourg, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mari, B (reprint author), Fac Med Pasteur, INSERM, U526, IFR50, F-06107 Nice, France. EM bernard.mari@unice.fr RI Mari, Bernard/F-8960-2013; Mari, Bernard/D-7445-2015; AUBERGER, Patrick/G-1491-2013; OI Mari, Bernard/0000-0002-0422-9182; AUBERGER, Patrick/0000-0002-2481-8275; Guerineau, Nathalie/0000-0003-2517-4210 NR 69 TC 11 Z9 11 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 JAN 14 PY 2005 VL 280 IS 2 BP 1272 EP 1283 DI 10.1074/jbc.M405482200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 885ZF UT WOS:000226195200052 PM 15509588 ER PT J AU Mawson, A Lai, A Carroll, JS Sergio, CM Mitchell, CJ Sarcevic, B AF Mawson, A Lai, A Carroll, JS Sergio, CM Mitchell, CJ Sarcevic, B TI Estrogen and insulin/IGF-1 cooperatively stimulate cell cycle progression in MCF-7 breast cancer cells through differential regulation of c-Myc and cyclin D1 SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE estrogen; insulin; IGF-1; c-Myc; cyclin D1 ID GROWTH-FACTOR-I; ACTIVATED PROTEIN-KINASE; RECEPTOR SUBSTRATE-1 EXPRESSION; S-PHASE ENTRY; PHOSPHATIDYLINOSITOL 3-KINASE; RETINOBLASTOMA PROTEIN; E-CDK2 ACTIVATION; CDK COMPLEXES; PHOSPHORYLATION; PATHWAY AB Estrogen and insulin/insulin-like growth factor-I (IGF-I) are major mitogens for breast epithelial cells and when co-administered, synergistically induce G(1)-S phase cell cycle progression. We investigated this cooperativity by evaluating if the key cell cycle regulators. c-Myc and cyclin D1, represent points of convergence in the action of these mitogens in MCF-7 breast cancer cells. These studies demonstrated that estrogen significantly increased both c-Myc and cyclin D1 protein, while insulin predominantly increased cyclin D1 levels. This cumulative increase in c-Myc and cyclin D1 contributes to the cooperativity of these mitogens, since ectopic expression of c-Myc or cyclin D1 cooperates with either the estrogen Or insulin signaling pathways to increase cell cycle progression. Inhibition of the MAPK or PI3-kinase pathway significantly reduced c-Myc and cyclin D1 protein levels and cell cycle progression. Ectopic expression of cyclin D1 partially overcame this inhibition, while ectopic expression of c-Myc partially overcame MAPK but not PI3-kinase inhibition. Therefore, estrogen and insulin/IGF-1 differentially regulate c-Myc and cyclin D1 to cooperatively stimulate breast cancer cell proliferation. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Garvan Inst Med Res, Canc Res Program, Darlinghurst, NSW 2010, Australia. Johnson & Johnson Res Labs, Eveleigh, NSW 1430, Australia. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Garvan Inst Med Res, Diabet & Obes Res Program, Darlinghurst, NSW 2010, Australia. RP Sarcevic, B (reprint author), Garvan Inst Med Res, Canc Res Program, 384 Victoria St, Darlinghurst, NSW 2010, Australia. EM b.sarcevic@garvan.org.au OI Sarcevic, Boris/0000-0002-8063-1050 NR 62 TC 83 Z9 89 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JAN 14 PY 2005 VL 229 IS 1-2 BP 161 EP 173 DI 10.1016/j.mce.2004.08.002 PG 13 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 891QU UT WOS:000226596400019 PM 15607540 ER PT J AU Niess, JH Brand, S Gu, XB Landsman, L Jung, S McCormick, BA Vyas, JM Boes, M Ploegh, HL Fox, JG Littman, DR Reinecker, HC AF Niess, JH Brand, S Gu, XB Landsman, L Jung, S McCormick, BA Vyas, JM Boes, M Ploegh, HL Fox, JG Littman, DR Reinecker, HC TI CX(3)CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance SO SCIENCE LA English DT Article ID PEYERS PATCH; IMMUNE-RESPONSES; FRACTALKINE; EPITHELIUM; LOCALIZATION; CHEMOKINE; SUBSETS; GUT AB Dendritic cells (DCs) and macrophages are critical to innate and adaptive immunity to the intestinal bacterial microbiota. Here, we identify a myeloid-derived mucosal DC in mice, which populates the entire lamina propria of the small intestine. Lamina propria DCs were found to depend on the chemokine receptor CX(3)CR1 to form transepithelial dendrites, which enable the cells to directly sample luminal antigens. CX(3)CR1 was also found to control the clearance of entero-invasive pathogens by DCs. Thus, CX(3)C1-dependent processes, which control host interactions of specialized DCs with commensal and pathogenic bacteria, may regulate immunological tolerance and inflammation. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat Gastroenterol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. NYU, Sch Med, Howard Hughes Med Inst, Mol Pathogenesis Program,Skirball Inst Biomol Med, New York, NY 10016 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. MIT, Div Comparat Med, Cambridge, MA 02139 USA. RP Reinecker, HC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. EM hans-christian-reinecker@hms.harvard.edu RI Vyas, Jatin/Q-1627-2016; Niess, Jan /E-8361-2017 OI Vyas, Jatin/0000-0002-9985-9565; Niess, Jan /0000-0001-6902-5650 FU NIAID NIH HHS [AI33856]; NIDDK NIH HHS [DK33506, DK54427] NR 18 TC 887 Z9 920 U1 6 U2 58 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 14 PY 2005 VL 307 IS 5707 BP 254 EP 258 DI 10.1126/science.1102901 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 888GJ UT WOS:000226361900043 PM 15653504 ER PT J AU Sales, AE Pineros, SL Magid, DJ Every, NR Sharp, ND Rumsfeld, JS AF Sales, AE Pineros, SL Magid, DJ Every, NR Sharp, ND Rumsfeld, JS TI The association between clinical integration of care and transfer of veterans with acute coronary syndromes from primary care VHA hospitals SO BMC HEALTH SERVICES RESEARCH LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; PRACTITIONERS REFERRAL DECISIONS; PRACTICE GUIDELINES COMMITTEE; ARTERY BYPASS-SURGERY; MEDICAL-CARE; AMERICAN-COLLEGE; UNSTABLE ANGINA; UNITED-STATES; TASK-FORCE; OUTCOMES AB Background: Few studies report on the effect of organizational factors facilitating transfer between primary and tertiary care hospitals either within an integrated health care system or outside it. In this paper, we report on the relationship between degree of clinical integration of cardiology services and transfer rates of acute coronary syndrome (ACS) patients from primary to tertiary hospitals within and outside the Veterans Health Administration (VHA) system. Methods: Prospective cohort study. Transfer rates were obtained for all patients with ACS diagnoses admitted to 12 primary VHA hospitals between 1998 and 1999. Binary variables measuring clinical integration were constructed for each primary VHA hospital reflecting: presence of on-site VHA cardiologist; referral coordinator at the associated tertiary VHA hospital; and/or referral coordinator at the primary VHA hospital. We assessed the association between the integration variables and overall transfer from primary to tertiary hospitals, using random effects logistic regression, controlling for clustering at two levels and adjusting for patient characteristics. Results: Three of twelve hospitals had a VHA cardiologist on site, six had a referral coordinator at the tertiary VHA hospital, and four had a referral coordinator at the primary hospital. Presence of a VHA staff cardiologist on site and a referral coordinator at the tertiary VHA hospital decreased the likelihood of any transfer (OR 0.45, 95% CI 0.27-0.77, and 0.46, p = 0.002, CI 0.27-0.78). Conversely, having a referral coordinator at the primary VHA hospital increased the likelihood of transfer (OR 6.28, CI 2.92-13.48). Conclusions: Elements of clinical integration are associated with transfer, an important process in the care of ACS patients. In promoting optimal patient care, clinical integration factors should be considered in addition to patient characteristics. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Denver VA Med Ctr, Denver, CO USA. Colorado Permanente Clin Res Unit, Denver, CO USA. VA Puget Sound Hlth Care Syst, Serv Cardiol, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. RP Sales, AE (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA. EM ann.sales@med.va.gov; sandra.pineros@med.va.gov; david.j.magid@kp.org; nathan@frazierco.com; nancy.sharp@med.va.gov; john.rumsfeld@med.va.gov RI Sales, Anne/D-9678-2012; OI Sales, Anne/0000-0001-9360-3334 NR 25 TC 2 Z9 2 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1472-6963 J9 BMC HEALTH SERV RES JI BMC Health Serv. Res. PD JAN 13 PY 2005 VL 5 AR 2 DI 10.1186/1472-6963-5-2 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 891US UT WOS:000226607100001 PM 15649313 ER PT J AU Wang, J Gines, S MacDonald, ME Gusella, JF AF Wang, J Gines, S MacDonald, ME Gusella, JF TI Reversal of a full-length mutant huntingtin neuronal cell phenotype by chemical inhibitors of polyglutamine-mediated aggregation SO BMC NEUROSCIENCE LA English DT Article ID KNOCK-IN MICE; DISEASE GENE HOMOLOG; MOUSE MODEL; NEURODEGENERATIVE DISEASE; INTERACTING PROTEINS; EMBRYONIC LETHALITY; STRIATAL CELLS; CAG REPEAT; MINOCYCLINE; IDENTIFICATION AB Background: Huntington's disease ( HD) is an inherited neurodegenerative disorder triggered by an expanded polyglutamine tract in huntingtin that is thought to confer a new conformational property on this large protein. The propensity of small amino-terminal fragments with mutant, but not wild- type, glutamine tracts to self-aggregate is consistent with an altered conformation but such fragments occur relatively late in the disease process in human patients and mouse models expressing full- length mutant protein. This suggests that the altered conformational property may act within the full- length mutant huntingtin to initially trigger pathogenesis. Indeed, genotype-phenotype studies in HD have defined genetic criteria for the disease initiating mechanism, and these are all fulfilled by phenotypes associated with expression of full- length mutant huntingtin, but not amino-terminal fragment, in mouse models. As the in vitro aggregation of amino-terminal mutant huntingtin fragment offers a ready assay to identify small compounds that interfere with the conformation of the polyglutamine tract, we have identified a number of aggregation inhibitors, and tested whether these are also capable of reversing a phenotype caused by endogenous expression of mutant huntingtin in a striatal cell line from the Hdh(QIII)/(QIII) knock-in mouse. Results: We screened the NINDS Custom Collection of 1,040 FDA approved drugs and bioactive compounds for their ability to prevent in vitro aggregation of Q58- htn 1 - 171 amino terminal fragment. Ten compounds were identified that inhibited aggregation with IC50 < 15 mu M, including gossypol, gambogic acid, juglone, celastrol, sanguinarine and anthralin. Of these, both juglone and celastrol were effective in reversing the abnormal cellular localization of full- length mutant huntingtin observed in mutant Hdh(QIII)/(QIII) striatal cells. Conclusions: At least some compounds identified as aggregation inhibitors also prevent a neuronal cellular phenotype caused by full- length mutant huntingtin, suggesting that in vitro fragment aggregation can act as a proxy for monitoring the disease- producing conformational property in HD. Thus, identification and testing of compounds that alter in vitro aggregation is a viable approach for defining potential therapeutic compounds that may act on the deleterious conformational property of full- length mutant huntingtin. C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02129 USA. Univ Barcelona, Fac Med, Dept Cellular Biol & Anat Patol, E-08036 Barcelona, Spain. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Wang, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02129 USA. EM jwang15@partners.org; silviagines@ub.edu; macdonam@helix.mgh.harvard.edu; gusella@helix.mgh.harvard.edu FU NINDS NIH HHS [NS32765, NS16367, P50 NS016367, R01 NS032765] NR 49 TC 64 Z9 71 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2202 J9 BMC NEUROSCI JI BMC Neurosci. PD JAN 13 PY 2005 VL 6 AR 1 DI 10.1186/1471-2202-6-1 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 895NS UT WOS:000226870700001 PM 15649316 ER PT J AU Batchelor, TT Buchbinder, BR Harris, NL AF Batchelor, TT Buchbinder, BR Harris, NL TI A 35-year-old woman with difficulty walking, headache, and nausea - Primary diffuse large-B-cell lymphoma of the brain. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CENTRAL-NERVOUS-SYSTEM; PRIMARY CNS LYMPHOMA; NON-HODGKINS-LYMPHOMA; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; HIGH-DOSE METHOTREXATE; MALIGNANT-LYMPHOMA; HISTOGENETIC SUBSETS; CHEMOTHERAPY; SURVIVAL; BCL-6 C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Batchelor, TT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 43 TC 2 Z9 3 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 13 PY 2005 VL 352 IS 2 BP 185 EP 194 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 886TG UT WOS:000226251700013 PM 15647582 ER PT J AU Elchuri, S Oberley, TD Qi, WB Eisenstein, RS Roberts, LJ Van Remmen, H Jepstein, CJ Huang, TT AF Elchuri, S Oberley, TD Qi, WB Eisenstein, RS Roberts, LJ Van Remmen, H Jepstein, CJ Huang, TT TI CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life SO ONCOGENE LA English DT Article DE CuZnSOD; hepatocellular carcinoma; aconitase; 8-oxo dG; cyclin D1; APEX1; Met ID HUMAN HEPATOCELLULAR-CARCINOMA; CARBONIC-ANHYDRASE-III; ZINC SUPEROXIDE-DISMUTASE; IRON REGULATORY PROTEINS; TRANSGENIC MICE; GLUTATHIONE-PEROXIDASE; ANTIOXIDANT ENZYMES; LIVER-REGENERATION; MITOCHONDRIAL-DNA; MAMMALIAN-CELLS AB Mice deficient in CuZn superoxide dismutase (CuZn-SOD) showed no overt abnormalities during development and early adulthood, but had a reduced lifespan and increased incidence of neoplastic changes in the liver. Greater than 70% of Sod1-/- mice developed liver nodules that were either nodular hyperplasia or hepatocellular carcinoma (HCC). Cross-sectional studies with livers collected from Sod1-/- and age-matched +/+ controls revealed extensive oxidative damage in the cytoplasm and, to a lesser extent, in the nucleus and mitochondria from as early as 3 months of age. A marked reduction in cytosolic aconitase, increased levels of 8-oxo dG and F2-isoprostanes, and a moderate reduction in glutathione peroxidase activities and porin levels were observed in all age groups of Sod1-/- mice examined. There were also age-related reductions in Mn superoxide dismutase activities and carbonic anhydrase III. Parallel to the biochemical changes, there were progressive increases in the DNA repair enzyme APEX1, the cell cycle control proteins cyclin D1 and D3, and the hepatocyte growth factor receptor Met. Increased cell proliferation in the presence of persistent oxidative damage to macromolecules likely contributes to hepatocarcinogenesis later in life. C1 Stanford Univ, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. Univ Wisconsin, Dept Pathol, Madison, WI 53706 USA. VA Hosp, Pathol Serv, Madison, WI 53705 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA. Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37232 USA. Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA. Audie L Murphy Mem Vet Adm Med Ctr, GRECC, San Antonio, TX 78229 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94341 USA. Palo Alto VA Hlth Care Syst, GRECC, Palo Alto, CA 94304 USA. RP Huang, TT (reprint author), Stanford Univ, Dept Neurol & Neurol Sci, 3801 Miranda Ave,Bldg 100,Room D3-101,Mail Stop 1, Palo Alto, CA 94304 USA. EM tthuang@stanford.edu RI Bell, Tiffany/F-4403-2010 FU NIA NIH HHS [AG16633, AG16998]; NIDDK NIH HHS [DK26657, DK47219]; NIGMS NIH HHS [GM15431, GM42056] NR 89 TC 314 Z9 331 U1 2 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 13 PY 2005 VL 24 IS 3 BP 367 EP 380 DI 10.1038/sj.onc.1208207 PG 14 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 887CH UT WOS:000226279700008 PM 15531919 ER PT J AU Singh, N Armstrong, DG Lipsky, BA AF Singh, N Armstrong, DG Lipsky, BA TI Preventing foot ulcers in patients with diabetes SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID LOWER-EXTREMITY AMPUTATION; QUALITY-OF-LIFE; LIMITED JOINT MOBILITY; PERIPHERAL NEUROPATHY; CONTROLLED TRIAL; HIGH-RISK; TUNING FORK; THERAPEUTIC FOOTWEAR; CLINICAL EXAMINATION; NONDIABETIC PATIENTS AB Context Among persons diagnosed as having diabetes mellitus, the prevalence of foot ulcers is 4% to 10%, the annual population-based incidence is 1.0% to 4.1%, and the lifetime incidence may be as high as 25%. These ulcers frequently become infected, cause great morbidity, engender considerable financial costs, and are the usual first step to lower extremity amputation. Objective To systematically review the evidence on the efficacy of methods advocated for preventing diabetic foot ulcers in the primary care setting. Data Sources, Study Selection, and Data Extraction The EBSCO, MEDLINE, and the National Guideline Clearinghouse databases were searched for articles published between January 1980 and April 2004 using database-specific keywords. Bibliographies of retrieved articles were also searched, along with the Cochrane Library and relevant Web sites. We reviewed the retrieved literature for pertinent information, paying particular attention to prospective cohort studies and randomized clinical trials. Data Synthesis Prevention of diabetic foot ulcers begins with screening for loss of protective sensation, which is best accomplished in the primary care setting with a brief history and the Semmes-Weinstein monofilament. Specialist clinics may quantify neuropathy with biothesiometry, measure plantar foot pressure, and assess lower extremity vascular status with Doppler ultrasound and ankle-brachial blood pressure indices. These measurements, in conjunction with other findings from the history and physical examination, enable clinicians to stratify patients based on risk and to determine the type of intervention. Educating patients about proper foot care and periodic foot examinations are effective interventions to prevent ulceration. Other possibly effective clinical interventions include optimizing glycemic control, smoking cessation, intensive podiatric care, debridement of calluses, and certain types of prophylactic foot surgery. The value of various types of prescription footwear for ulcer prevention is not clear. Conclusions Substantial evidence supports screening all patients with diabetes to identify those at risk for foot ulceration. These patients might benefit from certain prophylactic interventions, including patient education, prescription footwear, intensive podiatric care, and evaluation for surgical interventions. C1 Vet Affairs Puget Sound Healthcare Syst, Dept Med, Div Endocrinol & Metab, Seattle, WA 98108 USA. Vet Affairs Puget Sound Healthcare Syst, Dept Med, Div Gen Internal Med & Infect Dis, Seattle, WA 98108 USA. Univ Washington, Sch Med, Seattle, WA USA. Rosalind Franklin Univ Med & Sci, Dr William M Scholl Coll Podiatr Med, Ctr Lower Extrem Ambulatory Res, Chicago, IL USA. RP Singh, N (reprint author), Vet Affairs Puget Sound Healthcare Syst, Dept Med, Div Endocrinol & Metab, Mailcode S-111-ENDO,1660 S Columbian Way, Seattle, WA 98108 USA. EM Nalini.Singh2@med.va.gov OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 128 TC 779 Z9 861 U1 13 U2 139 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 12 PY 2005 VL 293 IS 2 BP 217 EP 228 DI 10.1001/jama.293.2.217 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 885QC UT WOS:000226171000038 PM 15644549 ER PT J AU Wang, SX Lim, G Zeng, Q Sung, B Yang, LL Mao, JR AF Wang, SX Lim, G Zeng, Q Sung, B Yang, LL Mao, JR TI Central glucocorticoid receptors modulate the expression and function of spinal NMDA receptors after peripheral nerve injury SO JOURNAL OF NEUROSCIENCE LA English DT Article DE glucocorticoid receptor; NMDA receptor; neuropathic pain; nerve injury; RU38486; interleukin; protein kinase C ID NECROSIS-FACTOR-ALPHA; NEUROPATHIC PAIN; MESSENGER-RNA; MOLECULAR-MECHANISMS; POSSIBLE INVOLVEMENT; CONSTRICTION INJURY; MORPHINE-TOLERANCE; SCIATIC-NERVE; RAT; NEURONS AB Central glucocorticoid receptors (GRs) and NMDA receptors (NMDARs) have been shown to play a significant role in the mechanisms of neuropathic pain after peripheral nerve injury; however, how central GRs and NMDARs interact in this process remains unknown. Here we show that the expression and function of spinal NMDARs after peripheral nerve injury were modulated by central GRs. Chronic constriction nerve injury (CCI) in rats induced a time-dependent upregulation of NR1 and NR2 subunits of the NMDAR within the spinal cord dorsal horn ipsilateral to CCI. The upregulation of NMDARs was significantly diminished by intrathecal administration (twice daily for postoperative days 1-6) of either the GR antagonist RU38486 or an antisense oligonucleotide against GRs. Moreover, this CCI-induced expression of NMDARs was significantly attenuated in rats receiving intrathecal treatment with an interleukin-6 (IL-6) antiserum and in mice with protein kinase Cgamma (PKCgamma) knock-out. Because IL-6 and PKCgamma mediated the upregulation of central GRs after CCI as demonstrated previously, the results suggest that IL-6 and PKCgamma served as cellular mediators contributing to the GR-mediated expression of NMDARs after CCI. Functionally, nociceptive behaviors induced by NMDAR activation and CCI were reversed by a single intrathecal administration of the GR antagonist RU38486. Conversely, a single intrathecal injection with the noncompetitive NMDAR antagonist MK-801 reversed neuropathic pain behaviors exacerbated by the GR agonist dexamethasone in CCI rats. These data suggest that interactions between central GRs and NMDARs through genomic and nongenomic regulation may be an important mechanism critical to neuropathic pain behaviors in rats. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Pain Ctr,Pain Res Grp, Boston, MA 02114 USA. RP Mao, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Pain Ctr,Pain Res Grp, WACC 324,15 Parkman St, Boston, MA 02114 USA. EM jmao@partners.org FU NIDA NIH HHS [R01 DA08835]; NINDS NIH HHS [R01 NS 45681, R01 NS 42661] NR 46 TC 76 Z9 98 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 12 PY 2005 VL 25 IS 2 BP 488 EP 495 DI 10.1523/JNEUROSCI.4127-04.2005 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 886ZI UT WOS:000226271400024 PM 15647493 ER PT J AU Weisskopf, MG O'Reilly, EJ McCullough, ML Calle, EE Thun, MJ Cudkowicz, M Ascherio, A AF Weisskopf, MG O'Reilly, EJ McCullough, ML Calle, EE Thun, MJ Cudkowicz, M Ascherio, A TI Prospective study of military service and mortality from ALS SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DISEASE; GULF-WAR VETERANS; OCCUPATIONAL EXPOSURES; PHYSICAL-ACTIVITY; DEATH; RISK; LEAD; SURVIVAL; DIAGNOSIS AB Background: Two recent studies suggest that the risk of ALS is increased among Gulf War veterans. It is not known whether military service outside of the Gulf War is associated with increased risk of ALS. Methods: The authors prospectively assessed the relation between service in the military and ALS mortality among participants in the Cancer Prevention Study II cohort of the American Cancer Society, a cohort that includes over 500,000 men from the 50 states, Washington, DC, and Puerto Rico. Participant follow-up was conducted from 1989 through 1998 for ALS mortality. There were a total of 280 deaths from ALS among 126,414 men who did not serve in the military and 281,874 who did. Adjusted relative risks (RRs) were calculated using Mantel-Haenszel weights and Cox proportional hazards. Results: Men who served in the military had an increased death rate from ALS (RR = 1.53; 95% CI: 1.12 to 2.09; p = 0.007) compared with those who did not serve. The increase in ALS mortality was observed among men who served in the Army or National Guard (RR = 1.54), Navy (RR = 1.87), Air Force (RR = 1.54), and Coast Guard (RR = 2.24); no increase in risk was found in men who served in the Marine Corps, although there were only 13,670 men in this group. The risk of ALS among men who served was elevated in every 5-year birth cohort from 1915 through 1939. Conclusions: Military personnel have an increased risk of ALS. This increase appeared to be largely independent of the branch of service and the time period served. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Trial Unit, Boston, MA USA. Amer Canc Soc, Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. RP Ascherio, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Channing Lab, 655 Huntington Ave,3rd Fl, Boston, MA 02115 USA. EM alberto.ascherio@channing.harvard.edu FU NINDS NIH HHS [R01 NS045893-01] NR 45 TC 99 Z9 101 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN 11 PY 2005 VL 64 IS 1 BP 32 EP 37 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 886GX UT WOS:000226216000008 PM 15642900 ER PT J AU Gaviani, P Gonzalez, RG Zhu, JJ Batchelor, TT Henson, JW AF Gaviani, P Gonzalez, RG Zhu, JJ Batchelor, TT Henson, JW TI Central neurogenic hyperventilation and lactate production in brainstem glioma SO NEUROLOGY LA English DT Editorial Material ID LYMPHOMA C1 Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Henson, JW (reprint author), Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Cox 315,Fruit St, Boston, MA 02114 USA. EM henson@helix.mgh.harvard.edu NR 8 TC 10 Z9 10 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 JAN 11 PY 2005 VL 64 IS 1 BP 166 EP 167 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 886GX UT WOS:000226216000039 PM 15642931 ER PT J AU Berghmans, S Murphey, RD Wienholds, E Neuberg, D Kutok, JL Fletcher, CDM Morris, JP Liu, TX Schulte-Merker, S Kanki, JP Plasterk, R Zon, LI Look, AT AF Berghmans, S Murphey, RD Wienholds, E Neuberg, D Kutok, JL Fletcher, CDM Morris, JP Liu, TX Schulte-Merker, S Kanki, JP Plasterk, R Zon, LI Look, AT TI tp53 mutant zebrafish develop malignant peripheral nerve sheath tumors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NEUROFIBROMATOSIS TYPE-1; MODEL ORGANISM; P53 MUTATIONS; MOUSE MODELS; DANIO-RERIO; DNA-DAMAGE; APOPTOSIS; SUPPRESSION; GENE; MICE AB TP53 is the most frequently mutated tumor suppressor gene in human cancer, with nearly 50% of all tumors exhibiting a loss-of-function mutation. To further elucidate the genetic pathways involving TP53 and cancer, we have exploited the zebrafish, a powerful vertebrate model system that is amenable to whole-genome forward-genetic analysis and synthetic-lethal screens. Zebrafish lines harboring missense mutations in the tp53 DNA-binding domain were identified by using a target-selected mutagenesis strategy. Homozygous mutant fish from two of these lines were viable and exhibited mutations similar to those found in human cancers (tp53(N168K) and tp53(M214K)). Although homozygous tp53(N168K) mutants were temperature-sensitive and suppressed radiation-induced apoptosis only at 37degreesC, cells in the tP53(M214K) embryos failed to undergo apoptosis in response to gamma radiation at both 28 and 37degreesC. Unlike wild-type control embryos, irradiated tp53(M214K) embryos also failed to up-regulate p21 and did not arrest at the G(1)/S checkpoint. Beginning at 8.5 months of age, 28% of tp53(M214K) mutant fish developed malignant peripheral nerve sheath tumors. In addition to providing a model for studying the molecular pathogenic pathways of malignant peripheral nerve sheath tumors, these mutant zebrafish lines provide a unique platform for modifier screens to identify genetic mutations or small molecules that affect tp53-related pathways, including apoptosis, cell-cycle delay, and tumor suppression. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Ctr Biomed Genet, Hubrecht Lab, NL-3584 CA Utrecht, Netherlands. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Exelixis Deutschland GmbH, D-72076 Tubingen, Germany. RP Look, AT (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu OI Berghmans, Stephane/0000-0001-5414-8674 FU NCI NIH HHS [CA-68484, P01 CA068484, P30 CA006516, P30CA6516] NR 60 TC 308 Z9 322 U1 1 U2 16 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 11 PY 2005 VL 102 IS 2 BP 407 EP 412 DI 10.1073/pnas.0406252102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 887OP UT WOS:000226315700028 PM 15630097 ER PT J AU Chen, ML Pittet, MJ Gorelik, L Flavell, RA Weissleder, R von Boehmer, H Khazaie, K AF Chen, ML Pittet, MJ Gorelik, L Flavell, RA Weissleder, R von Boehmer, H Khazaie, K TI Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-beta signals in vivoi SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GROWTH-FACTOR-BETA; EFFECTOR FUNCTION; DENDRITIC CELLS; IFN-GAMMA; ANTIGEN; RESPONSES; LYMPHOCYTES; INHIBITION; TOLERANCE; EXPANSION AB Cancer patients can harbor significant numbers of CD8 and CD4 T cells with specificities to tumor antigens (Ags). Yet, in most cases, such T cells fail to eradicate the tumor in vivo. Here, we investigated the interference of Ag-specific CD4(+)CD25(+) regulatory T cells (Treg) with the tumor-specific CD8 T cell immune response in vivo, by monitoring the homing, expansion, and effector function of both subsets in draining and nondraining lymph nodes. The results show that CD8 cells expand to the same extent and produce similar levels of IFN-gamma in the presence or absence of Ag-specific Treg. Nevertheless, these Treg abrogate CD8 T cell-mediated tumor rejection by specifically suppressing the cytotoxicity of expanded CD8 cells. The molecular mechanism of suppression involves TGF-beta because expression of a dominant-negative TGF-beta receptor by tumor-specific CD8 cells renders them resistant to suppression and is associated with tumor rejection and unimpaired cytotoxicity. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06520 USA. Yale Univ, Howard Hughes Med Inst, New Haven, CT 06520 USA. RP Khazaie, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Smith 736, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu; khashayarsha_khazaie@dfci.harvard.edu RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NCI NIH HHS [F33 CA097728, R33 CA97728-02] NR 41 TC 397 Z9 443 U1 1 U2 15 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 11 PY 2005 VL 102 IS 2 BP 419 EP 424 DI 10.1073/pnas.0408197102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 887OP UT WOS:000226315700030 PM 15623559 ER PT J AU Pallin, DJ Muennig, PA Emond, JA Kim, S Camargo, CA AF Pallin, DJ Muennig, PA Emond, JA Kim, S Camargo, CA TI Vaccination practices in US emergency departments, 1992-2000 SO VACCINE LA English DT Article DE vaccination; emergency department; influenza ID PNEUMOCOCCAL POLYSACCHARIDE VACCINE; COST-EFFECTIVENESS; INFLUENZA VACCINE; ELDERLY PERSONS; UNITED-STATES; ADULTS; EFFICACY; OPPORTUNITIES; IMMUNIZATION; FEASIBILITY AB To determine how frequently emergency department (ED) patients are vaccinated against influenza and pneumococcus, we analyzed all adult ED vaccinations in the combined databases of the annual National Hospital Ambulatory Medical Care Surveys, 1992-2000. During this period, EDs gave 27,738,000 vaccinations (95%CI: 25,878,000-29,598,000). Of these, 93% (87-100%) were against tetanus. The count of pneumococcal or influenza vaccinations was too small to permit estimation of a national total. Large-scale vaccination of ED patients appears feasible, given the tetanus experience, but ED patients are rarely vaccinated against influenza or pneumococcus. Reasons for this disconnect between burden of disease and preventive practices are discussed. (C) 2004 Elsevier Ltd. All rights reserved. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Hlth Policy & Management, New York, NY 10032 USA. Massachusetts Gen Hosp, EMNet Coordinating Ctr, Boston, MA 02114 USA. RP Pallin, DJ (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM dpallin@partners.org RI Pallin, Daniel/H-6382-2013; OI Pallin, Daniel/0000-0002-8517-9702; Muennig, Peter/0000-0002-4234-0498 FU NHLBI NIH HHS [HL63841] NR 47 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JAN 11 PY 2005 VL 23 IS 8 BP 1048 EP 1052 DI 10.1016/j.vaccine.2004.06.053 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 890XT UT WOS:000226545400010 PM 15620478 ER PT J AU Garber, JE Offit, K AF Garber, JE Offit, K TI Hereditary cancer predisposition syndromes SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID NONPOLYPOSIS COLORECTAL-CANCER; FAMILIAL ADENOMATOUS POLYPOSIS; LI-FRAUMENI-SYNDROME; BRCA2 MUTATION CARRIERS; CELL CARCINOMA SYNDROME; DIFFUSE GASTRIC-CANCER; GENOTYPE-PHENOTYPE CORRELATIONS; CUTANEOUS MALIGNANT-MELANOMA; HIPPEL-LINDAU-DISEASE; SHARED GENETIC SUSCEPTIBILITY AB Cancer genetics is increasingly becoming integrated into the practice of modern medical oncology. The ability to distinguish a growing proportion of the 5% to 10% of all cancers that develop in individuals who have inherited a genetic mutation conferring heightened susceptibility to specific cancers may permit targeted efforts in cancer surveillance and, prevention. While these individuals comprise a small proportion of the overall burden of cancer, strategies successful in reducing their remarkable cancer risks may be generalizable to the broader population. In this review, we highlight the most common hereditary cancer syndromes, most attributable to genes inherited in an autosomal dominant manner with incomplete penetrance, and a number of rare syndromes in which particular progress has been made. The prevalence, penetrance, tumor spectrum, and underlying genetic defects are discussed and summarized in a large table in which a more comprehensive enumeration of syndromes is provided. C1 Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY USA. RP Garber, JE (reprint author), Dana Farber Canc Inst, Div Populat Sci, 44 Binney St,SM 209, Boston, MA 02115 USA. EM judy_garber@dfci.harvard.edu; offitk@mskcc.org NR 197 TC 192 Z9 198 U1 1 U2 16 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2005 VL 23 IS 2 BP 276 EP 292 DI 10.1200/JCO.2005.10.042 PG 17 WC Oncology SC Oncology GA 887XG UT WOS:000226338200004 PM 15637391 ER PT J AU Bertagnolli, MM AF Bertagnolli, MM TI Surgical prevention of cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID FAMILIAL ADENOMATOUS POLYPOSIS; CARCINOMA IN-SITU; NONPOLYPOSIS COLORECTAL-CANCER; MULTIPLE ENDOCRINE NEOPLASIA; PAPILLARY MUCINOUS NEOPLASMS; BILATERAL PROPHYLACTIC MASTECTOMY; POUCH-ANAL ANASTOMOSIS; HIGH-GRADE DYSPLASIA; LONG-TERM SURVIVAL; BREAST-CANCER AB There have been many recent advances in cancer prevention, including improved understanding of cancer biology, better characterization of premalignant disease, significant advances in cancer surveillance, and identification of effective chemoprevention regimens. Despite this, surgery remains the best option for many individuals at high risk of cancer. Like all prevention modalities, surgical prevention involves balancing the factors governing cancer risk with the benefits and risks of treatment. The issues governing decision making for surgical prevention vary widely among different cancer types, and include consideration of the age and level of cancer risk of the individual, the effectiveness of cancer surveillance for the particular organ at risk, the aggressiveness of the cancer once present, and the morbidity of surgery. This article briefly reviews the use of surgery to prevent some of the most common epithelial malignancies, as well as some of the genetic cancer syndromes for which surgery plays an important role in improving survival. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bertagnolli, MM (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM mbertagnolli@partners.org NR 61 TC 7 Z9 7 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2005 VL 23 IS 2 BP 324 EP 332 DI 10.1200/JCO.2005.08.096 PG 9 WC Oncology SC Oncology GA 887XG UT WOS:000226338200008 PM 15637395 ER PT J AU Oreskovich, MR Saxon, AJ Ellis, MLK Malte, CA Reoux, JP Knox, PC AF Oreskovich, MR Saxon, AJ Ellis, MLK Malte, CA Reoux, JP Knox, PC TI A double-blind, double-dummy, randomized, prospective pilot study of the partial Mu opiate agonist, buprenorphine, for acute detoxification from heroin SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE treatment; opiate dependence; buprenorphine; clonidine; detoxification ID OPIOID DETOXIFICATION; CLINICAL-TRIALS; FOLLOW-UP; CLONIDINE; WITHDRAWAL; INPATIENT; METHADONE; SYMPTOMS; ADDICTS; EFFICACY AB The optimum dose of buprenorphine for acute inpatient heroin detoxification has not been determined. This randomized, double-blind. double-dummy, pilot study compares two buprenorphine sublingual tablet dosing schedules to oral clonidine. Heroin users (N = 30) who met DSM-IV criteria for opioid dependence and achieved a Clinical Opiate Withdrawal Scale (COWS) score of 13 (moderate withdrawal).were randomized to receive higher dose buprenorphine (HD, 8-8-8-4-2 mg/day on days 1-5), lower dose buprenorphine (LD. 2-4-84-2 mg/day on days 1-5). or clonidine (C, 0.2-0.3-0.3-0.2-0.1 mg QID on days 1-5). COWS scores were obtained QID. Twenty-four hours after randomization. the percentages of subjects who achieved suppression of withdrawal, as defined by four consecutive COWS scores < 12. were: C = 11%, LD 40%, and HD = 60%. Generalized estimating equation regression models. controlling for baseline COWS and time. indicated that COWS scores over the course of 5 days were lower in both LD and HD compared to C (chi(2)(2) = 13.28. P = 0.001). Similar analyses examining, scores over time on the Adjective Rating Scale for Withdrawal (ARSW) and on a Visual Analog Scale of Opiate Craving (VAS) indicated an overall treatment effect on the VAS accounted for by a significant difference between HD and C, but no overall treatment effect on the ARSW There were no discontinuations due to treatment-related adverse events. Both HD and LD regimens are safe, and efficacious treatment for opioid detoxification. but HD demonstrated superiority to C on a greater number of measures. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. Vet Affairs Puget Sound Healthcare Syst, Seattle, WA 98108 USA. Ctr Excellence Substance Abuse Treatment & Educ, Seattle, WA 98108 USA. Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. Recovery Ctr King Cty, Seattle, WA 98122 USA. RP Saxon, AJ (reprint author), Univ Washington, Sch Med, Dept Psychiat & Behav Sci, 1660 S Columbian Way, Seattle, WA 98108 USA. EM Andrew.Saxon@med.va.gov NR 37 TC 27 Z9 27 U1 2 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 7 PY 2005 VL 77 IS 1 BP 71 EP 79 DI 10.1016/j.drugalcdep.2004.07.008 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 888TQ UT WOS:000226397500009 PM 15607843 ER PT J AU Miller, AJ Levy, C Davis, IJ Razin, E Fisher, DE AF Miller, AJ Levy, C Davis, IJ Razin, E Fisher, DE TI Sumoylation of MITF and its related family members TFE3 and TFEB SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MICROPHTHALMIA TRANSCRIPTION FACTOR; NUCLEAR-PORE COMPLEX; SUMO E3 LIGASE; ANDROGEN RECEPTOR; WAARDENBURG-SYNDROME; UBIQUITIN; PROTEIN; GENE; MELANOCYTES; ACTIVATION AB MITF and its related family members TFE3 and TFEB heterodimerize with each other, recognize the same DNA sequences, and are subject to many of the same post-translational modifications. We show that lysine residues within conserved small ubiquitin-like modifier ( SUMO) consensus sites in these family members are subject to SUMO modification. Mutation of these sites significantly affects the transcriptional activity of MITF but does not alter dimerization, DNA binding, stability, or nuclear localization. Mutagenesis reducing the number of MITF binding sites in the promoter of TRPM1 from three to one eliminated the difference in transcriptional activity between the MITF mutants. Among other MITF target gene promoter constructs, differences in transcriptional activity between wild type and nonsumoylatable MITF were only seen in promoters with multiple MITF binding sites. These data support a synergy control model in which the functional consequences of MITF sumoylation depend on promoter context. Sumoylation, thus, provides a possible mechanism for altering the effects of MITF by affecting the target genes that it activates. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med,Childrens Hosp, Dept Pediat Hematol Oncol,Melanoma Program Med On, Dana Farber Canc Inst, Boston, MA 02115 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem, IL-91120 Jerusalem, Israel. RP Fisher, DE (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM David_Fisher@dfci.harvard.edu FU NIAMS NIH HHS [AR43369, AR45662] NR 63 TC 61 Z9 65 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 7 PY 2005 VL 280 IS 1 BP 146 EP 155 DI 10.1074/jbc.M411757200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 883PG UT WOS:000226025100019 PM 15507434 ER PT J AU Oh, KJ Barbuto, S Meyer, N Kim, RS Collier, RJ Korsmeyer, SJ AF Oh, KJ Barbuto, S Meyer, N Kim, RS Collier, RJ Korsmeyer, SJ TI Conformational changes in BID, a pro-apoptotic BCL-2 family member, upon membrane binding - A site-directed spin labeling study SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYTOCHROME-C RELEASE; TOXIN-T DOMAIN; OUTER MITOCHONDRIAL-MEMBRANE; DIPHTHERIA-TOXIN; CRYSTAL-STRUCTURE; CELL-DEATH; BACILLUS-THURINGIENSIS; OLIGOMERIZES BAK; DELTA-ENDOTOXIN; CONTACT SITES AB The BCL-2 family proteins constitute a critical control point in apoptosis. BCL-2 family proteins display structural homology to channel-forming bacterial toxins, such as colicins, transmembrane domain of diphtheria toxin, and the N-terminal domain of delta-endotoxin. By analogy, it has been hypothesized the BCL-2 family proteins would unfold and insert into the lipid bilayer upon membrane association. We applied the site-directed spin labeling method of electron paramagnetic resonance spectroscopy to the pro-apoptotic member BID. Here we show that helices 6-8 maintain an alpha-helical conformation in membranes with a lipid composition resembling mitochondrial outer membrane contact sites. However, unlike colicins and the transmembrane domain of diphtheria toxin, these helices of BID are bound to the lipid bilayer without adopting a transmembrane orientation. Our study presents a more detailed model for the reorganization of the structure of tBID on membranes. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Pathol & Med,Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Pathol & Med,Dana Farber Canc Inst, Boston, MA 02115 USA. EM Stanley_korsmeyer@dfci.harvard.edu FU NCI NIH HHS [P01 CA68484] NR 78 TC 56 Z9 57 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 7 PY 2005 VL 280 IS 1 BP 753 EP 767 DI 10.1074/jbc.M405428200 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 883PG UT WOS:000226025100089 PM 15501827 ER PT J AU Wei, J Sordella, R Chen, GC Hakre, S Roy, AL Settleman, J AF Wei, J Sordella, R Chen, GC Hakre, S Roy, AL Settleman, J TI An FF domain-dependent protein interaction mediates a signaling pathway for growth factor-induced gene expression SO MOLECULAR CELL LA English DT Article ID BRUTONS TYROSINE KINASE; RHO-FAMILY GTPASES; RNA-POLYMERASE-II; C-FOS PROMOTER; TFII-I; TRANSCRIPTIONAL ACTIVATION; SPLICING FACTOR; MECHANISM; BINDS; P190 AB FF domains are poorly understood protein motifs found in all eukaryotes but in a very small number of proteins. They typically occur in tandem arrays and appear predominantly in splicing and transcription factors. Curiously, they are also present in the p190 family of cytoplasmic Rho GTPase activating proteins (GAPs). We identified the serum-responsive transcriptional regulator TFII-I as a specific interactor with the p190 RhoGAP FF domains. p190 sequesters TFII-I in the cytoplasm via the FF domains, but upon PDGF receptor-mediated phosphorylation of an FF domain, TFII-I is released from p190 and translocates to the nucleus where it can activate transcription of serum-inducible genes including c-fos. These findings reveal a pathway by which mitogens promote gene transcription and indicate a role for FF domains in phosphorylation-mediated signal transduction. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Tufts Univ, Sch Med, Dept Pathol & Biochem, Boston, MA 02111 USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM settleman@helix.mgh.harvard.edu NR 28 TC 0 Z9 0 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JAN 7 PY 2005 VL 17 IS 1 BP 23 EP 35 DI 10.1016/j.molcel.2004.11.024 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 888JV UT WOS:000226371100003 ER PT J AU Ivanov, D Stone, JR Maki, JL Collins, T Wagner, G AF Ivanov, D Stone, JR Maki, JL Collins, T Wagner, G TI Mammalian SCAN domain dimer is a domain-swapped homolog of the HIV capsid C-terminal domain SO MOLECULAR CELL LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; GAG PROTEIN; DIMERIZATION DOMAIN; REGION; MORPHOGENESIS; STABILITY; DYNAMICS; BINDING; FAMILY; MODEL AB Retroviral assembly is driven by multiple interactions mediated by the Gag polyprotein, the main structural component of the forming viral shell. Critical determinants of Gag oligomerization are contained within the C-terminal domain (CTD) of the capsid protein, which also harbors a conserved sequence motif, the major homology region (MHR), in the otherwise highly variable Gag. An unexpected clue about the MHR function in retroviral assembly emerges from the structure of the zinc finger-associated SCAN domain we describe here. The SCAN dimer adopts a fold almost identical to that of the retroviral capsid CTD but uses an entirely different dimerization interface caused by swapping the MHR-like element between the monomers. Mutations in retroviral capsid proteins and functional data suggest that a SCAN-like MHR-swapped CTD dinner forms during immature particle assembly. In the SCAN-like dimer, the MHR contributes the major part of the large intertwined dimer interface explaining its functional significance. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Collins, T (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 240 Longwood Ave, Boston, MA 02115 USA. EM tcollins@rics.bwh.harvard.edu; gerhard_wagner@hms.harvard.edu RI Ivanov, Dmitri/B-4600-2011 FU NIGMS NIH HHS [GM47467, GM66516, P01 GM047467] NR 40 TC 59 Z9 62 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JAN 7 PY 2005 VL 17 IS 1 BP 137 EP 143 DI 10.1016/j.molcel.2004.12.015 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 888JV UT WOS:000226371100013 PM 15629724 ER PT J AU Jain, RK AF Jain, RK TI Normalization of tumor vasculature: An emerging concept in antiangiogenic therapy SO SCIENCE LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; COLORECTAL-CANCER; FACTOR-RECEPTOR; BLOOD-VESSELS; SOLID TUMORS; FACTOR ANTIBODY; BREAST-CANCER; NUDE-MICE; ANGIOGENESIS; BEVACIZUMAB AB Solid tumors require blood vessels for growth, and many new cancer therapies are directed against the tumor vasculature., The widely held view is that these antiangiogenic therapies should destroy the tumor vasculature, thereby depriving the tumor of oxygen and nutrients. Here, I review emerging evidence supporting an alternative hypothesis-that certain antiangiogenic agents. can also transiently "normalize" the abnormal structure and function of tumor vasculature to make it more efficient for oxygen and drug delivery. Drugs that induce vascular normalization can alleviate hypoxia and increase the efficacy of conventional therapies if both are carefully scheduled. A better understanding of the molecular and cellular underpinnings of vascular normalization may ultimately lead to more effective therapies not only for cancer but also for diseases with abnormal vasculature, as well as regenerative medicine, in which the goal is to create and maintain a functionally normal vasculature. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 7,100 Blossom St, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu NR 57 TC 2622 Z9 2756 U1 47 U2 378 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 7 PY 2005 VL 307 IS 5706 BP 58 EP 62 DI 10.1126/science.1104819 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 886GG UT WOS:000226214300031 PM 15637262 ER PT J AU Nishi, Y Isomoto, H Mukae, H Ishimoto, H Wen, CY Wada, A Ohnita, K Mizuta, Y Murata, I Hirayama, T Nakazato, M Kohno, S AF Nishi, Yoshito Isomoto, Hajime Mukae, Hiroshi Ishimoto, Hiroshi Wen, Chun-Yang Wada, Akihiro Ohnita, Ken Mizuta, Yohei Murata, Ikuo Hirayama, Toshiya Nakazato, Masamitsu Kohno, Shigeru TI Concentrations of alpha- and beta-defensins in gastric juice of patients with various gastroduodenal diseases SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Helicobacter pylori infection; Gastroduodenal diseases; alpha-defensins; beta-defensin AB AIM: To determine the concentration of alpha- and beta-defensins in gastric juice of patients with various gastroduodenal diseases. METHODS: Concentrations of human neutrophil peptides (HNPs) 1-3, the major forms of alpha-defensins, and human beta-defensin (HBD)-1 and HBD-2 were measured by radioimmunoassay in plasma and gastric juice of 84 subjects, consisting of 54 Helicobacter pylori-infected and 30 uninfected subjects. They included 33 patients with chronic gastritis (CG), 12 with gastric ulcer (GU), 11 with duodenal ulcer (DU), 11 with benign gastric polyp (BGP) and 16 with normal mucosa (N group) on upper endoscopy. Plasma pepsinogen I and II levels, biomarkers for gastric mucosal inflammation and atrophy, were also measured. RESULTS: Gastric juice HNPs 1-3 levels in patients with CG, GU and BGP were significantly higher than those in patients with DU and N. Gastric juice HBD-2 concentrations in patients with CG and GU were significantly higher than those in the N group, but were significantly lower in DU patients than in GU patients. Gastric juice HBD-1 levels and plasma levels of these peptides were similar in the patient groups. Concentrations of gastric juice HNPs 1-3 and HBD-2 of in H pylori-infected patients were significantly different from those in uninfected subjects. HNPs 1-3 concentrations in gastric juice correlated negatively with plasma pepsinogen I levels and I/II ratios. HBD-2 levels in gastric juice correlated positively and negatively with plasma pepsinogen II concentrations and I/II ratios, respectively. CONCLUSION: HNPs 1-3 and HBD-2 levels in gastric juice are diverse among various gastrointestinal diseases, reflecting the inflammatory and atrophic events of the background gastric mucosa affected by H pylori. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved. C1 [Nishi, Yoshito; Isomoto, Hajime; Mukae, Hiroshi; Ishimoto, Hiroshi; Ohnita, Ken; Mizuta, Yohei; Murata, Ikuo; Kohno, Shigeru] Nagasaki Univ, Sch Med, Dept Internal Med 2, Nagasaki 852, Japan. [Wen, Chun-Yang] Nagasaki Univ, Sch Med, Dept Mol Pathol, Atom Bomb Dis Inst, Nagasaki 852, Japan. [Wada, Akihiro; Hirayama, Toshiya] Nagasaki Univ, Sch Med, Dept Bacteriol, Inst Trop Med, Nagasaki 852, Japan. [Nakazato, Masamitsu] Miyazaki Med Coll, Dept Internal Med 3, Miyazaki 88916, Japan. RP Isomoto, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Jackson 706,55 Fruit St, Boston, MA 02114 USA. EM hajimei2002@yahoo.co.jp NR 31 TC 6 Z9 6 U1 0 U2 0 PU BAISHIDENG PUBL GRP CO LTD PI BEIJING PA RM 903, BLDG D, OCEAN INTERNATIONAL CTR, NO 62 DONGSIHUAN ZHONGLU, BEIJING, CHAOYANG DISTRICT 100025, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD JAN 7 PY 2005 VL 11 IS 1 BP 99 EP 103 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V19US UT WOS:000208097900019 PM 15609405 ER PT J AU Grinspoon, S Carr, A AF Grinspoon, S Carr, A TI Medical progress - Cardiovascular risk and body-fat abnormalities in HIV-infected adults. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; ACTIVE ANTIRETROVIRAL THERAPY; PROTEASE INHIBITOR THERAPY; CORONARY-HEART-DISEASE; RANDOMIZED CONTROLLED-TRIAL; ATHEROGENIC LIPID PROFILE; INSULIN-RESISTANCE; HIV-1-INFECTED PATIENTS; LIPODYSTROPHY SYNDROME; COMBINATION THERAPY C1 Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. St Vincents Hosp, HIV Immunol & Infect Dis Clin Serv Unit, Sydney, NSW 2010, Australia. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON207, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NHLBI NIH HHS [R01HL65953]; NIDDK NIH HHS [R01DK59535] NR 100 TC 609 Z9 631 U1 2 U2 12 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 6 PY 2005 VL 352 IS 1 BP 48 EP 62 DI 10.1056/NEJMra041811 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 884UP UT WOS:000226112500007 PM 15635112 ER PT J AU Warren, SM May, JW AF Warren, SM May, JW TI Lipodystrophy induced by antiretroviral therapy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Warren, SM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 6 PY 2005 VL 352 IS 1 BP 63 EP 63 DI 10.1056/NEJMicm040628 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 884UP UT WOS:000226112500008 PM 15635113 ER PT J AU Wijsman, EM Daw, EW Yu, XS Steinbart, EJ Nochlin, D Bird, TD Schellenberg, GD AF Wijsman, EM Daw, EW Yu, XS Steinbart, EJ Nochlin, D Bird, TD Schellenberg, GD TI APOE and other loci affect age-at-onset in Alzheimer's disease families with PS2 mutation SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE modifier gene; Markov chain; Monte-Carlo; segregation analysis; complex trait; oligogenic ID APOLIPOPROTEIN-E GENOTYPE; PRECURSOR PROTEIN GENE; OF-ONSET; MISSENSE MUTATIONS; COGNITIVE DECLINE; EPSILON-4 ALLELE; E POLYMORPHISM; CHROMOSOME-14; ASSOCIATION; SEGREGATION AB Several kindreds of Volga German (VG) ancestry have a single PS2 mutation that causes an autosomal dominant form of Alzheimer's disease (AD). These families show a wide range in age-at-onset, which suggests the existence of modifying factors other than the PS2 mutation. To examine evidence for a genetic basis of variation in onset age, we performed a Bayesian oligogenic segregation and linkage analysis on nine VG families confirmed to have at least one affected PS2 carrier. This analysis simultaneously estimated the effects of APOE and PS2 and the number and effects of additional loci affecting AD age-at-onset. In addition, a family effect accounted for shared environmental effects. This analysis approach has the advantage of full use of the complete pedigree structure, as well as use of information on unsampled individuals with phenotypic data. These analyses provide evidence that APOE plays a small, but significant, role in modifying the age-at-onset in these VG families. The effects estimated for the APOE epsilon3 and epsilon4 genotypes were consistent with those estimated in previous analysis of late-onset AD families, with evidence for a dose-dependent relationship between number of epsilon4 alleles and age-at-onset. We estimated an similar to83% posterior probability of at least one modifier locus in addition to APOE, and that the fraction of the variance in age-at-onset attributable to PS2, APOE, other loci, and family effects is similar to70, similar to2, similar to6.5, and similar to8.5%, respectively. These results provide evidence that APOE and other loci modify onset in AD caused by PS2 mutation. (C) 2004 Wiley-Liss, Inc. C1 Univ Washington, Div Med Genet, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Dept Genome Sci, Seattle, WA USA. Univ Washington, Dept Stat, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Neurol, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Univ Washington, Harborview Med Ctr, Neuropathol Lab, Seattle, WA 98104 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. RP Wijsman, EM (reprint author), Univ Washington, Div Med Genet, Dept Med, BOX 357720, Seattle, WA 98195 USA. EM Wijsman@u.washington.edu OI Wijsman, Ellen/0000-0002-2725-6669 FU NIA NIH HHS [AG 05136, AG 21544, P50 AG005136, AG 11762]; NIGMS NIH HHS [GM 46255] NR 50 TC 42 Z9 46 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JAN 5 PY 2005 VL 132B IS 1 BP 14 EP 20 DI 10.1002/ajmg.b.30087 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 885UG UT WOS:000226181900004 PM 15389756 ER PT J AU Li, J Wang, YF Zhou, RL Zhang, HB Yang, L Wang, B Khan, S Faraone, SV AF Li, J Wang, YF Zhou, RL Zhang, HB Yang, L Wang, B Khan, S Faraone, SV TI Serotonin 5-HT1B receptor gene and attention deficit hyperactivity disorder in Chinese Han subjects SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE attention deficit hyperactivity disorder (ADHD); serotonin; 5HT1B; genetic polymorphisms; TDT; haplotype analysis ID MICE LACKING; ASSOCIATION; ADHD; POLYMORPHISMS; DEPENDENCE; RELATIVES; COCAINE; ABUSE AB Serotonin is an endogenous neurotransmitter that regulates aggressive and impulsive behavior and may be involved in the development of attention deficit hyperactivity disorder (ADHD). 5-HT1B knockout mice display hyperactivity, increased exploratory activity and aggression, reduced anxiety, increased vulnerability to cocaine self-administration, and elevated alcohol consumption. Many of these same behaviors are seen in patients with ADHD. Prior studies reported excess transmission of the 861G allele of 5-HT1B to ADHD offspring. We used the transmission disequilibrium. test (TDT) and haplotype analysis to investigate the A-161T and G861C polymorphisms in the 5-HT1B receptor gene in ADHD trios from the Chinese Han population. We found no association with ADHD but did find a tendency for excess transmission of the 861G allele (x(2) = 3.766, P = 0.052) and the G/A haplotype (x(2) = 2.925, df = 1, P = 0.087), and under-transmission of C/A haplotype (x(2) = 3.707, df = 1, P = 0.054) to offspring with inattentive ADHD. (C) 2004 Wiley-Liss, Inc. C1 Peking Univ, Inst Mental Hlth, Hosp 6, Beijing 100083, Peoples R China. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Capella Univ, Minneapolis, MN USA. RP Wang, YF (reprint author), Peking Univ, Inst Mental Hlth, Hosp 6, Beijing 100083, Peoples R China. EM wangyufengbmu@hotmail.com OI Faraone, Stephen/0000-0002-9217-3982 NR 29 TC 18 Z9 23 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JAN 5 PY 2005 VL 132B IS 1 BP 59 EP 63 DI 10.1002/ajmg.b.30075 PG 5 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 885UG UT WOS:000226181900012 PM 15578608 ER PT J AU Levine, RJ Thadhani, R Qian, C Lam, C Lim, KH Yu, KF Blink, AL Sachs, BP Epstein, FH Sibai, BM Sukhatme, VP Karumanchi, SA AF Levine, RJ Thadhani, R Qian, C Lam, C Lim, KH Yu, KF Blink, AL Sachs, BP Epstein, FH Sibai, BM Sukhatme, VP Karumanchi, SA TI Urinary placental growth factor and risk of preeclampsia SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID TYROSINE KINASE-1; FACTOR RECEPTOR; HYPERTENSION; CALCIUM; TRIAL; WOMEN AB Context Preeclampsia may be caused by an imbalance of angiogenic factors. We previously demonstrated that high serum levels of soluble fms-like tyrosine kinase 1 (sFlt1), an antiangiogenic protein, and low levels of placental growth factor (PIGF), a proangiogenic protein, predict subsequent development of preeclampsia. In the absence of glomerular disease leading to proteinuria, sFlt1 is too large a molecule to be filtered into the urine, while PIGF is readily filtered. Objective To test the hypothesis that urinary PIGF is reduced prior to onset of hypertension and proteinuria and that this reduction predicts preeclampsia. Design, Setting, and Patients Nested case-control study within the Calcium for Preeclampsia Prevention trial of healthy nulliparous women enrolled at 5 US university medical centers during 1992-1995. Each woman with preeclampsia was matched to 1 normotensive control by enrollment site, gestational age at collection of the first serum specimen, and sample Storage time at -70degreesC. One hundred twenty pairs of women were randomly chosen for analysis of serum and urine specimens obtained before labor. Main Outcome Measure Cross-sectional urinary PIGF concentrations, before and after normalization for urinary creatinine. Results Among normotensive controls, urinary PIGF increased during the first 2 trimesters, peaked at 29 to 32 weeks, and decreased thereafter. Among cases, before onset of preeclampsia the pattern of urinary PIGF was similar, but levels were significantly reduced beginning at 25 to 28 weeks. There were particularly large differences between controls and cases of preeclampsia with subsequent early onset of the disease or small-for-gestational-age infants. After onset of clinical disease, mean urinary PIGF in women with preeclampsia was 32 pg/mL, compared with 234 pg/mL in controls with fetuses of similar gestational age (P<.001). The adjusted odds ratio for the risk of preeclampsia to begin before 37 weeks of gestation for specimens obtained at 21 to 32 weeks, which were in the lowest quartile of control PIGF concentrations (<118 pg/mL), compared with all other quartiles, was 22.5 (95% confidence interval, 7.4-67.8). Conclusion Decreased urinary PIGF at mid gestation is strongly associated with subsequent early development of preeclampsia. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Renal Div, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Allied Technol Grp, Rockville, MD USA. Univ Cincinnati, Coll Med, Dept Obstet & Gynecol, Cincinnati, OH 45267 USA. NICHHD, Div Epidemiol Stat & Prevent Res, US Dept HHS, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Obstet, Boston, MA 02114 USA. RP Karumanchi, SA (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Renal Div, Dana 517,330 Brookline Ave, Boston, MA 02215 USA. EM sananth@bidmc.harvard.edu FU NICHD NIH HHS [N01-HD-3154, N01-HD-1-3121, N01-HD-1-3122, N01-HD-1-3123, N01-HD-1-3124, N01-HD-1-3125, N01-HD-1-3126, N01-HD-5-3246, R01-HD-3-9223]; NIDDK NIH HHS [KO8-DK-002825] NR 20 TC 184 Z9 196 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 5 PY 2005 VL 293 IS 1 BP 77 EP 85 DI 10.1001/jama.293.1.77 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 884QY UT WOS:000226102100024 PM 15632339 ER PT J AU Pearce, CL Hirschhorn, JN Wu, AH Burtt, NP Stram, DO Young, S Kolonel, LN Henderson, BE Altshuler, D Pike, MC AF Pearce, CL Hirschhorn, JN Wu, AH Burtt, NP Stram, DO Young, S Kolonel, LN Henderson, BE Altshuler, D Pike, MC TI Clarifying the PROGINS allele association in ovarian and breast cancer risk: A haplotype-based analysis SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PROGESTERONE-RECEPTOR GENE; FRAGMENT-LENGTH-POLYMORPHISM; HORMONE REPLACEMENT THERAPY; ESTROGEN PLUS PROGESTIN; ORAL-CONTRACEPTIVES; MULTIETHNIC COHORT; GENOTYPE DATA; FUNCTIONAL POLYMORPHISM; POSTMENOPAUSAL WOMEN; NO ASSOCIATION AB Background: The PROGINS allele of the progesterone receptor (PGR) gene has been associated with an increased risk of ovarian cancer and a decreased risk of breast cancer. We set out to refine the association between common variation at the PGR gene locus and these two diseases. Methods: We characterized the haplotype structure of the PGR gene by genotyping 54 single-nucleotide polymorphisms (SNPs) in 349 women. We then selected a subset of 17 haplotypetagging SNPs that captured variation across the locus and typed them in 267 ovarian cancer case patients and 397 control subjects from two case-control studies and in 1715 breast cancer case patients and 2505 control subjects from a cohort study. Results: The PGR locus was characterized by four blocks of strong linkage disequilibrium. Two SNPs in block 4 were associated with an increased risk of ovarian cancer among homozygous carriers as compared with noncarriers: rs1042838 (PROGINS allele; odds ratio [OR] = 3.23, 95% confidence interval [CI] = 1.19 to 8.75, P = .022) and rs608995 (minor allele; OR = 3.10, 95% CI = 1.63 to 5.89, P<.001). The PROGINS allele was observed on a subset of chromosomes carrying the minor allele at rs608995, and its association with ovarian cancer was fully explained by its association with rs608995. In addition, rs608995 fell on two common haplotypes (4-D and 4-E), whose association with ovarian cancer was the same as that of rs608995. These same two haplotypes were associated with a non-statistically significantly reduced risk of breast cancer. Conclusions: Variation in PGR was associated with ovarian cancer risk, although the strongest result was not with the PROGINS allele. Instead, any causal allele(s) are likely in or downstream of block 4 and carried on haplotypes 4-D and 4-E. There was some evidence that the same variation was associated with a reduced risk of breast cancer, but the association was not statistically significant. C1 Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. MIT, Program Med & Populat Genet, Broad Inst, Ctr Genome Res, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Pediat Endocrinol, Boston, MA USA. Boston Childrens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. RP Pearce, CL (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Keck Sch Med, 1441 Eastlake Ave,Rm 4411A, Los Angeles, CA 90089 USA. EM cpearce@usc.edu RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 FU NCI NIH HHS [CA14089, CA 61132, R01-CA63464, CA 17054, N01-PC-67010] NR 51 TC 44 Z9 47 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 5 PY 2005 VL 97 IS 1 BP 51 EP 59 DI 10.1093/jnci/dji007 PG 9 WC Oncology SC Oncology GA 891RW UT WOS:000226599400013 PM 15632380 ER PT J AU Brown, JE Cook, RJ Major, P Lipton, A Saad, F Smith, M Lee, KA Zheng, M Hei, YJ Coleman, RE AF Brown, JE Cook, RJ Major, P Lipton, A Saad, F Smith, M Lee, KA Zheng, M Hei, YJ Coleman, RE TI Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer, and other solid tumors SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ADVANCED MULTIPLE-MYELOMA; PLACEBO-CONTROLLED TRIAL; ZOLEDRONIC ACID; BREAST-CANCER; DOUBLE-BLIND; RANDOMIZED-TRIAL; DOSE PAMIDRONATE; N-TELOPEPTIDE; PHASE-III; METASTASES AB Background: Whether bone markers have prognostic value in patients with bone metastases is unknown. We investigated this question in patients with bone metastases secondary to prostate cancer and to non-small-cell lung cancer (NSCLC) and other solid tumors assigned to the placebo arms of two phase III trials of zoledronic acid. Methods: Levels of the urinary bone resorption marker N-telopeptide and the serum bone formation marker bone-specific alkaline phosphatase were assessed every 3 months for patients with prostate cancer (n = 203) or NSCLC or other solid tumors (n = 238) and were categorized as low or high. Patients were monitored for skeletal-related events, bone disease progression, and death. The relative risks (RRs) and 95% confidence intervals (Cis) for these outcomes were estimated for patients with high versus low levels of each marker using intensity-based multiple event and Cox regression models. All statistical tests were two-sided. Results: In each disease group and overall, high levels of each marker at the beginning of the study were statistically significantly associated with an increased risk of negative outcomes. Use of recent marker assessments as time-dependent covariates gave even greater prognostic significance. High N-telopeptide levels were a stronger prognostic indicator of negative outcomes than bone-specific alkaline phosphatase levels. In recent assessments, patients with high N-telopeptide levels had an increased relative risk of skeletal-related events (prostate cancer, RR = 3.25, 95 % CI = 2.26 to 4.68, P < .001; NSCLC and other solid tumors, RR = 1.79, 95% CI = 1.15 to 2.79, P = .010), disease progression (prostate cancer, RR = 2.02, 95% CI = 1.48 to 2.74, P < .001; NSCLC and other solid tumors, RR = 1.91, 95% CI = 1.16 to 3.15, P = .011), and death (prostate cancer, RR = 4.59, 95% CI 2.82 to 7.46, P < .001; NSCLC and other solid tumors, RR 2.67,95% CI = 1.85 to 3.85, P < .001) compared with patients with low N-telopeptide levels. Conclusions: Baseline and recent bone marker levels were predictive of negative clinical outcomes in patients with bone metastases secondary to prostate cancer and to NSCLC and other solid tumors. N-telopeptide levels were more consistent prognostic indicators than bone-specific alkaline phosphatase for all tumor types, reflecting the key role of osteolysis in the development of skeletal complications. C1 McMaster Univ, Juravinski Canc Ctr, Dept Med Oncol, Hamilton, ON L8V 5C2, Canada. Weston Pk Hosp, Acad Unit Clin Oncol, Canc Res Ctr, Sheffield, S Yorkshire, England. Univ Waterloo, Waterloo, ON N2L 3G1, Canada. Milton S Hershey Med Ctr, Hershey, PA USA. Univ Montreal, Ctr Hosp, Hop Notre Dame, Montreal, PQ, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. RP Major, P (reprint author), McMaster Univ, Juravinski Canc Ctr, Dept Med Oncol, 699 Concess St, Hamilton, ON L8V 5C2, Canada. EM pierre.major@hrcc.on.ca NR 39 TC 336 Z9 349 U1 2 U2 18 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 5 PY 2005 VL 97 IS 1 BP 59 EP 69 DI 10.1093/jnci/dji002 PG 11 WC Oncology SC Oncology GA 891RW UT WOS:000226599400014 PM 15632381 ER PT J AU Grundner, C Li, YX Louder, M Mascola, J Yang, XZ Sodroski, J Wyatt, R AF Grundner, C Li, YX Louder, M Mascola, J Yang, XZ Sodroski, J Wyatt, R TI Analysis of the neutralizing antibody response elicited in rabbits by repeated inoculation with trimeric HIV-1 envelope glycoproteins SO VIROLOGY LA English DT Article DE antibody; inoculation; glycoprotein ID IMMUNODEFICIENCY-VIRUS TYPE-1; MONOCLONAL-ANTIBODIES; SOLUBLE CD4; DEPENDENT ENHANCEMENT; IMMUNE-RESPONSES; PRIMARY ISOLATE; GP120; INFECTION; BINDING; PROTECTION AB The elicitation of broadly neutralizing antibodies directed against the human immunodeficiency virus type I (HIV-1) envelope glycoproteins, gp120 and gp41, remains a major challenge. Attempts to utilize monomeric gp120 as an immunogen to elicit high titers of neutralizing antibodies have been disappointing. Envelope glycoprotein constructs that better reflect the trimeric structutre of the functional envelope spike have exhibited improved immunogenicity compared with monomeric gp120. We have described soluble gp140 ectodomain constructs with a heterologous trimerization motif, these have previously been shown to elicit antibodies in mice that were able to neutralize a number of HIV-1 isolates. among them primary isolate viruses. Recently, solid-phase proteoliposomes retaining the envelope glycoproteins as trimeric spikes in a physiologic membrane setting have been described. Here, we compare the immunogenic properties of these two trimeric envelope glycoprotein formulations and monomeric gp120 in rabbits. Both trimeric envelope glycoprotein preparation generated neutralizing antibodies more effectively than gp120. In contrast to monomeric gp120 the trinieric envelope glycoproteins elicited neutralizing antibodies with some breadth of neutralization. Furthermore, repeated boosting with the soluble trimeric formulations resulted in an increase in potency that allowed neutralization of a subset of neutralization-resistant HIV-1 primary isolates. We demonstrated that the neutralization is concentration-dependent, is mediated by serum IgG and that the major portion of the neutralizing activity is not directed against the gp120 V3 loop. Thus, mimics of the trimeric envelope glycoprotein spike described here elicit HIV-1-neutralizing antibodies that could contribute to a protective immune response and provide platforms for further modifications to improve the efficiency of this process. Published by Elsevier Inc. C1 NIH, Struct Virol Sect, Vaccine Res Ctr, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div Aids, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Wyatt, R (reprint author), NIH, Struct Virol Sect, Vaccine Res Ctr, 40 Convent Dr,Bldg 40,Room 4512, Bethesda, MD 20892 USA. EM richardwyatt@nih.gov FU NIAID NIH HHS [1R21AI-44328-02, 5R21AI-44328-02, AI 27742, AI 31783, AI28691, AI49099] NR 42 TC 73 Z9 75 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 5 PY 2005 VL 331 IS 1 BP 33 EP 46 DI 10.1016/j.virol.2004.09.022 PG 14 WC Virology SC Virology GA 886EU UT WOS:000226210500003 PM 15582651 ER PT J AU Devroe, E Silver, PA Engelman, A AF Devroe, E Silver, PA Engelman, A TI HIV-1 incorporates and proteolytically processes human NDR1 and NDR2 serine-threonine kinases SO VIROLOGY LA English DT Article DE HIV-1; NDR1; NDR2; kinase; protease; virus; microvesicle; subtilisin; localization; activity ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROTEIN-KINASE; SACCHAROMYCES-CEREVISIAE; CELL-CYCLE; VIRIONS; PHOSPHORYLATION; COMPLEX; MICROVESICLES; IDENTIFICATION; LOCALIZATION AB Mammalian genomes encode two related serine-threonine kinases, nuclear Dbf2 related (NDR)1 and NDR2, which are homologous to the Saccharomyces cerevisiae Dbf2 kinase. Recently, a yeast genetic screen implicated the Dbf2 kinase in Ty1 retrotransposition. Since several virion-incorporated kinases regulate the infectivity of human immunodeficiency virus type 1 (HIV-1), we speculated that the human NDR1 and NDR2 kinases might play a role in the HIV-1 life cycle. Here we show that the NDR1 and NDR-2 kinase were incorporated into HIV-1 particles. Furthermore, NDR1 and NDR2 were cleaved by the HIV-1 protease (PR). both within virions and within producer cells. Truncation at the PR cleavage site altered NDR2 subcellular localization and inhibited NDR1 and NDR2 enzymatic activity. These studies identify two new virion-associated host cell enzymes and suggest a novel mechanism by which HIV-1 alters the intracellular environment of human cells. (C) 2004 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM alan_engelman@dfci.harvard.edu FU NIAID NIH HHS [AI52014] NR 37 TC 21 Z9 21 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 5 PY 2005 VL 331 IS 1 BP 181 EP 189 DI 10.1016/j.virol.2004.10.023 PG 9 WC Virology SC Virology GA 886EU UT WOS:000226210500017 PM 15582665 ER PT J AU Beyth, RJ AF Beyth, RJ TI Patient self-management of anticoagulation: An idea whose time has come SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID CHRONIC ILLNESS; CLINICAL-TRIAL; THERAPY; QUALITY; CARE C1 Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Beyth, RJ (reprint author), Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM RebeccaJ.Beyth@med.va.gov NR 16 TC 3 Z9 3 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 4 PY 2005 VL 142 IS 1 BP 73 EP 74 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 916DS UT WOS:000228366200008 PM 15630111 ER PT J AU Lindenfeld, J Page, RL Zolty, R Shakar, SF Levi, M Lowes, B Wolfel, EE Miller, GG AF Lindenfeld, J Page, RL Zolty, R Shakar, SF Levi, M Lowes, B Wolfel, EE Miller, GG TI Drug therapy in the heart transplant recipient - Part III: Common medical problems SO CIRCULATION LA English DT Article DE transplantation; drugs; immunology; rejection ID CORONARY-ARTERY-DISEASE; GLUCOCORTICOID-INDUCED OSTEOPOROSIS; RENAL-ALLOGRAFT RECIPIENTS; CARDIAC TRANSPLANTATION; LUNG-TRANSPLANTATION; BONE LOSS; INTERNATIONAL-SOCIETY; BLOOD-PRESSURE; DOUBLE-BLIND; TRIMETHOPRIM-SULFAMETHOXAZOLE C1 Univ Colorado, Hlth Sci Ctr, Div Cardiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Ctr Womens Hlth Res, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Clin Pharm, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Div Infect Dis, Denver, CO 80262 USA. Vanderbilt Univ, Div Infect Dis, Nashville, TN USA. Denver VA Med Ctr, Div Cardiol, Denver, CO USA. RP Lindenfeld, J (reprint author), Univ Colorado, Hlth Sci Ctr, Div Cardiol, 4200 E 9th Ave,B-130, Denver, CO 80262 USA. EM joann.lindenfeld@UCHSC.edu OI Lowes, Brian/0000-0002-5919-2540 NR 81 TC 52 Z9 54 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 JAN 4 PY 2005 VL 111 IS 1 BP 113 EP 117 DI 10.1161/01.CIR.0000151609.60618.3C PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 884DR UT WOS:000226065300018 PM 15630040 ER PT J AU Groeneveld, PW Heidenreich, PA Garber, AM AF Groeneveld, PW Heidenreich, PA Garber, AM TI Trends in implantable cardioverter-defibrillator racial disparity - The importance of geography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ANTIARRHYTHMIC-DRUG THERAPY; ACUTE MYOCARDIAL-INFARCTION; REVASCULARIZATION PROCEDURES; VENTRICULAR ARRHYTHMIAS; MEDICARE BENEFICIARIES; SOCIOECONOMIC-STATUS; COMORBIDITY MEASURES; CARDIAC-ARREST; RATES; STATE AB OBJECTIVES The study was designed to determine whether racial disparity in utilization of the implantable cardioverter-defibrillator (ICD) has improved over time, and whether small-area geographic variation in ICD utilization contributed to national levels of racial disparity. BACKGROUND Although racial disparities in cardiac procedures have been well-documented, it is unknown whether there has been improvement over time. Low ICD utilization rates in predominantly black geographic areas may have exacerbated national levels of disparity. METHODS Discharge abstracts from elderly black and white Medicare beneficiaries hospitalized with ventricular arrhythmias from 1990 to 2000 were analyzed to determine if ICD implantation occurred within 90 days of initial hospitalization. Multivariate logistic regression models were constructed to assess the relationship between ICD implantation, year of admission, and the percentage of black inhabitants in each patient's county of hospitalization while controlling for clinical, hospital, and demographic characteristics. RESULTS There was improvement in ICD implantation racial disparity: In the period 1990 to 1992, black patients had an odds ratio of 0.52 (95% confidence interval [CI] 0.42 to 0.64) for receiving an ICD compared with whites. However, by 1999 to 2000, the odds ratio for blacks had risen to 0.69 (95% CI 0.61 to 0.78) (test-for-trend p = 0.01). Approximately 20% of this trend could be explained by reduction in geographic variation in ICD use between areas with larger black and predominantly white populations. CONCLUSIONS Rates of ICD implants became more equal among whites and blacks during the 1990s, although persistent disparity remained at the decade's end. Geographic equalization in cardiovascular procedure rates may be an essential mechanism in rectifying disparities in health care. (C) 2005 by the American College of Cardiology Foundation C1 Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Div Gen Internal Med, Philadelphia, PA USA. Vet Affairs Palo Alto Hlth Care Syst, Philadelphia, PA USA. Stanford Univ, Ctr Primary Care & Outcomes Res, Stanford, CA USA. Stanford Univ, Natl Bur Econ Res, Stanford, CA USA. RP Groeneveld, PW (reprint author), 1122 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM peter.groeneveld@med.va.gov RI Garber, Alan/F-1476-2010; OI Heidenreich, Paul/0000-0001-7730-8490 FU AHRQ HHS [T32-HS000028-17]; NIA NIH HHS [P01-AG005842-17] NR 36 TC 50 Z9 50 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 JAN 4 PY 2005 VL 45 IS 1 BP 72 EP 78 DI 10.1016/j.jacc.2004.07.061 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 883LF UT WOS:000226012600014 PM 15629377 ER PT J AU Rumsfeld, JS Peterson, ED AF Rumsfeld, JS Peterson, ED TI Care disparities - Moving from gray to black and white SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID RACIAL-DIFFERENCES; QUALITY C1 Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Denver, CO 80220 USA. Duke Univ, Ctr Med, Duke Clin Res Inst, Durham, NC USA. RP Rumsfeld, JS (reprint author), Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. EM John.Rumsfeld@med.va.gov NR 13 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 4 PY 2005 VL 45 IS 1 BP 79 EP 81 DI 10.1016/j.jacc.2004.10.012 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 883LF UT WOS:000226012600015 PM 15629378 ER PT J AU Ellinor, PT Low, AF Patton, KK Shea, MA MacRae, CA AF Ellinor, PT Low, AF Patton, KK Shea, MA MacRae, CA TI Discordant atrial natriuretic peptide and brain natriuretic peptide levels in lone atrial fibrillation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CONGESTIVE-HEART-FAILURE; GENE-EXPRESSION; NATURAL-HISTORY AB OBJECTIVES We sought to characterize natriuretic peptide levels in a cohort of rigorously characterized subjects with lone atrial fibrillation (AF). BACKGROUND Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are sensitive biomarkers of cardiac contractile dysfunction. Both peptides have been reported to be elevated in cohorts with AF, but previous studies have included subjects with underlying structural heart disease. We studied these hormones in 150 subjects with lone AF. METHODS Study subjects had electrocardiographic evidence of at least one episode of AF and a structurally normal heart on echocardiography. Subjects were excluded if they had a history of a myocardial infarction, rheumatic heart disease, cardiomyopathy, significant valvular disease, hyperthyroidism, or hypertension that preceded the onset of AF. Control subjects were obtained from a healthy outpatient primary care population. Plasma pro-ANP and N-terminal pro-BNP (nt-pro-BNP) levels were determined using commercially available immunoassays. RESULTS A total of 150 serial subjects with lone AF were enrolled and studied, the majority during normal sinus rhythm. Median levels of nt-pro-BNP were significantly elevated in subjects with lone AF as compared with control subjects (166 vs. 133 fmol/ml, p = 0.0003). There was no significant difference in pro-ANP levels between subjects with lone AF and control subjects (1,730 vs. 1,625 fmol/ml, p = 0.90). CONCLUSIONS Discordant natriuretic peptide levels were observed in this homogeneous population of subjects with lone AF. This biomarker pattern, which is present even in sinus rhythm, may represent an underlying subclinical predisposition to this common arrhythmia. (C) 2005 by the American College of Cardiology Foundation. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Charlestown, MA 02129 USA. RP MacRae, CA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM cmacrae@partners.org RI Patton, Kristen/A-5626-2008; OI Patton, Kristen K./0000-0002-9034-6966 FU NHLBI NIH HHS [HL-71632, R01 HL075431] NR 19 TC 93 Z9 104 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 4 PY 2005 VL 45 IS 1 BP 82 EP 86 DI 10.1016/j.jacc.2004.09.045 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 883LF UT WOS:000226012600016 PM 15629379 ER PT J AU Oakes, SA Scorrano, L Opferman, JT Bassik, MC Nishino, M Pozzan, T Korsmeyer, SJ AF Oakes, SA Scorrano, L Opferman, JT Bassik, MC Nishino, M Pozzan, T Korsmeyer, SJ TI Proapoptotic BAX and BAK regulate the type 1 inositol trisphosphate receptor and calcium leak from the endoplasmic reticulum SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID 1,4,5-TRISPHOSPHATE RECEPTORS; CA2+ HOMEOSTASIS; BCL-2; APOPTOSIS; STORES; PHOSPHORYLATION; CHANNELS; COMPLEX; CELLS; ER AB Proapoptotic BCL-2 family members BAX and BAK are required for the initiation of mitochondrial dysfunction during apoptosis and for maintaining the endoplasmic reticulum (ER) Ca2+ stores necessary for Ca2+-dependent cell death. Conversely, antiapoptotic BCL-2 has been shown to decrease Ca2+ concentration in the ER. We found that Bax(-/-)Bak(-/-) double-knockout (DKO) cells have reduced resting ER Ca2+ levels because of increased Ca2+ leak and an increase in the Ca2+-permeable, hyperphosphorylated state of the inositol trisphosphate receptor type 1 (IP3R-1). The ER Ca2+ defect of DKO cells is rescued by RNA interference reduction of IP3R-1, supporting the argument that this channel regulates the increased Ca2+ leak in these cells. BCL-2 and IP3R-1 physically interact at the ER, and their binding is increased in the absence of BAX and BAK. Moreover, knocking down BCL-2 decreases IP3R-1 phosphorylation and ER Ca2+ leak rate in the DKO cells. These findings support a model in which BCL-2 family members regulate IP3R-1 phosphorylation to control the rate of ER Ca2+ leak from intracellular stores. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Pathol, Dana Farber Canc Inst,Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med, Dana Farber Canc Inst,Howard Hughes Med Inst, Boston, MA 02115 USA. Dulbecco Telethon Inst, Dept Biomed Sci, I-35121 Padua, Italy. Univ Padua, Venetian Inst Mol Med, I-35121 Padua, Italy. Univ Padua, Dept Biomed Sci, I-35121 Padua, Italy. RP Korsmeyer, SJ (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Pathol, Dana Farber Canc Inst,Howard Hughes Med Inst, Boston, MA 02115 USA. EM stanley_korsmeyer@dfci.harvard.edu RI Scorrano, Luca/A-6652-2008 OI Scorrano, Luca/0000-0002-8515-8928 FU NCI NIH HHS [R37 CA050239]; NIAID NIH HHS [K08 AI054650]; Telethon [TCP02016] NR 35 TC 281 Z9 292 U1 2 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 4 PY 2005 VL 102 IS 1 BP 105 EP 110 DI 10.1073/pnas.0408352102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 886HB UT WOS:000226216400020 PM 15613488 ER PT J AU Renaud, EJ MacLaughlin, DT Oliva, E Rueda, BR Donahoe, PK AF Renaud, EJ MacLaughlin, DT Oliva, E Rueda, BR Donahoe, PK TI Endometrial cancer is a receptor-mediated target for Mullerian Inhibiting Substance SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE uterus; p130; e2F1; AN3CA; KLE ID IN-VIVO; II RECEPTOR; DEPENDENT KINASES; CELL-GROWTH; EXPRESSION; HORMONE; DIFFERENTIATION; PATHWAY; DUCT; PURIFICATION AB Mullerian Inhibiting Substance (MIS), a 140-kDa homodimer glycoprotein member of the TGF-beta superfamily of biological-response modifiers, causes regression of the Mullerian ducts in developing male embryos. MIS also can induce growth arrest and apoptosis in ovarian and cervical cancer cell lines. The embryonic progenitor of the ovarian and cervical epithelium is the coelomic epithelium, the same tissue that regresses under the direction of MIS in the male. The endometrium and uterus also arise from the coelomic epithelium and the Mullerian ducts. Here, we show that both normal human endometrium and endometrial cancers express the receptor for MIS and that MIS can inhibit the proliferation of a number of human endometrial cancer cell lines that express the MIS type II receptor. In the representative endometrial cancer cell line AN3CA, MIS affects the expression of key cell-cycle regulatory proteins. This work broadens the scope of tumors that MIS can potentially control and, by elucidating the MIS signaling pathway, identifies other potential avenues for intervention. C1 Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Donahoe, PK (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. EM pdonahoe@partners.org FU NCI NIH HHS [CA 17393, R01 CA017393]; NICHD NIH HHS [HD 31122] NR 39 TC 41 Z9 45 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 JAN 4 PY 2005 VL 102 IS 1 BP 111 EP 116 DI 10.1073/pnas.0407772101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 886HB UT WOS:000226216400021 PM 15618407 ER PT J AU Cerimele, F Battle, T Lynch, R Frank, DA Murad, E Cohen, C Macaron, N Sixbey, J Smith, K Watnick, RS Eliopoulos, A Shehata, B Arbiser, JL AF Cerimele, F Battle, T Lynch, R Frank, DA Murad, E Cohen, C Macaron, N Sixbey, J Smith, K Watnick, RS Eliopoulos, A Shehata, B Arbiser, JL TI Reactive oxygen signaling and MAPK activation distinguish Epstein-Barr virus (EBV)-positive versus EBV-negative Burkitt's lymphoma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE angiogenesis ID NF-KAPPA-B; CELL-LINES; LATENT MEMBRANE-PROTEIN-1; HEPATOCELLULAR-CARCINOMA; GROWTH TRANSFORMATION; PROMOTER METHYLATION; P16(INK4A) PROMOTER; PROTEIN; KINASE; HYPERMETHYLATION AB Burkitt's lymphoma (BL) is an aggressive B cell neoplasm, which is one of the most common neoplasms of childhood. It is highly widespread in East Africa, where it appears in endemic form associated with Epstein-Barr virus (EBV) infection, and around the world in a sporadic form in which EBV infection is much less common. In addition to being the first human neoplasm to be associated with EBV, BL is associated with a characteristic translocation, in which the Ig promoter is translocated to constitutively activate the c-myc oncogene. Although many BLs respond well to chemotherapy, a significant fraction fails to respond to therapy, leading to death. In this article, we demonstrate that EBV-positive BL expresses high levels of activated mitogen-activated protein kinase and reactive oxygen species (ROS), and that ROS directly regulate NF-kappaB activation. EBV-negative BLs exhibit activation of phosphoinositol 3-kinase, but do not have elevated levels of ROS. Elevated reactive oxygen may play a role in diverse forms of viral carcinogenesis in humans, including cancers caused by EBV, hepatitis B, C, and human T cell lymphotropic virus. Our findings imply that inhibition of ROS may be useful in the treatment of EBV-induced neoplasia. C1 Emory Univ, Sch Med, Dept Dermatol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Hematol Oncol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Microbiol & Immunol, Shreveport, LA 71130 USA. Univ Birmingham, Sch Med, Canc Res UK, Inst Canc Studies, Birmingham B15 2TT, W Midlands, England. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Arbiser, JL (reprint author), Emory Univ, Sch Med, Dept Dermatol, WMB 5309,1639 Pierce Dr, Atlanta, GA 30322 USA. EM jarbise@emory.edu FU NIAMS NIH HHS [P30 AR 42687, P30 AR042687, R01 AR 47901, R01 AR047901] NR 45 TC 74 Z9 78 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 4 PY 2005 VL 102 IS 1 BP 175 EP 179 DI 10.1073/pnas.0408381102 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 886HB UT WOS:000226216400032 PM 15611471 ER PT J AU D'Souza, I Schellenberg, GD AF D'Souza, I Schellenberg, GD TI Regulation of tau isoform expression and dementia SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Review DE tau; dementia ID FAMILIAL FRONTOTEMPORAL DEMENTIA; PROTEIN PHOSPHATASE 2A; MICROTUBULE-ASSOCIATED PROTEINS; GLYCOGEN-SYNTHASE KINASE-3; PONTO-NIGRAL DEGENERATION; MULTIPLE-SYSTEM TAUOPATHY; PAIRED HELICAL FILAMENTS; SPLICE-SITE MUTATIONS; EXON 10; ALZHEIMERS-DISEASE AB In the central nervous system (CNS), aberrant changes in tau mRNA splicing and consequently in protein isoform ratios cause abnormal aggregation of tau and neurodegeneration. Pathological tau causes neuronal loss in Alzheimer's disease (AD) and a diverse group of disorders called the frontotemporal dementias (FTD), which are two of the most common forms of dementia and afflict more than 10 % of the elderly population. Autosomal dominant mutations in the tau gene cause frontotemporal dementia with parkinsonism-chromosome 17 type (FTDP-17). Just over half the mutations affect tau protein function and decrease its affinity for microtubules (MTs) or increase self-aggregation. The remaining mutations occur within exon 10 (E 10) and intron 10 sequences and alter complex regulation of E10 splicing by multiple mechanisms. FTDP-17 splicing mutations disturb the normally balanced levels of distinct protein. isoforms that result in altered biochemical and structural properties of tau. In addition to FTDP-17, altered tau isoform levels are also pathogenically associated with other FTD disorders such as progressive supranuclear palsy (PSP), corticobasal degeneration and Pick's disease; however, the mechanisms remain undefined and mutations in tau have not been detected. FTDP-17 highlights the association between splicing mutations and the pronounced variability in pathology as well as phenotype that is characteristic of inherited disorders. (C) 2004 Elsevier B.V. All rights reserved. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, Dept Med, Div Geriatr & Geriat Med, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. RP Schellenberg, GD (reprint author), Univ Washington, Div Neurol, Dept Med, RG-27, Seattle, WA 98195 USA. EM neurol@u.washington.edu NR 117 TC 70 Z9 71 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD JAN 3 PY 2005 VL 1739 IS 2-3 BP 104 EP 115 DI 10.1016/j.bbadis.2004.08.009 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 884XQ UT WOS:000226120400003 PM 15615630 ER PT J AU Hyman, BT Augustinack, JC Ingelsson, M AF Hyman, BT Augustinack, JC Ingelsson, M TI Transcriptional and conformational changes of the tau molecule in Alzheimer's disease SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Review DE tau; microtubule; alternative splicing; qPCR; conformational changes; FRET ID PAIRED HELICAL FILAMENTS; PROGRESSIVE SUPRANUCLEAR PALSY; FAMILIAL FRONTOTEMPORAL DEMENTIA; PROTEIN-TAU; EXON 10; NEUROFIBRILLARY TANGLES; MESSENGER-RNA; PICKS-DISEASE; CORTICOBASAL DEGENERATION; BETA-STRUCTURE AB Mutations in the tau gene cause frontotemporal dementia with parkinsonism, presumably by affecting the balance between tau isoforms (with either three or four microtubule-binding repeats) or by impairing tau-tubulin binding. Although to date no mutations have been found for Alzheimer's disease, it is plausible that tangle pathology in this disorder is also driven by similar molecular modifications. Investigations of Alzheimer brain tissue with new technologies such as laser capture microscopy, quantitative PCR and fluorescence lifetime imaging will shed light on whether transcriptional or conformational alterations play a role in Alzheimer pathogenesis. (C) 2004 Elsevier B.V All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Dept Neurol, 114 16th St, Charlestown, MA 02129 USA. EM bhyman@partners.org NR 73 TC 31 Z9 34 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD JAN 3 PY 2005 VL 1739 IS 2-3 BP 150 EP 157 DI 10.1016/j.bbadis.2004.06.015 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 884XQ UT WOS:000226120400007 PM 15615634 ER PT J AU Riley, DE Krieger, JN AF Riley, DE Krieger, JN TI Short tandem repeat (STR) replacements in UTRs and introns suggest an important role for certain STRs in gene expression and disease SO GENE LA English DT Article DE short tandem repeats; prostate cancer; chronic prostatitis; hemophilia; tyrosine hydroxylase ID TYROSINE-HYDROXYLASE GENE; PROSTATE-CANCER RISK; DNA; ASSOCIATION; SUSCEPTIBILITY; SCHIZOPHRENIA; POLYMORPHISMS; SEQUENCES; SELECTION AB Some untranslated sequence (UTR)-localized, short tandem repeats (STRs) exhibit evidence of selection pressure, including STR-coupling preferences, STR conservation, interspecies STR-STR replacements, and STR variants implicated in certain diseases. We wished to determine if STR replacements occurred near disease-related genes, including previously unstudied STRs as well as some STRs already implicated in disease. Among nine strong-candidate prostate cancer (CaP)-predisposing genes, three [steroid 5-alpha-reductase 2 (Srd5A-2), macrophage scavenger receptor-1 (MSR-1), and tumor necrosis factor receptor-21 (Tnfr-21)] exhibited striking STR replacements (P<0.001). The glomerular disease-related gene, CD2AP, exhibited an STR replacement flanked by well-conserved sequences, suggesting an STR-focused process. Another glomerular disease-related gene, rabphilin 3A, exhibited at least two STR replacements at the same UTR position comparing Drosophila melanogaster, Mus musculus, and Homo sapiens. Two genes implicated in blood-clotting disorders, von Willebrand factor (vWA) and fibrinogen alpha (FGA), exhibited multiple-intron STR replacements among mammals, extending STR replacement phenomena to introns. Among primates, a tyrosine hydroxylase (THO1) intron STR, previously implicated in both schizophrenia and drug withdrawal delirium, exhibited frequent replacements. Some STR replacements were early events in gene divergence. When STR sequences of closely related species were available, sTR replacement was observed to be nearly as rapid as speciation. STR replacements expand the list of STR sequences that may contribute to genetic activity and to disease processes. (C) 2004 Elsevier B.V. All rights reserved. C1 VA Puget Sound Hlth Care Syst, Dept Res, Seattle, WA 98012 USA. Univ Washington, Dept Urol, Seattle, WA 98195 USA. RP Riley, DE (reprint author), VA Puget Sound Hlth Care Syst, Dept Res, Room 517,Bldg 1,1660 S Columbian Way, Seattle, WA 98012 USA. EM dri@u.washington.edu FU NIDDK NIH HHS [R01 DK38955] NR 30 TC 12 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JAN 3 PY 2005 VL 344 BP 203 EP 211 DI 10.1016/j.gene.2004.09.034 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 896HG UT WOS:000226924600020 PM 15656986 ER PT S AU Jovicich, J Beg, MF Pieper, S Priebe, C Miller, MM Buckner, R Rosen, B AF Jovicich, J Beg, MF Pieper, S Priebe, C Miller, MM Buckner, R Rosen, B GP IEEE Comp Soc TI Biomedical informatics research network: Integrating multi-site neuroimaging data acquisition, data sharing and brain morphometric processing SO 18th IEEE Symposium on Computer-Based Medical Systems, Proceedings SE COMPUTER-BASED MEDICAL SYSTEMS : PROCEEDINGS OF THE ANNUAL IEEE SYMPOSIUM LA English DT Proceedings Paper CT 18th IEEE Symposium on Computer-Based Medical Systems CY JUN 23-24, 2005 CL Dublin, IRELAND SP IEEE Comp Soc Tech Comm Computat Med, Trinity Coll Dublin, Dept Comp Sci, Sci Fdn Ireland ID SEGMENTATION AB The Biomedical Informatics Research Network (BIRN) is a National Institutes of Health (USA) initiative that fosters distributed collaborations in biomedical science by utilizing information technology innovations. Morphometry BIRN is one of its testbeds and has the goal to develop the ability to conduct clinical imaging studies across multiple sites, to analyze structural imaging data with the most powerful software regardless of development site, and to test new hypotheses on large collections of subjects with well-characterized image and clinical data. Through large-scale analyses of patient population data acquired and pooled across sites, we are investigating neuroanatomic correlates of Alzheimer's Disease Depression and Mild Cognitive Impairment subjects. This paper describes progress in multi-site image calibration and in software integration for multi-site image processing. C1 Massachusetts Gen Hosp, Charlestown, MA USA. RP Jovicich, J (reprint author), Massachusetts Gen Hosp, Charlestown, MA USA. RI Priebe, Carey E./A-3305-2010; OI Jovicich, Jorge/0000-0001-9504-7503 NR 6 TC 6 Z9 6 U1 1 U2 2 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 1063-7125 BN 0-7695-2355-2 J9 COMP MED SY PY 2005 BP 288 EP 293 DI 10.1109/CBMS.2005.38 PG 6 WC Computer Science, Interdisciplinary Applications; Medical Informatics; Medicine, Research & Experimental; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Research & Experimental Medicine; Radiology, Nuclear Medicine & Medical Imaging GA BCS05 UT WOS:000230987800047 ER PT S AU Napadow, V Dhond, RP Purdon, P Kettner, N Makris, N Kwong, KK Hui, KKS AF Vitaly, Napadow Dhond, R. P. Purdon, P. Kettner, N. Makris, N. Kwong, K. K. Hui, K. K. S. GP IEEE TI Correlating acupuncture fMRI in the human Brainstem with heart rate variability SO 2005 27TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-7 SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 27th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 31-SEP 03, 2005 CL Shanghai, PEOPLES R CHINA SP IEEE Engn Med & Biol Soc, Chinese Acad Engn Sci ID SPINAL-CORD; MOTION; SYSTEM; ELECTROACUPUNCTURE; STIMULATION AB Past neuroimaging studies of acupuncture have demonstrated variable results for important brainstem nuclei. We have employed cardiac-gated fMRI with T1-variability correction to study the processing of acupuncture by the human brain. Furthermore, our imaging experiments collected simultaneous ECG data in order to correlate heart rate variability (HRV) with fMRI signal intensity. Subjects experienced one of three stimulations over a 31.5 minute fMRI run: (1) electro-acupuncture at 2Hz/15Rz over the acupoint ST-36 (2) electro-acupuncture at a sham non-acupoint, or (3) sensory control tapping over ST-36. The ECG was analyzed with power spectral methods for low frequency and high frequency components, which reflect the balance in the autonomic nervous system. The HRV data was then correlated with the time-varying fMRI signal intensity. Our data suggests that fMRI activity in the hypothalamus, the dorsal raphe nucleus, the periaqueductal gray, and the rostroventral medulla showed significant correlation with LF/HF ratio calculated from simultaneous HRV data. The correlation of time-varying fMRI response with physiological parameters may provide insight into connections between acupuncture modulation of the autonomic nervous system and neuroprocessing. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA. RP Napadow, V (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA. NR 24 TC 6 Z9 7 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-8740-6 J9 P ANN INT IEEE EMBS PY 2005 BP 4496 EP 4499 DI 10.1109/IEMBS.2005.1615466 PG 4 WC Engineering, Biomedical SC Engineering GA BER00 UT WOS:000238998404008 ER PT B AU Guenat, OT Generelli, S Clerc, PA de Rooij, NF Koudelka-Hep, M Berthiaume, F Yarmush, ML AF Guenat, OT Generelli, S Clerc, PA de Rooij, NF Koudelka-Hep, M Berthiaume, F Yarmush, ML GP IEEE TI Development of a platform for microscale monitoring of cell function and differentiation SO 2005 3rd IEEE/EMBS Special Topic Conference on Microtechnology in Medicine and Biology SE IEEE Engineering in Medicine and Biology Society Annual Conference (EMBS) LA English DT Proceedings Paper CT 3rd IEEE/EMBS Special Topic Conference on Microtechnology in Medicine and Biology CY MAY 12-15, 2005 CL Oahu, HI SP IEEE, EMBS DE ion-selective electrode; micropipette; local drug delivery; cell differentiation AB We present the technological development of a platform aimed for the monitoring of cell function and differentiation. The platform is equipped with an array of 16 silicon nitride micropipettes (diameter = 3 mu m), located at the bottom of a 350 mu m deep microchannel, and with two microfluidic drug delivery systems placed on both sides of the microchannel. The micropipettes house ion selective microelectrodes and the microfluidics serve to deliver growth and differentiation factors to cells to be cultured at the bottom of the channels., We are currently developing such a system using NH4+ -selective microelectrodes to monitor the differentiation of stem cells into hepatocytes. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02115 USA. RP Guenat, OT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-8711-2 J9 ENG MED BIOL SOC ANN PY 2005 BP 343 EP 344 DI 10.1109/MMB.2005.1548468 PG 2 WC Engineering, Biomedical SC Engineering GA BDL92 UT WOS:000234204800105 ER PT B AU King, KR Wang, SH Jayaraman, A Yarmush, M Toner, M AF King, KR Wang, SH Jayaraman, A Yarmush, M Toner, M GP IEEE TI Screening cellular responses to cytokine pulses in a microfluidic device SO 2005 3rd IEEE/EMBS Special Topic Conference on Microtechnology in Medicine and Biology SE IEEE Engineering in Medicine and Biology Society Annual Conference (EMBS) LA English DT Proceedings Paper CT 3rd IEEE/EMBS Special Topic Conference on Microtechnology in Medicine and Biology CY MAY 12-15, 2005 CL Oahu, HI SP IEEE, EMBS DE cell culture; microfluidics; dynamics; GFP ID GENE-EXPRESSION AB The cellular response to a molecular stimulus depends on the concentration and duration of the stimulus. Conventional assays often neglect timing because the experiments are prohibitively tedious and time consuming. In this work, we describe a microfluidic living cell assay that allows efficient characterization of stimulus timing. A microfluidic network is designed to allow controlled parallel delivery of different stimulus regimens to downstream linear arrays of living GFP reporter cells. In contrast to conventional techniques that require a separate experiment for each exposure regimen and each response time point, this assay screens exposure durations and response dynamics in a single experiment. We demonstrate the approach by studying the effect of 7 durations of TNF-alpha exposure on activation of NF kappa B-mediated transcription at 17 time points, equivalent to 114 conventional experiments. This general approach to studying cell signaling dynamics has significant scaling potential and will be useful for high throughput drug development and investigation of dynamic signaling in basic cell biology. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Ctr Engn & Med, Dept Surg,Ctr Engn & Med,Harvard MIT Div Hlth Sci, Boston, MA 02114 USA. RP King, KR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Ctr Engn & Med, Dept Surg,Ctr Engn & Med,Harvard MIT Div Hlth Sci, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-8711-2 J9 ENG MED BIOL SOC ANN PY 2005 BP 361 EP 362 DI 10.1109/MMB.2005.1548474 PG 2 WC Engineering, Biomedical SC Engineering GA BDL92 UT WOS:000234204800111 ER PT S AU Ntziachristos, V Soubret, A Turner, G AF Ntziachristos, V Soubret, A Turner, G GP IEEE TI Early photon optical tomography SO 2005 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH, AND SIGNAL PROCESSING, VOLS 1-5: SPEECH PROCESSING SE International Conference on Acoustics Speech and Signal Processing ICASSP LA English DT Proceedings Paper CT 30th IEEE International Conference on Acoustics, Speech, and Signal Processing CY MAR 19-23, 2005 CL Philadelphia, PA SP IEEE DE optical tomography; fluorescence; molecular imaging ID RECONSTRUCTION AB Fluorescence tomography is an emerging tool for functional and molecular imaging of tissues. Inversion is however complicated by the high scattering that photons experience when propagating through tissue that reduces resolution. While continuous wave systems offer implementation simplicity, time-resolved systems offer the ability to improve resolution and reduce the ill-posed nature of the inverse problem by using early arriving photons. We present an overview of our current progress in complete-angle illumination early photon tomography and present the associated data processing steps employed for early photon inversions. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Lab Bioopt & Mol Imaging, Boston, MA 02129 USA. RP Massachusetts Gen Hosp, Ctr Mol Imaging Res, Lab Bioopt & Mol Imaging, CNY 149 13th St R5209, Boston, MA 02129 USA. EM vasilis@helix.mgh.harvard.edu NR 12 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1520-6149 BN 0-7803-8874-7 J9 INT CONF ACOUST SPEE PY 2005 BP 837 EP 840 PG 4 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BCI02 UT WOS:000229404204210 ER PT S AU Correia, JA Burnham, CA Kaufman, D Fischman, AJ AF Correia, J. A. Burnham, C. A. Kaufman, D. Fischman, A. J. BE Yu, B TI Coincidence measurements with a Quasi-continuous detector for small animal PET SO 2005 IEEE Nuclear Science Symposium Conference Record, Vols 1-5 SE IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD LA English DT Proceedings Paper CT Nuclear Science Symposium/Medical Imaging Conference CY OCT 23-29, 2005 CL Fajardo, PR SP IEEE Nucl & Plasma Sci Soc, Brookhaven Natl Lab, CEA Saclay, DOE, CERN, Lawrence Berkeley Natl Lab, Lawrence Livermore Natl Lab, Stanford Linear Accelerator Ctr, Univ Calif Davis, Univ Washington C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Correia, JA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 0-7803-9221-3 J9 IEEE NUCL SCI CONF R PY 2005 BP 2077 EP 2080 PG 4 WC Instruments & Instrumentation; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Instruments & Instrumentation; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA BFH22 UT WOS:000241851903056 ER PT J AU Green, WL AF Green, WL TI New questions regarding bioequivalence of levothyroxine preparations: A clinician's response SO AAPS JOURNAL LA English DT Review ID THYROTROPIN-SUPPRESSIVE THERAPY; RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; THYROID-HORMONE; SUBCLINICAL HYPERTHYROIDISM; PRIMARY HYPOTHYROIDISM; RISK-FACTOR; THYROXINE; DISEASE; WOMEN C1 VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. RP Green, WL (reprint author), VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. EM annebillgreen@earthlink.net NR 39 TC 14 Z9 16 U1 0 U2 4 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ALEXANDRIA PA 1650 KING ST, STE 200, ALEXANDRIA, VA 22314-2747 USA SN 1550-7416 J9 AAPS J PY 2005 VL 7 IS 1 BP E54 EP E58 DI 10.1208/aapsj070107 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 007SW UT WOS:000234991000007 PM 16146330 ER PT J AU Gracey, CF Haidet, P Branch, WT Weissmann, P Kern, DE Mitchell, G Frankel, R Inui, T AF Gracey, CF Haidet, P Branch, WT Weissmann, P Kern, DE Mitchell, G Frankel, R Inui, T TI Precepting humanism: Strategies for fostering the human dimensions of care in ambulatory settings SO ACADEMIC MEDICINE LA English DT Article ID ATTENDING PHYSICIANS; MEDICAL-EDUCATION; PERSONAL GROWTH; ROUNDS; COMMUNICATION; GUIDELINES; BEHAVIORS; ATTITUDES; EFFICIENT; AWARENESS AB Humanistic medical care is an important element of quality health care, and teaching humanism is increasingly recognized as an integral component of medical education. The goal of this article is to illustrate a series of tools that are effective in fostering both the provision and teaching of humanistic medical care in the ambulatory setting. Through a series of discussions, workshops, literature review, and practice, the authors have identified critical elements that promote the teaching of humanistic care. These elements include establishing a humanistic learning climate, creating clear individualized learning goals within a framework of humanism, developing an educational diagnosis of the learner, integrating psychosocial issues into the teaching intervention, reflecting on the learning experience with the learner, providing feedback throughout the teaching encounter, and planning follow-up with the learner. Strategies for implementation of these critical elements are presented with an emphasis on efficient educational interactions as required by busy ambulatory settings. Through the effective use of these teaching strategies, one can promote the teaching of the human dimensions of care in the outpatient setting. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Emory Univ, Sch Med, Dept Med, Atlanta, GA USA. Univ Minnesota, Sch Med, Fairview, MN USA. Johns Hopkins Bayview Med Ctr, Div Gen Internal Med, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Indiana Univ, Sch Med, Roudebush VA Med Ctr, Indianapolis, IN USA. Regenstrief Inst Hlth Care, Dept Med, Indianapolis, IN USA. RP Gracey, CF (reprint author), Univ Rochester, Sch Med & Dent, Gen Med Unit, 601 Elmwood Ave, Rochester, NY 14642 USA. EM catherine-gracey@urmc.rochester.edu NR 37 TC 35 Z9 36 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JAN PY 2005 VL 80 IS 1 BP 21 EP 28 DI 10.1097/00001888-200501000-00007 PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 885FS UT WOS:000226143100004 PM 15618087 ER PT J AU Haidet, P Kelly, A Chou, C AF Haidet, P Kelly, A Chou, C CA Culture Study Grp TI Characterizing the patient-centeredness of hidden curricula in medical schools: Development and validation of a new measure SO ACADEMIC MEDICINE LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med ID CONSENSUS STATEMENT; CARE; COMMUNICATION; EDUCATION; PERSPECTIVE; INTERVIEW; ATTITUDES; OUTCOMES AB Purpose The "hidden curriculum" has a powerful influence in shaping medical students' attitudes and behaviors toward patient care. The purpose of this project was to develop and test a tool (the C-3 Instrument) to help educators characterize and understand the hidden curriculum at their own institutions. Method In 2000, the authors developed survey items to measure three content areas of the hidden curriculum with respect to patient-centered care. These content areas include role modeling, students' patient-care experiences, and perceived support for students' own patient-centered behaviors. The survey was distributed to third- and fourth-year students at ten medical schools in the United States. Using factor analysis, the authors selected items for the final version of the C-3 Instrument. To examine validity, they compared instrument scores to results of a poll of members of two organizations devoted to teaching patient-centered care. Results A total of 890 students completed the survey. The mean age of students was 27 (SD 3). Fifty-two percent of students were women, and 70% were white. Twenty-nine items were selected for the C-3 Instrument, with internal consistency measures ranging from .67 to .93 for instrument subdimensions. In the validation analysis, summary scores for all three content areas of the C-3 Instrument were consistent with results of the poll of patient-centered organizations. Conclusion Despite some issues that still need to be resolved, the C-3 Instrument proved to be a reliable and valid tool that characterizes a medical school's hidden curriculum with respect to patient-centered care. It can be used to guide educational interventions by addressing the context that exists around formal teaching activities. It also makes possible the study of hidden curricula across multiple medical schools. Further research on the hidden curriculum should be aimed at developing a greater understanding of the dynamics between formal teaching activities and school culture. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Haidet, P (reprint author), Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM phaidet@bcm.tmc-edu NR 22 TC 49 Z9 50 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JAN PY 2005 VL 80 IS 1 BP 44 EP 50 DI 10.1097/00001888-200501000-00012 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 885FS UT WOS:000226143100008 PM 15618092 ER PT J AU McMahon, GT Monaghan, C Falchuk, K Gordon, JA Alexander, EK AF McMahon, GT Monaghan, C Falchuk, K Gordon, JA Alexander, EK TI A simulator-based curriculum to promote comparative and reflective analysis in an internal medicine clerkship SO ACADEMIC MEDICINE LA English DT Article ID EDUCATION; STUDENTS AB Purpose To develop and evaluate a novel curricular framework using high-fidelity patient simulation in an internal medicine clerkship. Method Two 90-minute simulator-based modules of ischemic heart failure and hypoxemic respiratory failure were developed from adult and experiential learning principles. Three short simulated cases focused on each pathophysiologic concept were intermixed with two short teaching sessions and a period of comparative analysis. In 2002-03, the program was piloted among 90 third-year medical students at Harvard Medical School assigned to complete their core internal medicine clerkship. An entry and two follow-up questionnaires were used to assess the process. The instructors conducted quantitative and qualitative data analysis and directly observed students' performances. Results Instructors consistently noted students' ability to appropriately extract a history, perform a basic examination, and order appropriate tests. However, students demonstrated repeated errors in the application of knowledge to the clinical circumstance. A final comparative discussion was essential to new learning and students recognized this integrative analysis as the most critical component of the exercise. Every student reported the experience as useful. Ninety-four percent (n = 85) felt the simulator should become a routine part of the clerkship and 68% (n = 71) desired three or more sessions during their internal medicine clerkship. Conclusions Simulator-based curricular modules are feasible in an internal medicine clerkship and can successfully complement existing curricula. By comparing similar cases in a compressed time frame, students may achieve enhanced efficiencies in reflective and meta-cognitive learning. As medical simulation is increasingly available, such a curriculum may represent valuable additions to the internal medicine educational environment. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, GS Beckwith Gilbert & Katherine S Gilbert Med Edu, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA USA. RP Alexander, EK (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, 221 Longwood Ave,2nd Floor, Boston, MA 02115 USA. EM ekalexander@partners.org RI McMahon, Graham/D-3740-2009 OI McMahon, Graham/0000-0003-4288-6535 FU NHLBI NIH HHS [K30 HL04095] NR 18 TC 21 Z9 24 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JAN PY 2005 VL 80 IS 1 BP 84 EP 89 DI 10.1097/00001888-200501000-00021 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 885FS UT WOS:000226143100015 PM 15618101 ER PT J AU Marder, SR AF Marder, SR TI Subjective experiences on antipsychotic medications: synthesis and conclusions SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE schizophrenia; antipsychotics; dysphoria; extrapyramidal symptoms; dopamine ID QUALITY-OF-LIFE; SCHIZOPHRENIA; HALOPERIDOL; DYSPHORIA; DRUGS; NEUROLEPTICS; OLANZAPINE; AKATHISIA AB Objective: This report synthesizes the literature describing the phenomenology, clinical importance and biology of subjective responses to antipsychotic medications in schizophrenia. A patient's experience of an antipsychotic is important because unpleasant or dysphoric responses can impair therapeutic relationships, lead to medication non-adherence, and have direct negative effects on a patient's quality of life. Method: The author selectively reviewed early studies of subjective responses to antipsychotics and integrated this literature with the work of the other investigators in this special section. Results: There is substantial evidence that second-generation antipsychotics have advantages in causing fewer dysphoric responses when compared with first-generation agents. Clinical and neuroimaging studies suggest that dopamine blockade is an important determinant of many of these dysphorias. At this point in time it is unclear whether dysphoria results from extrapyramidal symptoms particularly akathisia and akinesia - or whether they are a direct result of decreased dopamine activity. Conclusion: Clinicians and researchers should continue to monitor dysphorias in schizophrenia. Contributions by the authors in this supplement provide new and more refined methods for measuring subjective responses in future studies. C1 W Los Angeles Vet Affairs Med Ctr, Psychiat Serv 116A, MIRECC VISN 22, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Marder, SR (reprint author), W Los Angeles Vet Affairs Med Ctr, Psychiat Serv 116A, MIRECC VISN 22, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM marder@ucla.edu NR 23 TC 27 Z9 28 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PY 2005 VL 111 SU 427 BP 43 EP 46 DI 10.1111/j.1600-0447.2005.00544.x PG 4 WC Psychiatry SC Psychiatry GA 931JH UT WOS:000229481100007 ER PT S AU Pierce, MC Joo, CM Cense, B Weinberg, E Park, BH Mujat, M Borenstein, J Tearney, GJ Bouma, BE de Boer, JF AF Pierce, MC Joo, CM Cense, B Weinberg, E Park, BH Mujat, M Borenstein, J Tearney, GJ Bouma, BE de Boer, JF BE VoDinh, T Grundfest, WS Benaron, DA Cohn, GE TI Fluid flow analysis in microfluidic devices by spectral-domain optical Doppler tomography SO ADVANCED BIOMEDICAL AND CLINICAL DIAGNOSTIC SYSTEMS III SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Advanced Biomedical and Clinical Diagnostic Systems III CY JAN 23-26, 2005 CL San Jose, CA SP SPIE DE optical coherence tomography; Fourier-domain; microfluidic devices; non-invasive imaging; fluid dynamics ID RETINAL BLOOD-FLOW; COHERENCE TOMOGRAPHY; HIGH-SPEED; PERFORMANCE; VELOCIMETRY AB Microfluidic devices are becoming increasingly popular for many applications, enabling biological and chemical reactions to be performed with nano- and picoliter sample volumes. Accurate measurement and monitoring of fluid flow behavior in the small channels of microfluidic systems is important for evaluating the performance of existing devices, and in the modeling and design of new microfluidic networks. We present here the results of experiments using spectral-domain optical Doppler tomography (SD-ODT) to measure fluid flow in single-layer microfluidic devices. The principles behind flow imaging with SD-ODT are reviewed. a method for velocity calibration is described, and cross-sectional and en-face images of fluid velocity in microfluidic channels are presented. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Pierce, MC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, BAR 714,50 Blossom St, Boston, MA 02114 USA. EM pierce@helix.mgh.harvard.edu; deboer@helix.mgh.harvard.edu NR 16 TC 2 Z9 2 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5666-7 J9 PROC SPIE PY 2005 VL 5692 BP 174 EP 178 DI 10.1117/12.589862 PG 5 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BCF50 UT WOS:000229038700021 ER PT J AU Williams, ME Kitsen, J AF Williams, ME Kitsen, J TI The involuntarily discharged dialysis patient: Conflict (of interest) with providers SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article ID RENAL-TRANSPLANTATION; BEHAVIORAL COMPLIANCE; HEMODIALYSIS; NONCOMPLIANCE; SATISFACTION; MORTALITY; SURVIVAL; DISEASE; ISSUES; CARE AB As the following case exemplifies, the involuntary discharge of an end-stage renal disease (ESRD) patient from the dialysis facility can represent a state of protracted conflict between the patient and the nephrology staff/providers. With few workable solutions, such conflicts consume resources far out of proportion to the number of cases and are of growing interest to the dialysis community. C1 Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02215 USA. ESRD Network New England, Boston, MA USA. RP Williams, ME (reprint author), Joslin Diabet Ctr, Renal Unit, 1 Joslin Pl, Boston, MA 02215 USA. EM mark.williams@joslin.harvard.edu NR 25 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1548-5595 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD JAN PY 2005 VL 12 IS 1 BP 107 EP 112 DI 10.1053/j.ackd.2004.10.010 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 904MG UT WOS:000227501800016 PM 15719341 ER PT S AU Bouix, S Siddiqi, K AF Bouix, S Siddiqi, K BE Hawkes, PW TI Optics, mechanics, and Hamilton-Jacobi skeletons SO ADVANCES IN IMAGING AND ELECTRON PHYSICS, VOL 135 SE Advances in Imaging and Electron Physics LA English DT Review; Book Chapter ID MEDIAL AXIS TRANSFORM; THINNING ALGORITHM; DISTANCE MAPS; FRONTS; SHAPE; SET; TRANSITIONS; DIMENSIONS; SURFACES; POINTS C1 Harvard Univ, Sch Med, Dept Psychiat, Boston VA Healthcare Syst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Surg Planning Ctr, MRI Div,Brigham & Womens Hosp, Boston, MA 02115 USA. McGill Univ, Ctr Intelligent Machines, Montreal, PQ H3A 2A7, Canada. McGill Univ, Sch Comp Sci, Montreal, PQ H3A 2A7, Canada. RP Bouix, S (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Boston VA Healthcare Syst, Boston, MA 02115 USA. NR 56 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1076-5670 BN 0-12-014777-7 J9 ADV IMAG ELECT PHYS JI Adv. Imag. Electron Phys. PY 2005 VL 135 BP 1 EP 39 DI 10.1016/S1076-5670(04)35001-9 PG 39 WC Physics, Applied SC Physics GA BCR85 UT WOS:000230975300001 ER PT S AU Dudley, DD Chaudhuri, J Bassing, CH Alt, FW AF Dudley, DD Chaudhuri, J Bassing, CH Alt, FW BE Alt, FW TI Mechanism and control of V(D)J recombination versus class switch recombination: Similarities and differences SO ADVANCES IN IMMUNOLOGY, VOL 86 SE Advances in Immunology LA English DT Review; Book Chapter ID T-CELL-RECEPTOR; IMMUNOGLOBULIN HEAVY-CHAIN; DOUBLE-STRAND BREAKS; DEPENDENT PROTEIN-KINASE; INDUCED CYTIDINE DEAMINASE; ACTIVATION-INDUCED DEAMINASE; VARIABLE-REGION GENES; HYPER-IGM SYNDROME; LOOP-HELIX PROTEINS; DNA-LIGASE-IV AB V(D)J recombination is the process by which the variable region exons encoding the antigen recognition sites of receptors expressed on B and T lymphocytes are generated during early development via somatic assembly of component gene segments. In response to antigen, somatic hypermutation (SHM) and class switch recombination (CSR) induce further modifications of immunoglobulin genes in B cells. CSR changes the IgH constant region for an alternate set that confers distinct antibody effector functions. SHM introduces imitations, at a high rate, into variable region exons, ultimately allowing affinity maturation. All of these genomic alteration processes require tight regulatory control mechanisms, both to ensure development of a normal immune system and to prevent potentially oncogenic processes, such as translocations, caused by errors in the recombination/mutation processes. In this regard, transcription of substrate sequences plays a significant role in target specificity, and transcription is mechanistically coupled to CSR and SHM. However there are many mechanistic differences in these reactions. V(D)J recombination proceeds, via precise DNA cleavage initiated by the RAG proteins at short conserved signal sequences, whereas CSR and SHM are initiated over large target regions via activation-induced cytidine deaminase (AID)-mediated DNA deamination of transcribed the context of CSR via a general anchoring mechanism proposed to hold DSBs together in chromatin before their joining via NHEJ. In contrast, RAG-generated DSBs appear to be held together in a postcleavage synaptic complex by the RAGs themselves, which then recruit the NHEJ factors to complete the reaction. In both V(D)J recombination and CSR, however, we still know little about the actual process of synapsis and how the involved proteins contribute to it. C1 Childrens Hosp, Howard Hughes Med Inst, CBR, Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Dudley, DD (reprint author), Oklahoma Med Res Fdn, Immunobiol & Canc Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. FU NIAID NIH HHS [5P01 AI 31541-14] NR 479 TC 139 Z9 143 U1 3 U2 12 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 BN 0-12-022486-0 J9 ADV IMMUNOL JI Adv.Immunol. PY 2005 VL 86 BP 43 EP 112 DI 10.1016/S0065-2776(04)86002-4 PG 70 WC Immunology SC Immunology GA BBT46 UT WOS:000227698100002 PM 15705419 ER PT S AU Thai, TH Kearney, JF AF Thai, TH Kearney, JF BE Alt, FW TI Isoforms of terminal deoxynucleotidyltransferase: Developmental aspects and function SO ADVANCES IN IMMUNOLOGY, VOL 86 SE Advances in Immunology LA English DT Review; Book Chapter ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; DNA-POLYMERASE-BETA; DELTA GENE REARRANGEMENTS; DEPENDENT PROTEIN-KINASE; VARIABLE REGION GENES; T-CELL DEVELOPMENT; V(D)J RECOMBINATION; PROGNOSTIC-SIGNIFICANCE; ADULT MICE AB The immune system develops in a series of programmed developmental stages. Although recombination-activating gene (RAG) and nonhomologous end-joining (NHEJ) proteins are indispensable in the generation of immunoglobulins and T-cell receptors (TCRs), most CDR3 diversity is contributed by nontemplated addition of nucleotides catalyzed by the nuclear enzyme terminal deoxynucleotidyltransferase (TdT) and most nucleotide deletion is performed by exonucleases at V(D)J joins. Increasing TdT expression continuing into adult life results in N region addition and diversification of the T and B cell repertoires. In several species including mice and humans, there are multiple isoforms of TdT resulting from alternative mRNA splicing. The short form (TdTS) produces N additions during TCR and B-cell receptor (BCR) gene rearrangements. Other long isoforms, TdTL1 and TdTL2, have 3'-> 5' exonuclease activity. The two forms of TdT therefore have distinct and opposite functions in lymphocyte development. The enzymatic activities of the splice variants of TdT play an essential role in the diversification of lymphocyte repertoires by modifying the composition and length of the gene segments involved in the production of antibodies and T-cell receptors. C1 Univ Alabama, Dept Microbiol, Div Dev & Clin Immunol, Birmingham, AL 35204 USA. RP Thai, TH (reprint author), Inst Biomed Res, CBR, 138 Warren Alpert Bldg, Boston, MA 02115 USA. FU NCI NIH HHS [CA 13148]; NIAID NIH HHS [T32 AI 07051, AI 14594, AI 14782, T32 AI007051, R01 AI014782] NR 94 TC 16 Z9 18 U1 3 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 BN 0-12-022486-0 J9 ADV IMMUNOL JI Adv.Immunol. PY 2005 VL 86 BP 113 EP 136 DI 10.1016/S0065-2776(04)86003-6 PG 24 WC Immunology SC Immunology GA BBT46 UT WOS:000227698100003 PM 15705420 ER PT S AU Carroll, MC Holers, VM AF Carroll, MC Holers, VM BE Alt, FW TI Innate autoimmunity SO ADVANCES IN IMMUNOLOGY, VOL 86 SE Advances in Immunology LA English DT Review; Book Chapter ID ALTERNATIVE COMPLEMENT PATHWAY; ACUTE-RENAL-FAILURE; INTESTINAL ISCHEMIA-REPERFUSION; MEMBRANE COFACTOR PROTEIN; HEMOLYTIC-UREMIC SYNDROME; DECAY-ACCELERATING FACTOR; ISCHEMIA/REPERFUSION INJURY; ANTIPHOSPHOLIPID SYNDROME; NATURAL ANTIBODY; MONOCLONAL-ANTIBODIES AB The adaptive immune system has evolved highly specific pattern recognition proteins and receptors that, when triggered, provide a first line of host defense against pathogens. Studies reveal that these innate recognition proteins are also self-reactive and can initiate inflammation against self-tissues in a similar manner as with pathogens. This specific event is referred to as "innate autoirnmunity." In this review, we describe two classes of autoimmune responses, that is, reperfusion injury and fetal loss syndrome, in which the recognition and injury are mediated by innate immunity. Both disorders are common and are clinically important. Reperfusion injury (RI) represents an acute inflammatory response after a reversible ischemic event and subsequent restoration of blood flow. Findings that injury is IgM and complement dependent and that a single natural antibody prepared from a panel of B-1 cell hybridomas can restore injury in antibody-deficient mice suggest that RI is an autoimmune-type disorder. Fetal loss syndrome is also an antibody- and complement-dependent disorder. Although both immune and natural antibodies are likely involved in recognition of phospholipid self-antigens, inhibition of the complement pathway in rodent models can block fetal loss. As new innate recognition proteins and receptors are identified, it is likely that innate responses to self represent frequent events and possibly underlie many of the known chronic autoimmune disorders nom-tally attributable to dysregulation of adaptive immunity. C1 Harvard Univ, Sch Med, CBR, Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80217 USA. Univ Colorado, Hlth Sci Ctr, Dept Immunol, Denver, CO 80217 USA. RP Carroll, MC (reprint author), Harvard Univ, Sch Med, CBR, Inst Biomed Res, Boston, MA 02115 USA. NR 71 TC 56 Z9 59 U1 4 U2 8 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 BN 0-12-022486-0 J9 ADV IMMUNOL JI Adv.Immunol. PY 2005 VL 86 BP 137 EP 157 DI 10.1016/S0065-2776(04)86004-8 PG 21 WC Immunology SC Immunology GA BBT46 UT WOS:000227698100004 PM 15705421 ER PT S AU Chowdhury, D Novina, CD AF Chowdhury, D Novina, CD BE Alt, FW TI RNAi and RNA-based regulation of immune system function SO ADVANCES IN IMMUNOLOGY, VOL 88 SE Advances in Immunology LA English DT Review; Book Chapter ID HEPATITIS-DELTA VIRUS; NONSENSE-MEDIATED DECAY; EXON JUNCTION COMPLEX; CYTOPLASMIC MESSENGER-RNA; RETRACTED ARTICLE. SEE; DEAMINASE ADAR1 GENE; DOUBLE-STRANDED-RNA; MAMMALIAN-CELLS; CAENORHABDITIS-ELEGANS; C-ELEGANS AB Gene regulation by short RNAs is a ubiquitous and important mode of control. MicroRNAs are short, single-strand RNAs that bind with partial complementarity to the 3' untranslated region of several genes to silence their expression. This expanding class of endogenous short RNAs are evolutionarily conserved and participate in control of development and cell-specific gene function. Several of these microRNAs have been cloned uniquely from mammalian lymphocytes suggesting specialized roles in lymphocyte development and junction. In addition, several genes linked to RNAi in lower eukaryotes have mammalian homologs with specialized roles in adaptive immunity. For example, in worn-is, the nonsense-mediated decay (NMD) and RNAi pathways appear to be intricately linked. NMD plays a key role in regulating antigen-receptor expression in lymphocytes and there are mammalian homologs for factors identified in worms that appear to be common in both RNAi and NMD pathways. On the other hand, RNA editing and RNAi have an inverse relationship and RNA editing has an important role in viral immunity. These observations indicate unique roles for dsRNAs in the mammalian immune system. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Chowdhury, D (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 134 TC 9 Z9 9 U1 1 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 BN 0-12-022488-7 J9 ADV IMMUNOL JI Adv.Immunol. PY 2005 VL 88 BP 267 EP 292 DI 10.1016/S0065-2776(05)88008-3 PG 26 WC Immunology SC Immunology GA BDN19 UT WOS:000234420000008 PM 16227093 ER PT J AU Mayer, KH Chaguturu, SK AF Mayer, Kenneth H. Chaguturu, Sreekanth K. BE Mayer, KH Pizer, HF TI The Evolution of Comprehensive AIDS Clinical Care SO AIDS PANDEMIC: IMPACT ON SCIENCE AND SOCIETY LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; DIRECTLY OBSERVED THERAPY; ANTIRETROVIRAL THERAPY; HIV-1 INFECTION; UNITED-STATES; PLASMA; RECOMMENDATIONS; GUIDELINES; ZIDOVUDINE; SOCIETY C1 [Mayer, Kenneth H.] Brown Univ, Miriam Hosp, Providence, RI 02912 USA. [Mayer, Kenneth H.] Fenway Community Hlth, Boston, MA USA. [Chaguturu, Sreekanth K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Mayer, Kenneth H.] Brown Univ, AIDS Program, Providence, RI 02912 USA. RP Mayer, KH (reprint author), Brown Univ, Miriam Hosp, Providence, RI 02912 USA. NR 41 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-047580-6 PY 2005 BP 261 EP 285 DI 10.1016/B978-012465271-2/50013-3 PG 25 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BDZ50 UT WOS:000315720300011 ER PT J AU Kim, M Qiao, ZS Montefiori, DC Haynes, BF Reinherz, EL Liao, HX AF Kim, M Qiao, ZS Montefiori, DC Haynes, BF Reinherz, EL Liao, HX TI Comparison of HIV type 1 ADA gp120 monomers versus gp140 trimers as Immunogens for the induction of neutralizing antibodies SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN COMPLEX; GP41 TRANSMEMBRANE GLYCOPROTEIN; INTERMOLECULAR DISULFIDE BOND; N-LINKED GLYCANS; MONOCLONAL-ANTIBODIES; IMMUNE-RESPONSES; RESISTANCE PHENOTYPE; EPITOPE EXPOSURE; HUMORAL RESPONSE AB Designing an immunogen for effective neutralizing antibody induction against diverse primary isolates of human immunodeficiency virus type 1 ( HIV- 1) is a high priority for HIV- 1 vaccine development. Soluble gp120 envelope ( Env) glycoprotein subunit vaccines elicit high titers of antibodies that neutralize T cell line- adapted ( TCLA) strains but the antibodies possess poor neutralizing activity against many primary isolates. Previously, we generated soluble trimeric recombinant gp140 from the HIV- 1 primary isolate ADA. Here we compared monomeric ADAgp120 and trimeric ADAgp140 as immunogens for neutralizing antibody responses in guinea pigs. Both immunogens generated a neutralizing antibody response that was detectable against the vaccine strain and several heterologous strains. The magnitude of this response was significantly greater in ADAgp140- immunized animals when measured against the TCLA strain, MN, and the R5 primary isolate, Bal. Two additional isolates ( SS1196 and Bx08) were neutralized equally by sera from both groups of animals whereas other isolates were neutralized weakly or not at all. Despite equal titers of V3 loop specific binding antibodies in sera from both groups of animals, neutralization of ADA by sera from gp140- immunized animals was insensitive to the presence of ADA- V3 peptide, whereas addition of this peptide to sera from gp120-immunized animals blocked all detectable neutralizing activity against ADA. These results support the idea that trimeric gp140 is an improved immunogen compared to monomeric gp120 but that additional improvements are required to afford broad protection against a spectrum of heterologous primary HIV- 1 isolates. This ADAgp140 immunogen may be considered a starting point from which to engineer additional improvements for cross- reactive neutralizing antibody induction. C1 Childrens Hosp, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Human Vaccine Inst, Durham, NC 27710 USA. RP Kim, M (reprint author), Childrens Hosp, Dana Farber Canc Inst, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA. EM mikyung_kim@dfci.harvard.edu FU NIAID NIH HHS [2P01 AI43649, AI15351, N01-AI05397] NR 92 TC 55 Z9 58 U1 0 U2 4 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN PY 2005 VL 21 IS 1 BP 58 EP 67 DI 10.1089/aid.2005.21.58 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 895AE UT WOS:000226832200008 PM 15665645 ER PT J AU Abraham, NS Davila, JA Rabeneck, L Berger, DH El-Serag, HB AF Abraham, NS Davila, JA Rabeneck, L Berger, DH El-Serag, HB TI Increased use of low anterior resection for veterans with rectal cancer SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID QUALITY IMPROVEMENT PROGRAM; HOSPITAL PROCEDURE VOLUME; ADMINISTRATIVE DATABASES; CARE; SURVIVAL; OUTCOMES; ABDOMINOPERINEAL; ADENOCARCINOMA; MANAGEMENT; THERAPY AB Background: Two surgical procedures with curative intent are available to patients with rectal cancer: lower anterior resection and abdominoperineal resection; however, lower anterior resection may improve quality of life and functional status. Aim: To examine temporal changes in after lower anterior resection and abdominoperineal resection between 1989 and 2000. Potential factors associated with the use of lower anterior resection were evaluated. Methods: Using national administrative data, we identified patients who received lower anterior resection or abdominoperineal resection. Logistic regression models examined the association between use of lower anterior resection and time period of surgical resection. Results: A total of 5201 rectal cancer patients underwent resection. The use of lower anterior resection increased from 40.0% (1989-91) to 50.1% (1998-2000) paralleled by a corresponding decline in abdominoperineal resection (60.1 to 49.9%; P < 0.001). Patients who received surgery during 1992-94, 1995-97 and 1998-2000 were 6, 7 and 28% more likely to receive lower anterior resection, when compared with 1989-1991 after adjusting for demographic characteristics, co-morbidity and hospital surgical volume. Older age, lower co-morbidity score and lower hospital surgical volume were predictive of lower anterior resection. Conclusions: An increase in the use of lower anterior resection for rectal cancer was observed over time. This observed increase in use is not confined to high-volume hospitals. C1 Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Houston Ctr Gastroenterol, Houston, TX 77030 USA. Univ Toronto, Dept Med, Div Gastroenterol, Toronto, ON, Canada. Inst Clin Evaluat Sci, Toronto, ON, Canada. Houston VAMC, Houston Ctr Surg, Houston, TX USA. RP Abraham, NS (reprint author), Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM nabraham@bcm.tmc.edu FU NIDDK NIH HHS [K24 DK59318] NR 21 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD JAN 1 PY 2005 VL 21 IS 1 BP 35 EP 41 DI 10.1111/j.1365-2036.2004.02286.x PG 7 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 887VP UT WOS:000226333900005 PM 15644043 ER PT J AU Peskind, ER Tsuang, DW Bonner, LT Pascualy, M Riekse, RG Snowden, MB Thomas, R Raskind, MA AF Peskind, ER Tsuang, DW Bonner, LT Pascualy, M Riekse, RG Snowden, MB Thomas, R Raskind, MA TI Propranolol for disruptive behaviors in nursing home residents with probable or possible Alzheimer disease - A placebo-controlled study SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE Alzheimer disease; betas-adrenergic; disruptive behaviors; long-term care; propranolol ID CEREBROSPINAL-FLUID; SENILE DEMENTIA; CONTROLLED-TRIAL; LOCUS-CERULEUS; DOUBLE-BLIND; DISTURBANCES; NOREPINEPHRINE; NEURONS; GALANTAMINE; AGGRESSION AB Objective: Enhanced behavioral responsiveness to central nervous system (CNS) norepinephrine (NE) in Alzheimer disease (AD) may contribute to the pathophysiology of disruptive behaviors such as aggression, uncooperativeness with necessary care, irritability, and pressured pacing. We evaluated the efficacy of the beta-adrenergic antagonist propranolol for treatment-resistant disruptive behaviors and overall behavioral status in nursing home residents with probable or possible AD. Methods: Thirty-one subjects (age 85 +/- 8 [SD]) with probable or possible AD and persistent disruptive behaviors that interfered with necessary care were randomized to propranolol (n = 17) or placebo (n = 14) in a double-blind study. Stable doses of previously prescribed psychotropics were maintained at pre-study dose during the Study. Following a propranolol or placebo dose titration period of Lip to 9 days (per a dosing algorithm), subjects were maintained on maximum achieved dose for 6 weeks. Primary outcome measures were the Neuropsychiatric Inventory (NPI) and the Clinical Global Impression of Change (CGIC). Results: Propranolol augmentation (mean achieved dose 106 +/- 38 mg/d) was significantly more effective than placebo for improving overall behavioral status on the total NPI score and CGIC. Improvement in individual NPI items within propranolol subjects was significant only for "agitation/aggression" and "anxiety," and reached borderline statistical significance favoring propranolol over placebo only for " agitation/aggression." Pressured pacing and irritability did not appear responsive to propranolol. In propranolol subjects rated "moderately improved" or "markedly improved" on the CGIC at the end of the double-blind study phase, improvement of overall behavioral status had diminished substantially after 6 months of open-label propranolol treatment. Conclusion: Short-term propranolol augmentation treatment appeared modestly effective and well tolerated for overall behavioral status in nursing home residents with probable or possible AD complicated by disruptive behaviors. Propranolol may be helpful specifically for aggression and uncooperativeness (the behaviors assessed by the NPI ''agitation/aggressiveness" item). However, the usefulness of propranolol in this very old and frail population was limited by the high frequency of relative contraindications to beta-adrenergic antagonist treatment and diminution of initial behavioral improvements over time. C1 Mental Illness Res Educ & Clin Ctr, VA Puget Sound Hlth Care Syst, Dept Vet Affairs NW Network VISN 20, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Dept Psychiat & Behav Sci, Seattle, WA USA. VA Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Calif San Diego, Div Biostat, Dept Family Med, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. RP Peskind, ER (reprint author), Mental Illness Res Educ & Clin Ctr, VA Puget Sound Hlth Care Syst, Dept Vet Affairs NW Network VISN 20, S-116 MIREEC,1660 S Columbian Way, Seattle, WA 98108 USA. EM peskind@u.washington.edu RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 FU NIA NIH HHS [AG18644] NR 36 TC 37 Z9 37 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD JAN-MAR PY 2005 VL 19 IS 1 BP 23 EP 28 DI 10.1097/01.wad.0000155067.16313.5e PG 6 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 909IQ UT WOS:000227854000005 PM 15764868 ER PT J AU Tsai, TT Bossone, E Isselbacher, EM Nienaber, CA Evangelista, A Fang, JM Smith, DE Cooper, JV Hutchison, S O'Gara, P Eagle, KA Mehta, RH AF Tsai, TT Bossone, E Isselbacher, EM Nienaber, CA Evangelista, A Fang, JM Smith, DE Cooper, JV Hutchison, S O'Gara, P Eagle, KA Mehta, RH CA International Registry Acute TI Clinical characteristics of hypotension in patients with acute aortic dissection SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID RISK-FACTORS; ASCENDING AORTA; MANAGEMENT; MORTALITY; SURGERY AB To evaluate the clinical characteristics, risk factors, and outcomes of hypotension in unselected patients who had acute aortic dissection (AAD), we studied 1,073 such patients who were enrolled in the International Registry of Acute Aortic Dissection between 1996 and 2001. Hypotension was noted in 313 patients (29.2%) who had AAD (46.0% on admission). Multivariate logistic regression identified age :70 years (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.4 to 2.9), type A dissection (referent type B AAD; OR 2.1, 95% CI 1.4 to 3.2), neurologic deficit (OR 3.8, 95% CI 2.2 to 6.6), syncope (OR 2.9, 95% CI 1.8 to 4.7), aortic regurgitation requiring valve surgery (OR 1.9, 95% CI 1.1 to 3.3), cardiac tamponade (OR 5.1, 95% CI 3.0 to 8.8), and new Q-wave or ST-segment deviation on an electrocardiogram (OR 1.6, 95% CI 1.1 to 2.4) as independent associations of hypotension (c statistic 0.78). Hospital complications (neurologic deficits 22.7% vs 12.0%, altered mental status 26.1% vs 4.4%, myocardial ischemia 14.6% vs 6.9%, mesenteric ischemia 6.9% vs 2.6%, or limb ischernia 14.6% vs 6.9%, and death 55.0% vs; 10.3%) occurred more frequently in patients who had hypotension than in those who did not (p < 0.001 for all comparisons). We concluded that hypotension that occurred in >25% of patient's who had AAD was associated with a much higher rate of in-hospital adverse events. Our study also identified. factors associated with hypotension in patients who had AAD. (C)2005 by Excerpta Medica Inc. C1 Univ Michigan, Ann Arbor, MI 48109 USA. CNR, Brindisi, Italy. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Rostock, Rostock, Germany. Univ Vall Hebron, Gen Hosp, Barcelona, Spain. St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Brigham & Womens Hosp, Boston, MA 02115 USA. Duke Clin Res Inst, Durham, NC USA. RP Mehta, RH (reprint author), Duke Clin Res Inst, 2802 Leslie Pk Circle, Ann Arbor, MI 48105 USA. EM mehta007@dcri.duke.edu NR 21 TC 17 Z9 20 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 1 PY 2005 VL 95 IS 1 BP 48 EP 52 DI 10.1016/j.amjcard.2004.08.062 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 885XY UT WOS:000226191900009 PM 15619393 ER PT J AU Anwaruddin, S Januzzi, JL Baggish, AL Lewandrowski, EL Lewandrowski, KB AF Anwaruddin, S Januzzi, JL Baggish, AL Lewandrowski, EL Lewandrowski, KB TI Ischemia-modified albumin improves the usefulness of standard cardiac biomarkers for the diagnosis of myocardial ischemia in the emergency department setting SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE acute coronary syndrome; biomarkers; ischemia-modified albumin ID ACUTE CORONARY SYNDROMES; CHEST-PAIN; D-DIMER AB We studied the role of ischemia-modified albumin (IMA) with standard biomarkers (myoglobin, creatine kinase-MB [CK-MB], troponin I [TnI]) in assessment of 200 patients with suspected myocardial ischemia admitted to the emergency department. Every case was reviewed by a cardiologist. A clinical diagnosis of ischemia was assigned and correlated with biomarker test results. Of the patients, 25 (13.0%) had myocardial ischemia. Receiver operating characteristic curves demonstrated IMA as highly sensitive but somewhat poorly specific for the presence of ischemia (area under curve, 0.63; P = .01). With a cut point of 90 U/mL, the Albumin Cobalt Binding Test had 80% sensitivity and 31% specificity for diagnosing ischemia and a negative predictive value of 92%. IMA was positive in 4 of 5 patients with electrocardiographic (ECG) evidence of ischemia and 16 of 20 patients with coronary ischemia but negative ECG. Among the same patients, the myoglobin-CK-MB-TnI triad had a sensitivity of 57%. The combination of IMA-myoglobin-CK-MB-TnI increased the sensitivity for detecting ischemia to 97%, with a negative predictive value of 92%. IMA is highly sensitive and has a high negative predictive value, which might improve the usefulness of standard biomarkers of myocardial ischemia. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. RP Lewandrowski, KB (reprint author), Massachusetts Gen Hosp, Dept Pathol, GRB 5,55 Fruit St, Boston, MA 02114 USA. NR 11 TC 65 Z9 77 U1 0 U2 2 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 JAN PY 2005 VL 123 IS 1 BP 140 EP 145 PG 6 WC Pathology SC Pathology GA 884KP UT WOS:000226083900017 PM 15762290 ER PT J AU Vazirani, S Hays, RD Shapiro, MF Cowan, M AF Vazirani, S Hays, RD Shapiro, MF Cowan, M TI Effect of a multidisciplinary intervention on communication and collaboration among physicians and nurses SO AMERICAN JOURNAL OF CRITICAL CARE LA English DT Article AB BACKGROUND Improving communication and collaboration among doctors and nurses can improve satisfaction among participants and improve patients' satisfaction and quality of care. OBJECTIVE To determine the impact of a multidisciplinary intervention on communication and collaboration among doctors and nurses on an acute inpatient medical unit. METHODS During a 2-year period, an intervention unit was created that differed from the control unit by the addition of a nurse practitioner to each inpatient medical team, the appointment of a hospitalist medical director and the institution of daily multidisciplinary rounds. Surveys about communication and collaboration were administered to personnel in both units. Physicians were surveyed at the completion of each rotation on the unit; nurses, biannually. RESULTS Response rates for house staff (n = 111), attending physicians (n = 45), and nurses (n = 123) were 58%, 69% and 91%, respectively. Physicians in the intervention group reported greater collaboration with nurses than did physicians in the control group (P < .001); the largest effect was among the residents. Physicians in the intervention group reported better collaboration with the nurse practitioners than with the staff nurses (P < .001). Physicians in the intervention group also reported better communication with fellow physicians than did physicians in the control group (P = .006). Nurses in both groups reported similar levels of communication (P = .59) and collaboration (P = .47) with physicians. Nurses in the intervention group reported better communication with nurse practitioners than with physicians (P < .001). CONCLUSIONS The multidisciplinary intervention resulted in better communication and collaboration among the participants. C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. RP Vazirani, S (reprint author), Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. EM reprints@aacn.org RI Hays, Ronald/D-5629-2013 FU AHRQ HHS [1R01 HS 10734]; NIA NIH HHS [AG 02004]; NIMHD NIH HHS [P20 MD 00148-01, P20 MD000148, P20 MD000148-03] NR 13 TC 102 Z9 102 U1 1 U2 14 PU AMER ASSOC CRITICAL CARE NURSES PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 1062-3264 J9 AM J CRIT CARE JI Am. J. Crit. Care PD JAN PY 2005 VL 14 IS 1 BP 71 EP 76 PG 6 WC Critical Care Medicine; Nursing SC General & Internal Medicine; Nursing GA 882DF UT WOS:000225918100010 PM 15608112 ER PT J AU Winsor, G Thomas, SH Biddinger, PD Wedel, SK AF Winsor, G Thomas, SH Biddinger, PD Wedel, SK TI Inadequate hemodynamic management in patients undergoing interfacility transfer for suspected aortic dissection SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the American-College-of-Chest-Physicians CY OCT 25-30, 2003 CL ORLANDO, FL SP Amer Coll Chest Physicians ID DIAGNOSIS AB The study goal was the analysis of effectiveness of hemodynamic management of patients undergoing interfacility transport for suspected acute aortic dissection (SAAD). Our retrospective, consecutive-case review examined 62 nonhypotensive patients transported by an air emergency medical services (EMS) service during 1998 to 2002, with referral hospital diagnosis of SAAD. Of patients with systolic blood pressure (SBP) less than 120 upon air EMS arrival, antihypertensives had been given in only 23/42 (54.8%). In 19 cases where pretransport SBP is less than 120, with no referral hospital antihypertensive therapy given, median pretransport SBP was 158 (range, 122-212). In 20/62 cases (32.3%), the air EMS agency instituted antihypertensive therapy, which was successful; of 42 cases with pretransport SBP less than 120, mean intratransport SBP decrement was 24 (95% confidence interval, 16-32). In patients undergoing transport for SAAD, pretransport hemodynamic therapy was frequently omitted and often inadequate, generating an opportunity for air EMS intervention. Education to improve SAAD care should focus upon both referral hospitals and transport services. (C) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Boston MedFlight Crit Care Transport Serv, Boston, MA 02170 USA. Boston Med Ctr, Dept Surg, Boston, MA 02114 USA. Univ Sch Med, Boston, MA 02114 USA. RP Thomas, SH (reprint author), Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA. EM Thomas.Stephen@mgh.harvard.edu NR 15 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD JAN PY 2005 VL 23 IS 1 BP 24 EP 29 DI 10.1016/j.ajem.2004.01.008 PG 6 WC Emergency Medicine SC Emergency Medicine GA 896CN UT WOS:000226912300005 PM 15672333 ER PT J AU Maruti, SS Feskanich, D Colditz, GA Frazier, AL Sampson, LA Michels, KB Hunter, DJ Spiegelman, D Willett, WC AF Maruti, SS Feskanich, D Colditz, GA Frazier, AL Sampson, LA Michels, KB Hunter, DJ Spiegelman, D Willett, WC TI Adult recall of adolescent diet: Reproducibility and comparison with maternal reporting SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE adolescent; diet; mental recall; mothers; nutrition; questionnaires; reproducibility of results ID FOOD FREQUENCY QUESTIONNAIRE; ENERGY-INTAKE; BREAST-CANCER; FUNDAMENTAL PRINCIPLES; NURSES HEALTH; RELIABILITY; HISTORY; RISK; INFORMATION; CONSUMPTION C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Maruti, SS (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02215 USA. EM nhssm@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU CCR NIH HHS [N01-RC-17027]; NCI NIH HHS [CA050385, R01 CA050385-15, R01 CA050385] NR 35 TC 58 Z9 58 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 1 PY 2005 VL 161 IS 1 BP 89 EP 97 DI 10.1093/aje/kwi019 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 884OK UT WOS:000226094700011 PM 15615919 ER PT J AU Kramer, JR Giordano, TP Souchek, J Richardson, P Hwang, LY El-Serag, HB AF Kramer, JR Giordano, TP Souchek, J Richardson, P Hwang, LY El-Serag, HB TI The effect of HIV coinfection on the risk of cirrhosis and hepatocellular carcinoma in US. Veterans with hepatitis C SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 24-28, 2003 CL BOSTON, MA SP Amer Assoc Study Liver Diseases ID HUMAN-IMMUNODEFICIENCY-VIRUS; LIVER FIBROSIS PROGRESSION; NATURAL-HISTORY; UNITED-STATES; DRUG-USERS; INFECTION; HEMOPHILIACS; DISEASE; VIREMIA; COHORT AB OBJECTIVES: This study was conducted to determine whether HIV coinfection increases the risk of cirrhosis in HCV-infected patients in the HAART and pre-HAART eras. Further, the risk of hepatocellular carcinoma was also examined. METHODS: This retrospective cohort study was conducted among HCV-infected veterans who were seen at one of the 172 Veterans Health Administration hospitals between October 1, 1991 and September 30, 2000. Patients with prerecorded advanced liver disease were excluded. Incidence rates, cumulative incidence, and Cox proportional hazard ratios were calculated. RESULTS: There were 26,641 patients with HCV-only and 4,761 patients with HCV-HIV coinfection. The unadjusted incidence rate of cirrhosis was lower in patients with coinfection than HCV-only (p < 0.01). After controlling for demographics and confounders (including alcoholism and chronic hepatitis B), coinfection was not significantly associated with cirrhosis. However, there was an increased risk of cirrhosis in patients with coinfection compared to HCV-only during the pre-HAART era (before October 1, 1996) (hazard ratio = 1.48, 1.06-2.07, p = 0.02), but not among patients who entered the cohort during the HAART era. The unadjusted incidence rate of hepatocellular carcinoma in patients with coinfection and HCV-only was 1.3 and 2/1,000 person-years, respectively (p = 0.04). In the multivariate model, coinfection was not associated with hepatocellular carcinoma (hazard ratio = 0.84, p = 0.40). CONCLUSIONS: Coinfection was a significant risk factor for cirrhosis only during the pre-HAART era and was not associated with hepatocellular carcinoma, irrespective of time period. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Gastroenterol Sect, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, Houston, TX USA. RP El-Serag, HB (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, 152, Houston, TX 77030 USA. FU NIMH NIH HHS [1K23 MH 67505-01] NR 26 TC 93 Z9 94 U1 1 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 2005 VL 100 IS 1 BP 56 EP 63 DI 10.1111/j.1572-0241.2005.40670.x PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 883RJ UT WOS:000226033100011 PM 15654781 ER PT J AU Tran, T Davila, JA El-Serag, HB AF Tran, T Davila, JA El-Serag, HB TI The epidemiology of malignant gastrointestinal stromal tumors: An analysis of 1,458 cases from 1992 to 2000 SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID SMOOTH-MUSCLE TUMORS; OF-FUNCTION MUTATIONS; DIFFERENTIAL-DIAGNOSIS; C-KIT; SARCOMAS; TRACT; GRADE; LEIOMYOSARCOMAS; LEIOMYOMAS; PROGNOSIS AB OJECTIVES: The epidemiology of gastrointestinal stromal tumor has not been well examined, and prior studies often provide conflicting results. We conducted the first population-based study to evaluate the incidence and survival of malignant gastrointestinal stromal tumor in the United States. METHODS: We utilized the Surveillance, Epidemiology, and End Results registry from the National Cancer Institute to identify all cases of malignant gastrointestinal stromal tumor diagnosed from 1992 to 2000. The age-adjusted incidence rates and the survival rates were calculated. Cox proportional hazards models were used to examine the risk of mortality. RESULTS: Between 1992 and 2000, there were 1,458 cases of diagnosed gastrointestinal stromal tumor. The age-adjusted yearly incidence rate was 0.68/100,000. The mean age at diagnosis was 63 yr. Fifty-four percent were men and 46% were women. The incidence rate was higher among men and among Blacks. Fifty-one percent of cases were in the stomach, 36% small intestine, 7% colon, 5% rectum, and 1% in the esophagus. Fifty-three percent of cases were staged as localized, 19% regional, 23% distant, and 5% unstaged. The 1- and 5-yr relative survival rates were 80% and 45%, respectively. The Cox analysis showed that older age, Black race, advanced stage, and receipt of therapy were independent predictors of mortality. CONCLUSIONS: Malignant gastrointestinal stromal tumors rare, but are more common in the older population, men, and Blacks. Risk factors for mortality include older age, Black race, advanced stage, and no surgical intervention. C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Houston Dept Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX USA. Houston Dept Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr, 2002 Holcombe Blvd,152, Houston, TX 77030 USA. NR 38 TC 241 Z9 266 U1 2 U2 12 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 2005 VL 100 IS 1 BP 162 EP 168 DI 10.1111/j.1572-0241.2005.40709.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 883RJ UT WOS:000226033100026 PM 15654796 ER PT J AU Sung, YJ Dawson, G Munson, J Estes, A Schellenberg, GD Wijsman, EM AF Sung, YJ Dawson, G Munson, J Estes, A Schellenberg, GD Wijsman, EM TI Genetic investigation of quantitative traits related to autism: Use of multivariate polygenic models with ascertainment adjustment SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID RECIPROCAL SOCIAL-BEHAVIOR; PERVASIVE DEVELOPMENTAL DISORDERS; FAMILY HISTORY; DIAGNOSTIC INTERVIEW; PEDIGREE ANALYSIS; INFANTILE-AUTISM; SAMPLING PROBLEM; SYMPTOM DOMAINS; GENOMIC SCREEN; TWIN AB Autism is a severe developmental disorder of unknown etiology but with evidence for genetic influences. Here, we provide evidence for a genetic basis of several quantitative traits that are related to autism. These traits, from the Broader Phenotype Autism Symptom Scale (BPASS), were measured in nuclear families, each ascertained through two probands affected by autism spectrum disorder. The BPASS traits capture the continuum of severity of impairments and may be more informative for genetic studies than are the discrete diagnoses of autism that have been used by others. Using a sample of 201 nuclear families consisting of a total of 694 individuals, we implemented multivariate polygenic models with ascertainment adjustment to estimate heritabilities and genetic and environmental correlations between these traits. Our ascertainment adjustment uses conditioning on the phenotypes of probands, requires no modeling of the ascertainment process, and is applicable to multiplex ascertainment and multivariate traits. This appears to be the first such implementation for multivariate quantitative traits. The marked difference between heritability estimates of the trait for language onset with and without an ascertainment adjustment (0.08 and 0.22, respectively) shows that conclusions are sensitive to whether or not an ascertainment adjustment is used. Among the five BPASS traits that were analyzed, the traits for social motivation and range of interest/flexibility show the highest heritability (0.19 and 0.16, respectively) and also have the highest genetic correlation (0.92). This finding suggests a shared genetic basis of these two traits and that they may be most promising for future gene mapping and for extending pedigrees by phenotyping additional relatives. C1 Univ Washington, Div Med Genet, Autism Ctr, Seattle, WA 98195 USA. Univ Washington, Div Gerontol & Geriatr Med, Autism Ctr, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Psychol, Autism Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol & Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. RP Wijsman, EM (reprint author), Univ Washington, Div Med Genet, Autism Ctr, Box 357720, Seattle, WA 98195 USA. EM wijsman@u.washington.edu FU NICHD NIH HHS [U19 HD 35465, U19 HD035465]; NIGMS NIH HHS [R01 GM046255, R01 GM 46255] NR 67 TC 63 Z9 64 U1 6 U2 13 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN PY 2005 VL 76 IS 1 BP 68 EP 81 DI 10.1086/426951 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 878JR UT WOS:000225643600006 PM 15547804 ER PT J AU Freedman, ML Pearce, CL Penney, KL Hirschhorn, JN Kolonel, LN Henderson, BE Altshuler, D AF Freedman, ML Pearce, CL Penney, KL Hirschhorn, JN Kolonel, LN Henderson, BE Altshuler, D TI Systematic evaluation of genetic variation at the androgen receptor locus and risk of prostate cancer in a multiethnic cohort study SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID CAG REPEAT POLYMORPHISM; POPULATION STRATIFICATION; ALLELIC VARIANTS; ASSOCIATION; LENGTH; MEN; SUSCEPTIBILITY; PREDISPOSITION; SURVIVAL; LINKAGE AB Repeat length of the CAG microsatellite polymorphism in exon 1 of the androgen receptor (AR) gene has been associated with risk of prostate cancer in humans. This association has been the focus of greater than 120 primary epidemiological publications and multiple review articles, but a consistent and reproducible association has yet to be confirmed. We systematically addressed possible causes of false-negative and false-positive association in greater than 4,000 individuals from a multiethnic, prospective cohort study of prostate cancer, comprehensively studying genetic variation by microsatellite genotyping, direct resequencing of exons in advanced cancer cases, and haplotype analysis across the 180-kb AR genomic locus. These data failed to confirm that common genetic variation in the AR gene locus influences risk of prostate cancer. A systematic approach that assesses both coding and noncoding genetic variation in large and diverse patient samples can help clarify hypotheses about association between genetic variants and disease. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. Univ So Calif, Dept Prevent Med, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Los Angeles, CA 90089 USA. Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. RP Altshuler, D (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Wellman 8, Boston, MA 02114 USA. EM altshuler@molbio.mgh.harvard.edu RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 FU NCI NIH HHS [5R01 CA 63464, R01 CA063464] NR 44 TC 57 Z9 58 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN PY 2005 VL 76 IS 1 BP 82 EP 90 DI 10.1086/427224 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 878JR UT WOS:000225643600007 PM 15570555 ER PT J AU Shrank, WH Young, HN Ettner, SL Glassman, P Asch, SM Kravitz, RL AF Shrank, WH Young, HN Ettner, SL Glassman, P Asch, SM Kravitz, RL TI Do the incentives in 3-tier pharmaceutical benefit plans operate as intended? Results from a physician leadership survey SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID HEALTH MAINTENANCE ORGANIZATION; PRESCRIPTION DRUGS; FORMULARIES; MEDICARE; COST; COPAYMENTS; IMPACT; CARE AB Background: Three-tier pharmaceutical benefit systems use graded co-payments to steer patients toward "preferred" formulary medications. Objectives: To evaluate physicians' knowledge of formularies and out-of-pocket costs in such systems, as well as their perceived responsibility for helping patients manage out-of-pocket costs. Study Design: Self-administered written survey. Methods: Physician leaders participating in the California Medical Association Leadership Conference were surveyed. Results: A total of 133 responses were received from 205 participants (65% response rate). Physicians reported that they were often unaware of patients' out-of-pocket costs at the time of prescribing. Fifty-nine percent of physicians reported that they never or seldom were aware of patients' "preferred" (lower cost) formulary options when prescribing, and 70% never or seldom were aware of patients' out-of-pocket costs when prescribing. Although 88% of physicians agreed that it is important that patients' out-of-pocket costs for prescription drugs are managed, only 25% strongly or somewhat agreed that it is their "responsibility" to help. Instead, 69% of physicians believed that it is the responsibility of the pharmacist to be familiar with patients' out-of-pocket costs. Physicians reported that they receive phone calls from pharmacists concerning formulary issues after 18.6% of the prescriptions they write. Conclusions: Physician leaders reported that they often do not possess the knowledge to assist patients in managing out-of-pocket costs for prescription drugs and they depend on pharmacists to communicate patient preferences in making prescribing decisions. As a result, price preferences are communicated indirectly, likely less efficiently, rather than intentionally when prescribing decisions are made. C1 VA Greater Los Angeles Hlth Care Syst, Div Gen Internal Med, Vet Affairs Hlth Serv Res & Dev Fellow, Los Angeles, CA 90073 USA. Univ Calif Davis, Serv Res Primary Care, Sacramento, CA USA. Univ Calif Davis, Dept Internal Med, Sacramento, CA USA. Univ Calif Los Angeles, Div Gen Internal Med & Htlh Serv Res, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. RP Shrank, WH (reprint author), VA Greater Los Angeles Hlth Care Syst, Div Gen Internal Med, Vet Affairs Hlth Serv Res & Dev Fellow, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM William.Shrank@med.va.gov OI Kravitz, Richard/0000-0001-5575-529X NR 32 TC 35 Z9 35 U1 0 U2 0 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JAN PY 2005 VL 11 IS 1 BP 16 EP 22 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 886RF UT WOS:000226245300002 PM 15697096 ER PT J AU Spina, JR Glassman, PA Belperio, P Cader, R Asch, S AF Spina, JR Glassman, PA Belperio, P Cader, R Asch, S CA Primary Care Investigative Grp VA TI Clinical relevance of automated drug alerts from the perspective of medical providers SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE attitude of health personnel; clinical decision support systems; drug interactions; computer-assisted drug therapy; medication errors; prevention; control ID PHYSICIAN ORDER ENTRY; ERRORS; CARE; INTERVENTION; COMPUTER; SYSTEM AB The authors used a real-time survey instrument and subsequent focus group among primary care clinicians at a large healthcare system to assess usefulness of automated drug alerts. Of 108 alerts encountered, 0.9% (n = 1) represented critical alerts, and 16% (n = 17) were significant drug interaction alerts. Sixty-one percent (n = 66) involved duplication of a medication or medication class. The rest (n = 24) involved topical medications, inhalers, or vaccines. Of the 84 potentially relevant alerts, providers classified 11% (9/84), or about 1 in 9, as useful. Drug interaction alerts were more often deemed useful than drug duplication alerts (44.4% versus 1.5%, P<.001). Focus group participants generally echoed these results when ranking the relevance of 15 selected alerts, although there was wide variance in ratings for individual alerts. Hence, a "smarter" system that utilizes a set of mandatory alerts while allowing providers to tailor use of other automated warnings may improve clinical relevance of drug alert systems. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. RP Spina, JR (reprint author), 11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA. EM jeffrey.spina@med.va.gov NR 21 TC 41 Z9 42 U1 1 U2 1 PU AMER COLLEGE MEDICAL QUALITY PI BETHESDA PA 4334 MONTGOMERY AVE, 2ND FL, BETHESDA, MD 20814-4402 USA SN 1062-8606 J9 AM J MED QUAL JI Am. J. Med. Qual. PD JAN-FEB PY 2005 VL 20 IS 1 BP 7 EP 14 DI 10.1177/1062860604273777 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 894HO UT WOS:000226781900002 PM 15782750 ER PT J AU Sherman, SE Yano, EM Lanto, AB Simon, BF Rubenstein, LV AF Sherman, SE Yano, EM Lanto, AB Simon, BF Rubenstein, LV TI Smokers' interest in quitting and services received: Using practice information to plan quality improvement and policy for smoking cessation SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE smoking cessation; counseling; primary care; cross-sectional analysis ID DEPRESSION; CARE AB Given the prevalence of smoking, its impact, and the benefits of cessation, helping smokers quit should be a top priority for health care organizations. To restructure health care delivery and guide future policy, the authors used baseline survey data from an 18-site Veterans Health Administration group randomized trial to assess the level of interest in quitting smoking for a practice population and determine what smoking cessation services they reported receiving. Among 1941 current smokers, 55% did not intend to quit in the next 6 months, and the remainder intended to quit in the next month (13%) to 6 months (32%). Forty-five percent reported a quit attempt in the prior year. While nearly two thirds of smokers reported being counseled about cessation within the past year, only 29% were referred to a cessation program, and 25% received a prescription for nicotine patches. Tobacco control efforts within this population should focus on increasing the rate of assisting patients with quitting. C1 VA Greater Los Angeles Healthcare Syst, Ctr Excellence Study Healthcare Provider Behav, VAHSR&D, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA USA. RP Sherman, SE (reprint author), Sepulveda Ambulatory Care Ctr 00PG, 16111 Plummer St, Sepulveda, CA 91343 USA. EM ssherman@ucla.edu OI Sherman, Scott/0000-0003-1752-7303 NR 28 TC 19 Z9 19 U1 0 U2 1 PU AMER COLLEGE MEDICAL QUALITY PI BETHESDA PA 4334 MONTGOMERY AVE, 2ND FL, BETHESDA, MD 20814-4402 USA SN 1062-8606 J9 AM J MED QUAL JI Am. J. Med. Qual. PD JAN-FEB PY 2005 VL 20 IS 1 BP 33 EP 39 DI 10.1177/1062860604273776 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 894HO UT WOS:000226781900005 PM 15782753 ER PT J AU Groeneveld, PW Owens, DK AF Groeneveld, PW Owens, DK TI Cost-effectiveness of training unselected laypersons in cardiopulmonary resuscitation and defibrillation SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE cardiopulmonary resuscitation; cost-benefit analysis; education, non-professional; quality-adjusted life years; Markow chains ID HOSPITAL CARDIAC-ARREST; PUBLIC-ACCESS DEFIBRILLATION; IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; AUTOMATED EXTERNAL DEFIBRILLATORS; MINNESOTA HEART SURVEY; BYSTANDER CPR; VENTRICULAR-FIBRILLATION; ETHNIC DISPARITIES; WITNESSED COLLAPSE; FAMILY MEMBERS AB Purpose: The cost-effectiveness of cardiopulmonary resuscitation (CPR) and defibrillation training for laypersons unselected for risk of encountering cases of cardiac arrest is not known. We compared the costs and health benefits of alternative resuscitation training strategies for adults without professional first-responder duties who are at average risk of encountering cases of out-of-hospital cardiac arrest. Methods: We constructed a cost-effectiveness analytic model. Data on cardiac arrest epidemiology and the effectiveness of CPR/defibrillation training were obtained from the medical literature. Instructional costs were determined from a survey of training programs. Downstream cardiac arrest survivor quality-adjusted life expectancy and long-term health care costs were derived from prior Studies. We compared three strategies for training unselected laypersons: CPR/defibrillation training alone, training combined with home defibrillator purchase, and no training. The main outcome measures were total instructional costs for trainees combined with health care costs for additional cardiac arrest survivors, and quality-adjusted survival for additional patients resuscitated by trainees. Results: CPR/defibrillation training yielded 2.7 quality-adjusted hours of life at a cost of $62 per trainee ($202,400 per quality-adjusted life-year [QALY] gained). Training laypersons in CPR/defibrillation with subsequent defibrillator purchase cost $2,489,700 per QALY. In contrast. CPR/defibrillation training cost less than $75,000 per QALY if trainees lived with persons older than 75 years or with persons who had cardiac disease, or if total training costs were less than $10. Conclusion: Training unselected laypersons in CPR/defibrillation is costly compared with other public health initiatives. Conversely, training laypersons selected by occupation, low training costs. or having high-risk household companions is substantially more efficient. (C) 2005 Elsevier Inc. All rights reserved. C1 Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Div Gen Internal Med, Philadelphia, PA USA. Leonard Davis Inst Hlth Econ, Philadelphia, PA USA. Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. Stanford Univ, Ctr Primary Care & Outcomes Res, Stanford, CA 94305 USA. RP Groeneveld, PW (reprint author), 1122 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM peter.groeneveld@med.va.gov FU AHRQ HHS [T32-HS000028] NR 73 TC 22 Z9 22 U1 1 U2 7 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JAN PY 2005 VL 118 IS 1 BP 58 EP 67 DI 10.1016/j.amjmed.2004.08.014 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 888FN UT WOS:000226359700012 PM 15639211 ER PT J AU Williams, ME AF Williams, ME TI Diabetic nephropathy: The proteinuria hypothesis SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Review DE diabetic nephropathy; proteinuria, clinical trials; hypertension; angiotensin; converting enzyme inhibitors; angiotensin receptor blockers ID CONVERTING-ENZYME-INHIBITORS; NONDIABETIC RENAL-DISEASE; ANGIOTENSIN RECEPTOR BLOCKERS; ANTI-HYPERTENSIVE TREATMENT; RANDOMIZED CONTROLLED TRIAL; NATIONAL-KIDNEY-FOUNDATION; INSULIN-DEPENDENT PATIENTS; GLOMERULAR-FILTRATION RATE; CALCIUM-CHANNEL BLOCKERS; SLIT-DIAPHRAGM PROTEIN AB Background/Aims: Proteinuria, nearly a universal finding in progressive kidney disease, has been the subject of frequent recent analyses in the renal literature. Proteinuria is a hallmark of diabetic nephropathy: microalbuminuria is the principal early predictor for progression of diabetic glomerulopathy, and proteinuria may be viewed as a measure of the severity and promoter of progression of nephropathy. Methods: This article critically reviews for the first time the full scope of diabetic proteinuria - complex molecular mechanisms, natural history, and analysis of treatment trials - in order to address the validity of 'the proteinuria hypothesis', i.e., that diabetic proteinuria is a modifiable determinant of renal progression. This hypothesis is analyzed in detail, including recent studies on the primary therapy of diabetic nephropathy, renin-angiotensin blockade. Results: As fully developed, this hypothesis consists of three postulates: that higher amounts of proteinuria predict progressive loss of function, that proteinuria reduction correlates with slowing progression, and that proteinuria is a surrogate endpoint for clinical trials. The latter postulate has not before been adequately linked to growing information about the first two postulates as they apply to diabetic kidney disease. Conclusion: While diabetic nephropathy is a disease model for the potential use of proteinuria as a surrogate marker for renal progression, this shift in perspective will require prospective data from additional clinical trials, particularly of non-renin-angiotensin blocking drugs, to be complete. Copyright (C) 2005 S. Karger AG, Basel. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Williams, ME (reprint author), 1 Joslin Pl, Boston, MA 02215 USA. EM mark.williams@joslin.harvard.edu NR 178 TC 30 Z9 37 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2005 VL 25 IS 2 BP 77 EP 94 DI 10.1159/000084286 PG 18 WC Urology & Nephrology SC Urology & Nephrology GA 927RX UT WOS:000229219300001 PM 15746541 ER PT J AU Adrogue, HJ AF Adrogue, HJ TI Consequences of inadequate management of hyponatremia SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Review DE hyponatremia; vasopressin; water excretion; salt-water balance ID CONGESTIVE-HEART-FAILURE; VASOPRESSIN-INDUCED ANTIDIURESIS; SERUM SODIUM CONCENTRATION; EFFECTIVE WATER CLEARANCE; NEUROLOGIC COMPLICATIONS; SYMPTOMATIC HYPONATREMIA; INAPPROPRIATE SECRETION; ANTAGONIST CONIVAPTAN; RECEPTOR ANTAGONISTS; V-2 ANTAGONIST AB Dilutional hyponatremia is a commonly observed disorder in hospitalized patients. It represents an excess of water in relation to prevailing sodium stores and is most often associated with a high plasma level of arginine vasopressin, including that found in patients with the syndrome of inappropriate antidiuretic hormone secretion. Hyponatremia may be classified as either acute or chronic depending on the rate of decline of serum sodium concentration, and can lead to a wide range of deleterious changes involving almost all body systems. Serious complications of dilutional hyponatremia most frequently involve the central nervous system. In fact, acute severe hyponatremia is potentially life-threatening and must be treated promptly and aggressively. Chronic hyponatremia often develops in patients with nonrenal diseases and is associated with increased morbidity and mortality. In patients hospitalized for congestive heart failure, hyponatremia is linked to a poor prognosis and increased length of hospital stay. Prompt recognition and optimal management of hyponatremia in hospitalized patients may reduce in-hospital mortality and symptom severity, allow for less intensive hospital care, decrease the duration of hospitalization and associated costs, and improve the treatment of underlying comorbid conditions and patients' quality of life. The proper treatment of dilutional hyponatremia, especially when chronic, must avoid increasing serum sodium too rapidly, which can lead to permanent or fatal neurologic sequelae. The treatment of hyponatremia may be facilitated by emerging therapies that block the actions of arginine vasopressin at V-2 and V-1a receptors to promote aquaresis, the electrolyte-sparing elimination of free water, and elevate serum sodium concentrations. Copyright (C) 2005 S. Karger AG, Basel. C1 Baylor Coll Med, Nephrol Sect, Houston, TX 77030 USA. Methodist Hosp, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Renal Sect, Houston, TX USA. RP Adrogue, HJ (reprint author), Baylor Coll Med, Nephrol Sect, 6550 Fannin,SM 1273, Houston, TX 77030 USA. EM hadrogue@bcm.tcm.edu RI chen, xuanlan/H-4158-2011 NR 54 TC 77 Z9 81 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2005 VL 25 IS 3 BP 240 EP 249 DI 10.1159/000086019 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 942TQ UT WOS:000230306200008 PM 15914973 ER PT J AU Hathout, GM Fink, JR El-Saden, SM Grant, EG AF Hathout, GM Fink, JR El-Saden, SM Grant, EG TI Sonographic NASCET index: A new Doppler parameter for assessment of internal carotid artery stenosis SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID DIGITAL-SUBTRACTION-ANGIOGRAPHY; DUPLEX CRITERIA; ENDARTERECTOMY TRIAL; ULTRASOUND; US; DIAGNOSIS; 70-PERCENT; DISEASE; MRA AB BACKGROUND AND PURPOSE: Established Doppler parameters for carotid stenosis assessment do not reflect North American Symptomatic Carotid Endarterectomy Trial (NASCET)-style methodology. We derived a Doppler parameter, termed sonographic NASCET index (SNI), and hypothesized that the SNI would provide greater angiographic correlation and better accuracy in predicting stenosis of 70% or greater than that of currently used peak systolic velocity (PSV) measurements. METHODS: Inclusion criteria of angiographically proved carotid stenoses of 40-95% and measured proximal and distal internal carotid artery Doppler PSV values were established. Occlusions and near occlusions were specifically excluded. Doppler and angiographic data meeting the inclusion criteria from 32 carotid bifurcations were identified; actual angiographic stenoses ranged 40-89%. SNI values were calculated for each vessel. PSV and SNI were correlated with angiography by using linear regression analysis. Accuracies of SNI and PSV in predicting stenosis of 70% or greater were compared at two thresholds. RESULTS: Correlation between SNI and angiography was superior to that between PSV and angiography (r(2) = 0.64 vs 0.38). PSV and SNI values that corresponded to 70% angiographic stenosis were 345 cm/s and 45.5, respectively. Accuracy of PSV of 345 cm/s or greater in predicting stenosis of 70% or greater was 78%, compared with 88% for SNI of 45.5 or greater. The SNI value that corresponded to a PSV threshold of 250 cm/s was 33. Accuracy of PSV of 250 cm/s or greater in predicting stenosis of 70% or greater was 81%, compared with 88% for SNI of 33 or greater. CONCLUSION: Correlation between SNI and angiography was greater than that between PSV and angiography. Accuracy of SNI in predicting stenosis of 70% or greater was also superior to that of PSV at two thresholds. These results suggest that SNI may be a better predictor of high-grade carotid stenosis than is PSV. C1 W Los Angeles Vet Affairs Med Ctr, Dept Radiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA USA. Univ So Calif, Med Ctr, Dept Radiol, Los Angeles, CA USA. RP Hathout, GM (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Radiol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 32 TC 15 Z9 16 U1 0 U2 3 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JAN PY 2005 VL 26 IS 1 BP 68 EP 75 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 893OO UT WOS:000226729300018 PM 15661704 ER PT J AU Durrani, K Foster, CS AF Durrani, K Foster, CS TI Psoriatic uveitis: A distinct clinical entity? SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID PUSTULAR PSORIASIS; ANTERIOR UVEITIS; ARTHRITIS; SPONDYLOARTHROPATHIES; RECOMMENDATIONS; FEATURES; DISEASE AB PURPOSE: To describe the clinical characteristics of uveitis occurring in patients with psoriasis and to compare them with patients with idiopathic anterior uveitis and HLA-B27,associated anterior uveitis. DESIGN: Case-control study. METHODS: The charts of 36 patients with a diagnosis of uveitis and psoriasis visiting the Immunology and Uveitis Service at the Massachusetts Eye and Ear Infirmary between January 2000 and December 2001 were reviewed. Clinical characteristics, therapy, and outcomes of uveitis were compared with 30 randomly selected patients with either idiopathic anterior uveitis or with HLA-B27-associated anterior uveitis. RESULTS: The mean age at presentation for uveitis was significantly higher in patients with psoriasis compared with nonpsoriatic groups (44.6 years in HLA-B27-psoriatic patients vs 35.9 years in HLA-B27- nonpsoriatic patients, P = .034; 52.7 years in HLA-B27+ psoriatic vs 35.7 years in HLA-1327+ nonpsoriatic patients, P = .001). Uveitis in patients with psoriasis also tended to be bilateral (62%) and prolonged (11.2 weeks). HLA-1327+ patients with psoriasis required supplemental therapy with oral nonsteroidal anti-inflammatory drugs (95% confidence interval [CI] 1.41 to 5.36, P = .003) for anterior uveitis more often than did the HLA-B27+ nonpsoriatic group. Patients with lpsoriasis and uveitis who were HLA-1327+ required oral NSAIDs (95% CI 1.51 to 9.79, P = .001) for anterior uveitis more often than did HLA-B27- psoriatic patients. CONCLUSION: Uveitis inpatients with psoriasis may have distinguishing clinical features. Further epidemiologic studies are required to determine the strength of association between psoriasis without arthritis but with uveitis. (C) 2005 by Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. EM fosters@uveitis.org NR 29 TC 34 Z9 36 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 JAN PY 2005 VL 139 IS 1 BP 106 EP 111 DI 10.1016/j.ajo.2004.08.053 PG 6 WC Ophthalmology SC Ophthalmology GA 885XW UT WOS:000226191700013 PM 15652834 ER PT J AU Santangelo, SL Tsatsanis, K AF Santangelo, SL Tsatsanis, K TI What is known about autism - Genes, brain, and behavior SO AMERICAN JOURNAL OF PHARMACOGENOMICS LA English DT Review ID PERVASIVE DEVELOPMENTAL DISORDERS; SEROTONIN TRANSPORTER GENE; OBSESSIVE-COMPULSIVE BEHAVIORS; PLACEBO-CONTROLLED TRIAL; HIGH-FUNCTIONING AUTISM; RETT-SYNDROME; LINKAGE-DISEQUILIBRIUM; SUSCEPTIBILITY GENE; SPECTRUM DISORDERS; TRANSMISSION DISEQUILIBRIUM AB Autism is a neurodevelopmental disorder of genetic origins, with a heritability of about 90%. Autistic disorder is classed within the broad domain of pervasive developmental disorders (PDD) that also includes Rett syndrome, childhood disintegrative disorder, Asperger syndrome, and PDD not otherwise specified (PDD-NOS). Prevalence estimates suggest a rate of 0.1-0.2% for autism and 0.6% for the range of PDD disorders. There is considerable phenotypic heterogeneity within this class of disorders as well as continued debate regarding their clinical boundaries. Autism is the prototypical PDD, and is characterized by impairments in three core domains: social interaction, language development, and patterns of behavior (restricted and stereotyped). Clinical pattern and severity of impairment vary along these dimensions, and the level of cognitive functioning of individuals with autism spans the entire range, from profound mental retardation to superior intellect. There is no single biological or clinical marker for autism, nor is it expected that a single gene is responsible for its expression; as many as 15+ genes may be involved. However, environmental influences are also important, as concordance in monozygotic twins is less than 100% and the phenotypic expression of the disorder varies widely, even within monozygotic twins. Multiple susceptibility factors are being explored using varied methodologies, including genome-wide linkage studies, and family- and case-control candidate gene association studies. This paper reviews what is currently known about the genetic and environmental risk factors, neuropathology, and psychopharmacology of autism. Discussion of genetic factors focuses on the findings from linkage and association studies, the results of which have implicated the involvement of nearly every chromosome in the human genome. However, the most consistently replicated linkage findings have been on chromosome 7q, 2q, and 15q. The positive associations from candidate gene studies are largely unreplicated, with the possible exceptions of the GABRB3 and serotonin transporter genes. No single region of the brain or pathophysiological mechanism has yet been identified as being associated with autism. Postmortem findings, animal models, and neuroimaging studies have focused on the cerebellum, frontal cortex, hippocampus, and especially the amygdala. The cerebello-thalamo-cortical circuit may also be influential in autism. There is evidence that overall brain size is increased in some individuals with autism. Presently there are no drugs that produce major improvements in the core social or pragmatic language deficits in autism, although several have limited effects on associated behavioral features. The application of new techniques in autism research is being proposed, including the investigation of abnormal regulation of gene expression, proteomics, and the use of MRI and Postmortem analysis of the brain. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02115 USA. RP Santangelo, SL (reprint author), Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, 149 13th St, Charlestown, MA 02129 USA. EM ssantang@psych.mgh.harvard.edu NR 227 TC 96 Z9 100 U1 17 U2 73 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1175-2203 J9 AM J PHARMACOGENOMIC JI Am. J. Pharmacogenomics PY 2005 VL 5 IS 2 BP 71 EP 92 DI 10.2165/00129785-200505020-00001 PG 22 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 961XS UT WOS:000231695700001 PM 15813671 ER PT J AU Burns, SP Breuninger, A Kaplan, C Marin, H AF Burns, SP Breuninger, A Kaplan, C Marin, H TI Hand-held dynamometry in persons with tetraplegia - Comparison of make- versus break-testing techniques SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE spinal cord injuries; muscle strength; muscle spasticity; reproducibility of results ID SPINAL-CORD-INJURY; RELIABILITY; STRENGTH; INDIVIDUALS; MYOMETER; MUSCLES AB Objective: To compare make and break techniques for hand-held dynamometry in persons with tetraplegia. We compared the interrater and intrarater reliability, the relative forces, and variability between examiner techniques. Design: Two examiners with no previous hand-held dynamometry training performed hand-held dynamometry on the elbow flexors or extensors of 19 persons with upper limb weakness secondary to tetraplegia, using break and make techniques. Testing was performed in two sessions separated by 10 mins. Simultaneous recording from an electrogoniometer placed across the elbow was obtained for a subset of participants. Results: Break and make techniques both showed intraclass correlation coefficients exceeding 0.9 for interrater and intrarater reliability. The maximum expected difference for 95% of repeated measurements was 3.5 kg, with hand-held dynamometry strength values that averaged 7-11 kg. Average break/make ratios ranged from 1.38 +/- 0.29 to 1.49 +/- 0.37. The electrogoniometric data showed that the two examiners used similar testing technique, and small variations in technique were not associated with significant differences in strength recordings. Conclusion: Make and break techniques for hand-held dynamometry both show high reliability over a short intersession period when performed by inexperienced examiners on weak elbow flexors and extensors. C1 Vet Affairs Puget Sound Hlth Care Syst, Spinal Cord Injury Serv, Seattle, WA 98108 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Washington, Harborview Med Ctr, Harborview Injury Prevent & Res Ctr, Seattle, WA 98104 USA. RP Burns, SP (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Spinal Cord Injury Serv, SCI 128,1660 S Columbian Way, Seattle, WA 98108 USA. NR 26 TC 20 Z9 22 U1 0 U2 2 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 JAN PY 2005 VL 84 IS 1 BP 22 EP 29 DI 10.1097/01.PHM.0000150790.99514.C6 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 884EE UT WOS:000226066600005 PM 15632485 ER PT J AU Strangman, G O'Neil-Pirozzi, TM Burke, D Cristina, D Goldstein, R Rauch, SL Savage, CR Glenn, MB AF Strangman, G O'Neil-Pirozzi, TM Burke, D Cristina, D Goldstein, R Rauch, SL Savage, CR Glenn, MB TI Functional neuroimaging and cognitive rehabilitation for people with traumatic brain injury SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Review DE functional magnetic resonance Imaging; cognitive rehabilitation; traumatic brain injury; functional neuroimaging; review; Hemodynamic ID POSITRON-EMISSION-TOMOGRAPHY; CLOSED-HEAD-INJURY; OBSESSIVE-COMPULSIVE DISORDER; NEAR-INFRARED SPECTROSCOPY; ANTERIOR CINGULOTOMY; POTENTIAL PREDICTORS; CONTROLLED TRIAL; EPISODIC MEMORY; SELF-REGULATION; MOTOR RECOVERY AB Cognitive deficits are a common consequence of traumatic brain injury. Although such deficits are amenable to rehabilitation, methods for individualizing cognitive interventions are still unrefined. Functional neuroimaging methods such as positron emission tomography and functional magnetic resonance imaging are emerging as possible technologies for measuring and monitoring the cerebral consequences of plasticity associated with brain injury and for evaluating the effectiveness of rehabilitation interventions. Functional neuroimaging may even enable more customized and efficient selection, design, or adaptation of individual cognitive rehabilitation programs. We review the current literature on functional neuroimaging after traumatic brain injury, relating these findings to cognitive rehabilitation. Overall, functional neuroimaging after traumatic brain injury has shown reliable differences in brain activity within several regions of frontal cortex, partly but not uniformly consistent with neuropsychological and structural findings in traumatic brain injury. We also outline a number of promising research opportunities for applying functional neuroimaging in traumatic brain injury settings, along with associated challenges. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Neural Syst Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat Neurosci Div, Charlestown, MA USA. Northeastern Univ, Dept Speech Language Pathol & Audiol, Boston, MA 02115 USA. Univ Kansas, Med Ctr, Hoglund Brain Imaging Ctr, Kansas City, KS 66103 USA. RP Strangman, G (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Neural Syst Grp, 149 13th St,Room 2651, Charlestown, MA 02129 USA. FU NINDS NIH HHS [K25 NS 046554] NR 106 TC 43 Z9 45 U1 5 U2 12 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 JAN PY 2005 VL 84 IS 1 BP 62 EP 75 DI 10.1097/01.PHM.0000150787.26860.12 PG 14 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 884EE UT WOS:000226066600010 PM 15632490 ER PT J AU Jessen, N Djurhuus, CB Jorgensen, JOL Jensen, LS Moller, N Lund, S Schmitz, O AF Jessen, N Djurhuus, CB Jorgensen, JOL Jensen, LS Moller, N Lund, S Schmitz, O TI Evidence against a role for insulin-signaling proteins PI 3-kinase and Akt in insulin resistance in human skeletal muscle induced by short-term GH infusion SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE glucose transport; growth hormone; phosphatidylinositol 3-kinase; euglycemic hyperinsulinemic clamp ID RECEPTOR SUBSTRATE-1 PHOSPHORYLATION; STIMULATED GLUCOSE-UPTAKE; GROWTH-HORMONE TREATMENT; TYROSINE PHOSPHORYLATION; KINASE-ACTIVITY; NIDDM SUBJECTS; RAT-TISSUES; FATTY-ACIDS; IN-VIVO; METABOLISM AB Prolonged growth hormone (GH) excess is known to be associated with insulin resistance, but the underlying mechanisms remain unknown. The aim of this study was to assess the impact of GH on insulin-stimulated glucose metabolism and insulin signaling in human skeletal muscle. In a cross-over design, eight healthy male subjects (age 26.0+/-0.8 yr and body mass index 24.1+/-0.5 kg/m(2)) were infused for 360 min with either GH (Norditropin, 45 ng.kg(-1).min(-1)) or saline. During the final 180 min of the infusion, a hyperinsulinemic euglycemic clamp was performed (insulin infusion rate: 1.2 mU.kg(-1).min(-1)). Muscle biopsies from vastus lateralis were taken before GH/saline administration and after 60 min of hyperinsulinemia. GLUT4 content and insulin signaling, as assessed by insulin receptor substrate ( IRS)-1-associated phosphatidylinositol 3-kinase and Akt activity were determined. GH levels increased to a mean (+/-SE) level of 20.0+/-2.3 vs. 0.5+/-0.2 mug/l after saline infusion (P<0.01). During GH infusion, the glucose infusion rate during hyperinsulinemia was reduced by 38% (P<0.01). In both conditions, free fatty acids were markedly suppressed during hyperinsulinemia. Despite skeletal muscle insulin resistance, insulin still induced a similar similar to3-fold rise in IRS-1-associated PI 3-kinase activity (269+/-105 and 311+/-71% compared with baseline, GH vs. saline). GH infusion did not change Akt protein expression, and insulin caused an similar to13-fold increase in Akt activity (1,309+/-327 and 1,287+/-173%) after both GH and saline infusion. No difference in total GLUT4 content was noted (114.7+/-7.4 and 107.6+/-16.7 arbitrary units, GH vs. saline, compared with baseline). In conclusion, insulin resistance in skeletal muscle induced by short-term GH administration is not associated with detectable changes in the upstream insulin-signaling cascade or reduction in total GLUT4. Yet unknown mechanisms in insulin signaling downstream of Akt may be responsible. C1 Aarhus Univ Hosp, Med Res Lab, DK-8000 Aarhus, Denmark. Aarhus Univ Hosp, Med Dept Endocrinol & Diabet M, DK-8000 Aarhus, Denmark. Univ Aarhus, Dept Clin Pharmacol, Aarhus, Denmark. RP Jessen, N (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM Niels.Jessen@Joslin.Harvard.edu RI Jessen, Niels/E-1731-2011; Moller, Niels/E-5091-2011; OI Moller, Niels/0000-0001-5627-7322; Jorgensen, Jens Otto Lunde/0000-0001-7408-1526; Jessen, Niels/0000-0001-5613-7274 NR 40 TC 36 Z9 37 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JAN PY 2005 VL 288 IS 1 BP E194 EP E199 DI 10.1152/ajpendo.00149.2004 PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 893WC UT WOS:000226750200023 PM 15339744 ER PT J AU Shen, XX Li, QL Brent, GA Friedman, TC AF Shen, XX Li, QL Brent, GA Friedman, TC TI Regulation of regional expression in rat brain PC2 by thyroid hormone/characterization of novel negative thyroid hormone response elements in the PC2 promoter SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE posttranslational processing; hypothyroidism; prohormone convertase; pituitary; regulation ID PROHORMONE CONVERTASES PC1; GENE-EXPRESSION; MESSENGER-RNA; IN-VITRO; PROPROTEIN CONVERTASES; ANTERIOR-PITUITARY; INTERMEDIATE LOBE; PRO-PROTEIN; DNA-BINDING; HALF-SITES AB The prohormone convertases (PCs) PC1 and PC2 are involved in the tissue-specific endoproteolytic processing of neuropeptide precursors within the secretory pathway. We previously showed that changes in thyroid status altered pituitary PC2 mRNA and that this regulation was due to triiodothyronine-dependent interaction of the thyroid hormone receptor (TR) with negative thyroid hormone response elements (nTREs) contained in a large proximal region of the human PC2 promoter. In the current study, we examined the in vivo regulation of brain PC2 mRNA by thyroid status and found that 6-n-propyl-2-thiouracil-induced hypothyroidism stimulated, whereas thyroxine-induced hyperthyroidism suppressed, PC2 mRNA levels in the rat hypothalamus and cerebral cortex. To address the mechanism of T-3 regulation of the PC2 gene, we used human PC2 (hPC2) promoter constructs transiently transfected into GH3 cells and found that triiodothyronine negatively and 9-cis-retinoic acid positively regulated hPC2 promoter activity. EMSAs, using purified TRalpha1 and retinoid X receptor-beta (RXRbeta) proteins demonstrated that TRalpha bound th distal putative nTRE-containing oligonucleotide in the PC2 promoter, and RXR bound to both nTRE-containing oligonucleotides. EMSAs with oligonucleotides containing deletion mutations of the nTREs demonstrated that the binding to TR and RXR separately is reduced, but specific binding to TR and RXR together persists even with deletion of each putative nTRE. We conclude that there are two novel TRE-like sequences in the hPC2 promoter and that these regions act in concert in a unique manner to facilitate the effects of thyroid hormone and 9-cis-retinoic acid on PC2. C1 Charles R Drew Univ Med & Sci, Dept Med, Div Endocrinol, Los Angeles, CA 90059 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90059 USA. W Los Angeles Vet Affairs Med Ctr, Dept Med, Div Endocrinol, Los Angeles, CA 90073 USA. RP Friedman, TC (reprint author), Charles R Drew Univ Med & Sci, Dept Med, Div Endocrinol, 1731 E 120th St, Los Angeles, CA 90059 USA. EM tefriedm@cdrewu.edu FU NCRR NIH HHS [U54-RR-14616-01, G21-RR-03026-13]; NIDA NIH HHS [DA-14659]; NIDDK NIH HHS [DK-67233] NR 61 TC 16 Z9 16 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JAN PY 2005 VL 288 IS 1 BP E236 EP E245 DI 10.1152/ajpendo.00144.2004 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 893WC UT WOS:000226750200029 PM 15585599 ER PT J AU Nanthakumar, NN Young, C Ko, JS Meng, D Chen, J Buie, T Walker, WA AF Nanthakumar, NN Young, C Ko, JS Meng, D Chen, J Buie, T Walker, WA TI Glucocorticoid responsiveness in developing human intestine: possible role in prevention of necrotizing enterocolitis SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE cortisone acetate; interleukin-8; human ileum; intestinal inflammation; signal transduction ID BIRTH-WEIGHT INFANTS; IMMUNE-RESPONSE; EXPRESSION; THERAPY; PATHOGENESIS; INFLAMMATION; XENOGRAFT; ONTOGENY; OUTCOMES; DISEASE AB Necrotizing enterocolitis (NEC) is a major inflammatory disease of the premature human intestine that can be prevented by glucocorticoids if given prenatally before the 34th wk of gestation. This observation suggests that a finite period of steroid responsiveness exists as has been demonstrated in animal models. Human intestinal xenografts were used to determine whether a glucocorticoid responsive period exists in the developing human intestine. Developmental responsiveness was measured by lactase activity and inflammatory responsiveness by IL-8, IL-6, and monocyte chemotactic protein-1 (MCP-1) induction after an endogenous (IL-1beta) or exogenous (LPS) proinflammatory stimulus, respectively. Functional development of ileal xenografts were monitored for 30 wk posttransplantation, and the lactase activity recapitulated that predicted by in utero development. Cortisone acetate accelerated the ontogeny of lactase at 20 wk (immature) but the effect was lost by 30 wk (mature) posttransplant. Concomitant with accelerated maturation, the IL-8 response to both IL-1beta and LPS was significantly dampened (from 6- to 3-fold) by glucocorticoid pretreatment in the immature but not mature xenografts. The induction of IL-8 was reflected at the level of IL-8 mRNA, suggesting transcriptional regulation. The excessive activation of IL-8 in the immature gut was mediated by a prolonged activation of ERK and p38 kinases and nuclear translocation of NF-kappaB due to low levels of IkappaB. Steroid pretreatment in immature intestine dampens activation of all three signaling pathways in response to proinflammatory stimuli. Therefore, accelerating intestinal maturation by glucocorticoids within the responsive period by accelerating functional and inflammatory maturation may provide an effective preventive therapy for NEC. C1 Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Dev Gastroenterol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Depauw Univ, Greencastle, IN 46135 USA. RP Nanthakumar, NN (reprint author), Massachusetts Gen Hosp E, Dev Gastroenterol Lab, 114 16th St,Rm 3650, Charlestown, MA 02129 USA. EM nanthaku@helix.mgh.harvard.edu FU NICHD NIH HHS [R37-HD-12437, R01-HD-31852]; NIDDK NIH HHS [P01-DK-33506, P30-DK-33506, P30-DK-40561] NR 36 TC 36 Z9 38 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 JAN PY 2005 VL 288 IS 1 BP G85 EP G92 DI 10.1152/ajpgi.00169.2004 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 878PI UT WOS:000225658500012 PM 15591589 ER PT J AU Barbieri, R Matten, EC Alabi, AA Brown, EN AF Barbieri, R Matten, EC Alabi, AA Brown, EN TI A point-process model of human heartbeat intervals: new definitions of heart rate and heart rate variability SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE tilt table; inverse Gaussian; time-rescaling theorem; Kolmogorov-Smirnov test; autonomic regulation ID POWER SPECTRUM ANALYSIS; MYOCARDIAL-INFARCTION; WAVELET TRANSFORM; AUTONOMIC CONTROL; PRESSURE; FLUCTUATION; NEUROPATHY; MORTALITY; EXERCISE AB Heart rate is a vital sign, whereas heart rate variability is an important quantitative measure of cardiovascular regulation by the autonomic nervous system. Although the design of algorithms to compute heart rate and assess heart rate variability is an active area of research, none of the approaches considers the natural point-process structure of human heartbeats, and none gives instantaneous estimates of heart rate variability. We model the stochastic structure of heartbeat intervals as a history-dependent inverse Gaussian process and derive from it an explicit probability density that gives new definitions of heart rate and heart rate variability: instantaneous R-R interval and heart rate standard deviations. We estimate the time-varying parameters of the inverse Gaussian model by local maximum likelihood and assess model goodness-of-fit by Kolmogorov-Smirnov tests based on the time-rescaling theorem. We illustrate our new definitions in an analysis of human heartbeat intervals from 10 healthy subjects undergoing a tilt-table experiment. Although several studies have identified deterministic, nonlinear dynamical features in human heartbeat intervals, our analysis shows that a highly accurate description of these series at rest and in extreme physiological conditions may be given by an elementary, physiologically based, stochastic model. C1 Massachusetts Gen Hosp, Neurosci Stat Res Lab, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Hlth Sci & Technol, MIT, Boston, MA USA. RP Barbieri, R (reprint author), Massachusetts Gen Hosp, Neurosci Stat Res Lab, Dept Anesthesia & Crit Care, 55 Fruit St,Clin 3, Boston, MA 02114 USA. EM barbieri@neurostat.mgh.harvard.edu OI Barbieri, Riccardo/0000-0001-9381-3833 FU NIDA NIH HHS [DA-015644]; NIMH NIH HHS [MH-59733, MH-61637] NR 58 TC 93 Z9 93 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JAN PY 2005 VL 288 IS 1 BP H424 EP H435 DI 10.1152/ajpheart.00482.2003 PG 12 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 879QT UT WOS:000225733000057 PM 15374824 ER PT J AU Ikonomidis, JS Hendrick, JW Parkhurst, AM Herron, AR Escobar, PG Dowdy, KB Stroud, RE Hapke, E Zile, MR Spinale, FG AF Ikonomidis, JS Hendrick, JW Parkhurst, AM Herron, AR Escobar, PG Dowdy, KB Stroud, RE Hapke, E Zile, MR Spinale, FG TI Accelerated LV remodeling after myocardial infarction in TIMP-1-deficient mice: effects of exogenous MMP inhibition SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE transgenic model; heart failure; myocardial hypertrophy ID MATRIX-METALLOPROTEINASE INHIBITION; SMOOTH-MUSCLE-CELLS; HEART-FAILURE; OXIDATIVE STRESS; TISSUE INHIBITOR; EXTRACELLULAR-MATRIX; TARGETED DELETION; NITRIC-OXIDE; DYSFUNCTION; MATRIX-METALLOPROTEINASE-9 AB Alterations in matrix metalloproteinases ( MMPs) and tissue inhibitors of MMPs (TIMPs) have been implicated in adverse left ventricular (LV) remodeling after myocardial infarction (MI). However, the direct mechanistic role of TIMPs in the post-MI remodeling process has not been completely established. The goal of this project was to define the effects of altering endogenous MMP inhibitory control through combined genetic and pharmacological approaches on post-MI remodeling in mice. This study examined the effects of MMP inhibition (MMPi) with PD-166793 ( 30 mg.kg(-1).day(-1)) on LV geometry and function (conductance volumetry) after MI in wild-type (WT) mice and mice deficient in the TIMP-1 gene [TIMP-1 knockout (TIMP1-KO)]. At 3 days after MI (coronary ligation), mice were randomized into four groups: WT-MI/MMPi (n = 10), TIMP1-KO-MI/MMPi (n = 10), WT-MI (n = 22), and TIMP1-KO-MI (n = 23). LV end-diastolic volume (EDV) and ejection fraction were determined 14 days after MI. Age-matched WT (n = 20) and TIMP1-KO (n = 28) mice served as reference controls. LVEDV was similar under control conditions in WT and TIMP1-KO mice (36 +/- 2 and 40 +/- 2 mul, respectively) but was greater in TIMP1-KO-MI than in WT-MI mice (48 +/- 2 vs. 61 +/- 5 mul, P < 0.05). LVEDV was reduced from MI-only values in WT-MI/MMPi and TIMP1-KO-MI/MMPi mice (42 &PLUSMN; 2 and 36 &PLUSMN; 2 μl, respectively, P < 0.05) but was reduced to the greatest degree in TIMP1-KO mice (P < 0.05). LV ejection fraction was reduced in both groups after MI and increased in TIMP1-KO-MI/MMPi, but not in WT-MI/MMPi, mice. These unique results demonstrated that myocardial TIMP-1 plays a regulatory role in post-MI remodeling and that the accelerated myocardial remodeling induced by TIMP-1 gene deletion can be pharmacologically "rescued" by MMP inhibition. These results define the importance of local endogenous control of MMP activity with respect to regulating LV structure and function after MI. C1 Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Spinale, FG (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Rm 625,Strom Thurmond Res Bldg,770 MUSC Complex,1, Charleston, SC 29425 USA. FU NCRR NIH HHS [P20 RR-16434]; NHLBI NIH HHS [HL-59165, P01 HL-48788-08] NR 41 TC 78 Z9 82 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JAN PY 2005 VL 288 IS 1 BP H149 EP H158 DI 10.1152/ajpheart.00370.2004 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 879QT UT WOS:000225733000024 PM 15598866 ER PT J AU Nemoto, S Razeghi, P Ishiyama, M De Freitas, G Taegtmeyer, H Carabello, BA AF Nemoto, S Razeghi, P Ishiyama, M De Freitas, G Taegtmeyer, H Carabello, BA TI PPAR-gamma agonist rosiglitazone ameliorates ventricular dysfunction in experimental chronic mitral regurgitation SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE valvular heart disease; function; lipid accumulation ID CONGESTIVE-HEART-FAILURE; VOLUME-OVERLOAD HYPERTROPHY; IDIOPATHIC DILATED CARDIOMYOPATHY; BETA-ADRENERGIC-BLOCKADE; FATTY-ACID OXIDATION; CONTRACTILE DYSFUNCTION; GENE-EXPRESSION; DOUBLE-BLIND; TRIAL; BISOPROLOL AB Previously we reported that the beneficial effects of beta-adrenergic blockade in chronic mitral regurgitation (MR) were in part due to induction of bradycardia, which obviously affects myocardial energy requirements. From this observation we hypothesized that part of the pathophysiology of MR may involve faulty energy substrate utilization, which in turn might lead to potentially harmful lipid accumulation as observed in other models of heart failure. To explore this hypothesis, we measured triglyceride accumulation in the myocardia of dogs with chronic MR and then attempted to enhance myocardial metabolism by chronic administration of the peroxisome proliferator-activated receptor ( PPAR)-gamma agonist rosiglitazone. Cardiac tissues were obtained from three groups of dogs that included control animals, dogs with MR for 3 mo without treatment, and dogs with MR for 6 mo that were treated with rosiglitazone ( 8 mg/day) for the last 3 mo of observation. Hemodynamics and contractile function (end-systolic stress-strain relationship, as measured by K index) were assessed at baseline, 3 mo of MR, and 6 mo of MR ( 3 mo of the treatment). Lipid accumulation in MR ( as indicated by oil red O staining score and TLC analysis) was marked and showed an inverse correlation with the left ventricular (LV) contractility. LV contractility was significantly restored after PPAR therapy (K index: therapy, 3.01 +/- 0.11*; 3 mo MR, 2.12 +/- 0.34; baseline, 4.01 +/- 0.29; ANOVA, P = 0.038; * P < 0.05 vs. 3 mo of MR). At the same time, therapy resulted in a marked reduction of intramyocyte lipid. We conclude that 1) chronic MR leads to intramyocyte myocardial lipid accumulation and contractile dysfunction, and 2) administration of the PPAR-γ agonist rosiglitazone ameliorates MR-induced LV dysfunction accompanied by a decline in lipid content. C1 Houston Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Texas, Sch Med, Dept Internal Med, Div Cardiol, Houston, TX USA. RP Carabello, BA (reprint author), Houston Vet Affairs Med Ctr, Dept Med, 111MCL,2002 Holcombe Blvd, Houston, TX 77030 USA. EM blaseanthony.carabello@med.va.gov NR 33 TC 30 Z9 32 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JAN PY 2005 VL 288 IS 1 BP H77 EP H82 DI 10.1152/ajpheart.01246.2003 PG 6 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 879QT UT WOS:000225733000013 PM 15345480 ER PT J AU Wiegand, LC Warfield, SK Levitt, JJ Hirayasu, Y Salisbury, DF Heckers, S Bouix, S Schwartz, D Spencer, M Dickey, CC Kikinis, R Jolesz, FA McCarley, RW Shenton, ME AF Wiegand, LC Warfield, SK Levitt, JJ Hirayasu, Y Salisbury, DF Heckers, S Bouix, S Schwartz, D Spencer, M Dickey, CC Kikinis, R Jolesz, FA McCarley, RW Shenton, ME TI An in vivo MRI study of prefrontal cortical complexity in first-episode psychosis SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID FIRST-EPISODE SCHIZOPHRENIA; PLANUM TEMPORALE ASYMMETRY; CEREBRAL ASYMMETRY; COGNITIVE FUNCTION; BLADDER WALL; CT-SCANS; CORTEX; LOBE; GYRIFICATION; POSTMORTEM AB Objective: The purpose of this study was to investigate abnormalities in the surface complexity of the prefrontal cortex and in the hemispheric asymmetry of cortical complexity in first-episode patients with schizophrenia. Method: An estimate of the surface complexity of the prefrontal cortex was derived from the number of voxels along the boundary between gray matter and CSF. Magnetic resonance imaging scans were acquired from patients with a first episode of schizophrenia (N=17), patients with a first episode of affective psychosis (N=17), and normal comparison subjects (N=17), age-matched within a narrow age range (18-29 years). This study group was the focus of a previous study that showed lower prefrontal cortical volume in patients with schizophrenia. Results: Prefrontal cortical complexity was not significantly different among the groups. However. the schizophrenia patients differed significantly from the normal comparison subjects in asymmetry, with the schizophrenia patients showing less left-greater-than-right asymmetry in cortical complexity than the comparison subjects. Conclusions: An abnormal pattern of asymmetry in the prefrontal cortex of first-episode patients with schizophrenia provides evidence for a neurodevelopmental mechanism in the etiology of schizophrenia. C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton Div,Dept Psychiat, Brockton, MA 02301 USA. VA Boston Healthcare Syst, Brockton Div, Clin Neurosci Div, Neurosci Lab, Brockton, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Surg Planning Lab, MRI Div, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Psychot Disorders Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Psychiat Neuroimaging Res Grp, Boston, MA 02114 USA. Kyorin Univ, Sch Med, Dept Psychiat, Tokyo, Japan. McLean Hosp, Cognit Neurosci Lab, Belmont, MA 02178 USA. Brigham & Womens Hosp, Brigham Behav Neurol Grp, Boston, MA 02115 USA. RP McCarley, RW (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton Div,Dept Psychiat, 940 Belmont St,116A, Brockton, MA 02301 USA. EM robert_mccarley@hms.harvard.edu; martha_shenton@ahms.harvard.edu RI Heckers, Stephan/F-3051-2010; Warfield, Simon/B-3352-2009; McCarley, Robert/N-5562-2014; OI Heckers, Stephan/0000-0003-3601-9910; McCarley, Robert/0000-0001-5705-7495; Warfield, Simon/0000-0002-7659-3880 FU NCI NIH HHS [R01 CA086879, P01 CA-67165, P01 CA067165, R01 CA-83879]; NCRR NIH HHS [P41 RR-13218, P41 RR013218, R01 RR-11747]; NIMH NIH HHS [K02 MH-01110, K02 MH001110, K02 MH001110-10, R01 MH-40799, R01 MH-50740, R01 MH040799, R01 MH050740, R01 MH050740-10] NR 43 TC 28 Z9 28 U1 1 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2005 VL 162 IS 1 BP 65 EP 70 DI 10.1176/appi.ajp.162.1.65 PG 6 WC Psychiatry SC Psychiatry GA 886VW UT WOS:000226262000012 PM 15625203 ER PT J AU Lenze, EJ Mulsant, BH Shear, MK Dew, MA Miller, MD Pollock, BG Houck, P Tracey, B Reynolds, CF AF Lenze, EJ Mulsant, BH Shear, MK Dew, MA Miller, MD Pollock, BG Houck, P Tracey, B Reynolds, CF TI Efficacy and tolerability of citalopram in the treatment of late-life anxiety disorders: Results from an 8-week randomized, placebo-controlled trial SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ELIMINATION HALF-LIFE; BENZODIAZEPINE USE; COMORBID ANXIETY; CLINICAL-TRIALS; RATING-SCALE; DEPRESSION; COMMUNITY; RISK; POPULATION; PREVALENCE AB Objective: Anxiety disorders are highly prevalent in elderly persons. However, to date, the efficacy of selective serotonin reuptake inhibitors (SSRIs) for the treatment of anxiety disorders in this age group has not been established. Method: Thirty-four participants age 60 and older with a DSM-IV anxiety disorder (mainly generalized anxiety disorder) and a Hamilton Anxiety Rating Scale score of 17 or higher were randomly assigned under double-blind conditions to either citalopram or placebo. Response was defined as a score of 1 (very much improved) or 2 (much improved) on the Clinical Global improvement scale or a 50% reduction in the Hamilton anxiety scale score. Response and side effects with citalopram and placebo were compared by using chi-square tests and linear modeling. Results: Eleven (65%) of the 17 citalopram-treated participants responded by 8 weeks, versus four (24%) of the 17 placebo-treated participants. The most common and problematic side effect in the citalopram group was sedation. Conclusions: The authors believe this to be the first prospective controlled study to test the efficacy of an SSRI in the management of anxiety disorders among the elderly. These results support the efficacy of citalopram in late-life anxiety disorders. They need to be replicated in a larger study group. C1 Univ Pittsburgh, Sch Med, Dept Psychiat, Intervent Res Ctr Late Life Mood Disorders, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Lenze, EJ (reprint author), Western Psychiat Inst & Clin, 3811 OHara St,Rm E1124, Pittsburgh, PA 15213 USA. EM lenzeej@msx.upmc.edu FU NIMH NIH HHS [P30 MH-52247, K23 MH-64196, MH-65416] NR 36 TC 46 Z9 46 U1 1 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2005 VL 162 IS 1 BP 146 EP 150 DI 10.1176/appi.ajp.162.1.146 PG 5 WC Psychiatry SC Psychiatry GA 886VW UT WOS:000226262000022 PM 15625213 ER PT J AU Wirshing, DA Sergi, MJ Mintz, J AF Wirshing, DA Sergi, MJ Mintz, J TI A videotape intervention to enhance the informed consent process for medical and psychiatric treatment research SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 09-14, 2001 CL WAIKOLOA, HI SP Amer Coll Neuropsychopharmacol AB Objective: This study evaluated a brief educational video designed to enhance the informed consent process for people with serious mental and medical illnesses who are considering participating in treatment research. Method: Individuals with schizophrenia who were being recruited for ongoing clinical trials, medical patients without self-reported psychiatric comorbidity, and university undergraduates were randomly assigned to view either a highly structured instructional videotape about the consent process in treatment research or a control videotape that presented only general information about bioethical issues in human research. Knowledge about informed consent was measured before and after viewing. Results: Viewing the experimental videotape resulted in larger gains in knowledge about informed consent. Standardized effect sizes were large in all groups. Conclusions: The videotape was thus an effective teaching tool across diverse populations, ranging from individuals with severe chronic mental illness to university undergraduates. C1 Greater Los Angeles VA Healthcare Syst, Dept Psychiat, Los Angeles, CA 90073 USA. Calif State Univ Northridge, Dept Psychol, Northridge, CA 91330 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. RP Mintz, J (reprint author), Greater Los Angeles VA Healthcare Syst, Dept Psychiat, 11301 Wilshire Blvd,116AR, Los Angeles, CA 90073 USA. EM jmintz@ucla.edu FU NIMH NIH HHS [R01-MH-68100-02] NR 8 TC 28 Z9 30 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2005 VL 162 IS 1 BP 186 EP 188 DI 10.1176/appi.ajp.162.1.186 PG 3 WC Psychiatry SC Psychiatry GA 886VW UT WOS:000226262000030 PM 15625221 ER PT J AU Walensky, RP Losina, E Malatesta, L Barton, GE O'Connor, CA Skolnik, PR Hall, JM McGuire, JF Freedberg, KA AF Walensky, RP Losina, E Malatesta, L Barton, GE O'Connor, CA Skolnik, PR Hall, JM McGuire, JF Freedberg, KA TI Effective HIV case identification through routine HIV screening at urgent care centers in Massachusetts SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article AB Think HIV offered HIV counseling, testing, and referral to patients at 4 Massachusetts urgent care centers from January to September 2002. We compared the positive diagnosis yield of Think HIV with that of state-funded HIV counseling, testing, and referral sites. Think HIV found an HIV prevalence of 2.0% compared with 1.9% identified by self-referral testing. Urgent care center-based routine HIV counseling, testing, and referral programs are feasible, can have high positive diagnosis yields, and should be the standard of care in high HIV prevalence areas. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. Massachusetts Dept Publ Hlth, AIDS Bur, Boston, MA USA. Boston Med Ctr, Boston, MA USA. RP Walensky, RP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM rwalensky@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU NIAID NIH HHS [K25 AI 50436, P30 AI042851, K25 AI050436, K23 AI 01794, P30 AI 42851, K23 AI001794]; NIMH NIH HHS [R01 MH065869, R01 MH 65869-01] NR 5 TC 44 Z9 44 U1 0 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2005 VL 95 IS 1 BP 71 EP 73 DI 10.2105/AJPH.2003.031310 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 884SW UT WOS:000226107500014 PM 15623861 ER PT J AU Rigotti, NA Moran, SE Wechsler, H AF Rigotti, NA Moran, SE Wechsler, H TI US college students' exposure to tobacco promotions: Prevalence and association with tobacco use SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID YOUNG-ADULTS; INDUSTRY DOCUMENTS; NATIONAL-SURVEY; BINGE-DRINKING; SMOKING; HEALTH; BAR AB Objectives. We assessed young adults' exposure to the tobacco industry marketing strategy of sponsoring social events at bars, nightclubs, and college campuses. Methods. We analyzed data from the 2001 Harvard College Alcohol Study, a random sample of 10904 students enrolled in 119 nationally representative 4-year colleges and universities. Results. During the 2000-2001 school year, 8.5% of respondents attended a bar, nightclub, or campus social event where free cigarettes were distributed. Events were reported by students attending 118 of the 119 schools (99.2%). Attendance was associated with a higher student smoking prevalence after we adjusted for demographic factors, alcohol use, and recent bar/nightclub attendance. This association remained for students who did not smoke regularly before 19 years of age but not for students who smoked regularly by 19 years of age. Conclusions. Attendance at a tobacco industry-sponsored event at a bar, nightclub, or campus party was associated with a higher smoking prevalence among college students. Promotional events may encourage the initiation or the progression of tobacco use among college students who are not smoking regularly when they enter college. C1 Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Div Gen Med, 50 Staniford St,9th Fl, Boston, MA 02114 USA. EM nrigotti@partners.org FU NHLBI NIH HHS [HL 04440, K24 HL004440] NR 27 TC 87 Z9 91 U1 1 U2 5 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2005 VL 95 IS 1 BP 138 EP 144 DI 10.2105/AJPH.2003.026054 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 884SW UT WOS:000226107500027 PM 15623874 ER PT J AU Digamurthy, SR Sharma, A Wottram, C McGinnis, PJ Shepard, JO AF Digamurthy, SR Sharma, A Wottram, C McGinnis, PJ Shepard, JO TI Computer-aided diagnosis (CAD) for nodule detection in diffuse lung disease SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 1 EP 1 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800004 ER PT J AU Holalkere, NS Sahani, D Blake, M Setty, BN Hahn, PF Mueller, PR AF Holalkere, NS Sahani, D Blake, M Setty, BN Hahn, PF Mueller, PR TI Impact of liver MR imaging following MDCT in the management of focal liver lesions detected in patients with known primary malignancy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 9 EP 9 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800033 ER PT J AU Saokar, A Saksena, M Hahn, PF Mueller, PR Harisinghani, M AF Saokar, A Saksena, M Hahn, PF Mueller, PR Harisinghani, M TI Signal intensity drop on ferumoxtran 10-enhanced MR lymphangiography: Where should the threshold lie? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 16 EP 16 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800061 ER PT J AU Boriskin, HS Schweitzer, ME Keller, MS Jaramillo, D AF Boriskin, HS Schweitzer, ME Keller, MS Jaramillo, D TI Imaging of pediatric scoliosis: the referring physician's perspective SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 NYU, Med Ctr, Hosp Joint Dis, New York, NY 10016 USA. Alfred I duPont Hosp Children, Wilmington, DE USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 19 EP 20 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800075 ER PT J AU Sahani, DV Setty, B Kadavigere, RV Blake, M Fischman, AJ Mueller, PR AF Sahani, DV Setty, B Kadavigere, RV Blake, M Fischman, AJ Mueller, PR TI Extra-abdominal metastases in colorectal cancer: Is whole body PET/PET-CT justified? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 22 EP 22 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800085 ER PT J AU Kalva, SP Sahani, DV Desai, H AF Kalva, SP Sahani, DV Desai, H TI Performance of 16-slice multidetector CT angiography of renal arteries at various kilovoltage settings in living kidney donors: Impact on the image quality and radiation dose SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 24 EP 25 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800095 ER PT J AU Kalra, MK Rizzo, SMR Maher, MM Blake, MA Toth, TL Saini, SS AF Kalra, MK Rizzo, SMR Maher, MM Blake, MA Toth, TL Saini, SS TI A study of weight-based optimization of scanning protocol for Z-axis modulation technique in 16-slice MDCT scanning of the abdomen and pelvis in 245 patients SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Milan, I-20122 Milan, Italy. GE Med Syst, Waukesha, WI USA. Emory Univ, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 28 EP 28 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800110 ER PT J AU Rizzo, S Kalra, MK Dalal, T Schmidt, B Suess, C Flohr, T Blake, MA Saini, S AF Rizzo, S Kalra, MK Dalal, T Schmidt, B Suess, C Flohr, T Blake, MA Saini, S TI Comparison of angular and XYZ-axes automatic tube current modulation techniques with constant tube current CT scanning of the abdomen and pelvis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Milan, I-20122 Milan, Italy. Siemens Med Solut, Forccheim, Germany. Emory Univ, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 29 EP 29 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800114 ER PT J AU Rizzo, SMR Kalra, MK Blake, MA Maher, MM Schmidt, B Raupach, R Saini, SS AF Rizzo, SMR Kalra, MK Blake, MA Maher, MM Schmidt, B Raupach, R Saini, SS TI Effect of new non-linear three-dimensional noise reduction filters on image quality and lesion characteristics to improve image quality of low-dose abdominal CT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Milan, I-20122 Milan, Italy. Siemens Med Solut, Forchheim, Germany. Emory Univ, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 29 EP 29 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800111 ER PT J AU Singh, AK AF Singh, AK TI Neoplastic iliopsoas masses: Detection and implications on abdominal CT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 30 EP 30 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800117 ER PT J AU Rastogi, N Sahani, D Blake, M Ko, D AF Rastogi, N Sahani, D Blake, M Ko, D TI Can MPVR and 3D images alone from 16 slice MDCT be used for comprehensive evaluation of renal donors? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Dept Radiol & Transplantat Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 33 EP 33 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800129 ER PT J AU Kuester, LM Fischman, AJ Fan, CM Halpern, E Aquino, SL AF Kuester, LM Fischman, AJ Fan, CM Halpern, E Aquino, SL TI Lipomatous hypertrophy of the interatrial septum: Incidence and significant patterns on CT and FDG-PET SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 40 EP 40 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800154 ER PT J AU Singh, AK Apkinar, E Lawrason, JN Sacknoff, R Novelline, RA AF Singh, AK Apkinar, E Lawrason, JN Sacknoff, R Novelline, RA TI Thoracic and lumbar spine fractures: Utility of sagittal and coronal reconstructions SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 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. PY 2005 VL 184 IS 4 SU S BP 41 EP 41 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800159 ER PT J AU Albritton, RL AF Albritton, RL TI Comparison of multidetector chest CT and the plain film chest radiograph in 563 trauma patients: Evidence for the routine use of chest CT in the multiple trauma patient SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 42 EP 42 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800162 ER PT J AU Dalal, TA Kalra, MK Rizzo, S Maher, MM Schmidt, B Suess, C Saini, S AF Dalal, TA Kalra, MK Rizzo, S Maher, MM Schmidt, B Suess, C Saini, S TI New technique to avoid an increase in CT radiation dose from metallic prostheses with automatic tube current modulation: Phantom and patient study SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA USA. Siemens Med Solut, Forchheim, Germany. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 43 EP 43 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800167 ER PT J AU Joshi, M Sahani, D Ko, D Elias, N Blake, M AF Joshi, M Sahani, D Ko, D Elias, N Blake, M TI Study to assess how a simplified PMRIs can serve as an alternative to an advanced PMRI method to view renal anatomy for living kidney donors using 16-slice CT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 GE Co, Healthcare Technol, Waukesha, WI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 44 EP 44 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800173 ER PT J AU Lee, SI Dreyer, KJ Saokar, A Thrall, JH Hahn, PF AF Lee, SI Dreyer, KJ Saokar, A Thrall, JH Hahn, PF TI Radiologist recommendation to repeat exams: Is it a significant factor in the growing volume of high cost imaging? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 44 EP 44 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800171 ER PT J AU Rizzo, S Kalra, MK Maher, MM Halpern, EF Bellomi, E Saini, SS AF Rizzo, S Kalra, MK Maher, MM Halpern, EF Bellomi, E Saini, SS TI Path to publication of original research articles in major peer-reviewed radiology journals: An audit of time from initial submission to publication SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Milan, Milan, Italy. Emory Univ, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 44 EP 44 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800170 ER PT J AU Dalal, T Rizzo, SMR Kalra, MK Schmidt, B Suess, C Flohr, T Blake, MA Saini, S AF Dalal, T Rizzo, SMR Kalra, MK Schmidt, B Suess, C Flohr, T Blake, MA Saini, S TI New technique to avoid an increase in CT radiation dose from metallic prostheses with automatic tube current modulation: Phantom and patient study SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Milan, Milan, Italy. Siemens Med Solut, Forchheim, Germany. Emory Univ, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 51 EP 51 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800196 ER PT J AU Saokar, A Sahani, D Fernandez-del-Castillo, C Brugge, W Mueller, P AF Saokar, A Sahani, D Fernandez-del-Castillo, C Brugge, W Mueller, P TI Small (< 3 centimeters) pancreatic cysts: Are they ever malignant? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 52 EP 53 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800203 ER PT J AU Singh, AK AF Singh, AK TI CT findings following cholecystostomy catheter placement SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 54 EP 54 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800209 ER PT J AU Kalva, SP Sahani, DV Blake, MA Willette, CG Fischmann, AJ AF Kalva, SP Sahani, DV Blake, MA Willette, CG Fischmann, AJ TI CT perfusion as an Imaging marker for assessing response of rectal cancer to chemoradiation: Comparison with FDG-PET SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 55 EP 55 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800213 ER PT J AU Samir, AE Brooks, DM Orr, B Hall, C Wallace, A Moorhouse, A AF Samir, AE Brooks, DM Orr, B Hall, C Wallace, A Moorhouse, A TI A novel laser guidance device for ultrasound-guided interventional procedures SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. Austin Hlth, Dept Radiol, Melbourne, Vic, Australia. Swinburne Univ Technol, Melbourne, Vic, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 59 EP 59 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800228 ER PT J AU Uppot, RN Guimaraes, AS Hahn, PF Gervais, DA Arellano, RS AF Uppot, RN Guimaraes, AS Hahn, PF Gervais, DA Arellano, RS TI Abscesses requiring multi-catheter drainage at presentation: How successful are we? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 60 EP 60 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800229 ER PT J AU Rahman, AM Booth, S Ferencik, M Brady, TJ Siebert, U Hoffmann, U AF Rahman, AM Booth, S Ferencik, M Brady, TJ Siebert, U Hoffmann, U TI Calcium concentration of individual coronary calcified plaques as measured by multidetector row computed tomography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Tufts Univ, Dept Nutr, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 66 EP 66 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800254 ER PT J AU Teague, SD Abbarra, S Pena, A Cury, RC AF Teague, SD Abbarra, S Pena, A Cury, RC TI Myocardial bridges: Prevalence on multi-detector cardiac computed tomography examinations SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 67 EP 67 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800257 ER PT J AU Desai, JC Abbara, S Nieman, K Reddy, V AF Desai, JC Abbara, S Nieman, K Reddy, V TI Mapping epicardial fat using 16-slice multidetector CT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 74 EP 75 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800289 ER PT J AU Chen, L Suh, RD Barack, BM Ratib, O AF Chen, L Suh, RD Barack, BM Ratib, O TI Plain film diagnosis of congenital and acquired heart disease in adults SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. W Los Angeles Vet Adm Hosp, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 81 EP 81 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800320 ER PT J AU Sachdev, KJ Brady, T Hoffmann, U AF Sachdev, KJ Brady, T Hoffmann, U TI MDCT and screening for CAD SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Wake Forest Univ, Winston Salem, NC 27109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 81 EP 81 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800322 ER PT J AU Rahman, AM Booth, S Mezrich, J Brady, TJ Siebert, U Hoffmann, U AF Rahman, AM Booth, S Mezrich, J Brady, TJ Siebert, U Hoffmann, U TI Interobserver variability of coronary artery calcium measurements in individual coronary calcified plaques as detected by multidetector row computed tomography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Tufts Univ, Dept Nutr, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 82 EP 82 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800326 ER PT J AU Miller, JC Lee, SI Speroni, NJ Thrall, JH AF Miller, JC Lee, SI Speroni, NJ Thrall, JH TI Promoting efficient and effective utilization of radiology resources through an electronic newsletter for community physicians SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 83 EP 84 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800334 ER PT J AU Singh, AK AF Singh, AK TI Ocular trauma: CT imaging SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 85 EP 85 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800340 ER PT J AU Kalva, SP Sahani, DV Chen, J Kadavigere, R AF Kalva, SP Sahani, DV Chen, J Kadavigere, R TI Current and emerging role of ultrasound contrast agents in liver imaging SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 89 EP 89 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800359 ER PT J AU Sahani, DV Saokar, A Brugge, WR Kadavigere, R Ronald, AS Mueller, PR AF Sahani, DV Saokar, A Brugge, WR Kadavigere, R Ronald, AS Mueller, PR TI Established and emerging interventions in the management of pancreatic cysts SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 92 EP 92 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800373 ER PT J AU Sahani, DV Mueller, PR Barkley, JM AF Sahani, DV Mueller, PR Barkley, JM TI CT pancreatography: An emerging modality in the evaluation of pancreatic disorders SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 95 EP 95 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800386 ER PT J AU Setty, BN Sahani, DV Blake, M Holalkere, N Fischman, AJ Arellano, RS Mueller, PR AF Setty, BN Sahani, DV Blake, M Holalkere, N Fischman, AJ Arellano, RS Mueller, PR TI Role of PET-CT in planning various interventional procedures in abdominal malignancies SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 95 EP 95 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800388 ER PT J AU Setty, BN Sahani, DV Blake, M Holalkere, N Fischman, AJ Mueller, PR AF Setty, BN Sahani, DV Blake, M Holalkere, N Fischman, AJ Mueller, PR TI Current and emerging role of PET-CT in the diagnosis and management of colorectal cancer SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 95 EP 95 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800387 ER PT J AU Setty, BN Sahani, DV Blake, M Holalkere, N Fischman, AJ Aquino, SL Mueller, PR AF Setty, BN Sahani, DV Blake, M Holalkere, N Fischman, AJ Aquino, SL Mueller, PR TI Lymphadenopathy on PET-CT: A pictorial review SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 96 EP 96 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800390 ER PT J AU Uppot, RN Sahani, DV Blake, MA Lee, S Mueller, PR AF Uppot, RN Sahani, DV Blake, MA Lee, S Mueller, PR TI How coronal reformatted images on 16 slice CT can aid in detection and staging of abdominal tumors SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 97 EP 98 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800399 ER PT J AU Rastogi, N Sahani, D Grocela, J Uppot, R Ronald, A Mueller, P AF Rastogi, N Sahani, D Grocela, J Uppot, R Ronald, A Mueller, P TI Evaluation of small renal cancers with multislice CT or MRI: Implications on nephron-sparing surgery SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 102 EP 102 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800421 ER PT J AU Rastogi, N Uppot, R Sahani, D Grocela, J Ronald, A Mueller, P AF Rastogi, N Uppot, R Sahani, D Grocela, J Ronald, A Mueller, P TI Role of multi-detector computed tomography in evaluation of microscopic hematuria: Recent trends SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 102 EP 103 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800423 ER PT J AU Slattery, JM Blake, MA Kalra, MK Fischman, AJ Mueller, PR Boland, GW AF Slattery, JM Blake, MA Kalra, MK Fischman, AJ Mueller, PR Boland, GW TI Characterization of adrenal lesions with F-18-FDG PET/CT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 102 EP 102 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800422 ER PT J AU McKernan, MG Blake, MA Sahani, D Fischman, AJ Desai, HJ Mueller, PR AF McKernan, MG Blake, MA Sahani, D Fischman, AJ Desai, HJ Mueller, PR TI Non-neoplastic sources of FDG-PET activity on oncologic PET/CT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 15-20, 2005 CL New Orleans, LA SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2005 VL 184 IS 4 SU S BP 126 EP 126 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920VH UT WOS:000228717800529 ER PT J AU Fan, CM Fischman, AJ Kwek, BH Abbara, S Aquino, SL AF Fan, CM Fischman, AJ Kwek, BH Abbara, S Aquino, SL TI Lipomatous hypertrophy of the interatrial septum: Increased uptake on FDG PET SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article AB OBJECTIVE. The objective of our study was to evaluate FDG uptake in patients with cardiac lipomatous hypertrophy of the interatrial septum (LIES). CONCLUSION. Increased FDG uptake occurs in LHIS, a benigen fatty infiltration of the interatrial septurn. Increased uptake in the right heart on FDG PET warrants correlation with additional imaging to assess for LHIS and avoid false interpretation of malignancy. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Aquino, SL (reprint author), Massachusetts Gen Hosp, Dept Radiol, GRB 290,55 Fruit St, Boston, MA 02114 USA. NR 12 TC 30 Z9 30 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 JAN PY 2005 VL 184 IS 1 BP 339 EP 342 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 890JQ UT WOS:000226507900060 PM 15615998 ER PT J AU Li, GA DeFrate, LE Park, SE Gill, TJ Rubash, HE AF Li, GA DeFrate, LE Park, SE Gill, TJ Rubash, HE TI In vivo articular cartilage contact kinematics of the knee - An investigation using dual-orthogonal fluoroscopy and magnetic resonance image-based computer models SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE cartilage; in vivo knee kinematics; knee biomechanics; magnetic resonance imaging (MRI) ID JOINT; OSTEOARTHRITIS; MECHANICS; MOVEMENT; FLEXION; MOTION AB Background: Quantifying the in vivo cartilage contact mechanics of the knee may improve our understanding of the mechanisms of joint degeneration and may therefore improve the surgical repair of the joint after injury. Objective: To measure tibiofemoral articular cartilage contact kinematics during in vivo knee flexion. Study Design: Descriptive laboratory study. Methods: Orthogonal fluoroscopic images and magnetic resonance image-based computer models were used to measure the motion of the cartilage contact points during a quasi-static lunge in 5 human subjects. Results: On the tibial plateau, the contact point moved in both the anteroposterior and the mediolateral directions during knee flexion. On the medial tibial plateau, flexion angle did not have a statistically significant effect on the location of the contact points. The total translation of the contact point from full extension to 90 degrees of flexion was less than 1.5 mm in the anteroposterior direction, whereas the translation in the mediolateral direction was more than 5.0 mm. In the anteroposterior direction, the contact points were centered on the medial tibial plateau. On the lateral tibial plateau, there was a statistically significant difference between the location of the contact point at full extension and the locations of the contact points at other flexion angles in the anteroposterior direction. No significant difference was detected between the location of the contact points at other flexion angles. The overall range of contact point motion was about 9.0 mm in the anteroposterior direction and about 4.0 mm in the mediolateral direction. The contact points were primarily on the inner half of the medial and lateral tibial plateaus (the half closest to the tibial spine). The contact points on both femoral condyles were also on the inner half of the condyles (near the condylar notch). Conclusions: The tibiofemoral contact points move in 3 dimensions during weightbearing knee flexion. The medial tibiofemoral contact points remained within the central portion of the tibial plateau in the anteroposterior direction. Both the medial and lateral tibiofemoral contact points were located on the inner portions of the tibial plateau and femoral condyles (close to the tibial spine), indicating that the tibial spine may play an important role in knee stability. Clinical Relevance: The results of this study may provide important insight as to the mechanisms contributing to the development of osteoarthritis after ligament injuries. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02114 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, GA (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 NR 17 TC 111 Z9 122 U1 1 U2 15 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 JAN PY 2005 VL 33 IS 1 BP 102 EP 107 DI 10.1177/036354650235577 PG 6 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 910IB UT WOS:000227923300012 PM 15611005 ER PT J AU Kotton, CN Ryan, ET Fishman, JA AF Kotton, CN Ryan, ET Fishman, JA TI Prevention of infection in adult travelers after solid organ transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Review DE travel medicine; organ transplant; vaccination ID YELLOW-FEVER VACCINE; HEPATITIS-A VACCINE; LIVER-TRANSPLANTATION; POLYSACCHARIDE VACCINE; INFLUENZA VACCINE; B-VACCINE; RECIPIENTS; IMMUNOGENICITY; IMMUNIZATION; SAFETY AB Increasing numbers of solid organ transplant recipients are traveling to the developing world. Many of these individuals either do not seek or do not receive optimal medical care prior to travel. This review considers risks of international travel to adult solid organ transplant recipients and the use of vaccines and prophylactic agents in this population. C1 Massachusetts Gen Hosp, Div Infect Dis, Transplant Infect Dis & Compromised Host Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Travelers Advice & Immunizat Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Kotton, CN (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Transplant Infect Dis & Compromised Host Program, Boston, MA 02114 USA. EM ckotton@partners.org NR 37 TC 44 Z9 45 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2005 VL 5 IS 1 BP 8 EP 14 DI 10.1111/j.1600-6143.2004.00708.x PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA 880LF UT WOS:000225790600002 PM 15636606 ER PT J AU Delmonico, FL Sheehy, E Marks, WH Baliga, P McGowan, JJ Magee, JC AF Delmonico, FL Sheehy, E Marks, WH Baliga, P McGowan, JJ Magee, JC TI Organ donation and utilization in the United States, 2004 SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE deceased donors; donation rates; living donors; OPOs; organ donation; organ procurement; SRTR ID LIVER-TRANSPLANTATION; GRAFT-SURVIVAL; DONOR; ATTITUDES; KIDNEY; GLOMERULOSCLEROSIS; KNOWLEDGE; AMERICANS; ALTRUISM; PATIENT AB This article discusses issues directly related to the organ donation process, including donor consent, donor medical suitability, non-recovery of organs, organs recovered but not transplanted, expanded criteria donors (ECD), and donation after cardiac death (DCD). The findings and topics covered have important implications for how to evaluate and share best practices of organ donation as implemented by organ procurement organizations (OPOs) and major donor hospitals in the same donation service areas (DSAs). In 2002 and 2003, US hospitals referred more than one million deaths or imminent deaths to the OPOs of their DSA. Referrals increased by nearly 10% from 2002 to 2003 (1,022,280 to 1,121,392). Donor consents have increased by about 5% and the number of total deceased donors has risen from 6,187 to 6,455. Since multiple organs are recovered from most donors, this increase allowed more than 500 additional wait-listed candidates to receive an organ transplant than in the prior year. Non-traditional donor sources have experienced a large rate of increase; in 2003 the number of ECD kidney donors increased by 8% and the number of DCD donors increased by 43%, from 189 donors in year 2002 to 271 donors in 2003. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Assoc Organ Procurement Org, Newton, MA USA. Swedish Med Ctr, Seattle, WA USA. Med Univ S Carolina, Med Ctr, Charleston, SC 29425 USA. Univ Renal Res & Educ Assoc, Sci Registry Transplant Recipients, Ann Arbor, MI USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Delmonico, FL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM francis_delmonico@neob.org NR 37 TC 51 Z9 58 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2005 VL 5 IS 4 BP 862 EP 873 DI 10.1111/j.1600-6135.2005.00832.x PN 2 PG 12 WC Surgery; Transplantation SC Surgery; Transplantation GA 904YQ UT WOS:000227534900004 PM 15760414 ER PT J AU Nesterov, EE Skoch, J Hyman, BT Klunk, WE Bacskai, BJ Swager, TM AF Nesterov, EE Skoch, J Hyman, BT Klunk, WE Bacskai, BJ Swager, TM TI In vivo optical Imaging of amyloid aggregates in brain: Design of fluorescent markers SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE Alzheimer's disease; dyes/pigments; fluorescent probes; imaging agents; synthesis design ID CONGO RED; BINDING; ALZHEIMER; FIBRILS; TISSUE C1 Louisiana State Univ, Dept Chem, Baton Rouge, LA 70803 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. MIT, Inst Soldier Nanotechnol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Res Lab, Dept Neurol, Charlestown, MA 02129 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. RP Swager, TM (reprint author), Louisiana State Univ, Dept Chem, Baton Rouge, LA 70803 USA. EM tswager@mit.edu RI Swager, Timothy/H-7459-2012; OI Swager, Timothy/0000-0002-3577-0510; Klunk, William/0000-0001-5512-0251 FU NIBIB NIH HHS [EB00768] NR 21 TC 157 Z9 160 U1 5 U2 43 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2005 VL 44 IS 34 BP 5452 EP 5456 DI 10.1002/anie.200500845 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 961CL UT WOS:000231639400009 PM 16059955 ER PT J AU Schook, L Beattie, C Beever, J Donovan, S Jamison, R Zuckermann, F Niemi, S Rothschild, M Rutherford, M Smith, D AF Schook, L Beattie, C Beever, J Donovan, S Jamison, R Zuckermann, F Niemi, S Rothschild, M Rutherford, M Smith, D TI Swine in biomedical research: Creating the building blocks of animal models SO ANIMAL BIOTECHNOLOGY LA English DT Article C1 Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA. Univ Nevada, Reno, NV 89557 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Iowa State Univ, Ames, IA 50011 USA. Univ Minnesota, Minneapolis, MN 55455 USA. RP Schook, L (reprint author), Univ Illinois, Inst Genom Biol, 382 ERML,1201 W Gregory Ave, Urbana, IL 61801 USA. EM schook@uiuc.edu OI Schook, Lawrence/0000-0002-6580-8364; Donovan, Sharon/0000-0002-9785-4189 FU NCRR NIH HHS [RR020283] NR 1 TC 65 Z9 73 U1 2 U2 13 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1049-5398 J9 ANIM BIOTECHNOL JI Anim. Biotechnol. PY 2005 VL 16 IS 2 BP 183 EP 190 DI 10.1080/10495390500265034 PG 8 WC Agriculture, Dairy & Animal Science; Biotechnology & Applied Microbiology SC Agriculture; Biotechnology & Applied Microbiology GA 984JO UT WOS:000233299700008 PM 16342425 ER PT J AU Kobayashi, MS Haynes, CW Macaruso, P Hook, PE Kato, J AF Kobayashi, MS Haynes, CW Macaruso, P Hook, PE Kato, J TI Effects of mora deletion, nonword repetition, rapid naming, and visual search performance on beginning reading in Japanese SO ANNALS OF DYSLEXIA LA English DT Article; Proceedings Paper CT Meeting of the Society-of-Cognitive-Neuropsychology CY 2003 CL JAPAN SP Soc Cognit Neuropsychol DE Japanese kana; mora deletion; phonological awareness; rapid naming; reading ID DOUBLE-DEFICIT HYPOTHESIS; DEVELOPMENTAL DYSLEXIA; PHONOLOGICAL AWARENESS; DISABLED READERS; VERBAL MEMORY; CHILDREN; DISABILITIES; WORDS; KANA; SEGMENTATION AB This study examined the extent to which mora deletion (phonological analysis), nonword repetition (phonological inemory), rapid automatized naming (RAN), and visual search abilities predict reading in Japanese kindergartners and first graders. Analogous abilities have been identified as important predictors of reading skills in alphabetic languages like English. In contrast to English, which is based on grapheme-phoneme relationships, the primary components of Japanese orthography are two syllabaries-hiragana and katakana (collectively termed "kana")-and a system of morphosyllabic symbols (kanji). Three RAN tasks (numbers, objects, syllabary symbols; [hiragana]) were used with kindergartners, with an additional kanji RAN task included for first graders. Reading measures included accuracy and speed of passage reading for kindergartners and first graders, and reading comprehension for first graders. In kindergartners, hiragana RAN and number RAN were the only significant predictors of reading accuracy and speed. In first graders, kanji RAN and hiragana RAN predicted reading speed, whereas accuracy was predicted by mora deletion. Reading comprehension Was predicted by kanji RAN, mora deletion, and nonword repetition. Although number RAN did not contribitte unique variance to any reading measure, it correlated highly with kanji RAN. Iniplications of these findings,for research anti practice are discussed. C1 Sophia Univ, Tokyo 102, Japan. MGH Inst Hlth Profess, Boston, MA USA. Community Coll Rhode Isl, Lincoln, NE USA. Haskins Labs Inc, New Haven, CT USA. MGH Inst Hlth Profess, Boston, MA USA. Clin Kato & Japan Dyslexia Res Assoc, Kawasaki, Kanagawa, Japan. RP Haynes, CW (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, Grad Program Commun Sci & Disorders, 36 1st Ave, Boston, MA 02129 USA. EM chaynes@mghihp.edu FU NICHD NIH HHS [HD-01994] NR 66 TC 11 Z9 11 U1 0 U2 4 PU INT DYSLEXIA ASSOC PI BALTIMORE PA CHESTER BUILDING, STE 382, 8600 LA SALLE RD, BALTIMORE, MD 21286-2044 USA SN 0736-9387 J9 ANN DYSLEXIA JI Ann. Dyslexia PY 2005 VL 55 IS 1 BP 105 EP 128 DI 10.1007/s11881-005-0006-7 PG 24 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 936KF UT WOS:000229853200006 PM 16107782 ER PT J AU Laberge, MA Moore, KJ Freeman, MW AF Laberge, MA Moore, KJ Freeman, MW TI Atherosclerosis and innate immune signaling SO ANNALS OF MEDICINE LA English DT Article DE atherosclerosis; inflammation; innate immunity; toll-like receptors ID LOW-DENSITY-LIPOPROTEIN; RECEPTOR-DEFICIENT MICE; CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; MACROPHAGE SCAVENGER RECEPTORS; TOLL-LIKE RECEPTOR-4; KAPPA-B ACTIVATION; APOLIPOPROTEIN-E; OXIDIZED LDL; MYOCARDIAL-INFARCTION AB Atherosclerosis, the leading cause of death in developed countries, is characterized by chronic inflammation in the artery wall. It has been appreciated for decades that this disease is linked to hypercholesterolemia. and the accumulation of macrophages in the artery wall, yet the exact mechanisms underlying this inflammatory process remain unclear. The role of innate and adaptive immune responses in the pathogenesis of atherosclerosis has been an area of intense study. It now appears that activation of innate immune signaling pathways designed to protect us from microbes may be responsible for initiating and feeding the chronic inflammatory cascade that characterizes this disease. In this review, we discuss the recent identification of Toll-like receptors and their downstream signaling pathways as critical contributors to atherosclerosis. Unraveling the contribution of individual Toll-like receptors and identifying the ligands that activate these pathways will be a central focus of atherosclerosis research in the next few years. The involvement of these pathways in atherogenesis will not only open up new avenues of investigation, but it also provides new targets for therapeutic manipulation that could ameliorate the atherosclerotic inflammatory response directly. C1 Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. RP Freeman, MW (reprint author), Massachusetts Gen Hosp, Lipid Metab Unit, 55 Fruit St, Boston, MA 02114 USA. EM freeman@molbio.mgh.harvard.edu NR 84 TC 26 Z9 27 U1 0 U2 1 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0785-3890 J9 ANN MED JI Ann. Med. PY 2005 VL 37 IS 2 BP 130 EP 140 DI 10.1080/07853890510007304 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 923QO UT WOS:000228924600006 PM 16026120 ER PT J AU Mansour, HA Talkowski, ME Wood, J Pless, L Bamne, M Chowdari, KV Allen, M Bowden, CL Calabrese, J El-Mallakh, RS Fagiolini, A Faraone, SV Fossey, MD Friedman, ES Gyulai, L Hauser, P Ketter, TA Loftis, JM Marangell, LB Miklowitz, DJ Nierenberg, AA Patel, J Sachs, GS Sklar, P Smoller, JW Thase, ME Frank, E Kupfer, DJ Nimgaonkar, VL AF Mansour, HA Talkowski, ME Wood, J Pless, L Bamne, M Chowdari, KV Allen, M Bowden, CL Calabrese, J El-Mallakh, RS Fagiolini, A Faraone, SV Fossey, MD Friedman, ES Gyulai, L Hauser, P Ketter, TA Loftis, JM Marangell, LB Miklowitz, DJ Nierenberg, AA Patel, J Sachs, GS Sklar, P Smoller, JW Thase, ME Frank, E Kupfer, DJ Nimgaonkar, VL TI Serotonin gene polymorphisms and bipolar I disorder: Focus on the serotonin transporter SO ANNALS OF MEDICINE LA English DT Review DE association; bipolar disorder; genetic; polymorphism; serotonin; serotonin transporter ID MONOAMINE-OXIDASE-A; TRYPTOPHAN-HYDROXYLASE GENE; MANIC-DEPRESSIVE ILLNESS; 5-HT2A RECEPTOR GENE; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; TRANSMISSION DISEQUILIBRIUM TEST; FAMILY-BASED ASSOCIATION; LINKAGE DISEQUILIBRIUM; MOOD-DISORDERS; FUNCTIONAL POLYMORPHISM AB The pathogenesis of bipolar disorder may involve, at least in part, aberrations in serotonergic neurotransmission. Hence, serotonergic genes are attractive targets for association studies of bipolar disorder. We have reviewed the literature in this field. It is difficult to synthesize results as only one polymorphism per gene was typically investigated in relatively small samples. Nevertheless, suggestive associations are available for the 5HT2A receptor and the serotonin transporter genes. With the availability of extensive polymorphism data and high throughput genotyping techniques, comprehensive evaluation of these genes using adequately powered samples is warranted. We also report on our investigations of the serotonin transporter, SLC6A4 (17q11.1-q12). An insertion/deletion polymorphism (5HTTLPR) in the promoter region of this gene has been investigated intensively. However, the results have been inconsistent. We reasoned that other polymorphism/s may contribute to the associations and the inconsistencies may be due to variations in linkage disequilibrium (LD) patterns between samples. Therefore, we conducted LD analyses, as well as association and linkage using 12 polymorphisms, including 5HTTLPR. We evaluated two samples. The first sample consisted of 135 US Caucasian nuclear families having a proband with bipolar I disorder (BDI, DSM IV criteria) and available parents. For case-control analyses, the patients from these families were compared with cord blood samples from local Caucasian live births (n=182). Our second, independent sample was recruited through the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD, 545 cases, 548 controls). No significant associations were detected at the individual polymorphism or haplotype level using the case-control or family-based analyses. Our analyses do riot support association between SLC6A4 and BDI families. Further studies using sub-groups of BDI are worthwhile. C1 Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Case Western Reserve Univ, Univ Hosp Cleveland, Sch Med, Dept Psychiat,Mood Disorders Program, Cleveland, OH 44106 USA. Univ Louisville, Sch Med, Dept Psychiat & Behav Sci, Louisville, KY 40292 USA. SUNY Upstate Med Univ, Dept Psychiat & Human Behav, Syracuse, NY USA. Univ Oklahoma, Dept Psychiat, Tulsa, OK USA. Univ Penn, Med Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR USA. Oregon Hlth Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Bipolar Disorders Clin, Stanford, CA 94305 USA. Baylor Coll Med, Menninger Dept Psychiat, Houston, TX 77030 USA. Dept Vet Affairs, Houston, TX USA. Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Clin Depress & Res Program, Cambridge, MA 02138 USA. Univ Massachusetts, Sch Med, Bipolar Disorder Program, Schizophrenia Res Program, Worcester, MA USA. Univ Massachusetts, Sch Med, Ctr Psychopharmacol Res & Treatment, Dept Psychiat, Worcester, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Bipolar Clin, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Res Program, Boston, MA USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychiat Genet Program Mood & Anxiety Disorders, Dept Psychiat, Boston, MA 02114 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. RP Nimgaonkar, VL (reprint author), Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Room 441,3811 O'Hara St, Pittsburgh, PA 15213 USA. EM nimga+@pitt.edu RI Bamne, Mikhil/A-9519-2010; Allen, Michael/A-8776-2011; OI FAGIOLINI, ANDREA/0000-0001-5827-0853; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH 30915, MH 56242, MH 63420, MH 66263] NR 109 TC 27 Z9 27 U1 1 U2 3 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0785-3890 J9 ANN MED JI Ann. Med. PY 2005 VL 37 IS 8 BP 590 EP 602 DI 10.1080/07853890500357428 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 997PM UT WOS:000234258900005 PM 16338761 ER PT J AU Shah, K Bureau, E Kim, DE Yang, K Tang, Y Weissleder, R Breakefield, XO AF Shah, K Bureau, E Kim, DE Yang, K Tang, Y Weissleder, R Breakefield, XO TI Glioma therapy and real-time imaging of neural precursor cell migration and tumor regression SO ANNALS OF NEUROLOGY LA English DT Article ID IN-VIVO; MALIGNANT GLIOMA; STEM-CELLS; ANTITUMOR-ACTIVITY; DECOY RECEPTORS; TNF-FAMILY; APOPTOSIS; TRAIL; DEATH; APO2L/TRAIL AB Despite many refinements in current therapeutic strategies, the overall prognosis for a patient with glioblastoma is dismal. Neural precursor cells (NPCs) are capable of tracking glioma tumors and thus could be used to deliver therapeutic molecules. We have engineered mouse NPCs to deliver a secreted form of tumor necrosis factor-related apoptosis-inducing ligand (S-TRAIL); S-TRAIL is optimized to selectively kill neoplastic cells. Furthermore, we have developed means to simultaneously monitor both the migration of NSCs toward gliomas and the changes in glioma burden in real time. Using a highly malignant human glioma model expressing Renilla luciferase (Rluc), intracranially implanted NPC-FL-sTRAIL expressing both firefly luciferase (Fluc) and S-TRAIL was shown to migrate into the tumors and have profound antitumor effects. These studies demonstrate the potential of NPCs as therapeutically effective delivery vehicles for the treatment of gliomas and also provide important tools to evaluate the migration of NPCs and changes in glioma burden in vivo. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02129 USA. RP Shah, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, 13th St,Bldg 149,5421CMIR, Boston, MA 02129 USA. EM kshah@helix.mgh.harvard.edu FU NCI NIH HHS [CA 92782, CA 69246, CA 86355] NR 28 TC 119 Z9 127 U1 0 U2 10 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 JAN PY 2005 VL 57 IS 1 BP 34 EP 41 DI 10.1002/ana.20306 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 884SM UT WOS:000226106500006 PM 15622535 ER PT J AU Ascherio, A Weisskopf, MG O'Reilly, EJ Jacobs, EJ McCullough, ML Calle, EE Cudkowicz, M Thun, MJ AF Ascherio, A Weisskopf, MG O'Reilly, EJ Jacobs, EJ McCullough, ML Calle, EE Cudkowicz, M Thun, MJ TI Vitamin E intake and risk of amyotrophic lateral sclerosis SO ANNALS OF NEUROLOGY LA English DT Article ID AMERICAN-CANCER-SOCIETY; MOTOR-NEURON DISEASE; INCREASED OXIDATIVE DAMAGE; SUPEROXIDE-DISMUTASE; ALPHA-TOCOPHEROL; GLUTAMATE TRANSPORTER; CIGARETTE-SMOKING; DEATH; PREVENTION; PROTEIN AB Oxidative stress may contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS). We therefore examined prospectively whether individuals who regularly use supplements of the antioxidant vitamins E and C have a lower risk of ALS than nonusers. The study population comprised 957,740 individuals 30 years of age or older participating in the American Cancer Society's Cancer Prevention Study II. Information on vitamin use was collected at time of recruitment in 1982; participants then were followed up for ALS deaths from 1989 through 1998 via linkage with the National Death Index. During the follow-up, we documented 525 deaths from ALS. Regular use of vitamin E supplements was associated with a lower risk of dying of ALS. The age- and smoking-adjusted relative risk was 0.99 (95% confidence interval [CI], 0.69-1.41) among occasional users, 0.59 (95% CI, 0.36-0.96) in regular users for less than 10 years, and 0.38 (95% CI, 0.16-0.92) in regular users for 10 years or more as compared with nonusers of vitamin E (p for trend = 0.004). In contrast, no significant associations were found for use of vitamin C or multivitamins. These results suggest that vitamin E supplementation could have a role in ALS prevention. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Amer Canc Soc, Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurol Clin Trial Unit, Boston, MA 02115 USA. RP Ascherio, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM aascheri@hsph.harvard.edu FU NINDS NIH HHS [NS 045893] NR 41 TC 74 Z9 77 U1 0 U2 1 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 JAN PY 2005 VL 57 IS 1 BP 104 EP 110 DI 10.1002/ana.20316 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 884SM UT WOS:000226106500014 PM 15529299 ER PT J AU Janne, PA AF Janne, PA TI Patient selection in clinical trials of EGFR inhibitors SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 3rd International Symposium on Targeted Anticancer Therapies CY MAR 03-05, 2005 CL Amsterdam, NETHERLANDS SP AstraZeneca Oncol, Novartis Oncol, Pfizer Oncol, Bayer Healthcare Pharmaceut, Bristol-Mayers Squibb Co, Lilly, GlaxoSmithKline, ORTHO BIOTECH, MERCK, MDS Oncol, Roche Oncol, SCHERING C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2005 VL 16 SU 3 BP 16 EP 16 PG 1 WC Oncology SC Oncology GA 937RB UT WOS:000229942100005 ER PT J AU de Bazelaire, C Alsop, D Rofsky, N Wang, YY Mietlowski, W Reitsma, D Laurent, D Michaelson, D Kantoff, P George, D Oh, WK AF de Bazelaire, C Alsop, D Rofsky, N Wang, YY Mietlowski, W Reitsma, D Laurent, D Michaelson, D Kantoff, P George, D Oh, WK TI MRI-assessed changes in tumor blood flow after treatment with PTK787/ZK222584 (PTK/ZK) correlate with subsequent tumor shrinkage or growth in patients with metastatic renal cell carcinoma SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 3rd International Symposium on Targeted Anticancer Therapies CY MAR 03-05, 2005 CL Amsterdam, NETHERLANDS SP AstraZeneca Oncol, Novartis Oncol, Pfizer Oncol, Bayer Healthcare Pharmaceut, Bristol-Mayers Squibb Co, Lilly, GlaxoSmithKline, ORTHO BIOTECH, MERCK, MDS Oncol, Roche Oncol, SCHERING C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. Schering AG, D-1000 Berlin, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC USA. RI Alsop, David/J-5764-2013 OI Alsop, David/0000-0002-8206-1995 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2005 VL 16 SU 3 BP 17 EP 17 PG 1 WC Oncology SC Oncology GA 937RB UT WOS:000229942100009 ER PT J AU Chabner, BA Roberts, TG AF Chabner, BA Roberts, TG TI Recent changes in drug development guidelines and regulatory review in the USA SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 3rd International Symposium on Targeted Anticancer Therapies CY MAR 03-05, 2005 CL Amsterdam, NETHERLANDS SP AstraZeneca Oncol, Novartis Oncol, Pfizer Oncol, Bayer Healthcare Pharmaceut, Bristol-Mayers Squibb Co, Lilly, GlaxoSmithKline, ORTHO BIOTECH, MERCK, MDS Oncol, Roche Oncol, SCHERING C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2005 VL 16 SU 3 BP 26 EP 26 PG 1 WC Oncology SC Oncology GA 937RB UT WOS:000229942100028 ER PT J AU Treon, SP Emmanouilides, C Kimby, E Kelliher, A Preffer, F Branagan, AR Anderson, KC Frankel, SR AF Treon, SP Emmanouilides, C Kimby, E Kelliher, A Preffer, F Branagan, AR Anderson, KC Frankel, SR TI Extended rituximab therapy in Waldenstrom's macroglobulinemia SO ANNALS OF ONCOLOGY LA English DT Article DE Waldenstrom's macroglobulinemia; lymphoplasmacytic lymphoma; rituximab; CD46; CD55; CD59 ID ANTIBODY-MEDIATED IMMUNOTHERAPY; CONSENSUS PANEL RECOMMENDATIONS; ANTI-CD20 MONOCLONAL-ANTIBODY; CHRONIC LYMPHOCYTIC-LEUKEMIA; 2ND INTERNATIONAL WORKSHOP; CELL MALIGNANCIES; IN-VITRO; EXPRESSION; LYMPHOMA; COMPLEMENT AB Background: Waldenstrom's macroglobulinemia (WM) is a CD20 expressing B-cell malignancy represented by the pathological diagnosis of IgM secreting lymphoplasmacytic lymphoma. Major response rates of 30% have been reported in most studies with standard,dose rituximab, i.e. 4 weekly infusions at 375 mg/m(2)/week. Methods: In an effort to increase rituximab activity in WM, an extended dose schedule employing two sets of four (375 mg/m(2)/week) infusions at weeks 1-4 and 12-16 was evaluated. Expression of the complement resistance antigens CD46, CD55 and CD59 was also evaluated on tumor cells pre- and post-therapy to determine impact on response. Results: Twenty-nine patients were enrolled and 26 patients completed the intended therapy. On an intent to treat analysis, 14 (48.3%) patients achieved a partial response, and 5 (17.2%) patients achieved a minor response. Responses were observed in 18/24 (75%) patients with a serum IgM level of <6000 mg/dl, and only 1 of 5 (20%) patients with a level of >6000 mg/dl (P = 0.03). The median time to best response was 17 months, and only 2 of 19 responding patients progressed with a median follow-up of 29 months. No differences in baseline expression of the complement resistance antigens CD46, CD55 and CD59 were observed among responding and non-responding patients, although post-therapy CD55 expression was higher in non-responding, patients (P = 0.002). Conclusions: These data show that extended rituximab therapy is active and may lead to more major responses over standard dose rituximab in WM. WM patients with serum IgM levels of <6000 mg/dl are more likely to benefit from extended rituximab therapy. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Program Waldenstrons Macroglobulinemia, Boston, MA 02115 USA. Univ Calif Los Angeles, Ctr Med, Los Angeles, CA 90024 USA. Huddinge Univ Hosp, Karolinska Inst, Stockholm, Sweden. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Univ Maryland, Greenbaum Canc Ctr, Baltimore, MD 21201 USA. RP Treon, SP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Program Waldenstrons Macroglobulinemia, LG102,44 Binney St, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu FU NCI NIH HHS [K23CA087977-03] NR 26 TC 85 Z9 86 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 JAN PY 2005 VL 16 IS 1 BP 132 EP 138 DI 10.1093/annonc/mdi022 PG 7 WC Oncology SC Oncology GA 885JR UT WOS:000226153400025 PM 15598950 ER PT J AU Lim, DJ Hellstrom, SO Alper, CM Andalibi, A Bakaletz, LO Buchman, CA Caye-Thomasen, P Chole, RA Herman, P Lee, HY Kang, SH Hermansson, A Hussl, B Iino, Y Jung, TTK Kawauchi, H Kerschner, J Lin, JZ Merchant, SN Paparella, MM AF Lim, DJ Hellstrom, SO Alper, CM Andalibi, A Bakaletz, LO Buchman, CA Caye-Thomasen, P Chole, RA Herman, P Lee, HY Kang, SH Hermansson, A Hussl, B Iino, Y Jung, TTK Kawauchi, H Kerschner, J Lin, JZ Merchant, SN Paparella, MM TI Animal models; Anatomy and pathology; Pathogenesis; Cell biology and genetics SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT 8th Post Symposium Research Conference CY JUN 07-08, 2003 CL Ft Lauderdale, FL ID NONTYPABLE HAEMOPHILUS-INFLUENZAE; ACUTE OTITIS-MEDIA; MIDDLE-EAR MUCOSA; NECROSIS-FACTOR-ALPHA; EUSTACHIAN-TUBE DYSFUNCTION; OUTER-MEMBRANE PROTEIN; STREPTOCOCCUS-PNEUMONIAE INFECTION; IN-SITU HYBRIDIZATION; ROUND WINDOW MEMBRANE; VIRUS-40 HYBRID VIRUS C1 Hop Lariboisiere, Dept Otorhinolaryngol, F-75475 Paris, France. House Ear Res Inst, Gonda Dept Cell & Mol Biol, Los Angeles, CA USA. Umea Univ, Dept Otolaryngol, Umea, Sweden. Univ Pittsburgh, Childrens Hosp Pittsburgh, Sch Med, Dept Otolaryngol, Pittsburgh, PA USA. Childrens Res Inst, Wexner Inst Pediat Res, Dept Pediat, Columbus, OH USA. Univ Miami, Dept Otolaryngol, Miami, FL 33152 USA. Gentofte Univ Hosp, Dept Otorhinolaryngol, Hellerup, Denmark. Washington Univ, Sch Med, Dept Otolaryngol, St Louis, MO 63110 USA. Univ Lund Hosp, Dept Otorhinolaryngol, S-22185 Lund, Sweden. Univ Innsbruck, Dept Otolaryngol, A-6020 Innsbruck, Austria. Univ Tokyo, Sch Med, Dept Otolaryngol, Tokyo 113, Japan. Loma Linda Univ, Med Ctr, Div Otolaryngol, Loma Linda, CA 92350 USA. Shimane Med Univ, Dept Otolaryngol, Izumo, Shimane 693, Japan. Childrens Hosp Wisconsin, Dept Otolaryngol, Milwaukee, WI 53201 USA. Univ Minnesota, Dept Otolaryngol, Minneapolis, MN USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Minnesota Ear Head & Neck Clin, Otopathol Lab, Minneapolis, MN 55454 USA. RP Lim, DJ (reprint author), Hop Lariboisiere, Dept Otorhinolaryngol, F-75475 Paris, France. NR 126 TC 0 Z9 0 U1 0 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JAN PY 2005 VL 114 IS 1 SU 194 BP 31 EP 41 PN 2 PG 11 WC Otorhinolaryngology SC Otorhinolaryngology GA 888UJ UT WOS:000226399400005 ER PT J AU Hur, C Simon, LS Gazelle, GS AF Hur, C Simon, LS Gazelle, GS TI Analysis of aspirin-associated risks in healthy individuals SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE aspirin; chemoprevention; risk analysis ID NONVALVULAR ATRIAL-FIBRILLATION; PREVENT COLORECTAL ADENOMAS; LOW-DOSE ASPIRIN; COST-EFFECTIVENESS; CARDIOVASCULAR EVENTS; RANDOMIZED-TRIAL; HEART-DISEASE; TASK-FORCE; STROKE; CANCER AB Background: Aspirin therapy is widely accepted for patients with documented cardiovascular disease, but there is a growing trend among healthy individuals to use aspirin as primary prevention for both cardiovascular disease and cancer. Objective: To determine the impact of the complications of aspirin therapy on quality-adjusted life-years (QALYs) in healthy individuals. Methods: A computer-based decision-analytic model was constructed. In this model, healthy individuals taking aspirin were assumed to receive no advantages from the aspirin, but were at risk of developing its associated complications. Individuals took 325 mg of enteric-coated aspirin every day until death, discontinuing therapy only if an aspirin-induced complication occurred. The analysis was performed from a societal perspective, starting at age 50 years. Extensive sensitivity analyses were performed. Results: In the absence of any beneficial effect, aspirin reduced QALYs by 0.03 per individual. Unadjusted life expectancy was decreased by 0.04 years (2 wk). Lifetime aspirin use cost an average of $460/healthy person. The total complication rate over a lifetime of aspirin therapy was 6.79%, with a mortality rate of 0.18%. Alternatively stated, there was one complication for every 15 individuals treated and one death for every 556 individuals treated. Extensive sensitivity analysis showed the range of results possible when varying age, gender, length of follow-up, and other key parameters. Conclusions: Assuming no benefits, aspirin therapy in healthy individuals leads to a small reduction in QALYs at an overall low cost per person. However, approximately 1 in 15 individuals will experience an aspirin-induced complication and 1 in 556 individuals will die. C1 Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Hur, C (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Fl, Boston, MA 02114 USA. EM chur@mgh-ita.org OI Hur, Chin/0000-0002-2819-7576 NR 42 TC 5 Z9 5 U1 1 U2 3 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JAN PY 2005 VL 39 IS 1 BP 51 EP 57 DI 10.1345/aph.1E115 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 882DO UT WOS:000225919100008 PM 15590881 ER PT J AU Sosef, MN Baust, JM Sugimachi, K Fowler, A Tompkins, RG Toner, M AF Sosef, MN Baust, JM Sugimachi, K Fowler, A Tompkins, RG Toner, M TI Cryopreservation of isolated primary rat hepatocytes - Enhanced survival and long-term hepatospecific function SO ANNALS OF SURGERY LA English DT Article ID FULMINANT HEPATIC-FAILURE; AMC-BIOARTIFICIAL LIVER; PORCINE HEPATOCYTES; SANDWICH CONFIGURATION; XENOBIOTIC METABOLISM; ADULT HEPATOCYTES; CONTROLLED TRIAL; ASSIST DEVICE; GENE-THERAPY; VIABILITY AB Objective: To investigate the long-term effect of cryopreservation on hepatocyte function, as well as attempt to improve cell viability and function through the utilization of the hypothermic preservation solution, HypoThermosol (HTS), as the carrier solution. Summary Background Data: Advances in the field of bioartificial liver support have led to an increasing demand for successful, efficient means of cryopreservation of hepatocytes. Methods: Fresh rat hepatocytes were cryopreserved in suspension in culture media (Media-cryo group) or HTS (HTS-cryo group), both supplemented with 10% DMSO. Following storage up to 2 months in liquid nitrogen, cells were thawed and maintained in a double collagen gel culture for 14 days. Hepatocyte yield and viability were assessed up to 14 days postthaw. Serial measurements of albumin secretion, urea synthesis, deethylation of ethoxyresorufin (CYT P450 activity), and responsiveness to stimulation with interleukin-6 (IL-6) were performed. Results: Immediate postthaw viability was 60% in Media-cryo and 79% in HTS-cryo, in comparison with control (90%). Albumin secretion, urea synthesis and CYT P450 activity yielded 33%, 55%, and 59% in Media-cryo and 71%, 80%, and 88% in HTS-cryo, respectively, compared with control (100%). Assessment of cellular response to IL-6 following cryopreservation revealed a similar pattern of up-regulation in fibrinogen production and suppression of albumin secretion compared with nonfrozen controls. Conclusions: This study demonstrates that isolated rat hepatocytes cryopreserved using HTS showed high viability, long-term hepato-specific function, and response to cytokine challenge. These results may represent an important step forward to the utilization of cryopreserved isolated hepatocytes in bioartificial liver devices. C1 Shriners Hosp Children, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA USA. Univ Massachusetts, Dept Mech Engn, Dartmouth, MA USA. RP Toner, M (reprint author), Shriners Hosp Children, Ctr Engn Med & Surg Serv, 51 Blossom St, Boston, MA 02114 USA. EM mtoner@sbi.org FU NIDDK NIH HHS [DK46270] NR 32 TC 33 Z9 35 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JAN PY 2005 VL 241 IS 1 BP 125 EP 133 DI 10.1097/01.sla.0000149303.48692.0f PG 9 WC Surgery SC Surgery GA 884KC UT WOS:000226082600017 PM 15622000 ER PT J AU Stylopoulos, N Rattner, DW AF Stylopoulos, N Rattner, DW TI The history of hiatal hernia surgery - From Bowditch to laparoscopy SO ANNALS OF SURGERY LA English DT Article ID GASTROESOPHAGEAL FLAP VALVE; DIAPHRAGMATIC-HERNIA; ESOPHAGEAL ORIFICE; REPAIR; OPERATION; REFLUX; STRICTURES; DIAGNOSIS; STOMACH; CARDIA AB Objective: This review addresses the historical evolution of hiatal hernia (HH) repair and reports in a chronological fashion the major milestones in HH Surgery before the laparoscopic era. Methods: The medical literature and the collections of the History of Medicine Division of the National Library of Medicine were searched. Secondary references from all sources were studied. The senior author's experience and personal communications are also reported. Results: The first report of HH was published in 1853 by Bowditch. Rokitansky in 1855 demonstrated that esophagitis was due to gastroesophageal reflux, and Hirsch in 1900 diagnosed an HH using x-rays. Eppinger diagnosed an HH in a live patient, and Friedenwald and Feldman related the symptoms to the presence of an HH. In 1926, Akerlund proposed the term hiatus hernia and classified HH into the 3 types that we use today. The first elective surgical repair was reported in 1919 by Soresi. The physiologic link between HH and gastroesophageal reflux was made at the second half of the 20(th) century by Allison and Barrett. In the midst of a physiologic revolution, Nissen and Belsey developed their famous operations. In 1957, Collis published his innovative operation. Thal described his technique in 1965, and in 1967, Hill published his procedure. Many modifications of these procedures were published by Pearson and Henderson, Orringer and Sloan, Rossetti, Dor, and Toupet. Donahue and Demeester significantly improved Nissen's operation, and they were the first to truly understand its physiologic mechanism. Conclusion: Hiatal hernia Surgery has evolved from anatomic repair to physiological restoration. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. RP Rattner, DW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. EM drattner@partners.org NR 58 TC 48 Z9 50 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JAN PY 2005 VL 241 IS 1 BP 185 EP 193 DI 10.1097/01.sla.0000149430.83220.7f PG 9 WC Surgery SC Surgery GA 884KC UT WOS:000226082600024 PM 15622007 ER PT J AU Maggard, MA Lane, KE O'Connell, JB Nanyakkara, DD Ko, CY AF Maggard, MA Lane, KE O'Connell, JB Nanyakkara, DD Ko, CY TI Beyond the clinical trials: How often is sentinel lymph node dissection performed for breast cancer? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE breast cancer; administrative data; Sentinel lymph node dissection; quality of care ID BIOPSY; LYMPHADENECTOMY; CARE AB Background: Sentinel lymph node dissection (SLND) has been shown to be a reasonable treatment option for early-stage breast cancer. Until recently, SLND was limited to clinical trials. Because this technique is now offered outside of trials, its prevalence is unknown. Methods: All patients with stage I or II breast cancer in the Surveillance, Epidemiology, and End Results national cancer registry (1998-2000) were evaluated. Data were collected for demographics, tumor characteristics, surgical resection, lymph node evaluation (SLND or complete axillary dissection), registry site, and year of diagnosis. Multivariate regression analysis was performed to identify predictors for receiving SLND. Results: A total of 54,772 patients diagnosed with breast cancer had undergone surgical lymph node evaluation; 27.2 % patients with stage I disease underwent SLND, as compared with 22.7 % for stage II. Older patients and minority groups were less likely to receive SLND. Receipt of SLND varied by registry site (7.9 % - 32.7 %). Multivariate regression showed that older patients had lower odds of receiving SLND (60-69 years: odds ratio,.73; P < .0001) as compared with younger patients. Additionally, blacks, Hispanics, and Asians had lower odds of receiving SLND (odds ratio of .64, .58, and .80, respectively; P < .0001). SLND use increased over the 3 years in the study (P < .0001). Conclusions: This population-based analysis showed relatively infrequent use of SLND for early-stage breast cancer. These results suggest a slow transition of this procedure from clinical trials into the community. Future work should be targeted at improving the rate at which patients receive this procedure, particularly for elderly and minority groups and low-use regions. C1 Univ Calif Los Angeles, Sch Med, Dept Surg, Los Angeles, CA 90095 USA. Robert Wood Johnson VA Clin Scholars Program, Los Angeles, CA 90024 USA. UCSF Sch Med, Dept Surg, San Francisco, CA 94143 USA. W Los Angeles Vet Affairs Med Ctr, Dept Surg, Los Angeles, CA 90073 USA. RP Maggard, MA (reprint author), Univ Calif Los Angeles, Sch Med, Dept Surg, 10833 Le Conte Ave,CHS,Room 72-215, Los Angeles, CA 90095 USA. EM mmaggard@mednet.ucla.edu NR 16 TC 21 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 2005 VL 12 IS 1 BP 41 EP 47 DI 10.1245/ASO.2005.03.050 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 893YI UT WOS:000226756600010 PM 15827777 ER PT S AU Zamecnik, P AF Zamecnik, P TI From protein synthesis to genetic insertion SO ANNUAL REVIEW OF BIOCHEMISTRY SE Annual Review of Biochemistry LA English DT Review; Book Chapter DE tRNA; antisense; peptide formation; GTP; cofactor; Ap(4)A ID CYSTIC-FIBROSIS GENE; AMINO ACID INCORPORATION; LYSYL-SRNA SYNTHETASE; DNA POLYMERASE-ALPHA; RIBONUCLEIC ACID; DIADENOSINE 5',5'''-P1,P4-TETRAPHOSPHATE; ESCHERICHIA-COLI; RIBONUCLEOPROTEIN PARTICLES; RNA; OLIGONUCLEOTIDE AB In 1946, (14)C-cyanide made its appearance as an offshoot of the Atomic Energy Program. Our colleague Robert Loftfield built it into (14)C-alanine by the Strecker synthesis, and a lusty program directed toward uncovering the unknown mechanism of protein synthesis grew out of this beginning. The necessity for an undiscovered series of steps and enzymes was soon evident. A cell free system was developed, and a succession of components necessary for this new pathway tumbled out. ATP dependence, amino acid activation, the ribosome as the site of polypeptide formation, discovery of tRNA as the translation molecule linking the gene and protein sequence, and GTP as the essential energy ingredient in peptide chain extension all appeared from our laboratory within the next decade. A little later the AP(4)N family, whose functions remain imperfectly defined, of intracellular molecules was discovered. Isolation of specific species of RNA became a high priority, and we sequenced a small segment of the 3' end of the Rous sarcoma virus, just inside the poly(A) tail, at the same time the Gilbert group at Harvard was sequencing the 5' end. The sequence identity and polarity of the two ends suggested a circular intermediate in replication and predicted correctly that a synthetic antisense oligonucleotide targeted against this sequence might be a specific inhibitor of replication. More recently, we have evolved a technique that appears to achieve a trinucleotide insertion into tissue culture cells bearing a specific 0508 mRNA triplet deletion, resulting in phenotypic reversion in the tissue culture. C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Zamecnik, P (reprint author), Massachusetts Gen Hosp, Charlestown, MA 02129 USA. EM Paul_Zamecnik@hms.harvard.edu FU PHS HHS [R01-A1069872] NR 87 TC 4 Z9 4 U1 1 U2 5 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4154 BN 978-0-8243-0874-2 J9 ANNU REV BIOCHEM JI Annu. Rev. Biochem. PY 2005 VL 74 BP 1 EP 28 DI 10.1146/annurev.biochem.74.050304.091632 PG 28 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 955OH UT WOS:000231235100001 PM 15952879 ER PT S AU Kaelin, WG AF Kaelin, WG TI Proline hydroxylation and gene expression SO ANNUAL REVIEW OF BIOCHEMISTRY SE Annual Review of Biochemistry LA English DT Review; Book Chapter DE von Hippel-Lindau; hypoxia-inducible factor (HIF); hydroxylation; EGLN; FIH ID HYPOXIA-INDUCIBLE FACTOR; TUMOR-SUPPRESSOR PROTEIN; HIPPEL-LINDAU PROTEIN; ENDOTHELIAL GROWTH-FACTOR; MITOCHONDRIAL RESPIRATORY-CHAIN; UBIQUITIN-PROTEASOME PATHWAY; PAS DOMAIN PROTEIN; NITRIC-OXIDE; FACTOR 1-ALPHA; PROLYL-HYDROXYLASES AB Hypoxia-inducible factor (HIF) is a master transcriptional regulator of hypoxia-inducible genes and consists of a labile a subunit (such as HIF1 alpha) and a stable,B subunit (such as HIF1 beta or ARNT). In the presence of oxygen, HIF alpha family members are hydroxylated on one of two conserved prolyl residues by members of the egg-laying-defective nine (EGLN) family. Prolyl hydroxylation generates a binding site for a ubiquitin ligase complex containing the von Hippel-Lindau (VHL) tumor suppressor protein, which results in HIF alpha destruction. In addition, the HIF alpha transcriptional activation function is modulated further by asparagine hydroxylation by FIH (factor-inhibiting HIF), which affects recruitment of the coactivators p300 and CBP. These findings provide new mechanistic insights into oxygen sensing by metazoans and are the first examples of protein hydroxylation being used in intracellular signaling. The existence of three human EGLN family members, as well as other putative hydroxylases, raises the possibility that this signal is used in other contexts by other proteins. C1 Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. EM william_kaelin@dfci.harvard.edu NR 119 TC 253 Z9 262 U1 2 U2 22 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4154 BN 978-0-8243-0874-2 J9 ANNU REV BIOCHEM JI Annu. Rev. Biochem. PY 2005 VL 74 BP 115 EP 128 DI 10.1146/annurev.biochem.74.082803.133142 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 955OH UT WOS:000231235100005 PM 15952883 ER PT J AU Toner, M Irimia, D AF Toner, M Irimia, D TI Blood-on-a-chip SO ANNUAL REVIEW OF BIOMEDICAL ENGINEERING SE ANNUAL REVIEW OF BIOMEDICAL ENGINEERING LA English DT Review; Book Chapter DE lab-on-a-chip; point-of-care diagnostic; cell separation; sample preparation; microfluidic ID FIELD-FLOW-FRACTIONATION; INTEGRATED MICROFLUIDIC SYSTEM; CELL-SEPARATION; PARTICLE SEPARATION; SAMPLE PREPARATION; BIOLOGICAL CELLS; LIVING CELLS; DIELECTROPHORETIC SEPARATION; INFECTED ERYTHROCYTES; MAGNETIC SEPARATION AB Accurate, fast, and affordable analysis of the cellular component of blood is of prime interest for medicine and research. Yet, most often sample preparation procedures for blood analysis involve handling steps prone to introducing artifacts, whereas analysis methods commonly require skilled technicians and well-equipped, expensive laboratories. Developing more gentle protocols and affordable instruments for specific blood analysis tasks is becoming possible through the recent progress in the area of microfluidics and lab-on-a-chip-type devices. Precise control over the cell microenvironment during separation procedures and the ability to scale down the analysis to very small volumes of blood are among the most attractive capabilities of the new approaches. Here we review some of the emerging principles for manipulating blood cells at microscale and promising high-throughput approaches to blood cell separation using microdevices. Examples of specific single-purpose devices are described together with integration strategies for blood cell separation and analysis modules. C1 Massachusetts Gen Hosp, Shriners Hosp Children, Ctr Engn Med & Surg Sci, BioMEMS Resource Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Toner, M (reprint author), Massachusetts Gen Hosp, Shriners Hosp Children, Ctr Engn Med & Surg Sci, BioMEMS Resource Ctr, Boston, MA 02114 USA. EM mtoner@hms.harvard.edu; dirimia@hms.harvard.edu RI Sano, Michael/E-1715-2011; Yu, Tak For/O-2414-2014; OI Yu, Tak For/0000-0002-0209-7884; Irimia, Daniel/0000-0001-7347-2082 FU NIBIB NIH HHS [P41 EB 002503, P41 EB002503] NR 122 TC 408 Z9 417 U1 12 U2 191 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1523-9829 EI 1545-4274 J9 ANNU REV BIOMED ENG JI Annu. Rev. Biomed. Eng. PY 2005 VL 7 BP 77 EP 103 DI 10.1146/annurev.bioeng.7.011205.135108 PG 31 WC Engineering, Biomedical SC Engineering GA 959JE UT WOS:000231513200004 PM 16004567 ER PT S AU Arnaout, MA Mahalingam, B Xiong, JP AF Arnaout, MA Mahalingam, B Xiong, JP TI Integrin structure, allostery, and bidirectional signaling SO ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY SE Annual Review of Cell and Developmental Biology LA English DT Review; Book Chapter DE cell adhesion; inflammation; cancer; hemostasis; therapeutics ID FUNCTION-ASSOCIATED ANTIGEN-1; I-LIKE DOMAIN; CD11B A-DOMAIN; MURINE MONOCLONAL-ANTIBODY; CATION-BINDING SITE; LOW-AFFINITY STATE; REAL-TIME ANALYSIS; CRYSTAL-STRUCTURE; CYTOPLASMIC DOMAINS; LIGAND-BINDING AB alpha beta heterodimeric integrins mediate dynamic adhesive cell-cell and cell-extracellular matrix (ECM) interactions in metazoa that are critical in growth and development, hemostasis, and host defense. A central feature of these receptors is their capacity to change rapidly and reversibly their adhesive functions by modulating their ligandbinding affinity. This is normally achieved through interactions of the short cytoplasmic integrin tails with intracellular proteins, which trigger restructuring of the ligand-binding site through long-range conformational changes in the ectodomain. Ligand binding in turn elicits conformational changes that are transmitted back to the cell to regulate diverse responses. The publication of the integrin alpha V beta 3 crystal structure has provided the context for interpreting decades-old biochemical studies. Newer NMR, crystallographic, and EM data, reviewed here, are providing a better picture of the dynamic integrin structure and the allosteric changes that guide its diverse functions. C1 Massachusetts Gen Hosp, Dept Med, Struct Biol Program, Leukocyte Biol & Inflammat Program,Nephrol Div, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Arnaout, MA (reprint author), Massachusetts Gen Hosp, Dept Med, Struct Biol Program, Leukocyte Biol & Inflammat Program,Nephrol Div, Charlestown, MA 02129 USA. EM arnaout@receptor.mgh.harvard.edu; bmahalingam@partners.org; xiong@helix.mgh.harvard.edu FU NHLBI NIH HHS [HL70219]; NIDDK NIH HHS [DK48549, DK50305] NR 126 TC 286 Z9 296 U1 1 U2 43 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1081-0706 BN 978-0-8243-3121-4 J9 ANNU REV CELL DEV BI JI Annu. Rev. Cell Dev. Biol. PY 2005 VL 21 BP 381 EP 410 DI 10.1146/annurev.cellbio.21.090704.151217 PG 30 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 995HZ UT WOS:000234092700017 PM 16212500 ER PT S AU Halin, C Mora, JR Sumen, C von Andrian, UH AF Halin, C Mora, JR Sumen, C von Andrian, UH TI In vivo imaging of lymphocyte trafficking SO ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY SE Annual Review of Cell and Developmental Biology LA English DT Review; Book Chapter DE intravital microscopy; two-photon microscopy; lymph node; immune response ID CD4 T-CELLS; SELECTIN GLYCOPROTEIN LIGAND-1; BONE-MARROW MICROVESSELS; DENDRITIC CELLS; P-SELECTIN; INTRAVITAL MICROSCOPY; CENTRAL MEMORY; FLUORESCENCE MICROSCOPY; 2-PHOTON MICROSCOPY; ADHESION MOLECULE-1 AB Over the past decades, intravital microscopy (IVM4), the imaging of cells in living organisms, has become a valuable tool for studying the molecular determinants of lymphocyte trafficking. Recent advances in microscopy now make it possible to image cell migration and cell-cell interactions in vivo deep within intact tissues. Here, we summarize the principal techniques that are currently used in IVM, discuss options and tools for fluorescence-based visualization of lymphocytes in microvessels and tissues, and describe IVM models used to explore lymphoid and non-lymphoid organs. The latter will be introduced according to the physiologic itinerary of developing and differentiating T and B lymphocytes as they traffic through the body, beginning with their development in bone marrow and thymus and continuing with their migration to secondary lymphoid organs and peripheral tissues. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Halin, C (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM halin@cbr.med.harvard.edu; mora@cbr.med.harvard.edu; sumen@cbr.med.harvard.edu; uva@cbr.med.harvard.edu RI von Andrian, Ulrich/A-5775-2008 NR 100 TC 111 Z9 115 U1 1 U2 9 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1081-0706 BN 978-0-8243-3121-4 J9 ANNU REV CELL DEV BI JI Annu. Rev. Cell Dev. Biol. PY 2005 VL 21 BP 581 EP 603 DI 10.1146/annurev.cellbio.21.122303.133159 PG 23 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 995HZ UT WOS:000234092700025 PM 16212508 ER PT S AU de Jong, JLO Zon, LI AF de Jong, JLO Zon, LI TI Use of the zebrafish system to study primitive and definitive hematopoiesis SO ANNUAL REVIEW OF GENETICS SE Annual Review of Genetics LA English DT Review; Book Chapter DE hematopoiesis; zebrafish; blood; hematopoietic stem cell; genetic screen; mutant ID AUTOSOMAL-DOMINANT HEMOCHROMATOSIS; POSITIONAL CLONING; T-CELL; INSERTIONAL MUTAGENESIS; VERTEBRATE DEVELOPMENT; DEVELOPMENTAL BIOLOGY; TRANSGENIC ZEBRAFISH; MODEL SYSTEM; GLOBIN GENES; DANIO-RERIO AB The zebrafish (Danio rerio) has emerged as an ideal organism for the study of hematopoiesis, the process by which all the cellular elements of the blood are formed. These elements, including erythrocytes, granulocytes, monocytes, lymphocytes, and thrombocytes, are formed through complex genetic signaling pathways that are highly conserved throughout phylogeny Large-scale forward genetic screens have identified numerous blood mutants in zebrafish, helping to elucidate specific signaling pathways important for hematopoietic stem cells (HSCs) and the various committed blood cell lineages. Here we review both primitive and definitive hematopoiesis in zebrafish, discuss various genetic methods available in the zebrafish model for studying hematopoiesis, and describe some of the zebrafish blood mutants identified to date, many of which have known human disease counterparts. C1 Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP de Jong, JLO (reprint author), Childrens Hosp, Stem Cell Program, 300 Longwood Ave, Boston, MA 02115 USA. EM jill.dejong@childrens.harvard.edu; zon@enders.tch.harvard.edu FU NHLBI NIH HHS [T32 HL07574] NR 91 TC 142 Z9 149 U1 6 U2 18 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4197 BN 978-0-8243-1239-8 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 2005 VL 39 BP 481 EP 501 DI 10.1146/annurev.genet.39.073003.095931 PG 21 WC Genetics & Heredity SC Genetics & Heredity GA 003MB UT WOS:000234685200021 PM 16285869 ER PT S AU Giallourakis, C Henson, C Reich, M Xie, XH Mootha, VK AF Giallourakis, C Henson, C Reich, M Xie, XH Mootha, VK TI Disease gene discovery through integrative genomics SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS SE Annual Review of Genomics and Human Genetics LA English DT Review; Book Chapter DE human genetics; positional cloning; functional genomics; machine learning ID PROTEIN-PROTEIN INTERACTIONS; AUTOSOMAL RECESSIVE OSTEOPETROSIS; C-OXIDASE DEFICIENCY; SACCHAROMYCES-CEREVISIAE; MAMMALIAN-CELLS; DNA-REPAIR; RETINITIS-PIGMENTOSA; EXPRESSION PATTERNS; PROTEOMIC ANALYSIS; INTERFERING RNAS AB The availability of complete genome sequences and the wealth of large-scale biological data sets now provide an unprecedented opportunity to elucidate the genetic basis of rare and common human diseases. Here we review some of the emerging genomics technologies and data resources that can be used to infer gene function to prioritize candidate genes. We then describe some computational strategies for integrating these large-scale data sets to provide more faithful descriptions of gene function, and how such approaches have recently been applied to discover genes underlying Mendelian disorders. Finally, we discuss future prospects and challenges for using integrative genomics to systematically discover not only single genes but also entire gene networks that underlie and modify human disease. C1 Harvard Univ, Broad Inst, Cambridge, MA 02139 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02446 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Giallourakis, C (reprint author), Harvard Univ, Broad Inst, Cambridge, MA 02139 USA. EM vamsi@hms.harvard.edu NR 117 TC 50 Z9 51 U1 0 U2 8 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1527-8204 BN 978-0-8243-3706-3 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2005 VL 6 BP 381 EP 406 DI 10.1146/annurev.genom.6.080604.162234 PG 26 WC Genetics & Heredity SC Genetics & Heredity GA 972GE UT WOS:000232441500018 PM 16124867 ER PT S AU Call, ME Wucherpfennig, KW AF Call, ME Wucherpfennig, KW TI The T cell receptor: Critical role of the membrane environment in receptor assembly and function SO ANNUAL REVIEW OF IMMUNOLOGY SE Annual Review of Immunology LA English DT Review; Book Chapter DE antigen receptor; membrane protein oligomerization; lipid bilayer; signaling ID TRANSMEMBRANE HELICAL INTERACTIONS; PRE-GOLGI DEGRADATION; DI-LEUCINE MOTIF; ANTIGEN RECEPTOR; ALPHA-BETA; ENDOPLASMIC-RETICULUM; SIGNAL-TRANSDUCTION; PROTEIN TRANSLOCATION; SURFACE EXPRESSION; TCR/CD3 COMPLEX AB Recent studies have demonstrated that cell membranes provide a unique environment for protein-protein and protein-lipid interactions that are critical for the assembly and function of the T cell receptor (TCR)-CD3 complex. Highly specific polar interactions among transmembrane (TM) domains that are uniquely favorable in the lipid environment organize the association of the three signaling dimers with the TCR. Each of these three assembly steps depends on the formation of a three-helix interface between one basic and two acidic residues in the membrane environment. The same polar TM residues that drive assembly also play a central role in quality control and export by directing the retention and degradation of free subunits and partial complexes, while membrane proximal cytoplasmic signals control recycling and degradation of surface receptors. Recent studies also Suggest that interactions between the membrane and the cytoplasmic domains of CD3 proteins may be important for receptor triggering. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Call, ME (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM kai_wucherpfennig@dfci.harvard.edu OI Call, Matthew/0000-0001-5846-6469 NR 115 TC 125 Z9 131 U1 2 U2 17 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 BN 978-0-8243-3023-1 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2005 VL 23 BP 101 EP 125 DI 10.1146/annurev.immunol.23.021704.115625 PG 25 WC Immunology SC Immunology GA 923ZB UT WOS:000228947000004 PM 15771567 ER PT S AU Pillai, S Cariappa, A Moran, ST AF Pillai, S Cariappa, A Moran, ST TI Marginal zone B cells SO ANNUAL REVIEW OF IMMUNOLOGY SE Annual Review of Immunology LA English DT Review; Book Chapter DE follicular B cells; transitional B cells; B cell receptor; Notch2 ID LYMPHOTOXIN-BETA-RECEPTOR; SPLENIC WHITE PULP; HEAT-STABLE ANTIGEN(HI); SPLEEN DENDRITIC CELLS; KAPPA-B; IN-VIVO; POSITIVE SELECTION; IMMUNE-RESPONSES; B1B CELLS; T-CELL AB Our views regarding the origins and functions of splenic marginal zone B cells have changed considerably over the past few years. Perspectives regarding the development and function of these cells vary considerably between investigators studying human and rodent immunology. Marginal zone B cells are now recognized to constitute a distinct naive B lymphoid lineage. Considerable progress has been made regarding the mechanisms involved in marginal zone B cell development in the mouse. Many of the molecular events that participate in the retention of this lineage of B cells in the marginal zone have been identified. Here, we discuss the functions of these cells in both innate and adaptive immunity. We also attempt to reconcile differing viewpoints regarding the generation and function of marginal zone B cells in rodents and primates. C1 Harvard Univ, Sch Med, Boston, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02129 USA. RP Pillai, S (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02129 USA. EM pillai@helix.ingh.harvard.edu; cariappa@helix.mgh.harvard.edu; stmoran@fas.harvard.edu FU NCI NIH HHS [CA102793]; NIAID NIH HHS [AI 33507, AI54917, AI57486] NR 158 TC 296 Z9 306 U1 1 U2 11 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 BN 978-0-8243-3023-1 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2005 VL 23 BP 161 EP 196 DI 10.1146/annurev.immunol.23.021704.115728 PG 36 WC Immunology SC Immunology GA 923ZB UT WOS:000228947000006 PM 15771569 ER PT S AU Greenwald, RJ Freeman, GJ Sharpe, AH AF Greenwald, RJ Freeman, GJ Sharpe, AH TI The B7 family revisited SO ANNUAL REVIEW OF IMMUNOLOGY SE Annual Review of Immunology LA English DT Review; Book Chapter DE costimulation; B7; CD28; tolerance ID T-CELL-ACTIVATION; INDUCIBLE COSTIMULATOR PROTEIN; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; COLLAGEN-INDUCED ARTHRITIS; GAMMA-DEPENDENT MECHANISM; ISLET ALLOGRAFT SURVIVAL; DEATH-1 PD-1 PATHWAY; PROGRAMMED DEATH-1; IMMUNE-RESPONSES; RHEUMATOID-ARTHRITIS AB The discovery of new functions for the original B7 family members, together with the identification of additional B7 and CD28 family members, have revealed new ways in which the B7:CD28 family regulates T cell activation and tolerance. B7-1/B7-2:CD28 interactions not only promote initial T cell activation but also regulate self-tolerance by supporting CD4(+)CD25(+) T regulatory cell homeostasis. CTLA-4 can exert its inhibitory effects in both B7-1/B7-2 dependent and independent fashions. B7-1 and B7-2 can signal bidirectionally by engaging CD28 and CTLA-4 on T cells and by delivering signals into B7-expressing cells. The five new B7 family members, ICOS ligand, PD-L1 (B7-H1), PD-L2 (B7-DC), B7-H3, and B7-H4 (B7x/B7-S1) are expressed on professional antigen-presenting cells as well as on cells within nonlymphoid organs, providing new means for regulating T cell activation and tolerance in peripheral tissues. The new CD28 families members, ICOS, PD-1, and BTLA, are inducibly expressed on T cells, and they have important roles in regulating previously activated T cells. PD-1 and BTLA also are expressed on B cells and may have broader immunoregulatory functions. The ICOS:ICOSL pathway appears to be particularly important for stimulating effector T cell responses and T cell-dependent B cell responses, but it also has an important role in regulating T cell tolerance. In addition, the PD-1:PD-L1/PD-L2 pathway plays a critical role in regulating T cell activation and tolerance. In this review, we revisit the roles of the B7:CD28 family members in regulating immune responses, and we discuss their therapeutic potential. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Greenwald, RJ (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM rgreenwald@rics.bwh.harvard.edu; gordon_freeman@dfci.harvard.edu; asharpe@rics.bwh.harvard.edu NR 151 TC 1282 Z9 1389 U1 17 U2 114 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 BN 978-0-8243-3023-1 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2005 VL 23 BP 515 EP 548 DI 10.1146/annurev.immunol.23.021704.115611 PG 34 WC Immunology SC Immunology GA 923ZB UT WOS:000228947000017 PM 15771580 ER PT S AU Hijazi, RA Cunningham, GR AF Hijazi, RA Cunningham, GR TI Andropause: Is androgen replacement therapy indicated for the aging male? SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE hypogonadism; testosterone deficiency; testosterone replacement therapy ID BONE-MINERAL DENSITY; HORMONE-BINDING GLOBULIN; MIDDLE-AGED MEN; PROSTATIC INTRAEPITHELIAL NEOPLASIA; BIOAVAILABLE TESTOSTERONE LEVELS; RANDOMIZED CONTROLLED-TRIAL; ADIPOSE-TISSUE DISTRIBUTION; SEX STEROID-LEVELS; HEALTHY OLDER MEN; HYPOGONADAL MEN AB The number of men in the United States greater than or equal to65 years of age is projected to increase from 14,452,000 in 2000 to 31,343,000 in 2030. Approximately 30% of men 60-70 years of age and 70% of men 70-80 years of age have low bioavailable or free testosterone levels. Symptoms and findings of testosterone deficiency are similar to those associated with aging. They include loss of energy, depressed mood, decreased libido, erectile dysfunction, decreased muscle mass and strength, increased fat mass, frailty, osteopenia, and osteoporosis. Several small clinical trials indicate that testosterone replacement therapy can improve many of these findings; however, the studies have not been powered to assess potential risks, such as the need for invasive treatment of benign prostatic hyperplasia, development of a clinical prostate cancer, or cardiovascular events. Thus, the benefit/risk ratio of testosterone replacement therapy in aging men is not known. C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. RP Hijazi, RA (reprint author), Baylor Coll Med, Dept Med, Houston, TX 77030 USA. EM rhijazi@bcm.tmc.edu; glennc@bcm.tmc.edu NR 123 TC 63 Z9 68 U1 3 U2 4 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 BN 978-0-8243-0556-7 J9 ANNU REV MED JI Annu. Rev. Med. PY 2005 VL 56 BP 117 EP 137 DI 10.1146/annurev.med.56.082103.104518 PG 21 WC Medicine, General & Internal SC General & Internal Medicine GA 904ND UT WOS:000227504100008 PM 15660505 ER PT S AU Vijg, J Suh, Y AF Vijg, J Suh, Y TI Genetics of longevity and aging SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE oxidative stress; insulin signaling; energy metabolism; functional genomics; centenarians ID ADULT DROSOPHILA-MELANOGASTER; TRANSCRIPTION FACTOR FOXO3A; INSULIN SIGNALING PATHWAY; LIFE-SPAN EXTENSION; SNELL DWARF MOUSE; CAENORHABDITIS-ELEGANS; OXIDATIVE STRESS; C-ELEGANS; EXTENDED LONGEVITY; GROWTH-HORMONE AB Longevity, i.e., the property of being long-lived, has its natural limitation in the aging process. Longevity has a strong genetic component, as has become apparent from studies with a variety of organisms, from yeast to humans. Genetic screening efforts with invertebrates have unraveled multiple genetic pathways that suggest longevity is promoted through the manipulation of metabolism and the resistance to oxidative stress. To some extent, these same mechanisms appear to act in mammals also, despite considerable divergence during evolution. Thus far, evidence from population-based studies with humans suggests the importance of genes involved in cardiovascular disease as important determinants of longevity. The challenge is to test if the candidate longevity genes that have emerged from studies with model organisms exhibit genetic variation for life span in human populations. Future investigations are likely to involve large-scale case-control studies, in which large numbers of genes, corresponding to entire gene functional modules, will be assessed for all possible sequence variation and associated with detailed phenotypic information on each individual over extended periods of time. This should eventually unravel the genetic factors that contribute to each particular aging phenotype. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78245 USA. Ctr Geriatr Res Educ & Clin, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Vijg, J (reprint author), Univ Texas, Hlth Sci Ctr, San Antonio, TX 78245 USA. EM vijg@uthscsa.edu; suhy@uthscsa.edu FU NIA NIH HHS [R03 AG023292, AG17242, AG20438, AG23292, R01 AG024391, R01 AG024391-01, R01 AG024391-02, R01 AG024391-03, R01 AG024391-04, R01 AG024391-05, R03 AG023292-01, R03 AG023292-02]; NIEHS NIH HHS [ES11044] NR 91 TC 91 Z9 99 U1 3 U2 12 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 BN 978-0-8243-0556-7 J9 ANNU REV MED JI Annu. Rev. Med. PY 2005 VL 56 BP 193 EP 212 DI 10.1146/annurev.med.56.082103.104617 PG 20 WC Medicine, General & Internal SC General & Internal Medicine GA 904ND UT WOS:000227504100012 PM 15660509 ER PT S AU Dykxhoorn, DM Lieberman, J AF Dykxhoorn, DM Lieberman, J TI The silent revolution: RNA interference as basic biology, research tool, and therapeutic SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE small interfering RNA; miRNA; posttranscriptional gene silencing gene therapy ID DOUBLE-STRANDED-RNA; HEPATITIS-B-VIRUS; MAMMALIAN-CELLS; GENE-EXPRESSION; IN-VIVO; C-ELEGANS; MESSENGER-RNA; DROSOPHILA CELLS; SYNTHETIC SIRNAS; TRANSGENIC MICE AB RNA interference (RNAi) is an evolutionarily conserved mechanism for silencing gene expression. In primitive organisms, RNAi protects the genome from viruses and other insertable genetic elements and regulates gene expression during development. The antisense (guide) strand of short double-stranded RNAs is incorporated into an RNA-induced silencing complex that can either suppress protein expression or direct degradation of messenger RNAs that contain homologous sequence(s). The discovery that RNAi works in mammalian cells has sparked intense investigation into its role in normal mammalian cell function, its use as a tool to understand or screen for genes functioning in cellular pathways in healthy and diseased cells and animals, and its potential for therapeutic gene silencing. RNAi may provide an important new therapeutic modality for treating infection, cancer, neurodegenerative disease, and other illnesses, although in vivo delivery of small interfering RNAs into cells remains a significant obstacle. C1 Harvard Univ, Sch Med, CBR, Biomed Res Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Dykxhoorn, DM (reprint author), Harvard Univ, Sch Med, CBR, Biomed Res Inst, Boston, MA 02115 USA. EM dykxhoor@cbr.med.harvard.edu; lieberman@cbr.med.harvard.edu RI Lieberman, Judy/A-2717-2015; Dykxhoorn, Derek/D-1357-2015 FU NIAID NIH HHS [AI056900] NR 114 TC 215 Z9 235 U1 2 U2 32 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 BN 978-0-8243-0556-7 J9 ANNU REV MED JI Annu. Rev. Med. PY 2005 VL 56 BP 401 EP 423 DI 10.1146/annurev.med.56.082103.104606 PG 23 WC Medicine, General & Internal SC General & Internal Medicine GA 904ND UT WOS:000227504100022 PM 15660519 ER PT S AU Newburg, DS Ruiz-Palacios, GM Morrow, AL AF Newburg, DS Ruiz-Palacios, GM Morrow, AL TI Human milk glycans protect infants against enteric pathogens SO ANNUAL REVIEW OF NUTRITION SE Annual Review of Nutrition LA English DT Review; Book Chapter DE oligosaccharides; breastfeeding; diarrhea; mucosal immunity ID FIMBRIATED ESCHERICHIA-COLI; BLOOD GROUP ANTIGENS; BREAST-FED INFANTS; H3 INFLUENZA-A; FUCOSYLATED OLIGOSACCHARIDES; PSEUDOMONAS-AERUGINOSA; EPITHELIAL-CELLS; BLOCK BINDING; INHIBITION; RECEPTOR AB Breastfed infants have lower morbidity and mortality due to diarrhea than those fed artificially. This had been attributed primarily to the secretory antibodies and prebiotic factors in human milk. Oligosaccharides are the third largest component of human milk. They were initially considered to be functionless by-products of glycoprotein and glycolipid synthesis during milk production. However, in the past few decades it has become apparent that the human milk oligosaccharides are composed of thousands of components, at least some of which protect against pathogens. Oligosaccharide protection against infectious agents may result in part from their prebiotic characteristics, but is thought to be primarily due to their inhibition of pathogen binding to host cell ligands. Most human milk oligosaccharides are fucosylated, and their production depends on enzymes encoded by the genes associated with expression of the Lewis blood group system. The expression of specific fucosylated oligosaccharides in milk thus varies in relation to maternal Lewis blood group type, and is significantly associated with the risk of infectious disease in breastfed infants. Specific fucosylated moieties of oligosaccharides and related glycoconjugates (glycans) are able to inhibit binding and disease by specific pathogens. This review presents the argument that specific glycans, especially the oligosaccharides, are the major constituent of an innate immune system of human milk whereby the mother protects her infant from enteric and other pathogens through breastfeeding. The large input of energy expended by the mother in the synthesis of milk oligosaccharides is consistent with the human reproductive strategy of large parental input into rearing relatively few offspring through a prolonged period of maturation. These protective glycans may prove useful as a basis for the development of novel prophylactic and therapeutic agents that inhibit diseases caused by mucosal pathogens. C1 Massachusetts Gen Hosp, Div Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Infectol, Mexico City 14000, DF, Mexico. Univ Cincinnati, Childrens Hosp, Ctr Med, Ctr Biostat & Epidemiol, Cincinnati, OH 45229 USA. RP Newburg, DS (reprint author), Massachusetts Gen Hosp, Div Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. EM dnewburg@partners.org; gmrps@servidor.unam.mx; ardythe.morrow@cchmc.org RI Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 FU NICHD NIH HHS [HD13021]; NIDDK NIH HHS [DK59811, DK33506] NR 63 TC 279 Z9 296 U1 4 U2 66 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0199-9885 BN 978-0-8243-2825-2 J9 ANNU REV NUTR JI Annu. Rev. Nutr. PY 2005 VL 25 BP 37 EP 58 DI 10.1146/annurev.nutr.25.050304.092553 PG 28 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 962DD UT WOS:000231710300004 PM 16011458 ER PT S AU Chauhan, D Hideshima, T Anderson, KC AF Chauhan, D Hideshima, T Anderson, KC TI Proteasome inhibition in multiple myeloma: Therapeutic implication SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY SE Annual Review of Pharmacology and Toxicology LA English DT Review; Book Chapter DE plasma call neoplasm; proteasomes; growth; survival; apoptosis; drug-resistance ID NF-KAPPA-B; SQUAMOUS-CELL CARCINOMA; PHASE-I TRIAL; DRUG-RESISTANCE; CHEMOTHERAPEUTIC-AGENTS; MITOCHONDRIAL PROTEIN; MOLECULAR-MECHANISMS; INDUCED APOPTOSIS; PS-341; ACTIVATION AB Normal cellular functioning requires processing of proteins regulating cell cycle, growth, and apoptosis. The ubiquitin-proteasome pathway (UBP) modulates intracellular protein degradation. Specifically, the 26S proteasome is a multienzyme protease that degrades misfolded or redundant proteins; conversely, blockade of the proteasomal degradation pathways results in accumulation of unwanted proteins and cell death. Because cancer cells are more highly proliferative than normal cells, their rate of protein translation and degradation is also higher. This notion led to the development of proteasome inhibitors as therapeutics in cancer. The FDA recently approved the first proteasome inhibitor bortezomib (Velcade(TM)), formerly known as PS-341, for the treatment of newly diagnosed and relapsed/refractory multiple myeloma (MM). Ongoing studies are examining other novel proteasome inhibitors, in addition to bortezomib, for the treatment of MM and other cancers. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Chauhan, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. EM kenneth-anderson@dfci.harvard.edu RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 66 TC 92 Z9 101 U1 2 U2 5 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0362-1642 BN 978-0-8243-0444-7 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2005 VL 45 BP 465 EP 476 DI 10.1146/annurev.pharmtox.45.120403.100037 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 904NC UT WOS:000227504000019 PM 15822185 ER PT J AU Sepehr, A Kamangar, F Fahimi, S Saidi, F Abnet, CC Dawsey, SM AF Sepehr, A Kamangar, F Fahimi, S Saidi, F Abnet, CC Dawsey, SM TI Poor oral health as a risk factor for esophageal squamous dysplasia in northeastern Iran SO ANTICANCER RESEARCH LA English DT Article DE esophageal cancer; oral health; Iran ID CANCER AB Background: Northeastern Iran has one of the highest rates of esophageal squamous cell carcinoma (ESCC) in the world. The reasons for observing such high rates of ESCC in this area are not fully clear. The current study evaluates the association between some potential risk factors and squamous dysplasia, a precursor lesion of ESCC, in northeastern Iran. Materials and Methods: Using logistic regression, we compared potential risk factors of ESCC in 124 individuals with dysplasia and 50 normal individuals from northeastern Iran. Case/control status was histologically proven in all 174 study participants. Results: Poor oral health showed a dose-response association with ESCC risk (p for trend < 0.01). Edentulous individuals had 5-fold higher risk of dysplasia compared to participants with good oral health (p-value < 0.01). Conclusion: Our results are consistent with two other published studies that have shown oral health as a risk factor for ESCC. The high incidence of ESCC in northeastern Iran may be partly attributable to poor oral health. C1 NCI, Canc Prevent Studies Branch, CCR, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Int Agcy Res Canc, F-69372 Lyon, France. Iran Mehr Hosp, Dept Surg, Tehran, Iran. RP Kamangar, F (reprint author), NCI, Canc Prevent Studies Branch, CCR, 6116 Execut Blvd,Rm 705,Suite 705, Bethesda, MD 20892 USA. EM kamangaf@mail.nih.gov OI Abnet, Christian/0000-0002-3008-7843 NR 15 TC 25 Z9 25 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JAN-FEB PY 2005 VL 25 IS 1B BP 543 EP 546 PG 4 WC Oncology SC Oncology GA 913FW UT WOS:000228138000025 PM 15816626 ER PT J AU Tran, JH Jacoby, GA Hooper, DC AF Tran, JH Jacoby, GA Hooper, DC TI Interaction of the plasmid-encoded quinolone resistance protein Qnr with Escherichia coli DNA gyrase SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID TOPOISOMERASE-II; DETERMINING REGION; INHIBITOR GYRI; MICROCIN B17; DOUBLE HELIX; REPLICATION; MECHANISM; STRAND; GENE; FLUOROQUINOLONES AB Quinolone resistance normally arises by mutations in the chromosomal genes for type II topoisomerases and by changes in the expression of proteins that control the accumulation of quinolones inside bacteria. A novel mechanism of plasmid-mediated quinolone resistance was recently reported that involves DNA gyrase protection by a pentapeptide repeat family member called Qnr. This family includes two other members, McbG and MfpA, that are also involved in resistance to gyrase inhibitors. Purified Qnr-His(6) was shown to protect Escherichia coli DNA gyrase directly from inhibition by ciprofloxacin. Here we have provided a biochemical basis for the mechanism of quinolone resistance. We have shown that Qnr can bind to the gyrase holoenzyme and its respective subunits, GyrA and GyrB. The binding of Qnr to gyrase does not require the presence of the complex of enzyme, DNA, and quinolone, since binding occurred in the absence of relaxed DNA, ciprofloxacin, or ATP. We hypothesize that the formation of Qnr-gyrase complex occurs before the formation of the cleavage complex. Furthermore, there was a decrease in DNA binding by gyrase when the enzyme interacted with Qnr. Therefore, it is possible that the reaction intermediate recognized by Qnr is one early in the gyrase catalytic cycle, in which gyrase has just begun to interact with DNA. Quinolones bind later in the catalytic cycle and stabilize a ternary complex consisting of the drug, gyrase, and DNA. By lowering gyrase binding to DNA, Qnr may reduce the amount of holoenzyme-DNA targets for quinolone inhibition. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Lahey Clin Fdn, Dept Infect Dis, Burlington, MA USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org FU NIAID NIH HHS [AI43312, R01 AI057576, AI57576, R01 AI043312] NR 41 TC 154 Z9 191 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 2005 VL 49 IS 1 BP 118 EP 125 DI 10.1128/AAC.49.1.118-125.2005 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 883SF UT WOS:000226035300015 PM 15616284 ER PT J AU Kimmel, AD Goldie, SJ Walensky, RP Losina, E Weinstein, MC Paltiel, AD Zhang, H Freedberg, KA AF Kimmel, AD Goldie, SJ Walensky, RP Losina, E Weinstein, MC Paltiel, AD Zhang, H Freedberg, KA CA CEPAC Investigators TI Optimal frequency of CD4 cell count and HIV RNA monitoring prior to initiation of antiretroviral therapy in HIV-infected patients SO ANTIVIRAL THERAPY LA English DT Article ID MYCOBACTERIUM-AVIUM COMPLEX; IMMUNODEFICIENCY-VIRUS RNA; COST-EFFECTIVENESS; OPPORTUNISTIC INFECTIONS; MEASUREMENT ERROR; RANDOMIZED TRIAL; PLUS INDINAVIR; VIRAL LOAD; PLASMA; AIDS AB Context: Guidelines regarding the frequency of CD4 cell count and HIV RNA monitoring in HIV-infected patients vary, with recommended strategies ranging from every 2 to every 6 months. Objective: To determine optimal CD4 cell count and HIV RNA monitoring frequency in HIV-infected patients prior to antiretroviral therapy initiation. Design: Cost-effectiveness (CE) analysis using an HIV simulation model incorporating CD4 cell count and HIV RNA as immunological and virological predictors of clinical outcomes. Setting: Hypothetical clinical setting. Patients: Simulated cohort based on initial clinical presentation of HIV-infected patients in the US. Intervention: CD4 cell count and HIV RNA monitoring at frequencies ranging from every 2 to 24 months prior to antiretroviral initiation, as well as accelerated monitoring frequencies as CD4 cell counts approach a specified treatment threshold. Outcome measures: Life expectancy, quality-adjusted life expectancy and costs. Results: For patients presenting with median CD4 cell count 546/mm(3) and median HIV RNA 4.8 log(10) copies/ml, incremental CE ratios ranged from US$37800/quality-adjusted life year (QALY) gained for a constant testing frequency of every 18 months compared with every 24 months, to US$303300/QALY gained for a constant testing frequency of every 2 months compared with every 4 months when starting treatment at a CD4 cell count of 350/mm(3). Monitoring every 12 months until a warning CD4 cell count threshold of 450/mm(3) followed by every 3 months until 350/mm(3) had an incremental CE ratio of US$74700/QALY gained. When starting antiretroviral therapy at CD4 cell count 200/mm(3), monitoring every 12 months until, 300/mm(3) followed by every 2 months until treatment initiation yielded an incremental CE ratio of US$52200/QALY gained compared with the next best strategy. Increasing monitoring frequency as CD4 cell counts approached a treatment threshold yielded greater incremental clinical benefit for less cost than strategies using a constant frequency. Conclusions: Monitoring HIV-infected patients every 12 months until 100 CD4 cells/mm(3) prior to a specified treatment threshold followed by more frequent monitoring every 2 or 3 months until antiretroviral therapy initiation is both more effective and cost-effective than the current standard of care. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Harvard Ctr Risk Anal, Boston, MA 02115 USA. Harvard Univ, Inst Global Hlth, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. RP Kimmel, AD (reprint author), Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. EM akimmel@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU NIAID NIH HHS [K25 AI050436, K24 AI062476, 5 R01 AI42006, R01 AI042006, P30 AI042851, K23 AI001794]; ODCDC CDC HHS [U64/CCU114927, U64/CCU119525] NR 50 TC 13 Z9 13 U1 1 U2 2 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2005 VL 10 IS 1 BP 41 EP 52 PG 12 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 965PG UT WOS:000231962100004 PM 15751762 ER PT J AU Samet, JH Horton, NJ Meli, S Dukes, K Tripp, T Sullivan, L Freedberg, KA AF Samet, JH Horton, NJ Meli, S Dukes, K Tripp, T Sullivan, L Freedberg, KA TI A randomized controlled trial to enhance antiretroviral therapy adherence in patients with a history of alcohol problems SO ANTIVIRAL THERAPY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED PATIENTS; SOCIETY-USA PANEL; MEDICATION ADHERENCE; UPDATED RECOMMENDATIONS; SELF-REPORT; DRUG-USERS; INTERVENTION; SURVIVAL; EFFICACY AB Objective: To assess the effectiveness of an individualized multicomponent intervention to promote adherence to antiretroviral therapy (ART) in a cohort of HIV-infected individuals with a history of alcohol problems. Design: We conducted a randomized controlled trial to compare the usual medical follow-up with an adherence intervention. Setting: The principal enrolment site was Boston Medical Center, a private, not-for-profit, academic medical institution. Subjects: HIV-infected patients with a history of alcohol problems on ART. A total of 151 were enrolled and 141 (93%) were assessed at follow-up. Intervention: A nurse, trained in motivational interviewing, completed the following over 3 months in four encounters: addressed alcohol problems; provided a watch with a programmable timer. to facilitate pill taking; enhanced perception of treatment efficacy; and delivered individually tailored assistance to facilitate medication use. Main outcome measures: Prior 30-day adherence 2-95%, prior 3-day adherence of 100%, CD4 cell count, HIV RNA and alcohol consumption, each at both short- and long-term follow-up. Results: At follow-up, no significant differences in medication adherence, CD4 cell count, HIV RNA or alcohol consumption were found (all P values > 0.25). Conclusions: A multicomponent intervention to enhance adherence among HIV-infected individuals with a history of alcohol problems was not associated with changes in medication adherence, alcohol consumption or markers of HIV disease progression. The failure to change adherence in a group at high risk for poor adherence, despite utilizing an intensive individual-focused patient intervention, supports the idea of addressing medication adherence with supervised medication delivery or markedly simplified dosing regimens. C1 Boston Univ, Sch Med, CARE Unit, Gen Internal Med Sect, Boston, MA 02215 USA. Boston Univ, Sch Med, Med Ctr, Dept Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Med Ctr, Dept Social & Behav Sci, Boston, MA 02215 USA. Boston Univ, Sch Med, Med Ctr, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Med, Med Ctr, Dept Epidemiol, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Med Ctr, Dept Med, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Med Ctr, Dept Social & Behav Sci, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Med Ctr, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Med Ctr, Dept Epidemiol, Boston, MA 02215 USA. Smith Coll, Dept Math, Northampton, MA 01063 USA. DMSTAT, Medford, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA 02115 USA. RP Samet, JH (reprint author), Boston Univ, Sch Med, CARE Unit, Gen Internal Med Sect, Boston, MA 02215 USA. EM jsamet@bu.edu RI Horton, Nicholas/A-2493-2008; OI Horton, Nicholas/0000-0003-3332-4311 FU NCRR NIH HHS [M01 RR00533]; NIAAA NIH HHS [K24 AA015674, R01-AA10870, R01-AA11785] NR 55 TC 70 Z9 71 U1 1 U2 2 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2005 VL 10 IS 1 BP 83 EP 93 PG 11 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 965PG UT WOS:000231962100008 PM 15751766 ER PT J AU Kamin, D Hadigan, C Liebau, J Mazza, S Barrow, S Torriani, M Rubin, R Weiss, S Fischman, A Grinspoon, S AF Kamin, D Hadigan, C Liebau, J Mazza, S Barrow, S Torriani, M Rubin, R Weiss, S Fischman, A Grinspoon, S TI Depot specific regulation of glucose intake and insulin sensitivity in HIV lipodystrophy SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 7th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV CY NOV 13-16, 2005 CL Dublin, IRELAND C1 Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Musculoskeletal Radiol, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2005 VL 10 IS 8 BP L10 EP L11 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 009SN UT WOS:000235133100031 ER PT J AU Liebau, J Andersen, R Grinspoon, S Holalkere, N Sahani, D Hadigan, C AF Liebau, J Andersen, R Grinspoon, S Holalkere, N Sahani, D Hadigan, C TI Hepatic steatosis and insulin resistance in HIV infection SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 7th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV CY NOV 13-16, 2005 CL Dublin, IRELAND C1 Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2005 VL 10 IS 8 BP L30 EP L31 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 009SN UT WOS:000235133100063 ER PT J AU Johnson, VA Hazelwood, JD Kovacs, EZ Summers, WC Chu, WJ Den Hollander, JA Bush, BA Nabors, LB Kilby, JM Kinney, FC Raper, JL Shelton, BJ Hartley, S Madan, A Netson, KL Buchthal, S Benos, DJ AF Johnson, VA Hazelwood, JD Kovacs, EZ Summers, WC Chu, WJ Den Hollander, JA Bush, BA Nabors, LB Kilby, JM Kinney, FC Raper, JL Shelton, BJ Hartley, S Madan, A Netson, KL Buchthal, S Benos, DJ TI Comprehensive analyses of plasma and cerebrospinal fluid (CSF) compartments for HIV drug resistance, viral load, and chemokine/cytokine levels linked to neuropsychiatric testing and NMR spectroscopy findings in HIV-infected subjects treated at a university-based HIV clinic SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 14th International HIV Drug Resistance Workshop CY JUN 07-11, 2005 CL Quebec City, CANADA C1 Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Alabama, Sch Med, Dept Med, Birmingham, AL USA. Univ Alabama, Sch Med, Dept Physiol & Biophys, Birmingham, AL USA. Univ Alabama, Sch Med, Dept Radiol, Birmingham, AL 35233 USA. Univ Alabama, Sch Med, Dept Psychiat, Birmingham, AL USA. Univ Alabama, Sch Med, Dept Neurol, Birmingham, AL USA. Univ Alabama, Sch Med, Dept Biostat, Birmingham, AL USA. Univ Alabama, Sch Med, Dept Psychol, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2005 VL 10 SU 1 BP S181 EP S181 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 972RL UT WOS:000232470800169 ER PT J AU Johnson, VA Hazelwood, JD Kovacs, EZ Summers, WC Chu, WJ Den Hollander, JA Bush, BA Nabors, LB Kilby, JM Kinney, FC Raper, JL Shelton, BJ Hartley, S Madan, A Netson, KL Buchthal, S Benos, DJ AF Johnson, VA Hazelwood, JD Kovacs, EZ Summers, WC Chu, WJ Den Hollander, JA Bush, BA Nabors, LB Kilby, JM Kinney, FC Raper, JL Shelton, BJ Hartley, S Madan, A Netson, KL Buchthal, S Benos, DJ TI Comprehensive analyses of plasma and cerebrospinal fluid (CSF) compartments for HIV drug resistance, viral load, and chemokine/cytokine levels linked to neuropsychiatric testing and NMR spectroscopy findings in HIV-infected subjects treated at a university-based HIV clinic SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 14th International HIV Drug Resistance Workshop CY JUN 07-11, 2005 CL Quebec City, CANADA C1 Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Alabama, Sch Med, Dept Med, Birmingham, AL USA. Univ Alabama, Sch Med, Dept Physiol & Biophys, Birmingham, AL USA. Univ Alabama, Sch Med, Dept Radiol, Birmingham, AL 35233 USA. Univ Alabama, Sch Med, Dept Psychiat, Birmingham, AL USA. Univ Alabama, Sch Med, Dept Neurol, Birmingham, AL USA. Univ Alabama, Sch Med, Dept Biostat, Birmingham, AL USA. Univ Alabama, Sch Med, Dept Psychol, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2005 VL 10 IS 4 MA 166 BP S181 EP S181 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 965PQ UT WOS:000231963100182 ER PT J AU Mourdjeva, M Kyurkchiev, D Mandinova, A Altankova, I Kehayov, I Kyurkchiev, S AF Mourdjeva, M Kyurkchiev, D Mandinova, A Altankova, I Kehayov, I Kyurkchiev, S TI Dynamics of membrane translocation of phosphatidylserine during apoptosis detected by a monoclonal antibody SO APOPTOSIS LA English DT Article DE anti-phosphatidylserine monoclonal antibody; apoptosis; autoimmunity; phosphatidylserine translocation ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CELLS; RECOGNITION; EXPOSURE; SURFACE; PHOSPHOLIPIDS; LYMPHOCYTES; MACROPHAGES; ACTIVATION; DNA AB Translocation of phosphatidylserine (PS) to the outer leaflet of the cellular membrane seems to be a key step in apoptosis and cell activation. In this paper, the production and characterization of a monoclonal antibody designated as Mab 1H6 is described which does not show cross reactivity with others anionic phospholipids. It is demonstrated that Mab1H6 can recognize externalized PS at early stages after the induction of apoptosis shown by both flow cytometry and immunofluorescence. Our results show that translocation of PS can be detected as early as 5 min by immunofluorescence and 10 min by flow cytometry after the treatment of cells and a specific dynamics is observed concerning the location and distribution of the staining. These data prove that antibody Mab 1H6 can be used as a specific probe for detection of PS translocation. C1 Bulgarian Acad Sci, Inst Biol & Immunol Reprod, Dept Mol Immunol, BU-1113 Sofia, Bulgaria. Med Univ Sofia, Dept Clin Lab & Clin Immunol, Sofia, Bulgaria. Massachusetts Gen Hosp, Dept Dermatol, CRBC, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Kyurkchiev, S (reprint author), Bulgarian Acad Sci, Inst Biol & Immunol Reprod, Dept Mol Immunol, 73 Tzarigradsko Shosse, BU-1113 Sofia, Bulgaria. EM kyurkch@hotmail.com OI Mourdjeva, Milena/0000-0003-1416-1457 NR 23 TC 18 Z9 19 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1360-8185 J9 APOPTOSIS JI Apoptosis PD JAN PY 2005 VL 10 IS 1 BP 209 EP 217 DI 10.1007/s10495-005-6076-5 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 898IL UT WOS:000227070400021 PM 15711937 ER PT J AU Wald, LL Wiggins, GC Potthast, A Wiggins, CJ Triantafyllou, C AF Wald, LL Wiggins, GC Potthast, A Wiggins, CJ Triantafyllou, C TI Design considerations and coil comparisons for 7 T brain imaging SO APPLIED MAGNETIC RESONANCE LA English DT Article ID HIGH-FIELD MRI; BIRDCAGE COIL; PHASED-ARRAY; VOLUME COIL; RF COILS; NMR; STRENGTH; POWER; HEAD; BODY AB The development of 300 MHz radio-frequency (R-F) head coils analogous to those used at field strengths of 1.5 and 3 T is complicated by increased dissipative losses in conductive tissue, effects arising from the short RF wavelength in biological tissue (about 13 cm at 300 MHz), and the constraints imposed by the use of head gradient sets desirable for mitigating increased static field susceptibility effects. In this study, five RF head coils were constructed and tested on a 7 T scanner including 2 TEM designs, 2 birdcage designs and a local receive-only array. Signal-to-noise ratio, coil reception profiles and interactions between the coil and dielectric head were examined. Particular attention was placed on the coil's reception in the neck and shoulders, where the head gradient is unable to spatially encode the image. With the use of conductive shields and distributed capacitance, all of the coil designs could be made to image effectively at high field, but each design was found to have subtle differences in field distribution, interaction with the dielectric boundary conditions of the head and fringe fields in the neck and shoulders. In particular, the birdcage and array coils were found to have reduced B, reception field profiles in the neck and shoulders which helped reduce signal detection outside the linear region of the head gradient coil. Although the TEM coils exhibited higher signal detection in the neck and shoulders, all the coils picked up enough signal from these regions to produce artifacts in the brain. These artifacts could be mitigated through use of a conductive shield or by small local dephasing shims sewn into the shoulders of a jacket worn by the subject. Although homogeneous in low-dielectric-constant phantoms, the volume coil's B, profile was strongly peaked in the center of the head, rendering them spatially complementary to that observed in the surface coil array. The image profile of the surface coil was found to be less dramatically changed from patterns observed at lower field strength. Its dielectric brightening pattern was found to depend on the orientation of the coil with respect to the head. C1 Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Siemens Med Solut, Erlangen, Germany. RP Wald, LL (reprint author), Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, 13th St 149, Charlestown, MA 02129 USA. EM wald@nmr.mgh.harvard.edu RI Triantafyllou, Christina/E-7724-2011; Wald, Lawrence/D-4151-2009 NR 33 TC 29 Z9 29 U1 2 U2 3 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0937-9347 EI 1613-7507 J9 APPL MAGN RESON JI Appl. Magn. Reson. PY 2005 VL 29 IS 1 BP 19 EP 37 DI 10.1007/BF03166954 PG 19 WC Physics, Atomic, Molecular & Chemical; Spectroscopy SC Physics; Spectroscopy GA 970QB UT WOS:000232323600003 ER PT J AU Hillenbrand, AF Lo, KM Punchard, WFB Reese, TG Starewicz, PM AF Hillenbrand, AF Lo, KM Punchard, WFB Reese, TG Starewicz, PM TI High-order MR shimming: a simulation study of the effectiveness of competing methods, using an established susceptibility model of the human head SO APPLIED MAGNETIC RESONANCE LA English DT Article ID SPATIALLY LOCALIZED SIGNALS; MAGNETIC-FIELD; NMR; ACQUISITION; ARTIFACTS AB The first step in the process of shimming a magnetic field is to characterize it by obtaining a field map and decomposing that map into a convenient set of basis functions. The strength of each member of the set is then calculated. Finally, a set of correction elements which generate fields corresponding to the same spatial distribution as the basis functions is energized so that the sum of their fields and the error fields is substantially zero. The basis functions used typically are solutions to Laplace's equation and have been shown to be very effective when the region of interest is substantially free space. This paper addresses issues associated with shimming the magnetic field in a region in which there is a distribution of materials with different susceptibilities and which therefore is not free space. In such a region, Laplace's equation is no longer valid and in principle cannot be used to describe the magnetic field there. It is demonstrated that in spite of this, the same set of basis functions suffices for analyzing the field and the same set of elements suffices for correcting the field. The motivation for this study stems from the need to improve the magnetic field homogeneity when biological specimens are being imaged by magnetic resonance. In particular, this paper describes a study carried out by various simulated shimming strategies to improve the uniformity of the magnetic field over a multitissue model of susceptibility of the human head. The topics of magnetic susceptibility, the effect of shimming on MR images, shimming hardware and shimming methods are briefly reviewed. Two slices of the human head model were selected for detailed study, both offset inferior to the origin and including the base of the brain and the anterior sinus. The results of the study include comparisons between the strategies of global shimming, local slice-selective shimming and combinations of the two; the effects of shimming to various orders of spherical harmonies; and the effects of rotation and displacement of the head with respect to the shim frame of reference. C1 Resonance Res Inc, Billerica, MA 01821 USA. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA USA. RP Punchard, WFB (reprint author), Resonance Res Inc, 10 Cook St,Pinehurst Business Pk, Billerica, MA 01821 USA. NR 32 TC 14 Z9 14 U1 0 U2 6 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0937-9347 EI 1613-7507 J9 APPL MAGN RESON JI Appl. Magn. Reson. PY 2005 VL 29 IS 1 BP 39 EP 64 DI 10.1007/BF03166955 PG 26 WC Physics, Atomic, Molecular & Chemical; Spectroscopy SC Physics; Spectroscopy GA 970QB UT WOS:000232323600004 ER PT J AU Williams, DL Goldstein, G Minshew, NJ AF Williams, DL Goldstein, G Minshew, NJ TI Impaired memory for faces and social scenes in autism: clinical implications of memory dysfunction SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE autism; memory; information processing ID WORKING-MEMORY; DIAGNOSTIC INTERVIEW; RETRIEVAL SCHEMES; YOUNG-CHILDREN; VISUAL MEMORY; INDIVIDUALS; DISORDER; INTACT; RECALL; DISCRIMINATION AB A clinical memory test, the Wechsler Memory Scale-III (WMS-III), was used to study the auditory and visual memory of 29 high-functioning adults with autism and 34 group-matched normal controls. The individuals with autism performed as well as the controls on immediate and delayed memory for word pairs and stories and on a verbal working memory task. The autism group was impaired on immediate and delayed recall of faces and of family scenes and had impaired spatial working memory. The integrity of verbal working memory and impaired spatial working memory is consistent with the findings of other studies and may reflect the greater computational demands of the spatial task. Most importantly, the deficits in memory for faces and common social scenes, complex visual/spatial stimuli, demonstrate the contribution of memory dysfunction in autism to deficits in real life function. (C) 2004 National Academy of Neuropsychology. Published by Elsevier Ltd. All rights reserved. C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Minshew, NJ (reprint author), Univ Pittsburgh, Sch Med, Webster Hall Suite 300,3811 O Hara St, Pittsburgh, PA 15213 USA. EM minshewnj@upmc.edu FU NICHD NIH HHS [HD35469]; NINDS NIH HHS [NS33355] NR 53 TC 56 Z9 56 U1 7 U2 18 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6177 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD JAN PY 2005 VL 20 IS 1 BP 1 EP 15 DI 10.1016/j.acn.2002.08.001 PG 15 WC Psychology, Clinical; Psychology SC Psychology GA 886WI UT WOS:000226263200001 PM 15620811 ER PT J AU Zand, S Lio, PA Mackool, BT Duncan, LM AF Zand, S Lio, PA Mackool, BT Duncan, LM TI A slightly erythematous, firm papule on the upper arm SO ARCHIVES OF DERMATOLOGY LA English DT Article ID AMELANOTIC MELANOMA; DIAGNOSIS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Zand, S (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JAN PY 2005 VL 141 IS 1 BP 94 EP + PG 2 WC Dermatology SC Dermatology GA 887FB UT WOS:000226289900019 ER PT J AU Hadlock, TA Heaton, J Cheney, M Mackinnon, SE AF Hadlock, TA Heaton, J Cheney, M Mackinnon, SE TI Functional recovery after facial and sciatic nerve crush injury in the rat SO ARCHIVES OF FACIAL PLASTIC SURGERY LA English DT Article ID RETROGRADE AXONAL-TRANSPORT; MOTOR NUCLEUS; REGENERATION; MOUSE; NEURONS; MOTONEURONS; TRANSECTION; SUTURE; MUSCLE AB Objectives: To systematically record rat facial nerve recovery following crush injury to the main trunk with respect to ocular and vibrissial function and to compare the rates of facial and sciatic nerve recovery from crush injury in the same animals. This serves as a means of validating the functional parameters of facial nerve recovery against the well-known measure of hind limb function, the Sciatic Function Index. Methods: The main trunk of the facial nerve and the proximal segment of the sciatic nerve were exposed in all animals. Both nerves were subjected to standardized crush injury and subsequent daily functional testing. After a plateau of functional recovery was achieved, the animals were killed, and the distances between the sites of injury and the end musculature were measured, which allowed determination and comparison of recovery rates in both systems. Results: All crush injuries resulted in loss of electrical conductivity, as proven by intraoperative proximal nerve stimulation. Recovery of ocular and vibrissial motor function occurred starting at postoperative day (POD) 9 and continuing through POD 20. Hind limb function returned later (POD 14-34); however, when corrected for distance, the sciatic recovery rate (2.26 mm/d) appeared to match that of the facial nerve (1.5-2.4 mm/d). Conclusions: Recovery after facial nerve crush injury follows a predictable time course, and the rate of recovery is consistent with that of sciatic nerve injury. Return of the blink reflex, loss of vibrissial fibrillations, and return of vibrissial sweeping function appear to be internally consistent functional measures of facial recovery. These quantitative measures will be useful for future facial nerve manipulation studies. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Washington Univ, Sch Med, Div Plast & Reconstruct Surg, St Louis, MO USA. RP Hadlock, TA (reprint author), Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, 243 Charles St, Boston, MA 02114 USA. EM tessa_hadlock@meei.harvard.edu NR 18 TC 31 Z9 33 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1521-2491 J9 ARCH FACIAL PLAST S JI Arch. Facial Plast. Surg. PD JAN-FEB PY 2005 VL 7 IS 1 BP 17 EP 20 DI 10.1001/archfaci.7.1.17 PG 4 WC Surgery SC Surgery GA 983HC UT WOS:000233221100004 PM 15655169 ER PT J AU Henderson, DC Caglicro, E Copeland, PM Borba, CP Evins, E Hayden, D Weber, MT Anderson, J Allison, DB Daley, TB Schoenfeld, D Goff, DC AF Henderson, DC Caglicro, E Copeland, PM Borba, CP Evins, E Hayden, D Weber, MT Anderson, J Allison, DB Daley, TB Schoenfeld, D Goff, DC TI Glucose metabolism in patients with schizophrenia treated with atypical antipsychotic agents - A frequently sampled intravenous glucose tolerance test and minimal model analysis SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; INDUCED WEIGHT-GAIN; INSULIN SENSITIVITY; DIABETES-MELLITUS; CONVENTIONAL ANTIPSYCHOTICS; CLOZAPINE USE; RISK-FACTORS; OLANZAPINE; RISPERIDONE; DATABASE AB Background: While the incidence of new-onset diabetes mellitus may be increasing in patients with schizophrenia treated with certain atypical antipsychotic agents, it remains unclear whether atypical agents are directly affecting glucose metabolism or simply increasing known risk factors for diabetes. Objective: To study the 2 drugs most clearly implicated (clozapine and olanzapine) and risperidone using a frequently sampled intravenous glucose tolerance test. Design: A cross-sectional design in stable, treated patients with schizophrenia evaluated using a frequently sampled intravenous glucose tolerance test and the Bergman minimal model analysis. Setting: Subjects were recruited from an urban community mental health clinic and were studied at a general clinical research center. Patients: Fifty subjects signed informed consent and 41 underwent the frequently sampled intravenous glucose tolerance test. Thirty-six nonobese subjects with schizophrenia or schizoaffective disorder, matched by body mass index and treated with either clozapine, olanzapine, or risperidone, were included in the analysis. Main Outcome Measures: Fasting plasma glucose and fasting serum insulin levels, insulin sensitivity index, homeostasis model assessment of insulin resistance, and glucose effectiveness. Results: The mean +/- SD duration of treatment with the identified atypical antipsychotic agent was 68.3 +/- 28.9 months (clozapine), 29.5 +/- 17.5 months (olanzapine), and 40.9 +/- 33.7 (risperidone). Fasting serum insulin concentrations differed among groups (F-33=3.35; P=.047) (clozapine>olanzapine>risperidone) with significant differences between clozapine and risperidone (t(33)=2.32; P=.03) and olanzapine and risperidone (t(33)=2.15; P=.04). There was a significant difference in insulin sensitivity index among groups (F-33=10.66; P<.001) (clozapineolanzapine>risperidone) (clozapine vs risperidone, t(33)=2.94;P=.006;olanzapine vs risperidone, t(33)=2.42;P=.02). There was a significant difference among groups in glucose effectiveness (F-30=4.18; P =.02) (clozapine= 30 kg/m(2), N = 1914). The subscapular to triceps skinfold thickness ratio (SFR) was used to categorize body fat distribution into central (SFR > 1, N = 5211) and peripheral (SFR :5 :1, N = 6223). Results: Cirrhosis resulted in death or hospitalization of 88 participants during 149,888 person-years of follow-up (59/100,000 person-years). Among persons with a central body fat distribution, cirrhosis-related deaths or hospitalizations were more common in obese persons (115/100,000 person-years, adjusted hazard ratio 2.2, 95% confidence interval [CI] 1.1-4.6) and in overweight persons (94/100,000 person-years, adjusted hazard ratio 1.5, 95% CI 0.8-3.0) compared to normal-weight persons (59/100,000 person-years). However, among persons with a peripheral fat distribution, there was no association between obesity (adjusted hazard ratio 0.7, 95% CI 0.3-:1.6) or overweight (adjusted hazard ratio 0.8, 95% CI 0.2-2.8) and cirrhosis-related death or hospitalization. Conclusions: The risk of cirrhosis-related death or hospitalization appears to be increased in the presence of cirrhosis, but only among persons with a central fat distribution. The excess risk associated with central obesity might be related to insulin resistance and hepatic steatosis. C1 Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, NW Hepatitis C Resource Ctr, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Resource & Informat Ctr, Seattle, WA USA. Univ Washington, Sch Med, Div Gastroenterol, Seattle, WA USA. Univ Washington, Sch Med, Div Gen Internal Med, Seattle, WA USA. Univ Washington, Sch Med, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Ioannou, GN (reprint author), Seattle VA Med Ctr, S-111 Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu OI Kahn, Steven/0000-0001-7307-9002; Dominitz, Jason/0000-0002-8070-7086 FU NIDDK NIH HHS [DK 02456, DK02957] NR 51 TC 16 Z9 16 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JAN PY 2005 VL 3 IS 1 BP 67 EP 74 DI 10.1053/S1542-3565(04)00442-2 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 993UG UT WOS:000233980000011 PM 15645407 ER PT J AU Alper, CA Larsen, CE Yunis, EJ Husain, Z Awdeh, ZL AF Alper, CA Larsen, CE Yunis, EJ Husain, Z Awdeh, ZL TI The (Relatively) simple genetics of a polygenic disease: Type 1 diabetes (TID). SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 CBR Inst Biomed Res, Div Immunogenet, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med & Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S137 EP S137 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400384 ER PT J AU Awdeh, ZL Yunis, EJ Audeh, MJ Fici, DA Pugliese, A Larsen, CE Alper, CA AF Awdeh, ZL Yunis, EJ Audeh, MJ Fici, DA Pugliese, A Larsen, CE Alper, CA TI A single explanation for three puzzles in type 1 diabetes (T1D). SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 CBR Inst Biomed Res, Div Immunogenet, Boston, MA USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med & Pediat, Boston, MA 02115 USA. Boston Coll, Chestnut Hill, MA 02167 USA. Univ Miami, Diabet Res Inst, Miami, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S137 EP S137 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400383 ER PT J AU Bardwell, PD Shimizu, I Buchli, JC Sykes, M AF Bardwell, PD Shimizu, I Buchli, JC Sykes, M TI Successful induction of mixed chimerism and tolerance with non-myeloablative conditioning in mice presensitized with fully mismatched skin grafts. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02115 USA. RI Bardwell, Philip/H-2219-2014 OI Bardwell, Philip/0000-0002-3835-255X NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S25 EP S26 PG 2 WC Immunology SC Immunology GA 926DY UT WOS:000229104400067 ER PT J AU Benichou, G Germana, SK Akiyama, Y Tanaka, K LeGuern, C AF Benichou, G Germana, SK Akiyama, Y Tanaka, K LeGuern, C TI MHC class II controls CD4+, CD25+ regulatory tolerance to allogeneic transplants. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Massachusetts Gen Hosp, Transplant Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, TBRC, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S11 EP S11 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400027 ER PT J AU Chen, Z Benoist, C Mathis, D AF Chen, Z Benoist, C Mathis, D TI Collaboration between central tolerance and peripheral regulation to control autoimmunity. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S25 EP S25 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400064 ER PT J AU Cotta-De-Almeida, V Onaldi, D Maillard, M Alt, FW Snapper, SB AF Cotta-De-Almeida, V Onaldi, D Maillard, M Alt, FW Snapper, SB TI Defective intrathymic T cell development and early onset of IBD in mice devoid of WASP and N-WASP. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Genet, Boston, MA 02115 USA. Oswaldo Cruz Fdn, Dept Cell Biol, Rio De Janeiro, Brazil. Univ Lausanne Hosp, Lausanne, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S83 EP S83 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400229 ER PT J AU Cotta-de-Almeida, V Takeshima, F Maillard, M Michetti, P Snapper, SB AF Cotta-de-Almeida, V Takeshima, F Maillard, M Michetti, P Snapper, SB TI Regulatory T cell dysfunction and a unique autoreactive T cell population may be associated with the development of colitis in WASP-deficient mice. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. Oswaldo Cruz Fdn, Dept Cell Biol, Rio De Janeiro, Brazil. Nagasaki Univ, Sch Med, Nagasaki 852, Japan. Univ Lausanne Hosp, Lausanne, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S11 EP S11 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400026 ER PT J AU De, AK Laudanski, K Maier, RV Bankey, PE Minei, JP Elson, C Hayden, D Schoenfeld, DA Moldawer, LL Tompkins, RG Miller-Graziano, CL AF De, AK Laudanski, K Maier, RV Bankey, PE Minei, JP Elson, C Hayden, D Schoenfeld, DA Moldawer, LL Tompkins, RG Miller-Graziano, CL TI Alterations in Th1 subpopulations correspond to clinical pathology in severe trauma patients. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Univ Washington, Seattle, WA 98195 USA. SW Texas State Univ, Dallas, TX USA. Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Florida, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S163 EP S163 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400459 ER PT J AU Drouin, EE Falk, B Glickstein, LJ Klitz, W Kwok, WW Nepom, GT Baxter-Lowe, LA Steere, AC AF Drouin, EE Falk, B Glickstein, LJ Klitz, W Kwok, WW Nepom, GT Baxter-Lowe, LA Steere, AC TI Determination of Borrelia burgdorferi outer-surface protein A(161-175) peptide binding to HLA-DR molecules associated with antibiotic-refractory or antibiotic-responsive Lyme arthritis. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol,CIID, Boston, MA USA. Benaroya Res Inst, Seattle, WA USA. Univ Calif Berkeley, Oakland, CA USA. Univ Calif San Francisco, Immunogenet & Transplantat Lab, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S158 EP S159 PG 2 WC Immunology SC Immunology GA 926DY UT WOS:000229104400447 ER PT J AU Fehr, T Chittenden, M Wekerle, T Sykes, M AF Fehr, T Chittenden, M Wekerle, T Sykes, M TI Evidence for early anergy followed by rapid peripheral deletion of donor-specific CD8 T cells after non-myeloablative BMT with anti-CD154: In search of a tolerogenic donor cell. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Med Univ Vienna, Dept Surg, Vienna, Austria. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S36 EP S36 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400096 ER PT J AU Feske, S Prakriya, M Rao, A AF Feske, S Prakriya, M Rao, A TI Defect in CRAC Ca2+ channel function associated with altered K+ channel Gating properties in T cells from immunodeficient patients SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Stanford Univ, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S246 EP S246 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400692 ER PT J AU Jasinski, JM Yu, L Nakayama, M Liu, E Li, MM Miao, D Lipes, MA Wegmann, D Eisenbarth, GS AF Jasinski, JM Yu, L Nakayama, M Liu, E Li, MM Miao, D Lipes, MA Wegmann, D Eisenbarth, GS TI BDC 12-4.1 (anti-insulin B : 9-23) T cell receptor transgenic mice are lymphopenic but entrain early insulitis and can cause SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr, Denver, CO 80206 USA. Harvard Univ, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S33 EP S33 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400088 ER PT J AU Jin, Z Wan, D Wang, HB Ghiran, I Soberman, RJ Weller, PF AF Jin, Z Wan, D Wang, HB Ghiran, I Soberman, RJ Weller, PF TI 5-lipoxygenase locolization to cytosolic lipid bodies in rat basophil leukemia cells. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Allgery & Inflammat, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S55 EP S56 PG 2 WC Immunology SC Immunology GA 926DY UT WOS:000229104400154 ER PT J AU Kono, M Dunn, IS Rose, LB Durda, PJ Kurnick, JT AF Kono, M Dunn, IS Rose, LB Durda, PJ Kurnick, JT TI Role of the MAP kinase signaling pathway in the regulation of antigen expression by human melanomas. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 CytoCure LLC, Beverly, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S181 EP S181 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400511 ER PT J AU Kump, LI Castaneda, RAC Androudi, SN Reed, GF Foster, CS AF Kump, LI Castaneda, RAC Androudi, SN Reed, GF Foster, CS TI Visual outcomes in children with juvenile idiopathic arthritis-associated uveitis. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S186 EP S186 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400526 ER PT J AU Laouar, A Haridas, V van Lier, RAW Yagita, H Manjunath, N AF Laouar, A Haridas, V van Lier, RAW Yagita, H Manjunath, N TI A novel CD70+ APC imprints a unique pattern of NK receptors on gut mucosal CD8 T cells SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Harvard Univ, Sch Med, CBR, Biomed Res Inst,Dept Pediat, Boston, MA USA. Univ Amsterdam, Acad Med Ctr, Dept Lab Immunol, NL-1105 AZ Amsterdam, Netherlands. Juntendo Univ, Dept Med, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S71 EP S71 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400196 ER PT J AU Lin, JH Bashir, MM Zhang, W Werth, VP AF Lin, JH Bashir, MM Zhang, W Werth, VP TI Thalidomide, an anti-inflammatory medication, inhibits the induction of tumor necrosis factor-alpha (TNF alpha) in ultraviolet B (UVB)-irradiated human keratinocytes by destabilizing the TNF alpha mRNA SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S258 EP S258 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400724 ER PT J AU Mora, JR Cheng, G Picarella, D Briskin, M Buchanan, N von Andrian, UH AF Mora, JR Cheng, G Picarella, D Briskin, M Buchanan, N von Andrian, UH TI Dynamic control of T cell homing by gut and peripheral dendritic cells. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Harvard Univ, Sch Med, CBRI, Boston, MA 02115 USA. Millennium Pharmaceut, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S80 EP S81 PG 2 WC Immunology SC Immunology GA 926DY UT WOS:000229104400223 ER PT J AU O'Connor, KC Moore, NH Bregoli, L Bradshaw, E Wucherpfennig, K Hafler, DA AF O'Connor, KC Moore, NH Bregoli, L Bradshaw, E Wucherpfennig, K Hafler, DA TI Characterization of B cell immunoglobulin variable region genes derived from lesions of patients with MS SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S102 EP S102 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400284 ER PT J AU O'Connor, KC Robinson, W Weichsel, K Chitnis, T Wong, S Steinman, L Fukaura, H De Jager, P Wucherpfennig, K Hafler, D AF O'Connor, KC Robinson, W Weichsel, K Chitnis, T Wong, S Steinman, L Fukaura, H De Jager, P Wucherpfennig, K Hafler, D TI High-throughput analysis of autoantibodies recognizing myelin antigens in acute disseminated encephalomyelitis. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Stanford Univ, Dept Neurol & Neurol Sci, Palo Alto, CA 94304 USA. New York State Dept Hlth, Wadsworth Ctr Labs & Res, Diagnost Immunol Lab, Albany, NY 12201 USA. Iwate Med Univ, Dept Neurol, Morioka, Iwate 020, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S6 EP S6 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400011 ER PT J AU Ohmura, K Nguyen, LT Locksley, RM Benoist, C Mathis, D AF Ohmura, K Nguyen, LT Locksley, RM Benoist, C Mathis, D TI IL-4 can be a key positive regulator of inflammatory arthritis. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Dohgo Spa Hosp, Ctr Rheumat Dis, Matsuyama, Ehime, Japan. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S44 EP S44 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400118 ER PT J AU Paul, E Schneider, TJ Carroll, MC AF Paul, E Schneider, TJ Carroll, MC TI B cell receptor editing begins in the bone marrow. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S221 EP S222 PG 2 WC Immunology SC Immunology GA 926DY UT WOS:000229104400626 ER PT J AU Reddy, J Illes, Z Zhang, X Encinas, J Pyrdol, J Nicholson, L Sobel, R Wutcherpfennig, K Kuchroo, V AF Reddy, J Illes, Z Zhang, X Encinas, J Pyrdol, J Nicholson, L Sobel, R Wutcherpfennig, K Kuchroo, V TI Genetic resistance to Autoimmunity is mediated by autoantigen-specific CD4+CD25+ regulatory cells SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S102 EP S102 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400285 ER PT J AU Saito, TI Sykes, M AF Saito, TI Sykes, M TI Clinical relevance of recipient leukocyte infusion (RLI) therapy SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Massachusetts Gen Hosp, TBRC BMT Sect, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S64 EP S64 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400177 ER PT J AU Shimomura, Y Mizoguchi, E Bhan, K Mizoguchi, A AF Shimomura, Y Mizoguchi, E Bhan, K Mizoguchi, A TI BAFF-but not LT-dependent B cell expansion contributes to the suppression of lethal intestinal inflamation. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S13 EP S13 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400032 ER PT J AU Shirane, K Hokama, A Shimomura, Y Ogawa, A Yoshida, M Rietdijk, ST Snapper, SB Terhorst, C Blumberg, RS Mizoguchi, A AF Shirane, K Hokama, A Shimomura, Y Ogawa, A Yoshida, M Rietdijk, ST Snapper, SB Terhorst, C Blumberg, RS Mizoguchi, A TI Cross-linking of lipid rafts on CD4(+) T cells by an epitheliall lectin, gallectin-4, contributes to the exacerbation of intestinal inflammation. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Immunol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S232 EP S232 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400654 ER PT J AU Stock, P Akbari, O Freeman, GJ DeKruyff, RH Umetsu, DT AF Stock, P Akbari, O Freeman, GJ DeKruyff, RH Umetsu, DT TI Induction of THI-like regulatory cells that express Foxp3 and protect against airway hyperreactivity. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Univ Hosp Charite, Berlin, Germany. Harvard Univ, Childrens Hosp, Sch Med, Div Immunol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S11 EP S11 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400025 ER PT J AU Stuart, LM Takahshi, K Shi, L Savill, J Ezekowitz, RA AF Stuart, LM Takahshi, K Shi, L Savill, J Ezekowitz, RA TI MBLA/C deficienct mice display defective apoptotic cell clearance but no autoimmune phenotype. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. Univ Edinburgh, MRC, Ctr Inflammat Res, Edinburgh, Midlothian, Scotland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S225 EP S225 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400635 ER PT J AU Sugimoto, K Ogawa, A Mizoguchi, E Nagaishi, T Blumberg, RS Mizoguchi, A Bhan, AK AF Sugimoto, K Ogawa, A Mizoguchi, E Nagaishi, T Blumberg, RS Mizoguchi, A Bhan, AK TI Immature myeloid dendritic cells induce intestinal granulomas under certain environmental conditions. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S31 EP S31 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400083 ER PT J AU Umetsu, SE Lee, WL McIntire, JJ Downey, L Sanjanwala, B Akbari, O Berry, GJ Nagumo, H Freeman, GJ Umetsu, DT DeKryuff, RH AF Umetsu, SE Lee, WL McIntire, JJ Downey, L Sanjanwala, B Akbari, O Berry, GJ Nagumo, H Freeman, GJ Umetsu, DT DeKryuff, RH TI TIM-1 induces T cell activation and inhibits the development of peripheral tolerance. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Northwestern Univ, Dept Microbiol & Immunol, Chicago, IL USA. Stanford Univ, Sch Med, Stanford, CA USA. Harvard Univ, Sch Med, Div Immunol, Boston, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. NR 0 TC 1 Z9 2 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S17 EP S17 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400044 ER PT J AU Virella, G Derrick, MB Chassereau, C Thorpe, SR Lopes-Virella, MF AF Virella, G Derrick, MB Chassereau, C Thorpe, SR Lopes-Virella, MF TI The autoimmune response to modified human low-density lipoprotein. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC USA. Med Univ S Carolina, Dept Med, Charleston, SC USA. Ralph H Johnson VAMC, Charleston, SC USA. Univ S Carolina, Dept Chem & Biochem, Columbia, SC 29208 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S211 EP S211 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400596 ER PT J AU Wong, BS O'Malley, PE Tseng, YL Dor, FJMF Saidman, SL Yamada, K Sachs, DH AF Wong, BS O'Malley, PE Tseng, YL Dor, FJMF Saidman, SL Yamada, K Sachs, DH TI Lack of correlation between the presence of anti-human panel reactive antibodies (PRA) and anti-swine non-galactose-alpha 1,3-galactose (NonGal) cytotoxic antibodies in patients awaiting life-saving organ transplantation. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S280 EP S280 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400791 ER PT J AU Wu, CJ Biernacki, M Kutok, JL Rogers, SA Chen, LY Yang, XF Soiffer, RJ Ritz, J AF Wu, CJ Biernacki, M Kutok, JL Rogers, SA Chen, LY Yang, XF Soiffer, RJ Ritz, J TI Graft-versus-leukemia target antigens in chronic myelogenous leukemia (CML) are expressed on myeloid progenitor cells. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S12 EP S13 PG 2 WC Immunology SC Immunology GA 926DY UT WOS:000229104400031 ER PT J AU Yamagata, T Benoist, C Mathis, D AF Yamagata, T Benoist, C Mathis, D TI Identifying common "Innate signature" from gene expression profile in innate vs. adaptive lymphocytes SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S78 EP S78 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400215 ER PT J AU Zhang, M Alicot, EM Chiu, I Verna, N Vorap-Jensen, T Kessler, B Shimaoka, M Chan, R Friend, D Michael, LH Entman, ML Moore, FD Carroll, MC AF Zhang, M Alicot, EM Chiu, I Verna, N Vorap-Jensen, T Kessler, B Shimaoka, M Chan, R Friend, D Michael, LH Entman, ML Moore, FD Carroll, MC TI Identification of the target self-antigens in ischemia/reperfusion injury. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Harvard Univ, Sch Med, CBR, Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Baylor Coll Med, Debakery Heart Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Methodist Hosp, Houston, TX 77030 USA. Decimmune Therapeut, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S212 EP S212 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400600 ER PT J AU Zhang, M Takahashi, K Alicot, EM T Vorap-Jensen, T Kessler, B Jensenius, JC Ezekowitz, RAB Moore, FD Carroll, MC AF Zhang, M Takahashi, K Alicot, EM T Vorap-Jensen, T Kessler, B Jensenius, JC Ezekowitz, RAB Moore, FD Carroll, MC TI The role of mannose-binding lectin in natural IgM mediated ischemia/reperfusion injury SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Harvard Univ, Sch Med, CBR, Biomed Res Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Univ Aarhus, Dept Med Microbiol & Immunol, Aarhus C, Denmark. Decimmune Therapeut, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S75 EP S75 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400208 ER PT J AU Davis, AE AF Davis, AE TI The pathophysiology of hereditary angioedema SO CLINICAL IMMUNOLOGY LA English DT Review DE hereditary angioedema; C1 inhibitor; mucosa ID MOLECULAR-WEIGHT KININOGEN; HUMAN-ENDOTHELIAL-CELLS; C1 INHIBITOR; ANGIONEUROTIC-EDEMA; FACTOR-XII; PLASMA KALLIKREIN; BINDING-PROTEIN; PLASMINOGEN-ACTIVATOR; VASCULAR-PERMEABILITY; FUNCTIONAL-ANALYSIS AB Hereditary angioedema (HAE), characterized by recurrent episodes of angioedema involving the skin. or the mucosa of the upper respiratory or the gastrointestinal tracts, results from heterozygosity for deficiency of the serine proteinase inhibitor (serpin). C1 inhibitor (C1INH). The primary biological role of C1INH is to regulate activation of the complement system, the contact system, and the intrinsic coagulation system. Dining attacks of angioedema, together with decreasing levels of C1INH, the complement and contact system are activated: C2 and C4 levels fall and high molecular weight kininogen is cleaved. Although previous data suggested that symptoms in HAE might be mediated via complement system activation, a combination of recent clinical data, in vitro studies, and analysis of C1INH-deficient mice all indicate that the major mediator of angioedema is bradykinin: (1) a vascular penneability enhancing factor can be generated in vitro in C1INH-depleted, C2-deficient plasma, but not from C1INH-depleted, contact system-deficient plasma: this factor was identified by sequence analysis as bradykinin; (2) bradykinin can be detected in the plasma of HAE patients during attacks of angioedema: (3) in several members of one family, expression of a C1INH variant that inhibits contact system proteases but has defective inhibition of C1r and C1s does not result in HAE; (4) C1INH-deficient (C1INH(-/-)) mice have a defect in vascular permeability that is suppressed by treatment with specific plasma kallikrein inhibitors and by bradykinin type 2 receptor (Bk2R) antagonists. and is eliminated in C1INH Bk2R(-/-) double-deficient mice. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Pediat, Boston, MA 02115 USA. RP Davis, AE (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Pediat, 800 Huntington Ave, Boston, MA 02115 USA. EM aldavis@cbr.med.harvard.edu NR 77 TC 135 Z9 137 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JAN PY 2005 VL 114 IS 1 BP 3 EP 9 DI 10.1016/j.clim.2004.05.007 PG 7 WC Immunology SC Immunology GA 885YU UT WOS:000226194100003 PM 15596403 ER PT J AU Takayama, K Wang, C Besra, GS AF Takayama, K Wang, C Besra, GS TI Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis SO CLINICAL MICROBIOLOGY REVIEWS LA English DT Review ID ACYL CARRIER PROTEIN; KETOACYL-ACP SYNTHASE; CHAIN FATTY-ACIDS; CELL-FREE SYSTEM; CRYSTAL-STRUCTURE; CORYNEBACTERIUM-DIPHTHERIAE; PALMITIC ACID; BIOCHEMICAL-CHARACTERIZATION; ENZYMATIC CHARACTERIZATION; CYCLOPROPANE SYNTHETASE AB Mycobacterium tuberculosis is known to synthesize alpha-, methoxy-, and keto-mycolic acids. We propose a detailed pathway to the biosynthesis of all mycolic acids in M. tuberculosis. Fatty acid synthetase I provides C-20-S-coenzyme A to the fatty acid synthetase II system (FAS-IIA). Modules of FAS-IIA and FAS-IIB introduce cis unsaturation at two locations on a growing meroacid chain to yield three different forms of cis, cis-diunsaturated fatty acids (intermediates to alpha-, methoxy-, and keto-meroacids). These are methylated, and the mature meroacids and carboxylated C-26-S-acyl carrier protein enter into the final Claisen-type condensation with polyketide synthase-13 (Pks13) to yield mycolyl-S-Pks13. We list candidate genes in the genome encoding the proposed dehydrase and isomerase in the FAS-IIA and FAS-IIB modules. We propose that the processing of mycolic acids begins by transfer of mycolic acids from mycolyl-S-Pks13 to D-mannopyranosyl-1-phosphoheptaprenol to yield 6-O-mycolyl-beta-D-mannopyranosyl-1-phosphoheptaprenol and then to trehalose 6-phosphate to yield phosphorylated trehalose monomycolate (TMM-P). Phosphatase releases the phosphate group to yield TMM, which is immediately transported outside the cell by the ABC transporter. Antigen 85 then catalyzes the transfer of a mycolyl group from TMM to the cell wall arabinogalactan and to other TMMs to produce arabinogalactan-mycolate and trehalose dimycolate, respectively. We list candidate genes in the genome that encode the proposed mycolyltransferases I and II, phosphatase, and ABC transporter. The enzymes within this total pathway are targets for new drug discovery. C1 Univ Wisconsin, William S Middleton Mem Vet Hosp, Sch Med, Mycobacteriol Res Lab, Madison, WI 53705 USA. Univ Wisconsin, William S Middleton Mem Vet Hosp, Dept Med Microbiol & Immunol, Madison, WI 53705 USA. Univ Wisconsin, Dept Bacteriol, Madison, WI 53706 USA. Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England. RP Takayama, K (reprint author), Univ Wisconsin, William S Middleton Mem Vet Hosp, Sch Med, Mycobacteriol Res Lab, 2500 Overlook Terrace, Madison, WI 53705 USA. EM Kuni.Takayama@med.va.gov NR 126 TC 302 Z9 322 U1 9 U2 73 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0893-8512 J9 CLIN MICROBIOL REV JI Clin. Microbiol. Rev. PD JAN PY 2005 VL 18 IS 1 BP 81 EP + DI 10.1128/CMR.18.1.81-101.2005 PG 23 WC Microbiology SC Microbiology GA 891IU UT WOS:000226575300005 PM 15653820 ER PT J AU Harris, WH Muratoglu, OK AF Harris, WH Muratoglu, OK TI A review of current cross-linked polyethylenes used in total joint arthroplasty SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TOTAL HIP-ARTHROPLASTY; MOLECULAR-WEIGHT POLYETHYLENE; FOLLOW-UP REPORT; FEMORAL-HEAD; ACETABULAR COMPONENTS; WEAR; REPLACEMENT; HYLAMER; STERILIZATION; MOTION AB Major improvements have been made in new polyethylenes in regards to wear resistance and oxidation resistance. The background for and explanation of these improvements are presented in this study. The various manufacturing processes are described along with the possible features that the differences in manufacturing processes may have on wear, rate of particle generation, oxidation and mechanical properties. The role of some of the new polyethylenes in permitting the use of larger-diameter heads and the advantages of large-head diameters are discussed. Some of the advantages of metal-on-polyethylene versus hard-on-hard bearings also are described. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. RP Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, GRJ 1206, Boston, MA 02114 USA. EM orhun@alum.mit.edu NR 62 TC 34 Z9 36 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JAN PY 2005 IS 430 BP 46 EP 52 DI 10.1097/01.blo.0000152603.58384.e9 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 885GQ UT WOS:000226145500006 PM 15662303 ER PT J AU Brugge, WR AF Brugge, William R. BE DominguezMunoz, JE TI Management of chronic pancreatic pseudocyst: when to observe, when and how to drain SO CLINICAL PANCREATOLOGY: FOR PRACTISING GASTROENTEROLOGISTS AND SURGEONS LA English DT Article; Book Chapter ID ENDOSCOPIC MANAGEMENT; TRANSMURAL DRAINAGE; FLUID COLLECTION; CYSTIC LESIONS; ECHO ENDOSCOPE; PSEUDOANEURYSMS; PERFORMANCE; DIAGNOSIS; DUCT C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 28 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-47098-750-6 PY 2005 BP 323 EP 330 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BYA75 UT WOS:000297769100042 ER PT J AU Hutter, MM Warshaw, AL AF Hutter, Matthew M. Warshaw, Andrew L. BE DominguezMunoz, JE TI Pancreatic cancer: do we need a tissue diagnosis in order to proceed with resection? SO CLINICAL PANCREATOLOGY: FOR PRACTISING GASTROENTEROLOGISTS AND SURGEONS LA English DT Article; Book Chapter ID PERITONEAL CYTOLOGY C1 [Hutter, Matthew M.; Warshaw, Andrew L.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Warshaw, Andrew L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Hutter, MM (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-47098-750-6 PY 2005 BP 414 EP 418 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BYA75 UT WOS:000297769100051 ER PT J AU Jimenez, RE Fernandez-del Castillo, C AF Jimenez, Ramon E. Fernandez-del Castillo, Carlos BE DominguezMunoz, JE TI Staging laparoscopy and peritoneal cytology in pancreatic cancer SO CLINICAL PANCREATOLOGY: FOR PRACTISING GASTROENTEROLOGISTS AND SURGEONS LA English DT Article; Book Chapter ID ADENOCARCINOMA; HEAD; ULTRASONOGRAPHY; BILIARY; REGION C1 [Jimenez, Ramon E.] Univ Connecticut, Sch Med, Hartford, CT 06112 USA. [Jimenez, Ramon E.] Hartford Hosp, Hartford, CT 06115 USA. [Fernandez-del Castillo, Carlos] Harvard Univ, Sch Med, Boston, MA USA. [Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jimenez, RE (reprint author), Univ Connecticut, Sch Med, Hartford, CT 06112 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-47098-750-6 PY 2005 BP 419 EP 424 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BYA75 UT WOS:000297769100052 ER PT J AU Kharasch, ED Whittington, D Hoffer, C Krudys, K Craig, K Vicini, P Sheffels, P Lalovic, B AF Kharasch, ED Whittington, D Hoffer, C Krudys, K Craig, K Vicini, P Sheffels, P Lalovic, B TI Paradoxical role of cytochrome P450 3A in the bioactivation and clinical effects of levo-alpha-acetylmethadol - Importance of clinical investigations to validate in vitro drug metabolism studies SO CLINICAL PHARMACOKINETICS LA English DT Review ID LEVOMETHADYL ACETATE; NONINVASIVE PROBE; HUMAN HEPATOCYTES; OPIATE RECEPTORS; N-DEMETHYLATION; CYP3A4 ACTIVITY; LAAM; METHADONE; ALFENTANIL; DISPOSITION AB Objective: Levo-alpha-acetylmethadol (LAAM, levacetylmethadol) is a long-acting opioid agonist used for the prevention of opioid withdrawal. LAAM undergoes sequential N-demethylation to norLAAM and dinorLAAM, which are more potent and longer-acting than LAAM. Hepatic and intestinal microsomal N-demethylation in vitro is catalysed mainly by cytochrome P450 (CYP) 3A4; however, the role of CYP3A in LAAM disposition in humans in vivo is unknown. This investigation tested the hypothesis that CYP3A induction (or inhibition) would increase (or decrease) LAAM metabolism and bioactivation and, thus, clinical effects. It also related changes in LAAM disposition during enzyme inhibition or induction to any changes in pharmacological effect. Methods: Healthy volunteers (n = 13) completed the three-way, randomised, balanced crossover study. Subjects received oral LAAM (0.25 mg/kg) after CYP3A induction (rifampicin [rifampin]), inhibition (troleandomycin) or nothing (controls). Plasma and urine LAAM, norLAAM and dinorLAAM were determined by electrospray high-performance liquid chromatography/mass spectrometry (HPLC/MS). Dark-adapted pupil diameter change from baseline (miosis) was the LAAM effect measure. Results were analysed by noncompartmental methods and by a combined pharmacokinetic/pharmacodynamic model. Results: Compared with controls, CYP3A induction (or inhibition) decreased (or increased) plasma LAAM concentrations and mean area under the plasma concentration-time curve from time zero to infinity (AUC(infinity) 199 +/- 91 [control] versus 11.3 +/- 4.0 [rifampicin] and 731 +/- 229 ng center dot h/mL [troleandomycin]; p < 0.05), and increased (or decreased) median formation clearances of norLAAM (1740 versus 14 100 and 302 mL/h/kg; p < 0.05) and dinorLAAM (636 versus 7840 and 173 mL/h/kg; p < 0.05). Surprisingly, however, CYP3A induction (or inhibition) decreased (or increased) mean plasma metabolite AUC from 0 to 96 hours (AUC(96)) [norLAAM + dinorLAAM] (859 +/- 241 versus 107 +/- 48 and 1185 +/- 179 ng center dot h/mL; p < 0.05) and clinical effects (mean miosis AUC(96) 128 +/- 40 versus 22.5 +/- 14.9 and 178 +/- 81 mm 9 h; p < 0.05). Clinical effects were best correlated with plasma norLAAM concentrations. Conclusion: CYP3A mediates human LAAM N-demethylation and bioactivation to norLAAM and dinorLAAM in vivo. Paradoxically, however, CYP3A induction decreased and inhibition increased LAAM active metabolite concentrations and clinical effects. This suggests a CYP3A-mediated metabolic pathway leading to inactive metabolites, which predominates over CYP3A-dependent bioactivation. These results highlight the need for clinical investigations to validate in vitro drug metabolism studies. C1 Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Anesthesiol, Seattle, WA USA. Univ Washington, Dept Med Chem, Seattle, WA 98195 USA. Univ Washington, Dept Bioengn, Seattle, WA USA. Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA. RP Kharasch, ED (reprint author), Univ Washington, Dept Anesthesiol, 1959 NE Pacific St RR-442,Box 356540, Seattle, WA 98195 USA. EM kharasch@u.washington.edu FU NCRR NIH HHS [M01-RR00037]; NIBIB NIH HHS [9P41EB-01975]; NIDA NIH HHS [K24-DA00417, R01-DA14211]; NIDCR NIH HHS [T32DE-07023] NR 52 TC 9 Z9 9 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PY 2005 VL 44 IS 7 BP 731 EP 751 DI 10.2165/00003088-200544070-00005 PG 21 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 945NF UT WOS:000230508500005 PM 15966756 ER PT J AU Palevsky, PM O'Connor, T Zhang, JHY Star, RA Smith, MW AF Palevsky, PM O'Connor, T Zhang, JHY Star, RA Smith, MW CA VA NIH Acute Renal Failure Trial N TI Design of the VA/NIH Acute Renal Failure Trial Network (ATN) study: intensive versus conventional renal support in acute renal failure SO CLINICAL TRIALS LA English DT Article ID CONTINUOUS VENOVENOUS HEMOFILTRATION; RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; REPLACEMENT THERAPY; RANDOMIZED-TRIAL; TIDAL VOLUMES; CARE-UNIT; DIALYSIS; INTERMITTENT; HEMODIALYSIS AB The optimal management of renal replacement therapy (RRT) in acute renal failure (ARF) is uncertain. The VA/NIH Acute Renal Failure Trail Network Study (ATN Study) tests the hypothesis that a strategy of intensive RRT will decrease 60-day all-cause mortality in critically ill patients with ARF. Dose separation between the two treatment arms is achieved by increasing the frequency of intermittent hemodialysis (IHD) and sustained low efficiency dialysis (SLED) treatments from three times per week to six times per week, and by increasing continuous venovenous hemodiafiltration (CVVHDF) effluent volume from 20 mL/kg/hr to 35 mL/kg/hr. In both treatment arms, subjects convert between IHD and CVVHDF or SLED as hemodynamic status changes over time. This strategy attempts to replicate the conversion between modalities of RRT that occurs in clinical practice. However, in order to implement this strategy, flexible criteria needed to be developed to provide a balance between the need for uniformity of treatment between groups and practitioner discretion regarding modality of RRT to maintain patient safety. In order to address safety and ethical issues similar to those raised by the Office of Human Research Protections in its review of the ARDS Network studies, a survey of practitioner practices was performed and observational data on the management of RRT in comparable critically ill patients with ARF managed outside of the research context is being collected prospectively. These data will help inform the study's DSMB and site IRB's of the relationship between the study's treatment arms and concurrent clinical practice. C1 VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. VA Connecticut Healthcare Syst, Cooperat Studies Program, Coordinating Ctr, West Haven, CT USA. Natl Inst Hlth, Natl Inst Diab Digest & Kidney Dis, Bethesda, MD USA. VA Palo Alto Hlth Care Syst, Hlth Econ Resouce Ctr, Menlo Pk, CA USA. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Univ Dr, Pittsburgh, PA 15240 USA. EM palevsky@pitt.edu RI Smith, Mark/G-1522-2012; OI Smith, Mark/0000-0002-4582-9088; Palevsky, Paul/0000-0002-7334-5400 FU NIDDK NIH HHS [Y1-DK-3508-01/02/03, Y01 DK003508, Y01 DK003508-01, Y01 DK003508-02, Y01 DK003508-03, Y1-DK-3508-01] NR 35 TC 60 Z9 65 U1 0 U2 1 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2005 VL 2 IS 5 BP 423 EP 435 DI 10.1191/1740774505cn116oa PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 982RH UT WOS:000233178800006 PM 16317811 ER PT J AU Somoano, B Niendorf, KB Tsao, H AF Somoano, B Niendorf, KB Tsao, H TI Hereditary cancer syndromes of the skin SO CLINICS IN DERMATOLOGY LA English DT Review ID MULTIPLE ENDOCRINE NEOPLASIA; PEUTZ-JEGHERS-SYNDROME; BASAL-CELL CARCINOMA; HOGG-DUBE-SYNDROME; FAMILIAL ADENOMATOUS POLYPOSIS; MUIR-TORRE-SYNDROME; TUMOR-SUPPRESSOR GENE; MEDULLARY-THYROID-CARCINOMA; GENOTYPE-PHENOTYPE CORRELATIONS; NONPOLYPOSIS COLORECTAL-CANCER AB Hereditary cancer syndromes are a group of disorders characterized by a genetic susceptibility to the development of malignant tumors. Multiple cancers in the family or an abnormally early onset for the given cancer may suggest an underlying inherited predisposition. Awareness of their associated dermatologic manifestations can facilitate early detection of risk for neoplasms. This article provides an update on the clinical features, diagnostic criteria, and the use of genetic analysis in the detection of causative mutations of those hereditary cancer syndromes with cutaneous manifestations. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc Risk Anal, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. EM tsao.hensin@mgh.harvard.edu NR 240 TC 8 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0738-081X J9 CLIN DERMATOL JI Clin. Dermatol. PD JAN-FEB PY 2005 VL 23 IS 1 BP 85 EP 106 DI 10.1016/j.clindermatol.2004.09.012 PG 22 WC Dermatology SC Dermatology GA 905RJ UT WOS:000227587000012 PM 15708293 ER PT J AU Ballantyne, JC Carwood, CM AF Ballantyne, JC Carwood, CM TI Comparative efficacy of epidural, subarachnoid, and intracerebroventricular opioids in patients with pain due to cancer SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID CONTINUOUS INTRATHECAL MORPHINE; LONG-TERM; INTRACTABLE PAIN; INTRAVENTRICULAR MORPHINE; CONTINUOUS INFUSION; NARCOTIC ANALGESIA; TERMINALLY ILL; IMPLANTED PUMP; SYSTEM; RELIEF AB Background Since the 1970s, when endogenous opioids and opioid receptors were first isolated in the central nervous system, attempts have been made to optimize opioid therapy by delivering the medication centrally rather than systemically. Although the vast majority of cancer patients obtain satisfactory pain relief from individualized systemic treatment, there remain the few whose pain is refractory to systemic treatments. These patients may obtain relief from neuraxial opioid therapy: intracerebroventricular, epidural or subarachnoid. Objectives To compare intracerebroventricular therapy with other neuraxial treatments and to determine whether intracerebroventricular (ICV) has anything to offer over epidural (EPI) and subarachnoid (SA) catheters in terms of efficacy, adverse effects, and complications. Search strategy A number of electronic databases were searched to retrieve information for inclusion in this review. Non-English language reports are awaiting assessment. Unpublished data were not sought. Selection criteria Randomised studies of intracerebroventricular therapy for patients with intractable cancer pain were sought. However,this level of evidence was not available so data from uncontrolled trials, retrospective case series and uncontrolled prospective cohort studies were assessed. Data collection and analysis Our search did not retrieve any controlled trials. We therefore used data from uncontrolled studies to compare incidences of analgesic efficacy, adverse effects, and complications. We found 72 uncontrolled trials assessing ICV (13 trials, 337 patients), EPI (31 trials, 1343 patients), and SA (28 trials, 722 patients) in cancer patients. From these we extracted data on analgesic efficacy, common pharmacologic adverse effects, and complications. Main results Data from uncontrolled studies reported excellent pain relief among 73% of ICV patients compared with 72% EPI and 62% SA. Unsatisfactory pain relief was low in all treatment groups. Persistent nausea, persistent and transient urinary retention, transient pruritus, and constipation occurred more frequently with EPI and SA. Respiratory depression,sedation and confusion were most common with ICV. The incidence of major infection when pumps were used with EPI and SA was zero. There was a lower incidence of other complications with ICV therapy than with EPI or SA. Authors' conclusions Neuraxial opioid therapy is often effective for treating cancer pain that has not been adequately controlled by systemic treatment. However, long-term use of neuraxial therapy can be complicated by problems associated with the catheters. The data from uncontrolled studies suggests that ICV is at least as effective against pain as other neuraxial treatments and may be a successful treatment for patients whose cancer pain is resistant to other treatments. C1 Massachusetts Gen Hosp, Dept Anesthesia, Clin 3, Boston, MA 02114 USA. RP Ballantyne, JC (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, Clin 3, Fruit St, Boston, MA 02114 USA. EM ballantyne@etherdome.mgh.harvard.edu NR 73 TC 28 Z9 28 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1469-493X J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2005 IS 1 AR CD005178 DI 10.1002/14651858.CD005178 PG 24 WC Medicine, General & Internal SC General & Internal Medicine GA 967ND UT WOS:000232097000078 ER PT J AU Dellavalle, RP Drake, A Graber, M Heilig, LF Hester, EJ Johnson, KR McNealy, K Schilling, L AF Dellavalle, R. P. Drake, A. Graber, M. Heilig, L. F. Hester, E. J. Johnson, K. R. McNealy, K. Schilling, L. TI Statins and fibrates for preventing melanoma SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID CORONARY-HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; BASE-LINE CHARACTERISTICS; SCANDINAVIAN SIMVASTATIN SURVIVAL; RANDOMIZED CONTROLLED TRIAL; PLACEBO-CONTROLLED TRIAL; LONG-TERM INTERVENTION; RENAL-TRANSPLANT RECIPIENTS; ACUTE MYOCARDIAL-INFARCTION; EXTREMITY ARTERIAL-DISEASE AB Background Effective treatment for advanced melanoma is lacking. While no drug therapy currently exists for prevention of melanoma, in vitro, case-control, and animal model evidence suggest that lipid-lowering medications, commonly taken for high cholesterol, might prevent melanoma. Objectives To assess the effects of statin or fibrate lipid-lowering medications on melanoma outcomes. Search strategy We searched the Cochrane Skin Group Specialised Register (February 2003), CENTRAL (The Cochrane Library Issue 1, 2005), MEDLINE (to March 2003), EMBASE (to September 2003), CANCERLIT (to October 2002), Web of Science (to May 2003), and reference lists of articles. We approached study investigators and pharmaceutical companies for additional information (published or unpublished studies). Selection criteria Trials involving random allocation of study participants, where experimental groups used statins or fibrates and participants were enrolled for at least four years of therapy. Data collection and analysis Three authors screened 109 abstracts of articles with titles of possible relevance. We then thoroughly examined the full text of 72 potentially relevant articles. We requested unpublished melanoma outcomes data from the corresponding author of each qualifying trial. Main results We identified 16 qualifying randomised controlled trials (RCTs) (seven statin, nine fibrate). Thirteen of these trials (involving 62,197 participants) provided data on incident melanomas (six statin, seven fibrate). A total of 66 melanomas were reported in groups receiving the experimental drug and 86 in groups receiving placebo or other control therapies. For statin trials this translated to an odds ratio of 0.90 (95% confidence interval 0.56 to 1.44) and for fibrate trials an odds ratio of 0.58 (95% confidence interval 0.19 to 1.82). Subgroup analyses failed to show statistically significant differences in melanoma outcomes by gender, melanoma occurrence after two years of participation in trial, stage or histology, or trial funding. Subgroup analysis by type of fibrate or statin also failed to show statistically significant differences, except for the statin subgroup analysis which showed reduced melanoma incidence for lovastatin, based on one trial only (odds ratio 0.52, 95% confidence interval 0.27 to 0.99). Authors' conclusions The melanoma outcomes data collected in this review of RCTs of statins and fibrates does not exclude the possibility that these drugs prevent melanoma. There was a 10% and 42% reduction for participants on statins and fibrates, respectively, however these results were not statistically significant. Until further evidence is established, limiting exposure to ultraviolet radiation remains the most effective way to reduce the risk of melanoma. C1 Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Dellavalle, RP (reprint author), Denver Vet Affairs Med Ctr, 1055 Clermont St,Mail Stop 165, Denver, CO 80220 USA. EM robert.dellavalle@uchsc.edu NR 153 TC 16 Z9 16 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1469-493X J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2005 IS 4 AR CD003697 DI 10.1002/14651858.CD003697.pub2 PG 47 WC Medicine, General & Internal SC General & Internal Medicine GA 096UK UT WOS:000241402100028 ER PT J AU Shibolet, O Regushevskaya, E Brezis, M Soares-Weiser, K AF Shibolet, O Regushevskaya, E Brezis, M Soares-Weiser, K TI Cyclosporine A for induction of remission in severe ulcerative colitis SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID INFLAMMATORY-BOWEL-DISEASE; DOSE INTRAVENOUS CYCLOSPORINE; RANDOMIZED CONTROLLED-TRIAL; STEROID REFRACTORY ATTACKS; QUALITY-OF-LIFE; CLINICAL-TRIALS; DOUBLE-BLIND; TERM; EXPERIENCE; RESISTANT AB Background Ulcerative colitis (UC) is characterized by a life-long chronic course with remissions and exacerbations. Approximately 15% of patients have a severe attack requiring hospitalization at some time during their illness. These patients are traditionally treated with intravenous corticosteroids, with a response rate of approximately 60%. The patients who do not respond to steroid treatment usually require surgical removal of the large bowel (proctocolectomy or colectomy with an anal pouch). This surgical procedure essentially cures the patient from the disease but is associated with complications such as pouchitis. Few alternative treatments exist for severe ulcerative colitis: immunosuppressive medications (such as azathioprine) have a slow onset of action and are therefore usually ineffective. Antibiotics are not proven to be effective and biological treatments such as in infliximab are still under investigation. The introduction of cyclosporine-A (CsA) for use in patients with severe ulcerative colitis (UC) has provided an alternative to patients previously facing only surgical options. Cyclosporine acts mainly by inhibiting T lymphocyte function, which is essential for the propagation of inflammation. Unlike most other immunosuppressive agents, CsA does not suppress the activity of other hematopoietic cells, does not cause bone marrow suppression and has a rapid onset of action. This reviews aims to systematically assess the effectiveness and safety of CsA for severe UC. Objectives This review aimed to evaluate the effectiveness of cyclosporine A for patients with severe ulcerative colitis. Search strategy Electronic searches of The Cochrane Library (Issue 1, 2004), EMBASE (1980- 2004), and MEDLINE(1966-2004); hand searching the references of all identified studies; contacting the first author of each included trial. Selection criteria Randomised clinical trials comparing cyclosporine A with placebo or no intervention to obtain and maintain remission of idiopathic ulcerative colitis. Data collection and analysis Two reviewers independently appraised the quality of each trial and extracted the data from the included trials. Relative risks (RR) with 95% confidence intervals (CI) were estimated. The reviewers assumed an intention to treat analysis for the outcome measures. Main results Only two randomized controlled trials were identified that satisfied the inclusion criteria. These two trials could not be pooled for analysis because of major differences in design and patient populations. In the first trial, 11 patients received intravenous cyclosporine (4 mg/kg) and 9 received placebo. Two of 11 in the treatment group failed to respond to therapy compared with nine of nine in the placebo group (RR 0.18, 95% CI 0.05 - 0.64). However, 3/11 and 4/9 eventually underwent colectomy in the treatment and placebo groups respectively and follow-up was less than a month. In the second trial 15 patients were treated with intravenous cyclosporine and 15 with intravenous methylprednisolone. Five of 15 patients in the cyclosporine group failed to respond to therapy as compared to 7/15 in the methylprednisolone group (RR 0.71, 95% CI 0.29 - 1.75). After 1 year 7/ 9 responders in the cyclosporine group were still in remission compared with 4/8 in the steroid group (p > 0.05) and the colectomy rate was similar in both groups. The mean time to response in the cyclosporine group in the 2 trials was short (7 days and 5.2 days). These results should be interpreted with caution given the small numbers of trials and patients evaluated for comparison, and limited follow-up (few weeks in one trial to a year in the other). The precise assessment of the occurrence of adverse events was difficult because the trials described different adverse reactions, which reversed after discontinuation of cyclosporine. There was no evidence in the trials reviewed that cyclosporine was more effective than standard treatment for preventing colectomy but this effect cannot be excluded due to the small sample size and rarity of this outcome. Additional limitations of current research include lack of data on quality of life, costs and long-term results of cyclosporine therapy. Authors' conclusions There is limited evidence that cyclosporine is more effective than standard treatment alone for severe ulcerative colitis. The relatively quick response makes the short-term use of cyclosporine potentially attractive, but the long- term benefit is unclear, when adverse events such as cyclosporine-induced nephrotoxicity may become more obvious. There is a need for additional research on quality of life, costs and long- term results from cyclosporine therapy in severe ulcerative colitis. C1 Massachusetts Gen Hosp, Gastroenterol Unit GRJ715, Boston, MA USA. RP Shibolet, O (reprint author), Massachusetts Gen Hosp, Gastroenterol Unit GRJ715, 55 Fruit St, Boston, MA USA. EM shibolet@hadassah.org.il RI Brezis, Mayer/A-1041-2010 NR 56 TC 4 Z9 4 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1469-493X J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2005 IS 1 AR CD004277.pub2 DI 10.1002/14641858.CD004277.pub2 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 967ND UT WOS:000232097000038 ER PT S AU Pierce, MC Joo, C Cense, B Weinberg, E Park, BH Mujat, M Borenstein, J Tearney, GJ Bouma, BE de Boer, JF AF Pierce, MC Joo, C Cense, B Weinberg, E Park, BH Mujat, M Borenstein, J Tearney, GJ Bouma, BE de Boer, JF BE Tuchin, VV Izatt, JA Fujimoto, JG TI Fluid flow analysis in microfluidic devices by spectral-domain optical Doppler tomography SO COHERENCE DOMAIN OPTICAL METHODS AND OPTICAL COHERENCE TOMOGRAPHY IN BIOMEDICINE IX SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Coherence Domain Optical Methods and Optical Coherence Tomography in Biomedicine IX CY JAN 23-26, 2005 CL San Jose, CA SP SPIE DE optical coherence tomography; Fourier-domain; microfluidic devices; non-invasive imaging; fluid dynamics ID RETINAL BLOOD-FLOW; COHERENCE TOMOGRAPHY; HIGH-SPEED; PERFORMANCE; VELOCIMETRY AB Microfluidic devices are becoming increasingly popular for many applications, enabling biological and chemical reactions to be performed with nano- and picoliter sample volumes. Accurate measurement and monitoring of fluid flow behavior in the small channels of microfluidic systems is important for evaluating the performance of existing devices, and in the modeling and design of new microfluidic networks. We present here the results of experiments using spectral-domain optical Doppler tomography (SD-ODT) to measure fluid flow in single-layer microfluidic devices. The principles behind flow imaging with SD-ODT are reviewed, a method for velocity calibration is described, and cross-sectional and en-face images of fluid velocity in microfluidic channels are presented. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Pierce, MC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR 714,50 Blossom St, Boston, MA 02114 USA. EM pierce@helix.mgh.harvard.edu; deboer@helix.mgh.harvard.edu NR 16 TC 1 Z9 1 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5664-0 J9 PROC SPIE PY 2005 VL 5690 BP 271 EP 275 DI 10.1117/12.592864 PG 5 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BCF22 UT WOS:000229015500041 ER PT S AU Nathan, DG AF Nathan, DG BE Vichinsky, EP TI Thalassemia: The continued challenge SO COOLEY'S ANEMIA EIGHTH SYMPOSIUM SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 8th Cooleys Anemia Symposium CY MAR 17-19, 2005 CL Lake Buena Vista, FL SP New York Acad Sci, Cooleys Anemia Fdn, Apopharm Inc, Natl Inst Hlth, Off Rare Dis, Natl Heart, Lung, & Blood Inst, Natl Inst Diabetes & Digest & Kidney, Genzyme DE thalassemia; chelation therapy; transfusion therapy; hepatic iron; genetics; prenatal diagnosis; stem cell transplantation; gene therapy ID SICKLE-CELL-ANEMIA; FETAL-HEMOGLOBIN PRODUCTION; HOMOZYGOUS BETA-THALASSEMIA; MYOCARDIAL IRON OVERLOAD; PRENATAL-DIAGNOSIS; MOLECULAR PATHOLOGY; DNA POLYMORPHISMS; COMBINED THERAPY; COOLEYS ANEMIA; STEM-CELLS AB This overview describes the history of transfusion therapy and consequent iron overload in thalassemia. It emphasizes the importance of measurement of hepatic iron and reviews the history of chelation therapy. It briefly describes the discoveries of the genetic basis of thalassemia and the application of that knowledge in prenatal diagnosis. The review goes on to emphasize pharmaceutical efforts to induce fetal hemoglobin synthesis in thalassemic red cells and ends with a discussion of oral iron chelators, stem cell transplant, and the status of gene therapy. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Nathan, DG (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM David_Nathan@dfci.harvard.edu NR 54 TC 13 Z9 13 U1 0 U2 5 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-580-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1054 BP 1 EP 10 DI 10.1196/annal.1345.001 PG 10 WC Hematology; Multidisciplinary Sciences SC Hematology; Science & Technology - Other Topics GA BDU40 UT WOS:000235427600001 PM 16339645 ER PT J AU Parsons, PE Eisner, MD Thompson, BT Matthay, MA Ancukiewicz, M Bernard, GR Wheeler, AP AF Parsons, PE Eisner, MD Thompson, BT Matthay, MA Ancukiewicz, M Bernard, GR Wheeler, AP CA NHLB Acu Resp Dis Syn Cli Tri Net TI Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury SO CRITICAL CARE MEDICINE LA English DT Article DE acute lung injury; acute respiratory distress syndrome; interleukin-6; interleukin-8 interieukin-10; low tidal volume ventilation; sepsis ID RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; HYPERCAPNIC ACIDOSIS; MECHANICAL VENTILATION; CONTROLLED-TRIAL; PULMONARY-EDEMA; CLINICAL-TRIALS; SEPSIS SYNDROME; ENDOTOXIN; MODEL AB Objectives: To evaluate the association between interleukin-6, interleukin-8, and interleukin-10 and clinical outcomes including mortality in patients with acute lung injury and to determine whether lower tidal volume ventilation was associated with a decrease in plasma cytokines in patients with acute lung injury. Design: Multiple-center, randomized trial. Setting: Intensive care units in ten university centers. Patients: The study included 861 patients enrolled in the National Heart, Lung and Blood Institute Acute Respiratory Distress Syndrome Clinical Network trial of lower tidal volumes compared with traditional tidal volumes for acute lung injury. Interventions: Patients were randomized to a 6 mL/kg or a 12 mL/kg tidal volume strategy that has been previously described. Measurements and Main Results: Baseline plasma levels of interleukin-6, interleukin-8, and interleukin-10 were each associated with an increased risk of death in both logistic regression analyses controlling for ventilator group odds ratio 1.63 per log-10 increment, 95% confidence interval 1.33-1.98; odds ratio 2.33 per log-10 increment, 95% confidence interval 1.79-3.03; odds ratio 2.02 per log-10 increment, 95% confidence interval 1.47-2.76, respectively) and multivariate analyses controlling for ventilation strategy, Acute Physiology and Chronic Health Evaluation III score, Pao(2)/Fio(2) ratio, creatinine, platelet count, and vasopressor use (odds ratio 1.63 per log-10 increment, 95% confidence interval 0.93-1.49; odds ratio 1.73 per log-10 increment, 95% confidence interval 1.29-2.34; odds ratio 1.23 per log-10 increment, 95% confidence interval 0.86 -1.76, respectively). Interleukin-6 and interleukin-8 levels were also associated with a significant decrease in ventilator free and organ failure free days. Patients with sepsis had the highest cytokine levels and the greatest risk of death per cytokine elevation. By day 3, the 6 mL/kg strategy was associated with a greater decrease in interleukin-6 and interleukin-8 levels. There was a 26% reduction in interleukin-6 (95% confidence interval, 12-37%) and a 12% reduction in interleukin-8 (95% confidence interval, 1-23%) in the 6 mL/kg group compared with the 12 mL/Kg group. Conclusions: In patients with acute lung injury, plasma interleukin-6 and interleukin-8 levels are associated with morbidity and mortality. The severity of inflammation varies with clinical risk factor, suggesting that clinical risk factor should be considered when both developing and testing therapeutic interventions. Low tidal volume ventilation is associated with a more rapid attenuation of the inflammatory response. C1 Univ Vermont, Fletcher Allen Hlth Care, Dept Med, Div Pulm & Crit Care Med, Burlington, VT 05405 USA. Univ Calif San Francisco, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Environm & Occupat Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, Dept Med & Anesthesia, San Francisco, CA 94143 USA. Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA 94143 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm Unit, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Crit Care & Biostat Unit, Cambridge, MA 02138 USA. Vanderbilt Univ, Div Allergy Pulm & Crit Care Med, Nashville, TN USA. RP Parsons, PE (reprint author), Univ Vermont, Fletcher Allen Hlth Care, Dept Med, Div Pulm & Crit Care Med, Burlington, VT 05405 USA. FU NHLBI NIH HHS [N01-HR-46054-64] NR 40 TC 311 Z9 334 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2005 VL 33 IS 1 BP 1 EP 6 DI 10.1097/01.CCM.0000149854.61192.DC PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 887WN UT WOS:000226336300001 PM 15644641 ER PT J AU Cheng, IW Eisner, MD Thompson, BT Ware, LB Matthay, MA AF Cheng, IW Eisner, MD Thompson, BT Ware, LB Matthay, MA CA Acute Respitatory Distress Network TI Acute effects of tidal volume strategy on hemodynamics, fluid balance, and sedation in acute lung injury SO CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; pulmonary edema; mechanical ventilation; neuromuscular blockade; ventilator-associated lung injury ID RESPIRATORY-DISTRESS-SYNDROME; CRITICALLY-ILL PATIENTS; MECHANICAL VENTILATION; PERMISSIVE HYPERCAPNIA; PROTECTIVE-VENTILATION; OXYGEN-TRANSPORT; PULMONARY-EDEMA; GAS-EXCHANGE; ARDS; TRIAL AB Objective: To examine the effects of mechanical ventilation with a tidal volume of 6 mL/kg compared with 12 mL/kg predicted body weight on hemodynamics, vasopressor use, fluid balance, diuretics, sedation, and neuromuscular blockade within 48 hrs in patients with acute lung injury and acute respiratory distress syndrome. Design: Retrospective analysis of a previously conducted randomized, clinical trial. Setting: Two adult intensive care units at a tertiary university medical center and a large county hospital. Patients: One hundred eleven patients who were enrolled in the National Institutes of Health ARDS Network trial at the University of California, San Francisco. Interventions: None. Measurements and Main Results: Compared with 12 mL/kg predicted body weight, treatment with a tidal volume of 6 mL/kg predicted body weight had no adverse effects on hemodynamics. There were also no differences in the need for supportive therapies, including vasopressors, intravenous fluids, or diuretics. In addition, there were no differences in body weight, urine output, and fluid balance. Finally, there was no difference in the need for sedation or neuromuscular blockade between the two tidal volume protocols. Conclusions: When compared with ventilation with 12 mL/kg predicted body weight, patients treated with the lung-protective 6 mL/kg predicted body weight tidal volume protocol had no difference in their supportive care requirements. Therefore, concerns regarding potential adverse effects of this protocol should not preclude its use in patients with acute lung injury or the acute respiratory distress syndrome. C1 Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Med, Pulm Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, ARDS Network Clin Coordinating Ctr, Boston, MA 02114 USA. Vanderbilt Univ, Dept Med, Div Allergy Pulm & Crit Care Med, Nashville, TN USA. RP Cheng, IW (reprint author), Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA 94143 USA. FU NHLBI NIH HHS [HL51856, HL70521, P50 HL74005, HL03724]; PHS HHS [N0146059] NR 32 TC 52 Z9 54 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2005 VL 33 IS 1 BP 63 EP 70 DI 10.1097/01.CCM.0000149836.76063.71 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 887WN UT WOS:000226336300009 PM 15644650 ER PT J AU Rizvi, K DeBoisblanc, BP Truwit, JD Dhillon, G Arroliga, A Fuchs, BD Guntupalli, KK Hite, D Hayden, D AF Rizvi, K DeBoisblanc, BP Truwit, JD Dhillon, G Arroliga, A Fuchs, BD Guntupalli, KK Hite, D Hayden, D CA NIH NHLBI ARDS Clin Trials Net TI Effect of airway pressure display on interobserver agreement in the assessment of vascular pressures in patients with acute lung injury and acute respiratory distress syndrome SO CRITICAL CARE MEDICINE LA English DT Article DE acute lung injury; acute respiratory distress syndrome; central venous pressure; pulmonary artery occlusion pressure ID PULMONARY-ARTERY CATHETER; RIGHT-HEART CATHETERIZATION; CONTROLLED-TRIAL; KNOWLEDGE; CARE; VARIABILITY; OUTCOMES; SHOCK AB Background: Previous investigations have identified significant interobserver variability in the measurements of central venous pressure and pulmonary artery occlusion pressure in critically ill patents. Large interobserver variability in the measurement of vascular pressures could potentially lead to inappropriate treatment decisions. Objective: We postulated that adding an airway pressure signal (Paw) to pressure tracings of central venous pressure and pulmonary artery occlusion pressure would improve interobserver agreement by facilitating identification of end-expiration. Design: To test this hypothesis, six independent experts used a standard protocol to interpret strip-chart recordings of central venous pressure and pulmonary artery occlusion pressure with or without Paw. Two observers were said to agree if their measurements were within 2 mm Hg of each other. Setting/Subjects/interventions: A total of 459 strip-chart re- cordings (303 without Paw and 156 with Paw) were obtained from 121 patients enrolled in the ARDSnet Fluids and Catheters Treatment Trial (FACTT) in 16 different hospitals. Results: Agreement within 2 mm Hg between two measurements was 79% for central venous pressure strips without Paw vs. 86% with Paw. For pulmonary artery occlusion pressure, agreement increased from 71% without Paw to 83% with Paw. The increase in agreement with the addition of Paw was greater for strips demonstrating >8 mm Hg phasic respiratory variation compared with strips demonstrating less phasic respiratory variation. Conclusion: Paw display is a simple, inexpensive method to facilitate the identification of end-expiration that can significantly improve interobserver agreement. C1 Univ Chicago, Pritzker Sch Med, Div Biol Sci, Chicago, IL 60637 USA. Louisiana State Univ, Ctr Hlth Sci, Sect Pulm Crit Care Med, New Orleans, LA 70112 USA. Med Ctr Louisiana, Crit Care Serv, New Orleans, LA USA. Cleveland Clin Fdn, Cleveland Clin, Lerner Coll Med,Sect Crit Care Med, Dept Pulm Allergy & Crit Care Med, Cleveland, OH 44195 USA. Univ Virginia, Charlottesville, VA 22903 USA. Baylor Coll Med, Houston, TX 77030 USA. Hosp Univ Penn, Dept Pulm Allergy & Crit Care, Med Intens Care Unit, Philadelphia, PA 19104 USA. Hosp Univ Penn, Resp Care Serv, Philadelphia, PA 19104 USA. Wake Forest Univ, Hlth Sci Ctr, Winston Salem, NC 27109 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Rizvi, K (reprint author), Univ Chicago, Pritzker Sch Med, Div Biol Sci, Chicago, IL 60637 USA. FU NHLBI NIH HHS [N01-HR-16146-54, N01-HR-16054-64, N01-HR-16150] NR 19 TC 23 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2005 VL 33 IS 1 BP 98 EP 103 DI 10.1097/01.CCM.0000150350.70142.E9 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 887WN UT WOS:000226336300013 PM 15644654 ER PT J AU Gorry, PR Churchill, M Crowe, SM Cunningham, AL Gabuzda, D AF Gorry, PR Churchill, M Crowe, SM Cunningham, AL Gabuzda, D TI Pathogenesis macrophage tropic HIV-1 SO CURRENT HIV RESEARCH LA English DT Review DE HIV-1; CCR5; macrophage; coreceptor; pathogenesis ID IMMUNODEFICIENCY-VIRUS TYPE-1; MONOCYTE-DERIVED MACROPHAGES; ACTIVE ANTIRETROVIRAL THERAPY; PERIPHERAL-BLOOD MONOCYTES; QUINOLINIC ACID PRODUCTION; PROTEIN-COUPLED RECEPTOR; CORECEPTOR-BINDING-SITE; IN-VIVO; T-CELLS; CHEMOKINE RECEPTORS AB Despite numerous studies on the impact of viral diversity, human immunodeficiency virus type 1 (HIV-1)-specific immune responses and host factors on disease progression, we still do not have a firm understanding of the pathogenesis of HIV-1 infection. Rapid depletion of CD4+ T-lymphocytes has been associated with a switch in viral coreceptor usage from CCR5 to CXCR4 in approximately 40 to 50% of infected individuals. However, the majority of infected individuals who progress to AIDS harbor only CCR5-dependent (R5) viral strains. HIV-1 disease progression is associated with an enhanced tropism of R5 viral strains for cells of the monocyte/macrophage lineage (enhanced M-tropism). However, the underlying molecular mechanisms contributing to enhanced M-tropism by R5 HIV-1 strains, and how HIV-1 variants with enhanced M-tropism cause CD4+ T-cell depletion in vivo are unknown. This review examines the relationship between viral coreceptor usage, M-tropism, and pathogenicity of HIV-1. We highlight evidence supporting the hypothesis that enhanced M-tropism of R5 HIV-1 results from adaptive viral evolution, resulting in HIV-1 variants that have increased ability to utilize relatively low levels of CD4 and CCR5 expressed on macrophages. The evidence also suggests that these late-emerging, R5 viral strains have reduced sensitivity to entry inhibitors, and increased ability to cause CD4+ T-lymphocyte loss. These variants are likely to impact HIV-1 disease progression, particularly in patients \who persistently harbor only R5 viral strains. C1 Macfarlane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic 3001, Australia. Monash Univ, Dept Med, Melbourne, Vic 3004, Australia. Westmead Millennium Inst, Westmead, NSW, Australia. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Gorry, PR (reprint author), Macfarlane Burnet Inst Med Res & Publ Hlth, GPO Box 2284, Melbourne, Vic 3001, Australia. EM gorry@burnet.edu.au RI Cunningham, Tony/B-7011-2013 FU NIAID NIH HHS [1 R21 AI054207-01A1]; NINDS NIH HHS [NS 37277, NS35734] NR 138 TC 76 Z9 82 U1 1 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-162X J9 CURR HIV RES JI Curr. HIV Res. PD JAN PY 2005 VL 3 IS 1 BP 53 EP 60 DI 10.2174/1570162052772951 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 881YN UT WOS:000225905500005 PM 15638723 ER PT J AU Dale, BA Fredericks, LP AF Dale, BA Fredericks, LP TI Antimicrobial peptides in the oral environment: Expression and function in health and disease SO CURRENT ISSUES IN MOLECULAR BIOLOGY LA English DT Review ID PROTEASE-ACTIVATED RECEPTORS; HUMAN NEUTROPHIL DEFENSINS; TRACHEAL EPITHELIAL-CELLS; SINGLE-NUCLEOTIDE POLYMORPHISMS; HUMAN AIRWAY EPITHELIA; HUMAN BETA-DEFENSINS; INNATE HOST-DEFENSE; CATHEPSIN-C GENE; HUMAN BETA-DEFENSIN-3; PORPHYROMONAS-GINGIVALIS AB The oral cavity is a unique environment in which antimicrobial peptides play a key role in maintaining health and may have future therapeutic applications. Present evidence suggests that alpha - defensins, beta-defensins, LL-37, histatin, and other antimicrobial peptides and proteins have distinct but overlapping roles in maintaining oral health and preventing bacterial, fungal, and viral adherence and infection. The expression of the inducible hBD-2 in normal oral epithelium, in contrast to other epithelia, and the apparent differential signaling in response to commensal and pathogenic organisms, provides new insights into innate immunity in this body site. Commensal bacteria are excellent inducers of hBD-2 in oral epithelial cells, suggesting that the commensal bacterial community acts in a manner to benefit the overall innate immune readiness of oral epithelia. This may have major significance for understanding host defense in the complex oral environment. C1 Univ Washington, Dept Oral Biol, Seattle, WA 98195 USA. RP Dale, BA (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. EM bdale@u.washington.edu FU NIDCR NIH HHS [R01 DE013573-02, DE P60 013061, P60 DE013061-010001, P60 DE013061-01S10001, P60 DE013061-020001, P60 DE013061-030001, P60 DE013061-040001, R01 DE 13573, R01 DE013573, R01 DE013573-01A1, R01 DE013573-03, R01 DE013573-04, T32 DE007023, T32 DE007023-26, T32 DE007023-27, T32 DE07023] NR 138 TC 145 Z9 149 U1 0 U2 10 PU HORIZON SCIENTIFIC PRESS PI WYMONDHAM PA PO BOX 1, NORFOLK, WYMONDHAM NR18 0JA, ENGLAND SN 1467-3037 J9 CURR ISSUES MOL BIOL JI Curr. Issues Mol. Biol. PY 2005 VL 7 BP 119 EP 133 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 937RC UT WOS:000229942200001 PM 16053246 ER PT J AU Yu, XG Lichterfeld, M Addo, MM Altfeld, M AF Yu, XG Lichterfeld, M Addo, MM Altfeld, M TI Regulatory and accessory HIV-1 proteins: Potential targets for HIV-1 vaccines? SO CURRENT MEDICINAL CHEMISTRY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTES; CELLULAR IMMUNE-RESPONSES; TYPE-1 SUBTYPE-C; VPR INDUCES APOPTOSIS; RHESUS MACAQUES; CTL RESPONSES; IMMUNODOMINANT REGIONS; CYNOMOLGUS MONKEYS; MUCOSAL CHALLENGE AB The HIV-1 regulatory proteins Tat and Rev and the accessory proteins Vpr, Vpu and Vif are essential for efficient viral replication, and their cytoplasmic production suggests that they should be processed for recognition by cytotoxic T lymphocytes. However, only limited data is available, evaluating the role of immune responses directed against these proteins in natural HIV-1 infection. Recent advances in the methods used for the characterization of HIV-1-specific cellular immune responses, including quantification of antigen-specific IFN-gamma production by ELISpot assay and flow-cytometry-based intracellular cytokine quantification, have allowed for a much more comprehensive assessment of virus-specific immune responses. Emerging data show that the regulatory and accessory proteins serve as important targets for HIV-1-specific T cell responses, and multiple CTL epitopes have been identified in functionally important regions of these proteins. Moreover, the use of autologous peptides have allowed for the detection of significantly stronger HIV-1-specific T cell responses in the more variable regulatory and accessory HIV-1 proteins Tat and Vpr. These data indicate that despite the small size of these proteins, regulatory and accessory proteins are targeted by cellular immune responses in natural HIV-1 infection and contribute importantly to the total HIV-1-specific CD8+ T cell response. A multi-component vaccine, with the inclusion of these proteins plus structural proteins remains the most promising choice for an effective AIDS vaccine. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA 02115 USA. RP Altfeld, M (reprint author), Massachusetts Gen Hosp E, CNY 5212,149 13th St, Charlestown, MA 02129 USA. EM Maltfeld@partners.org FU NIAID NIH HHS [R01 AI 50429] NR 105 TC 11 Z9 12 U1 2 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PY 2005 VL 12 IS 6 BP 741 EP 747 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 899QF UT WOS:000227158900008 PM 15790309 ER PT J AU Avruch, J Lin, YS Long, XM Murthy, S Ortiz-Vega, S AF Avruch, J Lin, YS Long, XM Murthy, S Ortiz-Vega, S TI Recent advances in the regulation of the TOR pathway by insulin and nutrients SO CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE LA English DT Article DE LST8; raptor; Rheb; TOR; tuberous sclerosis complex ID P70 S6 KINASE; TUBEROUS SCLEROSIS COMPLEX; MESSENGER-RNA TRANSLATION; TUMOR-SUPPRESSOR PROTEINS; CELL-CYCLE PROGRESSION; REPRESSOR PHAS-I; MAMMALIAN TARGET; RPS6 PHOSPHORYLATION; 3-KINASE/AKT PATHWAY; BINDING PARTNER AB Purpose of Review The aim of this article is to summarize recent advances in the understanding of the regulation of the target of rapamycin (TOR), a protein kinase that is regulated independently by insulin, amino acids and energy sufficiency and which participates in the control of the component of protein synthesis responsible for cell growth. Recent findings These have been found in two major areas: genetic studies in Drosophila followed by studies in mammalian systems have identified the components of the Tuberous Sclerosis protein complex, a heterodimer of the proteins Hamartin and Tuberin, as inhibitors of TOR signaling, and as the major targets by which the insulin/IGF-1 signal transduction pathway, through the protein kinase PKB, and the energy status of the cell, through the AMP-activated protein kinase, regulate the TOR signaling. In turn, the inhibitory action of the tuberous sclerosis protein complex has been shown to be mediated by its ability to deactivate the small, ras-like GTPase Rheb. A second advance has been achieved by the identification of the TOR-associated protein raptor, as an indispensable substrate binding subunit of the TOR complex, and as the site at which the inhibitory effects on TOR signaling of rapamycin and amino acid deficiency converge. Summary These findings bring us closer to the understanding of how nutrients and insulin coordinate protein synthesis to regulate anabolic cell growth. C1 Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Avruch, J (reprint author), 50 Blossom St, Boston, MA 02114 USA. EM avruch@molbio.mgh.harvard.edu FU NCI NIH HHS [CA73818]; NIDDK NIH HHS [DK17776] NR 60 TC 77 Z9 84 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1363-1950 J9 CURR OPIN CLIN NUTR JI Curr. Opin. Clin. Nutr. Metab. Care PD JAN PY 2005 VL 8 IS 1 BP 67 EP 72 DI 10.1097/00075197-200501000-00010 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 886JJ UT WOS:000226223000009 PM 15586002 ER PT J AU Agrawal, J Syngal, S AF Agrawal, J Syngal, S TI Colon cancer screening strategies SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE colorectal cancer screening; stool testing; fecal occult blood test; fecal DNA tests ID FECAL OCCULT-BLOOD; COLORECTAL-CANCER; FLEXIBLE SIGMOIDOSCOPY; COST-EFFECTIVENESS; RANDOMIZED-TRIAL; STOOL; DNA; POPULATION; TESTS; RECOMMENDATIONS AB Purpose of review Screening and prevention of colorectal cancer is a public health priority. Fecal occult blood testing is a popular screening test because of its simplicity, noninvasiveness, and demonstrated mortality benefit. At the same time, guaiac tests suffer from poor sensitivity, limited ability to detect early lesions, the need for annual testing, low population compliance, and high costs of follow-up for false-positive tests. These limitations have sparked many innovations in stool testing. Recent findings Recent studies suggest that both community intervention and physician awareness are needed to improve patient compliance with fecal occult blood testing and colorectal cancer screening in general. Despite the low costs of the guaiac test, the high false positives and high false negatives of fecal occult blood testing lead to high costs and low cost-effectiveness when compared with endoscopic techniques. Fecal DNA testing promises to improve the performance characteristics of stool testing. Small trials of multitarget assays demonstrate a sensitivity for colorectal cancer of 62 to 91 % and a sensitivity for adenomas of 26 to 73%. The specificity of these assays is high, ranging from 93 to 100%. The major drawback of fecal DNA testing, compared with other fecal colorectal cancer screening tests, is the cost. Summary Preliminary data on fecal DNA tests show better performance characteristics than fecal occult blood tests. In their current form, however, it is not clear that the added sensitivity merits the additional cost. These tests must be studied in larger cohorts of asymptomatic patients before adequate comparison can be made to established colorectal cancer screening techniques. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Gastroenterol,Populat Sci Div, Boston, MA 02115 USA. RP Syngal, S (reprint author), Dana Farber Canc Inst, 44 Binney St,Smith 209, Boston, MA 02115 USA. EM ssyngal@partners.org NR 28 TC 11 Z9 11 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD JAN PY 2005 VL 21 IS 1 BP 59 EP 63 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 881NQ UT WOS:000225874600011 PM 15687886 ER PT J AU Dinh, T Veves, A AF Dinh, T Veves, A TI Microcirculation of the diabetic foot SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID VITAMIN-E SUPPLEMENTATION; OXIDE RELEASE ACCOUNTS; NITRIC-OXIDE; ENDOTHELIAL DYSFUNCTION; VASCULAR-DISEASE; INDEPENDENT VASODILATION; BLOOD-FLOW; SKIN MICROCIRCULATION; YOUNG-ADULTS; MELLITUS AB Studies over the last decade have revealed impairment of the microcirculation in the diabetic loot. Endothelial dysfunction along with derangements in numerous biochemical pathways has been implicated as causes of microcirculation impairment. Additionally, reduction or absence of the nerve-axon reflex renders the diabetic foot unable to mount a vasodilatory response under conditions of stress, such as injury or infection and makes it functionally ischemic even in the presence of satisfactory blood flow under normal conditions. Furthermore, these changes appear to be directly related to the presence of diabetic neuropathy. These alterations in the diabetic microcirculation may explain the poor wound healing commonly observed in diabetes. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Microcirculat Lab, Boston, MA 02215 USA. Joslin Beth Israel Deaconess Foot Ctr, Boston, MA USA. RP Veves, A (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Microcirculat Lab, Palmer 317,W Campus,1 Deaconess Rd, Boston, MA 02215 USA. EM aveves@bidmc.harvard.edu NR 67 TC 32 Z9 35 U1 1 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2005 VL 11 IS 18 BP 2301 EP 2309 DI 10.2174/1381612054367328 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 935ES UT WOS:000229763000003 PM 16022669 ER PT J AU Basilion, JP Yeon, S Botnar, R AF Basilion, JP Yeon, S Botnar, R TI Magnetic resonance imaging: Utility as a molecular imaging modality SO CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY, VOLUME 70 SE CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; GASTROINTESTINAL STROMAL TUMORS; SUPERPARAMAGNETIC IRON-OXIDE; TARGETED CONTRAST AGENT; HIGH-RESOLUTION MRI; GENE-EXPRESSION; IN-VIVO; NONINVASIVE DETECTION; TRANSGENE EXPRESSION; TRANSFERRIN RECEPTOR AB Significant scientific effort has gone into the deconvolution and understanding of complex biological systems. These efforts have yielded much information about the molecular changes that are causative or arise as a result of disease. Molecular imaging is a relatively newer field that is attempting to use these molecular data to generate images that report on changes in gene expression. It has been demonstrated that generating images based on molecular differences rather than anatomical differences between tissues has resulted in more sensitive detection of diseased tissues and has allowed imaging of drug efficacy against particular drug targets. This chapter discusses the application of magnetic resonance imaging (MRI) to molecular imaging. It begins with a review of the basis for magnetic resonance image generation and how manipulation of different parameters of the system can be applied to molecular imaging. It then specifically reviews some of the problematic areas for magnetic resonance application to molecular imaging and how these can be resolved by manipulating the magnetic resonance system, altering magnetic resonance probe characteristics, or exploiting the biology to be imaged. It concludes with several examples demonstrating the utility of MRI to generate high-resolution, noninvasive images of molecular events occurring in vivo. (c) 2005, Elsevier Inc. C1 Massachusetts Gen Hosp, NFCR, Ctr Mol Imaging Res, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Tech Univ Munich, Dept Nucl Med, D-81675 Munich, Germany. RP Basilion, JP (reprint author), Massachusetts Gen Hosp, NFCR, Ctr Mol Imaging Res, Dept Radiol, Boston, MA 02115 USA. RI Botnar, Rene/E-6875-2012 OI Botnar, Rene/0000-0003-2811-2509 NR 87 TC 17 Z9 17 U1 2 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2153 J9 CURR TOP DEV BIOL PY 2005 VL 70 BP 1 EP + DI 10.1016/S0070-2153(05)70001-6 PG 39 WC Developmental Biology SC Developmental Biology GA BDK76 UT WOS:000234003500001 PM 16338335 ER PT J AU Yang, HY Cusin, C Fava, M AF Yang, HY Cusin, C Fava, M TI Is there a placebo problem in antidepressant trials? SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE major depressive disorder (MDD); clinical trial; sequential parallel design ID MAJOR DEPRESSIVE DISORDER; DRUG-ADMINISTRATION DATABASE; CLINICAL-TRIALS; DOUBLE-BLIND; RUN-IN; RELEASE PAROXETINE; POOLED ANALYSIS; SHORT-TERM; EFFICACY; METAANALYSIS AB In psychiatry, particularly in antidepressant clinical studies, placebo-controlled trials often yield results that are very difficult to interpret because of robust placebo responses. Meta-analyses of trials in major depressive disorder (MDD) suggest that drug-placebo differences in response rates range from 11% to 18%. However, in trials of marketed antidepressants present in the FDA databases, antidepressant drugs were superior to placebo in only 45 out of 93 RCTs (48%), and the placebo response overall appears to have, increased over time. This gradual increase in placebo response rates may lead to delays in bringing new antidepressant treatments to the market, increased costs of antidepressant drug development and, in some cases, decisions to stop the development of certain compounds, or FDA decisions to not approve new treatments. A number of possible contributing factors to this significant placebo response in MDD have been identified, but further studies are needed. Many of the remedies used by researchers to minimize the placebo response, such as lead-in periods or shortening the duration of study visits, have failed to show consistent benefits. From our analysis of published studies, it appears that expectations about the speed of response may be shaped by the duration of the trial and that most of the placebo response occurs in the first half of the trial, regardless of its duration. These observations have led us to develop a novel approach to the placebo response problem called the Sequential Parallel Comparison Design. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 55 Fruit St,Bulfinch 351, Boston, MA 02114 USA. EM mfava@partners.org FU NIMH NIH HHS [N01MH90003] NR 74 TC 29 Z9 29 U1 1 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 EI 1873-4294 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2005 VL 5 IS 11 BP 1077 EP 1086 DI 10.2174/156802605774297092 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 974SE UT WOS:000232610900006 PM 16181132 ER PT J AU Mendez, MF Chen, AK Shapira, JS Miller, BL AF Mendez, MF Chen, AK Shapira, JS Miller, BL TI Acquired sociopathy and frontotemporal dementia SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE frontotemporal dementia; sociopathy; antisocial; aggression ID ANTISOCIAL PERSONALITY-DISORDER; FRONTAL-LOBE DEGENERATION; NON-ALZHEIMER TYPE; PREFRONTAL CORTEX; DECISION-MAKING; SOCIAL COGNITION; TEMPORAL VARIANT; CLINICAL PICTURE; HUMAN BRAIN; BEHAVIOR AB Background: It is not understood why some patients with frontotemporal dementia ( FTD) manifest sociopathic behavior. Objective: To examine the prevalence and characteristics of sociopathic behavior in FTD patients as compared to those with Alzheimer's disease ( AD). Methods and Participants: We surveyed a group of FTD patients and a group of AD patients for sociopathic behavior, evaluated the characteristics surrounding their acts, and compared the groups on neuropsychological tests and functional neuroimaging. Twenty-eight outpatients with FTD ( 15 men, 13 women; 61.9 +/- 7.1 years; Mini-Mental State Examination score 23.6 +/- 8.1) were compared with 28 patients with clinically probable AD ( 13 men, 15 women; 66.1 +/- 9.2 years; Mini-Mental State Examination score 21.3 +/- 5.3). Main outcome measures included: ( a) the prevalence of sociopathic acts; ( b) a structured interview; ( c) neuropsychological tests including the Frontal Assessment Battery, and ( d) clinically obtained positron emission tomography or single photon emission tomography scans. Results: Sixteen (57%) of the FTD patients had sociopathic behavior compared to two (7%) of the AD patients (chi(2) = 13.84, p < 0.001). Sociopathic acts among FTD patients included unsolicited sexual acts, traffic violations, physical assaults, and other unacceptable behaviors. On interview, the FTD patients with sociopathic acts were aware of their behavior and knew that it was wrong but could not prevent themselves from acting impulsively. They claimed subsequent remorse, but they did not act on it or show concern for the consequences. Among FTD patients with sociopathy, neuropsychological assessment showed impaired motor inhibition, and functional neuroimaging showed right frontotemporal involvement. Conclusion: The results suggest that sociopathy in FTD results from a combination of diminished emotional concern for the consequences of their acts and disinhibition consequent to right frontotemporal dysfunction. In many jurisdictions, FTD patients with sociopathy would not pass legal criteria for 'not guilty by reason of insanity'. Copyright (C) 2005 S. Karger AG, Basel. C1 VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit 691116AF, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit 691116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@UCLA.edu FU NIA NIH HHS [AG19724-01, P01 AG019724] NR 53 TC 50 Z9 51 U1 3 U2 13 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2005 VL 20 IS 2-3 BP 99 EP 104 DI 10.1159/000086474 PG 6 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 972YE UT WOS:000232488900008 PM 15980631 ER PT J AU Weintraub, D Moberg, PJ Culbertson, WC Duda, JE Katz, IR Stern, MB AF Weintraub, D Moberg, PJ Culbertson, WC Duda, JE Katz, IR Stern, MB TI Dimensions of executive function in Parkinson's disease SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Parkinson disease, executive impairment; planning function; inhibitory control ID POSITRON-EMISSION-TOMOGRAPHY; ANTERIOR CINGULATE CORTEX; DEMENTIA; DEPRESSION; PET; ASSOCIATION; IMPAIRMENT; MORTALITY; APATHY; SCALE AB Background: Executive impairment is common in Parkinson's disease (PD). However, it is unknown which dimensions of executive function are assessed by commonly used neuropsychological instruments and if clinical correlates of specific dimensions exist. Method: A convenience sample of 46 PD patients was evaluated with three executive function tests: the Tower of London-Drexel, the Trail-Making Test and the Stroop Color-Word Test. Factor analysis was used to probe for dimensions of executive control, and linear regression models were used to explore the association between the generated factors and other clinical features. Results: Factor analysis revealed two executive factors, one related to planning (eigenvalue = 4.2) and the other to inhibitory control ( eigenvalue = 1.8), together accounting for 75% of the variance in scores. In linear regression models, poorer planning was associated with increasing severity of apathy (t = 2.11, p = 0.041), and diminished inhibitory control was associated with increasing severity of parkinsonism ( t = 2.78, p = 0.008) and lower educational level ( t = - 2.23, p = 0.032). Conclusions: Planning deficits and diminished inhibitory control are two dimensions of executive impairment in PD, the former associated with decreased motivation and the latter with increased motor slowing. Similar performance on both executive and non-executive components of these instruments suggests that results of executive testing in PD may be confounded by non-executive deficits. Copyright (C) 2005 S. Karger AG, Basel. C1 Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. Drexel Univ, Dept Psychol, Philadelphia, PA 19104 USA. RP Weintraub, D (reprint author), 3535 Market St,Room 3003, Philadelphia, PA 19104 USA. EM weintrau@mail.med.upenn.edu FU NIMH NIH HHS [MH067894] NR 36 TC 36 Z9 37 U1 1 U2 14 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2005 VL 20 IS 2-3 BP 140 EP 144 DI 10.1159/000087043 PG 5 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 972YE UT WOS:000232488900013 PM 16020942 ER PT J AU Krishnan, LL Petersen, NJ Snow, AL Cully, JA Schulz, PE Graham, DP Morgan, RO Braun, U Moffett, ML Yu, HJ Kunik, ME AF Krishnan, LL Petersen, NJ Snow, AL Cully, JA Schulz, PE Graham, DP Morgan, RO Braun, U Moffett, ML Yu, HJ Kunik, ME TI Prevalence of dementia among Veterans Affairs medical care system users SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Veterans Affairs; Veterans Integrated Service Network; Alzheimer's disease; African-Americans ID WHITE COMMUNITY RESIDENTS; ALZHEIMERS-DISEASE; AFRICAN-AMERICANS; SENILE DEMENTIA; UNITED-STATES; OLDER PERSONS; POPULATION; HEALTH; DIAGNOSIS; AD AB Objectives: In an aging population, the number of veterans diagnosed with dementia is likely to increase. Knowledge of existing dementia prevalence will be beneficial in planning for future patient care needs. Our objectives were to assess the prevalence of the dementia diagnosis among those treated at Veterans Affairs (VA) medical centers and determine how it varies across race and Veterans Integrated Service Network (VISN). Materials and Methods: Data were collected on all veterans seen within the VA medical system from 1997 through the first half of 2001. Only veterans aged 65 and over were included in the study. Veterans were included if they had one of the following dementia ICD-9 codes: 290.XX, 291.2, 294.XX, 331.XX, 046.1, or 046.3. Results: The overall prevalence of dementia was 7.3%. The prevalence of dementia was similar among white patients and patients of other races, except African-American patients, in whom it was 50% higher. Across VISNs, the prevalence of dementia ranged from 5.8 to 9.4%. Alzheimer's disease was the most frequently diagnosed type of dementia within the VA, and inpatient service utilization and outpatient psychiatry visits by individuals with dementia were high relative to other VA patients. Discussion: The overall prevalence identified is consistent with that reported in the literature, as is the elevated prevalence in African-Americans versus whites. The data on prevalence by VISN may identify regional variation in either the types of dementia present or the diagnostic criteria used. The dementia diagnosis is clearly associated with substantial service use. Copyright (C) 2005 S. Karger AG, Basel. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurol, Behav Neurol Sect, Houston, TX 77030 USA. Baylor Coll Med, Div Neurosci, Houston, TX 77030 USA. Vet Affairs S Cent Mental Illness Res Educ & Clin, Houston, TX USA. Michael E DeBakey Vet Affairs Med Ctr, Neurol Care Line, Houston, TX USA. RP Kunik, ME (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, 152, Houston, TX 77030 USA. EM mkunik@bcm.tmc.edu RI Morgan, Robert/A-8577-2009; Moffett, Maurice/I-6664-2013; Graham, David /J-1158-2014 OI Moffett, Maurice/0000-0002-4536-9843; NR 42 TC 42 Z9 43 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2005 VL 20 IS 4 BP 245 EP 253 DI 10.1159/000087345 PG 9 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 972YF UT WOS:000232489000006 PM 16088141 ER PT J AU Roman, GC Wilkinson, DG Doody, RS Black, SE Salloway, SP Schindler, RJ AF Roman, GC Wilkinson, DG Doody, RS Black, SE Salloway, SP Schindler, RJ TI Donepezil in vascular dementia: Combined analysis of two large-scale clinical trials SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE vascular dementia; cholinesterase inhibitors; donepezil; cognitive benefit; global function benefit ID ALZHEIMERS-DISEASE; EFFICACY; TOLERABILITY; POPULATIONS; MULTICENTER; MEMANTINE; SAFETY; STATE; AD AB Background and Objective: There are currently no drugs approved to treat vascular dementia (VaD). The objective of this study was to determine if treatment with donepezil, an acetylcholinesterase inhibitor, may provide benefit for VaD patients. Methods: Combined analysis of 2 identical randomized, double-blind, placebo-controlled, 24-week studies involving 1,219 patients enrolled at 109 investigational sites in the USA, Europe, Canada and Australia. Patients were randomized to receive donepezil 5 mg/day (n = 406) or 10 mg/day (after brief titration; n = 421) or placebo (n = 392). Patients were assessed on cognition [ Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Mini-Mental State Examination (MMSE)], global function [Clinician's Interview-Based Impression of Change plus (CIBIC-plus), Clinical Dementia Rating-Sum of the Boxes (CDR-SB)] and function [ Alzheimer's Disease Functional Assessment and Change Scale (ADFACS); instrumental activities of daily living (ADFACS-IADL)]. Results: Both donepezil groups showed significant improvements in cognition compared with placebo (ADAS-cog, MMSE, p < 0.01). Significant global function benefits were seen on the CIBIC-plus in the 5 mg/day group (placebo vs. 5 mg/day, p < 0.001; vs. 10 mg/day, p = 0.006) and on the CDR-SB in the 10 mg/day group (placebo vs. 5 mg/day, p = 0.09; vs. 10 mg/day, p < 0.01). Significant functional benefits were also seen (ADFACS, placebo vs. 5 mg/day, p = 0.08; vs. 10 mg/day, p = 0.02; ADFACS-IADL, p < 0.05 for both donepezil groups). Donepezil was well tolerated, with low withdrawal rates due to adverse events. Conclusions: This combined analysis of the largest trial on VaD to date showed that donepezil-treated patients had significant benefits in cognition, global function and ability to perform IADL. Based on these findings and reported tolerability, donepezil should be considered as an important therapeutic element in the overall management of patients with VaD. Copyright (C) 2005 S. Karger AG, Basel. C1 Univ Texas, Hlth Sci Ctr, Sch Med, Dept Med,Div Neurol, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Brown Med Sch, Providence, RI USA. Pfizer Inc, New York, NY USA. Moorgreen Hosp, Memory Assessment & Res Ctr, Southampton, Hants, England. Univ Toronto, Sunnybrook & Womens Coll Hlth Sci Ctr, Dept Med Neurol, Toronto, ON, Canada. RP Roman, GC (reprint author), Univ Texas, Hlth Sci Ctr, Sch Med, Dept Med,Div Neurol, Mail Code 7883,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM romang@uthsca.edu OI Black, Sandra/0000-0001-7093-8289 NR 26 TC 48 Z9 56 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2005 VL 20 IS 6 BP 338 EP 344 DI 10.1159/000088494 PG 7 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 985GG UT WOS:000233364300002 PM 16192723 ER PT J AU Hinton, DE Pich, V Chhean, D Pollack, MH McNally, RJ AF Hinton, DE Pich, V Chhean, D Pollack, MH McNally, RJ TI Sleep paralysis among Cambodian refugees: Association with PTSD diagnosis and severity SO DEPRESSION AND ANXIETY LA English DT Article DE Khmer refugees; sleep paralysis; panic attacks; posttraumatic stress disorder; hallucinations ID POSTTRAUMATIC-STRESS-DISORDER; PANIC DISORDER; SYMPTOMS; PEOPLE AB Among Cambodian refugees attending a psychiatric clinic (n = 100), 49% (491 100) had at least one episode of sleep paralysis (SP) in the previous 12 months. The annual and monthly SP prevalences were much higher in posttraumatic stress disorder (PTSD) than in non-PTSD patients. Among the PTSD patients, 65% (30/46) bad monthly episodes of SP versus 14.85% (8/54) among non-PTSD patients (X-2 [2, n = 100] = 26.78, P<.001). Moreover, patients with SP in the last month (n = 30) versus those without SP had much higher PTSD severity scores. In the entire sample In = 100), the PTSD severity scores correlated significantly with the rate of SP in the last month. During SP, Cambodian refugees usually hallucinated an approaching figure (90%, 44/49). The rate of SP-associated and post-SP panic attacks was high, indicating the great distress caused by the phenomenon. SP seems to be a core aspect of the Cambodian refugee's response to trauma. When treating Cambodian refugees, and traumatized refugees in general, clinicians should assess for its presence. Depression and Anxiety 22:47-51, 2005. (c) 2005 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Arbour Counseliing Ctr, Lowell, MA USA. Harvard Univ, Dept Psychol, Boston, MA 02115 USA. RP Hinton, DE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM devon_hinton@hms.harvard.edu NR 27 TC 28 Z9 28 U1 1 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2005 VL 22 IS 2 BP 47 EP 51 DI 10.1002/da.20084 PG 5 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 980AD UT WOS:000232985400001 PM 16094659 ER PT J AU Biederman, J Petty, C Faraone, SV Hirshfeld-Becker, DR Henin, A Dougherty, M LeBel, TJ Pollack, M Rosenbaum, JE AF Biederman, J Petty, C Faraone, SV Hirshfeld-Becker, DR Henin, A Dougherty, M LeBel, TJ Pollack, M Rosenbaum, JE TI Parental predictors of pediatric panic disorder/agoraphobia: A controlled study in high-risk offspring SO DEPRESSION AND ANXIETY LA English DT Article DE children; youth; anxiety disorders; genetic; family ID OBSESSIVE-COMPULSIVE DISORDER; EARLY-ONSET; REFERRED CHILDREN; BIPOLAR DISORDER; MAJOR DEPRESSION; PSYCHOPATHOLOGY; COMORBIDITY; RELIABILITY; ADOLESCENTS; PHENOMENOLOGY AB Our objective was to evaluate parental risk factors for pediatric-onset panic disorderlagorapbobia (PD/AG) in offspring at high risk for PD/AG. Comparisons were made between parents with PD who bad a child with PD or AG (N = 27) and parents with PD without children with PD or AG (N = 79). Comparisons were also made between the spouses of these parents with PD. Separation anxiety disorder, social phobia, obsessive-compulsive disorder, and bipolar disorder in the parents with PD and their spouses accounted for the risk for childhood onset PD/AG in the offspring. This risk was particularly high if both parents were affected with social phobia. These findings suggest that psychiatric comorbidity with other anxiety disorders and with bipolar disorder in parents with PD and their spouses confer a particularly high risk in their offspring to develop PD/AG in childhood. C1 Massachusetts Gen Hosp, Yawkey Ctr Outpatient Ctr, Pediat Psychopharmacol Clin, Boston, MA 02114 USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Yawkey Ctr Outpatient Ctr, Pediat Psychopharmacol Clin, YAW-6A-6900,32 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [2 R01 MH47077] NR 28 TC 9 Z9 9 U1 2 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2005 VL 22 IS 3 BP 114 EP 120 DI 10.1002/da.20122 PG 7 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 982AX UT WOS:000233130200002 PM 16193490 ER PT J AU Bierderman, J Petty, C Faraone, SV Hirshfeld-Becker, DR Henin, A Pollack, MH Rosenbaum, JF AF Bierderman, J Petty, C Faraone, SV Hirshfeld-Becker, DR Henin, A Pollack, MH Rosenbaum, JF TI Patterns of comorbidity in panic disorder and major depression: Findings from a nonreferred sample SO DEPRESSION AND ANXIETY LA English DT Article DE panic disorder; comorbidity; children; major depression; adults ID DEFICIT HYPERACTIVITY DISORDER; HIGH-RISK CHILDREN; PSYCHOPATHOLOGY; PARENTS; PROBANDS; FAMILY; RELATIVES; SYMPTOMS; ANXIETY AB Previous findings in referred adult samples document major depression as having important moderating effects on the patterns of comorbidity for panic disorder and major depression. This study evaluated whether these patterns of comorbidity are moderated by referral bias. Panic disorder (PD) and major depression (MD) were used to predict the risk for comorbid psychiatric disorders and functional outcomes using data from a large sample of adults who had not been ascertained on the basis of clinical referral (N = 1,031). Participants were comprehensively assessed with structured diagnostic interview methodology to evaluate childhood and adult comorbid psychiatric disorders. PD increased the risk for anxiety disorders, independently of MD. MD increased the risk for mania, antisocial personality disorder psychoactive substance use disorder, disruptive behavior disorders, overanxious disorder, social phobia, and generalized anxiety disorder independently of PD. These results extend to nonreferred samples' previously reported findings documenting that MD has important moderating effects on patterns of comorbidity for PD and indicate that patterns of comorbidity for PD are not due to referral bias. (c) 2005 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Pediat Psychopharmacol Unit, Child Psychiat Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. SUNY Upstate Med Univ, Dept Child & Adolescent Psychiat, Syracuse, NY USA. RP Bierderman, J (reprint author), Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Pediat Psychopharmacol Unit, Child Psychiat Serv, YAW-6A-6900,32 Fruit St,WACC 705, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 NR 25 TC 1 Z9 2 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2005 VL 21 IS 2 BP 55 EP 60 DI 10.1002/da.20055 PG 6 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 926XN UT WOS:000229157100002 ER PT J AU Khachemoune, A Barkoe, D Braun, M Davison, SP AF Khachemoune, A Barkoe, D Braun, M Davison, SP TI Dermatofibrosarcoma protuberans of the forehead and scalp with involvement of the outer calvarial plate: Multistaged repair with the use of skin expanders SO DERMATOLOGIC SURGERY LA English DT Article ID TISSUE EXPANSION; RECONSTRUCTION; SURGERY; DEFECTS; PATIENT AB BACKGROUND AND OBJECTIVE. Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive and infiltrative tumor that requires Mobs' micrographic surgery or wide excision to treat. Adequate excision often leaves a cosmetic disfiguring defect, particularly if the tumor is located on the head and neck. Complex defects of the face present special problems, such as distortion, ectropion, and retraction of normal tissues. PATIENT AND METHODS. We present a case of an infiltrating DFSP of the forehead and scalp in a young woman. The tumor was removed, and the defect was reconstructed with multistaged repair, which included bone coverage, local and regional flaps, and the use of expanders. RESULTS. A multistaged repair was performed with good clinical outcome and satisfactory cosmetic results. CONCLUSION. Multistaged repair of the face is a viable alternative surgical approach to preserve facial contours and minimize distortion in the treatment of DFSP. This case illustrates the degree of complexity that the treatment of DFSP may involve. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, Boston, MA 02114 USA. Mt Sinai Med Ctr, Dept Gen Surg, Miami Beach, FL 33140 USA. George Washington Univ, Dept Dermatol, Washington, DC USA. Georgetown Univ, Med Ctr, Div Plast Surg, Washington, DC 20007 USA. RP Khachemoune, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, 40 Blossom St, Boston, MA 02114 USA. EM amorkh@pol.net NR 21 TC 6 Z9 6 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD JAN PY 2005 VL 31 IS 1 BP 115 EP 119 PG 5 WC Dermatology; Surgery SC Dermatology; Surgery GA 906MA UT WOS:000227645100021 PM 15720109 ER PT J AU Lepourcelet, M Tou, LQ Cai, L Sawada, J Lazar, AJF Glickman, JN Williamson, JA Everett, AD Redston, M Fox, EA Nakatani, Y Shivdasani, RA AF Lepourcelet, M Tou, LQ Cai, L Sawada, J Lazar, AJF Glickman, JN Williamson, JA Everett, AD Redston, M Fox, EA Nakatani, Y Shivdasani, RA TI Insights into developmental mechanisms and cancers in the mammalian intestine derived from serial analysis of gene expression and study of the hepatoma-derived growth factor (HDGF) SO DEVELOPMENT LA English DT Article DE developmental gene expression; epithelial-mesenchymal interaction; oncofetal genes; hepatoma-derived growth factor; heterogeneous nuclear ribonucleoprotein; mouse ID RNA-BINDING PROTEINS; GASTROINTESTINAL DEVELOPMENT; CELL-DIFFERENTIATION; ONCOPROTEIN TLS/FUS; CHROMATIN PROTEIN; TRANSGENIC MICE; SONIC HEDGEHOG; IN-VIVO; EPITHELIUM; NUCLEUS AB The vertebrate intestine is a model for investigating inductive cellular interactions and the roles of epithelial stem cells in tissue regeneration, and for understanding parallels between development and cancer. We have used serial analysis of gene expression to measure transcript levels across stages in mouse intestine development. The data (http://genome.dfci.harvard.edu/GutSAGE) identify novel differentiation products, potential effectors of epithelial-mesenchymal interactions, and candidate markers and regulators of intestinal epithelium. Transcripts that decline significantly during intestine development frequently are absent from the adult gut. We show that a significant proportion of such genes may be reactivated in human colon cancers. As an example, hepatoma-derived growth factor (HDGF) mRNA is expressed prominently in early gut tissue, with substantially reduced levels after villous epithelial differentiation. HDGF expression is dramatically increased in human colorectal cancers, especially in tumors proficient in DNA mismatch repair, and thus represents a novel marker for a distinctive tumor subtype. HDGF overexpression in fetal intestine explants inhibits maturation, suggesting a role in epithelial differentiation. To investigate the molecular basis for HDGF functions, we isolated components of a nuclear HDGF complex, including heterogeneous nuclear ribonucleoproteins implicated in processing RNA. These genes are regulated in tandem with HDGF during intestine development and one factor, TLS/Fus, is commonly overexpressed in colon cancers. Tumor expression of fetal genes may underlie similarities between developing and malignant tissues, such as self-renewal, invasion and angiogenesis. Our findings also advance understanding of HDGF functions and implicate this developmentally regulated gene in RNA metabolic pathways that may influence malignant behaviors in colorectal cancer. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Dept Pediat Cardiol, Baltimore, MD 21287 USA. RP Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM ramesh_shivdasani@dfci.harvard.edu RI Lazar, Alexander/A-3416-2008; OI Lazar, Alexander/0000-0002-6395-4499; Williamson, Jessica/0000-0002-5530-8657 FU NIDDK NIH HHS [R01DK61139] NR 65 TC 62 Z9 63 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD JAN PY 2005 VL 132 IS 2 BP 415 EP 427 DI 10.1242/dev.01579 PG 13 WC Developmental Biology SC Developmental Biology GA 896HQ UT WOS:000226925600018 PM 15604097 ER PT J AU Rhodes, J Hagen, A Hsu, K Deng, M Liu, TX Look, AT Kanki, JP AF Rhodes, J Hagen, A Hsu, K Deng, M Liu, TX Look, AT Kanki, JP TI Interplay of Pu.1 and gatal determines myelo-erythroid progenitor cell fate in zebrafish SO DEVELOPMENTAL CELL LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; EXPRESSION PATTERN; HEART FIELD; GENE; DIFFERENTIATION; CLOCHE; MUTATION; BLOOD; ERYTHROPOIESIS; MYELOPOIESIS AB The zebrafish is a powerful model system for investigating embryonic vertebrate hematopoiesis, allowing for the critical in vivo analysis of cell lineage determination. In this study, we identify zebrafish myeloerythroid progenitor cells (MPCs) that are likely to represent the functional equivalent of mammalian common myeloid progenitors. Utilizing transgenic pu.1-GFP fish, real-time MPC differentiation was correlated with dynamic changes in cell motility, morphology, and gene expression. Unlike mammalian hematopoiesis, embryonic zebrafish myelopoiesis and erythropoiesis occur in anatomically separate locations. Gene knockdown experiments and transplantation assays demonstrated the reciprocal negative regulation of pu.1 and gata1 and their non-cell-autonomous regulation that determines myeloid versus erythroid MPC fate in the distinct blood-forming regions. Furthermore, forced expression of pu.1 in the bloodless mutant cloche resulted in myelopoietic rescue, providing intriguing evidence that this gene can function in the absence of some stem cell genes, such as scl, in governing myelopoiesis. C1 Dana Farber Canc Inst, Dept Pediat Surg, Boston, MA 02115 USA. RP Kanki, JP (reprint author), Dana Farber Canc Inst, Dept Pediat Surg, Boston, MA 02115 USA. EM john_kanki@dfci.harvard.edu FU NCI NIH HHS [CA096785, CA93152]; NICHD NIH HHS [HD41330, P30 HD18655] NR 40 TC 203 Z9 209 U1 2 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JAN PY 2005 VL 8 IS 1 BP 97 EP 108 DI 10.1016/j.devcel.2004.11.014 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 887SL UT WOS:000226325700013 PM 15621533 ER PT J AU Seidman, LJ Biederman, J Monuteaux, MC Valera, E Doyle, AE Faraone, SV AF Seidman, LJ Biederman, J Monuteaux, MC Valera, E Doyle, AE Faraone, SV TI Impact of gender and age on executive functioning: Do girls and boys with and without attention deficit hyperactivity disorder differ neuropsychologically in preteen and teenage years? SO DEVELOPMENTAL NEUROPSYCHOLOGY LA English DT Article ID CLINICALLY REFERRED SAMPLE; OSTERRIETH COMPLEX FIGURE; DEFICIT/HYPERACTIVITY DISORDER; LEARNING-DISABILITIES; SUSTAINED ATTENTION; FAMILIAL SUBTYPE; SEX-DIFFERENCES; CHILDREN; ADHD; COMORBIDITY AB ADHD is known to have neuropsychological correlates, characterized mainly by executive function (EF) deficits. However, most available data are based on studies of boys through age 12. Our goal was to assess whether girls with ADHD express neuropsychological features similar to those found in boys, and whether these impairments are found in both preteen and teen samples. Participants were 101 girls and 103 boys with DSM-III-R ADHD, and 109 comparison girls and 70 boys without ADHD, ages 9 to 17 years. Information on neuropsychological performance was obtained in a standardized manner blind to clinical status. Primary regression analyses controlled for age, socioeconomic status, learning disability, and psychiatric comorbidity. Girls and boys with ADHD were significantly more impaired on some measures of EFs than healthy comparisons but did not differ significantly from each other. With the exception of I test score there were no significant Sex x Diagnosis interactions. Moreover, there were no more significant interactions among age, gender, and diagnosis than would be expected by chance. Neuropsychological measures of EFs were comparably impaired in girls compared to boys with ADHD, and these impairments are found at ages 9 to 12 and ages 13 to 17. These findings suggest that executive dysfunctions are correlates of ADHD regardless of gender and age, at least through the late teen years. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Mental Hlth Ctr, Commonwealth Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. RP Seidman, LJ (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Psychiat Serv, ACC 725,15 Parkman St, Boston, MA 02114 USA. EM larry_seidman@hms.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01MH-41314, R01MH-50657] NR 87 TC 84 Z9 86 U1 5 U2 15 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 8756-5641 J9 DEV NEUROPSYCHOL JI Dev. Neuropsychol. PY 2005 VL 27 IS 1 BP 79 EP 105 DI 10.1207/s15326942dn2701_4 PG 27 WC Psychology, Developmental; Psychology; Psychology, Experimental SC Psychology GA 896YF UT WOS:000226969800004 PM 15737943 ER PT J AU Chen, SY Charness, ME Wilkemeyer, MF Sulik, KK AF Chen, SY Charness, ME Wilkemeyer, MF Sulik, KK TI Peptide-mediated protection from ethanol-induced neural tube defects SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE ethanol; fetal alcohol spectrum disorders; L1 cell adhesion molecule; neuroprotective peptide NAPVSIPQ; neural tube defects; neuroprotective peptide SALLRSIPA ID FETAL ALCOHOL SYNDROME; CELL-CELL ADHESION; DEPENDENT NEUROTROPHIC FACTOR; NEUROPROTECTIVE PEPTIDE; PRENATAL EXPOSURE; OXIDATIVE STRESS; BASAL GANGLIA; MOUSE MODEL; CHILDREN; BRAIN AB Ethanol inhibition of L1-mediated cell adhesion may contribute to the spectrum of neurological, behavioral and morphological abnormalities associated with prenatal ethanol exposure. We showed previously that the neuroprotective peptides NAPVSIPQ (NAP) and SALLRSIPA (SAL) antagonize ethanol inhibition of L1 adhesion and prevent ethanol-induced growth retardation in mouse whole embryo culture. Here we ask whether NAP and SAL also prevent ethanol-induced major malformations of the nervous system. Gestational day 8.0 (3-5 somites) C57BL/6J mouse embryos were grown for 6 h in control medium, 100 m M ethanol and 10(-10) M peptides and then maintained for an additional 20 h in control medium. At the end of the culture period, only embryos having 18-19 somite pairs were examined and compared for the degree of neural tube closure. Ethanol exposure resulted in neural tube defects (NTDs) consistent with total dysraphia and anencephaly. Co-incubation with ethanol and L-NAP (all L-amino acids), D-NAP (all D-amino acids) or SAL significantly increased the percentage of embryos that had begun to close their neural folds at the level of the forebrain/midbrain junction or that had progressed beyond this stage of closure. P7A-NAP (NAPVSIAQ), which lacks neuroprotective activity, but retains activity as an antagonist of ethanol inhibition of L1 adhesion, was effective in preventing ethanol-induced NTDs. In contrast, 16A-NAP (NAPVSAPQ), which shows reduced efficacy as an ethanol antagonist but retains its neuroprotective efficacy, did not significantly diminish the induction of NTDs by ethanol. These findings demonstrate the ability of NAP and SAL to prevent ethanol-induced NTDs and support the hypothesis that ethanol teratogenesis is caused in part by ethanol inhibition of L1-mediated cell adhesion. Copyright © 2005 S. Karger AG, Basel. C1 Univ N Carolina, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA. VA Boston Healthcare Syst, Neurol Serv, W Roxbury, MA USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. RP Chen, SY (reprint author), Univ N Carolina, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA. EM syc@med.unc.edu OI Charness, Michael/0000-0002-3301-8966 FU NIAAA NIH HHS [K01 AA013908, AA12974, AA11605, AA013908] NR 47 TC 46 Z9 48 U1 2 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2005 VL 27 IS 1 BP 13 EP 19 DI 10.1159/000084528 PG 7 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 925ER UT WOS:000229034800002 PM 15886480 ER PT J AU Sfaello, I Daire, JL Husson, I Kosofsky, B Sebag, G Gressens, P AF Sfaello, I Daire, JL Husson, I Kosofsky, B Sebag, G Gressens, P TI Patterns of excitotoxin-induced brain lesions in the newborn rabbit: A neuropathological and MRI correlation SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE excitotoxin-induced brain lesions; newborn rabbit; cerebral palsy ID PERIVENTRICULAR WHITE-MATTER; EXCITATORY AMINO-ACIDS; CENTRAL-NERVOUS-SYSTEM; SUBPLATE NEURONS; CEREBRAL-PALSY; SELECTIVE VULNERABILITY; PREMATURE-INFANT; NEONATAL HYPOXIA; RHESUS-MONKEY; INJURY AB There is pressing need to employ new advances in structural MR brain imaging to better diagnose brain damage in newborn infants. Timely application of such technology will enable improved therapeutic interventions. Diffusion-weighted sequences are a sensitive marker of very early neuronal injury, the spatial pattern of which provides critical information regarding the underlying pathophysiology. We have modified our murine model of excitotoxic neonatal brain injury to the rabbit, an animal whose brain is larger and where the neuroanatomic organization of the subcortical white matter more closely resembles that of the human. Utilizing this rabbit model, we undertook an MRI/histopathologic correlation. We found that as with the mouse, there is a spatiotemporal selectivity to the pattern of brain injury, and that the period from postnatal day (P) 7 to P9 in rabbits corresponds to the time of maximum vulnerability of the brain to excitotoxic white matter damage, which neuropathologically simulates periventricular leukomalacia (PVL). We additionally noted that diffusion-weighted imaging provided the most sensitive means of detecting such lesions and that this method was sensitive to structural maturational changes accompanying the normal cortical ontogeny. Taken together, our findings suggest that this rabbit model of perinatal excitotoxic brain injury will be a valuable addition to experimental approaches to further our understanding of perinatal brain damage, that diffusion-weighted imaging will be an invaluable adjunct to the diagnosis of such injury, and that therapeutic strategies aimed at interrupting the evolution of PVL should include targeting the pathophysiologic cascade induced by excitotoxic neonatal brain injury. Copyright (c) 2005 S. Karger AG, Basel. C1 Hop Robert Debre, INSERM, U676, FR-75019 Paris, France. Hop Robert Debre, Serv Neurol Pediat, FR-75019 Paris, France. Hop Robert Debre, Serv Imagerie Med, FR-75019 Paris, France. Massachusetts Gen Hosp, Dept Neurol, Lab Mol & Dev Neurosci, Boston, MA 02114 USA. RP Gressens, P (reprint author), Hop Robert Debre, INSERM, U676, 48 Blvd Serurier, FR-75019 Paris, France. EM gressens@debre.inserm.fr OI Gressens, Pierre/0000-0002-0909-4221 NR 34 TC 10 Z9 11 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2005 VL 27 IS 2-4 SI SI BP 160 EP 168 DI 10.1159/000085988 PG 9 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 947XA UT WOS:000230679400011 PM 16046850 ER PT J AU Guerriero, RM Rajadhyaksha, A Crozatier, C Giros, B Nosten-Bertrand, M Kosofsky, BE AF Guerriero, RM Rajadhyaksha, A Crozatier, C Giros, B Nosten-Bertrand, M Kosofsky, BE TI Augmented constitutive CREB expression in the nucleus accumbens and striatum may contribute to the altered behavioral response to cocaine of adult mice exposed to cocaine in utero SO DEVELOPMENTAL NEUROSCIENCE LA English DT Review DE behavioral sensitization; prenatal cocaine; CREB; Nucleus accumbens; mouse behavior ID ELEMENT-BINDING-PROTEIN; VENTRAL TEGMENTAL AREA; MATERNAL LIFE-STYLE; GLUTAMATE-RECEPTOR SUBUNITS; FREELY MOVING RATS; PRENATAL COCAINE; GENE-EXPRESSION; DOPAMINE-RECEPTOR; INVIVO MICRODIALYSIS; DELTA-FOSB AB Neuroadaptations occurring in the mesolimbic dopamine pathway following recurrent exposure to drugs of abuse have been correlated with a behavioral phenomenon known as behavioral sensitization. We have developed an animal model of prenatal cocaine exposure and, using a postnatal sensitization protocol, have examined the subsequent sensitivity of offspring to cocaine. Pregnant Swiss Webster dams were injected twice daily from embryonic day 8 to 17, inclusive, with cocaine (COC40: administered cocaine HCl at a dose of 40 mg/kg/day, and COC20: administered cocaine HCl at a dose of 20 mg/kg/day), or saline ( SAL). The SPF40 group ( saline pair-fed), a nutritional control group, was 'pair-fed' with COC40 dams. Activity was recorded for 30 min during a 3-day saline habituation, a 14-day 'initiation' phase, when animals received cocaine ( 15 mg/kg) or saline every other day, and following a 21-day 'withdrawal' period when all mice were challenged with cocaine. COC40 offspring, as compared with SAL controls, did not habituate to a novel environment, demonstrated increased cocaine-induced stereotypy on Coc 1 (first cocaine injection), and blunted locomotor sensitization on challenge as measured by the percentage of each animal's baseline locomotion. Tissue samples of the nucleus accumbens (NAc) and striatum (Str) of all four prenatal treatment groups were examined to determine whether alterations in the transcription factor CREB or glutamate receptor subunit, GluR1, induced by prenatal cocaine treatment may have contributed to the altered behavioral responses. Immunoblot quantitation revealed significantly increased constitutive CREB expression in the NAc and Str of COC40 mice as compared with SAL controls. Such alterations in constitutive CREB levels may contribute to some of the behavioral differences reported in adult mice exposed to cocaine in utero. Copyright (c) 2005 S. Karger AG, Basel. C1 New York Presbyterian Hosp, Weill Cornell Med Coll, Div Pediat Neurol, Dept Pediat, New York, NY 10021 USA. Massachusetts Gen Hosp East, Lab Mol & Dev Neurosci, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. INSERM, U513, Fac Med, Creteil, France. RP Kosofsky, BE (reprint author), New York Presbyterian Hosp, Weill Cornell Med Coll, Div Child Neurol, 525 E 68th St,Box 91, New York, NY 10021 USA. EM bar2009@med.cornell.edu FU NIDA NIH HHS [DA 00354, DA 08648] NR 129 TC 15 Z9 16 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2005 VL 27 IS 2-4 SI SI BP 235 EP 248 DI 10.1159/000085997 PG 14 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 947XA UT WOS:000230679400020 PM 16046859 ER PT J AU Fukumoto, T Blakely, R Levin, M AF Fukumoto, T Blakely, R Levin, M TI Serotonin transporter function is an early step in left-right patterning in chick and frog embryos SO DEVELOPMENTAL NEUROSCIENCE LA English DT Review DE serotonin; 5-hydroxytryptamine; serotonin transporter; vesicular monoamine transporter; left-right asymmetry; Xenopus; chick ID LEFT-RIGHT ASYMMETRY; LEFT-RIGHT AXIS; SPECIES-SCANNING MUTAGENESIS; CHROMAFFIN GRANULE GHOSTS; REUPTAKE INHIBITORS; EARLY EMBRYOGENESIS; BINDING-PROTEINS; SMOOTH-MUSCLE; NEUROTRANSMITTER TRANSPORTERS; CRANIOFACIAL MORPHOGENESIS AB The neurotransmitter serotonin has been shown to regulate a number of embryonic patterning events in addition to its crucial role in the nervous system. Here, we examine the role of two serotonin transporters, the plasma membrane serotonin transporter (SERT) and the vesicular monoamine transporter (VMAT), in embryonic left-right asymmetry. Pharmacological or genetic inhibitors of either SERT or VMAT specifically randomized the laterality of the heart and viscera in Xenopus embryos. This effect takes place during cleavage stages, and is upstream of the left-sided gene XNR-1. Targeted microinjection of an SERT-dominant negative construct confirmed the necessity for SERT function in embryonic laterality and revealed that the descendants of the right ventral blastomere are the most dependant upon SERT signaling in left-right patterning. Moreover, the importance of SERT and VMAT in laterality is conserved in chick embryos, being upstream of the early left-sided gene Shh. Endogenous transcripts of SERT and VMAT are expressed from the initiation of the primitive streak in chick and are asymmetrically expressed in Hensen's node. Taken together our data characterize two new right-sided markers in chick gastrulation, identify a novel, early component of the left-right pathway in two vertebrate species, and reveal a new biological role for serotonin transport. Copyright (c) 2005 S. Karger AG, Basel. C1 Harvard Univ, Sch Med, Dept Oral & Dev Biol, Cytokine Biol Dept,Forsyth Inst, Boston, MA 02115 USA. Vanderbilt Univ Sch Med, Dept Pharmacol, Nashville, TN USA. RP Levin, M (reprint author), Harvard Univ, Sch Med, Dept Oral & Dev Biol, Cytokine Biol Dept,Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. EM mlevin@forsyth.org FU NCI NIH HHS [CO6RR11244] NR 120 TC 69 Z9 70 U1 1 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2005 VL 27 IS 6 BP 349 EP 363 DI 10.1159/000088451 PG 15 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 982ZT UT WOS:000233201600001 PM 16280633 ER PT J AU Economides, PA Khaodhiar, L Caselli, A Caballero, AE Keenan, H Bursell, SE King, GL Johnstone, MT Horton, ES Veves, A AF Economides, PA Khaodhiar, L Caselli, A Caballero, AE Keenan, H Bursell, SE King, GL Johnstone, MT Horton, ES Veves, A TI The effect of vitamin E on endothelial function of micro- and macrocirculation and left ventricular function in type 1 and type 2 diabetic patients SO DIABETES LA English DT Article ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; ALPHA-TOCOPHEROL SUPPLEMENTATION; RANDOMIZED CONTROLLED TRIAL; POSTMENOPAUSAL WOMEN; ANTIOXIDANT VITAMINS; BRACHIAL-ARTERY; MELLITUS; CORONARY; RISK; CARDIOMYOPATHY AB We examined the effects of high-dosage vitamin E treatment over a 12-month period on the vascular reactivity of micro- and macrocirculation and left ventricular function in diabetic patients. Subjects (n = 89) were randomized to vitamin E (1,800 IU daily) or placebo and were followed for 12 months. High-resolution ultrasound images were used to measure the flow-mediated dilation (FMD; endothelium dependent) and nitroglycerin-induced dilation (NID; endothelium independent) of the brachial artery. Laser Doppler perfusion imaging was used to measure vascular reactivity in the forearm skin. Left ventricular function was evaluated using transthoracic echocardiogram. At the end of the 6-month period, a worsening in endothelium-dependent skin vasodilation (P = 0.02) and rise in endothelin levels (P = 0.01) were found in the vitamin E compared with the placebo group. At the end of the 12-month period, a worsening was observed in NID (P = 0.02) and a marginal worsening was seen in systolic blood pressure (P = 0.04) and FMD (P = 0.04) in the vitamin E compared with the placebo group. In addition C-reactive protein levels decreased marginally in the vitamin E compared with the placebo group (P = 0.05). No changes were observed in left ventricular function. We concluded that long-term treatment with 1,800 IU of vitamin E has no beneficial effects on endothelial or left ventricular function in diabetic patients. Because vitamin E-treated patients had a worsening in some vascular reactivity measurements when compared with control subjects, the use of high dosages of vitamin E cannot be recommended. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Microcirculat Lab, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02115 USA. RP Veves, A (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Microcirculat Lab, Palmer 317,BIDMC W,1 Deaconess Rd, Boston, MA 02215 USA. EM aveves@bidmc.harvard.edu NR 37 TC 38 Z9 41 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2005 VL 54 IS 1 BP 204 EP 211 DI 10.2337/diabetes.54.1.204 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 886SA UT WOS:000226247500027 PM 15616030 ER PT J AU Silverstein, J Klingensmith, G Copeland, K Plotnick, L Kaufman, F Laffel, L Deeb, L Grey, M Anderson, B Holzmeister, LA Clark, N AF Silverstein, J Klingensmith, G Copeland, K Plotnick, L Kaufman, F Laffel, L Deeb, L Grey, M Anderson, B Holzmeister, LA Clark, N TI Care of children and adolescents with type 1 diabetes - A statement of the American Diabetes Association SO DIABETES CARE LA English DT Review ID CHOLESTEROL EDUCATION-PROGRAM; CARDIOVASCULAR RISK-FACTORS; GLUCOSE MONITORING-SYSTEM; IMPROVED GLYCEMIC CONTROL; INTIMA-MEDIA THICKNESS; INSULIN PUMP THERAPY; QUALITY-OF-LIFE; CELIAC-DISEASE; METABOLIC-CONTROL; EATING-DISORDERS C1 Amer Diabet Assoc, Alexandria, VA 22311 USA. Univ Florida, Dept Pediat, Div Endocrinol, Gainesville, FL 32611 USA. Barbara Davis Ctr, Dept Pediat, Denver, CO USA. Univ Oklahoma, Sch Med, Dept Pediat, Oklahoma City, OK USA. Johns Hopkins Med Institut, Dept Pediat, Div Endocrinol, Baltimore, MD USA. Univ So Calif, Childrens Hosp, Keck Sch Med, Dept Pediat, Los Angeles, CA 90089 USA. Joslin Diabet Ctr, Pediat & Adolescent Unit, Boston, MA 02215 USA. Childrens Clin, Tallahassee, FL USA. Yale Univ, Sch Nursing, New Haven, CT 06520 USA. Baylor Coll Med, Houston, TX 77030 USA. Holzmeister Nutr Commun, Tempe, AZ USA. RP Clark, N (reprint author), Amer Diabet Assoc, 1701 N Beauregard St, Alexandria, VA 22311 USA. EM nclark@diabetes.org NR 236 TC 636 Z9 659 U1 5 U2 36 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2005 VL 28 IS 1 BP 186 EP 212 DI 10.2337/diacare.28.1.186 PG 27 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 886SC UT WOS:000226247700031 PM 15616254 ER PT J AU Ehrenkranz, JRL Lewis, NG Kahn, CR Roth, J AF Ehrenkranz, JRL Lewis, NG Kahn, CR Roth, J TI Phlorizin: a review SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Review DE phlorizin; glycosuria; diabetes; Na+/D-glucose cotransporter ID AFFINITY NA+/GLUCOSE COTRANSPORTER; NA+-GLUCOSE COTRANSPORTERS; HUMAN INTESTINAL NA+/GLUCOSE; CORONARY-HEART-DISEASE; RENAL GLYCOSURIA; DIABETIC-RATS; INSULIN-RESISTANCE; HEXOSE-TRANSPORT; GENE SGLT1; IN-VITRO AB The dihydrochalcone phlorizin is a natural product and dietary constituent found in a number of fruit trees. It has been used as a pharmaceutical and tool for physiology research for over 150 years. Phlorizin's principal pharmacological action is to produce renal glycosuria and block intestinal glucose absorption through inhibition of the sodium-glucose syrnponers located in the proximal renal tubule and mucosa of the small intestine. This review covers the role phlorizin has played in the history of diabetes mellitus and its use as an agent to understand fundamental concepts in renal physiology as well as summarizes the physioiogy of cellular glucose transport and the pathophysiology of renal glycosuria. It reviews the biology and pathobiology of glucose transporters and discusses the medical botany of phlorizin and the potential effects of plant flavonoids. such as phlorizin, on human metabolism. Lastly. it describes the clinical pharmacology and toxicology of phlorizin. including investigational uses of phlorizin and phlorizin analogs in the treatment of diabetes, obesity, and stress hyperglycemia. Copyright (C) 2004 John Wiley Sons, Ltd. C1 Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Washington State Univ, Inst Biol Chem, Pullman, WA 99164 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Albert Einstein Coll Med, N Shore Long Isl Jewish Hlth Syst, New Hyde Pk, NY USA. RP Ehrenkranz, JRL (reprint author), Basic Res LLC, 5742 W Harold Gatty Dr, Salt Lake City, UT 84116 USA. EM JRLE@aol.com NR 112 TC 349 Z9 384 U1 11 U2 96 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD JAN-FEB PY 2005 VL 21 IS 1 BP 31 EP 38 DI 10.1002/dmrr.532 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 891PZ UT WOS:000226594300003 PM 15624123 ER PT J AU Greenbaum, CJ Eisenbarth, G Atkinson, M Yu, L Babu, S Schatz, D Zeidler, A Orban, T Wasserfall, C Cuthbertson, D Krischer, J AF Greenbaum, CJ Eisenbarth, G Atkinson, M Yu, L Babu, S Schatz, D Zeidler, A Orban, T Wasserfall, C Cuthbertson, D Krischer, J CA DPT-1 Study Grp TI High frequency of abnormal glucose tolerance in DQA1*0102/DQB1*0602 relatives identified as part of the Diabetes Prevention Trial - Type 1 Diabetes SO DIABETOLOGIA LA English DT Article DE Aetiology; human leucocyte antigen; insulin resistance; pathophysiology; prevention ID HOMEOSTASIS MODEL ASSESSMENT; ISLET-CELL ANTIBODIES; LONGITUDINAL CHANGES; INSULIN-RESISTANCE; YOUNG ADULTHOOD; RISK VARIABLES; MELLITUS; IDDM; AUTOANTIBODIES; SUSCEPTIBILITY AB Aims/hypothesis: Immunological and genetic markers can be used to assess risk of developing type 1 diabetes prior to the onset of clinical symptoms. Autoantibody-positive relatives of patients with type 1 diabetes are at increased risk for disease, while the presence of HLA DQA1* 0102/ DQB1* 0602 is thought to confer protection. Using the unique population identified by the Diabetes Prevention Trial - Type Diabetes (DPT-1), our aim was to determine if these individuals were protected from type 1 diabetes. Methods: We described metabolic and immunological characteristics of islet cell cytoplasmic autoantibodies-positive relatives with DQB1* 0602 identified as part of DPT-1. Results: We found that 32% of DQB1* 0602-positive relatives identified through the DPT1 had abnormalities of glucose tolerance despite the fact that only 19% had multiple type 1 diabetes-associated autoantibodies and only 13% had abnormal insulin secretion, markers typically associated with the disease. In addition, these markers were not associated with abnormal glucose tolerance. In contrast, the DQB1* 0602- positive relatives had elevated fasting insulin ( 117 +/- 10 pmol/l) and homeostasis model assessment of insulin resistance (HOMA-R) (4.90 +/- 0.5) values, which are more commonly associated with type 2 diabetes. The later marker of insulin resistance was associated with glucose tolerance status. Conclusions/ interpretation: Our data indicate that DQA1*0102/ DQB1* 0602 relatives identified through DPT-1 have a high frequency of abnormal glucose tolerance and a disease phenotype with characteristics of type 1 and type 2 diabetes. Thus, multiple pathways to abnormal glucose tolerance are present within families of these type 1 patients. C1 Benaroya Res Inst Virginia Mason, Seattle, WA 98101 USA. Barbara Davis Ctr Childhood Diabet, Denver, CO USA. Univ Florida, Gainesville, FL USA. Univ So Calif, Los Angeles, CA USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Univ S Florida, Tampa, FL USA. RP Greenbaum, CJ (reprint author), Benaroya Res Inst Virginia Mason, 1201 9th Ave, Seattle, WA 98101 USA. EM cjgreen@benaroyaresearch.org RI wasserfall, clive/J-9078-2012 OI wasserfall, clive/0000-0002-3522-8932 FU NIAID NIH HHS [R01 AI44431-03]; PHS HHS [39250, 42288] NR 34 TC 9 Z9 11 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JAN PY 2005 VL 48 IS 1 BP 68 EP 74 DI 10.1007/s00125-004-1608-z PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 889RI UT WOS:000226459700011 PM 15602651 ER PT J AU Bacci, S Ludovico, O Prudente, S Zhang, YY Di Paola, R Mangiacotti, D Rauseo, A Nolan, D Duffy, J Fini, G Amico, C Vigna, C Menzaghi, C Doria, A Trischitta, V AF Bacci, S Ludovico, O Prudente, S Zhang, YY Di Paola, R Mangiacotti, D Rauseo, A Nolan, D Duffy, J Fini, G Amico, C Vigna, C Menzaghi, C Doria, A Trischitta, V TI The K121Q polymorphism of the ENPP1/PC-1 gene is associated with earlier onset of insulin resistant-atherogenic phenotypes including type 2 diabetes and myocardial infarction SO DIABETOLOGIA LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 10-15, 2005 CL Athens, GREECE SP European Assoc Study Diabet C1 IRCCS, Endocrine Unit, San Giovanni Rotondo, Italy. CSS Mendel, Rome, Italy. Joslin Diabet Ctr, Boston, MA 02215 USA. IRCCS, Cardiol Unit, San Giovanni Rotondo, Italy. Univ Roma La Sapienza, Rome, Italy. RI Di Paola, Rosa/G-7813-2011; Prudente, Sabrina/H-2886-2016; Trischitta, Vincenzo/K-1487-2016 OI Di Paola, Rosa/0000-0001-5837-9111; Prudente, Sabrina/0000-0001-9220-8981; Trischitta, Vincenzo/0000-0003-1174-127X NR 0 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PY 2005 VL 48 SU 1 MA 1091 BP A395 EP A395 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962OX UT WOS:000231743202290 ER PT J AU Bavenholm, PN Ruderman, NB Kuhl, J Thorell, A Nygren, J Musi, N Goodyear, LJ Degerblad, M Brismar, T Saha, AK Efendic, S AF Bavenholm, PN Ruderman, NB Kuhl, J Thorell, A Nygren, J Musi, N Goodyear, LJ Degerblad, M Brismar, T Saha, AK Efendic, S TI Effects of chronic physical training on phenotype characteristics, insulin sensitivity and malonyl CoA regulation in subjects with type 2 diabetes SO DIABETOLOGIA LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 10-15, 2005 CL Athens, GREECE SP European Assoc Study Diabet C1 Karolinska Univ Hosp & Inst, Dept Med, Stockholm, Sweden. Boston Univ Hosp, Diabet & Metab Unit, Boston, MA USA. Karolinska Univ Hosp & Inst, Dept Mol Med, Stockholm, Sweden. Karolinska Inst, Dept Surg, Ersta Hosp, Stockholm, Sweden. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Karolinska Univ Hosp, Dept Radiol, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PY 2005 VL 48 SU 1 MA 709 BP A258 EP A258 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962OX UT WOS:000231743201307 ER PT J AU Belfort, RS Harrison, S Brown, K Darland, C Finch, J Tio, F Gastaldelli, A Hardies, J Berria, R Dwivedi, S Havranek, R Balas, B Fincke, C DeFronzo, R Cusi, K AF Belfort, RS Harrison, S Brown, K Darland, C Finch, J Tio, F Gastaldelli, A Hardies, J Berria, R Dwivedi, S Havranek, R Balas, B Fincke, C DeFronzo, R Cusi, K TI Role of pioglitazone (PIO) in patients with non-alcoholic steatohepatitis (NASH) SO DIABETOLOGIA LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 10-15, 2005 CL Athens, GREECE SP European Assoc Study Diabet C1 Univ Texas, Hlth Sci Ctr, Div Diabet, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Div Gastroenterol, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. Brooke Army Med Ctr, Div Gastroenterol, San Antonio, TX USA. Vet Adm Med Ctr, Div Pathol, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PY 2005 VL 48 SU 1 MA 770 BP A280 EP A280 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962OX UT WOS:000231743201367 ER PT J AU Kahn, SE Zinman, B Viberti, G Kravitz, BG Yu, D Heise, MA Freed, MI AF Kahn, SE Zinman, B Viberti, G Kravitz, BG Yu, D Heise, MA Freed, MI CA ADOPT Study Grp TI Obesity is a major determinant of the association of C-reactive protein levels with the number of metabolic syndrome components in recently diagnosed, drug-naive type 2 diabetes: the ADOPT study cohort SO DIABETOLOGIA LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 10-15, 2005 CL Athens, GREECE SP European Assoc Study Diabet C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. KCL Guys Hosp, London, England. GlaxoSmithKline Inc, King Of Prussia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PY 2005 VL 48 SU 1 MA 683 BP A249 EP A249 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962OX UT WOS:000231743201281 ER PT J AU Lipsky, BA Armstrong, DG Morgenstern, DE King, TR Abramson, MA AF Lipsky, BA Armstrong, DG Morgenstern, DE King, TR Abramson, MA TI Does a diabetic foot infection (DFI) wound score correlate with the clinical response to antibiotic treatment? Data from the SIDESTEP study SO DIABETOLOGIA LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 10-15, 2005 CL Athens, GREECE SP European Assoc Study Diabet C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Rosalind Franklin Univ Med, Chicago, IL USA. RI Lipsky, Benjamin/B-4645-2013 NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PY 2005 VL 48 SU 1 MA 974 BP A354 EP A354 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962OX UT WOS:000231743202174 ER PT J AU Njolstad, PR Abuelo, D Baevre, H Hansen, T Hatout, E Hogasen, AM Pedersen, O Phornphutkul, C Pontynen, S Pruhova, S Raeder, H Sagen, JV Shehadeh, N Silva, JL Sovik, O AF Njolstad, PR Abuelo, D Baevre, H Hansen, T Hatout, E Hogasen, AM Pedersen, O Phornphutkul, C Pontynen, S Pruhova, S Raeder, H Sagen, JV Shehadeh, N Silva, JL Sovik, O TI Apparently insulin-dependent patients with neonatal diabetes due to mutations in Kir6.2 may be managed on sulfonylurea with sustained metabolic control rather than insulin injections SO DIABETOLOGIA LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 10-15, 2005 CL Athens, GREECE SP European Assoc Study Diabet C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Rhode Isl Hosp, Providence, RI USA. Innlandet Hosp, Lillehammer, Norway. Steno Diabet Ctr, DK-2820 Gentofte, Denmark. Loma Linda Univ, Loma Linda, CA 92350 USA. Univ Oslo, Natl Hosp, Oslo, Norway. Dept Pediat, Rovaniemi, Finland. Charles Univ, CR-11636 Prague, Czech Republic. Univ Bergen, N-5020 Bergen, Norway. Rambam Med Ctr, Haifa, Israel. Piaui State Univ, Sch Med, Teresina Piaui, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PY 2005 VL 48 SU 1 MA 298 BP A113 EP A113 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962OX UT WOS:000231743200299 ER PT J AU Parikh, H Sjogren, M Mootha, V Groop, L AF Parikh, H Sjogren, M Mootha, V Groop, L TI Prioritizing genes under linkage peaks of genome wide scans for type 2 diabetes SO DIABETOLOGIA LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 10-15, 2005 CL Athens, GREECE SP European Assoc Study Diabet C1 Lund Univ, Dept Clin Sci Malmo Diabet & ZEndocrinol, Malmo, Sweden. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PY 2005 VL 48 SU 1 MA 285 BP A108 EP A108 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962OX UT WOS:000231743200286 ER PT J AU Robles-Osorio, L Millan-Ferro, A Aragon, A Salcido, F Ward, K Caballero, E AF Robles-Osorio, L Millan-Ferro, A Aragon, A Salcido, F Ward, K Caballero, E TI Cultural, social and demographic factors that influence adherence to treatment guidelines in Latino patients with diabetes within a multi-cultural society SO DIABETOLOGIA LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 10-15, 2005 CL Athens, GREECE SP European Assoc Study Diabet C1 Joslin Diabet Ctr, Latino Diabet Iniciat, Boston, MA 02215 USA. Hosp Univ Puerta de Hierro, Madrid, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PY 2005 VL 48 SU 1 MA 926 BP A337 EP A337 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962OX UT WOS:000231743202126 ER PT J AU Podolsky, DK AF Podolsky, DK TI IBD: the dialectic of clinical advances and challenges SO DIGESTIVE AND LIVER DISEASE LA English DT Article C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. EM dpodolsky@partners.org NR 0 TC 1 Z9 1 U1 0 U2 0 PU PACINI EDITORE PI PISA PA VIA DELLA GHERARDESCA-ZONA INDUSTRIALE OSPEDALETTO, 56121 PISA, ITALY SN 1590-8658 J9 DIGEST LIVER DIS JI Dig. Liver Dis. PD JAN PY 2005 VL 37 IS 1 BP 1 EP 2 DI 10.1016/j.dld.2004.09.009 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 894HJ UT WOS:000226781300001 PM 15702851 ER PT J AU Hur, C Wittenberg, E Nishioka, NS Gazelle, GS AF Hur, C Wittenberg, E Nishioka, NS Gazelle, GS TI Patient preferences for the management of high-grade dysplasia in Barrett's esophagus SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Barrett's esophagus; esophageal adenocarcinoma; medical decision markings; patient management ID QUALITY-OF-LIFE; SHARED DECISION-MAKING; LONG-TERM SURVIVAL; PHOTODYNAMIC THERAPY; COST-EFFECTIVENESS; HOSPITAL VOLUME; UNITED-STATES; FOLLOW-UP; ESOPHAGECTOMY; SURVEILLANCE AB Surgical esophagectomy, intensive endoscopic surveillance, and mucosal ablative techniques, particularly photodynamic therapy (PDT), have been proposed as possible management strategies for Barrett's high-grade dysplasia (HGD). Each option has advantages and disadvantages, and no firm consensus exists for the preferred strategy at this time. The purpose of this pilot study was to gain insight into patient preferences in Barrett's HGD management. Twenty patients with Barrett's esophagus were enrolled in a questionnaire study. The three possible management options for Barrett's HGD including each option's potential benefits and harms were presented to the subject in a formalized presentation that was designed to be easily comprehendible by patients. The subjects rated each strategy using a health-related quality of life instrument and chose one of the management strategies assuming they were found to have HGD. The average feeling thermometer rating scale values for the management strategies were as follows: endoscopic surveillance, 79; esophagectomy, 46; and PDT, 60. When asked to choose a strategy, 14 (70%) chose endoscopic surveillance, 3 (15%) chose esophagectomy, and 3 (15%) chose PDT. These findings were statistically significant (P = 0.0024). The patients who chose endoscopic surveillance felt "comfortable" with endoscopy, while the most common concern about esophagectomy, and PDT was the risk of death and the unknown risk of recurrence, respectively. In summary, when patients with Barrett's esophagus were presented with three options to manage HGD, the majority chose endoscopic surveillance. Familiarity with endoscopic surveillance was the predominant reason for the choice. C1 Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Hur, C (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM chur@mgh-ita.org OI Hur, Chin/0000-0002-2819-7576 NR 33 TC 8 Z9 8 U1 2 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JAN PY 2005 VL 50 IS 1 BP 116 EP 125 DI 10.1007/s10620-005-1288-7 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 894SB UT WOS:000226810800021 PM 15712648 ER PT J AU Minneci, PC Deans, KJ Haley, M Cui, XZ Natanson, C Eichacker, PQ AF Minneci, Peter C. Deans, Katherine J. Haley, Michael Cui, Xizhong Natanson, Charles Eichacker, Peter Q. BE Gad, SC TI FACTORS INFLUENCING THE EFFICACY OF MEDIATOR-SPECIFIC ANTI-INFLAMMATORY, GLUCOCORTICOID, AND ANTICOAGULANT THERAPIES FOR SEPSIS SO DRUG DISCOVERY HANDBOOK SE Pharmaceutical Development Series LA English DT Article; Book Chapter ID TUMOR-NECROSIS-FACTOR; PLACEBO-CONTROLLED TRIAL; INTERLEUKIN-1 RECEPTOR ANTAGONIST; FACTOR PATHWAY INHIBITOR; RANDOMIZED CONTROLLED-TRIAL; ACTIVATING-FACTOR ACETYLHYDROLASE; INFLAMMATORY RESPONSE SYNDROME; HIGH-DOSE METHYLPREDNISOLONE; CONTROLLED MULTICENTER TRIAL; FACTOR ANTIBODY-FRAGMENT C1 [Minneci, Peter C.; Deans, Katherine J.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Minneci, Peter C.; Deans, Katherine J.; Haley, Michael; Cui, Xizhong; Natanson, Charles; Eichacker, Peter Q.] Massachusetts Gen Hosp, Dept Chem, Boston, MA 02114 USA. RP Minneci, PC (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. NR 112 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-47172-878-8 J9 PHARM DEV PY 2005 BP 937 EP 959 DI 10.1002/0471728780.ch20 D2 10.1002/0471728780 PG 23 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BYH31 UT WOS:000298786800022 ER PT J AU Phan, J Peterfy, M Reue, K AF Phan, J Peterfy, M Reue, K TI Biphasic expression of lipin suggests dual roles in adipocyte development SO DRUG NEWS & PERSPECTIVES LA English DT Article ID FAMILIAL PARTIAL LIPODYSTROPHY; ADIPOSE-TISSUE DEVELOPMENT; PPAR-GAMMA; LAMIN A/C; IN-VITRO; DIFFERENTIATION; ADIPOGENESIS; GENE; MOUSE; MUTATION AB The identification of gene mutations that cause lipodystrophies, conditions characterized by a lack of normal adipose tissue, has revealed new proteins that play a role in adipocyte biology. Lipin is one such protein identified in a lipodystrophic mouse strain and found to be critical for normal adipocyte differentiation. Interestingly, lipin displays a biphasic expression pattern in adipocytes, with peaks of expression at two points during adipogenesis-a transient induction in preadipocytes prior to expression of peroxisome proliferator-activated receptor γ, and a second wave of expression in mature adipocytes. Thus, lipin appears to have critical roles in both adipocyte differentiation and in the function of mature adipocytes. © 2005 Prous Science. All rights reserved. C1 Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Reue, K (reprint author), 11301 Wilshire Blvd,Bldg 113 Room 312, Los Angeles, CA 90073 USA. EM reuek@ucla.edu FU NHLBI NIH HHS [HL28481]; NIGMS NIH HHS [GM08042] NR 37 TC 20 Z9 20 U1 0 U2 2 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0214-0934 J9 DRUG NEWS PERSPECT JI Drug News Perspect. PD JAN-FEB PY 2005 VL 18 IS 1 BP 5 EP 11 DI 10.1358/dnp.2005.18.1.877165 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 907TB UT WOS:000227739800001 PM 15753971 ER PT J AU Pierre, JM AF Pierre, JM TI Extrapyramidal symptoms with atypical antipsychotics - Incidence, prevention and management SO DRUG SAFETY LA English DT Review ID INDUCED TARDIVE-DYSKINESIA; PLACEBO-CONTROLLED TRIAL; VITAMIN-E TREATMENT; LOW-DOSE RISPERIDONE; LONG-TERM TREATMENT; DOUBLE-BLIND; SCHIZOAFFECTIVE DISORDER; SCHIZOPHRENIC-PATIENTS; MOVEMENT-DISORDERS; ACUTE EXACERBATION AB The treatment of schizophrenia changed drastically with the discovery of antipsychotic medications in the 1950s, the release of clozapine in the US in 1989 and the subsequent development of the atypical or novel antipsychotics. These newer medications differ from their conventional counterparts, primarily based on their reduced risk of extrapyramidal symptoms (EPS). EPS can be categorised as acute (dystonia, akathisia and parkinsonism) and tardive (tardive dyskinesia and tardive dystonia) syndromes. They are thought to have a significant impact on subjective tolerability and adherence with antipsychotic therapy in addition to impacting function. Unlike conventional antipsychotic medications, atypical antipsychotics have a significantly diminished risk of inducing acute EPS at recommended dose ranges. These drugs may also have a reduced risk of causing tardive dyskinesia and in some cases may have the ability to suppress pre-existing tardive dyskinesia. This paper reviews the available evidence regarding the incidence of acute EPS and tardive syndromes with atypical antipsychotic therapy. Estimates of incidence are subject to several confounds, including differing methods for detection and diagnosis of EPS, pretreatment effects and issues surrounding the administration of antipsychotic medications. The treatment of acute EPS and tardive dyskinesia now includes atypical antipsychotic therapy itself, although other adjunctive strategies such as antioxidants have also shown promise in preliminary trials. The use of atypical antipsychotics as first line therapy for the treatment of schizophrenia is based largely on their reduced risk of EPS compared with conventional antipsychotics. Nevertheless, EPS with these drugs can occur, particularly when prescribed at high doses. The EPS advantages offered by the atypical antipsychotics must be balanced against other important adverse effects, such as weight gain and diabetes mellitus, now known to be associated with these drugs. C1 VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP Pierre, JM (reprint author), VA Greater Los Angeles Healthcare Ctr, 11301 Wilshire Blvd,Bldg 210 Room 15, Los Angeles, CA 90073 USA. EM joseph.pierre2@med.va.gov NR 161 TC 91 Z9 95 U1 2 U2 12 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2005 VL 28 IS 3 BP 191 EP 208 DI 10.2165/00002018-200528030-00002 PG 18 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 906DB UT WOS:000227619600002 PM 15733025 ER PT J AU Sonis, ST AF Sonis, ST TI Palifermin in myelotoxic therapy-induced oral mucositis SO DRUGS LA English DT Editorial Material C1 Brigham & Womens Hosp, Div Oral Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sonis, ST (reprint author), Brigham & Womens Hosp, Div Oral Med, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 2005 VL 65 IS 15 BP 2149 EP 2149 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 985ET UT WOS:000233360400012 ER PT J AU Oh, WK AF Oh, WK TI Docetaxel in hormone-refractory metastatic prostate cancer SO DRUGS LA English DT Editorial Material C1 Harvard Univ, Sch Med, Lank Ctr Genitourinary Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Oh, WK (reprint author), Harvard Univ, Sch Med, Lank Ctr Genitourinary Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 2005 VL 65 IS 16 BP 2296 EP 2297 PG 2 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 990JF UT WOS:000233738300009 ER PT J AU Haas, L AF Haas, L TI Management of diabetes Mellitus medications in the nursing home SO DRUGS & AGING LA English DT Article ID GLYCEMIC CONTROL; DRUG-THERAPY; METFORMIN; HYPOGLYCEMIA; PREVALENCE; INSULIN; CARE; RESIDENTS; GLUCOSE AB Nursing home staff are well aware of the increasing number of residents who experience diabetes mellitus. These residents consume an inordinate amount of resources and often have major disabilities and co-morbidities. Although nonpharmacological therapies, such as consistent carbohydrate intake and increased activity levels, are always indicated in diabetes management, pharmacological therapies are often necessary to prevent the acute complications of diabetes and delay some of the long-term complications. Residents with type 2 diabetes may be managed with oral antidiabetic agents and insulin, whereas residents with type 1 diabetes will always require insulin. Oral antidiabetic agents include insulin secretagogues, which stimulate endogenous insulin secretion and are most effective in leaner persons with type 2 diabetes. Metformin is another oral antidiabetic agent; this decreases inappropriate hepatic glucose release and is most effective in obese residents with high fasting blood glucose levels. The thiazolidinediones, also called glitazones, are insulin sensitisers that enable peripheral tissues to utilise insulin more effectively. The alpha-glucosidase inhibitors delay intestinal absorption of ingested carbohydrates. In addition to oral antidiabetic agents, insulin is frequently used in diabetes management. Insulin is always indicated in type 1 diabetes and is often necessary for residents with type 2 diabetes to optimise glycaemic control. Insulin can be rapid, fast, intermediate or long acting. In addition, basal insulin is now available. These insulins can be combined with each other and, in type 2 diabetes, with oral antidiabetic agents. In order to use pharmacological therapies appropriately, the glycaemic patterns of nursing home residents should be identified, using capillary blood glucose monitoring. Once these patterns have been identified, nonpharmacological therapies can be used, usually in conjunction with the many oral antidiabetic agents and various insulins available, to optimise glycaemic control in each resident. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98108 USA. RP Haas, L (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, 1660 S Columbian Way 118, Seattle, WA 98108 USA. EM Linda.Haas@med.va.gov NR 45 TC 12 Z9 12 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PY 2005 VL 22 IS 3 BP 209 EP 218 DI 10.2165/00002512-200522030-00003 PG 10 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 917XW UT WOS:000228503600003 PM 15813654 ER PT J AU Hauser, RA Schwarzschild, MA AF Hauser, RA Schwarzschild, MA TI Adenosine A(2A) receptor antagonists for Parkinson's disease - Rationale, therapeutic potential and clinical experience SO DRUGS & AGING LA English DT Article ID MPTP-TREATED MONKEYS; C-FOS EXPRESSION; L-DOPA; 6-HYDROXYDOPAMINE-LESIONED RATS; ISTRADEFYLLINE KW-6002; COFFEE CONSUMPTION; MOTOR FLUCTUATIONS; TURNING BEHAVIOR; DYSKINESIA; CAFFEINE AB Long-term disability in Parkinson's disease (PD) is related to progression of the underlying disease and the emergence of complications of chronic levodopa therapy. There is a need for new medications that can slow the underlying progression of degeneration, improve PD symptoms in early disease without inducing dyskinesia, and improve motor fluctuations and 'off' time in advanced disease without worsening dyskinesia. Much interest has focused on the development of nondopaminergic therapies, with antagonists of the adenosine A(2A) receptor emerging as leading candidates. A(2A) receptors are selectively expressed in the basal ganglia and specific A(2A) antagonists reverse motor deficits without causing dyskinesia in animal models of PD. The antiparkinsonian potential of A(2A) receptor blockade has been expanded further by convergent epidemiological and laboratory findings suggesting a possible neuroprotective effect of A(2A) receptor antagonists in PD. Istradefylline (KW-6002) is the first of several adenosine A(2A) receptor antagonists in development for PD to advance to phase III clinical trials. Initial studies indicate that in patients with motor fluctuations on levodopa, addition of istradefylline reduces 'off' time. Additional studies are necessary to evaluate the benefit of istradefylline as monotherapy in early disease, its effect on the development of dyskinesia, and its effect on disease progression. C1 Univ S Florida, Parksons Dis & Movement Disorders Ctr, Dept Neurol, Tampa, FL 33606 USA. Univ S Florida, Parksons Dis & Movement Disorders Ctr, Dept Neurol, Tampa, FL 33606 USA. Univ S Florida, Dept Pharmacol & Expt Therapeut, Tampa, FL 33606 USA. Tampa Gen Healthcare, Tampa, FL USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hauser, RA (reprint author), Univ S Florida, Parksons Dis & Movement Disorders Ctr, Dept Neurol, 4 Columbia Dr,Suite 410, Tampa, FL 33606 USA. EM rhauser@hsc.usf.edu RI Hauser, Robert/I-5372-2012 NR 50 TC 46 Z9 48 U1 0 U2 2 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PY 2005 VL 22 IS 6 BP 471 EP 482 DI 10.2165/00002512-200522060-00002 PG 12 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 947YO UT WOS:000230683400002 PM 15974638 ER PT J AU Lang, K Earle, CC Foster, T Dixon, D Van Gool, R Menzin, J AF Lang, K Earle, CC Foster, T Dixon, D Van Gool, R Menzin, J TI Trends in the treatment of acute myeloid leukaemia in the elderly SO DRUGS & AGING LA English DT Article ID MEDICARE CLAIMS DATA; BREAST-CANCER; GEMTUZUMAB OZOGAMICIN; LINKED MEDICARE; OLDER PATIENTS; CHEMOTHERAPY; TRIAL; AML; THERAPY; ADULTS AB Introduction: Acute myeloid leukaemia (AML) is the most common type of leukaemia among adults in the US. However, data on longitudinal treatment patterns and outcomes associated with AML and its relapse are sparse, particularly among the elderly. This study documents changes in treatment patterns and outcomes among elderly AML patients over the past decade. Methods: Using the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we retrospectively evaluated trends in mortality, treatment patterns, healthcare resource utilisation and Medicare payments associated with AML and its relapse among Medicare beneficiaries >= 65 years of age who were initially diagnosed with AML in a SEER registry between 1991 and 1999. Chemotherapy was ascertained from examination of inpatient and outpatient bills. AML relapse and retreatment were identified using a validated algorithm. Costs of care were based on total Medicare payments. Results: A total of 3439 elderly patients with AML were identified. Median survival across all study patients was 2.4 months (mean +/- SD 5.6 +/- 6.8 months), with medians of 3.9, 2.2 and 1.4 months for patients 65-74 years of age, 75-84 years of age and >= 85 years of age, respectively. Fewer than 7% of patients were alive at 2 years, and there was very little variation during the decade of our analysis. Costs and overall healthcare utilisation patterns also changed very little, with the exception of those relating to hospice use and chemotherapy. Hospice use more than doubled during the decade (from 12% to 29% among patients diagnosed in 1991 and 1999, respectively; p < 0.0001), mostly among the oldest patients. Administration of chemotherapy also increased from 29% of patients diagnosed in 1991 to 38% of patients diagnosed in 1999 (p = 0.014), with the increase being seen mostly among younger patients and those treated in teaching hospitals. Average total costs ( SD) were US$51 888 +/- $54 825 and declined by age as a result of lower survival. A total of 192 patients (16% of treated patients) relapsed and received retreatment with chemotherapy. These patients survived a median 18 months, with a median duration of remission of 8 months, and average total costs three times higher than the overall sample. Conclusions: The high early mortality and costs associated with AML have not changed significantly over the past decade. However, treatment patterns appear to be changing, with increasing use of chemotherapy and hospice care. The ongoing introduction of new treatments for AML in the elderly is likely to further impact treatment patterns, and may change the economic burden of the disease. Our findings can be used as a baseline against which the benefits of new therapies can be compared. C1 Boston Hlth Econ Inc, Waltham, MA 02451 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Johnson & Johnson Pharmaceut Serv, Beerse, Belgium. RP Menzin, J (reprint author), Boston Hlth Econ Inc, 20 Fox Rd, Waltham, MA 02451 USA. EM jmenzin@bhei.com NR 47 TC 51 Z9 53 U1 2 U2 4 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PY 2005 VL 22 IS 11 BP 943 EP 955 DI 10.2165/00002512-200522110-00004 PG 13 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 999MR UT WOS:000234394200004 PM 16323971 ER PT J AU Priel, A Tuszynski, JA Cantiello, HF AF Priel, A Tuszynski, JA Cantiello, HF TI Electrodynamic signaling by the dendritic cytoskeleton: Toward an intracellular information processing model SO ELECTROMAGNETIC BIOLOGY AND MEDICINE LA English DT Article; Proceedings Paper CT International Symposium on Coherence and Electromagnetic Fields in Biological Systems CY JUL 01-04, 2005 CL Prague, CZECH REPUBLIC SP Acad Sci Czech Republic, Charles Univ, Med Fac, Minist Hlth Care Czech Republic, IEEE, Int Union Radio Sci DE actin filaments; denrites; information processing; ion channels; ionic waves propagation; microtubules ID ACTIN-FILAMENTS; CONTEXTUAL MEMORY; TERMINUS; BINDING AB A novel model for information processing in dendrites is proposed based on electrodynamic signaling mediated by the cytoskeleton. Our working hypothesis is that the dendritic cytoskeleton, including both microtubules (MTs) and actin filaments plays an active role in computations affecting neuronal function. These cytoskeletal elements are affected by, and in turn regulate, a key element of neuronal information processing, namely, dendritic ion channel activity. We present a molecular dynamics description of the C-termini protruding from the surface of an MT that reveals the existence of several conformational states, which lead to collective dynamical properties of the neuronal cytoskeleton. Furthermore, these collective states of the C-termini on MTs have a significant effect on ionic condensation and ion cloud propagation with physical similarities to those recently found in actin filaments. Our objective is to provide an integrated view of these phenomena in a bottom-up scheme, demonstrating that ionic wave interactions and propagation along cytoskeletal structures impacts channel functions and, thus, neuronal computational capabilities. C1 Univ Alberta, Dept Phys, Edmonton, AB T6G 2J1, Canada. Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Priel, A (reprint author), Univ Alberta, Dept Phys, Edmonton, AB T6G 2J1, Canada. EM apriel@phys.ualberta.ca NR 23 TC 15 Z9 15 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1536-8378 J9 ELECTROMAGN BIOL MED JI Electromagn. Biol. Med. PY 2005 VL 24 IS 3 BP 221 EP 231 DI 10.1080/15368370500379590 PG 11 WC Biology; Biophysics SC Life Sciences & Biomedicine - Other Topics; Biophysics GA 997MA UT WOS:000234248400007 ER PT J AU Sidis, Y Schneyer, AL Keutmann, HT AF Sidis, Y Schneyer, AL Keutmann, HT TI Heparin and activin-binding determinants in follistatin and FSTL3 SO ENDOCRINOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; FIBROBLAST-GROWTH-FACTOR; PROTEIN; SULFATE; SITE; GENE; INHIBITION; CELL; IDENTIFICATION; NEUTRALIZATION AB Local regulation of pituitary FSH secretion and many other cellular processes by follistatin (FS) can be ascribed to its potent ability to bind and bioneutralize activin, in conjunction with binding to cell surface heparan-sulfate proteoglycans through a basic heparin-binding sequence (HBS; residues 75 - 86) in the first of the three FS domains. The FS homolog, FSTL3, also binds activin, but lacks any HBS and cannot associate with cell surfaces. We have used mutational analyses to define the determinants for heparin binding and activin interaction in FS and to determine the effects of conferring heparin binding to FSTL3. Mutants expressed from 283F cells were tested for cell surface and heparin affinity binding, for competititive activin binding and for bioactivity by suppression of pituitary cell FSH secretion. Replacement of the HBS or the full-length FS-domain 1 abolished cell surface binding but enhanced activin binding 4- to 8-fold. Surface binding was partially reduced after mutation of either lysine pair 75/76 or 81/82 and eliminated after mutation of both pairs. The 75/76 mutation reduced activin binding and, therefore, pituitary cell bioactivity by 5-fold. However, insertion of the HBS into FSTL3 did not restore heparin binding or pituitary-cell bioactivity. These results show that 1) the residues within the HBS are necessary but not sufficient for heparin binding, and 2) the HBS also harbors determinants for activin binding. Introduction of the full domain from FS conferred heparin binding to FSTL3, but activin binding was abolished. This implies an evolutionary safeguard against surface binding by FSTL3, supporting other evidence for physiological differences between FS and FSTL3. C1 Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Keutmann, HT (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Wellman 501, Boston, MA 02114 USA. EM Keutmann@helix.mgh.harvard.edu FU NICHD NIH HHS [HD39777]; NIDDK NIH HHS [DK53828] NR 39 TC 25 Z9 26 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2005 VL 146 IS 1 BP 130 EP 136 DI 10.1210/en.2004-1041 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 880CN UT WOS:000225766500020 PM 15471966 ER PT J AU Cole, AJ AF Cole, AJ TI 2004 American Epilepsy Society Annual Course Genetics and Epilepsy Syndromes - Introduction SO EPILEPSIA LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Epilepsy Serv, Boston, MA 02115 USA. RP Cole, AJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Epilepsy Serv, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 10 BP 1 EP 1 DI 10.1111/j.1528-1167.2005.00348.x PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 999EV UT WOS:000234372500001 ER PT J AU Grant, PE AF Grant, PE TI Imaging the developing epileptic brain SO EPILEPSIA LA English DT Article; Proceedings Paper CT 24th Annual Merritt-Putnam Symposium CY DEC 04, 2004 CL New Orleans, LA SP Amer Epilepsy Soc DE imaging techniques; phased array; diffusion tensor imaging; diffusion spectroscopic imaging; white matter organization; neuronal circuit; cortical malformation ID WATER DIFFUSION; MRI; IDENTIFICATION; CHILDREN; INFANTS; LESIONS AB Accurate identification of cortical malformations in children with epilepsy can be crucial for successful clinical management. Although standard head-coil magnetic resonance imaging (MRI) at 1.5 tesla (T) can be used to view the macrostructure of the brain, phased array technology at both 1.5 and 3T significantly improves signal-to-noise ratio (SNR). As a result, spatial resolution and contrast can be optimized to increase visual detection of subtle macrostructural changes that occur with small epileptogenic lesions. In addition, these improvements in SNR allow more accurate quantitative analysis of brain macrostructure and more accurate assessment of brain microstructure using newer sophisticated imaging techniques. For example, phased array imaging enables more accurate diffusion tenser imaging (DTI), and 3T imaging, when combined with phased array technology, enables more informative diffusion spectroscopic imaging (DSI). Recent technological improvemerits therefore result in improved lesion detection and enable assessment of cerebral growth trajectories and associated longitudinal changes in tissue microstructural organization that occur in association with various types of epilepsy. This article presents a brief comparison of imaging techniques Currently in use, both clinically and experimentally, to diagnose, treat, and increase our understanding of the neuropathology of epilepsy in the developing brain. C1 Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. RP Grant, PE (reprint author), Massachusetts Gen Hosp, Dept Neuroradiol, Grey 2 B285,55 Fruit St, Boston, MA 02114 USA. EM ellen@nmr.mgh.harvard.edu NR 16 TC 12 Z9 12 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 7 BP 7 EP 14 DI 10.1111/j.1528-1167.2005.00303.x PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 974PR UT WOS:000232604400002 PM 16201990 ER PT J AU Shiraishi, H Ahlfors, SP Takano, K Okajima, M Asahina, N Sudo, A Kohsaka, S Knake, S Stufflebeam, SM Halgren, E Hatanaka, K Saitoh, S AF Shiraishi, H Ahlfors, SP Takano, K Okajima, M Asahina, N Sudo, A Kohsaka, S Knake, S Stufflebeam, SM Halgren, E Hatanaka, K Saitoh, S TI Dynamic statistical parametric mapping (dSPM) for localizing the irritative zone in analyzing the magnetoencephalographic epileptiform activity in patients with epilepsy. SO EPILEPSIA LA English DT Meeting Abstract CT 37th Congress of the Japan-Epilepsy-Society CY OCT 30-31, 2003 CL Sendai, JAPAN SP Japan Epilepsy Soc C1 Okayama Univ Sci, Dept Appl Phys, Okayama 700, Japan. Hokkaido Grad Sch Med, Dept Pediat, Sapporo, Hokkaido, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Boston, MA USA. Teine Keijinkai Hosp, Dept Pediat, Sapporo, Hokkaido, Japan. RI Shiraishi, Hideaki/A-8427-2012; Ahlfors, Seppo/P-3644-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 2 BP 18 EP 18 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 913XD UT WOS:000228188000045 ER PT J AU Duron, RM Medina, MT Martinez-Juarez, IE Bailey, JN Perez-Gosiengfiao, KT Ramos-Ramirez, R Lopez-Ruiz, M Alonso, ME Ortega, RHC Pascual-Castroviejo, I Machado-Salas, J Mija, L Delgado-Escueta, AV AF Duron, RM Medina, MT Martinez-Juarez, IE Bailey, JN Perez-Gosiengfiao, KT Ramos-Ramirez, R Lopez-Ruiz, M Alonso, ME Ortega, RHC Pascual-Castroviejo, I Machado-Salas, J Mija, L Delgado-Escueta, AV TI Seizures of idiopathic generalized epilepsies SO EPILEPSIA LA English DT Review DE seizures; epilepsy; generalized; classification; treatment ID JUVENILE MYOCLONIC EPILEPSY; CHILDHOOD ABSENCE EPILEPSY; LONG-TERM PROGNOSIS; FOLLOW-UP; SUSCEPTIBILITY LOCUS; CALCIUM-CHANNELS; ASTATIC EPILEPSY; EYELID MYOCLONIA; VIDEO-EEG; GENE AB Idiopathic generalized epilepsies (IGEs) comprise at least 40% of epilepsies in the United States, 20% in Mexico, and 8% in Central America. Here, we review seizure phenotypes across IGE syndromes, their response to treatment and advances in molecular genetics that influence nosology. Our review included the Medline database from 1945 to 2005 and our prospectively collected Genetic Epilepsy Studies (GENESS) Consortium database. Generalized seizures occur with different and similar semiologies, frequencies, and patterns, ages at onset, and outcomes in different IGEs, suggesting common neuroanatomical pathways for seizure phenotypes. However, the same seizure phenotypes respond differently to the same treatments in different IGEs, suggesting different molecular defects across syndromes. De novo mutations in SCN1A in sporadic Dravet syndrome and germline mutations in SCN1A, SCN1B, and SCN2A in generalized epilepsies with febrile seizures plus have unraveled the heterogenous myoclonic epilepsies of infancy and early childhood. Mutations in GABRA1, GABRG2, and GABRB3 are associated with absence seizures, while mutations in CLCN2 and myoclonin/EFHC1 substantiate juvenile myoclonic epilepsy as a clinical entity. Refined understanding of seizure phenotypes, their semiology, frequencies, and patterns together with the identification of molecular lesions in IGEs continue to accelerate the development of molecular epileptology. C1 Univ Calif Los Angeles, David Geffen Sch Med, VA GLAHS Med Ctr, Calif Comprehens Epilepsy Program,Epilepsy Ctr Ex, Los Angeles, CA 90073 USA. Natl Autonomous Univ, Tegucigalpa, Honduras. Univ Calif Los Angeles, David Geffen Sch Med, Genet Epilepsy Studies Int Consortium, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Inst Neuropsychiat, Los Angeles, CA USA. Natl Inst Neurol & Neurosurg, Mexico City, DF, Mexico. Mexico Gen Hosp, Neurol & Neurosurg Unit, Mexico City, DF, Mexico. Autonomous Univ Sonora, Hermosillo, Sonora, Mexico. Univ Hosp La Paz, Madrid, Spain. Inst Neurol Sci, Lima, Peru. RP Delgado-Escueta, AV (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA GLAHS Med Ctr, Calif Comprehens Epilepsy Program,Epilepsy Ctr Ex, 11301 Wilshire Blvd,Bldg 500,Suite 3405, Los Angeles, CA 90073 USA. EM escueta@ucla.edu OI Martinez-Juarez, Iris E./0000-0001-6512-5312; Duron, Reyna M./0000-0002-9425-2289 NR 104 TC 29 Z9 30 U1 2 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 9 BP 34 EP 47 DI 10.1111/j.1528-1167.2005.00312.x PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA 982ZP UT WOS:000233201200006 PM 16302874 ER PT J AU Holmes, LB Wyszynski, DF Baldwin, E Smith, CRR AF Holmes, LB Wyszynski, DF Baldwin, E Smith, CRR TI Update from the north American pregnancy registry SO EPILEPSIA LA English DT Meeting Abstract CT 26th International Epilepsy Congress CY AUG 28-SEP 01, 2005 CL Paris, FRANCE SP Int League Against Epilepsy, Int Bureau Epilepsy C1 MassGen Hosp Children, AED Pregnancy Registry, 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 6 BP 40 EP 40 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 964MN UT WOS:000231885300137 ER PT J AU Niquet, J Liu, TT Wasterlain, TG AF Niquet, J Liu, TT Wasterlain, TG TI Programmed neuronal necrosis and status epilepticus SO EPILEPSIA LA English DT Article; Proceedings Paper CT 7th Workshop on Neurobiology of Epilepsy CY OCT 07-11, 2003 CL Ericeira, PORTUGAL DE status epilepticus; programmed necrosis; neuronal loss ID TRANSIENT CEREBRAL-ISCHEMIA; GLOBAL-ISCHEMIA; CELL-DEATH; HIPPOCAMPUS; ACTIVATION; SEIZURES; APOPTOSIS; INDUCTION; SURVIVAL; BRAIN AB We examined the mechanism of neuronal necrosis induced by hypoxia in dentate gyrus cultures or by status epilepticus (SE) in adult mice. Our observations showed that hypoxic necrosis can be an active process starting with early mitochondrial swelling and loss of the mitochondrial membrane potential, followed by cytochrome c release and caspase-9-dependent activation of caspase-3. This sequence of events (or program) was independent of protein synthesis and may be induced by energy failure and/or calcium overloading of mitochondria. We called this form of necrosis "programmed necrosis." After SE in adult mice, CA1 and CA3 pyramidal neurons displayed a necrotic morphology, associated with caspase-3 immuncireactivity and with double-stranded DNA breaks, suggesting that 11 programmed necrosis" may be involved in SE-induced neuronal loss. Key Words: Status epilepticus-Programmed necrosis-Neuronal loss. C1 VA Greater Los Angeles Healthcare Syst, Epilepsy Res Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA USA. RP Niquet, J (reprint author), VA Greater Los Angeles Healthcare Syst, Epilepsy Res Lab, Res 151, Los Angeles, CA 90073 USA. EM jniquet@ucla.edu FU NINDS NIH HHS [NS 13 515] NR 18 TC 16 Z9 16 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 5 BP 43 EP 48 DI 10.1111/j.1528-1167.2005.01025.x PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 945JP UT WOS:000230499100008 PM 15987252 ER PT J AU Jansen, AC Sancak, O D'Agostino, MD Badhwar, A Roberts, P Gobbi, G Wilkinson, R Melanson, D Koenekoop, R Gans, M Van den Ouweland, AMW Nellist, M Pandolfo, M Sims, K Thiele, E Andermann, F Dubeau, F Kwiatkowski, D Halley, DJJ Andermann, E AF Jansen, AC Sancak, O D'Agostino, MD Badhwar, A Roberts, P Gobbi, G Wilkinson, R Melanson, D Koenekoop, R Gans, M Van den Ouweland, AMW Nellist, M Pandolfo, M Sims, K Thiele, E Andermann, F Dubeau, F Kwiatkowski, D Halley, DJJ Andermann, E TI Mild epilepsy phenotype in TSC2 patients with codon 905 mutations SO EPILEPSIA LA English DT Meeting Abstract CT 26th International Epilepsy Congress CY AUG 28-SEP 01, 2005 CL Paris, FRANCE SP Int League Against Epilepsy, Int Bureau Epilepsy C1 McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada. Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. McGill Univ, Dept Dermatol, Montreal, PQ, Canada. McGill Univ, Dept Radiol, Montreal, PQ, Canada. McGill Ocular Genet Lab, Montreal, PQ, Canada. Univ Libre Bruxelles, Dept Neurol, Brussels, Belgium. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. RI Gobbi, Gabriella/I-2786-2013; Jansen, Anna/P-3121-2014 OI Jansen, Anna/0000-0002-3835-2824 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 6 BP 52 EP 52 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 964MN UT WOS:000231885300184 ER PT J AU Morrell, MJ Hayes, FJ Sluss, P Warnock, CR Isojarvi, JIT AF Morrell, MJ Hayes, FJ Sluss, P Warnock, CR Isojarvi, JIT TI Higher incidence of components of polycystic ovary syndrome in young women with epilepsy treated with valproate versus lamotrigine SO EPILEPSIA LA English DT Meeting Abstract CT 26th International Epilepsy Congress CY AUG 28-SEP 01, 2005 CL Paris, FRANCE SP Int League Against Epilepsy, Int Bureau Epilepsy C1 Stanford Univ, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. GlaxoSmithKline Inc, Res Triangle Pk, NC 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 6 BP 71 EP 71 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 964MN UT WOS:000231885300248 ER PT J AU Morrell, MJ Hayes, FS Sluss, PM Warnock, CR Conklin, HS Isojarvi, JI AF Morrell, MJ Hayes, FS Sluss, PM Warnock, CR Conklin, HS Isojarvi, JI TI Higher incidence of components of polycystic ovary syndrome in young women with epilepsy treated with valproate versus lamotrigine SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 Stanford Univ, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. GlaxoSmithKline Inc, Neurosci MDC, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 88 EP 88 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540100257 ER PT J AU Cash, SS Ulbert, I Devinsky, O Bromfield, E Madsen, J Cole, A Halgren, E Doyle, W AF Cash, SS Ulbert, I Devinsky, O Bromfield, E Madsen, J Cole, A Halgren, E Doyle, W TI Lamiinar microelectrode recordings of human interictal discharges in neocortical epilepsy reveal complex high-frequency oscillation patterns SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Hungarian Acad Sci, Inst Psychol, H-1051 Budapest, Hungary. NYU Med Ctr, New York, NY 10016 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Martinos Ctr Biomed Imaging, 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 93 EP 94 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540100271 ER PT J AU Fujikawa, DG Chiueh, GM Allen, SG Shinmei, SS AF Fujikawa, DG Chiueh, GM Allen, SG Shinmei, SS TI Translocation of lysosomal cathepsin B and DNAse II to the nuclei of seizure-induced necrotic neurons SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 VA Greater Los Angeles Healthcare Syst, Expt Neurol Lab, North Hills, CA USA. Univ Calif Los Angeles, Geffen Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 102 EP 102 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540100296 ER PT J AU Baldinetti, F Lydiard, B Simon, N Zornberg, G AF Baldinetti, F Lydiard, B Simon, N Zornberg, G TI Anticonvulsant medication, pregabalin, efficaciously treats generalised anxiety disorder (GAD) SO EPILEPSIA LA English DT Meeting Abstract CT 26th International Epilepsy Congress CY AUG 28-SEP 01, 2005 CL Paris, FRANCE SP Int League Against Epilepsy, Int Bureau Epilepsy C1 Pfizer Inc, Pfizer Global Pharmaceut, New York, NY USA. SE Hlth Consultants LLC, Charlestown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 6 BP 117 EP 117 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 964MN UT WOS:000231885300417 ER PT J AU Wallis, RA Panizzon, K AF Wallis, RA Panizzon, K TI 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors provides protection against depolarization injury to CA1 pyramidal neurons in rat hippocampal slices SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 128 EP 128 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540100373 ER PT J AU Naylor, DE Wasterlain, CG AF Naylor, DE Wasterlain, CG TI GABA synapses and the rapid loss of inhibition to dentate gyrus granule cells after brief perforant-path stimulation SO EPILEPSIA LA English DT Article; Proceedings Paper CT 7th Workshop on Neurobiology of Epilepsy CY OCT 07-11, 2003 CL Ericeira, PORTUGAL DE epilepsy; status epilepticus; GABA(A) receptors; paired-pulse inhibition; hippocampus ID SUSTAINING STATUS EPILEPTICUS; ACTIVITY-DEPENDENT DISINHIBITION; PAIRED-PULSE INHIBITION; RAT HIPPOCAMPUS; ELECTRICAL-STIMULATION; GABAERGIC INHIBITION; SYNAPTIC INHIBITION; PILOCARPINE MODEL; RECEPTORS; SEIZURES AB Purpose: To study the pharmacologic and synaptic basis for the early loss of paired-pulse inhibition that occurs in the perforant-path stimulation model of status epilepticus. Methods: Hippocampal slices were prepared from mate Wistar rats. Test paired pulses (20- to 50-ms interstimulus interval) of the perforant path were used before and after an abbreviated period of perforant-path stimulation (1-5 min; 2-Hz continuous with 20 Hz of 10 s/min pulses) while either recording field potentials from the dentate gyrus granule cell layer or directly measuring whole-cell patch-clamp currents from granule cells. Paired-pulse field recordings also were obtained during perfusion of the gamma-aminobutyric acid (GABA)A antagonist bicuculline. Results: Prolonged loss of paired-pulse inhibition occurs after brief (< 5 min) perforant-path stimulation in vitro (similar to results in vivo) with the paired-pulse population spike amplitude ratio (P2/P1) increasing from a baseline of 0.53 +/- 0.29 to 1.17 +/- 0.09 after perforant-path stimulation (p < 0.05). After perfusion with the GABA(A) antagonist, bicuculline, the P2/P1 ratio also increased from a baseline of 0.52 +/- 0.16 to 1.15 +/- 0.26 (p < 0.05). After 1-2 min of perforant-path stimulation, a 22 6% (p < 0.05) decrease occurred in the P2/P1 amplitude ratio of paired-pulse evoked inhibitory postsynaptic currents. Conclusions: Similar to in vivo, loss of paired-pulse inhibition occurs with brief perforant-path stimulation in vitro. GABA(A) antagonism causes a similar loss of paired-pulse inhibition, and the effects of perforant-path stimulation on Postsynaptic inhibitory currents also are consistent with the involvement of GABA(A) synaptic receptors. The findings suggest that loss of inhibition at GABA synapses may be an important early event in the initiation of status epilepticus. C1 Univ Calif Los Angeles, Dept Neurol, Vet Adm Greater Los Angeles Healthcare Ctr, Los Angeles, CA 90073 USA. RP Naylor, DE (reprint author), Univ Calif Los Angeles, Dept Neurol, Vet Adm Greater Los Angeles Healthcare Ctr, Los Angeles, CA 90073 USA. EM dnaylor@ucla.edu FU PHS HHS [N13515] NR 34 TC 23 Z9 24 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 5 BP 142 EP 147 DI 10.1111/j.1528-1167.2005.01022.x PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 945JP UT WOS:000230499100025 PM 15987269 ER PT J AU Hadjiloizou, SM Bourgeois, BFD Duffy, FH Bergin, AM Takeoka, M Thiele, EA Holmes, G Riviello, JJ AF Hadjiloizou, SM Bourgeois, BFD Duffy, FH Bergin, AM Takeoka, M Thiele, EA Holmes, G Riviello, JJ TI Childhood-onset epileptic encephalopathies with sleep activated EEG (EESA_EEG) and high dose diazepam treatment (HDDT): Review of a 5-year experience at Children's Hospital Boston SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 150 EP 151 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540100440 ER PT J AU Morgan, AK Lyczkowki, DA Jersky, B Thiele, EA AF Morgan, AK Lyczkowki, DA Jersky, B Thiele, EA TI Neurocognitive profiles of a pediatric epilepsy population SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 157 EP 158 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540100463 ER PT J AU Gidal, BE Elliott, MB Jones, JC Molina, C AF Gidal, BE Elliott, MB Jones, JC Molina, C TI Treatment of hypovitaminosis D in patients receiving carbamazepine or phenytoin: Biopharmaceutical considerations SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA. Univ Wisconsin, Dept Neurol, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Med Ctr, Dept Neurol, Madison, WI 53705 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 175 EP 176 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540100517 ER PT J AU Gonzalez-Heydrich, J Whitney, J Hsin, O Mrakotsky, C MacMillan, C Torres, A Pravdova, I DeMaso, DR Bourgeois, B Biederman, J AF Gonzalez-Heydrich, J Whitney, J Hsin, O Mrakotsky, C MacMillan, C Torres, A Pravdova, I DeMaso, DR Bourgeois, B Biederman, J TI Tolerability of OROS-MPH 18 and 36MG in paediatric epilepsy plus attention deficit/hyperactivity disorder (ADHD) SO EPILEPSIA LA English DT Meeting Abstract CT 26th International Epilepsy Congress CY AUG 28-SEP 01, 2005 CL Paris, FRANCE SP Int League Against Epilepsy, Int Bureau Epilepsy C1 Harvard Univ, Childrens Hosp Boston, Boston, MA 02115 USA. Univ Miami, Miami, FL 33152 USA. Harvard Univ, Massachusetts Gen Hosp, 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 6 BP 179 EP 179 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 964MN UT WOS:000231885300652 ER PT J AU Mazarati, AM Lu, X Bartfai, T AF Mazarati, AM Lu, X Bartfai, T TI Serotonergic projection from dorsal raphe into the hippocampus: Role in seizures and regulation by galanin type 1 (GalR1) and type 2 (GalR2) receptors SO EPILEPSIA LA English DT Meeting Abstract CT 26th International Epilepsy Congress CY AUG 28-SEP 01, 2005 CL Paris, FRANCE SP Int League Against Epilepsy, Int Bureau Epilepsy C1 W Los Angeles VA Med Ctr, Los Angeles, CA USA. Scripps Res Inst, La Jolla, CA USA. Univ Calif Los Angeles, D Geffen Sch Med, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 6 BP 198 EP 198 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 964MN UT WOS:000231885301019 ER PT J AU Liu, HT Mazarati, A Wasterlai, C AF Liu, HT Mazarati, A Wasterlai, C TI Hippocampal circuitry during status epilepticus: Effect of neuropeptide plasticity and NMDA receptor trafficking. SO EPILEPSIA LA English DT Meeting Abstract CT 7th Workshop on the Neurobiology of Epilepsy CY OCT 07-11, 2003 CL Ericeira, PORTUGAL C1 Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Neurol, VA Greater Los Angeles, Hlth Care Syst, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 5 BP 205 EP 205 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 945JP UT WOS:000230499100058 ER PT J AU Hayes, FJ Caldwell, PT Sluss, PM Warnock, CR Isojarvi, JI AF Hayes, FJ Caldwell, PT Sluss, PM Warnock, CR Isojarvi, JI TI Body weight and serum lipid levels in young women with epilepsy treated with valproate versus lamotrigine SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. GlaxoSmithKline Inc, Neurosci MDC, Res Triangle Pk, NC 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 207 EP 207 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540100612 ER PT J AU Thompson, K AF Thompson, K TI Transplantation of genetically engineered GABA-producing cells into models of temporal lobe epilepsy. SO EPILEPSIA LA English DT Meeting Abstract CT 7th Workshop on the Neurobiology of Epilepsy CY OCT 07-11, 2003 CL Ericeira, PORTUGAL C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 5 BP 207 EP 207 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 945JP UT WOS:000230499100064 ER PT J AU Wasterlain, U Suchomelova, L Matagne, A Klitgaard, H Mazarati, A Shinmei, S Baldwin, R AF Wasterlain, U Suchomelova, L Matagne, A Klitgaard, H Mazarati, A Shinmei, S Baldwin, R TI Brivaracetam is a potent anticonvulsant in experimental status epilepticus SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 VA Greater Los Angeles Hlth Care Syst, Epilepsy Res Lab, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. UCB Bioprod SA, Preclin CNS Res, Pharma Sector, Braine Lalleud, Belgium. NR 0 TC 9 Z9 9 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 219 EP 220 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540101031 ER PT J AU Mazarati, A Sankar, R AF Mazarati, A Sankar, R TI Role of hippocampal serotonergic transmission in anticonvulsant effects of electroconvulsive treatment SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 W Los Angeles VA Med Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, D Geffen Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 224 EP 224 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540101042 ER PT J AU Pfeifer, HH Thiele, EA AF Pfeifer, HH Thiele, EA TI An updated look at the low glycemic index treatment in pediatric epilepsy SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 Massachusetts Gen Hosp, 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 231 EP 232 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540101064 ER PT J AU Costello, DJ Hoch, DB Chiappa, KH Cosgrove, GR Cole, AJ AF Costello, DJ Hoch, DB Chiappa, KH Cosgrove, GR Cole, AJ TI Surgery for epilepsy in the older patient - A plausible option SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 Massachusetts Gen Hosp, Epilepsy Serv, 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 239 EP 239 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540101085 ER PT J AU Hochberg, ER Suner, S Fellows, MR Friehs, GM Donoghue, JP AF Hochberg, ER Suner, S Fellows, MR Friehs, GM Donoghue, JP TI Intracortical recordings from a 96-microelectrode array: Potential applications in human neurophysiology SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 Brown Univ, Providence, RI 02912 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA USA. Brown Univ, Providence, RI 02912 USA. Cyberkinet Neurotechnol Syst Inc, Foxboro, 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 256 EP 256 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540101136 ER PT J AU Wang, CM Ulbert, I Doyle, WK Devinsky, O Kuzniecky, R Halgren, A AF Wang, CM Ulbert, I Doyle, WK Devinsky, O Kuzniecky, R Halgren, A TI Spatio-temporal stages in word processing: Intracranial-recorded potentials and current source density in the human frontal, temporal and occipital cortices SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 NYU, Comprehens Epilepsy Ctr, Dept Neurol, New York, NY USA. Hungarian Acad Sci, Inst Psychol, Budapest, Hungary. Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Charlestown, MA USA. INSERM, F-13258 Marseille, France. 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 323 EP 323 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540101322 ER PT J AU Goldenholz, DM Hamalainen, MS Stufflebeam, SM AF Goldenholz, DM Hamalainen, MS Stufflebeam, SM TI Utility of MEG and EEG in the localization of interictal spikes: A simulation study SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 Boston Univ, Boston, MA 02215 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr BIomed Imaging, Charlestown, MA USA. RI Hamalainen, Matti/C-8507-2013 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 325 EP 325 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540101329 ER PT J AU Poduri, A Beroukhim, R Apse, K Bourgeois, BFD Madsen, JR Black, PM Walsh, CA AF Poduri, A Beroukhim, R Apse, K Bourgeois, BFD Madsen, JR Black, PM Walsh, CA TI Single nucleotide polymorphism analysis suggests increased allele copy number at chromosome 1Q in focal malformations of cortical development SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 Childrens Hosp Boston, Dept Neurol, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp Boston, Dept Neurosurg, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 370 EP 370 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540101463 ER PT J AU Kuczynski, D Jozwiak, S Thiele, E Kmiec, T Kaczorowska, M Pakiela-Domanska, D Bachanski, M AF Kuczynski, D Jozwiak, S Thiele, E Kmiec, T Kaczorowska, M Pakiela-Domanska, D Bachanski, M TI Oral administration of high dose diazepam in children with continuous spike waves during slow sleep SO EPILEPSIA LA English DT Meeting Abstract CT 26th International Epilepsy Congress CY AUG 28-SEP 01, 2005 CL Paris, FRANCE SP Int League Against Epilepsy, Int Bureau Epilepsy C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Childrens Mem Hlth Unit,Dept Neurol & Epileptol, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Epilepsy Dept, Cambridge, MA 02138 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 6 BP 409 EP 409 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 964MN UT WOS:000231885302309 ER PT S AU Mitsiades, CS Mitsiades, N Hideshima, T Richardson, PG Anderson, KC AF Mitsiades, CS Mitsiades, N Hideshima, T Richardson, PG Anderson, KC BE Mayer, RJ Layfield, R TI Proteasome inhibitors as therapeutics SO ESSAYS IN BIOCHEMISTRY, VOL 41: THE UBIQUITIN-PROTEASOME SYSTEM SE ESSAYS IN BIOCHEMISTRY LA English DT Review; Book Chapter ID MULTIPLE-MYELOMA CELLS; NF-KAPPA-B; INDEPENDENT PROSTATE-CANCER; APOPTOTIC DEATH ACTIVATION; NON-HODGKINS-LYMPHOMA; PHASE I/II TRIAL; INCREASED SENSITIVITY; REFRACTORY MYELOMA; BORTEZOMIB PS-341; DRUG-RESISTANCE AB The ubiquitin-proteasome pathway is a principle intracellular mechanism for controlled protein degradation and has recently emerged as an attractive target for anticancer therapies, because of the pleiotropic cell-cycle regulators and modulators of apoptosis that are controlled by proteasome function. In this chapter, we review the current state of the field of proteasome inhibitors and their prototypic member, bortezomib, which was recently approved by the U.S. Food and Drug Administration for the treatment of advanced multiple myeloma. Particular emphasis is placed on the pre-clinical research data that became the basis for eventual clinical applications of proteasome inhibitors, an overview of the clinical development of this exciting drug class in multiple myeloma, and a appraisal of possible uses in other haematological malignancies, such non-Hodgkin's lymphomas. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Mitsiades, CS (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA 02115 USA. EM Constantine_Mitsaides@dfci.harvard.edu NR 51 TC 27 Z9 28 U1 0 U2 1 PU PORTLAND PRESS LTD PI LONDON PA 59 PORTLAND PL, LONDON W1N 3AJ, ENGLAND SN 0071-1365 BN 1-85578-153-0 J9 ESSAYS BIOCHEM JI Essays Biochem. PY 2005 VL 41 BP 205 EP 218 DI 10.1042/EB0410205 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDG15 UT WOS:000233336000014 PM 16250907 ER PT J AU Jaff, MR Mohler, ER AF Jaff, Michael R. Mohler, Emile R., III BE Mohler, ER GerhardHerman, M Jaff, MR TI Instrumentation SO ESSENTIALS OF VASCULAR LABORATORY DIAGNOSIS LA English DT Article; Book Chapter C1 [Jaff, Michael R.] Massachusetts Gen Hosp, Vasc Ultrasound Core Lab, Boston, MA 02114 USA. [Mohler, Emile R., III] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Mohler, Emile R., III] Univ Penn Hlth Syst, Vasc Med Program, Philadelphia, PA USA. RP Jaff, MR (reprint author), Massachusetts Gen Hosp, Vasc Ultrasound Core Lab, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-98741-4 PY 2005 BP 12 EP 19 DI 10.1002/9780470987414.ch2 D2 10.1002/9780470987414 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA BYC25 UT WOS:000297921300004 ER PT J AU Smith, EE Furie, KL Buonanno, FS Vijayappa, MB Kistler, JP AF Smith, Eric Edward Furie, Karen Lisa Buonanno, Ferdinando S. Vijayappa, Madhu B. Kistler, J. Philip BE Mohler, ER GerhardHerman, M Jaff, MR TI Neurosonology SO ESSENTIALS OF VASCULAR LABORATORY DIAGNOSIS LA English DT Article; Book Chapter ID DOPPLER ULTRASOUND CRITERIA; TRANSCRANIAL DOPPLER; ENDARTERECTOMY SPECIMENS; HEMORRHAGE; NEUROLOGY; INFARCTS; DEATH C1 [Smith, Eric Edward; Furie, Karen Lisa; Buonanno, Ferdinando S.; Vijayappa, Madhu B.; Kistler, J. Philip] Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. [Smith, Eric Edward; Furie, Karen Lisa; Buonanno, Ferdinando S.; Vijayappa, Madhu B.; Kistler, J. Philip] Harvard Univ, Sch Med, Boston, MA USA. RP Smith, EE (reprint author), Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-98741-4 PY 2005 BP 23 EP 36 D2 10.1002/9780470987414 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA BYC25 UT WOS:000297921300005 ER EF