FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Sosnovik, DE Nahrendorf, M Weissleder, R AF Sosnovik, David E. Nahrendorf, Matthias Weissleder, Ralph TI Molecular magnetic resonance imaging in cardiovascular medicine SO CIRCULATION LA English DT Article DE atherosclerosis; cardiovascular diseases; magnetic resonance imaging; myocardium; nanotechnology ID ULTRASMALL SUPERPARAMAGNETIC PARTICLES; TARGETED CONTRAST AGENT; MESENCHYMAL STEM-CELLS; POSITRON-EMISSION-TOMOGRAPHY; CARDIAC ALLOGRAFT-REJECTION; IN-VIVO DETECTION; IRON-OXIDE; ATHEROSCLEROTIC PLAQUES; MYOCARDIAL-INFARCTION; MULTIMODAL NANOPARTICLE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cardiol, Charlestown, MA 02129 USA. RP Sosnovik, DE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, 149 13th St, Charlestown, MA 02129 USA. EM sosnovik@nmr.mgh.harvard.edu FU NCI NIH HHS [P01CA117969-015904]; NHLBI NIH HHS [K08 HL079984, R01HL07864, U01HL080731]; NIBIB NIH HHS [R01EB004626] NR 83 TC 87 Z9 91 U1 0 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 17 PY 2007 VL 115 IS 15 BP 2076 EP 2086 DI 10.1161/CIRCULATIONAHA.106.658930 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 157SP UT WOS:000245741500015 PM 17438163 ER PT J AU Tseng, ASK Tapon, N Kanda, H Cigizoglu, S Edelmann, L Pellock, B White, K Hariharan, IK AF Tseng, Ai-Sun Kelly Tapon, Nicolas Kanda, Hiroshi Cigizoglu, Seden Edelmann, Lambert Pellock, Brett White, Kristin Hariharan, Iswar K. TI Capicua regulates cell proliferation downstream of the receptor tyrosine kinase/Ras signaling pathway SO CURRENT BIOLOGY LA English DT Article ID DROSOPHILA EYE; EGF RECEPTOR; GROWTH; SURVIVAL; TORSO; DIFFERENTIATION; PROGRESSION; REPRESSION; RHEB AB Signaling via the receptor tyrosine kinase (RTK)/Ras pathway promotes tissue growth during organismal development and is increased in many cancers [1]. It is still not understood precisely how this pathway promotes cell growth (mass accumulation). In addition, the RTK/Ras pathway also functions in cell survival, cell-fate specification, terminal differentiation, and progression through mitosis [2-7]. An important question is how the same canonical pathway can elicit strikingly different responses in different cell types. Here, we show that the HMG-box protein Capicua (Cic) restricts cell growth in Drosophila imaginal discs, and its levels are, in turn, downregulated by Ras signaling. Moreover, unlike normal cells, the growth of cic mutant cells is undiminished in the complete absence of a Ras signal. In addition to a general role in growth regulation, the importance of cic in regulating cell-fate determination downstream of Ras appears to vary from tissue to tissue. In the developing eye, the analysis of cic mutants shows that the functions of Ras in regulating growth and cell-fate determination are separable. Thus, the DNA-binding protein Cic is a key downstream component in the pathway by which Ras regulates growth in imaginal discs. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Hariharan, IK (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM ikh@berkeley.edu RI White, Kristin/D-7936-2013; Kanda, Hiroshi/L-1292-2013; OI Tapon, Nicolas/0000-0001-5267-6510 FU NIGMS NIH HHS [GM 55568, R01 GM061672, R01 GM061672-05, R01 GM061672-06, R01 GM61672] NR 25 TC 40 Z9 40 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 17 PY 2007 VL 17 IS 8 BP 728 EP 733 DI 10.1016/j.cub.2007.03.023 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 159KG UT WOS:000245864000031 PM 17398096 ER PT J AU Huttunen, HJ Greco, C Kovacs, DM AF Huttunen, Henri J. Greco, Christopher Kovacs, Dora M. TI Knockdown of ACAT-1 reduces amyloidogenic processing of APP SO FEBS LETTERS LA English DT Article DE RNAi; cholesterol; cholesteryl esters; amyloid-beta; Alzheimer's disease; amyloid precursor protein; ACAT ID ALZHEIMERS-DISEASE; ACYL-COENZYME; CHOLESTEROL ACYLTRANSFERASE AB Previous studies have shown that acyl-coenzyme A:cholesterol acyl transferase (ACAT), an enzyme that controls cellular equilibrium between free cholesterol and cholesteryl esters, modulates proteolytic processing of APP in cell-based and animal models of Alzheimer's disease. Here we report that ACAT-1 RNAi reduced cellular ACAT-1 protein by similar to 50% and cholesteryl ester levels by 22% while causing a slight increase in the free cholesterol content of ER membranes. This correlated with reduced proteolytic processing of APP and 40% decrease in A beta secretion. These data show that even a modest decrease in ACAT activity can have robust suppressive effects on A beta generation. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,MassGen Inst Neurodegenera, Neurobiol Dis Lab,Genet & Aging Res Unit, Charlestown, MA 02129 USA. RP Kovacs, DM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,MassGen Inst Neurodegenera, Neurobiol Dis Lab,Genet & Aging Res Unit, Charlestown, MA 02129 USA. EM Henri_Huttunen@hins.harvard.edu; Dora_Kovacs@hms.harvard.edu OI Huttunen, Henri/0000-0002-9867-4438 FU NINDS NIH HHS [R01 NS045860] NR 12 TC 32 Z9 32 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 17 PY 2007 VL 581 IS 8 BP 1688 EP 1692 DI 10.1016/j.febslet.2007.03.056 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 161PH UT WOS:000246027200024 PM 17412327 ER PT J AU Douglas, SM Chou, JJ Shih, WM AF Douglas, Shawn M. Chou, James J. Shih, William M. TI DNA-nanotube-induced alignment of membrane proteins for NMR structure determination SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE dipolar couplings; nanotechnology; liquid crystal; scaffolded origami ID LIQUID-CRYSTALLINE MEDIUM; RESIDUAL DIPOLAR COUPLINGS; VIRUS BM2 PROTEIN; POLYACRYLAMIDE GELS; MACROMOLECULES; MICELLES; REVEALS; PHASE AB Membrane proteins are encoded by 20-35% of genes but represent < 1% of known protein structures to date. Thus, improved methods for membrane-protein structure determination are of critical importance. Residual dipolar couplings (RDCs), commonly measured for biological macromolecules weakly aligned by liquid-crystalline media, are important global angular restraints for NMR structure determination. For alpha-helical membrane proteins > 15 kDa in size, Nuclear-Overhauser effect-derived distance restraints are difficult to obtain, and RDCs could serve as the main reliable source of NMR structural information. In many of these cases, RDCs would enable full structure determination that otherwise would be impossible. However, none of the existing liquid-crystalline media used to align water-soluble proteins are compatible with the detergents required to solubilize membrane proteins. We report the design and construction of a detergent-resistant liquid crystal of 0.8-mu m-long DNA-nanotubes that can be used to induce weak alignment of membrane proteins. The nanotubes are heterodimers of 0.4-mu m-long six-helix bundles each self-assembled from a 7.3-kb scaffold strand and > 170 short oligonucleotide staple strands. We show that the DNA-nanotube liquid crystal enables the accurate measurement of backbone N-H and C alpha H alpha RDCs for the detergent-reconstituted xi-xi transmembrane domain of the T cell receptor. The measured RDCs validate the high-resolution structure of this transmembrane dimer. We anticipate that this medium will extend the advantages of weak alignment to NMR structure determination of a broad range of detergent-solubilized membrane proteins. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Chou, JJ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM james_chou@hms.harvard.edu; william_shih@dfci.harvard.edu RI Chou, James/N-9840-2013; OI Douglas, Shawn/0000-0001-5398-9041 FU NIAID NIH HHS [AI067438, R01 AI067438] NR 34 TC 238 Z9 246 U1 15 U2 104 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 APR 17 PY 2007 VL 104 IS 16 BP 6644 EP 6648 DI 10.1073/pnas.0700930104 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 159ME UT WOS:000245869200029 PM 17404217 ER PT J AU Graham, RR Kyogoku, C Sigurdsson, S Vlasova, IA Davies, LRL Baechler, EC Plenge, RM Koeuth, T Ortmann, WA Hom, G Bauer, JW Gillett, C Burtt, N Graham, DSC Onofrio, R Petri, M Gunnarsson, I Svenungsson, E Ronnblom, L Nordmark, G Gregersen, PK Moser, K Gaffney, PM Criswell, LA Vyse, TJ Syvanen, AC Bohjanen, PR Daly, MJ Behrens, TW Altshuler, D AF Graham, Robert R. Kyogoku, Chieko Sigurdsson, Snaevar Vlasova, Irina A. Davies, Leela R. L. Baechler, Emily C. Plenge, Robert M. Koeuth, Thearith Ortmann, Ward A. Hom, Geoffrey Bauer, Jason W. Gillett, Clarence Burtt, Noel Graham, Deborah S. Cunninghame Onofrio, Robert Petri, Michelle Gunnarsson, Iva Svenungsson, Elisabet Ronnblom, Lars Nordmark, Gunnel Gregersen, Peter K. Moser, Kathy Gaffney, Patrick M. Criswell, Lindsey A. Vyse, Timothy J. Syvanen, Ann-Christine Bohjanen, Paul R. Daly, Mark J. Behrens, Timothy W. Altshuler, David TI Three functional variants of IFN regulatory factor 5 (IRF5) define risk and protective haplotypes for human lupus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE interferon pathway; systemic lupus erythematosus ID GENOME-WIDE ASSOCIATION; HUMAN GENE-EXPRESSION; SIB-PAIR FAMILIES; MACULAR DEGENERATION; COMMON HAPLOTYPE; ERYTHEMATOSUS; INDUCTION; DISEASE; AGE; SUSCEPTIBILITY AB Systematic genome-wide studies to map genomic regions associated with human diseases are becoming more practical. Increasingly, efforts will be focused on the identification of the specific functional variants responsible for the disease. The challenges of identifying causal variants include the need for complete ascertainment of genetic variants and the need to consider the possibility of multiple causal alleles. We recently reported that risk of systemic lupus erythematosus (SLE) is strongly associated with a common SNP in IFN regulatory factor 5 (IRFS), and that this variant altered spicing in a way that might provide a functional explanation for the reproducible association to SLE risk. Here, by resequencing and genotyping in patients with SLE, we find evidence for three functional alleles of IRF5: the previously described exon 1B splice site variant, a 30-bp in-frame insertion/deletion variant of exon 6 that alters a proline-, glutamic acid-, serine- and threonine-rich domain region, and a variant in a conserved polyA+ signal sequence that alters the length of the 3'UTR and stability of IRFS mRNAs. Haplotypes of these three variants define at least three distinct levels of risk to SLE. Understanding how combinations of variants inf luence IRF5 function may offer etiological and therapeutic insights in SLE; more generally, IRF5 and SUE illustrates how multiple common variants of the same gene can together influence risk of common disease. C1 Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. MIT, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Univ Minnesota, Sch Med, Ctr Immunol, Minneapolis, MN 55455 USA. Uppsala Univ, Dept Med Sci, SE-751 Uppsala, Sweden. Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Rheumatol Sect, London W12 0NN, England. Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, SE-771 Stockholm, Sweden. Univ Uppsala, Dept Med Sci, Rheumatol Sect, SE-771 Stockholm, Sweden. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY 11030 USA. RP Altshuler, D (reprint author), Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. EM altshuler@molbio.mgh.harvard.edu RI Altshuler, David/A-4476-2009; Gillespie, Emily/N-1265-2013; Bohjanen, Paul/B-2329-2015; OI Altshuler, David/0000-0002-7250-4107; Gillespie, Emily/0000-0001-5261-3931; Bohjanen, Paul/0000-0002-2772-3597; Svenungsson, Elisabet/0000-0003-3396-3244 FU NCRR NIH HHS [M01-RR-00052, 5 M01 RR-00079, M01 RR000052, M01 RR000079]; NIAID NIH HHS [K02 AI052170, R01 AI049494, R56 AI057484]; NIAMS NIH HHS [AR 43727, R01 AR043727] NR 32 TC 264 Z9 275 U1 0 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 17 PY 2007 VL 104 IS 16 BP 6758 EP 6763 DI 10.1073/pnas.0701266104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 159ME UT WOS:000245869200049 PM 17412832 ER PT J AU Tischkowitz, M Xia, B Sabbaghian, N Reis-Filho, JS Hamel, N Li, GL van Beers, EH Li, LL Khalil, T Quenneville, LA Omeroglu, A Poll, A Lepage, P Wong, N Nederlof, PM Ashworth, A Tonin, PN Narod, SA Livingston, DM Foulkes, WD AF Tischkowitz, Marc Xia, Bing Sabbaghian, Nelly Reis-Filho, Jorge S. Hamel, Nancy Li, Guilan van Beers, Erik H. Li, Lili Khalil, Tayma Quenneville, Louise A. Omeroglu, Atilla Poll, Aletta Lepage, Pierre Wong, Nora Nederlof, Petra M. Ashworth, Alan Tonin, Patricia N. Narod, Steven A. Livingston, David M. Foulkes, William D. TI Analysis of PALB2/FANCN-associated breast cancer families SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA repair; FANCN; Fanconi anemia; hereditary predisposition ID COMPARATIVE GENOMIC HYBRIDIZATION; FRENCH-CANADIAN DESCENT; SUSCEPTIBILITY GENES; OVARIAN-CANCER; BRCA2 MUTATIONS; FANCONI-ANEMIA; PALB2; IMBALANCES; PARTNER; REGIONS AB No more than approximate to 30% of hereditary breast cancer has been accounted for by mutations in known genes. Most of these genes, such as BRCA1, BRCA2, TP53, CHEK2, ATM, and FANCJ/BRIP1, function in DNA repair, raising the possibility that germ line mutations in other genes that contribute to this process also predispose to breast cancer. Given its close relationship with BRCA2, PALB2 was sequenced in affected probands from 68 BRCAl/BRCA2-negative breast cancer families of Ashkenazi Jewish, French Canadian, or mixed ethnic descent. The average BRCAPRO score was 0.58. A truncating mutation (229delT) was identified in one family with a strong history of breast cancer (seven breast cancers in three female mutation carriers). This mutation and its associated breast cancers were characterized with another recently reported but unstudied mutation (2521delA) that is also associated with a strong family history of breast cancer. There was no loss of heterozygosity in tumors with either mutation. Moreover, comparative genomic hybridization analysis showed major similarities to that of BRCA2 tumors but with some notable differences, especially loss of 18q, a change that was previously unknown in BRCA2 tumors and less common in sporadic breast cancer. This study supports recent observations that PALB2 mutations are present, albeit not frequently, in breast cancer families. The apparently high penetrance noted in this study suggests that at least some PALB2 mutations are associated with a substantially increased risk for the disease. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. McGill Univ, Dept Pathol, Sir Mortimer B Davis Jewish Hosp, Montreal, PQ H3T 1E2, Canada. McGill Univ, Segal Canc Ctr, Sir Mortimer B Davis Jewish Hosp, Montreal, PQ H3T 1E2, Canada. McGill Univ, Program Canc Genet, Dept Oncol, Montreal, PQ H2W 1S6, Canada. McGill Univ, Program Canc Genet, Dept Human Genet, Montreal, PQ H2W 1S6, Canada. McGill Univ, Dept Med, Montreal, PQ H2W 1S6, Canada. McGill Univ, Dept Human Genet, Montreal, PQ H2W 1S6, Canada. Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ H3G 1A4, Canada. Netherlands Canc Inst, Div Expt Therapy, NL-1066 CX Amsterdam, Netherlands. Netherlands Canc Inst, Dept Pathol, NL-1066 CX Amsterdam, Netherlands. McGill Univ, Dept Pathol, Montreal, PQ H3A 2B4, Canada. Womens Coll Hosp, Womens Coll Res Inst, Toronto, ON M5G 1N9, Canada. Genome Quebec Innovat Ctr, Montreal, PQ H3A 1A4, Canada. RP Foulkes, WD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM william.foulkes@mcgill.ca OI foulkes, william/0000-0001-7427-4651 NR 25 TC 130 Z9 132 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 17 PY 2007 VL 104 IS 16 BP 6788 EP 6793 DI 10.1073/pnas.0701724104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 159ME UT WOS:000245869200054 PM 17420451 ER PT J AU Pizzato, M Helander, A Popova, E Calistri, A Zamborlini, A Palu, G Gottlinger, HG AF Pizzato, Massimo Helander, Anna Popova, Elena Calistri, Arianna Zamborlini, Alessia Palu, Giorgio Gottlinger, Heinrich G. TI Dynamin 2 is required for the enhancement of HIV-1 infectivity by Nef SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HIV accessory protein; host factor; virion infectivity ID CD4 DOWN-REGULATION; VIRUS TYPE-1 NEF; CLASS-I MOLECULES; CELL-SURFACE CD4; VIRAL INFECTIVITY; DILEUCINE MOTIF; LIPID RAFTS; HUMAN THIOESTERASE; ENDOCYTIC PATHWAY; TARGETING SIGNAL AB Nef is a virulence factor of HIV-1 and other primate lentivinuses that is crucial for rapid progression to AIDS. In cell culture, Nef increases the infectivity of HIV-1 progeny virions by an unknown mechanism. We now show that dynamin 2 (Dyn2), a key regulator of vesicular trafficking, is a binding partner of Nef that is required for its ability to increase viral infectivity. Dominant-negative Dyn2 or the depletion of Dyn2 by small interfering RNA potently inhibited the effect of Nef on HIV-1 infectivity. Furthermore, in Dyn2-depleted cells, this function of Nef could be rescued by ectopically expressed Dyn2 but not by Dyn1, a closely related isoform that does not bind Nef. The infectivity enhancement by Nef also depended on clathrin, because it was diminished in clathrin-depleted cells and profoundly inhibited in cells expressing the clathrin-binding domain of AP180, which blocks clathrin-coated pit formation but not clathrin-independent enclocytosis. Together, these findings imply that the infectivity enhancement activity of Nef depends on Dyn2- and clathrin-mediated membrane invagination events. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Padua, Dept Histol Microbiol & Med Biotechnol, I-35121 Padua, Italy. Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis, Div Med, London W2 1PG, England. RP Gottlinger, HG (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM m.pizzato@imperial.ac.uk; heinrich.gottlinger@umassmed.edu FU NIAID NIH HHS [R01 AI029873, R21 AI054261, AI29873, R37 AI029873, AI54261] NR 59 TC 72 Z9 73 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 APR 17 PY 2007 VL 104 IS 16 BP 6812 EP 6817 DI 10.1073/pnas.0607622104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 159ME UT WOS:000245869200058 PM 17412836 ER PT J AU Waisman, A Kraus, M Seagal, J Ghosh, S Melamed, D Song, JA Sasaki, Y Classen, S Lutz, C Brombacher, F Nitschke, L Rajewsky, K AF Waisman, Ari Kraus, Manfred Seagal, Jane Ghosh, Snigdha Melamed, Doron Song, Jian Sasaki, Yoshiteru Classen, Sabine Lutz, Claudia Brombacher, Frank Nitschke, Lars Rajewsky, Klaus TI IgG1 B cell receptor signaling is inhibited by CD22 and promotes the development of B cells whose survival is less dependent on Ig alpha/beta SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ALLELIC EXCLUSION; ANTIGEN RECEPTOR; TRANSGENIC MICE; REGULATED EXPRESSION; BONE-MARROW; LYMPHOCYTES; MATURATION; GENE; TAIL; AUTOIMMUNITY AB We describe a mouse strain in which B cell development relies either on the expression of membrane-bound immunoglobulin ( Ig) gamma 1 or mu heavy chains. Progenitor cells expressing gamma 1 chains from the beginning generate a peripheral B cell compartment of normal size with all subsets, but a partial block is seen at the pro- to pre-B cell transition. Accordingly, gamma 1-driven B cell development is disfavored in competition with developing B cells expressing a wild-type ( WT) IgH locus. However, the mutant B cells display a long half-life and accumulate in the mature B cell compartment, and even though partial truncation of the Ig alpha cytoplasmic tail compromises their development, it does not affect their maintenance, as it does in WT cells. IgG1-expressing B cells showed an enhanced Ca2+ response upon B cell receptor cross-linking, which was not due to a lack of inhibition by CD22. The enhanced Ca2+ response was also observed in mature B cells that had been switched from IgM to IgG1 expression in vivo. Collectively, these results suggest that the gamma 1 chain can exert a unique signaling function that can partially replace that of the Ig alpha/beta. heterodimer in B cell maintenance and may contribute to memory B cell physiology. C1 Univ Cologne, Inst Genet, D-50674 Cologne, Germany. Univ Cologne, Ctr Mol Med, D-50674 Cologne, Germany. Univ Mainz, Dept Med 1, D-55131 Mainz, Germany. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Erlangen Nurnberg, Dept Genet, D-91058 Erlangen, Germany. Technion Israel Inst Technol, Ruth & Bruce Rappaport Fac Med, Dept Immunol, IL-31096 Haifa, Israel. Technion Israel Inst Technol, Rappaport Family Inst Res Med Sci, IL-31096 Haifa, Israel. Max Planck Inst Immunobiol, D-79011 Freiburg, Germany. Univ Cape Town, Groote Schuur Hosp, Dept Immunol, ZA-7925 Cape Town, South Africa. RP Waisman, A (reprint author), Univ Cologne, Inst Genet, D-50674 Cologne, Germany. EM waisman@uni-mainz.de; rajewsky@cbr.med.harvard.edu RI Waisman, Ari/C-7383-2015 OI Waisman, Ari/0000-0003-4304-8234 FU NIAID NIH HHS [1R37 AI054636-01, R37 AI054636] NR 38 TC 65 Z9 66 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 16 PY 2007 VL 204 IS 4 BP 747 EP 758 DI 10.1084/jem.20062024 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 160DP UT WOS:000245920600007 PM 17420268 ER PT J AU O'Hearn, DJ Giraud, GD Sippel, JM Edwards, C Chan, B Holden, WE AF O'Hearn, Daniel J. Giraud, George D. Sippel, Jeffrey M. Edwards, Chad Chan, Benjamin Holden, William E. TI Exhaled nasal nitric oxide output is reduced in humans at night during the sleep period SO RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY LA English DT Article DE sleep; somnolence; nitric oxide; nose ID NATURAL SLEEP; L-NAME; GAS; AIR; VENTILATION; ABSORPTION; ROLES AB The physiologic function of nasal nitric oxide (NO) release is unknown. In prior experiments, topical N-G-nitro-L-arginine methyl ester (L-NAME) on nasal mucosa reduced exhaled nasal NO output and caused daytime sleepiness. We hypothesized that nasal NO output is reduced at night during the sleep period. We measured exhaled nasal NO concentration and minute ventilation and calculated nasal NO output in humans over 24 h. Daytime awake NO output was greater than NO output at night during sleep or transient wakefulness. Exhaled NO concentration decreased during sleep along with minute ventilation. A daytime voluntary reduction in minute ventilation also decreased nasal NO output but exhaled NO concentration increased. Nasal NO output was not changed by body position. We conclude that exhaled nasal NO output is decreased at night due to decreased mass flow of NO into nasal air in addition to decreased minute ventilation. Our findings suggest a role of nasal NO in sleep or in the physiologic processes accompanying sleep. (c) 2006 Elsevier B.V. All rights reserved. C1 Portland VA Med Ctr, Med Serv, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Portland, OR USA. RP O'Hearn, DJ (reprint author), Portland VA Med Ctr, Med Serv, P3-PULM,3710 SW,US Vet Hosp Rd, Portland, OR 97201 USA. EM ohearnd@ohsu.edu NR 42 TC 3 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-9048 J9 RESP PHYSIOL NEUROBI JI Respir. Physiol. Neuro. PD APR 16 PY 2007 VL 156 IS 1 BP 94 EP 101 DI 10.1016/j.resp.2006.08.002 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 147KI UT WOS:000245001500012 PM 16978930 ER PT J AU Abraham, NS El-Serag, HB Hartman, C Richardson, P Deswal, A AF Abraham, N. S. El-Serag, H. B. Hartman, C. Richardson, P. Deswal, A. TI Cyclooxygenase-2 selectivity of non-steroidal anti-inflammatory drugs and the risk of myocardial infarction and cerebrovascular accident SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID CARDIOVASCULAR THROMBOTIC EVENTS; UPPER GASTROINTESTINAL EVENTS; VETERANS-AFFAIRS; CYCLO-OXYGENASE-2 INHIBITORS; COX-2 INHIBITORS; CELECOXIB; ROFECOXIB; TOXICITY; OUTCOMES; PRESCRIPTION AB Aim To assess degree of cyclooxygenase-2 (COX-2) selectivity of a non-steroidal anti-inflammatory drug (NSAID) and risk of myocardial infarction (MI) or cerebrovascular accident (CVA). Methods Prescription fill data were linked to medical records of a merged VA-Medicare dataset. NSAIDs were categorized by Cox-2 selectivity. Incidence of CVA and MI within 180 days of index prescription was assessed using Cox-proportional hazards models adjusted for gender, race, cardiovascular and pharmacological risk factors and propensity for prescription of highly COX-2 selective NSAIDs. Results Of 384 322 patients (97.5% men and 85.4% white), 79.4% were prescribed a poorly selective, 16.4% a moderately selective and 4.2% a highly selective NSAID. There were 985 incident cases of MI and 586 cases of CVA in > 145 870 person-years. Highly selective agents had the highest rate of MI (12.3 per 1000 person-years; [95% CI: 12.2-12.3]) and CVA (8.1 per 1000 person-years; [95% CI: 8.0-8.2]). Periods without NSAID exposure were associated with lowest risk. In adjusted models, highly selective COX-2 selective NSAIDs were associated with a 61% increase in CVA and a 47% increase in MI, when compared with poorly selective NSAIDs. Conclusions The risk of MI and CVA increases with any NSAID. Highly COX-2 selective NSAIDs confer the greatest risk. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Abraham, NS (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM nabraham@bcm.tmc.edu NR 57 TC 54 Z9 56 U1 1 U2 3 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 APR 15 PY 2007 VL 25 IS 8 BP 913 EP 924 DI 10.1111/j.j.1365-2036.2007.03292.x PG 12 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 151SQ UT WOS:000245311500007 PM 17402995 ER PT J AU Takano, M Inami, S Jang, IK Yamamoto, M Murakami, D Seimiya, K Ohba, T Mizuno, K AF Takano, Masamichi Inami, Shigenobu Jang, Ik-Kyung Yamamoto, Masanori Murakami, Daisuke Seimiya, Koji Ohba, Takayoshi Mizuno, Kyoichi TI Evaluation by optical coherence tomography of neointimal coverage of sirolimus-eluting stent three months after implantation SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY; THROMBOSIS; LESIONS; HUMANS AB Confirming complete neointimal coverage after implantation of a drug-eluting stent is clinically important because incomplete stent coverage is responsible for late thrombosis and sudden cardiac death. Optical coherence tomography is a high-resolution (approximate to 10 mu m) imaging technique capable of detecting a thin layer of neointimal hyperplasia (NIH) inside a sirolimus-eluting stent (SES) and stent malapposition. This investigation evaluated stent exposure and malapposition 3 months after SES implantation using optical coherence tomography in a different clinical presentations, such as acute coronary syndrome (ACS) and non-ACS. Motorized optical coherence tomographic pullback (1 mm/s) was performed at 3-month follow-up to examine consecutive implanted 31 SESs in 21 lesions in 21 patients (9 with ACS and 12 with non-ACS). NIH thickness inside each strut and percent NIH area in each cross section were measured. In total, 4,516 struts in 567-mm single-stented segments were analyzed. Overall, NIH thickness and percent NIH area were 29 +/- 41 mu m and 10 +/- 4%, respectively. Rates of exposed struts and exposed struts with malapposition were 15% and 6%, respectively. These were more frequent in patients with ACS than in those with non-ACS (18% vs 13%, p < 0.0001; 8% vs 5%, p < 0.005, respectively). In conclusion, neointimal coverage over a SES at 3-month follow-up is incomplete in ACS and non-ACS. Our study suggests that dual antiplatelet therapy might be continued > 3 months after SES implantation. (c) 2007 Elsevier Inc. All rights reserved. C1 Chiba Hokusoh Hosp, Nippon Med Sch, Dept Internal Med, Chiba, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. RP Takano, M (reprint author), Chiba Hokusoh Hosp, Nippon Med Sch, Dept Internal Med, Chiba, Japan. EM takanom@nms.ac.jp NR 10 TC 136 Z9 144 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 2007 VL 99 IS 8 BP 1033 EP 1038 DI 10.1016/j.amjcard.2006.11.068 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 159ZH UT WOS:000245906000002 PM 17437723 ER PT J AU Singla, I Zahid, M Good, CB Macioce, A Sonel, AF AF Singla, Ish Zahid, Maliha Good, Chester B. Macioce, Alanna Sonel, Ali F. TI Impact of blood transfusions in patients presenting with anemia and suspected acute coronary syndrome SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MYOCARDIAL-INFARCTION; CLINICAL-OUTCOMES; HEMOGLOBIN LEVELS; CELL TRANSFUSION; TASK-FORCE; STRATEGIES; MORTALITY; THERAPY AB Anemia has been shown to predict adverse events in patients presenting with acute coronary syndromes and non-ST-elevation myocardial infarctions (MIs). Less is known about the value of blood transfusions in this setting. We sought to evaluate the impact of red blood cell transfusions on outcomes. Transfusion in anemic patients admitted with suspected acute coronary syndrome/non-ST-elevation MIs led to a significant increase in 30-day recurrent MI or death (odds ratio 3.05, 95% confidence interval 1.80 to 5.17, p < 0.001). This relation persisted after adjusting for significant univariate predictors: hypotension on presentation, pulmonary edema, and increased troponin-I levels (odds ratio 2.57, 95% confidence interval 1.41 to 4.69, p < 0.001). In conclusion, the risk versus benefit of transfusion in patients presenting with an acute coronary syndrome needs careful assessment. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Ctr Healthy Equ & Res Promot, Pittsburgh, PA USA. RP Zahid, M (reprint author), Univ Pittsburgh, Pittsburgh, PA 15260 USA. EM maz7@pitt.edu NR 15 TC 31 Z9 33 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 2007 VL 99 IS 8 BP 1119 EP 1121 DI 10.1016/j.amjcard.2006.11.056 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 159ZH UT WOS:000245906000018 PM 17437739 ER PT J AU Shapiro, MD Butler, J Rieber, J Sheth, TN Cury, RC Ferencik, M Nichols, JH Goehler, A Abbara, S Pena, AJ Brady, TJ Hoffmann, U AF Shapiro, Michael D. Butler, Javed Rieber, Johannes Sheth, Tej N. Cury, Ricardo C. Ferencik, Maros Nichols, John H. Goehler, Alexander Abbara, Sulmy Pena, Antonio J. Brady, Thomas J. Hoffmann, Udo TI Analytic approaches to establish the diagnostic accuracy of coronary computed tomography angiography as a tool for clinical decision making SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ARTERY-DISEASE AB Although 64-slice multidetector coronary computed tomography angiography (CTA) has been reported to have excellent test characteristics for the detection of significant coronary artery disease, current analytic approaches may, not appropriately reflect the process of clinical decision making. Thirty-seven patients (29 men; mean age 63 +/- 11 years) who underwent coronary CTA for clinical indications followed by invasive coronary angiography within 4 weeks were studied. Computed tomography angiograms were analyzed independently for the presence of significant coronary artery stenosis ( >= 50% luminal narrowing) by 2 observers blinded to invasive coronary angiographic results. The diagnostic test performance of coronary CTA was determined with and without inclusion of unassessable segments. Because stenosis could not be excluded in unassessable segments, these segments were counted as positive for stenosis. Sensitivity, specificity, and positive (PPV) and negative predictive values of CTA for detecting significant stenoses on assessable segments were 85% (51 of 60, 95% confidence interval [CI] 76% to 94%), 99% (414 of 416, 95% CI 99 to 100), 96% (95% CI 51 of 53), and 98% (95% CI 414 of 423), respectively. Overall, 13% of coronary segments (70 of 546) were not assessable using CTA (heavy calcium in 48 segments). By including these segments, PPV decreased from 96% to 60% (74 of 123), whereas sensitivity improved from 85% to 89% (95% CI 74 of 83). In conclusion, the clinical utility of coronary CTA may be limited by a low PPV in patients with a high prevalence of coronary artery disease. (c) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Cardiac MR PET CT Program, Boston, MA 02115 USA. RP Hoffmann, U (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Cardiac MR PET CT Program, Boston, MA 02115 USA. EM uhoffman@partners.org FU NHLBI NIH HHS [1T32 HL076136-02] NR 9 TC 13 Z9 15 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 2007 VL 99 IS 8 BP 1122 EP 1127 DI 10.1016/j.amjcard.2006.11.053 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 159ZH UT WOS:000245906000019 PM 17437740 ER PT J AU Song, JS Maghsoudi, K Li, W Fox, E Quackenbush, J Liu, XS AF Song, Jun S. Maghsoudi, Kaveh Li, Wei Fox, Edward Quackenbush, John Liu, X. Shirley TI Microarray blob-defect removal improves array analysis SO BIOINFORMATICS LA English DT Article ID LOCALIZATION; IMAGES AB Motivation: New generation Affymetrix oligonucleotide microarrays often have blob-like image defects that will require investigators to either repeat their hybridization assays or analyze their data with the defects left in place. We investigated the effect of analyzing a spike-in experiment on Affymetrix ENCODE tiling arrays in the presence of simulated blobs covering between 1 and 9% of the array area. Using two different ChIP-chip tiling array analysis programs (Affymetrix tiling array software, TAS, and model-based analysis of tiling arrays, MAT), we found that even the smallest blob defects significantly decreased the sensitivity and increased the false discovery rate (FDR) of the spike-in target prediction. Results: We introduced a new software tool, the microarray blob remover (MBR), which allows rapid visualization, detection and removal of various blob defects from the .CEL files of different types of Affymetrix microarrays. It is shown that using MBR significantly improves the sensitivity and FDR of a tiling array analysis compared to leaving the affected probes in the analysis. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Dana Farber Canc Inst,Dept Biostat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Dept Canc Biol, Microarray Core Facil, Boston, MA 02115 USA. RP Liu, XS (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Dana Farber Canc Inst,Dept Biostat, Cambridge, MA 02138 USA. EM xsliu@jimmy.harvard.edu RI Li, Wei/A-8544-2009 NR 8 TC 15 Z9 15 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD APR 15 PY 2007 VL 23 IS 8 BP 966 EP 971 DI 10.1093/bioinformatics/btm043 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 165GS UT WOS:000246293000007 PM 17332024 ER PT J AU Iosifescu, DV Jensen, JE Nierenberg, AA Bolo, NR Fava, M Renshaw, PF AF Iosifescu, Dan V. Jensen, J. Eric Nierenberg, Andrew A. Bolo, Nicolas R. Fava, Maurizio Renshaw, Perry F. TI Bloenergetic metabolism during antidepressant treatment in MDD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Harvard Med Sch, Dept Psychiat, Boston, MA USA. McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 10 BP 4S EP 4S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100012 ER PT J AU Olvera, RL Pliszka, SR Dierschke, NA Stanley, JA Nicoletti, MA Hatch, JR Li, J Soares, JC AF Olvera, Rene L. Pliszka, Steven R. Dierschke, Nicole A. Stanley, Jeffrey A. Nicoletti, Mark A. Hatch, John R. Li, John Soares, Jair C. TI A proton magnetic spectroscopy study of juvenile offenders with mood and impulse control disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Wayne State Univ, Sch Med, Detroit, MI USA. Audie Murphy Div, S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Res Imaging Ctr, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 12 BP 4S EP 5S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100014 ER PT J AU Quinones, MR Ahmadi, S Nery, FG Estrada, C Olvera, R Hatch, JR Vipraio, G Pliszka, S Soares, JC AF Quinones, Marlon R. Ahmadi, Sara Nery, Fabiano G. Estrada, Carlos Olvera, Rene Hatch, John R. Vipraio, Gil Pliszka, Steve Soares, Jair C. TI Plasma TNF-RII as a new specific biomarker for the pathogenesis of bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 17-20, 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie L Murphy, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders,MOOD CNS Program, San Antonio, TX 78284 USA. Univ Sao Paulo, Sch Med, Sao Paulo, Brazil. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 16 BP 6S EP 6S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100018 ER PT J AU Mansour, H Chowdari, KV Wood, J Pless, L McClendon, TB King, AJ 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 McQueen, MB Nierenberg, AA Patel, J Sachs, GS Sklar, P AF Mansour, Hader Chowdari, Kodavali V. Wood, Joel Pless, Lora McClendon, T. Brooke King, Abbegail J. Allen, Michael Bowden, Charles L. Calabrese, Joseph El-Mallakh, Rif S. Fagiolini, Andrea Faraone, Stephen V. Fossey, Mark D. Friedman, Edward S. Gyulai, Laszlo Hauser, Peter Ketter, Terence A. Loftis, Jennifer M. Marangell, Lauren B. Miklowitz, David J. McQueen, Matthew B. Nierenberg, Andrew A. Patel, Jayendra Sachs, Gary S. Sklar, Pamela TI Circadian gene polymorphisms and liability to bipolar I disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA 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 & Behav Sci, Syracuse, NY USA. Univ Oklahoma, Tulsa Med Coll, 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, Dept Vet Affairs, Houston, TX 77030 USA. Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. Univ Colorado, Dept Psychiat, Boulder, CO 80309 USA. Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. Massachusetts Gen Hosp, Harvard Med Sch, Dept Psychiat, Bipolar Clin & Res Program, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Psychiat & Neurodev Genet Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 17 BP 7S EP 7S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100019 ER PT J AU Morrow, EM Yoo, SY Hill, RS Bodell, A Apse, KA Balkhy, S Gascon, G Herguner, S Mukaddes, NM Walsh, CA AF Morrow, Eric M. Yoo, Seung-Yun Hill, Robert Sean Bodell, Adria Apse, Kira A. Balkhy, Soher Gascon, Generoso Herguner, Sabri Mukaddes, Nahit M. Walsh, Christopher A. CA Autism Int Homozygos Mapp Coll TI Autosomal recessive loci in familial autism using a systematic homozygosity mapping strategy SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Childrens Hosp, Div Genet, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Howard Hughes Med Inst, Dept Neurol, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. King Faisal Specialist Hosp & Res Ctr, Jeddah, Saudi Arabia. Istanbul Med Fac, Istanbul, Turkey. RI Morrow, Eric/J-2767-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 25 BP 10S EP 10S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100027 ER PT J AU Quinones, MP Torres, V Nery, FG Ahmadi, S Estrada, C Olvera, R Hatch, JP Vipraio, G Pliszka, S Soares, JC AF Quinones, Marlon P. Torres, Victor Nery, Fabiano G. Ahmadi, Sara Estrada, Carlos Olvera, Rene Hatch, John P. Vipraio, Gil Pliszka, Steve Soares, Jair C. TI Differential involvement of inflammatory markers in adult and pediatric bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 17-20, 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie L Murphy, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders,MOOD CNS Program, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Sao Paulo, Brazil. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 27 BP 11S EP 11S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100029 ER PT J AU New, AS Hazlett, EA Newmark, RE Meyerson, D Goldstein, K Goodman, M Koenigsberg, H Trisdorfer, R Siever, LJ Buchsbaum, MS AF New, Antonia S. Hazlett, Erin A. Newmark, Randall E. Meyerson, David Goldstein, Kim Goodman, Marianne Koenigsberg, Harold Trisdorfer, Roanna Siever, Larry J. Buchsbaum, Monte S. TI Laboratory induced aggression: A PET study of borderline personality disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Mt Sinai Sch Med, New York, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. Mt Sinai Sch Med, Neurosci PET Lab, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 35 BP 14S EP 14S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100037 ER PT J AU Gold, AL Negreira, AM Britton, JC Barrett, LF Williams, D Wright, CI AF Gold, Andrea L. Negreira, Alyson M. Britton, Jennifer C. Barrett, Lisa Feldman Williams, Danielle Wright, Christopher I. TI Brain responses to novel faces in the young and elderly SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Lab Aging & Emot, Psychiatr Neuroimaging Res Program, Charlestown, MA USA. Boston Coll, Dept Psychol, Chestnut Hill, MA 02167 USA. Brigham & Womens Hosp, Dept Neurol, Div Cognit & Behav Neurol, Boston, MA 02115 USA. RI Britton, Jennifer/J-4501-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 89 BP 30S EP 30S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100091 ER PT J AU Linnman, CN Shin, LM Milad, MR Rauch, SL Pitman, RK AF Linnman, Clas N. Shin, Lisa M. Milad, Mohammed R. Rauch, Scott L. Pitman, Roger K. TI Hippocampal activation during a recognition memory task in identical twins discordant for combat exposure: Relationship to PTSD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Uppsala Univ, Dept Psychol, Uppsala, Sweden. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 165 BP 53S EP 53S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100167 ER PT J AU Del Debbio, A Dias, RD Calkins, AW Armistead, MS Tilley, CA Lund, HG Ostacher, MJ Nierenberg, AA Sachs, GS AF Del Debbio, Alessandro da Silva Dias, Rodrigo Calkins, Armanda W. Armistead, Molly S. Tilley, Claire A. Lund, Hannah G. Ostacher, Michael J. Nierenberg, Andrew A. Sachs, Gary S. TI Prognostic implication of typing bipolar disorder by correspondence to classic phenotype: Bipolarity index SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Bipolar Clin & Res Program, Boston, MA USA. Univ Pisa, Dept Psychiat Neurobiol Pharmacol & Biotechnol, Pisa, Italy. Univ Sao Paulo, Inst Psychiat, Sao Paulo, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 181 BP 58S EP 58S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100183 ER PT J AU Frey, BN Walls-Bass, C Hatch, JP Nery, FG Nicoletti, MA Chen, HH Monkul, ES Matsuo, K Zunta, G Stanley, JA Escamilla, MA Soares, JC AF Frey, Benicio N. Walls-Bass, Consuelo Hatch, John P. Nery, Fabiano G. Nicoletti, Mark A. Chen, Hua H. Monkul, E. Serap Matsuo, Koji Zunta, Giovana Stanley, Jeffrey A. Escamilla, Michael A. Soares, Jair C. TI Effects of BDNF val66met polymorphism on brain neurochemistry in bipolar disorder patients: A 1H MRS study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 17-20, 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Fed Rio Grande do Sul, Porto Alegre, RS, Brazil. Hosp Clin Porto Alegre, Lab Psiquiatria Mol, Porto Alegre, RS, Brazil. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Sao Paulo, Brazil. Wayne State Univ, Sch Med, Detroit, MI USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 186 BP 59S EP 59S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100188 ER PT J AU Morrow, EM Joshi, G Wozniak, J Fried, R Monuteaux, MC Doyle, RL Mick, E Biederman, J AF Morrow, Eric M. Joshi, Gagan Wozniak, Janet Fried, Ronna Monuteaux, Michael C. Doyle, Robert L. Mick, Eric Biederman, Joseph TI Pervasive developmental disorder and patterns of psychiatric comorbidity in 758 clinically referred children SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Harvard Med Sch, Pediat Psychopharmacol Unit, Pervas Dev Disorders Program, Boston, MA 02114 USA. RI Morrow, Eric/J-2767-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 204 BP 64S EP 65S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100206 ER PT J AU Leuchter, AF Cook, IA Marangell, LB Gilmer, WS Burgoyne, KS Howland, RH Trivedi, MH Zisook, S Jain, R Iosifescu, D Fava, M Manberg, P AF Leuchter, Andrew F. Cook, Ian A. Marangell, Lauren B. Gilmer, William S. Burgoyne, Karl S. Howland, Robert H. Trivedi, Madhukar H. Zisook, Sidney Jain, Rakesh Iosifescu, Daniel Fava, Maurizio Manberg, Paul TI Biomarkers for rapid identification of treatment effectiveness in major depression (BRITE-MD): Predictors of clinical treatment response SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Calif Los Angeles, Inst Neuropsychiat, Lab Brain Behav & Pharmacol, Los Angeles, CA 90024 USA. Baylor Coll Med, Houston, TX 77030 USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Calif San Diego, San Diego, CA 92103 USA. RD Clin Res Res, Houston, TX USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Aspect Med Syst, Norwood, MA USA. RI Howland, Robert/K-6937-2015 OI Howland, Robert/0000-0002-6533-6010 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 229 BP 72S EP 72S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100230 ER PT J AU Fava, M Pollack, M Rubens, R Amato, D Krystal, A Hayduk, R McCall, WV AF Fava, Maurizio Pollack, Mark Rubens, Robert Amato, David Krystal, Andrew Hayduk, Roza McCall, W. Vaughn TI Evaluation of the Hamilton depression scale following eszopiclone treatment for insomnia in patients with insomnia co-morbid with major depressive disorder or generalized anxiety disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 17-20, 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Depress & Clin Res Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Anxiety Disorders Program, Boston, MA 02114 USA. Sepracor Inc, Marlborough, MA USA. Sepracor Inc, Marlborough, MA USA. Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. Quintiles, Med & Sci Serv, San Diego, CA USA. Wake Forest Univ, Dept Psychiat, Winston Salem, NC 27109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 267 BP 84S EP 84S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100268 ER PT J AU Krystal, A Fava, M Pollack, M Rubens, R Schaefer, K Amato, D Roth, T AF Krystal, Andrew Fava, Maurizio Pollack, Mark Rubens, Robert Schaefer, Kendyl Amato, David Roth, Thomas TI Sleep outcomes following eszopiclone discontinuation in patients with primary insomnia co-existing with major depressive disorder or generalized anxiety disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. Massachusetts Gen Hosp, Depress & Clin Res Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Anxiety Disorders Program, Boston, MA 02114 USA. Sepracor Inc, Marlborough, MA USA. Henry Ford Hosp Syst, Sleep Disorders Ctr, Detroit, MI USA. RI Krystal, Andrew/J-7109-2013 OI Krystal, Andrew/0000-0002-6702-781X NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 268 BP 84S EP 84S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100269 ER PT J AU Roth, T Wilson, P Schaefer, K Pfleeger, K Rubens, R Fava, M Pollack, M AF Roth, Thomas Wilson, Phebe Schaefer, Kendyl Pfleeger, Kimberly Rubens, Robert Fava, Maurizio Pollack, Mark TI Insomnia severity in patients with primary insomnia and insomnia co-morbid with major depressive disorder or generalized anxiety disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 17-20, 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Henry Ford Hosp Syst, Sleep Ctr, Detroit, MI USA. Sepracor Inc, Marlborough, MA USA. Sepracor Inc, Marlborough, MA USA. Massachusetts Gen Hosp, Depress & Clin Res Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Anxiety Disorders Program, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 269 BP 84S EP 85S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100270 ER PT J AU Rubens, R McCall, WV Wilson, P Schaefer, K Fava, M Pollack, M Roth, T AF Rubens, Robert McCall, W. Vaughn Wilson, Phebe Schaefer, Kendyl Fava, Maurizio Pollack, Mark Roth, Thomas TI Changes in sleep outcomes with hypnotic placebo in patients with primary insomnia (PI) and insomnia co-morbid with major derpessive disorder (MDD) or generalized anxiety disorder (GAD) SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 17-20, 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Sepracor Inc, Marlborough, MA USA. Wake Forest Univ, Dept Psychiat, Winston Salem, NC 27109 USA. Sepracor Inc, Marlborough, MA USA. Massachusetts Gen Hosp, Depress & Clin Res Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Anxiety Disorders Program, Boston, MA 02114 USA. Henry Ford Hosp Syst, Sleep Disorders Ctr, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 270 BP 85S EP 85S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100271 ER PT J AU Mezzomo, KM Rene, OL Caetan, SC Matsuo, K Hatch, JR Dierschke, N Nicoletti, M Fonseca, M Belardinelli, C Zunta, G Pliszka, SR Soares, JC AF Mezzomo, Kelin M. Rene, Olvera L. Caetan, Sheila C. Matsuo, Koji Hatch, John R. Dierschke, Nicole Nicoletti, Mark Fonseca, Manoela Belardinelli, Cecilia Zunta, Giovana Pliszka, Steven R. Soares, Jair C. TI White matter abnormalities in pediatric bipolar disorder - A voxel-based morphometry (VBM) study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 17-20, 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Audie L Murphy, S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Univ Texas, Hlth Sci Ctr, Dept Orthodont, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 299 BP 94S EP 94S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100300 ER PT J AU Dracheva, S Marcus, SM Siever, LJ Haroutunian, V AF Dracheva, Stella Marcus, Sue M. Siever, Larry J. Haroutunian, Vahrarn TI Increased serotonin 2C receptor mRNA editing in suicide: A possible psychiatric diagnosis-independent risk factor SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Bronx Vet Adm Med Ctr, Bronx, NY USA. Mt Sinai Sch Med, New York, NY USA. Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 302 BP 95S EP 95S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100303 ER PT J AU Quinones, MP Nery, FG Ahmadi, S Torres, V Estrada, C Olvera, R Hatch, JP Vipraio, G Pliszka, S Soares, JC AF Quinones, Marlon P. Nery, Fabiano G. Ahmadi, Sara Torres, Victor Estrada, Carlos Olvera, Rene Hatch, John P. Vipraio, Gil Pliszka, Steve Soares, Jair C. TI Plasma level of CC chemokine ligand (CCL)-22 and CCL5 as biomarkers in adult or pediatric mood disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders,MOOD CNS Program, San Antonio, TX 78284 USA. Univ Sao Paulo, Sch Med, Sao Paulo, Brazil. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 306 BP 96S EP 97S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100307 ER PT J AU Koenigsberg, HW Provhovnik, I Lee, H Pizzarello, S New, AS Siever, LJ AF Koenigsberg, Harold W. Provhovnik, Isak Lee, Hedok Pizzarello, Scott New, Antonia S. Siever, Larry J. TI Neural correlates of the processing of negative and positive social scenes in borderline personality disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. James J Peters VA Med Ctr, Bronx, NY USA. James J Peters VA Med Ctr, Mirecc, Bronx, NY USA. NR 0 TC 1 Z9 1 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 APR 15 PY 2007 VL 61 IS 8 SU S MA 334 BP 104S EP 104S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100329 ER PT J AU Green, MF Horan, W Nuechterlein, KH Stone, W Seidman, L AF Green, Michael F. Horan, William Nuechterlein, Keith H. Stone, William Seidman, Larry TI Neurocognitive endophenotypes in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 354 BP 110S EP 110S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100349 ER PT J AU Yao, JK Matson, WR Reddy, RD Bogdanov, M Keshavan, MS AF Yao, Jeffrey K. Matson, Wayne R. Reddy, Ravinder D. Bogdanov, Mikhail Keshavan, Matcheri S. TI Evaluation of plasma metabolome in first-episode schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Vet Affairs Pittsburgh Hlth Syst, Med Res Serv, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA USA. Bedford Vet Affairs Med Ctr, Med Res Serv, Bedford, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 386 BP 119S EP 119S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100381 ER PT J AU Yao, JK Dougherty, GG van Kammen, DP Peters, JL Gurklis, JA AF Yao, Jeffrey K. Dougherty, George G. van Kammen, Daniel P. Peters, Jeffrey L. Gurklis, John A. TI Multivariate comparisons of CSF amino acids in healthy controls and schizophrenic patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Vet Affairs Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA USA. ACADIA Pharmaceut Inc, Clin Dev, San Diego, CA USA. Vet Affairs Pittsburgh Healthcare Syst, Behav Hlth Product Line, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 387 BP 120S EP 120S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100382 ER PT J AU Milad, MR Orr, SR Rauch, SL Pitman, RK AF Milad, Mohammed R. Orr, Scott R. Rauch, Scott L. Pitman, Roger K. TI Recall of fear extinction in twins discordant for combat exposure: Relationship to PTSD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Harvard Med Sch, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 423 BP 130S EP 130S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100418 ER PT J AU Taylor, F Mellman, TA Gross, C Peskind, ER Raskind, MA AF Taylor, Fletcher Mellman, Thomas A. Gross, Christopher Peskind, Elaine R. Raskind, Murray A. TI Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma PTSD: A placebo controlled study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Washington, Seattle, WA 98195 USA. Howard Univ, Dept Psychiat, Washington, DC 20059 USA. VA Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 428 BP 132S EP 132S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100423 ER PT J AU Tang, Y Anderson, GM Zabetian, CR Cubells, JF AF Tang, Yilang Anderson, George M. Zabetian, Cyrus R. Cubells, Joseph F. TI Genotypic and haplotypic associations of the DBH gene with plasma dopamine beta-hydroxylase activity in African Americans SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Emory Univ, Atlanta, GA 30322 USA. Yale Univ, Sch Med, VA Connecticut Healthcare Syst, New Haven, CT USA. Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. Univ Washington, Sch Med, Geriatr Res Educ & Clin Ctr, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 439 BP 135S EP 135S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100434 ER PT J AU Peskind, ER Lil, G Petrie, EC Leverenz, J Raskind, MA Galasko, D AF Peskind, Elaine R. Lil, Gail Petrie, Eric C. Leverenz, James Raskind, Murray A. Galasko, Douglas TI Gender, age, and APOE genotype effects on CSF abeta-42 in cognitively normal adults SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. Univ Calif San Diego, Dept Neurol, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 464 BP 143S EP 143S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100459 ER PT J AU Denninger, JW Iosifescu, DV Charles, DL Homberger, CH Wu, SL Greenwald, SD Alpert, JE Fava, M AF Denninger, John W. Iosifescu, Dan V. Charles, Dana L. Homberger, Caitlin H. Wu, Shirley L. Greenwald, Scott D. Alpert, Jonathan E. Fava, Maurizio TI Frontal EEG predicts clinical response to escitalopram treatment in major depressive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Deppress Clin, Depress Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Aspect Med Syst Inc, Dept Neurosci, Norwood, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 470 BP 144S EP 145S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100465 ER PT J AU Sauder, CL Kinreich, S Warfield, GA McSweeney, LB Zanarini, MC Rauch, SL Kim, DS Roenen, I Putnam, KM AF Sauder, Colin L. Kinreich, Sivan Warfield, Garrett A. McSweeney, Lauren B. Zanarini, Mary C. Rauch, Scott L. Kim, Dae-Shik Roenen, Itamar Putnam, Katherine M. TI Neuro-anatomical correlates of disordered emotion regulation in borderline personality disorder: An event-related fMRI study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. Harvard Univ, McLean Hosp, Belmont, MA 02178 USA. Boston Univ, Sch Med, Ctr Biomed Imaging, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 504 BP 155S EP 155S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100499 ER PT J AU Kubicki, M Styner, M Markant, D Bouix, S Kikinis, R McCarley, RW Shenton, ME AF Kubicki, Marek Styner, Martin Markant, Douglas Bouix, Sylvain Kikinis, Ron McCarley, Robert W. Shenton, Martha E. TI Corpus callosum and schizophrenia-diffusion tensor imaging study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Brigham & Womens Hosp, Harvard Med Sch, Psychiat Neuroimaging Lab, Boston, MA 02115 USA. Univ N Carolina, Neurodev Disorders Res Ctr, Chapel Hill, NC USA. Psychiat Neuroimaging Lab, Boston, MA USA. MRI Div, Surg Planning Lab, Boston, MA USA. Harvard Med Sch, Clin Neurosci Div, Neurosci Lab, Brockton Div,VA Boston Healthcare Syst, Brockton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 519 BP 159S EP 159S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100514 ER PT J AU Kaddurah-Daouk, R McEvoy, J Baillie, RA Yao, JK Doraiswamy, PM Krishnan, KRR AF Kaddurah-Daouk, Rima McEvoy, Joseph Baillie, Rebecca A. Yao, Jeffrey K. Doraiswamy, P. Murali Krishnan, K. Ranga R. TI Metabolomic mapping of schizophrenia and atypical antipsychotic effects SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Duke Univ, Med Ctr, Durham, NC USA. Lipom Technol, Sacramento, CA USA. Univ Pittsburgh, Med Ctr, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 535 BP 164S EP 164S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100530 ER PT J AU Nery, FG Monkul, ES Hatch, JP Fonseca, M Zunta, GB Frey, BN Bowden, CL Soares, JC AF Nery, Fabiano G. Monkul, E. Serap Hatch, John P. Fonseca, Manoela Zunta, Giovana B. Frey, Benicio N. Bowden, Charles L. Soares, Jair C. TI Cox-2 inhibitor (Celecoxib) as an adjunct in the treatment of depressive or mixed episodes of bipolar disorder: A double-blind, randomized, placebo-controlled study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX USA. Audie L Murphy Div, Psychiat Serv, South Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Univ Texas, Hlth Sci Ctr, Dept Orthodont, San Antonio, TX USA. Univ Fed Rio Grande do Sul, ICBS, Dept Biochem, Porto Alegre, RS, Brazil. Hosp Clin, Bipolar Disorder Program, Porto Alegre, RS, Brazil. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 555 BP 171S EP 171S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100550 ER PT J AU Spencer, TJ Muniz, R McCague, K AF Spencer, Thomas J. Muniz, Rafael McCague, Kevin TI Long-term effects of extended-release dexmethylphenidate on hemodynamic variables and body weight in adults with ADHD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 17-20, 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Nova Pharmaceut Corp, E Hanover, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 556 BP 171S EP 171S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100551 ER PT J AU Spencer, TJ Anderson, CS Silverberg, A Youcha, SH AF Spencer, Thomas J. Anderson, Colleen S. Silverberg, Arthur Youcha, Sharon H. TI Triple-bead mixed amphetamine salts (SPD465) improves hyperactivity/impulsivity and inattentiveness in adults with ADHD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 17-20, 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Boston, MA 02114 USA. Shire Dev Inc, Clin Res & Dev, Wayne, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 557 BP 171S EP 172S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100552 ER PT J AU Binder, EB Owens, MJ Liu, W Fava, M Rush, AJ Trivedi, MH Cubells, JF Nemeroff, CB AF Binder, Elisabeth B. Owens, Michael J. Liu, Wei Fava, Maurizio Rush, A. John Trivedi, Madhukar H. Cubells, Joseph F. Nemeroff, Charles B. TI Genetic variants in genes regulating the corticotropin releasing hormone (CRH) system and response to citalopram in the STAR*D sample SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Emory Univ, Sch Med, Atlanta, GA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. RI Owens, Michael/G-5191-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 559 BP 172S EP 172S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100554 ER PT J AU Spencer, TJ Anderson, CS Silverberg, A Youcha, S AF Spencer, Thomas J. Anderson, Colleen S. Silverberg, Arthur Youcha, Sharon TI Improvement in hyperactivity/impulsivity and inattentiveness associated with adult ADHD after triple-bead mixed amphetamine salts (SPD465) treatment SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Boston, MA 02114 USA. Shire Dev Inc, Clin Res & Dev, Wayne, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 558 BP 172S EP 172S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100553 ER PT J AU Katsel, P Davis, KL Li, C Greenstein, E Haroutunian, V AF Katsel, Pavel Davis, Kenneth L. Li, Celeste Greenstein, Elizabeth Haroutunian, Vahram TI Ectopic cell cycle activity in the cingulate cortex of subjects with schizophrenia and myelin deficiency animal models SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Mt Sinai Med Ctr, New York, NY 10029 USA. James J Peters Vet Affairs Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 563 BP 173S EP 174S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100558 ER PT J AU Bearden, CE Soares, JC Klunder, AD Nicoletti, M Dierschke, N Hayashi, KM Brambilla, P Sassi, RB Ryan, N Birmaher, B Axelson, D Thompson, PM AF Bearden, Carrie E. Soares, Jair C. Klunder, Andrea D. Nicoletti, Mark Dierschke, Nicole Hayashi, Kiralee M. Brambilla, Paolo Sassi, Roberto B. Ryan, Neal Birmaher, Boris Axelson, David Thompson, Paul M. TI Three-dimensional mapping of hippocampal anatomy in adolescents with early-onset bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 17-20, 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX USA. Univ Calif Los Angeles, Dept Neurol, Lab NeuroImaging, Los Angeles, CA USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX USA. Sci Inst IRCCS, Dept Psychiat, E Medea, Italy. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. RI brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 593 BP 184S EP 184S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100588 ER PT J AU Camprodon, JA Martinez-Raga, J Alonso, M Shih, MC Pascual-Leone, A AF Camprodon, Joan A. Martinez-Raga, Jose Alonso, Miguel Shih, Mei-Chiung Pascual-Leone, Alvaro TI High frequency rTMS to the right prefrontal cortex reduces cocaine craving SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Harvard Med Sch, BIDMC, Boston, MA USA. Univ Cardenal Herrera CEU, Unit Conduct Addict Area 11, Inst Drug & Conduct Addict, Valencia, Spain. Childrens Hosp, Harvard Med Sch, Harvard Sch Publ Hlth, BIDMC,Clin Res Program, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 604 BP 188S EP 188S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100599 ER PT J AU Fava, M AF Fava, Maurizio TI Moderators of response to next-step strategies in resistant depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 639 BP 199S EP 199S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100634 ER PT J AU Koenigsberg, HW Fan, J Ochsner, K Pizzarello, S New, AS Sievert, LJ AF Koenigsberg, Harold W. Fan, Jin Ochsner, Kevin Pizzarello, Scott New, Antonia S. Sievert, Larry J. TI Neural correlates of efforts to downregulate emotion in borderline personality disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. James J Peter VA Med Ctr, Bronx, NY USA. Columbia Univ, Dept Psychol, New York, NY 10027 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 642 BP 200S EP 200S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100637 ER PT J AU Houston, J Perlis, R Sutton, V Adams, DH Farmen, M Breier, A AF Houston, John Perlis, Roy Sutton, Virginia Adams, David H. Farmen, Mark Breier, Alan TI Genetic association study of treatment response with olanzapine/fluoxetine combination or lamotrigine in bipolar I depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 17-20, 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Eli Lilly & Co, Neurosci, Indianapolis, IN 46285 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 664 BP 206S EP 206S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100659 ER PT J AU McFarland, MJ Balaraman, Y Le-Niculescu, H Ogden, CA Patel, S Tan, JH Rich, ME Nicastro, I Paulus, M Edenberg, HJ Nurnberger, JI Geyer, MA Glatt, SJ Sklar, P Faraone, SV Kuczenski, R Tsuang, MT Niculescu, AB AF McFarland, Matthew J. Balaraman, Yokesh Le-Niculescu, Helen Ogden, Corey A. Patel, Sagar Tan, Jiahuai Rich, Michael E. Nicastro, Ian Paulus, Martin Edenberg, Howard J. Nurnberger, John I. Geyer, Mark A. Glatt, Stephen J. Sklar, Pamela Faraone, Steven V. Kuczenski, Ronald Tsuang, Ming T. Niculescu, Alexander B. TI Convergent functional genomics studies in mice lacking the circadian clock gene DBP: A genetic animal model of bipolar (manic-depressive) disorder and co-morbid alcoholism SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Indiana Univ Sch Med, Indianapolis, IN USA. Univ Calif San Diego, La Jolla, CA 92093 USA. SUNY Upstate Med Univ, Syracuse, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RI Niculescu, Alexander/A-3328-2012 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 707 BP 218S EP 219S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100702 ER PT J AU Nery, FG Stanley, JA Chen, HH Hatch, JP Nicoletti, MA Monkul, ES Lafer, B Soares, JC AF Nery, Fabiano G. Stanley, Jeffrey A. Chen, Hua-Hsuan Hatch, John P. Nicoletti, Mark A. Monkul, E. Serap Lafer, Beny Soares, Jair C. TI Low glutamate concentrations in the left dorsolateral prefrontal cortex of patients with bipolar disorder and comorbid alcoholism: A 1H spectroscopy study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Wayne State Univ, Sch Med, Dept Psychiat & Behav Sci, Detroit, MI USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Orthodont, San Antonio, TX USA. RI Lafer, Beny/C-1055-2012; Lafer, Beny/F-9390-2015 OI Lafer, Beny/0000-0002-6132-9999; Lafer, Beny/0000-0002-6132-9999 NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 725 BP 224S EP 224S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100720 ER PT J AU Nery, FG Matsuo, K Nicoletti, MA Dierschke, N Monkul, ES Fonseca, M Zunta, GB Hatch, JP Lafer, B Soares, JC AF Nery, Fabiano G. Matsuo, Koji Nicoletti, Mark A. Dierschke, Nicole Monkul, E. Serap Fonseca, Manoela Zunta, Giovana B. Hatch, John P. Lafer, Beny Soares, Jair C. TI Small gray and white matter volumes in bipolar disorder patients with comorbid alcoholism: An optimized voxel-based morphometry study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 17-20, 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Univ Texas, Hlth Sci Ctr, Dept Orthodont, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. RI Lafer, Beny/C-1055-2012; Lafer, Beny/F-9390-2015 OI Lafer, Beny/0000-0002-6132-9999; Lafer, Beny/0000-0002-6132-9999 NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 726 BP 225S EP 225S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100721 ER PT J AU Nery, FG Chen, HH Hatch, JP Nicoletti, MA Mallinger, AG Soares, JC AF Nery, Fabiano G. Chen, Hua-Hsuan Hatch, John P. Nicoletti, Mark A. Mallinger, Alan G. Soares, Jair C. TI Orbitofrontal cortex volumes correlate with mood state in bipolar disorder: A structural MRI study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 17-20, 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Orthodont, San Antonio, TX USA. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 728 BP 225S EP 226S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100723 ER PT J AU Nery, FG Hatch, JP Monkul, ES Peluso, MA Fonseca, M Zunta, GB Bowden, CL Soares, JC AF Nery, Fabiano G. Hatch, John P. Monkul, E. Serap Peluso, Marco A. Fonseca, Manoela Zunta, Giovana B. Bowden, Charles L. Soares, Jair C. TI Association between impulsivity and alcoholism in bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 17-20, 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Univ Texas, Hlth Sci Ctr, Dept Orthodont, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 727 BP 225S EP 225S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100722 ER PT J AU Nery, FG Glahn, DC Bearden, CE Monkul, ES Zunta, GB Fonseca, M Soares, JC AF Nery, Fabiano G. Glahn, David C. Bearden, Carrie E. Monkul, E. Serap Zunta, Giovana B. Fonseca, Manoela Soares, Jair C. TI Neurocognitive deficits in bipolar disorder with comorbid alcoholism SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 729 BP 226S EP 226S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100724 ER PT J AU Quinones, MP Nery, F Ahmadi, S Torres, V Estrada, C Olvera, R Hatch, JP Vipraio, G Pliszka, S Soares, J AF Quinones, Marlon P. Nery, Fabiano Ahmadi, Sara Torres, Victor Estrada, Carlos Olvera, Rene Hatch, John P. Vipraio, Gil Pliszka, Steve Soares, Jair TI Infectious agents and the pathogenesis of pediatric and adult mood disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 UTHSCSA, San Antonio, TX USA. UTHSCSA, Dept Psychiat, Div Mood & Anxiety Disorders, MOOD CNS Program, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Sao Paulo, Brazil. S Texas Vet Hlth Care Syst, Audie L Murphy, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Dept Psychiat, Div Mood & Anxiety Disorders, MOOD CNS Program, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 733 BP 227S EP 228S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100728 ER PT J AU Quinones, MP Estrada, C Ahmadi, S Nery, FG Torres, V Olvera, R Hatch, JP Vipraio, G Pliszka, S Escamilla, MA Walss-Bass, C Soares, JC AF Quinones, Marion P. Estrada, Carlos Ahmadi, Sara Nery, Fabiano G. Torres, Victor Olvera, Rene Hatch, John P. Vipraio, Gil Pliszka, Steve Escamilla, Michael A. Walss-Bass, Consuelo Soares, Jair C. TI Reduction in the availability of the neurotrophic factor insulin growth factor (IGF)-1, but not brain derived neurotrophic factor (BDNF), in individuals with mood disorders may result from synergistic effects of disease-specific processes and normal age-associated reduction in circulating levels SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 UTHSCSA, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie L Murphy, San Antonio, TX USA. UTHSCSA, Dept Psychiat, Div Mood & Anxiety Disorders, MOOD CNS Program, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Sao Paulo, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 734 BP 228S EP 228S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100729 ER PT J AU Leung, WW McClure, MM Siever, LJ Harvey, PD AF Leung, Winnie W. McClure, Margaret M. Siever, Larry J. Harvey, Philip D. TI COMT genotype and context processing in healthy and personality disorder individuals SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. Mt Sinai Sch Med, New York, NY USA. James J Peters Bronx VA Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 789 BP 245S EP 245S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100784 ER PT J AU Levitt, JJ Markant, DM McCarley, RW Kawashima, T Nakamura, M Bouix, S Kubicki, M Shenton, ME AF Levitt, James J. Markant, Doug M. McCarley, Robert W. Kawashima, Toshiro Nakamura, Motoaki Bouix, Sylvain Kubicki, Marek Shenton, Martha E. TI Inferior frontal gyrus and thalamic volume reduction in schizophrenia: An MRI study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 VA Boston Healthcare Syst, Brockton Campus, Brockton, MA USA. Brigham & Womens Hosp, Harvard Med Sch, Psychiat Neuroimaging Lab, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 790 BP 245S EP 245S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100785 ER PT J AU Radant, AD Dobie, DJ Meichle, SR Calkins, ME Olincy, A Tsuang, DW AF Radant, Allen D. Dobie, Dorcas J. Meichle, Sean R. Calkins, Monica E. Olincy, Ann Tsuang, Debby W. CA Consortium Genet Schizophrenia TI Are smooth pursuit eye movements a practical schizophrenia endophenotype? Evidence from the multisite consortium on the genetics of schizophrenia (COGS) study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 802 BP 249S EP 249S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100797 ER PT J AU Roffman, JL Goff, DC Ellis, CB Weiss, AR AF Roffman, Joshua L. Goff, Donald C. Ellis, Cameron B. Weiss, Anthony R. TI Neural activation during encoding of auditory source information in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Charlestown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 804 BP 249S EP 249S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100799 ER PT J AU Raskind, MA Peskind, ER Hoff, DJ Hart, KL Holmes, HA Warren, D Shofer, J O'Connell, J Taylor, F Gross, C Rohde, K McFall, ME AF Raskind, Murray A. Peskind, Elaine R. Hoff, David J. Hart, Kimberly L. Holmes, Hollie A. Warren, Daniel Shofer, Jane O'Connell, James Taylor, Fletcher Gross, Christopher Rohde, Kirsten McFall, Miles E. TI A parallel group placebo controlled study of prazosin for trauma nightmares and sleep disturbance in combat veterans with post-traumatic stress disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE adrenergic antagonist; military; nightmare; post-traumatic stress disorder; prazosin; sleep ID CORTICOTROPIN-RELEASING HORMONE; ALPHA-ADRENOCEPTOR ANTAGONISTS; VIETNAM VETERANS; QUALITY INDEX; PTSD; NOREPINEPHRINE; METHOXAMINE; RAT; YOHIMBINE; RESPONSES AB Background: Excessive brain responsiveness to norepinephrine appears to contribute to post-traumatic stress disorder (PTSD), particularly at night. Prazosin, a brain active alpha-1 adrenergic receptor antagonist, significantly reduced trauma nightmares and sleep disturbance in 10 Vietnam War combat veterans in a previous placebo-controlled crossover study. The current parallel group trial in a larger sample of veterans evaluated prazosin effects on trauma nightmares, sleep quality, global clinical status, dream characteristics, and comorbid depression. Methods: Forty veterans (mean age 56 +/- 9) with chronic PTSD and distressing trauma nightmares and sleep disturbance were randomized to evening prazosin (13.3 +/- 3 mg/day) or placebo for 8 weeks. Results: In the evaluable sample (n = 34), primary outcome measures demonstrated that prazosin was significantly superior to placebo for reducing trauma nightmares and improving sleep quality and global clinical status with large effect sizes. Prazosin shifted dream characteristics from those typical of trauma-related nightmares toward those typical of normal dreams. Blood pressure changes from baseline to end study did not differ significantly between prazosin and placebo. Conclusions: Prazosin is an effective and well-tolerated treatment for trauma nightmares, sleep disturbance and global clinical status in veterans with chronic PTSD. C1 Vet Affairs NW Network Mental Illness Res, Educ & Clin Ctr MIRECC, Seattle, WA USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Raskind, MA (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-116, Seattle, WA 98108 USA. EM murray.raskind@med.va.gov FU NIMH NIH HHS [R01MH069867] NR 41 TC 212 Z9 218 U1 3 U2 22 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 APR 15 PY 2007 VL 61 IS 8 BP 928 EP 934 DI 10.1016/j.biopsych.2006.06.032 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 156GP UT WOS:000245636400002 PM 17069768 ER PT J AU Goldstein, JM Seidman, LJ Makris, N Ahern, T O'Brien, LM Caviness, VS Kennedy, DN Faraone, SV Tsuang, MT AF Goldstein, Jill M. Seidman, Larry J. Makris, Nikos Ahern, Todd O'Brien, Liam M. Caviness, Verne S., Jr. Kennedy, David N. Faraone, Stephen V. Tsuang, Ming T. TI Hypothalamic abnormalities in schizophrenia: Sex effects and genetic vulnerability SO BIOLOGICAL PSYCHIATRY LA English DT Article DE genetic vulnerability; hypothalamus; MRI; schizophrenia; sex differences ID CORTICOTROPIN-RELEASING HORMONE; ADULT HUMAN BRAIN; MAMMILLARY BODY; PARAVENTRICULAR NUCLEUS; PARANOID SCHIZOPHRENIA; NONPSYCHOTIC RELATIVES; ANTERIOR HYPOTHALAMUS; MORPHOMETRIC-ANALYSIS; 1ST-DEGREE RELATIVES; HIPPOCAMPAL VOLUME AB Background: This is a unique hypothalamic magnetic resonance imaging (MRI) study in schizophrenia, an important region in the limbic system. We hypothesized abnormal volumetric increases, with greater severity in multiplex families (more than one ill member) compared with simplex families (one ill). We tested the hypothesis that normal hypothalamic sexual dimorphism is disrupted in schizophrenia. Methods: Eighty-eight DSM-III-R schizophrenia cases (40 simplex and 48 multiplex), 43 first-degree nonpsychotic relatives, and 48 normal comparisons systematically were compared. A 1.5-Tesla General Electric scanner was used to acquire structural MRI scans, and contiguous 3.1-mm slices were used to segment anterior and posterior hypothalamus. General linear model for correlated data and generalized estimating equations were used to compare cases, relatives, and controls on right and left hypothalamus, controlled for age, sex, and total cerebral volume. Spearman's correlations of hypothalamic volumes with anxiety were calculated to begin to examine arousal correlates with structural abnormalities. Results: Findings demonstrated significantly increased hypothalamic volume in cases and nonpsychotic relatives, particularly in regions of paraventricular and mammillary body nuclei, respectively. This increase was linear from simplex to multiplex cases, was positively correlated with anxiety, and had a greater propensity in women. Conclusions: Findings suggest important implications for understanding genetic vulnerability of schizophrenia and the high rate of endocrine abnormalities. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Psychiat & Med, Div Womens Hlth, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Div Publ Psychiat, Dept Psychiat, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Athisnoula Martinos Ctr Biomed Imaging, Charlestown, MA USA. MIT, Charlestown, MA USA. Harvard Univ, Sch Med, Ctr Morphometr Anal, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Morphometr Anal, Dept Radiol Serv, Boston, MA 02115 USA. Colby Coll, Dept Math, Waterville, ME 04901 USA. SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY USA. Univ Calif San Diego, Dept Psychiat MTT, Inst Behav Genom, La Jolla, CA 92093 USA. Harvard Univ, Sch Publ Hlth, Inst Psychiat Epidemiol & Genet, Dept Epidemiol MTT, Boston, MA 02115 USA. RP Goldstein, JM (reprint author), Brigham & Womens Hosp, Div Womens Hlth, 1 Brigham Circle,3rd Floor,1620 Tremont St, Boston, MA 02120 USA. EM jill_goldstein@hms.harvard.edu RI Kennedy, David/H-3627-2012; OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH56956, MH 43518, MH 46318] NR 91 TC 98 Z9 101 U1 4 U2 11 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 APR 15 PY 2007 VL 61 IS 8 BP 935 EP 945 DI 10.1016/j.biopsych.2006.06.027 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 156GP UT WOS:000245636400003 PM 17046727 ER PT J AU Mulligan, G Mitsiades, C Bryant, B Zhan, FH Chng, WJ Roels, S Koenig, E Fergus, A Huang, YS Richardson, P Trepicchio, WL Broyl, A Sonneveld, P Shaughnessy, JD Bergsagel, PL Schenkein, D Esseltine, DL Boral, A Anderson, KC AF Mulligan, George Mitsiades, Constantine Bryant, Barb Zhan, Fenghuang Chng, Wee J. Roels, Steven Koenig, Erik Fergus, Andrew Huang, Yongsheng Richardson, Paul Trepicchio, William L. Broyl, Annemiek Sonneveld, Pieter Shaughnessy, John D., Jr. Bergsagel, P. Leif Schenkein, David Esseltine, Dixie-Lee Boral, Anthony Anderson, Kenneth C. TI Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib SO BLOOD LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol ID B-CELL LYMPHOMA; UNFOLDED PROTEIN RESPONSE; MEDIATED DRUG-RESISTANCE; MULTIPLE-MYELOMA CELLS; HIGH-DOSE THERAPY; FACTOR-KAPPA-B; STAGING SYSTEM; PLASMA-CELLS; CHROMOSOME-13 ABNORMALITIES; MOLECULAR CLASSIFICATION AB The aims of this study were to assess the feasibility of prospective pharmacogenomics research in multicenter international clinical trials of bortezomib in multiple myeloma and to develop predictive classifiers of response and survival with bortezomib. Patients with relapsed myeloma enrolled in phase 2 and phase 3 clinical trials of bortezomib and consented to genomic analyses of pretreatment tumor samples. Bone marrow aspirates were subject to a negative-selection procedure to enrich for tumor cells, and these samples were used for gene expression profiling using DNA microarrays. Data quality and correlations with trial outcomes were assessed by multiple groups. Gene expression in this dataset was consistent with data published from a single-center study of newly diagnosed multiple myeloma. Response and survival classifiers were developed and shown to be significantly associated with outcome via testing on independent data. The survival classifier improved on the risk stratification provided by the International Staging System. Predictive models and biologic correlates of response show some specificity for bortezomib rather than dexamethasone. Informative gene expression data and genomic classifiers that predict clinical outcome can be derived from prospective clinical trials of new anticancer agents. C1 Millennium Pharmaceut Inc, Clin Res Translat Med, Cambridge, MA 02139 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. Mayo Clin, Scottsdale, AZ USA. Erasmus MC, Dept Hematol, Rotterdam, Netherlands. RP Mulligan, G (reprint author), Millennium Pharmaceut Inc, Clin Res Translat Med, 40 Landsdowne St, Cambridge, MA 02139 USA. EM george.mulligan@mpi.com RI Bergsagel, Peter/A-7842-2011 OI Bergsagel, Peter/0000-0003-1523-7388 NR 65 TC 159 Z9 162 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2007 VL 109 IS 8 BP 3177 EP 3188 DI 10.1182/blood-2006-09-044974 PG 12 WC Hematology SC Hematology GA 156OJ UT WOS:000245658500019 PM 17185464 ER PT J AU Tubman, VN Levine, JE Campagna, DR Monahan-Earley, R Dvorak, AM Neufeld, EJ Fleming, MD AF Tubman, Venee N. Levine, Jason E. Campagna, Dean R. Monahan-Earley, Rita Dvorak, Ann M. Neufeld, Ellis J. Fleming, Mark D. TI X-linked gray platelet syndrome due to a GATA1 Arg216Gln mutation SO BLOOD LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol ID THROMBOCYTOPENIA; MACROTHROMBOCYTOPENIA; THALASSEMIA; DISEASE; ANEMIA AB We identified a family with gray platelet syndrome (GPS) segregating as a sex-inked trait. Affected males had a mild bleeding disorder, thrombocytopenia, and large agranular platelets characteristic of GPS, while obligate carrier females were asymptomatic but had dimorphic platelets on peripheral smear. Associated findings included mild erythrocyte abnormalities in affected males. Linkage analysis revealed a 63 cM region on the X chromosome between markers G10578 and DXS6797, which segregated with the platelet phenotype and included the GATA1 gene. Sequencing of GATA1 revealed a G-to-A mutation at position 759 corresponding to amino acid change Arg216Gln. This mutation was previously described as a cause of X-linked thrombocytopenia with thalassemia (XLTT) but not of gray platelet syndrome. Our findings suggest that XLTT is within a spectrum of disorders constituting the gray platelet syndrome, and we propose that GATA1 is an upstream regulator of the genes required for platelet ci-granule biogenesis. C1 Childrens Hosp, Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Med Ctr, Dept Pathol, Boston, MA USA. RP Fleming, MD (reprint author), Childrens Hosp, Dana Farber Canc Inst, Div Hematol Oncol, 320 Longwood Ave,Enders 1116-1, Boston, MA 02115 USA. EM mark.fleming@childrens.harvard.edu RI Neufeld, Ellis/F-9331-2011; Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 NR 17 TC 43 Z9 44 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2007 VL 109 IS 8 BP 3297 EP 3299 DI 10.1182/blood-2006-02-004101 PG 3 WC Hematology SC Hematology GA 156OJ UT WOS:000245658500035 PM 17209061 ER PT J AU Miletic, AV Graham, DB Montgrain, V Fujikawa, K Kloeppel, T Brim, K Weaver, B Schreiber, R Xavier, R Swat, W AF Miletic, Ana V. Graham, Daniel B. Montgrain, Vivianne Fujikawa, Keiko Kloeppel, Tracie Brim, Karry Weaver, Brian Schreiber, Robert Xavier, Ramnik Swat, Wojciech TI Vav proteins control MyD88-dependent oxidative burst SO BLOOD LA English DT Article ID NUCLEOTIDE EXCHANGE FACTOR; PHAGOCYTE NADPH OXIDASE; TOLL-LIKE RECEPTOR-4; NF-KAPPA-B; NEUTROPHIL FUNCTIONS; SIGNALING PATHWAYS; TYROSINE KINASE; INNATE IMMUNITY; SUPEROXIDE-PRODUCTION; DEPENDENT ACTIVATION AB The importance of reactive oxygen intermediate (ROI) production in antimicrobial responses is demonstrated in human patients who suffer from chronic granulomatous disease (CGD) due to defective NADPH oxidase function. Exactly how bacterial products activating Toll-like receptors (TLRs) induce oxidative burst is unknown. Here, we identify the Vav family of Rho guanine nucleotide exchange factors (GEFs) as critical mediators of LPS-induced MyD88-dependent activation of Rac2, NADPH oxidase, and ROI production using mice deficient in Vav1, Vav2, and Vav3. Vav proteins are also required for p38 MAPK activation and for normal regulation of proinflammatory cytokine production, but not for other MyD88-controlled effector pathways such as those involving JNK, COX2, or NOS and the production of reactive nitrogen intermediates (RNIs). Thus, our data indicate that Vav specifically transduces a subset of signals emanating from MyD88. C1 Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. Siteman Canc Ctr, St Louis, MO USA. Hokkaido Univ, Sch Med, Dept Biochem, Sapporo, Hokkaido, Japan. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Swat, W (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, 660 S Euclid Ave, St Louis, MO 63110 USA. EM swat@wustl.edu FU NIAID NIH HHS [AI 063024-02, AI 061077-03]; NIDDK NIH HHS [P30 DK040561-12, P30 DK040561] NR 54 TC 46 Z9 46 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2007 VL 109 IS 8 BP 3360 EP 3368 DI 10.1182/blood-2006-07-033662 PG 9 WC Hematology SC Hematology GA 156OJ UT WOS:000245658500043 PM 17158234 ER PT J AU Gupta, V Gylling, A Alonso, JL Sugimori, T Ianakiev, P Xiong, JP Arnaout, MA AF Gupta, Vineet Gylling, Annette Alonso, Jose Luis Sugimori, Takashi Ianakiev, Petre Xiong, Jiang-Ping Arnaout, M. Amin TI The beta-tail domain (beta TD) regulates physiologic ligand binding to integrin CD11b/CD18 SO BLOOD LA English DT Article ID I-LIKE DOMAIN; A-DOMAIN; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; EXTRACELLULAR SEGMENT; OUTSIDE-IN; ACTIVATION; SUBUNIT; LFA-1; AFFINITY AB Crystallographic and electron microscopy studies revealed genuflexed (bent) integrins in both unliganded (inactive) and physiologic ligandbound (active) states, suggesting that local conformational changes are sufficient for activation. Herein we have explored the role of local changes in the contact region between the membrane-proximal beta-tail domain (beta TD) and the ligand-binding RA domain of the bent conformation in regulating interaction of integrin CD11b/CD18 (alpha M beta 2) with its physiologic ligand iC3b. We replaced the beta TD CD loop residues D658GMD of the CD18 (beta 2) subunit with the equivalent D672SSG of the beta 3 subunit, with AGAA or with NGTD, expressed the respective heterodimeric receptors either transiently in epithelial HEK293T cells or stably in leukocytes (K562), and measured their ability to bind iC3b and to conformation-sensitive mAbs. In the presence of the physiologic divalent cations Ca2+ plus Mg2+ (at 1 mM each), the modified integrins showed increased (in HEK293) or constitutive (in K562) binding to iC3b compared with wild-type receptors. K562 expressing the beta TD-modified integrins bound in Ca2+Mg2+ to the beta A-directed high-affinity reporter mAb 24 but not to mAb KIM127, a reporter of the genu-straightened state. These data identify a role for the membrane proximal beta TD as an allosteric modulator of integrin activation. C1 Harvard Univ, Med Sch, Massachusetts Gen Hosp, Struct Biol Program,Nephrol Div,Leukocyte Biol &, Charlestown, MA 02138 USA. RP Arnaout, MA (reprint author), Harvard Univ, Med Sch, Massachusetts Gen Hosp, Struct Biol Program,Nephrol Div,Leukocyte Biol &, Charlestown, MA 02138 USA. EM arnaout@receptor.mgh.harvard.edu RI Gupta, Vineet/B-1134-2009; Alonso, Jose Luis/G-7961-2012; OI Gupta, Vineet/0000-0001-6987-2550 FU NIDDK NIH HHS [K01 DK068253-05S1, DK 068253, DK 48549, DK 50305, K01 DK068253, K01 DK068253-01, K01 DK068253-02, K01 DK068253-03, K01 DK068253-04, K01 DK068253-05, P01 DK050305, R01 DK048549] NR 51 TC 23 Z9 23 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2007 VL 109 IS 8 BP 3513 EP 3520 DI 10.1182/blood-2005-11-056689 PG 8 WC Hematology SC Hematology GA 156OJ UT WOS:000245658500063 PM 17170130 ER PT J AU Efstathiou, JA Chen, MH Renshaw, AA Loffredo, MJ D'Amico, AV AF Efstathiou, Jason A. Chen, Ming-Hui Renshaw, Andrew A. Loffredo, Marian J. D'Amico, Anthony V. TI Influence of body mass index on prostate-specific antigen failure after androgen suppression and radiation therapy for localized prostate cancer SO CANCER LA English DT Article DE BMI; obesity; prostate cancer; PSA failure; radiation therapy; hormonal therapy ID RANDOMIZED CONTROLLED-TRIAL; RADICAL PROSTATECTOMY; UNITED-STATES; PATHOLOGICAL VARIABLES; DEPRIVATION THERAPY; INSULIN-RESISTANCE; PROSPECTIVE COHORT; DIABETES-MELLITUS; RISK-FACTORS; SERUM LEVELS AB BACKGROUND. Increasing body mass index (BMI) is associated with shorter time to prostate-specific antigen (PSA) failure after radical prostatectomy. whether BMI is associated with time to PSA failure was investigated in men treated with androgen suppression therapy (AST) and radiation therapy (RT) for clinically localized prostate cancer. METHODS. The observational prospective cohort study consisted of 102 men with clinically localized prostate cancer who received 70 Gy RT with 6 months of AST on a single arm of a randomized trial between December 1995 and April 2001. Height and weight data were available at baseline for 99 (97%) of the men, from which BMI was calculated. Adjusting for age (continuous) and known prognostic factors including PSA level (continuous), Gleason score, and T-category, Cox regression analyses were performed to analyze whether BMI (continuous) was associated with time to PSA failure (PSA >1.0 ng/mL and increasing >0.2 ng/mL on 2 consecutive visits). RESULTS. Median age and median BMI (interquartile range [IQR]) at baseline was 72 (69.1-74.7) years and 27.4 (24.8-30.7) kg/m,(2) respectively. In addition to an increasing PSA level (P = .006) and Gleason 8-10 cancer (P = .024), after a median follow-up (IQR) of 6.9 (5.6-8.5) years, an increasing BMI was also significantly associated with a shorter time to PSA failure (adjusted hazard ratio [HR]: 1.10; 95% confidence interval [Cl]: 1.01-1.19; P = .026) after RT and AST. CONCLUSIONS. After adjusting for known prognostic factors, baseline BMI is significantly associated with time to PSA failure after RT and AST for men with clinically localized prostate cancer. Further study is warranted to assess the impact of an increasing BMI after AST administration on PSA failure, prostate cancer-specific, and all-cause mortality. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Efstathiou, JA (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L2, Boston, MA 02115 USA. EM jefstathiou@partners.org NR 66 TC 21 Z9 22 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD APR 15 PY 2007 VL 109 IS 8 BP 1493 EP 1498 DI 10.1002/cncr.22564 PG 6 WC Oncology SC Oncology GA 155IK UT WOS:000245570900007 PM 17340594 ER PT J AU Talcott, JA Spain, P Clark, JA Carpenter, WR Do, YK Hamilton, RJ Galanko, JA Jackman, A Godley, PA AF Talcott, James A. Spain, Pamela Clark, Jack A. Carpenter, William R. Do, Young Kyung Hamilton, Robert J. Galanko, Joseph A. Jackman, Anne Godley, Paul A. TI Hidden barriers between knowledge and behavior the North Carolina prostate cancer screening and treatment experience SO CANCER LA English DT Article DE prostatic neoplasms; diagnosis; treatment; African Americans/psychology; European Continental Ancestry Group/psuchology; attitude to health; socioeconomic factors; access to health care; trust ID RACIAL-DIFFERENCES; MEDICARE RECIPIENTS; AFRICAN-AMERICANS; BREAST-CANCER; UNITED-STATES; TRENDS; WILLINGNESS; PARTICIPATE; DISPARITIES; MORTALITY AB BACKGROUND. Prostate cancer (PC) mortality is much greater for African American than for Caucasian men. To identify patient factors that might account for some of this disparity, men within 6 months of diagnosis were surveyed about health attitudes and behavior. METHODS. Using Rapid Identification in the North Carolina Cancer Registry, 207 African American and 348 Caucasian recently diagnosed PC patients were identified and surveyed. RESULTS. African American men were younger and less often currently married, and had lesser education, job status, and income than Caucasian men (all P <.001). African American men were at no greater distance to medical care, but had less access: poorer medical insurance coverage, more use of public clinics and emergency wards, less continuity with a primary physician, and more often omitted physician visits they felt they needed. They also expressed less trust in physicians. African American men acknowledged their greater risk of PC, accepted greater responsibility for their health, and reported more personal failures that delayed diagnosis. African American men more often requested the tests that diagnosed their cancers, which resulted more often from routinely ordered screening tests for Caucasian men. African American men expressed less interest in nontraditional treatments. CONCLUSIONS. Despite lesser education, African American men in North Carolina are aware of their increased risk of cancer, the importance of treatment, and their responsibility for their health. Obstacles to timely diagnosis and appropriate care, including greater physician distrust, appear more likely to arise from reduced access and continuity of medical care arising from their worse socioeconomic position. C1 Massachusetts Gen Hosp, Ctr Outcomes Res, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ N Carolina, Cecil G Sheps Ctr Hlth Serv Res, Chapel Hill, NC USA. Edit Nourse Rogers Mem Vet Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. UNC Dept Hlth Policy & Adm, Chapel Hill, NC USA. Univ Toronto, Dept Surg Urol, Toronto, ON, Canada. UNC Dept Med, Sch Med, Chapel Hill, NC USA. UNC Sch Publ Hlth, Chapel Hill, NC USA. RP Talcott, JA (reprint author), Massachusetts Gen Hosp, Ctr Outcomes Res, Ctr Canc, 1 Hawthorne Pl,Suite 107, Boston, MA 02114 USA. EM jtalcott@partners.org RI Carpenter, William/E-5125-2013; OI Hamilton, Robert/0000-0002-6715-5934; Clark, Jack/0000-0002-7424-1670 FU AHRQ HHS [5 P01 HS010861]; NCI NIH HHS [R25T CA 57726, 1 U01 CA114629-01]; NIDDK NIH HHS [P30 DK 034987]; NIMHD NIH HHS [1 P60 MD0024-01] NR 33 TC 46 Z9 47 U1 2 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD APR 15 PY 2007 VL 109 IS 8 BP 1599 EP 1606 DI 10.1002/cncr.22583 PG 8 WC Oncology SC Oncology GA 155IK UT WOS:000245570900021 PM 17354220 ER PT J AU Hatjiharissi, E Ngo, H Leontovich, AA Leleu, X Timm, M Melhem, M George, D Lu, GW Ghobrial, J Alsayed, Y Zeismer, S Cabanela, M Nehme, A Jia, X Moreau, AS Treon, SP Fonseca, R Gertz, MA Anderson, KC Witzig, TE Ghobrial, IM AF Hatjiharissi, Evdoxia Ngo, Hai Leontovich, Alexey A. Leleu, Xavier Timm, Michael Melhem, Mona George, Diane Lu, Ganwei Ghobrial, Joanna Alsayed, Yazan Zeismer, Steven Cabanela, Miguel Nehme, Alex Jia, Xiaoying Moreau, Anne Sophie Treon, Steven P. Fonseca, Rafael Gertz, Morie A. Anderson, Kenneth C. Witzig, Thomas E. Ghobrial, Irene M. TI Prioteomic analysis of Waldenstrom macroglobulinemia SO CANCER RESEARCH LA English DT Article ID MULTIPLE-MYELOMA; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; PROGNOSTIC-FACTORS; PROTEOMIC ANALYSIS; PROTEIN; INHIBITION; EXPRESSION; THERAPY; COMBINATION AB To better understand the molecular changes that occur in Waldenstrom macroglobulinemia (WM), we employed antibody-based protein microarrays to compare patterns of protein expression between untreated WM and normal bone marrow controls. Protein expression was defined as a > 2-fold or 1.3-fold change in at least 67% of the tumor samples. Proteins up-regulated by > 2-fold included Ras family proteins, such as Rab-4 and p62DOK, and Rho family proteins, such as CDC42GA-P and ROK alpha. Other proteins up-regulated by > 1.3-fold included cyclin-dependent kinases, apoptosis regulators, and historic deacetylases (HDAC). We then compared the samples of patients with symptomatic and asymptomatic WM and showed similar protein expression signatures, indicating that the dysregulation of signaling pathways occurs early in the disease course. Three proteins were different by > 2-fold in symptomatic versus asymptomatic, including the heat shock protein HSP90. Elevated protein expression was confirmed by immunohistochemistry and immunoblotting. Functional significance was validated by the induction of apoptosis And inhibition of proliferation using specific HDAC and HSP90 inhibitors. This study, therefore, identifies, for the first time, multiple novel proteins that are dysregulated in VVM, which both enhance our understanding of disease pathogenesis and represent targets of novel therapeutics. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Mayo Clin, Coll Med, Dept Internal Med, Div Hematol, Rochester, MN USA. VA Pittsburgh Healthcare Syst, Dept Pathol, Pittsburgh, PA USA. Univ Pittsburgh, Inst Canc, Dept Internal Med, Div Hematol & Oncol, Pittsburgh, PA USA. RP Ghobrial, IM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Mayer 547, Boston, MA 02115 USA. EM Irene_ghobrial@dfci.harvard.edu NR 34 TC 40 Z9 40 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2007 VL 67 IS 8 BP 3777 EP 3784 DI 10.1158/0008-5472.CAN-06-3089 PG 8 WC Oncology SC Oncology GA 158GL UT WOS:000245779600040 PM 17440091 ER PT J AU Meeran, SM Katiyar, S Elmets, CA Katiyar, SK AF Meeran, Syed M. Katiyar, Suchitra Elmets, Craig A. Katiyar, Santosh K. TI Interleukin-12 deficiency is permissive for angiogenesis in UV radiation-induced skin tumors SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; GREEN TEA POLYPHENOLS; IFN-GAMMA PRODUCTION; INDUCED IMMUNOSUPPRESSION; MOUSE SKIN; MATRIX METALLOPROTEINASES; CANCER-THERAPY; DNA-REPAIR; T-CELLS; IL-12 AB We have shown previously that endogenous deficiency of interleukin (IL)-12 promotes photocarcinogenesis in mice. To characterize the role of IL-12 deficiency in tumor angiogenesis, we developed IL-12p35 knockout (IL-12 KO) mice on a C3H/HeN background. IL-12 KO mice and their wild-type (WT) counterparts were subjected to a photocarcinogenesis protocol. When tumor yield was stabilized, samples of tumor and tumor-uninvolved UVB-exposed skin were collected and subjected to immunohistochemistry, gelatinolytic zymography, real-time PCR, and Western blot analysis of angiogenic factors. We found that the protein, mRNA expression and/or activity of the matrix metalloproteinases (MMP)-2, MMP-3, MNIP-7, and MMP-9, and basic fibroblast growth factor, which play crucial roles in tumor growth, were significantly higher in UVB-exposed skin and tumors of IL-12 KO mice compared with WT mice. With respect to the tumor vasculature, the expression of CD31-positive cells and the expression of vascular endothelial growth factor were higher in the tumors of IL-12 KO mice than WTs. The proliferative capacity of tumor cells of the IL-12 KO mice was significantly higher than their WT counterparts when determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and by analyzing the expression of cyclin D1. The level of the proinflammatory cytokine IL-6 and the expression of IL-23 in tumors of IL-12 KO mice were markedly higher than in the tumors of WT mice. IL-23 has been shown to promote tumor growth. Together, these data indicate for the first time that IL-12 deficiency promotes proangiogenic stimuli in UVB-induced skin tumors and suggest that endogenous enhancement of IL-12 levels maybe effective in the prevention and treatment of UV-induced skin cancers. C1 Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. Univ Alabama, Skin Dis Res Ctr, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557,POB 202, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU NCCIH NIH HHS [R01 AT002536, AT 002536, R01 AT002536-01A2]; NIAMS NIH HHS [P30 AR050948, AR 050948-01, P30 AR050948-030001] NR 40 TC 15 Z9 16 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2007 VL 67 IS 8 BP 3785 EP 3793 DI 10.1158/0008-5472.CAN-06-3134 PG 9 WC Oncology SC Oncology GA 158GL UT WOS:000245779600041 PM 17440092 ER PT J AU Tilly, JL Johnson, J AF Tilly, Jonathan L. Johnson, Joshua TI Recent arguments against germ cell renewal in the adult human ovary - Is an absence of marker gene expression really acceptable evidence of an absence of oogenesis? SO CELL CYCLE LA English DT Article DE germline stem cell; oogenesis; oocyte; ovary; bone marrow; peripheral blood ID MARROW STEM-CELLS; FANCONI-ANEMIA; BONE-MARROW; REDUCED FERTILITY; EGGS FOREVER; MICE; FOLLICLES; OOCYTE; CHEMOTHERAPY; DERIVATION AB In 2004, a study from our lab published in the journal Nature reignited a world wide debate over the validity of the dogma that mammalian females are incapable of oocyte and follicle production during postnatal life. Amidst widespread skepticism, we forged ahead and published a second study in 2005 in the journal Cell, which not only reaffirmed with different experimental approaches that this dogma is invalid but also identified cells in bone marrow ( BM) and blood of adult female mice that could generate oocytes contained within immature follicles in the ovaries of recipient females following transplantation. Although this work has been the subject of extensive critical commentary as well, two recent reports from others have confirmed the germline potential of adult BM-derived cells in mice. Further, independent corroboration of the results and conclu sions presented in our earlier Nature paper is also now available. However, three papers have been published that purportedly question our work and conclusions. The first is a paper by Eggan et al. published in the journal Nature, which attempts to draw conclu sions about the germline potential of BM-derived cells after focusing solely on ovulated eggs while ignoring what may be occurring at the level of oogenesis in the ovaries. The second, from Veitia and colleagues, attempts to draw the same conclusions as Eggan et al. from a single clinical case report of a female Fanconi anemia patient who conceived a genetically - related daughter after allogeneic bone marrow transplantation. The third is a report from Liu et al. just released in the journal Developmental Biology that claims to provide evidence refuting the possibility that adult female mammals produce new oocytes. However, all of the data presented in this latter report are derived from gene expression studies that the authors say fail to show the occurrence of meiosis or germ cell mitosis in adult human ovaries. Given that more than three years have passed since our initial study challenging the dogma was published, it is our belief that continuing arguments against the possibility of postnatal oogenesis in mammals should be based on more rigorous experimental approaches than simply an absence of evidence, especially from gene expression analyses. Further, the interpretations offered by Liu et al. of their results are not as straightforward as they contend since some of their data can also be viewed as supportive of postnatal oogenesis in reproductive age women. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent Obstet & Gynecol, Boston, MA 02114 USA. Yale Univ, Dept Obstet Gynecol & Reprod Sci, Sch Med, New Haven, CT USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent Obstet & Gynecol, THR-901B,55 Fruit St, Boston, MA 02114 USA. EM jtilly@partners.org NR 34 TC 25 Z9 27 U1 0 U2 5 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD APR 15 PY 2007 VL 6 IS 8 BP 879 EP 883 DI 10.4161/cc.6.8.4185 PG 5 WC Cell Biology SC Cell Biology GA 160NC UT WOS:000245948300001 PM 17438374 ER PT J AU Chabner, B AF Chabner, Bruce TI Phase II cancer trials: Out of control? SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID BREAST-CANCER; CHEMOTHERAPY; THERAPY C1 Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02114 USA. RP Chabner, B (reprint author), Massachusetts Gen Hosp, MGH Canc Ctr, 55 Fruit St,LH 214, Boston, MA 02114 USA. EM BCHABNER@PARTNERS.ORG NR 13 TC 4 Z9 3 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 APR 15 PY 2007 VL 13 IS 8 BP 2307 EP 2308 DI 10.1158/1078-0432.CCR-07-0163 PG 2 WC Oncology SC Oncology GA 159RK UT WOS:000245883800001 PM 17438086 ER PT J AU McCormick, AW Walensky, RP Lipsitch, M Losina, E Hsu, H Weinstein, MC Paltiel, AD Freedberg, KA Seage, GR AF McCormick, Alethea W. Walensky, Rochelle P. Lipsitch, Marc Losina, Elena Hsu, Heather Weinstein, Milton C. Paltiel, A. David Freedberg, Kenneth A. Seage, George R., III TI The effect of antiretroviral therapy on secondary transmission of HIV among men who have sex with men SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; COST-EFFECTIVENESS; VIRAL LOAD; HETEROSEXUAL TRANSMISSION; INFECTED PATIENTS; RISK BEHAVIORS; PLUS INDINAVIR; DISEASE STAGE; UNITED-STATES; COITAL ACT AB Background. Antiretroviral therapy (ART) reduces human immunodeficiency virus (HIV) RNA load and the probability of transmitting HIV to an HIV-uninfected partner. However, the potential reduction in secondary transmission associated with ART may be offset by the longer duration of infectiousness. Methods. To estimate the effects of ART on the secondary transmission of HIV among men who have sex with men, we used a previously published state-transition model of HIV disease to simulate the clinical and virologic course of HIV infection among 2 cohorts of men who have sex with men: (1) a cohort of individuals who were not receiving ART and (2) a cohort of individuals treated with US guideline-concordant ART. The model tracked the number of acts of unprotected insertive anal intercourse, transmission risk per act as determined by HIV RNA level, and the number of secondary cases generated in each cohort. Results. The estimated mean number of secondary transmissions from an HIV-infected individual after 10, 20, and 30 years of infection were 1.9, 2.5, and 2.5, respectively, in the untreated cohort, compared with 1.4, 1.8, and 2.3, respectively, in the treated cohort. The total number of transmissions for the treated cohort began to exceed the total number of transmissions for the untreated cohort 33 years after infection; over the entire course of infection, treatment with ART led to a 23% increase in secondary infections. All estimates of the impact of ART on secondary transmission were sensitive to changes in risk behaviors. Conclusions. These results suggest that ART must be accompanied by effective HIV-related risk reduction interventions. Programs that target prevention to decrease further HIV transmission are crucial to epidemic control. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, AIDS Res Ctr, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. Yale Univ, Sch Med, Dept Hlth Policy & Adm, New Haven, CT 06520 USA. RP McCormick, AW (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM amccormi@hsph.harvard.edu OI Walensky, Rochelle P./0000-0002-8795-379X; Lipsitch, Marc/0000-0003-1504-9213 FU NCRR NIH HHS [5-M01-RR-00722, M01 RR000722]; NIAID NIH HHS [U01 AI035039, K23 AI001794, K23 AI001794-05, K23-AI-01794, K24 AI062476, K24 AI062476-04, K24-AI-062476, K25 AI050436, K25 AI050436-05, K25-AI-50436, R01 AI058736, R01 AI058736-03S1, R01-AI-058736, R37 AI042006, R37 AI042006-10A1, R37-AI-42006, T32 AI007433, T32 AI007433-16, T32-AI-07433, U01 AI035040, U01 AI035041, U01 AI035042, U01 AI035043, U01 AI037613, U01 AI037984, U01-AI-35039, U01-AI-35040, U01-AI-35041, U01-AI-35042, U01-AI-35043, U01-AI-37613, U01-AI-37984]; NIMH NIH HHS [R01 MH065869, R01 MH065869-03, R01-MH-65869-03] NR 45 TC 39 Z9 40 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 15 PY 2007 VL 44 IS 8 BP 1115 EP 1122 DI 10.1086/512816 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 146IR UT WOS:000244928200019 PM 17366461 ER PT J AU Kashiwagi, M Morgan, BA Georgopoulos, K AF Kashiwagi, Mariko Morgan, Bruce A. Georgopoulos, Katia TI The chromatin remodeler Mi-2 beta is required for establishment of the basal epidermis and normal differentiation of its progeny SO DEVELOPMENT LA English DT Article DE Mi-2 beta (Chd4); chromatin; epidermis; stem cells ID HAIR-FOLLICLE DEVELOPMENT; RNA-POLYMERASE-II; STEM-CELL; P63; SKIN; MORPHOGENESIS; LIMB; EXPRESSION; COMPLEX; BINDING AB Using conditional gene targeting in mice, we show that the chromatin remodeler Mi-2 beta is crucial for different aspects of skin development. Early (E10.5) depletion of Mi-2 beta in the developing ventral epidermis results in the delayed reduction of its suprabasal layers in late embryogenesis and to the ultimate depletion of its basal layer. Later (E13.5) loss of Mi-2 beta in the dorsal epidermis does not interfere with suprabasal layer differentiation or maintenance of the basal layer, but induction of hair follicles is blocked. After initiation of the follicle, some subsequent morphogenesis of the hair peg may proceed in the absence of Mi-2 beta, but production of the progenitors that give rise to the inner layers of the hair follicle and hair shaft is impaired. These results suggest that the extended self-renewal capacity of epidermal precursors arises early during embryogenesis by a process that is critically dependent on Mi-2 beta. Once this process is complete, Mi-2 beta is apparently dispensable for the maintenance of established repopulating epidermal stem cells and for the differentiation of their progeny into interfollicular epidermis for the remainder of gestation. Mi-2 beta is however essential for the reprogramming of basal cells to the follicular and, subsequently, hair matrix fates. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Georgopoulos, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM katia.georgopoulos@cbrc2.mgh.harvard.edu FU NIAID NIH HHS [R01 AI380342] NR 39 TC 40 Z9 40 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD APR 15 PY 2007 VL 134 IS 8 BP 1571 EP 1582 DI 10.1242/dev.001750 PG 12 WC Developmental Biology SC Developmental Biology GA 149AJ UT WOS:000245118300013 PM 17360773 ER PT J AU Sherwood, RI Jitianu, C Cleaver, O Shaywitz, DA Lamenzo, JO Chen, AE Golub, TR Melton, DA AF Sherwood, Richard I. Jitianu, Cristian Cleaver, Ondine Shaywitz, David A. Lamenzo, Julia O. Chen, Alice E. Golub, Todd R. Melton, Douglas A. TI Prospective isolation and global gene expression analysis of definitive and visceral endoderm SO DEVELOPMENTAL BIOLOGY LA English DT Article DE endoderm; embryonic stem cell; extraembryonic endoderm; embryonic germ layers; flow cytometry; transcriptional profiling ID EMBRYONIC STEM-CELLS; GERM-LAYER FORMATION; MOUSE EMBRYO; EXTRAEMBRYONIC ENDODERM; PRIMITIVE ENDODERM; VENTRAL FOREGUT; DIFFERENTIATION; FATE; GASTRULATION; MESODERM AB In spite of the therapeutic importance of endoderm derivatives such as the pancreas, liver, lung, and intestine, there are few molecular markers specific for early endoderm. In order to identify endoderm-specific genes as well as to define transcriptional differences between definitive and visceral endoderm, we performed microarray analysis on E8.25 definitive and visceral endoderm. We have developed an early endoderm gene expression signature, and clarified the transcriptional similarities and differences between definitive and visceral endoderm. Additionally, we have developed methods for flow cytometric isolation of definitive and visceral endoderm. These results shed light on the mechanism of endoderm formation and should facilitate investigation of endoderm formation from embryonic stem cells. (c) 2007 Elsevier Inc. All rights reserved. C1 MIT, Broad Inst, Cambridge, MA 02141 USA. Harvard Univ, Stem Cell Inst, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Sherwood, RI (reprint author), Harvard Univ, Stem Cell Inst, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. EM rsherw@fas.harvard.edu OI Cleaver, Ondine/0000-0003-2454-6641 NR 55 TC 93 Z9 94 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD APR 15 PY 2007 VL 304 IS 2 BP 541 EP 555 DI 10.1016/j.ydbio.2007.01.011 PG 15 WC Developmental Biology SC Developmental Biology GA 158UE UT WOS:000245819600008 PM 17328885 ER PT J AU Zou, L AF Zou, Lee TI Single- and double-stranded DNA: building a trigger of ATR-mediated DNA damage response SO GENES & DEVELOPMENT LA English DT Article DE hints from yeast; Xenopus; and human ID XENOPUS EGG EXTRACTS; REPEATED PHOSPHOPEPTIDE MOTIFS; STALLED REPLICATION FORKS; DEPENDENT CHECKPOINT; CHK1 ACTIVATION; PHOSPHORYLATION; PROTEIN; CLASPIN; STRESS; YEAST C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. RP Zou, L (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM zou.lee@mgh.harvard.edu FU NIGMS NIH HHS [GM076388] NR 54 TC 61 Z9 65 U1 1 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 APR 15 PY 2007 VL 21 IS 8 BP 879 EP 885 DI 10.1101/gad.1550307 PG 7 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 157TM UT WOS:000245743900001 PM 17437994 ER PT J AU Grabiner, BC Blonska, M Lin, PC You, Y Wang, DH Sun, JY Darnay, BG Dong, C Lin, X AF Grabiner, Brian C. Blonska, Marzenna Lin, Pei-Chun You, Yun Wang, Donghai Sun, Jiyuan Darnay, Bryant G. Dong, Chen Lin, Xin TI CARMA3 deficiency abrogates G protein-coupled receptor-induced NF-kappa B activation SO GENES & DEVELOPMENT LA English DT Article DE NF-kappa B; GPCR; CARMA3; neural tube ID LYSOPHOSPHATIDIC ACID; IMMUNE-RESPONSES; KINASE COMPLEX; FAMILY MEMBER; BCL10; PHOSPHORYLATION; PATHWAY; TAK1; UBIQUITINATION; REQUIREMENT AB G protein-coupled receptors (GPCRs) play pivotal roles in regulating various cellular functions. Although many GPCRs induce NF-kappa B activation, the molecular mechanism of GPCR-induced NF-kappa B activation remains largely unknown. CARMA3 (CARD and MAGUK domain-containing protein 3) is a scaffold molecule with unknown biological functions. By generating CARMA3 knockout mice using the gene targeting approach, here we show CARMA3 is required for GPCR-induced NF-kappa B activation. Mechanistically, we found that CARMA3 deficiency impairs GPCR-induced kappa B kinase (IKK) activation, although it does not affect GPCR-induced IKK alpha/beta phosphorylation, indicating that inducible phosphorylation of IKK alpha/beta alone is not sufficient to induce its kinase activity. We also found that CARMA3 is physically associated with NEMO/IKK gamma, and induces polyubiquitination of an unknown protein(s) that associates with NEMO, likely by linking NEMO to TRAF6. Consistently, we found TRAF6 deficiency also abrogates GPCR-induced NF-kappa B activation. Together, our results provide the genetic evidence that CARMA3 is required for GPCR-induced NF-kappa B activation. C1 Univ Texas, MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Lin, X (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA. EM xllin@mdanderson.org RI dong, chen /B-3181-2009; sun, jiyuan/B-3828-2010; Lin, Pei-Chun/A-3200-2013; OI dong, chen /0000-0002-0084-9130; Blonska, Marzenna/0000-0001-5237-8732 FU NIAID NIH HHS [AI050848, R01 AI050848, R56 AI050848]; NIGMS NIH HHS [GM065899, R01 GM065899, R01 GM079451, R56 GM065899] NR 46 TC 70 Z9 72 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 15 PY 2007 VL 21 IS 8 BP 984 EP 996 DI 10.1101/gad.1502507 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 157TM UT WOS:000245743900010 PM 17438001 ER PT J AU Chen, RY Westfall, AO Hardin, JM Miller-Hardwick, C Stringer, JSA Raper, JL Vermund, SH Gotuzzo, E Allison, J Saag, MS AF Chen, Ray Y. Westfall, Andrew O. Hardin, J. Michael Miller-Hardwick, Cassandra Stringer, Jeffrey S. A. Raper, James L. Vermund, Sten H. Gotuzzo, Eduardo Allison, Jeroan Saag, Michael S. TI Complete blood cell count as a surrogate CD4 cell marker for HIV monitoring in resource-limited settings SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE AIDS; CD4(+) cell count; complete blood cell count; decision tree; HIV; total lymphocyte count ID TOTAL LYMPHOCYTE COUNT; ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; AFRICAN PATIENTS; STAGING SYSTEM; DECISION-TREE; CONSTRAINED COUNTRIES; INFECTED INDIVIDUALS; RAPID DECLINES; HOMOSEXUAL-MEN AB Background: A total lymphocyte count (TLC) of 1200 cells/mL has been used as a surrogate for a CD4 count of 200 cells/mu L in resourcelimited settings with varying results. We developed a more effective method based on a decision tree algorithm to classify subjects. Methods: A decision tree was used to develop models with the variables TLC, hemoglobin, platelet count, gender, body mass index, and antiretroviral treatment status of subjects from the University of Alabama at Birmingham (UAB) observational database. Models were validated on data from the Birmingham Veterans Affairs Medical Center (BVAMC) and Zambia, with primary decision trees also generated from these data. Results: A total of 1189 patients from the UAB observational database were included. The UAB decision tree classified a CD4 count <= 200 cells/mu L as better than a TLC cut-point of 1200 cells/mL, based on the area under the curve of the receiver-operator characteristic curve (P < 0.0001). When applied to data from the BVAMC and Zambia, the UAB-based decision tree performed better than the TLC cut-point of 1200 cells/mL (BVAMC: P < 0.0001; Zambia: P = 0.0009) but worse than a decision tree based on local data (BVAMC: P <= 0.0001; Zambia: P < 0.0001). Conclusion: A decision tree algorithm based on local data identifies low CD4 cell counts better than one developed from a different population or a TLC cut-point of 1200 cells/mL. C1 Univ Alabama, HIV Outpatient Clin, Dept Med, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Alabama, Dept Biostat, Sch Publ Hlth, Birmingham, AL 35294 USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Univ Alabama, Dept Epidemiol, Sch Publ Hlth, Birmingham, AL 35294 USA. Hosp Cayetano Heredia, Dept Transmissible Dis, Lima, Peru. RP Saag, MS (reprint author), Univ Alabama, HIV Outpatient Clin, Dept Med, Community Care Bldg,Room 142,908 20th St, Birmingham, AL 35294 USA. EM msaag@uab.edu OI Chen, Ray/0000-0001-6344-1442; Allison, Jeroan/0000-0003-4472-2112; Vermund, Sten/0000-0001-7289-8698 FU NIAID NIH HHS [P30 AI 27767] NR 45 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR 15 PY 2007 VL 44 IS 5 BP 525 EP 530 DI 10.1097/QAI.0b013e318032385e PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 152YZ UT WOS:000245399700005 PM 17259910 ER PT J AU Battaglino, R Vokes, M Schulze-Spate, U Sharma, A Graves, D Kohler, T Muller, R Yoganathan, S Stashenko, P AF Battaglino, R. Vokes, M. Schulze-Spate, U. Sharma, A. Graves, D. Kohler, T. Mueller, R. Yoganathan, S. Stashenko, P. TI Fluoxetine treatment increases trabecular bone formation in mice (fluoxetine affects bone mass) SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE fluoxetine; serotonin; bone ID SEROTONIN-REUPTAKE INHIBITORS; OVARIAN-STEROID REGULATION; MINERAL DENSITY; IN-VIVO; NICOTINIC RECEPTORS; TRANSPORTER; EXPRESSION; DEPRESSION; BLOCKAGE; BINDING AB Mounting evidence exists for the operation of a functional serotonin (5-HT) system in osteoclasts and osteoblasts, which involves both receptor activation and 5-HT reuptake. In previous work we showed that the serotonin transporter (5-HTT) is expressed in osteoclasts and that its activity is required by for osteoclast differentiation in vitro. The purpose of the current study was to determine the effect of treatment with fluoxetine, a specific serotonin reuptake inhibitor, on bone metabolism in vivo. Systemic administration of fluoxetine to Swiss-Webster mice for 6 weeks resulted in increased trabecular BV and BV/TV in femurs and vertebrae as determined by micro-computed tomography (mu CT). This correlated with an increase in trabecular number, connectivity, and decreased trabecular spacing. Fluoxetine treatment also resulted in increased volume in vertebral trabecular bone. However, fluoxetine-treated mice were not protected against bone loss after ovariectomy, suggesting that its anabolic effect requires the presence of estrogen. The effect of blocking the 5-HTT on bone loss following an LPS-mediated inflammatory challenge was also investigated. Subcutaneous injections of LPS over the calvariae of Swiss-Webster mice for 5 days resulted in increased numbers of osteoclasts and net bone loss, whereas new bone formation and a net gain in bone mass was seen when LPS was given together with fluoxetine. We conclude that fluoxetine treatment in vivo leads to increased bone mass under normal physiologic or inflammatory conditions, but does not prevent bone loss associated with estrogen deficiency. These data suggest that commonly used anti-depressive agents may affect bone mass. J. Cell. Biochem. 100: 1387-1394, 2007. (c) 2006 Wiley-Liss, Inc. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Boston Univ, Sch Dent Med, Boston, MA USA. Univ Zurich, Inst Biomed Engn, Zurich, Switzerland. ETH, Zurich, Switzerland. RP Battaglino, R (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM rbattaglino@Forsyth.org RI Muller, Ralph/A-1198-2008; battaglino, ricardo/D-2892-2015 OI Muller, Ralph/0000-0002-5811-7725; FU NIDCR NIH HHS [DE007378-18] NR 45 TC 32 Z9 40 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 15 PY 2007 VL 100 IS 6 BP 1387 EP 1394 DI 10.1002/jcb.21131 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 152ZF UT WOS:000245400300006 PM 17041947 ER PT J AU Lankowski, AJ Hohmann, EL AF Lankowski, Alexander J. Hohmann, Elizabeth L. TI Killed but metabolically active Salmonella typhimurium: Application of a new technology to an old vector SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID T-CELL RESPONSES; PROTECTIVE IMMUNITY; ANTIGEN; VACCINE; IMMUNOGENICITY; EXPRESSION; VIRULENCE; SYSTEM; MODEL; MICE AB Previous studies have shown that attenuated salmonellae utilized as vaccine vectors engender strong immune responses; however, balancing immunogenicity with reactogenicity remains problematic. Recent work in other bacteria has shown that photochemical treatment of DNA excision repair mutants (DuvrAB) renders organisms "killed but metabolically active" (KBMA). Here, we extend this concept to Salmonella typhimurium. A strain of attenuated S. typhimurium previously evaluated in human volunteers was further deleted for uvrAB genes and designated CKS362. Photochemical treatment of CKS362 resulted in significant inactivation. These KBMA organisms were metabolically active as shown by radioactive methionine incorporation and lactate dehydrogenase activity. In mice inoculated intraperitoneally, KBMA CKS362 was markedly less reactogenic and stimulated a humoral immune equivalent to its live counterpart. Because the parental strain has previously been found to elicit strong immune responses to Salmonella antigens, we propose CKS362 as a prototype strain to test the immunogenicity of KBMA organisms in humans. C1 Harvard Univ, Div Infect Dis, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Hohmann, EL (reprint author), Harvard Univ, Div Infect Dis, Massachusetts Gen Hosp, Sch Med, Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM ehohmann@partners.org FU NIAID NIH HHS [R01 AI67103] NR 21 TC 11 Z9 12 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 15 PY 2007 VL 195 IS 8 BP 1203 EP 1211 DI 10.1086/512618 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 153AW UT WOS:000245405100019 PM 17357059 ER PT J AU Louey, S Jonker, SS Giraud, GD Thornburg, KL AF Louey, Samantha Jonker, Sonnet S. Giraud, George D. Thornburg, Kent L. TI Placental insufficiency decreases cell cycle activity and terminal maturation in fetal sheep cardiomyocytes SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID INTRAUTERINE GROWTH RESTRICTION; CARDIAC MYOCYTES; POSTNATAL-GROWTH; BLOOD-FLOW; RAT-HEART; EMBOLIZATION; HYPERTROPHY; GESTATION; REGENERATION; HYPERPLASIA AB Umbilicoplacental embolization (UPE) in sheep has been used to investigate the effects of placental insufficiency on fetal development. However, its specific effects on the heart have been little studied. The aim of this study was to determine the effects of placental insufficiency, induced by UPE, on cardiomyocyte size, maturation and proliferation. Instrumented fetal sheep underwent UPE for either 10 or 20 days. Hearts were collected at 125 +/- 1 days (10 day group) or 136 +/- 1 days (20 day group) of gestation (term similar to 145 days). Cell size, maturational state (as measured by the proportion of binucleated myocytes) and cell cycle activity (as measured by positive staining of cells for Ki-67) were determined in dissociated cardiomyocytes. UPE fetuses were hypoxaemic, but mean arterial pressures were not different from controls. UPE fetuses were lighter than control fetuses (10 days: -21%, P < 0.05; 20 days: -27%, P < 0.01) and had smaller hearts, but heart weight was appropriate for body weight. Neither lengths nor widths were different between control and UPE cardiomyocytes at either age. Ten days of UPE did not significantly alter the proportion of binucleated myocytes or cell cycle activity in either ventricle. However, 20 days of UPE reduced cell cycle activity in both ventricles by similar to 70% (P < 0.05); the proportion of binucleated myocytes was also lower in UPE fetuses at this age (left ventricle: 31.1 +/- 12.0 versus 46.0 +/- 6.6%, P < 0.05; right ventricle: 29.4 +/- 12.3 versus 46.3 +/- 5.3%, P < 0.05). It is concluded that in the absence of fetal arterial hypertension, placental insufficiency is associated with substantially depressed growth of the heart through suppressed proliferation and maturation of cardiomyocytes. C1 Oregon Hlth & Sci Univ, Heart Res Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Med Cardiovasc, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97207 USA. RP Louey, S (reprint author), Oregon Hlth & Sci Univ, Heart Res Ctr, L464,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM loueys@ohsu.edu OI Thornburg, Kent/0000-0002-5561-4785; Jonker, Sonnet/0000-0002-1097-2562 FU NICHD NIH HHS [P01 HD034430, P01HD34430] NR 34 TC 46 Z9 47 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD APR 15 PY 2007 VL 580 IS 2 BP 639 EP 648 DI 10.1113/jphysiol.2006.122200 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 156KN UT WOS:000245646900026 PM 17234700 ER PT J AU Mainero, C Zhang, WT Kumar, A Rosen, BR Sorensen, AG AF Mainero, Caterina Zhang, Wei-Ting Kumar, Ashok Rosen, Bruce R. Sorensen, A. Gregory TI Mapping the spinal and supraspinal pathways of dynamic mechanical allodynia in the human trigeminal system using cardiac-gated fMRI SO NEUROIMAGE LA English DT Article DE fMRI; allodynia; mechanical; brainstem; pain modulation ID DORSAL-HORN NEURONS; BRUSH-EVOKED ALLODYNIA; PERIAQUEDUCTAL GRAY-MATTER; NEUROPATHIC PAIN PATIENTS; BRAIN-STEM; SECONDARY HYPERALGESIA; ELECTRICAL-STIMULATION; NEURAL ACTIVATION; LOCUS-COERULEUS; HAIRY SKIN AB Following injury and inflammation, pain to light stroking (dynamic mechanical allodynia) might develop at the damaged site (primary area) or in adjacent normal tissue (secondary area). Using fMRI we mapped changes in the spinal trigeminal nucleus (spV), and supraspinal brainstem nuclei following heat/capsaicin-induced primary and secondary dynamic mechanical allodynia in the human trigeminal system. The role of these structures in dynamic mechanical allodynia has not been clarified yet in humans. During the control session we applied the same mechanical stimuli to the same untreated trigeminal area. Primary and secondary mechanical allodynia showed equal levels of perceived pain intensity, and compared to control mechanical stimulation exhibited similar responses in the ipsilateral spV and contralateral ventrolateral periaqueductal gray (APAG). Activity in the spV was significantly higher during both conditions versus the control mechanical stimulation, indicating that central sensitization of second-order neurons is similar for primary and secondary mechanical allodynia. The APAG showed decreased activity that inversely correlated with pain ratings during primary allodynia, i.e. the more deactivated the APAG the higher the pain intensity (p < 0.05, Pearson's correlation). Primary and secondary dynamic mechanical allodynia were also characterized by significant differences involving distinct supraspinal structures mainly involved in pain modulation and including the rostroventromedial medulla, pons reticular formation, dorsolateral PAG, all more active during primary versus secondary allodynia, and the medial reticular formation of the caudal medulla that was more active during secondary versus primary allodynia. These results indicate that the pain modulatory system is involved to a different extent during primary versus secondary mechanical allodynia. (C) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Mainero, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149 2301,13th St, Charlestown, MA 02129 USA. EM caterina@nmr.mgh.harvard.edu FU NCRR NIH HHS [M01-RR-01066, P41 RR014075, P41RR014075, M01 RR001066]; NINDS NIH HHS [5P01 NS35611-07, P01 NS035611, P01 NS035611-07] NR 53 TC 36 Z9 36 U1 2 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR 15 PY 2007 VL 35 IS 3 BP 1201 EP 1210 DI 10.1016/j.neuroimage.2007.01.024 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 160PZ UT WOS:000245956100020 PM 17336547 ER PT J AU Schendan, HE Stem, CE AF Schendan, Haline E. Stem, Chantal E. TI Mental rotation and object categorization share a common network of prefrontal and dorsal and ventral regions of posterior cortex SO NEUROIMAGE LA English DT Article ID LATERAL OCCIPITAL COMPLEX; DISTINCT NEURAL MECHANISMS; VISUAL-SPATIAL ATTENTION; PARIETAL CORTEX; WORKING-MEMORY; CORTICAL ACTIVITY; FRONTAL-CORTEX; HUMAN BRAIN; FUNCTIONAL-ORGANIZATION; 3-DIMENSIONAL OBJECTS AB The multiple-views - plus-transformation variant of object model verification theories predicts that parietal regions that are critical for mental rotation contribute to visual object cognition. Some neuroimaging studies have shown that the intraparietal sulcus region is critically involved in mental rotation. Other studies indicate that both ventral and dorsal posterior regions are object-sensitive and involved in object perception and categorization tasks. However, it is unknown whether dorsal object-sensitive areas overlap with regions recruited for object mental rotation. Functional magnetic resonance imaging was used to test this directly. Participants performed standard tasks of object categorization, mental rotation, and eye movements. Results provided clear support for the prediction, demonstrating overlap between dorsal object-sensitive regions in ventral-caudal intraparietal sulcus (vcIPS) and an adjacent dorsal occipital area and the regions that are activated during mental rotation but not during saccades. In addition, object mental rotation (but not saccades) activated object-sensitive areas in lateral dorsal occipitotemporal cortex (DOT), and both mental rotation and object categorization recruited ventrolateral prefrontal cortex areas implicated in attention, working memory, and cognitive control. These findings provide clear evidence that a prefrontal-posterior cortical system implicated in mental rotation, including the occipitoparietal regions critical for this spatial task, is recruited during visual object categorization. Altogether, the findings provide a key link in understanding the role of dorsal find ventral visual areas in spatial and object perception and cognition: Regions in occipitoparietal cortex, as well as DOT cortex, have a general role in visual object cognition, supporting not only mental rotation but also categorization. (c) 2007 Elsevier Inc. All rights reserved. C1 Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Tufts Univ, Dept Psychol, Ctr Memory & Brain, Medford, MA 02215 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Schendan, HE (reprint author), Tufts Univ, Dept Psychol, 490 Boston Ave, Medford, MA 02155 USA. EM Haline_E.Schendan@tufts.edu OI Schendan, Haline/0000-0001-8925-5605 FU NCRR NIH HHS [P41RR14075]; NIA NIH HHS [F32 AG05914]; NIMH NIH HHS [P50 MH071702]; NINDS NIH HHS [9R01 NS052914] NR 98 TC 29 Z9 30 U1 1 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR 15 PY 2007 VL 35 IS 3 BP 1264 EP 1277 DI 10.1016/j.neuroimage.2007.01.012 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 160PZ UT WOS:000245956100027 PM 17346989 ER PT J AU Greene, AK Austen, WG May, JW AF Greene, Arin K. Austen, William G., Jr. May, James W., Jr. TI Flap ischemia after pedicled tissue transfer to a lateral thigh wound: An example of complication assessment using the end result system of E. A. Codman SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID INFERIOR EPIGASTRIC FLAP C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02114 USA. RP May, JW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, 15 Fruit St,WACC 453, Boston, MA 02114 USA. EM jwmay@partners.org NR 5 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD APR 15 PY 2007 VL 119 IS 5 BP 1599 EP 1603 DI 10.1097/01.prs.0000258526.72868.e8 PG 5 WC Surgery SC Surgery GA 157IH UT WOS:000245711700025 PM 17415256 ER PT J AU Greene, AK May, JW AF Greene, Arin K. May, James W., Jr. TI Ernest Amory Codman, MD (1869 to 1940): The influence of the end result idea on plastic and reconstructive surgery SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. RP May, JW (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg, 15 Fruit St, Boston, MA 02114 USA. EM jwmay@partners.org NR 10 TC 4 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD APR 15 PY 2007 VL 119 IS 5 BP 1606 EP 1609 DI 10.1097/01.prs.0000258529.62886.c1 PG 4 WC Surgery SC Surgery GA 157IH UT WOS:000245711700027 PM 17415258 ER PT J AU Netscher, DT Baumholtz, MA AF Netscher, David T. Baumholtz, Michael A. TI Treatment of congenital upper extremity problems SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article AB Learning Objectives: After studying this article, the participant should be able to: 1. Describe the terminology and classification of congenital hand anomalies. 2. Describe the incidence and embryogenesis of some common congenital hand anomalies. 3. Discuss the general principles and goals for treatment of congenital hand anomalies. 4. Describe the management of five of the more common congenital hand anomalies (syndactyly, short digits, thumb duplication, hypoplastic thumb, and radial dysplasia). Summary: Congenital hand anomalies can cause substantial emotional and functional problems. This article reviews the etiology, classification, and management of some of the more common hand anomalies. A general approach to the patient and the goals of treatment are reviewed, as is the approach to five specific congenital hand anomalies: syndactyly, short digits, thumb duplication, hypoplastic thumb, and radial dysplasia. C1 Baylor Coll Med, Div Plast Surg, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Plast Surg Sect, Houston, TX USA. RP Netscher, DT (reprint author), Baylor Coll Med, Div Plast Surg, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD APR 15 PY 2007 VL 119 IS 5 BP 1611 EP 1612 DI 10.1097/01.prs.0000258535.31613.43 PG 2 WC Surgery SC Surgery GA 157IH UT WOS:000245711700028 ER PT J AU Rauch, SL Wright, CI Savage, CR Martis, B McMullin, KG Wedig, MM Gold, AL Keuthen, NJ AF Rauch, Scott L. Wright, Christopher I. Savage, Cary R. Martis, Brian McMullin, Katherine G. Wedig, Michelle M. Gold, Andrea L. Keuthen, Nancy J. TI Brain activation during implicit sequence learning in individuals with trichotillomania SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE serial reaction time; striatum; imaging; obsessive-compulsive disorder ID OBSESSIVE-COMPULSIVE DISORDER; SPECTRUM DISORDERS; STRIATAL DYSFUNCTION; HAIR PULLERS; DOUBLE-BLIND; PET; PHENOMENOLOGY; COMORBIDITY; FLUOXETINE; INVENTORY AB Trichotillomania (TTM) may be related to obsessive-compulsive disorder (OCD) and other neuropsychiatric conditions characterized by cortico-striatal dysfunction. Functional imaging studies of OCD using an implicit learning task have found abnormalities in striatal and hippocampal activation. The current study investigated whether similar abnormalities occur in TTM. Functional MRI and the serial reaction time (SRT) task were used to assess striatal and hippocampal activation during implicit sequence learning in TTM and healthy control (HQ subjects. The results for 20 age- and education-matched participants (10 TTM, 10 HQ are reported. In comparison with HC participants, those with TTM exhibited no significant differences in implicit learning, or in activation within the striatum, hippocampus, or other brain regions. The current findings do not provide evidence for cortico-striatal dysfunction in TTM. Future studies directly comparing OCD and TTM subjects are warranted to confirm the specificity of abnormal striatal and hippocampal findings during implicit sequence learning in OCD. (C) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Univ Kansas, Med Ctr, Hoglund Brain Imaging Ctr, Kansas City, KS 66103 USA. Univ Kansas, Med Ctr, Dept Psychiat, Kansas City, KS 66103 USA. Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Rauch, SL (reprint author), McLean Hosp, Dept Psychiat, 115 Mill St, Belmont, MA 02478 USA. EM srauch@partners.org RI Citations, TLC SAB/C-4006-2011; OI Gold, Andrea/0000-0003-4447-776X FU NIMH NIH HHS [MH60219, MH64806] NR 41 TC 21 Z9 21 U1 3 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD APR 15 PY 2007 VL 154 IS 3 BP 233 EP 240 DI 10.1016/j.pscychresns.2006.09.002 PG 8 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 163AY UT WOS:000246132000004 PM 17321724 ER PT J AU Fu, RW Harris, EL Helfand, M Nelson, HD AF Fu, Rongwei Harris, Emily L. Helfand, Mark Nelson, Heidi D. TI Estimating risk of breast cancer in carriers of BRCA1 and BRCA2 mutations: A meta-analytic approach SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT 10th Biennial Symposium on Statistical Methods CY 2007 CL Washington, DC SP CDC, ATSDR, Washington Statist Soc, Rutgers Univ, Ctr Discrete Math & Comp Sci, SAG, Statist Advisory Grp DE penetrance; BRCA mutations; meta-analysis; breast cancer risk; prevalence; family history ID OVARIAN-CANCER; FAMILY-HISTORY; JEWISH WOMEN; FOUNDER MUTATIONS; ASHKENAZI WOMEN; COMMON BRCA1; CASE SERIES; POPULATION; PENETRANCE; PREVALENCE AB Estimates of penetrance (or risk) of breast cancer among BRCA mutation carriers in published studies are heterogeneous, prohibiting direct combined estimates. Estimates of prevalence of hRCA mutations are more homogeneous and could allow combined estimates of prevalence. We propose a combined estimator of penetrance from combined estimates of the prevalence of BRCA mutations in women with and without breast cancer and from the probability of breast cancer by using Bayes' Theorem. The relative risk of having breast cancer with positive family history and the prevalence of positive family history contribute to the combined estimate of penetrance if family history is present. The combined estimate incorporates variation in estimates from different resources. The method is illustrated by using data from Ashkenazi Jewish women unselected for family history and for those with family history. Risks of breast cancer conferred by BRCA1 and BRCA2 mutations are estimated to be 8.39 per cent (6.56, 10.68 per cent) and 2.66 per cent (1.85, 3.82 per cent) by 40 years old, and 47.45 per cent (37.39, 57.72 per cent) and 31.85 per cent (23.72, 41.26 per cent) by 75 years old, respectively. For those with family history, risks of breast cancer conferred by BRCA mutations appear to be higher. Copyright (c) 2007 John Wiley & Sons, Ltd. C1 Oregon Hlth & Sci Univ, Oregon Evidence Based Pract Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Emergency Med, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. Providence Hlth & Serv, Portland, OR USA. RP Fu, RW (reprint author), Oregon Hlth & Sci Univ, Oregon Evidence Based Pract Ctr, 3181 SW Sam Jackson Pk Rd,CB669, Portland, OR 97239 USA. EM fur@ohsu.edu FU PHS HHS [290-02-0024] NR 40 TC 6 Z9 6 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD APR 15 PY 2007 VL 26 IS 8 BP 1775 EP 1787 DI 10.1002/sim.2811 PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 149JI UT WOS:000245142800011 PM 17243094 ER PT J AU Perlis, RH AF Perlis, Roy H. TI Cytochrome P450 genotyping and antidepressants - An imperfect measure of a modest predictor of response to antidepressants may not be ready for clinical application SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Depress & Bipolar Clin & Res Programs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Depress & Bipolar Clin & Res Programs, Boston, MA 02114 USA. EM rperlis@partners.org NR 0 TC 9 Z9 9 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8146 J9 BRIT MED J JI Br. Med. J. PD APR 14 PY 2007 VL 334 IS 7597 BP 759 EP 759 DI 10.1136/bmj.39169.547512.80 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 161SX UT WOS:000246037300004 PM 17431233 ER PT J AU Riley, DE Jeon, JS Krieger, JN AF Riley, Donald E. Jeon, Joon Seong Krieger, John N. TI Simple repeat evolution includes dramatic primary sequence changes that conserve folding potential SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE short tandem repeats; STR replacements; secondary structure preservation; simple repeats; microsatellites; evolution; non-coding sequences; UTRs ID SHORT TANDEM REPEATS; MESSENGER-RNA; ALLELE SIZE; MICROSATELLITES; HYBRIDIZATION; REPLACEMENTS; CONSTRAINTS; PREDICTION; MULTIPLE; ELEMENTS AB We previously demonstrated that many "weak-folding" simple repeats were replaced during evolution by alternative weak-folding repeats. This suggested repeat selection at the level of higher order structure potential. Here, we demonstrate similar phenomena for "strong-folding" simple repeats in non-coding DNA. The Rabgap1 gene's 3' UTR contained the self-complementary repeat (AT)n in Homo sapiens but, in Mus musculus, this site was occupied by the complementary repeats (GT)n and (AC)n. Similarly, primate Plag1 UTRs contained various (GT)n-(AC)n palindromes but in rodents, this site was occupied by (AT)n, preserving folding potential more than primary sequence. The Znf516, Senp1, Rock2, and other UTRs exhibited similar replacements. In the Bnc2 UTR, (AT)n was replaced by sequences that evolved with approximate symmetry about a central axis, a pattern difficult to explain without invoking selection to preserve secondary structure. These observations reflect a predictable evolutionary pattern for some common non-coding genomic sequences. (c) 2007 Elsevier Inc. All rights reserved. C1 VA Puget Sound Healthcare Syst, Dept Res, Seattle, WA 98012 USA. Univ Washington, Dept Urol, Seattle, WA 98195 USA. Inje Univ, Iksan Paik Hosp, Dept Urol, Koyang Si 411706, Kyunggi Do, South Korea. RP Riley, DE (reprint author), VA Puget Sound Healthcare 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 25 TC 8 Z9 8 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 13 PY 2007 VL 355 IS 3 BP 619 EP 625 DI 10.1016/j.bbrc.2007.01.200 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 147KG UT WOS:000245001300004 PM 17320822 ER PT J AU Scremin, OU Li, MG Scremin, AME AF Scremin, O. U. Li, M. G. Scremin, A. M. E. TI Cortical contusion induces trans-hemispheric reorganization of blood flow maps SO BRAIN RESEARCH LA English DT Article DE cerebrovascular circulation; brain injury; cerebral ischemia; functional imaging ID BRAIN-INJURY; RAT SMI; MODULATION; MECHANISMS; CORTEX AB Cerebral blood flow (CBF), a surrogate of neural activity in the identification of brain regions involved in specific functions, has been used in this report to trace the compensatory enhancement of activity in non-traumatized areas of the brain following a focal lesion. We have previously shown activation of CBF in the cortex contralateral to a focal contusion, 24 h after the event. The present report extends the characterization of this trans-hemispheric cortical blood flow activation by studying its time course and regional distribution from 4 days to 4 weeks post-trauma. Adult male Sprague-Dawley rats received a cortical impact through a 6.3 mm craniotomy under halothane anesthesia. CBF was measured with the quantitative autoradio graphic C-14-lodoantipyrine technique, in conscious animals, 4 days, 2 weeks and 4 weeks post-trauma. CBF was severely decreased at the site of impact where necrosis developed later, and it remained depressed in the surrounding areas throughout the observation period. Trans-hemispheric CBF enhancement was maximal at 4 days and it returned to control levels 28 days post-trauma. This phenomenon was present in all cortical regions symmetrical to the impact zone, but also in auditory, visual, entorhinal and insular cortex. These results suggest that the participation of the contralateral cortex in the recovery from unilateral brain trauma is not limited to the regions homologous to those that received the impact. The time course of CBF changes was found to be consistent with the recovery of motor function in this model. (c) 2007 Elsevier B.V. All rights reserved. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. RP Scremin, OU (reprint author), VA Greater Los Angeles Healthcare Syst, Bldg 15,Room 319,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM oscremin@ucla.edu NR 20 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 13 PY 2007 VL 1141 BP 235 EP 241 DI 10.1016/j.brainres.2007.01.006 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 154FG UT WOS:000245491700026 PM 17275796 ER PT J AU Baran, Y Salas, A Senkal, CE Gunduz, U Bielawski, J Obeid, LM Ogretmen, B AF Baran, Yusuf Salas, Arelis Senkal, Can E. Gunduz, Ufuk Bielawski, Jacek Obeid, Lina M. Ogretmen, Besim TI Alterations of ceramide/sphingosine 1-phosphate rheostat involved in the regulation of resistance to imatinib-induced apoptosis in K562 human chronic myeloid leukemia cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; LONGEVITY ASSURANCE GENE-1; HUMAN ACID CERAMIDASE; SPHINGOSINE 1-PHOSPHATE; TYROSINE KINASE; DIHYDROCERAMIDE SYNTHASE; FAMILY-MEMBERS; CANCER-THERAPY; HUMAN HEAD; PROTEIN AB In this study, mechanisms of resistance to imatinib-induced apoptosis in human K562 cells were examined. Continuous exposure to stepwise increasing concentrations of imatinib resulted in the selection of K562/IMA-0.2 and -1 cells, which expressed similar to 2.3- and 19-fold resistance, respectively. Measurement of endogenous ceramides by high performance liquid chromatography/mass spectroscopy showed that treatment with imatinib increased the generation of ceramide, mainly C-18-ceramide, which is generated by the human longevity assurance gene 1 (hLASS1), in sensitive, but not in resistant cells. Inhibition of hLASS1 by small interfering RNA partially prevented imatinib-induced cell death in sensitive cells. In reciprocal experiments, overexpression of hLASS1, and not hLASS6, in drug-resistant cells caused a marked increase in imatinib-induced C-18-ceramide generation, and enhanced apoptosis. Interestingly, there were no defects in the levels of mRNA and enzyme activity levels of hLASS1 for ceramide generation in K562/IMA-1 cells. However, expression levels of sphingosine kinase-1 (SK1) and generation of sphingosine 1-phosphate (S1P) were increased significantly in K562/IMA-1 cells, channeling sphingoid bases to the sphingosine kinase pathway. The partial inhibition of SK1 expression by small interference RNA modulated S1P levels and increased sensitivity to imatinib-induced apoptosis in resistant cells. On the other hand, forced expression of SK1 in K562 cells increased the ratio between total S1P/C-18-ceramide levels similar to 6-fold and prevented apoptosis significantly in response to imatinib. Additional data indicated a role for SK1/S1P signaling in the up-regulation of the Bcr-Abl expression at the post-transcriptional level, which suggested a possible mechanism for resistance to imatinib-mediated apoptosis. In conclusion, these data suggest a role for endogenous C-18-ceramide synthesis mainly via hLASS1 in imatinib-induced apoptosis in sensitive cells, whereas in resistant cells, alterations of the balance between the levels of ceramide and S1P by overexpression of SK1 result in resistance to imatinib-induced apoptosis. C1 Med Univ S Carolina, Div Gen Internal Med, Ralph H Johnson Vet Adm Hosp, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Ralph H Johnson Vet Adm Hosp, Charleston, SC 29425 USA. Med Univ S Carolina, Hollings Canc Ctr, Ralph H Johnson Vet Adm Hosp, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Middle E Tech Univ, Dept Biol, TR-06531 Ankara, Turkey. RP Ogretmen, B (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, Hollings Canc Ctr, 173 Ashley Ave, Charleston, SC 29425 USA. EM ogretmen@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [CA097132, CA88932]; NIDCR NIH HHS [DE01657] NR 56 TC 126 Z9 131 U1 2 U2 21 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 APR 13 PY 2007 VL 282 IS 15 BP 10922 EP 10934 DI 10.1074/jbc.M610157200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 160LG UT WOS:000245941500012 PM 17303574 ER PT J AU Copeland, LA Mortensen, EM Zeber, JE Pugh, MJ Restrepo, MI Dalack, GW AF Copeland, Laurel A. Mortensen, Eric M. Zeber, John E. Pugh, Mary Jo Restrepo, Marcos I. Dalack, Gregory W. TI Pulmonary disease among inpatient decedents: Impact of schizophrenia SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE health services; mortality; respiratcry disorders; schizophrenia; veterans ID PLACEBO-CONTROLLED TRIAL; OF-VETERANS-AFFAIRS; MENTAL-ILLNESS; OLDER PATIENTS; INFLUENZA VACCINATION; PSYCHOTIC DISORDERS; TARDIVE-DYSKINESIA; SMOKING-CESSATION; MEDICAL-SERVICES; HEALTH-STATUS AB Objectives: Determine the risk associated with schizophrenia for common pulmonary illness (pneumonia and chronic obstructive pulmonary disorder (COPD)) during the last year of life. Methods: Inpatient decedents in Veterans (VA) hospitals in 2002 (N=27,798) were identified. Logistic regression modeled diagnosis of pulmonary illness in either the final year or final admission as a function of schizophrenia, smoking history and other covariates. Results: Among decedents, 943 (3%) had schizophrenia, 3% were women, most were white (76%) or African-American (18%), and average age at death was 72.4 years (SD 11.5). Three-fifths received VA outpatient care in the year prior to death. Among those with schizophrenia, only twofifths had outpatient care. Pneumonia was more common among schizophrenia patients (3 8% vs 3 1 %) as was COPD (46% vs 3 8%), In models controlling for history of smoking and other covariates, schizophrenia was a risk factor for pulmonary disease in the last year of life (OR= 1.9, 95% CI 1.6-2.2) but less so for final-stay pulmonary disease (OR= 1.5, 95% CI 1.3-1.7). Conclusions: VA inpatient decedents with schizophrenia were at increased risk for pneumonia and COPD, independent of smoking indicators. Clinicians treating schizophrenia patients need to be especially alert to potential comorbid medical conditions and ensure vulnerable patients receive appropriate care. Published by Elsevier Inc. C1 S Texas Vet Hlth Care Syst VERDICT, HSR&D, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. VA Ann Arbor Healthcare Syst, Dept Psychiat, Ann Arbor, MI 48105 USA. Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Copeland, LA (reprint author), S Texas Vet Hlth Care Syst VERDICT, HSR&D, 7400 Merton Minter,11c6, San Antonio, TX 78229 USA. EM copelandl@uthsesa.edu RI Restrepo, Marcos/H-4442-2014; OI Pugh, Mary Jo/0000-0003-4196-7763; Mortensen, Eric/0000-0002-3880-5563; Copeland, Laurel/0000-0002-9478-0209 NR 50 TC 24 Z9 24 U1 2 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD APR 13 PY 2007 VL 31 IS 3 BP 720 EP 726 DI 10.1016/j.pnpbp.2007.01.008 PG 7 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 163NH UT WOS:000246166100019 PM 17292522 ER PT J AU Romero, V Larsen, CE Duke-Cohan, JS Fox, EA Romero, T Clavijo, OP Fici, DA Husain, Z Almeciga, I Alford, DR Awdeh, ZL Zuniga, J El-Dahdah, L Alper, CA Yunis, EJ AF Romero, Viviana Larsen, Charles E. Duke-Cohan, Jonathan S. Fox, Edward A. Romero, Tatiana Clavijo, Olga P. Fici, Dolores A. Husain, Zaheed Almeciga, Ingrid Alford, Dennis R. Awdeh, Zuheir L. Zuniga, Joaquin El-Dahdah, Lama Alper, Chester A. Yunis, Edmond J. TI Genetic fixity in the human major histocompatibility complex and block size diversity in the class I region including HLA-E SO BMC GENETICS LA English DT Article ID CONSERVED EXTENDED HAPLOTYPES; LINKAGE DISEQUILIBRIUM; HUMAN GENOME; HUMAN MHC; DISEASE; POPULATION; CD94/NKG2A; DNA; RECOMBINATION; ALLELE AB Background: The definition of human MHC class I haplotypes through association of HLA-A, HLA-Cw and HLA-B has been used to analyze ethnicity, population migrations and disease association. Results: Here, we present HLA-E allele haplotype association and population linkage disequilibrium (LD) analysis within the similar to 1.3 Mb bounded by HLA-B/Cw and HLA-A to increase the resolution of identified class I haplotypes. Through local breakdown of LD, we inferred ancestral recombination points both upstream and downstream of HLA-E contributing to alternative block structures within previously identified haplotypes. Through single nucleotide polymorphism (SNP) analysis of the MHC region, we also confirmed the essential genetic fixity, previously inferred by MHC allele analysis, of three conserved extended haplotypes (CEHs), and we demonstrated that commercially-available SNP analysis can be used in the MHC to help define CEHs and CEH fragments. Conclusion: We conclude that to generate high-resolution maps for relating MHC haplotypes to disease susceptibility, both SNP and MHC allele analysis must be conducted as complementary techniques. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. CBR Inst Biomed Res, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Mol Diagnost Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Inst Nacl Enfermed Resp, Mexico City, DF, Mexico. Mayo Clin & Mayo Fdn, Dept Med Genet, Rochester, MN 55905 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Yunis, EJ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM Viviana_romero@dfci.harvard.edu; larsen@cbr.med.harvard.edu; Jonathan_Duke-Cohan@dfci.harvard.edu; Edward_Fox@dfci.harvard.edu; tatianapantazopoulos@gmail.com; olga_clavijo@dfci.harvard.eud; fici@cbrinstitute.org; husain@cbrinstitute.org; ialmeci@yahoo.com; alford@cbrinstitute.org; awdeh@cbrinstitute.org; Joaquin_zuniga@dfci.harvard.edu; l-el@md.northwestern.edu; alper@cbr.med.harvard.edu; edmond_yunis@dfci.harvard.edu OI Duke-Cohan, Jonathan/0000-0002-9478-9609 FU NHLBI NIH HHS [P01 HL029583, HL-29583, HL-59838, R01 HL059838] NR 39 TC 15 Z9 15 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD APR 12 PY 2007 VL 8 AR 14 DI 10.1186/1471-2156-8-14 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 158OP UT WOS:000245801100001 PM 17430593 ER PT J AU Golub, TR AF Golub, Todd R. TI Genomics - Global views of leukaemia SO NATURE LA English DT Editorial Material ID FUSION; GENE C1 Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. MIT, Cambridge, MA 02142 USA. Dana Farber Canc Inst, Cambridge, MA 02142 USA. RP Golub, TR (reprint author), Harvard Univ, Broad Inst, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM golub@broad.harvard.edu NR 5 TC 4 Z9 4 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 12 PY 2007 VL 446 IS 7137 BP 739 EP 740 DI 10.1038/446739a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 156CX UT WOS:000245626800024 PM 17429386 ER PT J AU Wright, AA Katz, IT AF Wright, Alexi A. Katz, Ingrid T. TI Tobacco tightrope - Balancing disease prevention and economic development in China SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Wright, AA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 4 TC 31 Z9 33 U1 1 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 12 PY 2007 VL 356 IS 15 BP 1493 EP 1496 DI 10.1056/NEJMp078018 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 156CA UT WOS:000245624400001 PM 17429080 ER PT J AU Boden, WE O'Rourke, RA Teo, KK Hartigan, PM Maron, DJ Kostuk, WJ Knudtson, M Dada, M Casperson, P Harris, CL Chaitman, BR Shaw, L Gosselin, G Nawaz, S Title, LM Gau, G Blaustein, AS Booth, DC Bates, ER Spertus, JA Berman, DS Mancini, GBJ Weintraub, WS Boden, W O'Rourke, R Teo, K Hartigan, P Weintraub, W Maron, D Mancini, J Weintraub, W Boden, W O'Rourke, R Teo, K Hartigan, P Knudtson, M Maron, D Bates, E Blaustein, A Booth, D Carere, R Ellis, S Gosselin, G Gau, G Jacobs, A King, S Kostuk, W Harris, C Spertus, J Peduzzi, P Ryan, T Turnbull, B Feldman, T Bonow, R Haskell, W Diehr, P Lachenbruch, P Waters, D Johnstone, D Cohen, L Cantin, B Hager, W Samaha, F Januzzi, J Arrighi, J Chaitman, B Weintraub, W Hartigan, P O'Rourke, R Boden, W Barnett, P Spertus, J Goeree, R Maron, D Boden, W O'Rourke, R Teo, K Weintraub, W Peduzzi, P Antonelli, M Smith, J Kilstrom, R Hunter, B O'Neil, S Economou, T Nabors, J Kossack, A Sather, M Harris, C Gagne, W Fye, C Marottoli, R Allore, H Beckwith, D Farrell, W Feldman, R Mehta, R Neiderman, J Perry, E Kasl, S Zeman, M O'Leary, T Huang, G Boden, W Dada, M Potter, K Rivera, T O'Rourke, R Casperson, P O'Shea, A Teo, K Woodcock, G Weintraub, W Barnett, P Goeree, R O'Brien, B Mancini, GBJ Yeoh, E Ladenson, J Thompson, V Chaitman, B Bertran, T Berman, D Gerlach, J Littman, R Shaw, L Calfas, K Sallis, J O'Rourke, R Baker, P Bolton, J Blaustein, A Rowe, C Morris, K Hoffman, S Sedlis, S Keary, M Duvernoy, C Majors, C Shockey, M Zoble, R Fernandez, I Lehmann, K Sorley, A Abel, M Sheldon, M Wagoner, K Murphy, E Avalos, K Rossen, J Schneider, K Molavi, B Garza, L Barton, P Mavromatis, K Forghani, Z Smith, R Mitchell, C Ramanathan, K Touchstone, T Kostuk, W Sridhar, K Carr, S Wiseman, D Nawaz, S Dion, C Gosselin, G Theberge, J Cuso, M Title, L Simon, P Carroll, L Courtney-Cox, K Cohen, E Hsu, E Dzavik, V Lan, J Knudtson, M Lundberg, D Natarajan, M Cappelli, G Kutryk, M DiMarco, A Strauss, B Fung, A Chow, J Marr, D Fitzgerald, F Carere, R Nacario, T Tymchak, W Harris, L Lazzam, C Carter, A Palisaitis, D Mercure, C Bell, M Peterson, M Vicari, R Carroll, M Bates, E Luciano, A Mahrer, P Reyes, S Saucedo, J Vanwieren, D O'Keefe, J Kennedy, P Jacobs, A Berger, C Mayo, S Miller, J Arnold, T Kiernan, F Murphy, D Kugelmass, A Pangilinan, R Schwartz, R Caufield, L Hansen, D Mitchell, C Carhart, R Pennella, A Ellis, S Stevenson, C Krone, R Humphrey, J Appleton, C Wisbey, J Stillabower, M Davidson, M Mathien, J AF Boden, William E. O'Rourke, Robert A. Teo, Koon K. Hartigan, Pamela M. Maron, David J. Kostuk, William J. Knudtson, Merril Dada, Marcin Casperson, Paul Harris, Crystal L. Chaitman, Bernard R. Shaw, Leslee Gosselin, Gilbert Nawaz, Shah Title, Lawrence M. Gau, Gerald Blaustein, Alvin S. Booth, David C. Bates, Eric R. Spertus, John A. Berman, Daniel S. Mancini, G. B. John Weintraub, William S. Boden, W. O'Rourke, R. Teo, K. Hartigan, P. Weintraub, W. Maron, D. Mancini, J. Weintraub, W. Boden, W. O'Rourke, R. Teo, K. Hartigan, P. Knudtson, M. Maron, D. Bates, E. Blaustein, A. Booth, D. Carere, R. Ellis, S. Gosselin, G. Gau, G. Jacobs, A. King, S., III Kostuk, W. Harris, C. Spertus, J. Peduzzi, P. Ryan, T. Turnbull, B. Feldman, T. Bonow, R. Haskell, W. Diehr, P. Lachenbruch, P. Waters, D. Johnstone, D. Cohen, L. Cantin, B. Hager, W. Samaha, F. Januzzi, J. Arrighi, J. Chaitman, B. Weintraub, W. Hartigan, P. O'Rourke, R. Boden, W. Barnett, P. Spertus, J. Goeree, R. Maron, D. Boden, W. O'Rourke, R. Teo, K. Weintraub, W. Peduzzi, P. Antonelli, M. Smith, J. Kilstrom, R. Hunter, B. O'Neil, S. Economou, T. Nabors, J. Kossack, A. Sather, M. Harris, C. Gagne, W. Fye, C. Marottoli, R. Allore, H. Beckwith, D. Farrell, W. Feldman, R. Mehta, R. Neiderman, J. Perry, E. Kasl, S. Zeman, M. O'Leary, T. Huang, G. Boden, W. Dada, M. Potter, K. Rivera, T. O'Rourke, R. Casperson, P. O'Shea, A. Teo, K. Woodcock, G. Weintraub, W. Barnett, P. Goeree, R. O'Brien, B. Mancini, G. B. J. Yeoh, E. Ladenson, J. Thompson, V. Chaitman, B. Bertran, T. Berman, D. Gerlach, J. Littman, R. Shaw, L. Calfas, K. Sallis, J. O'Rourke, R. Baker, P. Bolton, J. Blaustein, A. Rowe, C. Morris, K. Hoffman, S. Sedlis, S. Keary, M. Duvernoy, C. Majors, C. Shockey, M. Zoble, R. Fernandez, I. Lehmann, K. Sorley, A. Abel, M. Sheldon, M. Wagoner, K. Murphy, E. Avalos, K. Rossen, J. Schneider, K. Molavi, B. Garza, L. Barton, P. Mavromatis, K. Forghani, Z. Smith, R. Mitchell, C. Ramanathan, K. Touchstone, T. Kostuk, W. Sridhar, K. Carr, S. Wiseman, D. Nawaz, S. Dion, C. Gosselin, G. Theberge, J. Cuso, M. Title, L. Simon, P. Carroll, L. Courtney-Cox, K. Cohen, E. Hsu, E. Dzavik, V. Lan, J. Knudtson, M. Lundberg, D. Natarajan, M. Cappelli, G. Kutryk, M. DiMarco, A. Strauss, B. Fung, A. Chow, J. Marr, D. Fitzgerald, F. Carere, R. Nacario, T. Tymchak, W. Harris, L. Lazzam, C. Carter, A. Palisaitis, D. Mercure, C. Bell, M. Peterson, M. Vicari, R. Carroll, M. Bates, E. Luciano, A. Mahrer, P. Reyes, S. Saucedo, J. vanWieren, D. O'Keefe, J. Kennedy, P. Jacobs, A. Berger, C. Mayo, S. Miller, J. Arnold, T. Kiernan, F. Murphy, D. Kugelmass, A. Pangilinan, R. Schwartz, R. Caufield, L. Hansen, D. Mitchell, C. Carhart, R. Pennella, A. Ellis, S. Stevenson, C. Krone, R. Humphrey, J. Appleton, C. Wisbey, J. Stillabower, M. Davidson, M. Mathien, J. CA COURAGE Trial Res Grp TI Optimal medical therapy with or without PCI for stable coronary disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID EVALUATION COURAGE TRIAL; BARE-METAL STENTS; OUTCOMES UTILIZING REVASCULARIZATION; RANDOMIZED CLINICAL-TRIALS; SIROLIMUS-ELUTING STENTS; MYOCARDIAL-INFARCTION; ARTERY-DISEASE; CARDIOVASCULAR EVENTS; HEART-DISEASE; RITA-2 TRIAL AB Background: In patients with stable coronary artery disease, it remains unclear whether an initial management strategy of percutaneous coronary intervention (PCI) with intensive pharmacologic therapy and lifestyle intervention (optimal medical therapy) is superior to optimal medical therapy alone in reducing the risk of cardiovascular events. Methods: We conducted a randomized trial involving 2287 patients who had objective evidence of myocardial ischemia and significant coronary artery disease at 50 U.S. and Canadian centers. Between 1999 and 2004, we assigned 1149 patients to undergo PCI with optimal medical therapy (PCI group) and 1138 to receive optimal medical therapy alone (medical-therapy group). The primary outcome was death from any cause and nonfatal myocardial infarction during a follow-up period of 2.5 to 7.0 years (median, 4.6). Results: There were 211 primary events in the PCI group and 202 events in the medical-therapy group. The 4.6-year cumulative primary-event rates were 19.0% in the PCI group and 18.5% in the medical-therapy group (hazard ratio for the PCI group, 1.05; 95% confidence interval [CI], 0.87 to 1.27; P=0.62). There were no significant differences between the PCI group and the medical-therapy group in the composite of death, myocardial infarction, and stroke (20.0% vs. 19.5%; hazard ratio, 1.05; 95% CI, 0.87 to 1.27; P=0.62); hospitalization for acute coronary syndrome (12.4% vs. 11.8%; hazard ratio, 1.07; 95% CI, 0.84 to 1.37; P=0.56); or myocardial infarction (13.2% vs. 12.3%; hazard ratio, 1.13; 95% CI, 0.89 to 1.43; P=0.33). Conclusions: As an initial management strategy in patients with stable coronary artery disease, PCI did not reduce the risk of death, myocardial infarction, or other major cardiovascular events when added to optimal medical therapy. C1 SUNY Buffalo, Buffalo Gen Hosp, Div Cardiol, Buffalo, NY 14203 USA. Western New York Vet Affairs VA Healthcare Networ, Buffalo, NY USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. McMaster Univ, Med Ctr, Hamilton, ON, Canada. VA Connecticut Healthcare Syst, Cooperat Studies Program Coordinating Ctr, West Haven, CT USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. London Hlth Sci Ctr, London, ON, Canada. Foothills Prov Gen Hosp, Calgary, AB T2N 2T9, Canada. Hartford Hosp, Hartford, CT 06115 USA. VA Cooperat Studies Program Clin Res Pharm Coordi, Albuquerque, NM USA. St Louis Univ, St Louis, MO 63103 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. Sudbury Reg Hosp, Sudbury, ON, Canada. Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. Mayo Clin, Rochester, MN USA. Houston VA Med Ctr, Houston, TX USA. Lexington VA Med Ctr, Lexington, KY USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. Vancouver Hosp & Hlth Sci Ctr, Vancouver, BC V5Z 1M9, Canada. Christiana Care Hlth Syst, Newark, DE USA. RP Boden, WE (reprint author), SUNY Buffalo, Buffalo Gen Hosp, Div Cardiol, 100 High St, Buffalo, NY 14203 USA. EM wboden@kaleidahealth.org NR 51 TC 1832 Z9 1952 U1 10 U2 66 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 APR 12 PY 2007 VL 356 IS 15 BP 1503 EP 1516 DI 10.1056/NEJMoa070829 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 156CA UT WOS:000245624400004 PM 17387127 ER PT J AU Greer, DM Plotkin, SR Hasserjian, RP Harris, NL Steere, AC AF Greer, David M. Plotkin, Scott R. Hasserjian, Robert P. Harris, Nancy Lee Steere, Allen C. TI A 59-year-old man with neck pain, weakness in the arms, and cranial-nerve palsies - Lyme disease of the nervous system (neuroborreliosis). SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CEREBROSPINAL-FLUID; BORRELIA-BURGDORFERI; BANNWARTHS SYNDROME; ERYTHEMA MIGRANS; LYMPHOMA; BABESIOSIS; CELLS; MANIFESTATIONS; PARALYSIS; DIAGNOSIS 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. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. RP Greer, DM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 35 TC 7 Z9 8 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 12 PY 2007 VL 356 IS 15 BP 1561 EP 1570 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 156CA UT WOS:000245624400011 PM 17429088 ER PT J AU Fuchs, BB Tang, RJ Mylonakis, E AF Fuchs, Beth Burgwyn Tang, Robin J. Mylonakis, Eleftherios TI The Temperature-Sensitive Role of Cryptococcus neoformans ROM2 in Cell Morphogenesis SO PLOS ONE LA English DT Article AB ROM2 is associated with Cryptococcus neoformans virulence. We examined additional roles of ROM2 in C. neoformans and found that ROM2 plays a role in several cell functions specifically at high temperature conditions. Morphologically rom2 mutant cells demonstrated a "tear"-like shape and clustered together. A sub-population of cells had a hyperelongated phenotype at restrictive growth conditions. Altered morphology was associated with defects in actin that was concentrated at the cell periphery and with abnormalities in microtubule organization. Interestingly, the ROM2 associated defects in cell morphology, location of nuclei, and actin and microtubule organization were not observed in cells grown at temperatures below 37 degrees C. These results indicate that in C. neoformans, ROM2 is important at restrictive temperature conditions and is involved in several cell maintenance functions. C1 [Fuchs, Beth Burgwyn; Tang, Robin J.; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Mylonakis, E (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM emylonakis@partners.org FU NIH [AI63084-01]; Ellison Medical Foundation FX Funding: A K08 award AI63084-01 from the NIH and a New Scholar Award in Global Infectious Diseases from the Ellison Medical Foundation, to EM, supported this work. NR 39 TC 7 Z9 8 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 11 PY 2007 VL 2 IS 4 AR e368 DI 10.1371/journal.pone.0000368 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10DT UT WOS:000207445400008 PM 17426816 ER PT J AU Mack, JW Cook, EF Wolfe, J Grier, HE Cleary, PD Weeks, JC AF Mack, Jennifer W. Cook, E. Francis Wolfe, Joanne Grier, Holcombe E. Cleary, Paul D. Weeks, Jane C. TI Understanding of prognosis among parents of children with cancer: Parental optimism and the parent-physician interaction SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INFORMATION NEEDS; PALLIATIVE CARE; BAD-NEWS; PREFERENCES; COMMUNICATION; PATIENT; PROGNOSTICATION; ONCOLOGISTS; DISCLOSURE; WANT AB Purpose Patients often overestimate their chances of surviving cancer. Factors that contribute to accurate understanding of prognosis are not known. We assessed understanding of likelihood of cure and functional outcome among parents of children with cancer and sought to identify factors that place parents at risk for overly optimistic beliefs about prognosis. Patients and Methods We conducted a cross-sectional survey of 194 parents of children with cancer ( response rate, 70%) who were treated at the Dana-Farber Cancer Institute and Children's Hospital in Boston, MA, and the children's physicians. Parent and physician expectations for likelihood of cure and functional outcome were compared. In 152 accurate or optimistic parents, we determined factors associated with accurate understanding of likelihood of cure compared with optimism. Results The majority of parents (61%) were more optimistic than physicians about the likelihood of cure. Parents' beliefs about other outcomes of cancer treatment were similar (quality-of-life impairment, P =.70) or more pessimistic ( physical impairment, P =.01; intellectual impairment, P =.01) than physicians' beliefs. Parents and physicians were more likely to agree about chances of cure when physicians had confidence in knowledge of prognosis ( odds ratio [ OR] = 2.55, P =.004) and allowed parents to take their preferred decision-making role ( OR = 1.89, P =.019). Conclusion Parents of children with cancer are overly optimistic about chances of cure but not about other outcomes of cancer therapy. Parents tend to be overly optimistic about cure when physicians have little confidence and when the decision-making process does not meet parents' preferences. These findings suggest that physicians are partly responsible for parents' unrealistic expectations about cure. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Childrens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Dept Epidemiol, Harvard Sch Publ Hlth, Boston, MA USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Mack, JW (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 44 Binney St, Boston, MA 02115 USA. EM jennifer_mack@dfci.harvard.edu FU AHRQ HHS [T32 HS00063] NR 40 TC 51 Z9 51 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 10 PY 2007 VL 25 IS 11 BP 1357 EP 1362 DI 10.1200/JCO.2006.08.3170 PG 6 WC Oncology SC Oncology GA 159FX UT WOS:000245851900011 PM 17416854 ER PT J AU Li, X Gold, B O'hUigin, C Diaz-Griffero, F Song, B Si, ZH Li, Y Yuan, W Stremlau, M Mische, C Javanbakht, H Scally, M Winkler, C Dean, M Sodroski, J AF Li, Xing Gold, Bert O'hUigin, Cohn Diaz-Griffero, Felipe Song, Byeongwoon Si, Zhihai Li, Yuan Yuan, Wen Stremlau, Matthew Mische, Claudia Javanbakht, Hassan Scally, Mark Winkler, Cheryl Dean, Michael Sodroski, Joseph TI Unique features of TRIM5 alpha among closely related human TRIM family members SO VIROLOGY LA English DT Article DE tripartite motif; restriction factor; retrovirus; nonsynonymous/synonymous; positive selection; capsid binding; B30.2(SPRY) domain; RING; RBCC ID IMMUNODEFICIENCY-VIRUS TYPE-1; RESTRICTION FACTOR TRIM5-ALPHA; COILED-COIL DOMAINS; RETROVIRAL RESTRICTION; POSTENTRY RESTRICTION; PRIMATE TRIM5-ALPHA; MONKEY TRIM5-ALPHA; CYTOPLASMIC BODIES; ADAPTIVE EVOLUTION; MOLECULAR-CLONING AB The tripartite motif (TRIM) protein, TRIM5 alpha, restricts some retroviruses, including human immunodeficiency virus (HIV-1), from infecting the cells of particular species. TRIM proteins contain RING, B-box, coiled-coil and, in some cases, B30.2(SPRY) domains. We investigated the properties of human TRIM family members closely related to TRIM5. These TRIM proteins, like TRIM5 alpha, assembled into homotrimers and colocalized in the cytoplasm with TRIM5 alpha. TRIM5 alpha turned over more rapidly than related TRIM proteins. TRIM5 alpha, TRIM34 and TRIM6 associated with HIV-1 capsid-nucleocapsid complexes assembled in vitro; the TRIM5 alpha and TRIM34 interactions with these complexes were dependent on their B30.2(SPRY) domains. Only TRIM5 alpha potently restricted infection by the retroviruses studied; overexpression of TRIM34 resulted in modest inhibition of simian immunodeficiency virus (SIVmac) infection. In contrast to the other TRIM genes examined, TRIM5 exhibited evidence of positive selection. The unique features of TRIM5 alpha among its TRIM relatives underscore its special status as an antiviral factor. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NCI, Lab Genom Divers, Frederick, MD 21702 USA. SAIC Frederick, Frederick, MD 21702 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu RI Li, Xing/D-3852-2009; Dean, Michael/G-8172-2012; Li, Yuan/B-4098-2013 OI Dean, Michael/0000-0003-2234-0631; FU NHLBI NIH HHS [HL54785]; NIAID NIH HHS [AI063987, AI28691, R01 AI063987] NR 61 TC 44 Z9 53 U1 1 U2 2 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 APR 10 PY 2007 VL 360 IS 2 BP 419 EP 433 DI 10.1016/j.virol.2006.10.035 PG 15 WC Virology SC Virology GA 155GO UT WOS:000245566100017 PM 17156811 ER PT J AU Wang, JH Huang, XD Huang, WD AF Wang, Jinhui Huang, Xudong Huang, Weidong TI A quantitative kinetic model for ATP-induced intracellular Ca2+ oscillations SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article DE calcium oscillations; sudden disappearance; biphasic release; endoplasmic reticulum; quantitative model ID INDUCED CALCIUM OSCILLATIONS; CYTOPLASMIC FREE CALCIUM; ENDOPLASMIC-RETICULUM; POSSIBLE MECHANISMS; MATHEMATICAL-MODEL; HELA-CELLS; CALRETICULIN; SIGNAL; BIRHYTHMICITY; PURINOCEPTORS AB A quantitative kinetic model is proposed to simulate the ATP-induced intracellular Ca2+ oscillations. The quantitative effect of ATP concentration upon the oscillations was successfully simulated. Our simulation results support previous experimental explanations that the Ca2+ oscillations are mainly due to interaction of Ca2+ release from the endoplasmic reticulum (ER) and the ATP-dependent Ca2+ pump back into the ER, and the oscillations are prolonged by extracellular Ca2+ entry that maintains the constant Ca2+ supplies to its intracellular stores. The model is also able to simulate the sudden disappearance phenomenon of the Ca2+ oscillations observed in some cell types by taking into account of the biphasic characteristic of the Ca2+ release from the endoplasmic reticulum (ER). Moreover, the model simulation results for the Ca2+ oscillations characteristics such as duration, peak [Ca2+](cyt), and average interval, etc., lead to prediction of some possible factors responsible for the variations of Ca2+ oscillations in different types of cells. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Sci & Technol China, Sch Earth & Space Sci, Environm Sci Div, Anhua 230026, Peoples R China. Massachusetts Gen Hosp, Neurochem Lab, Dept Psychiat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neurochem Lab, Genet & Aging Res Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neurochem Lab, Genet & Aging Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02120 USA. Brigham & Womens Hosp, Conjugate & Med Chem Lab, Dept Radiol, Funct & Mol Imaging Ctr, Boston, MA 02120 USA. RP Huang, WD (reprint author), Univ Sci & Technol China, Sch Earth & Space Sci, Environm Sci Div, Anhua 230026, Peoples R China. EM huangwd@ustc.edu.cn NR 50 TC 7 Z9 8 U1 0 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD APR 7 PY 2007 VL 245 IS 3 BP 510 EP 519 DI 10.1016/j.jtbi.2006.11.007 PG 10 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 156TF UT WOS:000245672100011 PM 17188305 ER PT J AU Craft, D AF Craft, David TI Local beam angle optimization with linear programming and gradient search SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID INTENSITY-MODULATED RADIOTHERAPY; RADIATION-THERAPY; MAP OPTIMIZATION; ORIENTATIONS; MINIMA; IMRT; ALGORITHM; SELECTION; NUMBER AB The optimization of beam angles in IMRT planning is still an open problem, with literature focusing on heuristic strategies and exhaustive searches on discrete angle grids. We show how a beam angle set can be locally refined in a continuous manner using gradient-based optimization in the beam angle space. The gradient is derived using linear programming duality theory. Applying this local search to 100 random initial angle sets of a phantom pancreatic case demonstrates the method, and highlights the many-local- minima aspect of the BAO problem. Due to this function structure, we recommend a search strategy of a thorough global search followed by local refinement at promising beam angle sets. Extensions to nonlinear IMRT formulations are discussed. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Craft, D (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM dcraft@partners.org FU NCI NIH HHS [1 R01 CA103904-01A1] NR 21 TC 27 Z9 27 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD APR 7 PY 2007 VL 52 IS 7 BP N127 EP N135 DI 10.1088/0031-9155/52/7/N02 PG 9 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 163LV UT WOS:000246162200020 PM 17374906 ER PT J AU Ceron, J Rual, JF Chandra, A Dupuy, D Vidal, M van den Heuvel, S AF Ceron, Julian Rual, Jean-Francois Chandra, Abha Dupuy, Denis Vidal, Marc van den Heuvel, Sander TI Large-scale RNAi screens identify novel genes that interact with the C-elegans retinoblastoma pathway as well as splicing-related components with synMuv B activity SO BMC DEVELOPMENTAL BIOLOGY LA English DT Article ID SYNTHETIC MULTIVULVA GENES; MEDIATED VULVAL INDUCTION; CELL-CYCLE ARREST; CAENORHABDITIS-ELEGANS; LIN-35 RB; TUMOR-SUPPRESSOR; TRANSCRIPTIONAL REPRESSOR; LARVAL DEVELOPMENT; SM PROTEINS; INTERFERENCE AB Background: The retinoblastoma tumor suppressor (Rb) acts in a conserved pathway that is deregulated in most human cancers. Inactivation of the single Rb-related gene in Caenorhabditis elegans, lin-35, has only limited effects on viability and fertility, yet causes changes in cell-fate and cell-cycle regulation when combined with inactivation of specific other genes. For instance, lin-35 Rb is a synthetic multivulva (synMuv) class B gene, which causes a multivulva phenotype when inactivated simultaneously with a class A or C synMuv gene. Results: We used the ORFeome RNAi library to identify genes that interact with C. elegans lin-35 Rb and identified 57 genes that showed synthetic or enhanced RNAi phenotypes in lin-35 mutants as compared to rrf-3 and eri-1 RNAi hypersensitive mutants. Based on characterizations of a deletion allele, the synthetic lin-35 interactor zfp-2 was found to suppress RNAi and to cooperate with lin-35 Rb in somatic gonad development. Interestingly, ten splicing-related genes were found to function similar to lin-35 Rb, as synMuv B genes that prevent inappropriate vulval induction. Partial inactivation of specific spliceosome components revealed further similarities with lin-35 Rb functions in cell-cycle control, transgene expression and restricted expression of germline granules. Conclusion: We identified an extensive series of candidate lin-35 Rb interacting genes and validated zfp-2 as a novel lin-35 synthetic lethal gene. In addition, we observed a novel role for a subset of splicing components in lin-35 Rb-controlled processes. Our data support novel hypotheses about possibilities for anti-cancer therapies and multilevel regulation of gene expression. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Univ Utrecht, Dept Dev Biol, NL-3584 CH Utrecht, Netherlands. RP van den Heuvel, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM jceron@ir.vhebron.net; JRUAL@partners.org; abha_6@hotmail.com; denis_dupuy@dfci.harvard.edu; marc_vidal@dfci.harvard.edu; S.J.L.vandenheuvel@bio.uu.nl RI van den Heuvel, Sander/B-8892-2011; Dupuy, Denis/M-7299-2014; OI Rual, Jean-Francois/0000-0003-4465-8819; Dupuy, Denis/0000-0002-4781-5595 FU NCI NIH HHS [P01 CA095281, P01 CA95281] NR 65 TC 56 Z9 64 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-213X J9 BMC DEV BIOL JI BMC Dev. Biol. PD APR 6 PY 2007 VL 7 AR 30 DI 10.1186/1471-213X-7-30 PG 16 WC Developmental Biology SC Developmental Biology GA 166CS UT WOS:000246355400001 PM 17417969 ER PT J AU Schuller, U Rowitch, DH AF Schuller, Ulrich Rowitch, David H. TI beta-catenin function is required for cerebellar morphogenesis SO BRAIN RESEARCH LA English DT Article DE development; cerebellum; swaying mutant; vermis; catenin; Wnt1 ID INT-1 PROTOONCOGENE; SIGNALING PATHWAY; NERVOUS-SYSTEM; GENE; EXPRESSION; MIDBRAIN; BRAIN; WNT-1; CNS; PROGENITORS AB Because of the failure to form embryonic mid-hindbrain structures in conventional Wnt1 knockout animals, ongoing roles for Wnt signaling at later stages have been difficult to resolve. Here, we used Nestin-cre to ablate beta-catenin at midgestation in developing CNS precursors to investigate beta-catenin-dependent Writ signaling in the development of late-derived structures such as the cerebellum. At 14.5 dpc, we found evidence for premature neural precursor cell fate commitment. At PO, we observed vermian hypoplasia and failure to fuse the cerebellar hemispheres and caudal midbrain, a phenotype reminiscent of the swaying (Wnt1(sw/sw)) mouse mutant. Our findings indicate general functions for beta-catenin beyond the neural plate stage during brain development and a particular role for beta-catenindependent Writ signaling during morphogenesis of the caudal midbrain and the cerebellum. We discuss our results with respect to genetic pathways that regulate formation of derivatives of the embryonic midbrain-hindbrain region. (c) 2006 Elsevier B.V. All rights reserved. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Newborn Med & Hematol, Boston, MA 02115 USA. RP Rowitch, DH (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Dana 640D,44 Binney St, Boston, MA 02115 USA. EM david_rowitch@dfci.harvard.edu NR 34 TC 31 Z9 32 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 6 PY 2007 VL 1140 BP 161 EP 169 DI 10.1016/j.brainres.2006.05.105 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 154WS UT WOS:000245539200015 PM 16824494 ER PT J AU Rivier, J Gulyas, J Kunitake, K DiGruccio, M Cantle, JP Perrin, MH Donaldson, C Vaughan, J Million, M Gourcerol, G Adelson, DW Rivier, C Tache, Y Vale, W AF Rivier, Jean Gulyas, Jozsef Kunitake, Koichi DiGruccio, Michael Cantle, Jeffrey P. Perrin, Marilyn H. Donaldson, Cindy Vaughan, Joan Million, Mulugeta Gourcerol, Guillaume Adelson, David W. Rivier, Catherine Tache, Yvette Vale, Wylie TI Stressin(1)-A, a potent corticotropin releasing factor receptor 1 (CRF1)-selective peptide agonist SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID I-(I+3) GLU-LYS; FACTOR CRF; COMPETITIVE ANTAGONISTS; UROCORTIN-II; ASTRESSIN ANALOGS; STRESS; RAT; MICE; ADAPTATIONS; SUBTYPE-1 AB The potencies and selectivity of peptide CRF antagonists is increased through structural constraints, suggesting that the resulting ligands assume distinct conformations when interacting with CRF1 and CRF2 receptors. To develop selective CRF receptor agonists, we have scanned the sequence -Gln-Ala-His-Ser-Asn-Arg- (residues 30-35 of [DPhe(12),Nle(21,38)]Ac-hCRF(4-41)) with an i-(i+3) bridge consisting of the Glu(i)-Xaa-Xbb-Lys(i+3) scaffold, where residues i = 30, 31, and 32. When i = 31, stressin(1)-A, a potent CRF1 receptor-selective agonist was generated. In vitro, stressin(1)-A was equipotent to h/rCRF to release ACTH. Astressin(1)-A showed a low nanomolar affinity for CRF1 receptor (K-i = 1.7 nM) and greater than 100-fold selectivity versus CRF2 receptor (K-i = 222 nM). Stressin(1)-A released slightly less ACTH than oCRF in adult adrenal-intact male rats, with increased duration of action. Stressin(1)-A, injected intraperitoneally in rats, induced fecal pellet output (a CRF1 receptor-mediated response) and did not influence gastric emptying and blood pressure (CRF2 receptor-mediated responses). C1 Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, La Jolla, CA 92037 USA. CURE, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Ctr Neurovisceral Sci Womens Hlth, VA Greater Los Angeles Healthcare Syst, Dept Med,Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. RP Rivier, J (reprint author), Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM jrivier@salk.edu OI DiGruccio, Michael/0000-0002-9375-2425; Adelson, David/0000-0002-4623-6030 FU NIDDK NIH HHS [DK 057238, R21 DK068155, R01 DK057238, P30 DK041301-199006, P30 DK041301, DK026741, DK 041301, R21 DK068155-02, R01 DK057238-08, P01 DK026741-280010, P01 DK026741, DK 068155] NR 34 TC 30 Z9 31 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 5 PY 2007 VL 50 IS 7 BP 1668 EP 1674 DI 10.1021/jm0613875 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 150ZV UT WOS:000245259000026 PM 17335188 ER PT J AU Sweeney, MO McGee, TL Berson, EL Dryja, TP AF Sweeney, Meredith O. McGee, Terri L. Berson, Eliot L. Dryja, Thaddeus P. TI Low prevalence of LRAT mutations in patients with Leber congenital amaurosis and autosomal recessive retinitis pigmentosa SO MOLECULAR VISION LA English DT Article ID LECITHIN-RETINOL ACYLTRANSFERASE; ALPHA-SUBUNIT; NULL MUTATION; RPE65 GENE; CRB1 GENE; SPECTRUM; CRX; DEGENERATION; PHENOTYPE; PHOSPHODIESTERASE AB Purpose: To determine the the prevalence of pathogenic mutations in the gene encoding lecithin retinol acyltransferase (LRAT) in patients from North America with either Leber congenital amaurosis (LCA) or autosomal recessive retinitis pigmentosa (ARRP). Methods: Exon 1, exon 2, and the coding region of exon 3 of LRAT were PCR-amplified and directly sequenced from the leukocyte DNA of 82 unrelated patients with LCA and 190 unrelated patients with ARRP. Results: One isocoding change was found in this screen of LRAT (Glu114 GAG>GAA; c.342), and 5 other sequence changes were found in intronic or untranslated regions of the gene. None of these changes were predicted to affect the encoded protein and were therefore deemed non-pathogenic. Conclusions: LRAT mutations are likely a rare cause of LCA among patients from North America. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. RP Dryja, TP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, 243 Charles St, Boston, MA 02114 USA. EM thaddeus_dryja@meei.harvard.edu FU NEI NIH HHS [R37 EY000169, P30 EY014104, R01 EY008683, R01 EY000169, EY08683, EY00169] NR 52 TC 9 Z9 10 U1 1 U2 1 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD APR 5 PY 2007 VL 13 IS 62-63 BP 588 EP 593 PG 6 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 157KW UT WOS:000245719600002 PM 17438524 ER PT J AU Chauhan, D Velankar, M Brahmandam, M Hideshima, T Podar, K Richardson, P Schlossman, R Ghobrial, I Raje, N Munshi, N Anderson, KC AF Chauhan, D. Velankar, M. Brahmandam, M. Hideshima, T. Podar, K. Richardson, P. Schlossman, R. Ghobrial, I. Raje, N. Munshi, N. Anderson, K. C. TI A novel Bcl-2/Bcl-X-L/Bcl-w inhibitor ABT-737 as therapy in multiple myeloma SO ONCOGENE LA English DT Article DE multiple myeloma; mitochondria; apoptosis; Bcl-2 ID BCL-2 FAMILY; INDUCED APOPTOSIS; CELLS; DEXAMETHASONE; OVEREXPRESSION; ACTIVATION; BORTEZOMIB; PROTEINS; GROWTH; DEATH AB Bcl-2 or Bcl-X-L confers resistance to chemotherapy in multiple myeloma ( MM). Here we characterized the effects of ABT-737, a potent small-molecule inhibitor of antiapoptotic proteins Bcl-2, Bcl-X-L and Bcl-w with markedly higher affinity than previously reported compounds, on human MM cells. ABT-737 induces apoptosis in MM cells, including those resistant to conventional therapy. Examination of purified patient MM cells demonstrated similar results, without significant toxicity against normal peripheral blood mononuclear cells and MM bone marrow stromal cells. Importantly, ABT-737 decreases the viability of bortezomib-, dexamethasone-(Dex) and thalidomide-refractory patient MM cells. Additionally, ABT-737 abrogates MM cell growth triggered by interleukin-6 or insulin-like growth factor-1. Mechanistic studies show that ABT-737-induced apoptosis is associated with activation of caspase-8, caspase-9 and caspase-3, followed by poly(ADP-ribose) polymerase cleavage. Combining ABT- 737 with proteasome inhibitor bortezomib, melphalan or dexamethasone induces additive anti-MM activity. Taken together, our study provides the rationale for clinical protocols evaluating ABT-737, alone and together with botezomib, mephalan or dexamethasone, to enhance MM cell killing, overcome drug resistance conferred by Bcl-2 and improve patient outcome in MM. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Anderson, KC (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 FU NCI NIH HHS [R0-1 CA50947, P0-1 CA 78373, IP50CA10070] NR 27 TC 134 Z9 137 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 5 PY 2007 VL 26 IS 16 BP 2374 EP 2380 DI 10.1038/sj.onc.1210028 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 153WC UT WOS:000245466000013 PM 17016430 ER PT J AU Gerhart-Hines, Z Rodgers, JT Bare, O Kim, CLSH Kim, SH Mostoslavsky, R Alt, FW Wu, ZD Puigserver, P AF Gerhart-Hines, Zachary Rodgers, Joseph T. Bare, Olivia Lerin, Carles Kim, Seung-Hee Mostoslavsky, Raul Alt, Frederick W. Wu, Zhidan Puigserver, Pere TI Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1 alpha SO EMBO JOURNAL LA English DT Article DE caloric restriction; gene transcription; lipid metabolism; mitochondrial oxidation; sirtuins ID LIFE-SPAN EXTENSION; CALORIE RESTRICTION; SACCHAROMYCES-CEREVISIAE; RECEPTOR-ALPHA; ERR-ALPHA; TRANSCRIPTIONAL CONTROL; INSULIN-RESISTANCE; COACTIVATOR PGC-1; SKELETAL-MUSCLE; GENE-EXPRESSION AB In mammals, maintenance of energy and nutrient homeostasis during food deprivation is accomplished through an increase in mitochondrial fatty acid oxidation in peripheral tissues. An important component that drives this cellular oxidative process is the transcriptional coactivator PGC-1 alpha. Here, we show that fasting induced PGC-1 alpha deacetylation in skeletal muscle and that SIRT1 deacetylation of PGC-1 alpha is required for activation of mitochondrial fatty acid oxidation genes. Moreover, expression of the acetyltransferase, GCN5, or the SIRT1 inhibitor, nicotinamide, induces PGC-1 alpha acetylation and decreases expression of PGC-1 alpha target genes in myotubes. Consistent with a switch from glucose to fatty acid oxidation that occurs in nutrient deprivation states, SIRT1 is required for induction and maintenance of fatty acid oxidation in response to low glucose concentrations. Thus, we have identified SIRT1 as a functional regulator of PGC-1 alpha that induces a metabolic gene transcription program of mitochondrial fatty acid oxidation. These results have implications for understanding selective nutrient adaptation and how it might impact lifespan or metabolic diseases such as obesity and diabetes. C1 Harvard Univ, Sch Med, Dept Cell Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD USA. Novartis Inst Biomed Res Inc, Cambridge, MA USA. Harvard Univ, Sch Med, Childrens Hosp, CBR Inst Biomed Res,Dept Genet,Howard Hughes Med, Boston, MA 02115 USA. RP Puigserver, P (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Dana Farber Canc Inst, 1 Jimmu Fund Way Smith 936C, Boston, MA 02115 USA. EM pere_puigserver@dfci.harvard.edu FU NIDDK NIH HHS [R01 DK 069966, R01 DK069966] NR 37 TC 584 Z9 603 U1 9 U2 42 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD APR 4 PY 2007 VL 26 IS 7 BP 1913 EP 1923 DI 10.1038/sj.emboj.7601633 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 153WB UT WOS:000245465800015 PM 17347648 ER PT J AU Higgins, JP Higgins, JA AF Higgins, John P. Higgins, Johanna A. TI Electrocardiographic exercise stress testing: An update beyond the ST segment SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Review DE stress testing; treadmill testing; gender; score ID CORONARY-ARTERY-DISEASE; BLOOD-PRESSURE RESPONSE; DUKE TREADMILL SCORE; ACUTE MYOCARDIAL-INFARCTION; HEART-RATE RECOVERY; BUNDLE-BRANCH-BLOCK; SYNDROME EVALUATION WISE; PROGNOSTIC VALUE; RISK STRATIFICATION; NONCARDIAC SURGERY AB Routine exercise testing is frequently ordered to evaluate a patient's cardiovascular performance. The test is more direct and less expensive than imaging technology, and derives valuable information. New variables such as dyspnea and heart rate recovery, as well as integrated scores, provide incremental value to conventional analysis of exercise-induced angina or electrocardiographic changes. Considerations relating to test accuracy in women need to be weighed. This paper seeks to make physicians aware of the current status of the test, and improve their understanding of and ability to integrate new variables and scores to more effectively manage their patients. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Cardiol Sect, VA Boston Healthcare Syst, Med Sch,Cardiac Stress Lab, Boston, MA 02132 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Higgins, JP (reprint author), Harvard Univ, Cardiol Sect, VA Boston Healthcare Syst, Med Sch,Cardiac Stress Lab, 2C-120,1400 VFW Pkwy, Boston, MA 02132 USA. EM John.Higgins@va.gov NR 140 TC 21 Z9 22 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD APR 4 PY 2007 VL 116 IS 3 BP 285 EP 299 DI 10.1016/j.ijcard.2006.04.047 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 149ST UT WOS:000245167600001 PM 16837082 ER PT J AU Margaretten, ME Kohlwes, J Moore, D Bent, S AF Margaretten, Mary E. Kohlwes, Jeffrey Moore, Dan Bent, Stephen TI Does this adult patient have septic arthritis? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SYNOVIAL-FLUID LEUKOCYTOSIS; BACTERIAL ARTHRITIS; INFECTIOUS ARTHRITIS; CLINICAL-FEATURES; JOINT DISEASE; LACTIC-ACID; RHEUMATOID-ARTHRITIS; GONOCOCCAL ARTHRITIS; ACUTE MONOARTHRITIS; RISK-FACTORS AB Context In patients who present with an acutely painful and swollen joint, prompt identification and treatment of septic arthritis can substantially reduce morbidity and mortality. Objective To review the accuracy and precision of the clinical evaluation for the diagnosis of nongonococcal bacterial arthritis. Data Sources Structured PubMed and EMBASE searches ( 1966 through January 2007), limited to human, English-language articles and using the following Medical Subject Headings terms: arthritis, infectious, physical examination, medical history taking, diagnostic tests, and sensitivity and specificity. Study Selection Studies were included if they contained original data on the accuracy or precision of historical items, physical examination, serum, or synovial fluid laboratory data for diagnosing septic arthritis. Data Extraction Three authors independently abstracted data from the included studies. Data Synthesis Fourteen studies involving 6242 patients, of whom 653 met the gold standard for the diagnosis of septic arthritis, satisfied all inclusion criteria. Two studies examined risk factors and found that age, diabetes mellitus, rheumatoid arthritis, joint surgery, hip or knee prosthesis, skin infection, and human immunodeficiency virus type 1 infection significantly increase the probability of septic arthritis. Joint pain ( sensitivity, 85%; 95% confidence interval [CI], 78%-90%), a history of joint swelling ( sensitivity, 78%; 95% CI, 71%-85%), and fever ( sensitivity, 57%; 95% CI, 52%-62%) are the only findings that occur in more than 50% of patients. Sweats ( sensitivity, 27%; 95% CI, 20%-34%) and rigors ( sensitivity, 19%; 95% CI, 15%-24%) are less common findings in septic arthritis. Of all laboratory findings readily available to the clinician, the 2 most powerful were the synovial fluid white blood cell (WBC) count and percentage of polymorphonuclear cells from arthrocentesis. The summary likelihood ratio (LR) increased as the synovial fluid WBC count increased ( for counts < 25 000/mu L: LR, 0.32; 95% CI, 0.23-0.43; for counts >= 25 000/ mu L: LR, 2.9; 95% CI, 2.5-3.4; for counts > 50 000/ mu L: LR, 7.7; 95% CI, 5.7-11.0; and for counts > 100 000/ mu L: LR, 28.0; 95% CI, 12.0-66.0). On the same synovial fluid sample, a polymorphonuclear cell count of at least 90% suggests septic arthritis with an LR of 3.4 ( 95% CI, 2.8-4.2), while a polymorphonuclear cell count of less than 90% lowers the likelihood ( LR, 0.34; 95% CI, 0.25-0.47). Conclusions Clinical findings identify patients with peripheral, monoarticular arthritis who might have septic arthritis. However, the synovial WBC and percentage of polymorphonuclear cells from arthrocentesis are required to assess the likelihood of septic arthritis before the Gram stain and culture test results are known. C1 Univ Calif San Francisco, Div Rheumatol, Dept Med, Prime Program, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Margaretten, ME (reprint author), Univ Calif San Francisco, Div Rheumatol, Dept Med, Prime Program, U-384,533 Parnassus Ave, San Francisco, CA 94143 USA. EM mary.margaretten@ucsf.edu FU PHS HHS [1 K08 ATO1338-01] NR 58 TC 134 Z9 140 U1 2 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 4 PY 2007 VL 297 IS 13 BP 1478 EP 1488 DI 10.1001/jama.297.13.1478 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 153AM UT WOS:000245404100024 PM 17405973 ER PT J AU Crandall, JE McCarthy, DM Araki, KY Sims, JR Ren, JQ Bhide, PG AF Crandall, James E. McCarthy, Deirdre M. Araki, Kiyomi Y. Sims, John R. Ren, Jia-Qian Bhide, Pradeep G. TI Dopamine receptor activation modulates GABA neuron migration from the basal forebrain to the cerebral cortex SO JOURNAL OF NEUROSCIENCE LA English DT Article DE striatum; basal ganglia; ganglionic eminence; dopamine D-1 receptor; dopamine D-2 receptor; tangential neuronal migration ID CAUDAL GANGLIONIC EMINENCE; CORTICAL PRECURSOR CELLS; GABAERGIC INTERNEURONS; PRENATAL EXPOSURE; MESSENGER-RNA; COCAINE; TELENCEPHALON; DYNEIN; CYCLE; BRAIN AB GABA neurons of the cerebral cortex and other telencephalic structures are produced in the basal forebrain and migrate to their final destinations during the embryonic period. The embryonic basal forebrain is enriched in dopamine and its receptors, creating a favorable environment for dopamine to influence GABA neuron migration. However, whether dopamine receptor activation can influence GABA neuron migration is not known. We show that dopamine D-1 receptor activation promotes and D-2 receptor activation decreases GABA neuron migration from the medial and caudal ganglionic eminences to the cerebral cortex in slice preparations of embryonic mouse forebrain. Slice preparations from D1 or D2 receptor knock-out mouse embryos confirm the findings. In addition, D1 receptor electroporation into cells of the basal forebrain and pharmacological activation of the receptor promote migration of the electroporated cells to the cerebral cortex. Analysis of GABA neuron numbers in the cerebral wall of the dopamine receptor knock-out mouse embryos further confirmed the effects of dopamine receptor activation on GABA neuron migration. Finally, dopamine receptor activation mobilizes striatal neuronal cytoskeleton in a manner consistent with the effects on neuronal migration. These data show that impairing the physiological balance between D1 and D2 receptors can alter GABA neuron migration from the basal forebrain to the cerebral cortex. The intimate relationship between dopamine and GABA neuron development revealed here may offer novel insights into developmental disorders such as schizophrenia, attention deficit or autism, and fetal cocaine exposure, all of which are associated with dopamine and GABA imbalance. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Cambridge, MA 02139 USA. Univ Massachusetts, Sch Med, Eunice Kennedy Shriver Ctr Mental Retardat Inc, Waltham, MA 02452 USA. RP Bhide, PG (reprint author), Massachusetts Gen Hosp, Dept Neurobiol, 149 13th St, Cambridge, MA 02139 USA. EM bhide@helix.mgh.harvard.edu FU NICHD NIH HHS [P01 HD005515, HD05515]; NIDA NIH HHS [R01 DA020796, R01 DA020796-03, DA020796]; NINDS NIH HHS [R01 NS043426-05, R01 NS043426, P30 NS045776-05, P30 NS045776, NS43426, NS45776] NR 57 TC 73 Z9 74 U1 0 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 4 PY 2007 VL 27 IS 14 BP 3813 EP 3822 DI 10.1523/JNEUROSCI.5124-06.2007 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 153WU UT WOS:000245468300023 PM 17409246 ER PT J AU Friedel, RH Kerjan, G Rayburn, H Schuller, U Sotelo, C Tessier-Lavigne, M Chedotal, A AF Friedel, Roland H. Kerjan, Geraldine Rayburn, Helen Schuller, Ulrich Sotelo, Constantino Tessier-Lavigne, Marc Chedotal, Alain TI Plexin-b2 controls the development of cerebellar granule cells SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cerebellum; granule cell; semaphorin; cell proliferation; plexin; migration ID DOUBLECORTIN-LIKE-KINASE; GTPASE-ACTIVATING PROTEIN; SONIC HEDGEHOG; NEURONAL MIGRATION; NERVOUS-SYSTEM; EXPRESSION PATTERNS; RECEPTOR PLEXIN-B1; AXON OUTGROWTH; CYCLE EXIT; R-RAS AB Cerebellar granule cell progenitors proliferate postnatally in the upper part of the external granule cell layer (EGL) of the cerebellum. Postmitotic granule cells differentiate and migrate, tangentially in the EGL and then radially through the molecular and Purkinje cell layers. The molecular control of the transition between proliferation and differentiation in cerebellar granule cells is poorly understood. We show here that the transmembrane receptor Plexin-B2 is expressed by proliferating granule cell progenitors. To study Plexin-B2 function, we generated a targeted mutation of mouse Plexin-B2. Most Plexin-B2(-/-) mutants die at birth as a result of neural tube closure defects. Some mutants survive but their cerebellum cytoarchitecture is profoundly altered. This is correlated with a disorganization of the timing of granule cell proliferation and differentiation in the EGL. Many differentiated granule cells migrate inside the cerebellum and keep proliferating. These results reveal that Plexin-B2 controls the balance between proliferation and differentiation in granule cells. C1 Univ Paris 06, CNRS, UMR 7102, F-75005 Paris, France. Stanford Univ, Howard Hughes Med Inst, Dept Biol Sci, Stanford, CA 94305 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. Univ Miguel Hernandez Elche, Catedra Neurobiol Desarrollo Remedios Caro Almela, Inst Neurociencias, Consejo Nacl Invest Cient, Alicante 03550, Spain. RP Chedotal, A (reprint author), Univ Paris 06, CNRS, UMR 7102, 9 Quai St Bernard, F-75005 Paris, France. EM marctl@gene.com OI Sotelo, Constantino/0000-0001-8051-2492; Friedel, Roland/0000-0002-7513-3604; Chedotal, Alain/0000-0001-7577-3794 FU NHLBI NIH HHS [U01HL66600]; NIMH NIH HHS [R01MH60612] NR 68 TC 41 Z9 41 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 4 PY 2007 VL 27 IS 14 BP 3921 EP 3932 DI 10.1523/JNEUROSCI.4710-06.2007 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 153WU UT WOS:000245468300034 PM 17409257 ER PT J AU Beaser, RS Levy, P AF Beaser, Richard S. Levy, Philip TI A work in progress, but a useful construct SO CIRCULATION LA English DT Editorial Material ID NUTRITION EXAMINATION SURVEY; CORONARY-HEART-DISEASE; 3RD NATIONAL-HEALTH; CHOLESTEROL EDUCATION-PROGRAM; METABOLIC SYNDROME; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; ADIPOSE-TISSUE; US ADULTS C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Arizona, Coll Med, Phoenix, AZ USA. RP Beaser, RS (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM Richard.beaser@joslin.harvard.edu NR 35 TC 22 Z9 24 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 APR 3 PY 2007 VL 115 IS 13 BP 1812 EP 1818 DI 10.1161/CIRCULATIONAHA.106.673616 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 152ZX UT WOS:000245402300020 PM 17404172 ER PT J AU Nadkarni, SK Pierce, MC Park, BH de Boer, JF Whittaker, P Bouma, BE Bressner, JE Halpern, E Houser, SL Tearney, GJ AF Nadkarni, Seemantini K. Pierce, Mark C. Park, B. Hyle de Boer, Johannes F. Whittaker, Peter Bouma, Brett E. Bressner, Jason E. Halpern, Elkan Houser, Stuart L. Tearney, Guillermo J. TI Measurement of collagen and smooth muscle cell content in atherosclerotic plaques using polarization-sensitive optical coherence tomography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID RUPTURE; BIREFRINGENCE; ORGANIZATION; INSTABILITY; LESIONS; DEATH; SKIN AB Objectives The purpose of this study was to investigate the measurement of collagen and smooth muscle cell (SMC) content in atherosclerotic plaques using pofarization-sensitive optical coherence tomography (PSOCT). Background A method capable of evaluating plaque collagen content and SMC density can provide a measure of the mechanical fidelity of the fibrous cap and can enable the identification of high-risk lesions. Optical coherence tomography has been demonstrated to provide cross-sectional images of tissue microstructure with a resolution of 10 mu m. A recently developed technique, PSOCT measures birefringence, a material property that is elevated in tissues such as collagen and SMCs. Methods We acquired PSOCT images of 87 aortic plaques obtained from 20 human cadavers. Spatially averaged PSOCT birefringence, (D, was measured and compared with plaque collagen and SMC content, quantified morphometrically by picrosirius red and smooth muscle actin staining at the corresponding locations. Results There was a high positive correlation between PSOCT measurements of (D and total collagen content in all plaques (r = 0.67, p < 0.001) and in fibrous caps of necrotic core fibroatheromas (r = 0.68, p < 0.001). Polarization-sensitive optical coherence tomography measurements of (D demonstrated a strong positive correlation with thick collagen fiber content (r = 0.76, p < 0.001) and SMC density (r 0.74, p < 0.01). Conclusions Our results demonstrate that PSOCT enables the measurement of birefringence in plaques and in fibrous caps of necrotic core fibroatheromas. Given its potential to evaluate coflagen content, collagen fiber thickness, and SMC density, we anticipate that PSOCT will significantly improve our ability to evaluate plaque stability in patients. C1 Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Massachusetts, Dept Emergency Med, Sch Med, Amherst, MA 01003 USA. Univ Massachusetts, Dept Anesthesiol, Sch Med, Amherst, MA 01003 USA. RP Nadkarni, SK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 40 Blossom St,BAR 718, Boston, MA 02114 USA. EM snadkarni@hms.harvard.edu RI Whittaker, Peter/F-1234-2011; de Boer, Johannes/B-7590-2012 OI Whittaker, Peter/0000-0002-5627-2166; de Boer, Johannes/0000-0003-1253-4950 FU NHLBI NIH HHS [R01 HL076398, R01 HL076398-03, R01-HL076398] NR 33 TC 96 Z9 100 U1 1 U2 5 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 APR 3 PY 2007 VL 49 IS 13 BP 1474 EP 1481 DI 10.1016/j.jacc.2006.11.040 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 154QP UT WOS:000245522700010 PM 17397678 ER PT J AU Tamayo, P Scanfeld, D Ebert, BL Gillette, MA Roberts, CWM Mesirov, JP AF Tamayo, Pablo Scanfeld, Daniel Ebert, Benjamin L. Gillette, Michael A. Roberts, Charles W. M. Mesirov, Jill P. TI Metagene projection for cross-platform, cross-species characterization of global transcriptional states SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer; dimension reduction; expression analysis; noise reduction; sample contamination ID GENE-EXPRESSION PROFILES; ACUTE LYMPHOBLASTIC-LEUKEMIA; NONNEGATIVE MATRIX FACTORIZATION; SINGULAR-VALUE DECOMPOSITION; ACUTE MYELOID-LEUKEMIA; MOLECULAR CLASSIFICATION; LUNG ADENOCARCINOMA; MICROARRAY DATA; CANCER; CELL AB The high dimensionality of global transcription profiles, the expression level of 20,000 genes in a much small number of samples, presents challenges that affect the sensitivity and general applicability of analysis results. In principle, it would be better to describe the data in terms of a small number of metagenes, positive linear combinations of genes, which could reduce noise while still capturing the invariant biological features of the data. Here, we describe how to accomplish such a reduction in dimension by a metagene projection methodology, which can greatly reduce the number of features used to characterize microarray data. We show, in applications to the analysis of leukemia and lung cancer data sets, how this approach can help assess and interpret similarities and differences between independent data sets, enable cross-platform and cross-species analysis, improve clustering and class prediction, and provide a computational means to detect and remove sample contamination. C1 MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02141 USA. Harvard Univ, Cambridge, MA 02141 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Mesirov, JP (reprint author), MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02141 USA. EM mesirov@broad.mit.edu FU NCI NIH HHS [T32 CA009172] NR 44 TC 68 Z9 71 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 APR 3 PY 2007 VL 104 IS 14 BP 5959 EP 5964 DI 10.1073/pnas.0701068104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 156OA UT WOS:000245657600047 PM 17389406 ER PT J AU Raffel, GD Mercher, T Shigematsu, H Williams, IR Cullen, DE Akashi, K Bernard, OA Gilliland, DG AF Raffel, Glen D. Mercher, Thomas Shigematsu, Hirokazu Williams, Ifor R. Cullen, Dana E. Akashi, Koichi Bernard, Olivier A. Gilliland, D. Gary TI Ott1(Rbm15) has pleiotropic roles in hematopoietic development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE lymphocyte; megakaryocytic leukemia; hematopoietic stem cell ID B-CELL DEVELOPMENT; ACUTE MEGAKARYOBLASTIC LEUKEMIA; NUCLEAR RECEPTOR COREPRESSOR; SIGNALING PATHWAY; LYMPHOCYTE DEVELOPMENT; GENE REARRANGEMENTS; BINDING-PROTEIN; SPEN PROTEINS; C/EBP-ALPHA; SPLIT-ENDS AB OTT1(RBM15) was originally described as a 5' translocation partner of the MAL(MKL1) gene in t(1,22)(p13;q13) infant acute megakaryocytic leukemia. OTT1 has no established physiological function, but it shares homology with the spen/Mint/SHARP family of proteins defined by three amino-terminal RNA recognition motifs and a carboxyl-terminal SPOC (Spen paralog and ortholog carboxyl-terminal) domain believed to act as a transcriptional repressor. To define the role of OTT1 in hematopoiesis and help elucidate the mechanism of t(1,22) acute megakaryocytic leukemia pathogenesis, a conditional allele of Ott1 was generated in mice. Deletion of Ott1 in adult mice caused a loss of peripheral B cells due to a block in pro/pre-B differentiation. There is myeloid and megakaryocytic expansion in spleen and bone marrow, an increase in the Lin(-)Sca-1(+)c-Kit(+) compartment that includes hematopoietic stem cells, and a shift in progenitor fate toward granulocyte differentiation. These data show a requirement for Ott1 in B lymphopoiesis, and inhibitory roles in the myeloid, megakaryocytic, and progenitor compartments. The ability of Ott1 to affect hematopoietic cell fate and expansion in multiple lineages is a novel attribute for a spen family member and delineates Ott1 from other known effectors of hematopoietic development. It is plausible that dysregulation of Ott1-dependent hematopoietic developmental pathways, in particular those affecting the megakaryocyte lineage, may contribute to OTT1-MAL-mediated leukemogenesis. C1 Harvard Univ, Div Hematol, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. INSERM, F-75743 Paris, France. Univ Paris 05, F-75270 Paris, France. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Gilliland, DG (reprint author), Harvard Univ, Div Hematol, Brigham & Womens Hosp, Sch Med, 1 Blackfan Circle, Boston, MA 02115 USA. EM ggilliland@rics.bwh.harvard.edu RI Williams, Ifor/D-3648-2011; Mercher, Thomas/J-2446-2014; Bernard, Olivier/E-5721-2016 OI Williams, Ifor/0000-0002-8810-2911; Mercher, Thomas/0000-0003-1552-087X; FU NCI NIH HHS [K08 CA111399, P01 CA066996, R01 CA66996] NR 40 TC 34 Z9 37 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 APR 3 PY 2007 VL 104 IS 14 BP 6001 EP 6006 DI 10.1073/pnas.0609041104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 156OA UT WOS:000245657600054 PM 17376872 ER PT J AU Bond, WF Lammers, RL Spillane, LL Smith-Coggins, R Fernandez, R Reznek, MA Vozenilek, JA Gordon, JA AF Bond, William F. Lammers, Richard L. Spillane, Linda L. Smith-Coggins, Rebecca Fernandez, Rosemarie Reznek, Martin A. Vozenilek, John A. Gordon, James A. CA Soc Acad Emergency Med TI The use of simulation in emergency medicine: A research agenda SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE simulation; research agenda; emergency medicine ID CRISIS RESOURCE-MANAGEMENT; HIGH-FIDELITY SIMULATION; HUMAN PATIENT SIMULATOR; ENDOTRACHEAL INTUBATION; VIRTUAL-REALITY; AIRWAY MANAGEMENT; PROCEDURAL SKILLS; TECHNICAL SKILLS; TRAINING-PROGRAM; PERFORMANCE AB Medical simulation is a rapidly expanding area within medical education. In 2005, the Society for Academic Emergency Medicine Simulation Task Force was created to ensure that the Society and its members had adequate access to information and resources regarding this new and important topic. One of the objectives of the task force was to create a research agenda for the use of simulation in emergency medical education. The authors present here the consensus document from the task force regarding suggested areas for research. These include opportunities to study reflective experiential learning, behavioral and team training, procedural simulation, computer screen-based simulation, the use of simulation for evaluation and testing, and special topics in emergency medicine. The challenges of research in the field of simulation are discussed, including the impact of simulation on patient safety. Outcomes-based research and multicenter efforts will serve to advance simulation techniques and encourage their adoption. C1 Penn State Univ, Sch Med, Dept Emergency Med, Lehigh Valley Hosp & Hlth Network, Allentown, PA USA. Michigan State Univ, Dept Emergency Med, Kalamazoo Ctr Med Studies, Kalamazoo, MI USA. Univ Rochester, Sch Med & Dent, Dept Emergency Med, Rochester, NY USA. Stanford Univ, Sch Med, Div Emergency Med, Stanford, CA 94305 USA. Wayne State Univ, Sch Med, Dept Emergency Med, Detroit, MI USA. Northwestern Univ, Div Emergency Med, Feinberg Sch Med, Evanston, IL USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Gilbert Program Med Simulat, Boston, MA 02115 USA. Emory Univ, Sch Med, Dept Emergency Med, Atlanta, GA 30322 USA. RP Bond, WF (reprint author), Penn State Univ, Sch Med, Dept Emergency Med, Lehigh Valley Hosp & Hlth Network, Allentown, PA USA. EM william.bond@lvh.com OI Vozenilek, John/0000-0001-7955-4089 NR 99 TC 58 Z9 58 U1 2 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD APR PY 2007 VL 14 IS 4 BP 353 EP 363 DI 10.1197/j.aem.2006.11.021 PG 11 WC Emergency Medicine SC Emergency Medicine GA 155LQ UT WOS:000245579300010 PM 17303646 ER PT J AU Vanderweil, SG Pelletier, AJ Hamedani, AG Gonzales, R Metlay, JP Camargo, CA AF Vanderweil, Stefan G. Pelletier, Andrea J. Hamedani, Azita G. Gonzales, Ralph Metlay, Joshua P. Camargo, Carlos A., Jr. TI Declining antibiotic prescriptions for upper respiratory infections, 1993-2004 SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE respiratory tract infections; antibiotics; emergency departments; NHAMCS ID ADULTS AB Objectives: To examine antibiotic prescribing trends for U.S. emergency department (ED) visits with upper respiratory tract infections (URIs) between 1993 and 2004. Methods: Data were compiled from the National Hospital Ambulatory Medical Care Survey (NHAMCS). URI visits were identified by using ICD-9-CM code 465.9, whereas antibiotics were identified using the National Drug Code Directory class Antimicrobials. A multivariate logistic regression model revealed sociodemographic and geographic factors that were independently associated with receipt of an antibiotic prescription for URIs. Results: There were approximately 23.4 million ED visits diagnosed as URIs between 1993 and 2004. Although the proportion of URI diagnoses remained relatively stable (p(trend) = 0.26), a significant decrease in provision of antibiotic prescriptions for URIs occurred during this 12-year period, from a maximum of 55% in 1993, to a minimum of 35% in 2004. Patients who were prescribed antibiotics were more likely to be white than African American and to have been treated in EDs located in the southern United States. Conclusions: Antibiotic prescribing for URIs continues to decrease, a favorable trend that suggests that national efforts to reduce inappropriate antibiotic usage are having some success. Nevertheless, the frequency of antibiotic treatment for URI in the ED remains high (35%). Future efforts to reduce inappropriate antibiotic prescribing may focus on patients and physicians in southern U.S. EDs. Additional work is needed to address continued evidence of race-related disparities in care. C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Univ Calif San Francisco, Div Gen Internal Med, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Gen Internal Med, Dept Med, Philadelphia, PA 19104 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. EM emnet@partners.org FU AHRQ HHS [R01 HS013915] NR 12 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD APR PY 2007 VL 14 IS 4 BP 366 EP 369 DI 10.1197/j.aem.2006.10.096 PG 4 WC Emergency Medicine SC Emergency Medicine GA 155LQ UT WOS:000245579300011 PM 17296803 ER PT J AU Mansbach, J Acholonu, U Clark, S Camargo, CA AF Mansbach, Jonathan Acholonu, Uchechi Clark, Sunday Camargo, Carlos A., Jr. TI Variation in institutional review board - Responses to a standard, observational, pediatric research protocol SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE institutional review board; Health Insurance Portability and Accountability Act; multicenter studies; Privacy Rule ID HEALTH-SERVICES RESEARCH; TRIALS; IMPACT AB Background: Multicenter studies are becoming more common, and variability in local institutional review board (IRB) assessments can be problematic. Objective: To investigate the variability of IRB responses to a multicenter observational study of children presenting to emergency departments. Methods: The authors collected the original IRB applications, subsequent correspondence, and a survey assessing submission timing and response and the nature of IRB queries. The study was conducted as part of the Emergency Medicine Network (http://www.emnet-usa.org). Results: Of 37 sites initiating the IRB process, 34 (92%) participated in this IRB-approved study. Institutional review boards returned initial applications in a median of 19 days (IQR, 11-34 d), and 91% considered the protocol to be minimal risk. Of 34 submissions, 13 required no changes, 18 received conditional approvals, and 3 were deferred. The median time from initial submission to final approval was 42 days (IQR, 27-61 d). Seven sites did not participate in patient recruitment: two had institutional issues, one obtained IRB approval too late for participation, and four sites (12%) reported that IRB hurdles contributed to their lack of participation. Nonetheless, 68% of sites that recruited patients reported that the overall experience made them more likely to participate in future multicenter research. Conclusions: There was substantial variation in IRB assessment of a standard protocol in this study. The burden of the application process contributed to some investigators not participating, but the majority of investigators remain enthusiastic about multicenter research. A national IRB may streamline the review process and facilitate multicenter clinical research. C1 Childrens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Mansbach, J (reprint author), Childrens Hosp, Dept Med, 300 Longwood Ave, Boston, MA 02115 USA. EM jonathan.mansbach@childrens.harvard.edu NR 9 TC 40 Z9 40 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD APR PY 2007 VL 14 IS 4 BP 377 EP 380 DI 10.1197/j.aem.2006.11.031 PG 4 WC Emergency Medicine SC Emergency Medicine GA 155LQ UT WOS:000245579300014 PM 17312334 ER PT J AU Watnick, S AF Watnick, Suzanne TI Pregnancy and contraceptive counseling of women with chronic kidney disease and kidney transplants SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE chronic kidney disease; kidney transplantation; pregnancy; dialysis; counseling ID RENAL-DISEASE; DIALYSIS PATIENTS; REPRODUCTIVE ISSUES; INSUFFICIENCY; MANAGEMENT; RECIPIENTS; DEVICE AB Women with kidney disease of childbearing age should expect proactive counseling regarding pregnancy and contraception. Discussions should include the impact of pregnancy on their kidney disease and the impact of kidney disease on maternal and fetal outcomes. However, nephrologists rarely discuss sexual dysfunction, infertility, menstrual irregularities, and contraception with their premenopausal women patients. This review will consider pregnancy-related issues to discuss when counseling women with all stages of chronic kidney disease. Issues related to contraception in women on dialysis, women with functioning kidney transplants, and those with chronic kidney disease will also be reviewed. (c) 2007 by the National Kidney Foundation, Inc. C1 Oregon Hlth & Sci Univ, Portland VA Med Ctr, VA Dialysis Unit, Portland, OR 97201 USA. RP Watnick, S (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, VA Dialysis Unit, 3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. EM watnicks@ohsu.edu NR 42 TC 20 Z9 21 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1548-5595 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD APR PY 2007 VL 14 IS 2 BP 126 EP 131 DI 10.1053/j.ackd.2007.01.003 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 156PI UT WOS:000245661000005 PM 17395115 ER PT J AU Tsai, SB Tucci, V Uchiyama, J Fabian, NJ Lin, MC Bayliss, PE Neuberg, DS Zhdanova, IV Kishi, S AF Tsai, Stephanie B. Tucci, Valter Uchiyama, Junzo Fabian, Niora J. Lin, Mao C. Bayliss, Peter E. Neuberg, Donna S. Zhdanova, Irina V. Kishi, Shuji TI Differential effects of genotoxic stress on both concurrent body growth and gradual senescence in the adult zebrafish SO AGING CELL LA English DT Article DE aging; genotoxic stress; growth; melatonin; regeneration; reproduction; senescence; zebrafish ID AGE-RELATED-CHANGES; BETA-GALACTOSIDASE ACTIVITY; ORYZIAS-LATIPES; LIFE-SPAN; FIN REGENERATION; MELATONIN BIOSYNTHESIS; ATAXIA-TELANGIECTASIA; CELLULAR SENESCENCE; IONIZING-RADIATION; VERTEBRATE MODEL AB Among vertebrates, fish and mammals show intriguing differences in their growth control properties with age. The potential for unlimited or indeterminate growth in a variety of fish species has prompted many questions regarding the senescent phenomena that appear during the aging process in these animals. Using zebrafish as our model system, we have attempted in our current study to examine the growth phenomena in fish in relation to the onset of senescence-associated symptoms, and to evaluate the effects of genotoxic stress on these processes. We observed in the course of these analyses that the zebrafish undergoes continuous growth, irrespective of age, past the point of sexual maturation with gradually decreasing growth rates at later stages. Animal population density, current body size and chronological age also play predominant roles in regulating zebrafish growth and all inversely influence the growth rate. Interestingly, the induction of genotoxic stress by exposure to ionizing radiation (IR) did not adversely affect this body growth ability in zebrafish. However, IR was found to chronically debilitate the regeneration of amputated caudal fins and thereby induce high levels of abnormal fin regeneration in the adult zebrafish. In addition, by resembling and mimicking the natural course of aging, IR treatments likewise enhanced several other symptoms of senescence, such as a decline in reproductive abilities, increased senescence-associated beta-galactosidase activity and a reduction in melatonin secretion. Our current data thus suggest that during the lifespan of zebrafish, the onset of senescence-associated symptoms occurs in parallel with continuous growth throughout mid-adulthood. Moreover, our present findings indicate that genotoxic DNA damage may play a role as a rate-limiting factor during the induction of senescence, but not in the inhibition of continuous, density-dependent growth in adult zebrafish. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Boston Univ, Coll Arts & Sci, Dept Biol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. Boston Univ, Sch Med, Div Grad Med Sci, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Kishi, S (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM shuji.kishi@schepens.harvard.edu NR 85 TC 37 Z9 38 U1 2 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1474-9718 J9 AGING CELL JI Aging Cell PD APR PY 2007 VL 6 IS 2 BP 209 EP 224 DI 10.1111/j.1474-9726.2007.00278.x PG 16 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 147AK UT WOS:000244975600009 PM 17376146 ER PT J AU Yang, D McCrann, DJ Nguyen, H Hilaire, CS DePinho, RA Jones, MR Ravid, K AF Yang, Dan McCrann, Donald J. Nguyen, Hao Hilaire, Cynthia St. DePinho, Ronald A. Jones, Matthew R. Ravid, Katya TI Increased polyploidy in aortic vascular smooth muscle cells during aging is marked by cellular senescence SO AGING CELL LA English DT Article DE aging; cellular senescence; polyploidy; senescence-associated beta-galactosidase; vascular smooth muscle ID REPLICATIVE SENESCENCE; BIOMARKER; MICE AB We previously reported that the frequency of polyploid aortic vascular smooth muscle cells (VSMC) serves as a biomarker of aging. Cellular senescence of somatic cells is another marker of aging that is characterized by the inability to undergo cell division. Here, we examined whether polyploidy is associated with the development of cellular senescence in vivo. Analysis of aortic tissue preparations from young and old Brown Norway rats showed that expression of senescence markers such as p16(INK4a) and senescence-associated beta-galactosidase activity are detected primarily in the old tissues. VSMC from p16(INK4a) knockout and control mice display similar levels of polyploid cells. Intriguingly, senescence markers are expressed in most, but not all, polyploid VSMC. Moreover, the polyploid cells exhibit limited proliferative capacity in comparison to their diploid counterparts. This study is the first to demonstrate in vivo that polyploid VSMC adopt a senescent phenotype. C1 Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. Dana Farber Canc Inst, Ctr Appl Canc Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Ravid, K (reprint author), Boston Univ, Sch Med, Dept Biochem, K225, Boston, MA 02118 USA. EM ravid@biochem.bumc.bu.edu RI St. Hilaire, Cynthia/I-4713-2014; OI Ravid, Katya/0000-0002-9918-3024; St. Hilaire, Cynthia/0000-0003-1871-6915 FU NIA NIH HHS [AG022623, R03 AG022623-01, R03 AG022623] NR 16 TC 36 Z9 39 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1474-9718 J9 AGING CELL JI Aging Cell PD APR PY 2007 VL 6 IS 2 BP 257 EP 260 DI 10.1111/j.1474-9726.2007.00274.x PG 4 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 147AK UT WOS:000244975600013 PM 17291294 ER PT J AU Chamberlain, CK Cornell, JE Saunders, MJ Hatch, JP Shinkai, RS Yeh, CK AF Chamberlain, Cheryl K. Cornell, John E. Saunders, Michele J. Hatch, John P. Shinkai, Rosemary S. Yeh, Chih-Ko TI Intra-oral tactile sensation and aging in a community-based population SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID SENSITIVITY; AGE; VIBROTACTILE; ADULTS; YOUNG; TOUCH AB Background and aims: Intra-oral sensory function plays an important role in swallowing and food intake, yet the impact of aging on oral tactile perception is uncertain. This study examined the effects of age, ethnicity, and gender on tactile perception at specific intra-oral sites in a community-based sample of 372 Mexican-Americans (MAs) and European-Americans (EAs). Methods: Four levels of air-pressure were delivered to sites on the anterior and posterior thirds of the tongue and on the velum. Intensity judgments for suprathreshold air puffs were obtained with a direct scaling procedure. Data were analyzed by mixed model multivariate repeated measures ANOVA. Results: Mean judgments of intensity, slopes of intensity functions and intraclass correlation coefficients (ICCs) for intensity judgments, indicated that stimuli delivered to the anterior tongue elicited significantly larger and more consistent responding than at the other sites. MAs produced lower mean stimulus intensity judgments for all sites compared to EAs. No significant age-, gender- or ethnic group-related differences were found at any of the sites for the slopes of the intensity functions or for ICCs. Conclusions: Stimuli are judged more intense at the anterior tongue compared to the posterior tongue or velum and EAs gave higher estimates of intensity than did MAs. However, there are no age-, gender-, or ethnic group-related differences for the repeatability of intensity judgments or the slopes of intensity functions. Intra-oral tactile perception seems to be preserved during aging. C1 S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin 182, Audie L Murphy Div, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Dent Diagnost Sci, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Orthodont, San Antonio, TX 78284 USA. Pontificia Univ Catolica Rio Grande do Sul, Dept Prosthodont, Porto Alegre, RS, Brazil. RP Yeh, CK (reprint author), S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin 182, Audie L Murphy Div, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM Yeh@uthscsa.edu RI Shinkai, Rosemary/I-3510-2013 OI Shinkai, Rosemary/0000-0002-4107-5661 FU NIDCR NIH HHS [DE10756] NR 28 TC 1 Z9 1 U1 0 U2 1 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 1594-0667 J9 AGING CLIN EXP RES JI Aging Clin. Exp. Res. PD APR PY 2007 VL 19 IS 2 BP 85 EP 90 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 163XH UT WOS:000246196000001 PM 17446717 ER PT J AU Thomas, ER Dunfee, RL Stanton, J Bogdan, D Kunstman, K Wolinsky, SM Gabuzda, D AF Thomas, Elaine R. Dunfee, Rebecca L. Stanton, Jennifer Bogdan, Derek Kunstman, Kevin Wolinsky, Steven M. Gabuzda, Dana TI High frequency of defective vpu compared with tat and rev genes in brain from patients with HIV type 1-associated dementia SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; REPLICATION-COMPETENT; INDEPENDENT EVOLUTION; MACROPHAGE-TROPISM; PARTICLE RELEASE; LYMPHOID-TISSUES; ENVELOPE PROTEIN; NEURONAL INJURY; ENV GENES; SEQUENCES AB Human immunodeficiency virus type 1 ( HIV) infection of the central nervous system frequently causes HIV-associated dementia ( HAD) and other neurological disorders. The role of HIV regulatory and accessory proteins in the pathogenesis of these disorders is unclear. Here we analyzed sequences of tat, rev, and vpu genes in 55 subgenomic clones previously shown to encode functional env genes from brain and lymphoid tissues of four AIDS patients with HAD. Phylogenetic analysis showed distinct compartmentalization of tat, rev, and vpu genes in brain versus lymphoid tissues. Nine of 19 vpu sequences from brain of two patients had premature stop codons at positions between amino acids 2 and 30, compared with 0 of 8 from lymphoid tissues. Tat sequences from brain ( n = 8 of 8) but not lymphoid ( n = 0 of 6) tissue from one patient had a 35 amino acid truncation at the C-terminus. Rev sequences from the brain of one patient ( n = 6 of 8) had a 5 amino acid truncation. These results demonstrate a high frequency of defective vpu compared with tat and rev genes in brain from HAD patients, and identify sequence variants of these regulatory/accessory genes that may influence the pathogenesis of HIV-associated neurological disease. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, JFB 816,44 Binney St, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu RI Wolinsky, Steven/B-2893-2012; OI Wolinsky, Steven/0000-0002-9625-6697 FU NINDS NIH HHS [NS 37277] NR 45 TC 15 Z9 15 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2007 VL 23 IS 4 BP 575 EP 580 DI 10.1089/aid.2006.0246 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 160AN UT WOS:000245909300014 PM 17451348 ER PT J AU Hara, M Nakase, K Kozuka, T Nawa, Y AF Hara, Masamichi Nakase, Koichi Kozuka, Teruhiko Nawa, Yuichiro TI Bone marrow transplantation from unrelated donors for patients with adult T cell leukemia/lymphoma: Single center experience SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 13th International Conference on Human Retrovirology - HTLV and Related Viruses CY MAY 21-25, 2007 CL Hakone, JAPAN C1 Ehime Prefectural Cent Hosp, Div Hematol, Matsuyama, Ehime, Japan. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA. EM ma-hara@ja2.so-net.ne.jp NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2007 VL 23 IS 4 BP 612 EP 612 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 160AN UT WOS:000245909300102 ER PT J AU Nose, H Usuku, K Seth, N Kubota, R Goon, P Tanaka, Y Izumo, S Arimura, K Ohara, Y Wucherpfennig, K Bangham, C Osame, M Saito, M AF Nose, Hirohisa Usuku, Koichiro Seth, Nilufer Kubota, Ryuji Goon, Peter Tanaka, Yuetsu Izumo, Shuji Arimura, Kimiyoshi Ohara, Yoshiro Wucherpfennig, Kai Bangham, Charles Osame, Mitsuhiro Saito, Mineki TI In vivo selection of HTLV-1 specific CD4(+) cells by disease susceptive class II allele and immunodominant peptide complex in HTLV-1-associated neurological disease SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 13th International Conference on Human Retrovirology - HTLV and Related Viruses CY MAY 21-25, 2007 CL Hakone, JAPAN C1 Kagoshima Univ, Kagoshima 890, Japan. Univ London Imperial Coll Sci & Technol, London, England. Kumamoto Univ, Kumamoto, Japan. Dana Farber Canc Inst, Boston, MA 02115 USA. Kagoshima Univ, Ctr Chron Viral Dis, Kagoshima 890, Japan. Univ Ryukyus, Okinawa, Japan. Kanazawa Med Univ, Kanazawa, Ishikawa, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2007 VL 23 IS 4 BP 643 EP 643 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 160AN UT WOS:000245909300192 ER PT J AU Yaffe, K AF Yaffe, Kristine TI Metabolic syndrome and cognitive disorders - Is the sum greater than its parts? SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Review DE metabolic syndrome; cognition; dementia; insulin resistance; inflammation ID TYPE-2 DIABETES-MELLITUS; C-REACTIVE PROTEIN; ALZHEIMER-DISEASE; OLDER WOMEN; ELDERLY-WOMEN; RISK; INFLAMMATION; DEMENTIA; OBESITY; LEPTIN AB Given the anticipated exponential increase in both the incidence and prevalence of dementia, it is critical to identify preventative strategies and improved treatments for this disorder. The metabolic syndrome is comprised of 5 cardiovascular risk factors that include abdominal obesity, hypertriglyceridemia, low high-density lipoprotein levels, hypertension, and hyperglycemia. The prevalence of the metabolic syndrome, similar to that for cognitive disorders, increases dramatically with age. Several possible mechanisms may explain an association between the metabolic syndrome and cognitive decline including microvascular and macrovascular disease, inflammation, adiposity, and insulin resistance. Although some of the individual components of the metabolic syndrome have been linked to risk of developing dementia and cognitive impairment, few studies have looked at the components of the metabolic syndrome as a whole. We found, in 3 separate studies involving elders of different ethnicities, that the metabolic syndrome is a risk factor for accelerated cognitive aging. This was especially true for elders with the metabolic syndrome and with elevated serum level of inflammation. If metabolic syndrome is associated with increased risk of developing cognitive impairment, regardless of mechanism, then early identification and treatment of these individuals might offer avenues for disease course modification. C1 Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, Box 181,4150 Clemnent St, San Francisco, CA 94121 USA. EM Kristine.yaffe@ucsf.edu FU NIDDK NIH HHS [DK070713] NR 39 TC 89 Z9 93 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD APR-JUN PY 2007 VL 21 IS 2 BP 167 EP 171 DI 10.1097/WAD.0b013e318065bfd6 PG 5 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 177AO UT WOS:000247126200017 PM 17545744 ER PT J AU Bartzokis, G Lu, PH Mintz, J AF Bartzokis, George Lu, Po H. Mintz, Jim TI Human brain myelination and amyloid beta deposition in Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE myelin; oligodendrocyte; white matter; amyloid; iron; Alzheimer's disease; PIB; degeneration; dementia; aging; medications; treatment; prevention ID PITTSBURGH COMPOUND-B; WHITE-MATTER DAMAGE; NEURODEGENERATIVE DISORDERS; IN-VIVO; PARKINSONS-DISEASE; COGNITIVE DECLINE; TRANSGENIC MICE; MR EVALUATION; DOWN-SYNDROME; IRON STORES AB We hypothesized that myelin breakdown in vulnerable late-myelinating regions releases oligodendrocyte- and myelin-associated iron that promotes amyloid beta (A beta) oligornerization, its associated toxicity, and the deposition of oligomerized A beta and iron in neuritic plaques observed in Alzheimer's disease (AD). The model was tested by using published maps of cortical myelination from 1901 and recent in vivo imaging maps of A beta deposits in humans. The data show that in AD, radiolabeled ligands detect A beta deposition in a distribution that matches the map of late-myelinating regions. Furthermore, the strikingly lower ability of this imaging ligand to bind A beta in animal models is consistent with the much lower levels of myelin and associated iron levels in rodents when compared with humans. The hypotheses derived from the "myelin model" are testable with current imaging methods and have important implications for therapeutic interventions that should be expanded to include novel targets such as oligodendrocytes, myelin, and brain iron. (c) 2007 The Alzheimer's Association. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Brain Mapping, Dept Neurol,Lab Neuroimaging, Los Angeles, CA USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. RP Bartzokis, G (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA USA. EM gbar@ucla.edu RI Bartzokis, George/K-2409-2013 FU NIA NIH HHS [P50 AG016570, P50 AG016570-06, R01 AG027342]; NIMH NIH HHS [R01 MH066029, R01 MH066029-01A2] NR 55 TC 49 Z9 51 U1 2 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD APR PY 2007 VL 3 IS 2 BP 122 EP 125 DI 10.1016/j.jalz.2007.01.019 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 212FV UT WOS:000249579900007 PM 18596894 ER PT J AU de Lemos, JA Morrow, DA AF de Lemos, James A. Morrow, David A. TI Use of natriuretic peptides in clinical decision-making for patients with non-ST-elevation acute coronary syndromes SO AMERICAN HEART JOURNAL LA English DT Editorial Material ID ARTERY-DISEASE; PROGNOSTIC VALUE; MYOCARDIAL-INFARCTION; HEART-DISEASE; RISK MARKERS; MORTALITY; STRATEGIES C1 Univ Texas, SW Med Ctr, Donald W Reynolds Cardiovasc Clin Res Ctr, Dallas, TX 75390 USA. Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div, Boston, MA 02115 USA. RP de Lemos, JA (reprint author), Univ Texas, SW Med Ctr, Donald W Reynolds Cardiovasc Clin Res Ctr, 5909 Harry Hines Blvd,HA9-133, Dallas, TX 75390 USA. EM james.delemos@utsouthwestern.edu NR 19 TC 11 Z9 11 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 2007 VL 153 IS 4 BP 450 EP 453 DI 10.1016/j.ahj.2007.02.012 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 158IE UT WOS:000245784200002 PM 17383278 ER PT J AU Patel, P White, DL Deswal, A AF Patel, Parag White, Donna L. Deswal, Anita TI Translation of clinical trial results into practice: Temporal patterns of beta-blocker utilization for heart failure at hospital discharge and during ambulatory follow-up SO AMERICAN HEART JOURNAL LA English DT Article ID CARDIAC-INSUFFICIENCY BISOPROLOL; RANDOMIZED-TRIAL; MANAGEMENT; CARVEDILOL; OUTCOMES; THERAPY; MORTALITY; SURVIVAL; PROGRAM; TRENDS AB Background Underutilization of beta-blockers in heart failure (HF) has been widely reported at hospital discharge and in the ambulatory setting. We examined recent temporal patterns of beta-blocker utilization in HF with systolic dysfunction at hospital discharge and over 2-year follow-up. Methods Annual trends of beta-blocker use were examined in a clinical database of patients with ejection fraction <= 40% discharged after HF hospitalization in 1998-2004 (n = 735). More detailed data on beta-blocker use at discharge and over 2-year follow-up were abstracted for 200 consecutive patients each in 1999-2001 and 2003-2004. Results Annual rates of p-blocker use at discharge increased steadily by 10% per year from 1998-2004 (P < .001), with no sharp increase noted in any single year after publication of clinical trials or guidelines. Use among patients without contraindications increased markedly from 1999-2001 to 2003-2004 at hospital discharge (38.7% vs 82.6%, P <.001) and 2-year follow-up (53.0% vs 84.5%, P <.001). The increase was significant in all examined subgroups. Although > 50% of patients remained on low doses of beta-blockers, a 9 eater proportion trended to reach target doses at 2 years in the later period (25.6% vs 12.5%, P =.13). Conclusions Substantial increase in beta-blocker utilization in HIF with systolic dysfunction occurred from 1998 to 2004, demonstrating that high rates of p-blocker use are being achieved at hospital discharge and maintained in the ambulatory setting after discharge. However, the time lag in translation of scientific evidence into maximal use of beneficial therapy in practice remains a target for quality improvement. C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Michael E DeBakey Vet Affairs Med Ctr, Sect Cardiol, Houston, TX USA. Baylor Coll Med, Winters Ctr Heart Failure Res, Houston, TX 77030 USA. RP Deswal, A (reprint author), VA Med Ctr, 111B,2002 Holcombe Blvd, Houston, TX 77030 USA. EM adeswol@bcm.tmc.edu NR 21 TC 13 Z9 13 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 2007 VL 153 IS 4 BP 515 EP 522 DI 10.1016/j.ahj.2007.01.037 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 158IE UT WOS:000245784200011 PM 17383287 ER PT J AU Bagheri, R Schutta, M Cumaranatunge, RG Wolfe, ML Terembula, K Hoffman, B Schwartz, S Kimmel, SE Farouk, S Iqbal, N Reilly, MP AF Bagheri, Roshanak Schutta, Mark Cumaranatunge, Reshmaal Gomes Wolfe, Megan L. Terembula, Karen Hoffman, Barry Schwartz, Stan Kimmel, Stephen E. Farouk, Samira Iqbal, Nayyar Reilly, Muredach P. TI Value of electrocardiographic and ankle-brachial index abnormalities for prediction of coronary atherosclerosis in asymptomatic subjects with type 2 diabetes mellitus SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ELECTRON-BEAM TOMOGRAPHY; CARDIOVASCULAR RISK-FACTORS; ARTERY CALCIUM; COMPUTED-TOMOGRAPHY; OLDER ADULTS; QT INTERVAL; DISEASE; CALCIFICATION; EVENTS; GUIDELINES AB Type 2 diabetes mellitus (DM) is associated with increased cardiovascular risk, in part due to accelerated subclinical atherosclerosis. Electrocardiographic (ECG) and ankle-brachial index (ABI) abnormalities are used to screen for cardiovascular risk in the clinic. However, their capacity to identify patients with type 2 DM with nonobstructive subclinical atherosclerosis is unknown. Associations of ECG and ABI abnormalities with coronary artery calcium (CAC), a measure of coronary atherosclerosis, were examined using multivariable ordinal regression modeling in 589 asymptomatic patients with type 2 DM. Sensitivity, specificity, and positive and negative predictive values were determined. CAC was prevalent (44% CAC >100; 32% CAC >75th percentile score) despite normal electrocardiograms (64%) and ABIs (97%) in most subjects. Neither ECG nor ABI changes predicted CAC after adjusting for age, gender, and race. ECG abnormalities were neither sensitive nor specific for detection of CAC > 100, > 400, or > 75th percentile (sensitivities 0.43, 0.45, and 0.34; specificities 0.69, 0.66, and 0.63, respectively). ABI abnormalities were not sensitive (0.03, 0.04, and 0.03) but had high specificity (0.98, 0.98, and 0.98). In subjects with normal electrocardiograms and ABIs, extensive CAC was remarkably prevalent (CAC > 100 in 24%). In conclusion, ECG and ABI abnormalities failed to detect patients with subclinical coronary atherosclerosis and therefore may be of limited value in identifying many asymptomatic patients with type 2 DM at increased risk of cardiovascular disease. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Penn, Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. Univ Connecticut, Hlth Ctr, Div Cardiol, Farmington, CT USA. RP Reilly, MP (reprint author), Univ Penn, Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA. EM muredach@spirit.gcrc.upenn.edu FU NCRR NIH HHS [M01-RR00040]; NHLBI NIH HHS [R01-HL73278-01]; NIDDK NIH HHS [DK19525, R01-DK071224-01A1] NR 29 TC 12 Z9 12 U1 1 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 1 PY 2007 VL 99 IS 7 BP 951 EP 955 DI 10.1016/j.amjcard.2006.11.040 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 156LQ UT WOS:000245649900015 PM 17398190 ER PT J AU Pandya, KJ Hu, P Osborne, K Falkson, G Tormey, DC AF Pandya, Kishan J. Hu, Ping Osborne, Kent Falkson, Geoffrey Tormey, Douglass C. TI Phase III study of standard combination versus rotating regimen of induction chemotherapy in patients with hormone insensitive metastatic breast cancer - An Eastern Cooperative Oncology Group intergroup study (E3185) SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE hormone-insensitive breast cancer; chemotherapy ID STUDY-GROUP PROJECT; ESTROGEN-RECEPTOR; RANDOMIZED TRIAL; ADRIAMYCIN; THERAPY; METHOTREXATE; SURVIVAL; VATH; CYCLOPHOSPHAMIDE; 5-FLUOROURACIL AB Objective: The objective of this multicenter phase III trial was to study the impact on time to treatment failure (TTF) and survival of cyclophosphamide, Adriamycin, and 5-fluorouracil (CAF) versus CAF/thiotepa, Adriamycin, vinblastine, and Halotestin (TsAVbH), a partially noncross-resistant regimen used in a rotating schedule in the treatment of hormone insensitive metastatic breast cancer in accordance with the Goldie and Coldman hypothesis. Methods: Three hundred forty-three patients received 6 cycles of induction treatment with one of 2 regimens. Patients with estrogen receptor-negative tumors or those with estrogen receptor-positive or estrogen receptor-unknown tumors with demonstrated unresponsiveness to hormone treatment were eligible. Complete responders were randomized to either observation or maintenance therapy with cyclophosphamide, methotrexate, 5-fluorouracil, prednisone, tamoxifen, and Halotestin (CMF[P]TH). Patients with partial response or stable disease on completion of induction therapy were maintained on CMF plus Halotestin. Results: There were no differences in the primary end point of TTF (median 7.3 and 7.4 months, respectively). There was a significant difference in TTF and survival by duration of disease-free interval: a median of 8.8 and 21.2 months for those with a disease-free interval of >= 2 years versus 6 to 8 and 13.3 months for those with a disease-free interval <2 years (P = 0.016 and <0.001), respectively. Toxicity of the 2 treatment regimens was similar. Conclusion: There were no differences observed in TTF, survival, and toxicities between the 2 treatment arms, both of which contained doxorubicin (Adriamycin) as the most active agent. The results of observation versus maintenance in complete responders were reported separately. C1 Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY 14642 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Pretoria, ZA-0002 Pretoria, South Africa. Univ Colorado, Denver, CO 80202 USA. RP Pandya, KJ (reprint author), Univ Rochester, James P Wilmot Canc Ctr, 601 Elmwood Ave,Box 704, Rochester, NY 14642 USA. EM Kishan_Pandya@urmc.rochester.edu FU NCI NIH HHS [CA32102, CA22433, CA66636, CA23318, CA21115, CA16116, CA11083] NR 22 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD APR PY 2007 VL 30 IS 2 BP 113 EP 125 DI 10.1097/01.coc.0000251244.60473.c5 PG 13 WC Oncology SC Oncology GA 156GW UT WOS:000245637100003 PM 17414459 ER PT J AU Soupir, CP Vergilio, JA Dal Cin, P Muzikansky, A Kantarjian, H Jones, D Hasserjian, RP AF Soupir, Chad P. Vergilio, Jo-Anne Dal Cin, Paola Muzikansky, Alona Kantarjian, Hagop Jones, Dan Hasserjian, Robert P. TI Philadelphia chromosome-positive acute myeloid leukemia - A rare aggressive leukemia with clinicopathologic features distinct from chronic myeloid leukemia in myeloid blast crisis SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE hematopathology; genetics; cytogenetics; leukemia; Philadelphia chromosome ID CHRONIC MYELOGENOUS LEUKEMIA; BIPHENOTYPIC ACUTE-LEUKEMIA; TRIAL COMPARING IDARUBICIN; BONE-MARROW CELLULARITY; IMATINIB MESYLATE; CHRONIC PHASE; MECHANISMS; ABNORMALITIES; DAUNORUBICIN; CYTOGENETICS AB We performed a multi-institutional retrospective analysis of the morphologic features, immunophenotype, cytogenetics, and BCR-ABL transcript characterization of cases of Philadelphia chromosome-positive acute myeloid leukemia (Ph+ AML). We compared these cases with cases of documented chronic myelogenous leukemia in myeloid blast crisis (CML-MBC). Patients with Ph+ AML were less likely to have splenomegaly or peripheral basophilia and had lower bone marrow cellularity and myeloid/erythroid ratios than patients with CML-MBC. Additional specific cytogenetic abnormalities that typically occur in CML-MBC were less common in Ph+ AML. Of 7 patients with Ph+ AML treated with imatinib mesylate, 6 showed at least a partial hematologic response, but the responses were of a short duration (median, 2.5 months). The median survival of patients with Ph+ AML was 9 months, similar to that of patients with CML-MBC (7 months). Ph+ AML is a rare aggressive acute leukemia with some features distinct from CML-MBC. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Univ Texas, MD Anderson Canc Ctr, Dept Hematol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. RP Hasserjian, RP (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. RI Jones, Daniel/I-7399-2015 NR 45 TC 59 Z9 66 U1 0 U2 1 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 APR PY 2007 VL 127 IS 4 BP 642 EP 650 DI 10.1309/B4NVER1AJJ84CTUU PG 9 WC Pathology SC Pathology GA 150VQ UT WOS:000245248100019 PM 17369142 ER PT J AU Garcia-Godoy, F de Jager, M AF Garcia-Godoy, Franklin de Jager, Marko TI Effect of manual and powered toothbrushes on orthodontic bracket bond strength SO AMERICAN JOURNAL OF DENTISTRY LA English DT Article ID COUNTERROTATIONAL TOOTHBRUSHES; SONIC TOOTHBRUSH AB Purpose: To assess in vitro the effect of manual and powered toothbrushes on the bond strength of orthodontic brackets. Methods: Specimens of orthodontic brackets bonded to the surfaces of extracted teeth were exposed to one of two powered toothbrushes (Sonicare Elite, Braun Oral-B 3D Excel) or a manual toothbrush (Oral-B 35) for the equivalent of a 2-year exposure to brushing in the presence of toothpaste slurry. Control specimens underwent no brushing. For each treatment, 10 specimens were tested and evaluated. Shear bond strength of the orthodontic bracket to the tooth surface was assessed after exposure to simulated brushing. ANOVA was used to analyze the data. Results: No differences in orthodontic bracket bond strength were observed between any of the three treatments and the control. The evaluated toothbrushes did not adversely affect the in vitro bonding strength of orthodontic brackets, suggesting they are safe to use in orthodontic patients. C1 Nova SE Univ, Coll Dent Med, Biosci Res Ctr, Ft Lauderdale, FL 33328 USA. Nova SE Univ, Coll Dent Med, Clin Res Ctr, Ft Lauderdale, FL 33328 USA. Forsyth Inst, Boston, MA USA. Philips Oral Healthcare, Clin & Sci Affairs, Washington, DC USA. RP Garcia-Godoy, F (reprint author), Nova SE Univ, Coll Dent Med, Biosci Res Ctr, S Univ Dr, Ft Lauderdale, FL 33328 USA. EM fgarciagodoy@gmail.com NR 9 TC 5 Z9 5 U1 1 U2 1 PU MOSHER & LINDER, INC PI WESTON PA 318 INDIAN TRACE SUITE 500, WESTON, FL 33326 USA SN 0894-8275 J9 AM J DENT JI Am. J. Dent. PD APR PY 2007 VL 20 IS 2 BP 90 EP 92 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 160GV UT WOS:000245929800005 PM 17542201 ER PT J AU Garcia-Godoy, F Tay, FR Pashley, DH Feilzer, A Tjaderhane, L Pashley, EL AF Garcia-Godoy, Franklin Tay, Franklin R. Pashley, David H. Feilzer, Albert Tjaderhane, L. Pashley, Edna L. TI Degradation of resin-bonded human dentin after 3 years of storage SO AMERICAN JOURNAL OF DENTISTRY LA English DT Article ID MATRIX METALLOPROTEINASES; COLLAGEN DEGRADATION; WATER STORAGE; GELATINASE-A; IN-SITU; INHIBITION; EXPRESSION; CLEAVAGE; ENZYME; TISSUE AB Purpose: To test, in vitro, the null hypothesis that there was no difference in the ultrastructure of adhesive-bonded, acid-etched dentin aged under accelerated conditions in mineral oil or artificial saliva. Methods: Beams of human dentin bonded with three total-etch adhesives were retrieved from the two storage media after 3 years and prepared for transmission electron microscopy. Results: Hybrid layers from specimens aged in mineral oil exhibited structural integrity of the collagen network. Conversely, abnormal hybrid layers were seen in specimens aged in artificial saliva, with progressive disintegration of the fibrillar network to the extent that it was beyond detection by collagen staining. Self-destruction of collagen matrices can occur in resin-infiltrated dentin, and to a lesser degree, in mineralized dentin in the absence of bacterial or salivary enzymes. C1 Nova SE Univ, Coll Dent Med, Biosci Res Ctr, Ft Lauderdale, FL 33328 USA. Forsyth Inst, Boston, MA USA. Med Coll Georgia, Sch Dent, Dept Oral Biol & Maxillofacial Surg, Augusta, GA 30912 USA. ACTA, Dept Dent Mat Sci, Amsterdam, Netherlands. Med Coll Georgia, Sch Dent, Dept Oral Diag, Augusta, GA 30912 USA. RP Garcia-Godoy, F (reprint author), Nova SE Univ, Coll Dent Med, Biosci Res Ctr, 3200 S Univ Dr, Ft Lauderdale, FL 33328 USA. EM fgarciagodoy@gmail.com RI Tjaderhane, Leo/J-5017-2015 OI Tjaderhane, Leo/0000-0002-5018-478X FU NIDCR NIH HHS [DE014911, DE015306] NR 31 TC 18 Z9 18 U1 0 U2 1 PU MOSHER & LINDER, INC PI WESTON PA 318 INDIAN TRACE SUITE 500, WESTON, FL 33326 USA SN 0894-8275 J9 AM J DENT JI Am. J. Dent. PD APR PY 2007 VL 20 IS 2 BP 109 EP 113 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 160GV UT WOS:000245929800009 PM 17542205 ER PT J AU Pietrzak, RH Morasco, BJ Blanco, C Grant, BF Petry, NM AF Pietrzak, Robert H. Morasco, Benjamin J. Blanco, Carlos Grant, Bridget F. Petry, Nancy M. TI Gambling level and psychiatric and medical disorders in older adults: Results from the national epidemiologic survey on alcohol and related conditions SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article; Proceedings Paper CT Summer Training on Aging Research Topics in Mental Health Conference CY AUG 05-07, 2005 CL San Diego, CA DE older adults; problem gambling; pathological gambling; recreational gambling; health; substance abuse; epidemiology ID INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; QUALITY-OF-LIFE; DSM-IV ALCOHOL; UNITED-STATES; PATHOLOGICAL GAMBLERS; PERSONALITY-DISORDERS; RHEUMATOID-ARTHRITIS; SOCIAL ACTIVITY; FAMILY-HISTORY AB Objective: This study examined the association between gambling level and psychiatric and medical disorders in a nationally representative sample of older adults. Method: Data on 10,563 U. S. older adults (age 60 or older) were analyzed from the National Epidemiologic Survey on Alcohol and Related Conditions. Results: A total 28.74% of older adults were lifetime recreational gamblers and 0.85% were lifetime disordered gamblers. Compared with older adults without a history of regular gambling, recreational gamblers had significantly elevated rates of alcohol (30.1% versus 12.8%), nicotine (16.9% versus 8.0%), mood (12.6% versus 11.0%), anxiety (15.0% versus 11.6%), and personality disorders (11.3% versus 7.3%) and obesity (25.6% versus 20.8%), but were less likely to have past-year diagnoses of arteriosclerosis (4.7% versus 6.0%) or cirrhosis (0.2% versus 0.4%). Disordered gamblers were significantly more likely than older adults without a history of regular gambling to have alcohol (53.2% versus 12.8%), nicotine (43.2% versus 8.0%), drug (4.6% versus 0.7%), mood (39.5% versus 11.0%), anxiety (34.5% versus 11.6%), and personality (43.0% versus 7.3%) disorders, and to have past-year diagnoses of arthritis (60.2% versus 44.3%) or angina (22.7% versus 8.8%). These results remained significant even after controlling for demographic, psychiatric, and behavioral risk factors. Conclusions: Lifetime recreational gamblers were more likely than nonregular gamblers to have psychiatric disorders but were less likely to have some medical conditions. Lifetime disordered gamblers had a range of lifetime psychiatric disorders and were more likely than nonregular gamblers to have past-year diagnoses of angina and arthritis. C1 Univ Connecticut, Ctr Hlth, Dept Psychiat, Farmington, CT 06030 USA. Portland VA Med Ctr, Div Behav Hlth & Clin Neurosci, Portland, OR USA. Columbia Univ, Dept Psychiat, New York, NY USA. NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD USA. RP Petry, NM (reprint author), Univ Connecticut, Ctr Hlth, Dept Psychiat, 263 Farmington Ave, Farmington, CT 06030 USA. EM petry@psychiatry.uchc.edu RI Blanco, Carlos/I-4906-2013 OI Blanco, Carlos/0000-0001-6187-3057 FU Intramural NIH HHS; NIAAA NIH HHS [P50-AA03510]; NIDA NIH HHS [P50-DA09241, R01-DA016855, R01-DA13444, R01-DA14618]; NIMH NIH HHS [R01-MH60417, R01-MH60417-SUPP] NR 58 TC 51 Z9 51 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD APR PY 2007 VL 15 IS 4 BP 301 EP 313 DI 10.1097/01.JGP.0000239353.40880.cc PG 13 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 149NX UT WOS:000245154800005 PM 17095749 ER PT J AU Lu, WN van Eerde, AM Fan, XP Quintero-Rivera, F Kulkarni, S Ferguson, H Kim, HG Fan, YL Xi, QC Li, QG Sanlaville, D Andrews, W Sundaresan, V Bi, WM Yan, J Giltay, JC Wijmenga, C de Jong, TPVM Feather, SA Woolf, AS Rao, Y Lupski, JR Eccles, MR Quade, BJ Gusella, JF Morton, CC Maas, RL AF Lu, Weining van Eerde, Albertien M. Fan, Xueping Quintero-Rivera, Fabiola Kulkarni, Shashikant Ferguson, Heather Kim, Hyung-Goo Fan, Yanli Xi, Qiongchao Li, Qing-Gang Sanlaville, Damien Andrews, William Sundaresan, Vasi Bi, Weimin Yan, Jiong Giltay, Jacques C. Wijmenga, Cisca de Jong, Tom P. V. M. Feather, Sally A. Woolf, Adrian S. Rao, Yi Lupski, James R. Eccles, Michael R. Quade, Bradley J. Gusella, James F. Morton, Cynthia C. Maas, Richard L. TI Disruption of ROBO2 is associated with urinary tract anomalies and confers risk of vesicoureteral reflux SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SMITH-MAGENIS-SYNDROME; AXON GUIDANCE; CONGENITAL-ANOMALIES; NEURONAL MIGRATION; IN-VIVO; MICE; SLIT; GENE; DELETION; MOUSE AB Congenital anomalies of the kidney and urinary tract (CAKUT) include vesicoureteral reflux (VUR). VUR is a complex, genetically heterogeneous developmental disorder characterized by the retrograde flow of urine from the bladder into the ureter and is associated with reflux nephropathy, the cause of 15% of end-stage renal disease in children and young adults. We investigated a man with a de novo translocation, 46, X, t(Y;3)(p11;p12)dn, who exhibits multiple congenital abnormalities, including severe bilateral VUR with ureterovesical junction defects. This translocation disrupts ROBO2, which encodes a transmembrane receptor for SLIT ligand, and produces dominant-negative ROBO2 proteins that abrogate SLIT-ROBO signaling in vitro. In addition, we identified two novel ROBO2 intracellular missense variants that segregate with CAKUT and VUR in two unrelated families. Adult heterozygous and mosaic mutant mice with reduced Robo2 gene dosage also exhibit striking CAKUT-VUR phenotypes. Collectively, these results implicate the SLIT-ROBO signaling pathway in the pathogenesis of a subset of human VUR. C1 Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Gynecol & Reprod Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Human Genet Res, Massachusetts Gen Hosp, Boston, MA 02115 USA. Boston Univ, Renal Sect, Boston, MA 02215 USA. Univ Utrecht, Ctr Med, Dept Med Genet, NL-3508 TC Utrecht, Netherlands. Univ Utrecht, Ctr Med, Dept Pediat Urol, NL-3508 TC Utrecht, Netherlands. Northwestern Univ, Inst Neurosci, Chicago, IL 60611 USA. Kings Coll London, Med Res Council Ctr Dev Neurobiol, London WC2R 2LS, England. Hop Necker Enfants Malad, Dept Genet, F-75730 Paris, France. UCL, Nephrourol Unit, Inst Child Hlth, London WC1E 6BT, England. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. St James Univ Hosp, Dept Pediat Nephrol, Leeds, W Yorkshire, England. Univ Otago, Dept Pathol, Dunedin, New Zealand. RP Maas, RL (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet, NRB 458,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM maas@genetics.med.harvard.edu RI Wijmenga, Cisca/D-2173-2009; sanlaville, damien/M-4716-2014; OI sanlaville, damien/0000-0001-9939-2849; Fan, Xueping/0000-0002-3715-6864; de Jong, Tom P.V.M./0000-0002-9091-1099; Lu, Weining/0000-0002-6570-3044; Woolf, Adrian/0000-0001-5541-1358; Wijmenga, Cisca/0000-0002-5635-1614 FU NIDDK NIH HHS [R01 DK063316]; NIGMS NIH HHS [P01 GM061354] NR 44 TC 89 Z9 98 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 2007 VL 80 IS 4 BP 616 EP 632 DI 10.1086/512735 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 153VV UT WOS:000245465200004 PM 17357069 ER PT J AU Reich, D Patterson, N Ramesh, V De Jager, PL McDonald, GJ Tandon, A Choy, E Hu, DL Tamraz, B Pawlikowska, L Wassel-Fyr, C Huntsman, S Waliszewska, A Rossin, E Li, RL Garcia, M Reiner, A Ferrell, R Cummings, S Kwok, PY Harris, T Zmuda, JM Ziv, E AF Reich, David Patterson, Nick Ramesh, Vijaya De Jager, Philip L. McDonald, Gavin J. Tandon, Arti Choy, Edwin Hu, Donglei Tamraz, Bani Pawlikowska, Ludmila Wassel-Fyr, Christina Huntsman, Scott Waliszewska, Alicja Rossin, Elizabeth Li, Rongling Garcia, Melissa Reiner, Alexander Ferrell, Robert Cummings, Steve Kwok, Pui-Yan Harris, Tamara Zmuda, Joseph M. Ziv, Elad CA Hlth ABC Study TI Admixture mapping of an allele affecting interleukin 6 soluble receptor and interleukin 6 levels SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; NECROSIS-FACTOR-ALPHA; LINKAGE-DISEQUILIBRIUM; CARDIOVASCULAR HEALTH; INFLAMMATORY MARKERS; OLDER-ADULTS; GENOME; ASSOCIATION; GENES AB Circulating levels of inflammatory markers can predict cardiovascular disease risk. To identify genes influencing the levels of these markers, we genotyped 1,343 single-nucleotide polymorphisms (SNPs) in 1,184 African Americans from the Health, Aging and Body Composition (Health ABC) Study. Using admixture mapping, we found a significant association of interleukin 6 soluble receptor (IL-6 SR) with European ancestry on chromosome 1 (LOD 4.59), in a region that includes the gene for this receptor (IL-6R). Genotyping 19 SNPs showed that the effect is largely explained by an allele at 4% frequency in West Africans and at 35% frequency in European Americans, first described as associated with IL-6 SR in a Japanese cohort. We replicate this association (P << 1.0 x 10(-12)) and also demonstrate a new association with circulating levels of a different molecule, IL-6 (P < 3.4 x 10(-5)). After replication in 1,674 European Americans from Health ABC, the combined result is even more significant: P << 1.0 x 10(-12) for IL-6 SR, and P < 2.0 x 10(-9) for IL-6. These results also serve as an important proof of principle, showing that admixture mapping can not only coarsely localize but can also fine map a phenotypically important variant. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Richard B Simches Res Ctr, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Neurol, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Partners Healthcare Ctr Genet & Genom, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Program Med & Populat Genet, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. Univ Calif San Francisco, Div Gen Internal Med, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Grad Program Pharmaceut Sci & Pharmacogenom, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Calif Pacific Med Ctr Res Inst, San Francisco Coordinating Ctr, San Francisco, CA USA. Univ Tennessee, Hlth Sci Ctr, Knoxville, TN 37996 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Washington, Sch Publ Hlth & Community Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. Univ Pittsburgh, Dept Epidemiol & Human Genet, Pittsburgh, PA 15260 USA. RP Reich, D (reprint author), Harvard Univ, Sch Med, Dept Genet, New Res Bldg,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM reich@genetics.med.harvard.edu RI Kwok, Pui-Yan/F-7725-2014; Ziv, Elad/L-5396-2014; OI Kwok, Pui-Yan/0000-0002-5087-3059; Choy, Edwin/0000-0001-9896-8084 FU NCI NIH HHS [K22 CA109351]; NCRR NIH HHS [U54 RR020278]; NIA NIH HHS [N01 AG062101, N01 AG062103, N01 AG062106, R01 AG021024]; NIGMS NIH HHS [T32 GM007753]; NINDS NIH HHS [P30 NS045776] NR 43 TC 111 Z9 114 U1 0 U2 2 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 APR PY 2007 VL 80 IS 4 BP 716 EP 726 DI 10.1086/513206 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 153VV UT WOS:000245465200012 PM 17357077 ER PT J AU Leach, NT Sun, Y Michaud, S Zheng, Y Ligon, KL Ligon, AH Sander, T Korf, BR Lu, WN Harris, DJ Gusella, JF Maas, RL Quade, BJ Cole, AJ Kelz, MB Morton, CC AF Leach, Natalia T. Sun, Yi Michaud, Sebastien Zheng, Yi Ligon, Keith L. Ligon, Azra H. Sander, Thomas Korf, Bruce R. Lu, Weining Harris, David J. Gusella, James F. Maas, Richard L. Quade, Bradley J. Cole, Andrew J. Kelz, Max B. Morton, Cynthia C. TI Disruption of diacylglycerol kinase delta (DGKD) associated with seizures in humans and mice SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID IDIOPATHIC GENERALIZED EPILEPSIES; FUNCTIONAL-CHARACTERIZATION; FEBRILE SEIZURES; IN-VITRO; MUTATIONS; SUSCEPTIBILITY; DELETION; RECEPTOR; GENE; STIMULATION AB We report a female patient with a de novo balanced translocation, 46, X, t(X;2)(p11.2;q37)dn, who exhibits seizures, capillary abnormality, developmental delay, infantile hypotonia, and obesity. The 2q37 breakpoint observed in association with the seizure phenotype is of particular interest, because it lies near loci implicated in epilepsy in humans and mice. Fluorescence in situ hybridization mapping of the translocation breakpoints showed that no known genes are disrupted at Xp11.2, whereas diacylglycerol kinase delta (DGKD) is disrupted at 2q37. Expression studies in Drosophila and mouse suggest that DGKD is involved in central nervous system development and function. Electroencephalographic assessment of Dgkd mutant mice revealed abnormal epileptic discharges and electrographic seizures in three of six homozygotes. These findings implicate DGKD disruption by the t( X; 2)( p11.2; q37) dn in the observed phenotype and support a more general role for DGKD in the etiology of seizures. C1 Brigham & Womens Hosp, Dept Obstet, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Gynecol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Reprod Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Epilepsy Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Epilepsy Res Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Boston Univ, Ctr Med, Dept Med, Boston, MA 02215 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Penn, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. CRCHUL, Unite Rech Pediat, Quebec City, PQ, Canada. Max Delbruck Ctr, GMC, Berlin, Germany. Univ Alabama, Dept Genet, Tuscaloosa, AL 35487 USA. RP Morton, CC (reprint author), Brigham & Womens Hosp, Dept Obstet, 77 Ave Louis Pasteur,NRB160, Boston, MA 02115 USA. EM cmorton@partners.org RI Kelz, Max/E-4054-2010; OI Kelz, Max/0000-0002-2803-6078; Lu, Weining/0000-0002-6570-3044; Ligon, Keith/0000-0002-7733-600X FU NCI NIH HHS [P30 CA006516, P30 CA06516]; NICHD NIH HHS [F32 HD043627, F32 HD43627]; NIGMS NIH HHS [K08 GM077357, P01 GM061354] NR 36 TC 24 Z9 25 U1 0 U2 2 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 APR PY 2007 VL 80 IS 4 BP 792 EP 799 DI 10.1086/513019 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 153VV UT WOS:000245465200019 PM 17357084 ER PT J AU Moran, A Roux, AVD Jackson, SA Kramer, H Manolio, TA Shrager, S Shea, S AF Moran, Andrew Roux, Ana V. Diez Jackson, Sharon A. Kramer, Holly Manolio, Teri A. Shrager, Sandi Shea, Steven TI Acculturation is associated with hypertension in a multiethnic sample SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE hypertension; acculturation; ethnicity; Chinese; hispanic; African-American ID MEXICAN-AMERICAN ADULTS; HIGH BLOOD-PRESSURE; RISK-FACTORS; UNITED-STATES; NHANES-III; PREVALENCE; HEALTH; IMMIGRANTS; BEHAVIORS; MIGRATION AB Background: Hypertension varies in prevalence among race/ethnic groups in the United States. Within-ethnic group differences associated with acculturation have been less frequently examined. We studied the association of three measures of acculturation (language spoken at home, place of birth, and years living in the US) with hypertension in a population sample of 2619 white, 1898 African American, 1,494 Hispanic, and 803 Chinese participants in the Multiethnic Study of Atherosclerosis. Methods: Multivariate Poisson regression was used to estimate the association between the acculturation variables and hypertension. Results: Birthplace outside the US and speaking a non-English language at home were each associated with a lower prevalence of hypertension after adjustment for age, gender, and socioeconomic status (prevalence ratio [95% confidence intervals] 0.82 (0.77-0.87) for non-US born versus US born and 0.80 (0.74-0.85) for those not speaking English at home versus speakers of English at home, both P<.001). For participants born outside of the US, each 10-year increment of years in the US was associated with a higher prevalence of hypertension after adjustment for age, gender, and socioeconomic status (P for trend <.01). The associations between acculturation variables and hypertension were weakened after adjustment for race/ethnic category and risk factors for hypertension. Compared to US-born Hispanics, those born in Mexico or South America had lower prevalence of hypertension, but those born in the Caribbean and Central America had higher prevalence of hypertension. Conclusions: Acculturation and place of birth are associated with hypertension in a multiethnic sample. C1 Univ Michigan, Ctr Social Epidemiol & Populat Hlth, Dept Epidemiol, Ann Arbor, MI 48104 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Loyola Univ, Dept Prevent Med, Maguire Ctr, Maywood, IL 60153 USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA. Columbia Univ, Dept Med, New York, NY USA. Columbia Univ, Dept Epidemiol, Joseph Mailman Sch Publ Hlth, New York, NY USA. RP Roux, AVD (reprint author), Univ Michigan, Ctr Social Epidemiol & Populat Hlth, Dept Epidemiol, 1214 S Univ, Ann Arbor, MI 48104 USA. EM adiezrou@umich.edu OI Kramer, Holly/0000-0002-6374-837X FU NHLBI NIH HHS [N01-HC-95159, N01-HC-95166, N01 HC095161, N01-HC-95165] NR 29 TC 53 Z9 53 U1 4 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD APR PY 2007 VL 20 IS 4 BP 354 EP 363 DI 10.1016/j.amjhyper.2006.09.025 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 156YQ UT WOS:000245686200003 PM 17386340 ER PT J AU Gelber, RP Gaziano, JM Manson, JE Buring, JE Sesso, HD AF Gelber, Rebecca P. Gaziano, J. Michael Manson, Joann E. Buring, Julie E. Sesso, Howard D. TI A prospective study of body mass index and the risk of developing hypertension in men SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE hypertension; obesity; body mass index ID HIGH BLOOD-PRESSURE; WEIGHT-LOSS; LONG-TERM; PRIMARY PREVENTION; MILD HYPERTENSION; SODIUM REDUCTION; CONTROLLED TRIAL; FINAL REPORT; PHASE-II; OVERWEIGHT AB Background: Although obesity is known to increase the risk of hypertension, few studies have prospectively evaluated body mass index (BMI) across the range of normal weight and overweight as a primary risk factor. Methods: In this prospective cohort, we evaluated the association between BMI and risk of incident hypertension. We studied 13,563 initially healthy, nonhypertensive men who participated in the Physicians' Health Study. We calculated BMI from self-reported weight and height and defined hypertension as self-reported systolic blood pressure (BP) >= 140 mm Hg, diastolic BP >= 90 mm Hg, or new antihypertensive medication use. Results: After a median 14.5 years, 4920 participants developed hypertension. Higher baseline BMI, even within the "normal" range, was consistently associated with increased risk of hypertension. Compared to participants in the lowest BMI quintile (< 22.4 kg/m(2)), the relative risks (95% confidence interval) of developing hypertension for men with a BMI of 22.4 to 23.6, 23.7 to 24.7, 24.8 to 26.4, and > 26.4 kg/m(2) were 1.20 (1.09-1.32), 1.31 (1.19-1.44), 1.56 (1.42-1.72), and 1.85 (1.69-2.03), respectively (P for trend, < 0001). Further adjustment for diabetes, high cholesterol, and baseline BP did not substantially alter these results. We found similar associations using other BMI categories and after excluding men with smoking history, those who developed hypertension in the first 2 years, and those with diabetes, obesity, or high cholesterol at baseline. Conclusions: In this large cohort, we found a strong gradient between higher BMI and increased risk of hypertension, even among men within the "normal" and mildly "overweight" BMI range. Approaches to reduce the risk of developing hypertension may include prevention of overweight and obesity. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging,Dept Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. RP Gelber, RP (reprint author), 677 Huntington Ave,Kresge Bldg,9th Fl, Boston, MA 02115 USA. EM rgelber@hsph.harvard.edu FU NCI NIH HHS [CA 34944, R01 CA034944, CA 40360, R01 CA097193, R01 CA040360]; NHLBI NIH HHS [HL 34595, R01 HL034595, HL 26490, R01 HL026490]; NIA NIH HHS [T32 AG000158] NR 31 TC 81 Z9 91 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD APR PY 2007 VL 20 IS 4 BP 370 EP 377 DI 10.1016/j.amjhyper.2006.10.011 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 156YQ UT WOS:000245686200005 PM 17386342 ER PT J AU Primo, V Zhang, QY Amaout, MA Nikolic, B AF Primo, Valeria Zhang, Qing-Ying Amaout, M. Amin Nikolic, Boris TI Anti-PR3 immune response mediates renal injury SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of the National-Kidney-Foundation CY APR 10-14, 2007 CL Orlando, FL SP Natl Kidney Fdn C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2007 VL 49 IS 4 MA 151 BP A62 EP A62 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 155QN UT WOS:000245593100163 ER PT J AU Smirnakis, KV Plati, A Wolf, M Thadhani, R Ecker, JL AF Smirnakis, Karen V. Plati, Alicia Wolf, Myles Thadhani, Ravi Ecker, Jeffrey L. TI Predicting gestational diabetes: choosing the optimal early serum marker SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the American-Gynecological-and-Obstetrical-Society CY SEP 14-16, 2006 CL Willamsburg, VA SP Amer Gynecol & Obstetr Soc DE C-reactive protein; gestational diabetes mellitus; homeostasis model assessment; sex hormone-binding globulin ID RANDOMIZED CONTROLLED TRIAL; INSULIN-RESISTANCE; MELLITUS; PREGNANCY; GLUCOSE AB OBJECTIVE: Serum markers measured early in pregnancy have been associated with the later diagnosis of gestational diabetes mellitus. To select an optimal early (<20 weeks) marker, we prospectively compared 3 serum markers examined simultaneously in a single cohort. STUDY DESIGN: A nested case-control design was used to evaluate the association of sex hormone-binding globulin, high-sensitive C-reactive protein, and measures of fasting glucose and insulin (homeostasis assessment model) obtained in the late first trimester and early second trimester of pregnancy with the diagnosis of gestational diabetes mellitus. Multivariate modeling and log likelihood ratios were used to identify the optimal biomarker associated with gestational diabetes mellitus. RESULTS: In both first and second trimester samples, sex hormone-binding globulin was lower and high-sensitive C-reactive protein higher among women who subsequently developed gestational diabetes mellitus. Similarly an elevated second-trimester homeostasis assessment model was associated with gestational diabetes mellitus. Multivariate analysis suggested that sex hormone-binding globulin measured from nonfasting first-trimester sera was the best predictor of gestational diabetes mellitus in our population. CONCLUSION: Among 3 biomarkers examined prospectively, first-trimester nonfasting sex hormone-binding globulin appeared to be the optimal marker to predict subsequent gestational diabetes mellitus. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. RP Smirnakis, KV (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit,Dept Med, Boston, MA 02115 USA. NR 18 TC 5 Z9 5 U1 2 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD APR PY 2007 VL 196 IS 4 AR 410.e1 DI 10.1016/j.ajog.2006.12.011 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 157UT UT WOS:000245747600055 PM 17403439 ER PT J AU Hanson, DB AF Hanson, Douglas B. TI The archaeology of disease SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Book Review C1 Forsyth Inst, Boston, MA USA. RP Hanson, DB (reprint author), Forsyth Inst, Boston, MA USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PD APR PY 2007 VL 132 IS 4 BP 650 EP 651 DI 10.1002/ajpa.20572 PG 2 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 149QA UT WOS:000245160500018 ER PT J AU Kunkel, CF Figoni, SF Baumgarten, JM Carvalho, CM Kim, HS Oshiro, RL Zirovich, MD Scremin, OU Scremin, AME AF Kunkel, Charles F. Figoni, Stephen F. Baumgarten, Jana M. Carvalho, Claudio M. Kim, Hyung S. Oshiro, Resa L. Zirovich, Milena D. Scremin, Oscar U. Scremin, A. M. Erika TI Scanning laser-Doppler imaging of leg- and foot-skin perfusion in normal subjects - Analysis of age, gender, site, and laser-type effects SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE microcirculation; laser Doppler flowmetry; rehabilitation; wound healing ID TRANS-CUTANEOUS OXYGEN; AMPUTATION LEVEL SELECTION; BLOOD-FLOW; ARTERIAL-DISEASE; PRESSURE; FLOWMETER; TENSION AB Objectives: To report normal values of skin perfusion in healthy subjects in three age groups using a laser Doppler imager; to determine differences attributable to gender, age, site, and use of red or near-infrared lasers; and to correlate transcutaneous oxygen with laser flux values Design: Flux and transcutaneous oxygen were measured at ten sites in the lower extremity in 60 subjects from three age groups. Heated and unheated sites were scanned with red and near-infrared lasers. Results: Heat hyperemia was prominent at all sites. Small, statistically significant mean +/- SD differences were found between heated and nonheated sites for the red and near-infrared lasers (P = 0.02). All flux ratios were independent of gender but were higher in the oldest group. Plantar sites demonstrated higher flux in unheated areas and lower flux ratios compared with leg sites. Transcutaneous oxygen did not correlate significantly with flux for either laser type. Conclusions: Scanning laser-Doppler imaging flux values provide a reference for identifying patients at risk for tissue ischemia. and poor healing potential caused by impaired circulatory reserve in the legs and distal feet. The lack of correlation between flux and transcutaneous oxygen in healthy individuals suggests that they measure different physiologic processes. C1 VA Greater Los Angeles Healthcare Ctr, Dept Phys Med & Rehabil, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Ctr, Res Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Physiol, David Geffen Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, VA Greater Los Angeles Phys Med & Rehabil Residen, Los Angeles, CA USA. RP Kunkel, CF (reprint author), VA W Los Angeles Healthcare Ctr, 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 33 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD APR PY 2007 VL 86 IS 4 BP 262 EP 271 DI 10.1097/PHM.0b013e3180353526 PG 10 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 150QV UT WOS:000245232200003 PM 17413539 ER PT J AU Hafezi-Moghadam, A Thomas, KL Wagner, DD AF Hafezi-Moghadam, Ali Thomas, Kennard L. Wagner, Denisa D. TI ApoE deficiency leads to a progressive age-dependent blood-brain barrier leakage SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE apolipoprotein E; aging; age-related neurodegeneration; inflammation ID APOLIPOPROTEIN-E; ALZHEIMERS-DISEASE; ENDOTHELIAL-CELLS; COGNITIVE DECLINE; MICE; VOLUME; FLOW; PERMEABILITY; PATHOGENESIS; ALLELE AB Previously, we reported a defect in the blood-brain barrier ( BBB) of apolipoprotein E-deficient ( apoE(-/-)) mice ( 24). Here, we investigate BBB permeability in wild- type ( WT) and apoE(-/-) mice as a function of age. Both WT and apoE(-/-) mice showed significantly increased cortical BBB leakage with age. However, in apoE(-/-) mice, the leakage increased at a 3.7 x higher rate compared with WT mice. Surprisingly, the cerebellum showed significantly more leakage than other brain regions across age, while there was no difference between the two hemispheres. To determine the contribution of tissue- vs. blood- borne apoE to vascular permeability, we generated chimeric mice by bone marrow transplantation and measured their BBB leakage. These experiments suggest that both blood- and tissue- derived apoE are equally important for BBB function. In sum, we find an age-dependent defect in the BBB that is exacerbated in apoE(-/-) mice. Since vascular defects are found in patients with age- related neurodegenerative diseases, such as Alzheimer's, age- related BBB leakage could underlie these defects and may thus be an important contributor to the cumulative neuronal damage of these diseases. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hafezi-Moghadam, A (reprint author), 325 Cambridge St,3rd Fl, Boston, MA 02114 USA. EM AHM@meei.harvard.edu OI Hafezi-Moghadam, Ali/0000-0002-5336-0697 FU NEI NIH HHS [EY-14104]; NHLBI NIH HHS [HL-53756, R01 HL053756]; NIAID NIH HHS [K08 AI-50775] NR 47 TC 57 Z9 57 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD APR PY 2007 VL 292 IS 4 BP C1256 EP C1262 DI 10.1152/ajpcell.00563.2005 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 188RG UT WOS:000247936400006 PM 16870825 ER PT J AU Huang, D Khoe, M Befekadu, M Chung, S Takata, Y Ilic, D Bryer-Ash, M AF Huang, Danshan Khoe, Michelle Befekadu, Merone Chung, Sue Takata, Yasunori Ilic, Dusko Bryer-Ash, Michael TI Focal adhesion kinase mediates cell survival via NF-kappa B and ERK signaling pathways SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE apoptosis; ERK1/2; insulin; TNF-alpha; IGF-1 ID TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR-I; INSULIN-RECEPTOR SUBSTRATE-1; ALPHA-INDUCED APOPTOSIS; PEROXIDE-INDUCED APOPTOSIS; PHOSPHATIDYLINOSITOL 3-KINASE; MOLECULAR-MECHANISMS; BROWN ADIPOCYTES; GENE-EXPRESSION; GLUCOSE-UPTAKE AB Focal adhesion kinase ( FAK) is important to cellular functions such as proliferation, migration, and survival of anchorage- dependent cells. We investigated the role of FAK in modulating normal cellular responses, specifically cell survival in response to inflammatory stimuli and serum withdrawal, using FAK- knockout ( FAK(-/-)) embryonic fibroblasts. FAK(-/-) fibroblasts were more vulnerable to TNF-alpha- induced apoptosis, as measured by terminal deoxynucleotidyl transferase positivity. FAK(-/-) fibroblasts also demonstrated increased procaspase- 3 cleavage to p17 subunit, whereas this was undetectable in FAK(-/-) fibroblasts. Insulin receptor substrate- 1 expression was completely abolished and NF-kappa B activity was reduced, with a concomitant decrease in abundance of the anti- apoptotic protein Bcl- x(L) in FAK(-/-) cells. Upon serum withdrawal, FAK(-/-) cells exhibited marked attenuation of basal ERK phosphorylation, while FAK(-/-) cells, in contrast, maintained high basal ERK phosphorylation. Moreover, inhibition of ERK phosphorylation potentiated serum withdrawal- induced caspase- 3 activity. This was paralleled by increased insulin receptor substrate ( IRS)- 2 expression in FAK(-/-) cells, although both insulin- and IGF-1-mediated phosphorylation of Akt/ PKB and GSK-3 were impaired. This suggests that IRS-2 protects against apoptosis upon serum withdrawal via the ERK signaling pathway. The specific role of FAK to protect cells from apoptosis is regulated by activation and phosphorylation of NF-kappa B and interaction between activated growth factor anti-apoptotic signaling pathways involving both phosphatidylinositol 3- kinase/ Akt and MAPK/ ERK1/2. We demonstrate that FAK is necessary for upregulation of the anti- apoptotic NF-kappa B response, as well as for normal expression of growth factor signaling proteins. Thus we propose a novel role for FAK in protection from cytokine- mediated apoptosis. C1 Univ Calif Los Angeles, Div Endocrinol Diabet & Hypertens, David Geffen Sch Med, W Los Angeles Vet Adm Med Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Div Endocrinol Diabet & Hypertens, David Geffen Sch Med, Gonda Goldschmied Diabet Ctr, Los Angeles, CA 90095 USA. Univ Calif San Francisco, Dept Stomatol & Anat, San Francisco, CA 94143 USA. RP Bryer-Ash, M (reprint author), Univ Calif Los Angeles, Div Endocrinol Diabet & Hypertens, David Geffen Sch Med, W Los Angeles Vet Adm Med Ctr, 900 Vet Ave,Warren Hall,Rm 24-130, Los Angeles, CA 90095 USA. EM mbryerash@mednet.ucla.edu NR 69 TC 44 Z9 48 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD APR PY 2007 VL 292 IS 4 BP C1339 EP C1352 DI 10.1152/ajpcell.00144.2006 PG 14 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 188RG UT WOS:000247936400016 PM 17135301 ER PT J AU Morinelli, TA Raymond, JR Baldys, A Yang, Q Lee, MH Luttrell, L Ullian, ME AF Morinelli, Thomas A. Raymond, John R. Baldys, Aleksander Yang, Qing Lee, Mi-hye Luttrell, Louis Ullian, Michael E. TI Identification of a putative nuclear localization sequence within ANG II AT(1A) receptor associated with nuclear activation SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE G protein-coupled receptors; cyclooxygenase 2 transcription; laser scanning confocal microscopy ID SMOOTH-MUSCLE-CELLS; INTRACELLULAR ANGIOTENSIN-II; SIGNAL-TRANSDUCTION; CYTOPLASMIC TAIL; BINDING SITES; MESSENGER-RNA; PROTEIN; TRANSCRIPTION; INTERNALIZATION; PATHWAY AB Angiotensin II ( ANG II) type 1 ( AT(1)) receptors, similar to other G protein- coupled receptors, undergo desensitization and internalization, and potentially nuclear localization, subsequent to agonist interaction. Evidence suggests that the carboxy- terminal tail may be involved in receptor nuclear localization. In the present study, we examined the carboxyterminal tail of the receptor for specific regions responsible for the nuclear translocation phenomenon and resultant nuclear activation. Human embryonic kidney cells stably expressing either a wild- type AT(1A) receptor- green fluorescent protein ( AT(1A)R/ GFP) construct or a site- directed mutation of a putative nuclear localization sequence ( NLS) [ K307Q] AT(1A)R/ GFP ( KQ/ AT(1A)R/ GFP), were examined for differences in receptor nuclear trafficking and nuclear activation. Receptor expression, intracellular signaling, and ANG II- induced internalization of the wild- type/ GFP construct and of the KQ/ AT(1A)R/ GFP mutant was similar. Laser scanning confocal microscopy showed that in cells expressing the AT(1A)R/ GFP, trafficking of the receptor to the nuclear area and colocalization with lamin B occurred within 30 min of ANG II ( 100 nM) stimulation, whereas the KQ/ AT(1A)R/ GFP mutant failed to demonstrate nuclear localization. Immunoblotting of nuclear lysates with an anti- GFP antibody confirmed these observations. Nuclear localization of the wild- type receptor correlated with increase transcription for both EGR- 1 and PTGS- 2 genes while the nucleardeficient KQ/ AT(1A)R/ GFP mutant demonstrated increases for only the EGR- 1 gene. These results suggest that a NLS ( KKFKKY; aa307 312) is located within the cytoplasmic tail of the AT(1A) receptor and that nuclear localization of the receptor corresponds with specific activation of transcription for the COX- 2 gene PTGS- 2. C1 Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Div Endocrinol, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Hosp, Charleston, SC USA. RP Morinelli, TA (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 829 Clin Sci Bldg,96 Jonathan Lucas St, Charleston, SC 29425 USA. EM morinelt@musc.edu RI Yang, Qing /H-5342-2012 OI Yang, Qing /0000-0002-5068-6085 NR 45 TC 27 Z9 27 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD APR PY 2007 VL 292 IS 4 BP C1398 EP C1408 DI 10.1152/ajpcell.00337.2006 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 188RG UT WOS:000247936400022 PM 17166941 ER PT J AU Yamamoto, M Reeve, JR Green, GM AF Yamamoto, Mitsuyoshi Reeve, Joseph R., Jr. Green, Gary M. TI Supramaximal CCK-58 does not induce pancreatitis in the rat: role of pancreatic water secretion SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE pancreatic fluid secretion; cholecystokinin 8; cholecystokinin 58; acinar fluid secretion; pancreatic chloride secretion ID ACINAR-CELL; ENDOGENOUS CHOLECYSTOKININ; ZYMOGEN ACTIVATION; EXOCRINE PANCREAS; ENZYME-SECRETION; SUBSTANCE-P; CERULEIN; ANTAGONIST; GRANULES; CHANNELS AB In contrast to supramaximal CCK- 8 or caerulein, acute or prolonged supraphysiological levels of endogenous CCK- 58 do not cause pancreatitis. Compared with CCK- 8, CCK- 58 is a much stronger stimulant of pancreatic chloride and water secretion, equivalent to maximally effective secretin, but with a chloride- to- bicarbonate ratio characteristic of acinar fluid. Because supraphysiological endogenous CCK does not cause pancreatitis and because coadministration of secretin ameliorated caerulein- or CCK- 8- induced pancreatitis, coincident with restoring pancreatic water secretion, we hypothesized that supramaximal CCK- 58 would not induce pancreatitis. Conscious rats were infused intravenously with 2 or 4 nmol . kg(-1) . h(-1) of CCK-8 or synthetic rat CCK- 58 for 6 h, and pancreases were examined for morphological and biochemical indexes of acute pancreatitis. A second group was treated as above while monitoring pancreatic protein and water secretion. CCK- 8 at 2 nmol . kg(-1) . h(-1) caused severe edematous pancreatitis as evidenced by morphological and biochemical criteria. CCK- 58 at this dose had minimal or no effect on these indexes. CCK- 58 at 4 nmol . kg(-1) . h(-1) increased some indexes of pancreatic damage but less than either the 2 or 4 nmol . kg(-1) . h(-1) dose of CCK- 8. Pancreatic water and protein secretion were nearly or completely abolished within 3 h of onset of CCK- 8 infusion, whereas water and protein secretion were maintained near basal levels in CCK- 58- treated rats. We hypothesize that supramaximal CCK- 58 does not induce pancreatitis because it maintains pancreatic acinar chloride and water secretion, which are essential for exocytosis of activated zymogens. We conclude that CCK- 58 may be a valuable tool for investigating events that trigger pancreatitis. C1 CURE, Digest Dis Res Ctr, Res Serv 151, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. Univ Calif Los Angeles, Sch Med, Div Digest Dis, Los Angeles, CA USA. RP Reeve, JR (reprint author), CURE, Digest Dis Res Ctr, Res Serv 151, Vet Affairs Greater Los Angeles Healthcare Syst, Bldg 115,Rm 117, Los Angeles, CA 90073 USA. EM jreeve@ucla.edu FU NIDDK NIH HHS [DK-33850, DK-41301, DK-37482] NR 46 TC 11 Z9 11 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD APR PY 2007 VL 292 IS 4 BP G964 EP G974 DI 10.1152/ajpgi.00338.2004 PG 11 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 153KP UT WOS:000245433400003 PM 17158258 ER PT J AU Syrkina, OL Quinn, DA Jung, W Ouyang, B Hales, CA AF Syrkina, Olga L. Quinn, Deborah A. Jung, Walter Ouyang, Bin Hales, Charles A. TI Inhibition of JNK activation prolongs survival after smoke inhalation from fires SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE fire victims; apoptosis; c-Jun NH2-terminal kinase inhibitor ID N-TERMINAL KINASE; POLY(ADP-RIBOSE) POLYMERASE; INDUCED APOPTOSIS; CELL-DEATH; SIGNAL-TRANSDUCTION; PULMONARY INJURY; LUNG INJURY; CLEAVAGE; SHEEP; BURN AB Initial injury from smoke inhalation is mainly to the trachea and bronchi and is characterized by mucosal hyperemia and increased microvascular permeability, exfoliation of epithelial lining, mucous secretion, mucous plugging, and an acute inflammatory cell influx. In this study, we explore the role of the c- Jun N- terminal protein kinase ( JNK) pathway in smoke inhalation lung injury using a rat model of exposure to smoke from burning cotton. Male Sprague- Dawley rats were exposed to smoke from burning cotton for 15 min, and 1 h after injury a JNK inhibitor ( SP- 600125) or vehicle was injected. We measured neutrophil influx, cytokine release, percent of apoptotic cells, airway plugging, and survival. Administration of a JNK inhibitor 1 h after smoke inhalation decreased airway apoptosis, mucous plugging, influx of inflammatory cells, and the release of cytokines and significantly prolonged animal survival ( P < 0.05). These in vivo data show that the JNK pathway plays a critical role in smoke- induced lung injury and offer an attractive therapeutic approach for this injury. C1 Harvard Univ, Pulm & Crit Care Unit, Dept Med, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. Shriners Burn Hosp, Boston, MA USA. RP Syrkina, OL (reprint author), Harvard Univ, Pulm & Crit Care Unit, Dept Med, Massachusetts Gen Hosp,Med Sch, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. EM osyrkina@partners.org NR 46 TC 12 Z9 13 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD APR PY 2007 VL 292 IS 4 BP L984 EP L991 DI 10.1152/ajplung.00248.2006 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 188QX UT WOS:000247935500019 PM 17209141 ER PT J AU Million, M Wang, L Stenzel-Poore, MP Coste, SC Yuan, PQ Lamy, C Rivier, J Buffington, T Tache, Y AF Million, M. Wang, L. Stenzel-Poore, M. P. Coste, S. C. Yuan, P. Q. Lamy, C. Rivier, J. Buffington, T. Tache, Y. TI Enhanced pelvic responses to stressors in female CRF-overexpressing mice SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE chronic stress; colon; urine; locomotor activity; astressin B; mouse urocortin 2 ID CORTICOTROPIN-RELEASING-FACTOR; IRRITABLE-BOWEL-SYNDROME; ESTROGEN-RECEPTOR-BETA; ENTERIC NERVOUS-SYSTEM; INDUCED VISCERAL PAIN; ANXIETY-LIKE BEHAVIOR; GASTROINTESTINAL-TRACT; INTERSTITIAL CYSTITIS; TRANSGENIC MICE; BARRINGTONS NUCLEUS AB Acute stress affects gut functions through the activation of corticotropin-releasing factor (CRF) receptors. The impact of acute stress on pelvic viscera in the context of chronic stress is not well characterized. We investigated the colonic, urinary, and locomotor responses monitored as fecal pellet output (FPO), urine voiding, and ambulatory activity, respectively, in female and male CRF-overexpressing (CRF-OE) mice, a chronic stress model, and their wild-type littermates (WTL). Female CRF-OE mice, compared with WTL, had enhanced FPO to 2-min handling (150%) and 60-min novel environment (155%) but displayed a similar response to a 60-min partial restraint stress. Female CRF-OE mice, compared with WTL, also had a significantly increased number of urine spots (7.3 +/- 1.4 vs. 1.3 +/- 0.8 spots/h) and lower locomotor activity (246.8 +/- 47.8 vs. 388.2 +/- 31.9 entries/h) to a novel environment. Male CRF-OE mice and WTL both responded to a novel environment but failed to show differences between them in colonic and locomotor responses. Male WTL, compared with female WTL, had higher FPO (113%). In female CRF-OE mice, the CRF1/CRF2 receptor antagonist astressin B and the selective CRF2 receptor agonist mouse urocortin 2 (injected peripherally) prevented the enhanced defecation without affecting urine or locomotor responses to novel environment. RT-PCR showed that CRF1 and CRF2 receptors are expressed in the mouse colonic tissues. The data show that chronic stress, due to continuous central CRF overdrive, renders female CRF-OE mice to have enhanced pelvic and altered behavioral responses to superimposed mild stressors and that CRF1-initiated colonic response is counteracted by selective activation of CRF2 receptor. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Ctr Neurovisceral Sci & Womens Hlth, Dept Med, Div Digest Dis, Los Angeles, CA 90024 USA. Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, La Jolla, CA 92037 USA. Ohio State Univ, Dept Vet Clin Sci, Columbus, OH 43210 USA. RP Million, M (reprint author), VA Greater Los Angeles Healthcare Syst, CURE CNS Bldg,115 Rm 118B, Los Angeles, CA 90073 USA. EM mmuluget@ucla.edu RI Lamy, Christophe/B-6432-2016 OI Lamy, Christophe/0000-0001-6944-9787 FU NIDDK NIH HHS [DK-26741, P50 DK-64539, R01 DK-33061, R01 DK-57238, R21 DK-068155]; NIMH NIH HHS [R01 MH-65689] NR 78 TC 33 Z9 33 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD APR PY 2007 VL 292 IS 4 BP R1429 EP R1438 DI 10.1152/ajpregu.00626.2006 PG 10 WC Physiology SC Physiology GA 153KM UT WOS:000245432800007 PM 17194724 ER PT J AU Orton, S Umble, K Zelt, S Porter, J Johnson, J AF Orton, Stephen Umble, Karl Zelt, Sue Porter, Janet Johnson, Jim TI Management academy for public health: Creating entrepreneurial managers SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PARTNERSHIP; COUNTY; IMPACT; CARE AB The Management Academy for Public Health develops public health managers' management skills. Ultimately, the program aims to develop civic entrepreneurs who can improve the efficiency and the effectiveness of their organizations. With help from a coach, teams write public health business plans to meet needs in their communities. An external evaluation found that 119 teams trained during the first 3 years of the program generated more than $6 million in enhanced revenue-including grants, contracts, and fees through their business plans-from $2 million in program funding. Approximately 38% of the teams expected to generate revenue from an academy business plan or a spin-off plan. Action-learning methods can help miccareer managers transfer their training to the workplace and build entrepreneurial skills. C1 [Orton, Stephen; Umble, Karl; Zelt, Sue] Univ N Carolina, N Carolina Inst Publ Hlth, Sch Publ Hlth, Chapel Hill, NC 27599 USA. [Porter, Janet] Dana Farber Canc Inst, Boston, MA 02115 USA. [Johnson, Jim] Kenan Flagler Business Sch, Chapel Hill, NC USA. RP Orton, S (reprint author), Univ N Carolina, N Carolina Inst Publ Hlth, Sch Publ Hlth, Campus Box 8165, Chapel Hill, NC 27599 USA. EM stephen_orton@unc.edu NR 24 TC 3 Z9 3 U1 0 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2007 VL 97 IS 4 BP 601 EP 605 DI 10.2105/AJPH.2005.082263 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 297WG UT WOS:000255647500011 PM 17329658 ER PT J AU Parimon, T Chien, JW Bryson, CL McDonell, MB Udris, EM Au, DH AF Parimon, Tanyalak Chien, Jason W. Bryson, Chris L. McDonell, Mary B. Udris, Edmunds M. Au, David H. TI Inhaled corticosteroids and risk of lung cancer among patients with chronic obstructive pulmonary disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE chronic obstructive pulmonary disease; pharmacoepidemiology; lung cancer; adherence ID RANDOMIZED CONTROLLED-TRIAL; FLUTICASONE PROPIONATE; CHLAMYDIA-PNEUMONIAE; AIRWAY INFLAMMATION; SMOKING-CESSATION; PHARMACY RECORDS; DOUBLE-BLIND; A/J MICE; COPD; HEALTH AB Rationale and Objectives: Lung cancer is a frequent cause of death among patients with chronic obstructive pulmonary disease (COPD). We examined whether the use of inhaled corticosteroids among patients with COPD was associated with a decreased risk of lung cancer. Methods: We performed a cohort study of United States veterans enrolled in primary care clinics between December 1996 and May 2001. Participants had received treatment for, had an International Classification of Disease, 9th edition, diagnosis of, or a self-reported diagnosis of COPD. Patients with a history of lung cancer were excluded. To be exposed, patients must have been at least 80% adherent to inhaled corticosteroids. We used Cox regression models to estimate the risk of cancer and adjust for potential confounding factors. Findings: We identified 10,474 patients with a median follow-up of 3.8 years. In comparison to nonusers of inhaled corticosteroids, adjusting for age, smoking status, smoking intensity, previous history of non-lung cancer malignancy, coexisting illnesses, and bronchodilator use, there was a dose-dependent decreased risk of lung cancer associated with inhaled corticosteroids (ICS dose < 1,200 mu g/d: adjusted HR, 1.3; 95% confidence interval, 0.67-1.90; ICS dose >= 1,200 mu g/d: adjusted HR, 0.39; 95% confidence interval, 0.16-0.96). Changes in cohort definitions had minimal effects on the estimated risk. Analyses examining confounding by indication suggest biases in the opposite direction of the described effects. Interpretation: Results suggest that inhaled corticosteroids may have a potential role in lung cancer prevention among patients with COPD. These initial findings require confirmation in separate and larger cohorts. C1 VA Puget Sound Healthcare Syst, Hlth Serv Red & Dev MS152, Seattle, WA 98101 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. RP Au, DH (reprint author), VA Puget Sound Healthcare Syst, Hlth Serv Red & Dev MS152, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM dau@u.washington.edu FU NHLBI NIH HHS [K23HL69860] NR 77 TC 87 Z9 93 U1 0 U2 7 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 APR 1 PY 2007 VL 175 IS 7 BP 712 EP 719 DI 10.1164/rccm.200608-1125OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 152RS UT WOS:000245380100014 PM 17185647 ER PT J AU Ackerman, KG Wang, JL Luo, LQ Fujiwara, Y Orkin, SH Beier, DR AF Ackerman, Kate G. Wang, Jianlong Luo, Liqing Fujiwara, Yuko Orkin, Stuart H. Beier, David R. TI Gata4 is necessary for normal pulmonary lobar development SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE lung; accessory lobe; Gata; Fog; branching ID CONGENITAL DIAPHRAGMATIC-HERNIA; LUNG MORPHOGENESIS; GENE-EXPRESSION; HEART-DEFECTS; MOUSE EMBRYO; TRANSCRIPTION; DIFFERENTIATION; MICE; EPITHELIUM; MUTATIONS AB Mutations of Fog2 in mice result in a phenotype that includes pulmonary lobar defects. To determine whether formation of the accessory lobe bronchus is mediated by a Gata family cofactor, we evaluated embryonic lungs from mice carrying missense mutations that cause loss of FOG-GATA protein interaction. Lungs from embryos carrying a missense mutation in Gata6 were structurally normal, while lungs from embryos carrying mutations of either Gata4 or of both Gata4 and Gata6 had a structural phenotype that matched the Fog2 mutant phenotype. Expression analysis showed that Gata4 and Fog2 are expressed in the ventral and medial pulmonary mesenchyme during secondary budding. Although Gata4 has not previously been suspected as playing a role in lung development, we have found that a Fog2-Gata4 interaction is critical for the development of normal pulmonary lobar structure, and this phenotype is not influenced by the additional loss of Gata6 interaction. Fog2 and Gata4 in the early pulmonary mesenchyme participate in patterning the secondary bronchus of the accessory lobe. C1 Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Div Emergency Med, Boston, MA 02115 USA. Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ackerman, KG (reprint author), Brigham & Womens Hosp, Div Genet, New Res Bldg 458,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM kackerman@rics.bwh.harvard.edu FU NHLBI NIH HHS [HL032259, HL076286, K08 HL076286]; NICHD NIH HHS [HD36404] NR 34 TC 27 Z9 27 U1 0 U2 4 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD APR PY 2007 VL 36 IS 4 BP 391 EP 397 DI 10.1165/rcmb.2006-0211RC PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 155LC UT WOS:000245577900001 PM 17142311 ER PT J AU del Carmen, MG Halpern, EF Kopans, DB Moy, B Moore, RH Goss, PE Hughes, KS AF del Carmen, Marcela G. Halpern, Elkan F. Kopans, Daniel B. Moy, Beverly Moore, Richard H. Goss, Paul E. Hughes, Kevin S. TI Mammographic breast density and race SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE breast; breast cancer; breast density; mammography ID CANCER RISK; PARENCHYMAL PATTERNS; INCIDENCE RATES; POPULATION; CARCINOMA; SURVIVAL; FEATURES; HAWAII; JAPAN; WOMEN AB OBJECTIVE. Women with increased mammographic breast density are known to be at higher risk of developing breast cancer. Reports of differences in breast density by race have implied that genetic and environmental factors may in part determine breast density. We first compared breast density among white, African American, and Asian women and then correlated breast density and race with age, body mass index (BMI), and breast or cup size. MATERIALS AND METHODS. A retrospective review of data collected from 15,292 women was conducted. A stepwise multiple regression for an ordered response (breast density) was used to test for a relationship between race or ethnicity and breast density. We then determined whether differences in breast density by race might be caused by differences among races and ethnic groups in the age at imaging and BMI. We informally assessed the strength of the contribution of each term by means of the incremental change in the percent concordance. We also compared models using bra and cup sizes and age with models using BMI and age to try to determine whether the effects of breast size are local or systemic. RESULTS. We did not find evidence that mammographic breast density differences exist across racial groups (p < 0.0001) other than those associated with BMI and age at screening. Ignoring age and BMI, breast density depends on race for all comparisons (p < 0.0001). To generalize, we found that breast density appears to be greater in Asian women and least in African American women. However, when controlling for BMI and age, breast density differences by race disappeared in all groups except Asians (p < 0.0001). In all racial groups, bra and cup size in addition to age correlated with breast density after controlling for BMI (P < 0.0001). Except in Asian women, in women of any racial group, age and any of the following parameters accounted for all of the breast density differences: BMI, bra size, and cup size. CONCLUSION. Although breast density is associated with breast cancer risk, our results indicate that innate mammographic breast density differences across racial groups do not explain the risk differences known for the development of breast cancer. Age and BMI or age, bra size, and cup size can account for the reported density differences except among Asians. There may be no innate racial differences in breast density beyond those associated with racial differences in age and body habitus. C1 Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA. RP del Carmen, MG (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM mdelcarmen@partners.org OI Hughes, Kevin/0000-0003-4084-6484 NR 20 TC 50 Z9 50 U1 0 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2007 VL 188 IS 4 BP 1147 EP 1150 DI 10.2214/AJR.06.0619 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 156QI UT WOS:000245663700057 PM 17377060 ER PT J AU Jordan, SS DeFrate, LE Nha, KW Papannagari, R Gill, TJ Li, GA AF Jordan, Susan S. DeFrate, Louis E. Nha, Kyung Wook Papannagari, Ramprasad Gill, Thomas J. Li, Guoan TI The in vivo kinematics of the anteromedial and posterolateral bundles of the anterior cruciate ligament during weightbearing knee flexion SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE in vivo knee kinematics; anterior cruciate ligament (ACL); ACL bundles; ACL reconstruction ID SITU FORCES; BIOMECHANICAL ANALYSIS; HAMSTRING TENDONS; RECONSTRUCTION; OSTEOARTHRITIS; GRAFTS; MOTION; JOINT; DEFICIENCY; FIXATION AB Background: Recently, double-bundle anterior cruciate ligament reconstruction has been advocated. However, there are little data on the in vivo biomechanics of the anteromedial and posterolateral bundles of the anterior cruciate ligament. Our objective was to measure the kinematics of the 2 bundles during weightbearing flexion. Study Design: Descriptive laboratory study. Hypothesis: The bundles of the anterior cruciate ligament are longest at low flexion angles during in vivo weightbearing flexion. Methods: Magnetic resonance images from 7 healthy subjects were used to create 3-dimensional models of the knee. The attachments of the anteromedial and posterolateral bundles were outlined on each model. Next, the subjects performed a quasi-static lunge from full extension to 1351 while being imaged using a dual orthogonal fluoroscopic system. The models and fluoroscopic images were used to reproduce the motion of the knee. The length, elevation, deviation, and twist of the functional bundles were measured. Results: The anteromedial and posterolateral bundles were longest at low flexion angles and shortened significantly with increasing flexion. The elevation and deviation angles of both bundles were similar at low flexion angles (< 45 degrees). The twist of the bundles was minimal (< 5 degrees) at low flexion. Conclusion: With in vivo flexion, the anteromedial and posterolateral bundles did not demonstrate the reciprocal behavior noted in previous cadaveric studies. Both bundles were parallel and maximally elongated at low flexion angles. Our data suggest that if a double-bundle reconstruction is performed, 2 tunnels might need to be drilled in the femur and tibia to reproduce the orientation of the anterior cruciate ligament. Both anteromedial and posterolateral grafts should be fixed at low flexion angles to prevent over-constraint. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Inje Univ, Dept Orthopaed Surg, Ilsan, South Korea. Illsanpaik Hosp, Ilsan, South Korea. RP Li, GA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU NIAMS NIH HHS [R21 AR051078] NR 39 TC 52 Z9 58 U1 1 U2 12 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 APR PY 2007 VL 35 IS 4 BP 547 EP 554 DI 10.1177/0363546506295941 PG 8 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 155PJ UT WOS:000245590100005 PM 17261571 ER PT J AU Turbiner, J Amin, MB Humphrey, PA Srigley, JR De Leval, L Radhakrishnan, A Oliva, E AF Turbiner, Julia Amin, Mahul B. Humphrey, Peter A. Srigley, John R. De Leval, Laurence Radhakrishnan, Anuradha Oliva, Esther TI Cystic nephroma and mixed epithelial and stromal tumor of kidney: A detailed clinicopathologic analysis of 34 cases and proposal for renal epithelial and stromal tumor (REST) as a unifying term SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 94th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2005 CL San Antonio, TX SP US & Canadian Acad Pathol DE kidney; cystic nephroma; mixed epithelial and stromal tumor; ovarian-type stroma; immunohistochemistry ID CONGENITAL MESOBLASTIC NEPHROMA; OVARIAN-TYPE STROMA; MUCINOUS CYSTADENOCARCINOMA; HEPATOBILIARY CYSTADENOMA; PANCREAS; HAMARTOMA; NEOPLASMS; PELVIS; PATHOGENESIS; FEATURES AB cCystic nephroma (CN) and mixed epithelial and stromal tumor (MEST) are rare benign renal neoplasms that have overlapping clinical and morphologic features, including predominance in middle-aged women, variably cystic architecture, eosinophilic cells, and hobnail cells lining the cysts and ovarian-type stroma. The aim of this study was to analyze and compare the histologic features and immunohistochemical profile of these tumors. We studied 34 cases from 5 large academic institutions. Twenty tumors were diagnosed as CNs, 18 in women and 2 in men, their age ranged from 24 to 63 (mean 48; median 50) years. Fourteen tumors were diagnosed as MESTs, all in women, their age ranged from 26 to 84 (mean 52; median 51) years. Histologically, all tumors were weil-circumscribed except for one MEST. The stromal/epithelial ratio was approximately 2.3 in MESTs versus 0.3 in CNs; cellular ovarian-type stroma composed 45% of the stroma in MESTs and 12% of the stroma of CNs. Stromal hyalinization was prominent in both. Five MESTs showed stromal luteinization. In the epithelial component, the relative amount of large cysts, medium to small cysts, and phyllodes-type glands was: 65%/ 25%/10% in CNs versus 25%/40%/35% in MESTs. The epithelial component ranged from flat to cuboidal to hobnail cells in both types of tumors. No significant atypia of either component was seen, although the epithelial cells showed reactive changes. Immunohistochemical stains for estrogen receptors and progesterone receptors showed 62% and 85% positivity in the stromal component of MESTs versus 19% and 40% in CNs. CD10 positivity was seen in 77% of MESTs versus 50% of CNs. calretinin was seen in 69% of MESTs versus 41% of CNs. and inhibin in 42% of MESTs versus 36% of CNs, although the staining was focal. Follow-up in both categories of tumors (mean 3.2 y, median 3 y for CNs and mean 2.5 y, median of 2 y for MESTs) showed no evidence of recurrence, or metastases in keeping with their benign nature. This study highlights the remarkable similarity between CN and MEST in sex predilection, age distribution, and morphologic attributes of both the epithelial and stromal components and immunohistochemical profile albeit with variation in individual categories with higher prevalence of stromal to epithelial ratio, prominent ovarian stroma, smaller cysts with phyllodes glands pattern and stromal luteinization being more common in MESTI- and large cysts, thin septae and low stromal to epithelial ratio in CN. The presence of ovarian-type stroma and mollerian related immunohistochemical markers raises the possibility that these tumors may originate from mullerian remnants misplaced during embryogenesis. On the basis of detailed morphologic analysis of this series of CN and MEST, we propose a unifying term of "renal epithelial and stromal tumor" (REST) to encompass the spectrum of findings observed in these tumors at least until new molecular studies can prove or disprove this challenging hypothesis. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Emory Univ, Atlanta, GA 30322 USA. Washington Univ, St Louis, MO USA. McMaster Univ, Hamilton, ON, Canada. CHU Sart Tilman, B-4000 Liege, Belgium. RP Turbiner, J (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,55 Fruit St, Boston, MA 02114 USA. EM jturbiner@partners.org NR 42 TC 73 Z9 88 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 2007 VL 31 IS 4 BP 489 EP 500 DI 10.1097/PAS.0b013e31802bdd56 PG 12 WC Pathology; Surgery SC Pathology; Surgery GA 154VO UT WOS:000245536100001 PM 17414095 ER PT J AU Wang, LL Perlman, EJ Vujanic, GM Zuppan, C Brundler, MA Cheung, CRLH Calicchio, ML Dubois, S Cendron, M Murata-Collins, JL Wenger, GD Strzelecki, D Barr, FG Collins, T Perez-Atayde, AR Kozakewich, H AF Wang, Larry L. Perlman, Elizabeth J. Vujanic, Gordan M. Zuppan, Craig Brundler, Marie-Anne Cheung, C. Ronny L. H. Calicchio, Monica L. Dubois, Steven Cendron, Marc Murata-Collins, Joyce L. Wenger, Gail D. Strzelecki, Donna Barr, Frederic G. Collins, Tucker Perez-Atayde, Antonio R. Kozakewich, Harry TI Desmoplastic small round cell tumor of the kidney in childhood SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE renal sarcoma; kidney tumor ID SOFT-TISSUE SARCOMAS; DIVERGENT DIFFERENTIATION; CHROMOSOMAL TRANSLOCATIONS; BONE; PERITONEUM; PRODUCT; FUSION AB Background: Desmoplastic small round cell tumor (DSRCT) is a rare malignant tumor that generally manifests as abdominal paraserosal masses and affects mainly male adolescents and young adults. When presenting within visceral organs, the diagnosis of DSRCT poses significant difficulties. Methodology: Four primary renal DSRCT in children diagnosed during a 3-year period are the basis of this report. The medical records and pathologic material were reviewed, including immunohistochemical, ultrastructural, and cytogenetic/molecular studies. Results: The age at presentation was 6 to 8 years, and all children presented with a left renal mass. The tumors measured 3.7 to 13.4cm and consisted of nests, cords, or sheets of small undifferentiated cells with foci of necrosis and calcification. Desmoplasia was not seen. Tumor cells were immunopositive for vimentin, WT-1 (monoclonal and polyclonal), desmin, cytokeratin, and epithelial membrane antigen. A distinct paranuclear dotlike pattern was observed with vimentin and desmin. Tumor cells possessed rare or focal immuno reactivity for platelet derived growth factor-A and transforming growth factor-beta 3, which have been implicated in the pathogenesis of desmoplasia in DSRCT. The EWS-WT1 t(11;22)(p13;q12) translocation was demonstrated in all 4 tumors by fluorescence in situ hybridization and/or reverse transcription-polymerase chain reaction. Conclusions: DSRCT should be considered in the differential diagnosis of renal tumors composed of small round cells. Undifferentiated morphology and lack of desmoplasia contribute to the difficulty in its recognition. Ancillary studies such as immunohistochemistry may suggest the diagnosis, but cytogenetic and molecular genetic studies are required for confirmation. C1 Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dept Urol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Mem Hosp, Chicago, IL 60614 USA. Univ Cardiff Wales, Sch Med, Cardiff, Wales. Childrens Hosp, Birmingham B16 8ET, W Midlands, England. Loma Linda Univ, Loma Linda, CA 92350 USA. Childrens Hosp, Loma Linda, CA USA. Genzyme Genet, Santa Fe, NM USA. Childrens Hosp, Columbus, OH 43205 USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Kozakewich, H (reprint author), Childrens Hosp, Dept Pathol, 300 Longwood Ave, Boston, MA 02115 USA. EM harry.kozakewich@childrens.harvard.edu FU NCI NIH HHS [T32 CA009172]; NHLBI NIH HHS [HL35716] NR 27 TC 32 Z9 34 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 2007 VL 31 IS 4 BP 576 EP 584 DI 10.1097/01.pas.0000213432.14740.14 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 154VO UT WOS:000245536100011 PM 17414105 ER PT J AU McCluggage, WG Young, RH AF McCluggage, W. Glenn Young, Robert H. TI Ovarian Sertoli-Leydig cell tumors with pseudoendometrioid tubules (pseudoendometrioid Sertoli-Leydig cell tumors) SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ovary; Sertoli-Leydig cell tumor; endometrioid neoplasm; immunohistochemistry ID CORD-STROMAL TUMORS; CLINICOPATHOLOGICAL ANALYSIS; DIAGNOSIS; GRANULOSA AB The propensity for ovarian endometrioid adenocarcinomas to morphologically mimic Sertoli, Sertoli-Leydig, and granulosa cell tumors, is well known. The converse situation, mimicry of an endometrioid neoplasm by a sex cord-stromal tumor, has not been emphasized. In this report, we describe 9 ovarian Sertoli-Leydig cell tumors (5 well differentiated, 4 of intermediate differentiation) with areas containing hollow, sometimes dilated, tubules which resemble endometrioid glands; we refer to these as pseudoendometrioid tubules. The age of the patients ranged from 14 to 57. The tumors, all of which were unilateral except for one, ranged from 3.5 to 19 cm, and were variously described as tan, pale, yellow, or gold. The proportion of the tumor made up of pseudoendometrioid tubules ranged from 10% to > 90%. When widespread, their presence sometimes resulted in consideration of a borderline endometrioid adenofibroma or a well-differentiated endometrioid adenocarcinoma. However, all the neoplasms contained typical Sertoli tubules and one or more of the characteristic patterns of Sertoli-Leydig cell tumors as well as Leydig cells, although the latter cells were inconspicuous in some cases. Immunohistochemistry, performed in 4 cases, showed that the pseudoendometrioid tubules, as well as the more typical Sertoli cell elements, were either positive for alpha inhibin (3 of 4 cases) or calretinin (3 of 4 cases) or both, although sometimes focally so. These elements were negative with epithelial membrane antigen and cytokeratin 7. In all 4 cases, the pseudoendometrioid tubules were positive with the broad spectrum cytokeratin AE1/3. This report illustrates the potential for ovarian Sertoli-Leydig cell tumors to contain tubules with a pseudoendometrioid appearance which mimic a borderline or malignant endometrioid neoplasm. The presence of more typical Sertoli cell elements and Leydig cells, an absence of squamous elements, endometriosis or associated adenofibroma, and the characteristic immunophenotype assist in diagnosis. C1 Royal Grp Hosp Trust, Dept Pathol, Belfast BT12 6BA, Antrim, North Ireland. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP McCluggage, WG (reprint author), Royal Grp Hosp Trust, Dept Pathol, Grosvenor Rd, Belfast BT12 6BA, Antrim, North Ireland. EM glenn.mccluggage@bll.n-i.nhs.uk NR 14 TC 15 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 2007 VL 31 IS 4 BP 592 EP 597 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 154VO UT WOS:000245536100013 PM 17414107 ER PT J AU Veronese, F Rotman, S Smith, RN Pelle, TD Farrell, ML Kawai, T Cosimi, AB Colvin, RB AF Veronese, F. Rotman, S. Smith, R. N. Pelle, T. D. Farrell, M. L. Kawai, T. Cosimi, A. Benedict Colvin, R. B. TI Pathological and clinical correlates of FOXP3(+) cells in renal allografts during acute rejection SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE acute rejection; FOXP3; regulatory T cells; renal allograft ID REGULATORY T-CELLS; IMMUNOLOGICAL SELF-TOLERANCE; TRANSCRIPTION FACTOR FOXP3; TRANSPLANTATION TOLERANCE; TGF-BETA; IN-VIVO; MINIATURE SWINE; INDUCTION; AUTOIMMUNITY; MICE AB The localization and significance of regulatory T cells (Treg) in allograft rejection is of considerable clinical and immunological interest. We analyzed 80 human renal transplant biopsies (including seven donor biopsies) with a double immunohistochemical marker for the Treg transcription factor FOXP3, combined with a second marker for CD4 or CD8. Quantitative FOXP3 cell counts were performed and analyzed for clinical and pathologic correlates. FOXP3(+) cells were present in the interstitium in acute cellular rejection (ACR) type I and II, at a greater density than in acute humoral rejection or CNI toxicity (p < 0.01). Most FOXP3(+) cells were CD4(+) (96%); a minority expressed CD8. FOXP3(+)CD4(+) cells were concentrated in the tubules (p < 0.001), suggesting a selective attraction or generation at that site. Considering only patients with ACR, a higher density of FOXP3(+) correlated with HLA class II match (p = 0.03), but paradoxically with worse graft survival. We conclude that infiltration of FOXP3(+) cells occurs in ACR to a greater degree than in humoral rejection, however, within the ACR group, no beneficial effect on outcome was evident. Tregs concentrate in tubules, probably contributing to FOXP3 mRNA in urine; the significance and pathogenesis of 'Treg tubulitis' remains to be determined. C1 Massachusetts Gen Hosp, Pathol & Surg Serv, Boston, MA 02114 USA. Hosp Clin Porto Alegre, Div Renal, Porto Alegre, RS, Brazil. RP Veronese, F (reprint author), Massachusetts Gen Hosp, Pathol & Surg Serv, Boston, MA 02114 USA. EM franvero@via-rs.net NR 46 TC 111 Z9 118 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2007 VL 7 IS 4 BP 914 EP 922 DI 10.1111/j.1600-6143.2006.01704.x PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 149MR UT WOS:000245151500024 PM 17286616 ER PT J AU Musch, G Venegas, JG Bellani, G Winkler, T Schroeder, T Petersen, B Harris, RS Melo, MFV AF Musch, Guido Venegas, Jose G. Bellani, Giacomo Winkler, Tito Schroeder, Tobias Petersen, Bodil Harris, R. Scott Melo, Marcos F. Vidal TI Regional gas exchange and cellular metabolic activity in ventilator-induced lung injury SO ANESTHESIOLOGY LA English DT Article ID END-EXPIRATORY PRESSURE; POSITRON-EMISSION-TOMOGRAPHY; HIGH AIRWAY PRESSURE; SURFACTANT-DEPLETED LUNG; BRAIN TRANSFER CONSTANTS; TIME UPTAKE DATA; CELLS IN-VITRO; MECHANICAL VENTILATION; RESPIRATORY-FAILURE; PULMONARY-EDEMA AB Background: Alveolar overdistension and repetitive derecruitment-recruitment contribute to ventilator-induced lung injury (VILI). The authors investigated (1) whether inflammatory cell activation due to VILI was assessable by positron emission tomography and (2) whether cell activation due to dynamic overdistension alone was detectable when other manifestations of VILI were not yet evident. Methods: The authors assessed cellular metabolic activity with [F-18]fluorodeoxyglucose and regional gas exchange with [N-13]nitrogen. In 12 sheep, the left ("test") lung was overdistended with end-inspiratory pressure of 50 cm H2O for 90 min, while end-expiratory derecruitment of this lung was either promoted with end-expiratory pressure of -10 CM H2O in 6 of these sheep (negative end-expiratory pressure [NEEP] group) or prevented with +10 CM H2O in the other 6 (positive end-expiratory pressure [PEEP] group) to isolate the effect of overdistension. The right ("control") lung was protected from VILI. Results: Aeration decreased and shunt fraction increased in the test lung of the NEEP group. [F-18]fluorodeoxyglucose uptake of this lung was higher than that of the control lung and of the test lung of the PEEP group, and correlated with neutrophil count. When normalized by tissue fraction to account for increased aeration of the test lung in the PEEP group, [F-18]fluorodeoxyglucose uptake was elevated also in this group, despite the fact that gas exchange had not yet deteriorated after 90 min of overdistension alone. Conclusion: The authors could detect regional neutrophil activation in VIM even when end-expiratory derecruitment was prevented and impairment of gas exchange was not evident. Concomitant end-expiratory derecruitment converted this activation into profound inflammation with decreased aeration and regional shunting. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Musch, G (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, CLN 309,55 Fruit St, Boston, MA 02114 USA. EM gmusch@partners.org RI Bellani, Giacomo/D-2379-2010; Winkler, Tilo/B-5337-2009 OI Bellani, Giacomo/0000-0002-3089-205X; Winkler, Tilo/0000-0002-7276-5550 FU NHLBI NIH HHS [R01 HL086827-01, R01 HL086827, HL-076464, HL-068011]; NIGMS NIH HHS [GM-007592] NR 71 TC 49 Z9 53 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2007 VL 106 IS 4 BP 723 EP 735 DI 10.1097/01.anes.0000264748.86145.ac PG 13 WC Anesthesiology SC Anesthesiology GA 152FP UT WOS:000245346900013 PM 17413910 ER PT J AU Culley, DJ Crosby, G Xie, ZC Vacanti, CA Kitz, RJ Zapol, WM AF Culley, Deborah J. Crosby, Gregory Xie, Zhongcong Vacanti, Charles A. Kitz, Richard J. Zapol, Warren M. TI Career National Institutes of Health funding and Scholarship of Chairpersons of Academic Departments of Anesthesiology and Surgery SO ANESTHESIOLOGY LA English DT Article ID PHYSICIAN SCIENTISTS; TRENDS C1 Brigham & Womens Hosp, Dept Anesthesiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Perioperat & Pain Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Crosby, G (reprint author), Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA. EM gcrosby@zeus.bwh.harvard.edu FU NHLBI NIH HHS [HL042397]; NIA NIH HHS [AG20253, AG000294, AG008812]; NIGMS NIH HHS [GM077057]; NINDS NIH HHS [NS048140] NR 9 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2007 VL 106 IS 4 BP 836 EP 842 DI 10.1097/01.anes.0000264768.79415.26 PG 7 WC Anesthesiology SC Anesthesiology GA 152FP UT WOS:000245346900025 PM 17413922 ER PT J AU Woolf, CJ AF Woolf, Clifford J. TI Central sensitization - Uncovering the relation between pain and plasticity SO ANESTHESIOLOGY LA English DT Article ID RAT SPINAL-CORD; DORSAL-HORN; AFFERENT INPUT; HYPERSENSITIVITY; MECHANISMS; INDUCTION; NEURONS; REFLEX AB Noxious skin stimuli which are sufficiently intense to produce tissue injury, characteristically generate prolonged poststimulus sensory disturbances that include continuing pain, an increased sensitivity to noxious stimuli and pain following innocuous stimuli. This could result from either a reduction in the thresholds of skin nociceptors (sensitization) or an increase in the excitability of the central nervous system so that normal inputs now evoke exaggerated responses. Because sensitization of peripheral receptors occurs following injury, a peripheral mechanism is widely held to be responsible for postinjury hypersensitivity. To investigate this I have now developed an animal model where changes occur in the threshold and responsiveness of the flexor reflex following peripheral injury that are analogous to the sensory changes found in man. Electrophysiological analysis of the injury-induced increase in excitability of the flexion reflex shows that it in part arises from changes in the activity of the spinal cord. The longterm consequences of noxious stimuli result, therefore, from central as well as from peripheral changes. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 149 13th St,Room 4309, Charlestown, MA 02129 USA. EM cwoolf@partners.org NR 13 TC 114 Z9 125 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2007 VL 106 IS 4 BP 864 EP 867 DI 10.1097/01.anes.0000264769.87038.55 PG 4 WC Anesthesiology SC Anesthesiology GA 152FP UT WOS:000245346900027 PM 17413924 ER PT J AU Deitrick, G Charalel, J Bauman, W Tuckman, J AF Deitrick, George Charalel, Joseph Bauman, William Tuckman, John TI Reduced arterial circulation to the legs in spinal cord injury as a cause of skin breakdown lesions SO ANGIOLOGY LA English DT Article ID PERIPHERAL VASCULAR-DISEASE; DOPPLER TISSUE FLOWMETERS; SUBCUTANEOUS BLOOD-FLOW; CUTANEOUS MICROCIRCULATION; FEMORAL-ARTERY; REFLEX; POSTURE; OCCLUSION; RESPONSES; VETERANS AB Skin breakdown lesions (SBLs) of the legs are common in spinal cord injury (SCI). It is assumed that the cause is deficient sensitivity and immobility of the limbs, which result in areas subjected to prolonged pressures. However, poor circulation may also be a significant factor. Indeed, strong reasons suggest that small vessel circulation is decreased in SCI because these patients have increased arteriosclerotic risk factors. Patients in the SCI population have advanced age, are sedentary, often have abnormal carbohydrate and lipid metabolism, and many use tobacco products. Total blood flow (TBF) to the legs and skin blood flows (SBFs) to 4 areas of the feet were measured simultaneously by duplex Doppler sonography and laser Doppler flowmetry in 10 healthy control and 10 chronic subjects with SCI when supine and during 30 minutes in a wheelchair. The average supine control TBF was 540 mL/minute, but greatly reduced between 24-76 mL/minute in 4 of the subjects. During sitting, the average TBF fell by 41% in the controls and increased by 6% in SCI. Nonetheless, in all control and SCI subjects the average sitting SBFs were severely decreased in all areas between 53-75%, similar to results found by others elsewhere in the foreleg. Ischemia of the skin and underlying muscles is important as a cause for the poor healing of SBLs in persons with SCI who daily spend many hours in a wheelchair. C1 Bronx Vet Adm Med Ctr, Bronx, NY 10468 USA. Mt Sinai Med Ctr, Div Diagnost Serv, New York, NY 10021 USA. Mt Sinai Med Ctr, Spinal Cord Damage Res Ctr, New York, NY 10021 USA. Mt Sinai Med Ctr, Vet Affairs Rehabil Res & Dev Ctr Excellence, New York, NY 10021 USA. Bronx Vet Adm Med Ctr, Dept Surg, Bronx, NY 10468 USA. Bronx Vet Adm Med Ctr, Dept Radiol, Bronx, NY 10468 USA. Bronx Vet Adm Med Ctr, Dept Med, Bronx, NY 10468 USA. Bronx Vet Adm Med Ctr, Dept Rehabil, Bronx, NY 10468 USA. RP Deitrick, G (reprint author), Bronx Vet Adm Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM george.deitrick@med.va.gov NR 30 TC 16 Z9 17 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0003-3197 J9 ANGIOLOGY JI Angiology PD APR-MAY PY 2007 VL 58 IS 2 BP 175 EP 184 DI 10.1177/0003319707300353 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 161QQ UT WOS:000246030900006 PM 17495266 ER PT J AU Bender, BG Long, A Parasuraman, B Tran, ZV AF Bender, Bruce G. Long, Aidan Parasuraman, Bhash Tran, Zung Vu TI Factors influencing patient decisions about the use of asthma controller medication SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID UNINTENTIONAL NONADHERENCE; INHALED CORTICOSTEROIDS; PATIENTS BELIEFS; ADHERENCE; PERSISTENCE; EMERGENCY; CHILDREN; ADULTS; VISIT AB Background: Patient nonadherence with asthma controller medication is pervasive and impedes successful adoption of national treatment guidelines. Objective: To survey adult patients with asthma about the factors influencing their decisions about when to use their asthma controller medications. Methods: Two hundred adults with asthma were randomly selected from a national database and were surveyed by telephone about medication use, barriers to adherence, and treatment preferences. Results: Adherence to daily controller medication in the group was generally well below the prescribed level despite the fact that many had relatively severe asthma and inadequately controlled symptoms. Thirty percent of the respondents indicated that they had been instructed by their physician to use their controller medication intermittently as guided by their symptoms. Most respondents expressed a desire to be more in control of their treatment and for that treatment to be more immediately effective and long-lasting but did not perceive inadequate information to be a barrier to adherence. Conclusion: These insights into patient perception and motivation suggest the importance of developing treatment plans that allow patients some degree of control over medication use. C1 Natl Jewish Med & Res Ctr, Dept Pediat, Denver, CO 80206 USA. Univ Colorado, Dept Psychiat, Denver, CO 80202 USA. Hlth Sci Ctr, Denver, CO USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. AStraZeneca, Hlth Econ & Outcomes Res, Wilmington, DE USA. Univ Colorado, Dept Prevent Med & Biometr, Denver, CO 80202 USA. RP Bender, BG (reprint author), Natl Jewish Med & Res Ctr, Dept Pediat, 1400 Jackson St, Denver, CO 80206 USA. EM benderb@njc.org NR 23 TC 43 Z9 45 U1 2 U2 8 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD APR PY 2007 VL 98 IS 4 BP 322 EP 328 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 156YY UT WOS:000245687000004 PM 17458427 ER PT J AU Gaeta, TJ Clark, S Pelletier, AJ Camargo, CA AF Gaeta, Theodore J. Clark, Sunday Pelletier, Andrea J. Camargo, Carlos A. TI National study of US emergency department visits for acute allergic reactions, 1993 to 2004 SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID ANAPHYLAXIS; MANAGEMENT; MULTICENTER; DEFINITION; FOOD AB Background: The clinical epidemiology of acute allergic reactions in the emergency department (ED) is uncertain. Objectives: To characterize ED visits for acute allergic reactions and to evaluate national trends in ED management. Methods: The National Hospital Ambulatory Medical Care Survey was used to identify a nationally representative sample of ED visits between 1993 and 2004. Cases with a diagnosis of acute allergic reaction were identified by International Classification of Diseases, Ninth Revision (ICD-9) codes (9950, 9951, 9952, 9953, 9956). Results: A total of 12.4 million allergy-related ED visits occurred from 1993 to 2004, representing 1.0% (95% confidence interval, 0.93%-1.10%) of all ED visits or 1.03 million ED visits per year. The number of allergy-related ED visits remained relatively stable, averaging 3.8 per 1,000 US population per year (95% confidence interval, 3.4-4.1; P for trend = .39). Although 63% of all visits were coded as urgent, only 4% required hospitalization. Anaphylaxis coding was rare (1%). ED staff prescribed medications in 87% of visits, especially histamine, blockers (62%; P for trend = .29). Increases were noted from 1993 to 2004 for corticosteroids (22% to 50%; P < .001), histamine, blockers (7% to 18%; P < .001), and inhaled beta-agonists (2% to 6%; P = .008). Epinephrine use was infrequent and declining (19% to 7%; P = .04). Conclusion: Between 1993 and 2004, significant variability has occurred in ED management of acute allergic reactions. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. New York Methodist Hosp, Brooklyn, NY USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org NR 36 TC 76 Z9 77 U1 0 U2 0 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD APR PY 2007 VL 98 IS 4 BP 360 EP 365 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 156YY UT WOS:000245687000010 PM 17458433 ER PT J AU Sun, BC Mangione, CM Merchant, G Weiss, T Shlamovitz, GZ Zargaraff, G Shiraga, S Hoffman, JR Mower, WR AF Sun, Benjamin C. Mangione, Carol M. Merchant, Guy Weiss, Timothy Shlamovitz, Gil Z. Zargaraff, Gelareh Shiraga, Sharon Hoffman, Jerome R. Mower, William R. TI External validation of the San Francisco Syncope Rule SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID EMERGENCY ROOM PATIENTS; RISK STRATIFICATION; SERIOUS OUTCOMES; PREDICT PATIENTS; POPULATION; SCORE AB Study objective: We externally validate the ability of the San Francisco Syncope Rule to accurately identify syncope patients who will experience a 7-day serious clinical event. Methods: Patients who presented to a single academic emergency department (ED) between 8 AM and 10 Pm with syncope or near-syncope were prospectively enrolled. Treating physicians recorded the presence or absence of all San Francisco Syncope Rule risk factors. Patients were contacted by telephone at 14 days for a structured interview. A 3-physician panel, blinded to the San Francisco Syncope Rule score, reviewed ED medical records, hospital records, and telephone interview forms to identify predefined serious clinical events. The primary outcome was the ability of the San Francisco Syncope Rule to predict any 7-day serious clinical event. A secondary outcome was the ability of the San Francisco Syncope Rule to predict 7-day serious clinical events that were not identified during the initial ED evaluation. Results: Of 592 eligible patients, 477 (81%) provided informed consent. Direct telephone contact or admission/outpatient records were successfully obtained for 463 (97%) patients. There were 56 (12%) patients who had a serious 7-day clinical event, including 16 (3%) who received a diagnosis after the initial ED evaluation. Sensitivity and specificity of the San Francisco Syncope Rule for the primary outcome were 89% (95% confidence interval [CI] 81% to 97%) and 42% (95% Cl 37% to 48%), respectively, and 69% (95% Cl 46% to 92%) and 42% (95% Cl 37% to 48%), respectively, for the secondary outcome. Estimates of sensitivity were minimally affected by missing data and most optimistic assumptions for missing follow-up information. Conclusion: In this external validation cohort, the San Francisco Syncope Rule had a lower sensitivity and specificity than in previous reports. C1 W Los Angeles Vet Affairs Med Ctr, Off 3214A, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Ctr Emergency Med, Los Angeles, CA 90024 USA. RP Sun, BC (reprint author), W Los Angeles Vet Affairs Med Ctr, Off 3214A, Dept Med, Mail Stop 111,Bldg 500,Wing 3E,11301 Wilshire Blv, Los Angeles, CA 90073 USA. EM bsun@post.harvard.edu FU NIA NIH HHS [AG 02-004, K12AG001004] NR 19 TC 55 Z9 58 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD APR PY 2007 VL 49 IS 4 BP 420 EP 427 DI 10.1016/j.annemergmed.2006.11.012 PG 8 WC Emergency Medicine SC Emergency Medicine GA 151ME UT WOS:000245293700005 PM 17210201 ER PT J AU Tsai, HK Li, S Ng, AK Silver, B Stevenson, MA Mauch, PM AF Tsai, H. K. Li, S. Ng, A. K. Silver, B. Stevenson, M. A. Mauch, P. M. TI Role of radiation therapy in the treatment of stage I/II mucosa-associated lymphoid tissue lymphoma SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 05-09, 2006 CL Philadelphia, PA SP Amer Soc Therapeut Radiol & Oncol DE chemotherapy; MALT lymphoma; outcome; radiotherapy; surgery ID B-CELL LYMPHOMA; HELICOBACTER-PYLORI ERADICATION; TERM-FOLLOW-UP; POSITRON-EMISSION-TOMOGRAPHY; GASTRIC MALT LYMPHOMA; NON-HODGKINS-LYMPHOMA; MALIGNANT-LYMPHOMA; RADIOTHERAPY; CLASSIFICATION; ORBIT AB Background: Few large studies exist on the outcome of patients treated for stage I/II mucosa-associated lymphoid tissue (MALT) lymphoma. Patients and methods: We retrospectively reviewed the records of 77 patients consecutively treated for stage I (n = 66) or II (n = 11) MALT lymphoma at our institution. Progression-free survival (PFS), freedom from treatment failure (FFTF), and overall survival (OS) were calculated using the Kaplan-Meier method. Results: The median follow-up time was 61 months (range 2-177 months). Fifty-two patients (68%) received local radiation therapy (RT) alone, 17 (22%) had surgery followed by adjuvant RT, five (6%) had surgery alone, two (3%) had surgery and chemotherapy, and one patient had chemotherapy alone. The median RT dose was 30 Gy (range 18-40 Gy). The 5-year PFS, FFTF, and OS rates were 76%, 78%, and 91%, respectively. The 5-year PFS (79% versus 50%; P = 0.002) and FFTF (81% versus 50%; P = 0.0004) rates were higher for patients who received RT as compared with patients who did not. Conclusions: The prognosis following treatment of stage I/II MALT lymphoma is excellent. RT improves PFS and FFTF and has an important role in the curative treatment of patients with localized disease. C1 Harvard Univ, Radiat Oncol Program, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. RP Mauch, PM (reprint author), 75 Francis St, Boston, MA 02115 USA. EM pmauch@lroc.harvard.edu NR 28 TC 18 Z9 20 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 APR PY 2007 VL 18 IS 4 BP 672 EP 678 DI 10.1093/annonc/mdl468 PG 7 WC Oncology SC Oncology GA 152GM UT WOS:000245349500010 PM 17218489 ER PT J AU Keshaviah, A Dellapasqua, S Rotmensz, N Lindtner, J Crivellari, D Collins, J Colleoni, M Thurlimann, B Mendiola, C Aebi, S Price, KN Pagani, O Simoncini, E Gertsch, MC Gelber, RD Coates, AS Goldhirsch, A AF Keshaviah, A. Dellapasqua, S. Rotmensz, N. Lindtner, J. Crivellari, D. Collins, J. Colleoni, M. Thuerlimann, B. Mendiola, C. Aebi, S. Price, K. N. Pagani, O. Simoncini, E. Gertsch, M. Castiglione Gelber, R. D. Coates, A. S. Goldhirsch, A. CA Int Breast Canc Study Grp TI CA15-3 and alkaline phosphatase as predictors for breast cancer recurrence: a combined analysis of seven International Breast Cancer Study Group trials SO ANNALS OF ONCOLOGY LA English DT Article DE alkaline phosphatase; breast cancer; CA15-3; tumor marker ID FOLLOW-UP; RANDOMIZED-TRIAL; CA 15-3; ADJUVANT CHEMOTHERAPY; TUMOR-MARKERS; MONOCLONAL-ANTIBODY; PROGNOSTIC VALUE; ANTIGEN LEVELS; CARCINOMA; CEA AB Background: We evaluated the ability of CA15-3 and alkaline phosphatase (ALP) to predict breast cancer recurrence. Patients and methods: Data from seven International Breast Cancer Study Group trials were combined. The primary end point was relapse-free survival (RFS) (time from randomization to first breast cancer recurrence), and analyses included 3953 patients with one or more CA15-3 and ALP measurement during their RFS period. CA15-3 was considered abnormal if > 30 U/ml or > 50% higher than the first value recorded; ALP was recorded as normal, abnormal, or equivocal. Cox proportional hazards models with a time-varying indicator for abnormal CA15-3 and/or ALP were utilized. Results: Overall, 784 patients (20%) had a recurrence, before which 274 (35%) had one or more abnormal CA15-3 and 35 (4%) had one or more abnormal ALP. Risk of recurrence increased by 30% for patients with abnormal CA15-3 [hazard ratio (HR) = 1.30; P = 0.0005], and by 4% for those with abnormal ALP (HR = 1.04; P = 0.82). Recurrence risk was greatest for patients with either (HR = 2.40; P < 0.0001) and with both (HR = 4.69; P < 0.0001) biomarkers abnormal. ALP better predicted liver recurrence. Conclusions: CA15-3 was better able to predict breast cancer recurrence than ALP, but use of both biomarkers together provided a better early indicator of recurrence. Whether routine use of these biomarkers improves overall survival remains an open question. C1 European Inst Oncol, Dept Med, IBCSG, I-20141 Milan, Italy. Dana Farber Canc Inst, Int Breast Canc Study Grp Stat Ctr, Boston, MA 02115 USA. Inst Oncol, Ljubljana, Slovenia. Ctr Riferimento Oncol, I-33081 Aviano, Italy. Royal Melbourne Hosp, Dept Surg, Melbourne, Vic, Australia. Kantonsspital, St Gallen, Switzerland. Swiss Grp Clin Canc Res, Bern, Switzerland. Hosp 12 Octubre, E-28041 Madrid, Spain. Inselspital Bern, Inst Med Oncol, CH-3010 Bern, Switzerland. Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. Oncol Inst So Switzerland, Bellinzona, Switzerland. Spedali Civili Brescia, I-25125 Brescia, Italy. Int Breast Canc Study Grp Coordinating Ctr, Bern, Switzerland. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Sydney, Sydney, NSW 2006, Australia. RP Goldhirsch, A (reprint author), European Inst Oncol, Dept Med, IBCSG, Via Ripamonti 435, I-20141 Milan, Italy. EM aron.goldhirsch@ibcsg.org RI Aebi, Stefan/F-2004-2010 OI Aebi, Stefan/0000-0002-3383-9449 FU NCI NIH HHS [CA 75362] NR 40 TC 36 Z9 38 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD APR PY 2007 VL 18 IS 4 BP 701 EP 708 DI 10.1093/annonc/mdl492 PG 8 WC Oncology SC Oncology GA 152GM UT WOS:000245349500014 PM 17237474 ER PT J AU Klein, MB Hayden, D Elson, C Nathens, AB Gamelli, RL Gibran, NS Herndon, DN Arnoldo, B Silver, G Schoenfeld, D Tompkins, RG AF Klein, Matthew B. Hayden, Douglas Elson, Constance Nathens, Avery B. Gamelli, Richard L. Gibran, Nicole S. Herndon, David N. Arnoldo, Brett Silver, Geoff Schoenfeld, David Tompkins, Ronald G. TI The association between fluid administration and outcome following major burn - A multicenter study SO ANNALS OF SURGERY LA English DT Article ID ABDOMINAL COMPARTMENT SYNDROME; SHOCK RESUSCITATION; INHALATION INJURY; MANAGEMENT; REQUIREMENTS; FORMULA; OUTPUT AB Objective: To determine patient and injury variables that influence fluid requirements following burn injury and examine the association between fluid volume received and outcome. Background: Fluid resuscitation remains the cornerstone of acute burn management. Recent studies suggest that patients today are receiving more fluid per percent total body surface area (TBSA) than in the past. Therefore, there is a need to better define the factors that impact fluid requirements and to determine the effects of fluid volumes on outcome. Methods: This study was part of a federally funded multicenter study. Multilinear regression analyses were performed to determine the patient and injury characteristics that most influenced fluid resuscitation volumes received. To assess the association of fluid volumes on outcome, propensity scores were developed to provide a predicted volume of fluid for each patient. Logistic models were then used to assess the impact of excess fluid beyond predicted volumes on outcome. Results: Seventy-two patients were included in this analysis. Average patient age was 40.6 years and average TBSA was 44.5%. Average fluid volume received during the first 24 hours after injury was 5.2/mL/kg/TBSA. Significant predictors of fluid received included % TBSA, age, intubation status, and weight. Increased fluid volume received increased risk of development of pneumonia (odds ratio [OR] = 1.92), bloodstream infections (OR = 2.33), adult respiratory distress syndrome (OR = 1.55), multiorgan failure (OR = 1.49), and death (OR = 1.74). Conclusion: TBSA, age, weight, and intubation status on admission were significant predictors of fluid received. Patients who received larger volumes of resuscitation fluid were at higher risk for injury complications and death. C1 Univ Washington, Harborview Med Ctr, Univ Washington Burn Ctr, Seattle, WA 98121 USA. Univ Washington, Harborview Med Ctr, Div Trauma Surg, Seattle, WA 98104 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Loyola Univ, Med Ctr, Dept Surg, Maywood, IL 60153 USA. Univ Texas, Med Branch, Dept Surg, Galveston, TX 77550 USA. Shriners Hosp Crippled Children, Galveston, TX USA. Univ Texas SW, Parkland Mem Hosp, Dept Surg, Dallas, TX USA. RP Klein, MB (reprint author), Univ Washington, Harborview Med Ctr, Univ Washington Burn Ctr, 325 9th Ave,Box 359796, Seattle, WA 98121 USA. EM mbklein@u.washington.edu FU NICHD NIH HHS [K12 HD049100]; NIGMS NIH HHS [U54 GM062119, U54 GM062119-1] NR 37 TC 95 Z9 97 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 APR PY 2007 VL 245 IS 4 BP 622 EP 628 DI 10.1097/01.sla.0000252572.50684.49 PG 7 WC Surgery SC Surgery GA 150RB UT WOS:000245232900019 PM 17414612 ER PT J AU Aslam, S Trautner, BW Ramanathan, V Darouiche, RO AF Aslam, Saima Trautner, Barbara W. Ramanathan, Venkat Darouiche, Rabih O. TI Combination of tigecycline and N-acetylcysteine reduces biofilm-embedded bacteria on vascular catheters SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID BLOOD-STREAM INFECTIONS; CRITICALLY-ILL PATIENTS; IN-VITRO; STAPHYLOCOCCUS-EPIDERMIDIS; ANTIBIOTIC LOCK; ATTRIBUTABLE MORTALITY; HEMODIALYSIS; VANCOMYCIN; PREVENTION; MODEL AB To assess the efficacy of an antibiofilm/antimicrobial agent combination, we incubated catheter segments colonized with one of six studied bacterial organisms in N-acetylcysteine, tigecycline, N-acetylcysteine-tigecy-cline, or saline. Segments were washed, sonicated, and cultured. N-acetylcysteine-tigecycline significantly decreased all viable biofilm-associated bacteria and was synergistic for methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. C1 Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Med Serv, Houston, TX 77030 USA. Baylor Coll Med, Infect Dis Sect, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Nephrol Sect, Dept Med, Houston, TX 77030 USA. RP Aslam, S (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Med Serv, Room 4B-370,2002 Holcombe Blvd, Houston, TX 77030 USA. EM saslam@bcm.tmc.edu; rdarouiche@aol.com FU NICHD NIH HHS [K23 HD042014, K23 HD042014-04, K23 HD042014-05] NR 27 TC 65 Z9 69 U1 0 U2 4 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 APR PY 2007 VL 51 IS 4 BP 1556 EP 1558 DI 10.1128/AAC.00893-06 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 153FD UT WOS:000245416500069 PM 17220399 ER PT J AU Takai, Y Matikainen, T Jurisicova, A Kim, MR Trbovich, AM Fujita, E Nakagawa, T Lemmers, B Flavell, RA Hakem, R Momoi, T Yuan, J Tilly, JL Perez, GI AF Takai, Y. Matikainen, T. Jurisicova, A. Kim, M. R. Trbovich, A. M. Fujita, E. Nakagawa, T. Lemmers, B. Flavell, R. A. Hakem, R. Momoi, T. Yuan, J. Tilly, J. L. Perez, G. I. TI Caspase-12 compensates for lack of caspase-2 and caspase-3 in female germ cells SO APOPTOSIS LA English DT Article DE oocyte; apoptosis; chemotherapy; caspases; DNA damage ID ENDOPLASMIC-RETICULUM STRESS; PREIMPLANTATION EMBRYO DEVELOPMENT; BCL-2 GENE FAMILY; INDUCED APOPTOSIS; DEATH; OOCYTES; BAX; EXPRESSION; AGE; ACTIVATION AB Previously, we analyzed mice lacking either caspase-2 or caspase-3 and documented a role for caspase-2 in developmental and chemotherapy-induced apoptosis of oocytes. Those data also revealed dispensability of caspase-3, although we found this caspase critical for ovarian granulosa cell death. Because of the mutual interdependence of germ cells and granulosa cells, herein we generated caspase-2 and -3 double-mutant (DKO) mice to evaluate how these two caspases functionally relate to each other in orchestrating oocyte apoptosis. No difference was observed in the rate of spontaneous oocyte apoptosis between DKO and wildtype (WT) females. In contrast, the oocytes from DKO females were more susceptible to apoptosis induced by DNA damaging agents, compared with oocytes from WT females. This increased sensitivity to death of DKO oocytes appears to be a specific response to DNA damage, and it was associated with a compensatory upregulation of caspase-12. Interestingly, DKO oocytes were more resistant to apoptosis induced by methotrexate (MTX) than WT oocytes. These results revealed that in female germ cells, insults that directly interfere with their metabolic status (e.g. MTX) require caspase-2 and caspase-3 as obligatory executioners of the ensuing cell death cascade. However, when DNA damage is involved, and in the absence of caspase-2 and -3, caspase-12 becomes upregulated and mediates apoptosis in oocytes. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Univ Toronto, Dept Obstet & Gynecol, Toronto, ON, Canada. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON, Canada. NCNP, Natl Inst Neurosci, Div Dev, Kodaira, Tokyo, Japan. NCNP, Natl Inst Neurosci, Div Differentiat, Kodaira, Tokyo, Japan. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Univ Toronto, Ontario Canc Inst, Dept Med Biophys, Div Cellular & Mol Biol, Toronto, ON, Canada. Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06510 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. RP Perez, GI (reprint author), Michigan State Univ, Dept Physiol, 4173 BPS, E Lansing, MI 48824 USA. EM perezg@msu.edu RI Jurisicova, Andrea/E-4580-2013 NR 44 TC 24 Z9 26 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1360-8185 J9 APOPTOSIS JI Apoptosis PD APR PY 2007 VL 12 IS 4 BP 791 EP 800 DI 10.1007/s10495-006-0022-z PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 145HV UT WOS:000244856800014 PM 17245644 ER PT J AU Faris, GW Ntziachristos, V Rector, DM Wang, LH AF Faris, Gregory W. Ntziachristos, Vasilis Rector, David M. Wang, Lihong TI Topics in biomedical optics: Introduction SO APPLIED OPTICS LA English DT Editorial Material AB This Applied Optics feature issue on Topics in Biomedical Optics highlights papers presented at the 2006 Biomedical Optics Topical Meeting sponsored by the Optical Society of America. The feature includes 40 papers that represent a cross section of topics that were covered at the meeting. (c) 2007 Optical Society of America. C1 SRI Int, Mol Phys Lab, Menlo Pk, CA 94025 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Bioopt & Mol Imaging,Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Washington State Univ, Dept Vet & Comparat Anat Pharmacol & Physiol, Pullman, WA 99164 USA. Washington Univ, Dept Biomed Engn, St Louis, MO 63130 USA. RP Faris, GW (reprint author), SRI Int, Mol Phys Lab, Menlo Pk, CA 94025 USA. EM gregory.faris@sri.com NR 0 TC 0 Z9 0 U1 0 U2 2 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD APR 1 PY 2007 VL 46 IS 10 BP 1595 EP 1596 DI 10.1364/AO.46.001595 PG 2 WC Optics SC Optics GA 151KZ UT WOS:000245290300001 ER PT J AU Heiskala, J Neuvonen, T Grant, PE Nissila, I AF Heiskala, Juha Neuvonen, Tuomas Grant, P. Ellen Nissila, Ilkka TI Significance of tissue anisotropy in optical tomography of the infant brain SO APPLIED OPTICS LA English DT Article; Proceedings Paper CT Biomedical Optics Topical Meeting of the Optical-Society-of-America CY MAR 19-22, 2006 CL Ft Lauderdale, FL SP Opt Soc Amer ID LIGHT-PROPAGATION; PHOTON MIGRATION; MRI; REGISTRATION; IMAGES; HEAD AB We study the effect of tissue anisotropy in optical tomography of neonates. A Monte Carlo method capable of modeling photon migration in an arbitrary 3D tissue model with spatially varying optical properties and tissue anisotropy is used for simulating measurements of neonates. Anatomical and diffusion tensor magnetic resonance imaging of neonates are used for creating the anatomical models. We find that tissue anisotropy affects the measured signal and the pattern of sensitivity in optical measurements. (c) 2007 Optical Society of America. C1 Univ Helsinki, Cent Hosp, Biomag Lab, FIN-00029 Helsinki, Finland. Univ Helsinki, Cent Hosp, Dept Clin Neurophysiol, FIN-00029 Helsinki, Finland. Univ Helsinki, Brain Res Ctr, FIN-00014 Helsinki, Finland. Aalto Univ, Lab Biomed Engn, FIN-02015 Helsinki, Finland. Univ Helsinki, Dept Physiol, Neurosci Unit, Inst Biomed, FIN-00014 Helsinki, Finland. Massachusetts Gen Hosp, Dept Pediat Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp East, Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Heiskala, J (reprint author), Univ Helsinki, Cent Hosp, Biomag Lab, POB 340, FIN-00029 Helsinki, Finland. EM juha.heiskala@iki.fi RI Nissila, Ilkka/G-6879-2012 OI Nissila, Ilkka/0000-0001-6534-8436 NR 21 TC 8 Z9 9 U1 0 U2 0 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD APR 1 PY 2007 VL 46 IS 10 BP 1633 EP 1640 DI 10.1364/AO.46.001633 PG 8 WC Optics SC Optics GA 151KZ UT WOS:000245290300006 PM 17356605 ER PT J AU Ma, GB Delorme, JF Gallant, P Boas, DA AF Ma, Guobin Delorme, Jean-Francois Gallant, Pascal Boas, David A. TI Comparison of simplified Monte Carlo simulation and diffusion approximation for the fluorescence signal from phantoms with typical mouse tissue optical properties SO APPLIED OPTICS LA English DT Article; Proceedings Paper CT Biomedical Optics Topical Meeting of the Optical-Society-of-America CY MAR 19-22, 2006 CL Ft Lauderdale, FL SP Opt Soc Amer ID PHOTON MIGRATION; RADIATIVE-TRANSFER; TURBID MEDIUM; MEDIA; LIGHT; MODEL; TOMOGRAPHY; SCATTERING; EQUATION; RECONSTRUCTION AB A simplified approach is proposed to simulate the fluorescence signal from a fluorophore submerged inside a turbid medium using the Monte Carlo method. Based on the reversibility of photon propagation, the fluorescence signal can be obtained from a single Monte Carlo simulation of the excitation light. This is computationally less expensive and also allows for the direct use of well-validated nonfluorescence photon migration Monte Carlo codes. Fluorescence signals from a mouse tissuelike phantom were computed using both the simplified Monte Carlo simulation and the diffusion approximation. The relative difference of signal intensity was found to be at most 30% for a fluorophore placed in the medium at various depths and horizontally midway between a source-detector pair separated by 3 mm. The difference in time characteristics of the signal is also examined. (c) 2007 Optical Society of America. C1 Adv Res Technol Inc, St Laurent, PQ H4S 2A4, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Ma, GB (reprint author), Adv Res Technol Inc, 2300 Alfred Nobel Blvd, St Laurent, PQ H4S 2A4, Canada. EM gma@art.ca NR 34 TC 22 Z9 22 U1 0 U2 2 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD APR 1 PY 2007 VL 46 IS 10 BP 1686 EP 1692 DI 10.1364/AO.46.001686 PG 7 WC Optics SC Optics GA 151KZ UT WOS:000245290300012 PM 17356611 ER PT J AU Miklowitz, DJ Otto, MW Frank, E Reilly-Harrington, NA Wisniewski, SR Kogan, JN Nierenberg, AA Calabrese, JR Marangell, LB Gyulai, L Araga, M Gonzalez, JM Shirley, ER Thase, ME Sachs, GS AF Miklowitz, David J. Otto, Michael W. Frank, Ellen Reilly-Harrington, Noreen A. Wisniewski, Stephen R. Kogan, Jane N. Nierenberg, Andrew A. Calabrese, Joseph R. Marangell, Lauren B. Gyulai, Laszlo Araga, Mako Gonzalez, Jodi M. Shirley, Edwin R. Thase, Michael E. Sachs, Gary S. TI Psychosocial treatments for bipolar depression - A 1-year randomized trial from the systematic treatment enhancement program SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID WEEKLY SYMPTOMATIC STATUS; RELAPSE PREVENTION; AFFECTIVE-DISORDER; COGNITIVE THERAPY; REGRESSION-MODEL; NATURAL-HISTORY; CLINICAL-TRIAL; I DISORDER; MANIA; PSYCHOEDUCATION AB Context: Psychosocial interventions have been shown to enhance pharmacotherapy outcomes in bipolar disorder. Objective: To examine the benefits of 4 disorder-specific psychotherapies in conjunction with pharmacotherapy on time to recovery and the likelihood of remaining well after an episode of bipolar depression. Design: Randomized controlled trial. Setting: Fifteen clinics affiliated with the Systematic Treatment Enhancement Program for Bipolar Disorder. Patients: A total of 293 referred outpatients with bipolar I or II disorder and depression treated with protocol pharmacotherapy were randomly assigned to intensive psychotherapy (n = 163) or collaborative care (n = 130), a brief psychoeducational intervention. Interventions: Intensive psychotherapy was given weekly and biweekly for up to 30 sessions in 9 months according to protocols for family-focused therapy, interpersonal and social rhythm therapy, and cognitive behavior therapy. Collaborative care consisted of 3 sessions in 6 weeks. Main Outcome Measures: Outcome assessments were performed by psychiatrists at each pharmacotherapy visit. Primary outcomes included time to recovery and the proportion of patients classified as well during each of 12 study months. Results: All analyses were by intention to treat. Rates of attrition did not differ across the intensive psychotherapy (35.6%) and collaborative care (30.8%) conditions. Patients receiving intensive psychotherapy had significantly higher year-end recovery rates (64.4% vs 51.5%) and shorter times to recovery than patients in collaborative care (hazard ratio, 1.47; 95% confidence interval, 1.08-2.00; P = .01). Patients in intensive psychotherapy were 1.58 times (95% confidence interval, 1.17-2.13) more likely to be clinically well during any study month than those in collaborative care (P = .003). No statistically significant differences were observed in the outcomes of the 3 intensive psychotherapies. Conclusions: Intensive psychosocial treatment as an adjunct to pharmacotherapy was more beneficial than brief treatment in enhancing stabilization from bipolar depression. Future studies should compare the cost-effectiveness of models of psychotherapy for bipolar disorder. C1 Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. Univ Colorado, Dept Psychiat, Boulder, CO 80309 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Med Ctr, Pittsburgh, PA 15213 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Case Western Reserve Univ, Univ Hosp Cleveland, Sch Med, Dept Psychiat, Cleveland, OH 44106 USA. Baylor Coll Med, Menninger Dept Psychiat, Houston, TX 77030 USA. VISN Mental Illness Res Educ & Clin Ctr 16, Dept Vet Affairs, Houston, TX USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. RP Miklowitz, DJ (reprint author), Univ Colorado, Dept Psychol, Muenzinger Bldg, Boulder, CO 80309 USA. EM miklow@psych.colorado.edu OI Wisniewski, Stephen/0000-0002-3877-9860 FU NIMH NIH HHS [MH29618, MH43931, MH55101, N01 MH080001, N01MH80001, R01 MH029618, R01 MH073871, R21 MH062555, R37 MH029618] NR 50 TC 251 Z9 254 U1 1 U2 15 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD APR PY 2007 VL 64 IS 4 BP 419 EP 427 DI 10.1001/archpsyc.64.4.419 PG 9 WC Psychiatry SC Psychiatry GA 152PT UT WOS:000245374800004 PM 17404119 ER PT J AU Fong, DS Strauber, SF Aiello, LP Beck, RW Callanan, DG Danis, RP Davis, MD Feman, SS Ferris, F Friedman, SM Garcia, CA Glassman, AR Han, DP le, D Kollman, C Lauer, AK Recchia, FM Solomon, SD AF Fong, Donald S. Strauber, Samara F. Aiello, Lloyd Paul Beck, Roy W. Callanan, David G. Danis, Ronald P. Davis, Matthew D. Feman, Stephen S. Ferris, Frederick Friedman, Scott M. Garcia, Charles A. Glassman, Adam R. Han, Dennis P. le, Darma Kollman, Craig Lauer, Andreas K. Recchia, Franco M. Solomon, Sharon D. CA Writing Comm Diabet Retinopathy TI Comparison of the modified early treatment diabetic retinopathy study and mild macular grid laser photocoagulation strategies for diabetic macular edema SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID GROWTH-FACTOR; RETINA; DDME AB Objective: To compare 2 laser photocoagulation techniques for treatment of diabetic macular edema: the modified Early Treatment Diabetic Retinopathy Study (ETDRS) direct/grid photocoagulation technique and a potentially milder (but potentially more extensive) mild macular grid (MMG) laser technique in which microaneurysms are not treated directly and small mild burns are placed throughout the macula, whether or not edema is present. Methods: Two hundred sixty-three subjects (mean age, 59 years) with previously untreated diabetic macular edema were randomly assigned to receive laser photocoagulation by either the modified ETDRS (162 eyes) or MMG (161 eyes) technique. Visual acuity, fundus photographs, and optical coherence tomography measurements were obtained at baseline and at 3.5, 8, and 12 months. Treatment was repeated if diabetic macular edema persisted. Main Outcome Measure: Change in optical coherence tomography measurements at 12-month follow-up. Results: Among eyes with a baseline central subfield thickness of 250 mu m or greater, central subfield thickening decreased by an average of 88 mu m in the modified ETDRS group and by 49 mu m in the MMG group at 12-month follow-up (adjusted mean difference, 33 mu m; 95% confidence interval, 5-61 mu m; P =. 02). Weighted inner zone thickening by optical coherence tomography decreased by 42 mu m in the modified ETDRS group and by 28 mu m in the MMG group (adjusted mean difference, 14 mu m; 95% confidence interval, 1-27 mu m; P =. 04); maximum retinal thickening ( maximum thickening of the central and 4 inner subfields) decreased by 66 and 39 mu m, respectively (adjusted mean difference, 27 mu m; 95% confidence interval, 6- 47 mu m; P =. 01), and retinal volume decreased by 0.8 and 0.4 mm(3), respectively (adjusted mean difference, 0.3 mm(3); 95% confidence interval, 0.02-0.53 mm(3); P =. 03). At 12 months, the mean change in visual acuity was 0 letters in the modified ETDRS group and 2 letters worse in the MMG group (adjusted mean difference, 2 letters; 95% confidence interval, -0.5 to 5 letters; P =. 10). Conclusions: At 12 months after treatment, the MMG technique was less effective at reducing optical coherence tomography-measured retinal thickening than the more extensively evaluated current modified ETDRS laser photocoagulation approach. However, the visual acuity outcome with both approaches is not substantially different. Given these findings, a larger long-term trial of the MMG technique is not justified. Application to Clinical Practice: Modified ETDRS focal photocoagulation should continue to be a standard approach for treating diabetic macular edema. C1 Jaeb Ctr Hlth Res, Diabet Retinopathy Clin Res Network, Tampa, FL 33647 USA. Wilmer Eye Inst, Baltimore, MD USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Palmetto Retina Ctr, Columbia, SC USA. Retina Ctr, Aiea, HI USA. Texas Retina Associates, Arlington, TX USA. Austin Retina Associates, Austin, TX USA. Elman Retina Grp PA, Baltimore, MD USA. NEI, NIH, Bethesda, MD 20892 USA. Charlotte Eye Ear Nose & Throat Associates PA, Charlotte, NC USA. Texas Retina Associates, Dallas, TX USA. Denver Hlth Med Ctr, Denver, CO USA. Henry Ford Hlth Syst, Dept Ophthalmol, Detroit, MI USA. Henry Ford Hlth Syst, Eye Care Serv, Detroit, MI USA. Retinal Consultants Inc, Dublin, OH USA. Retina Consultants SW Florida, Ft Myers, FL USA. Retina Vitreous Consultants, Ft Lauderdale, FL USA. Univ Texas, Med Branch, Dept Ophthalmol & Visual Sci, Galveston, TX USA. Associted Retinal Consultants, Grand Rapids, MI USA. Charles A Garcia PA & Associates, Houston, TX USA. Vitreoretinal Consultants, Houston, TX USA. Midw Eye Inst, Indianapolis, IN USA. Cent Florida Retina Inst, Lakeland, FL USA. Delaware Valley Retina Associates, Lawrenceville, NJ USA. Eldorado Retina Associates PC, Louisville, CO USA. Univ Wisconsin, Dept Ophthalmol, Retina Serv, Madison, WI USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Dean A McGee Eye Inst, Oklahoma City, OK USA. Paducah Retinal Ctr, Paducah, KY USA. Lahey Clin Inc, Inst Eye, Peabody, MA USA. Rocky Mt Retina Consultants, Salt Lake City, UT USA. W Coast Retina Med Grp Inc, San Francisco, CA USA. Univ Washington, Med Ctr, Seattle, WA USA. Retina Consultants PLLC, New Lions Eye Inst, Slingerlands, NY USA. St Louis Univ, Inst Eye, St Louis, MO 63103 USA. REtina Vitreous Surg Cent New York PC, Syracuse, NY USA. Int Eye Ctr, Tampa, FL USA. Wake Forest Univ, Ctr Eye, Winston Salem, NC USA. Med Coll Georgia, Augusta, GA 30912 USA. Retina Associates Cleveland Inc, Beachwood, OH USA. Univ N Carolina, Dept Ophthalmol, Chapel Hill, NC USA. Horizon Eye Care PA, Charlotte, NC USA. Vitreo Retinal Asociates, Grand Rapids, MI USA. Retina Grp Washington, Greenbelt, MD USA. Retina Associates Hawaii Inc, Honolulu, HI USA. SE Retina Associates PC, Kingsport, TN USA. Doheny Eye Inst, Los Angeles, CA 90033 USA. Univ Rochester, Rochester, NY 14627 USA. No Illinois Retina Ltd, Rockford, IL USA. So Calif Permanente Med Grp, Santa Ana, CA USA. W Texas Retina Consultants PA, Abilene, TX USA. Retina Consultants Alabama, Birmingham, AL USA. Rush Univ, Ctr Med, Chicago, IL USA. Duke Univ, Ctr Eye, Durham, NC USA. Univ Calif Irvine, Irvine, CA USA. Univ Kentucky, Lexington, KY USA. Loma Linda Univ Hlth Care, Dept Ophthalmol, Loma Linda, CA USA. Virginia Eye Inst, Richmond Retina Associates, Richmond, VA USA. Associated Retinal Consultants PC, Royal Oak, MI USA. Barnes Retina Inst, St Louis, MO USA. Retina Specialists, Towson, MD USA. Miramar Eye Specialist Med Grp, Ventura, CA USA. Northwestern Med Fac Fdn, Chicago, IL USA. Retina NW PC, Portland, OR USA. George Washington Univ, Dept Ophthalmol, Washington, DC USA. RP Fong, DS (reprint author), Jaeb Ctr Hlth Res, Diabet Retinopathy Clin Res Network, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA. EM drcrnet@jaeb.org NR 22 TC 101 Z9 110 U1 2 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD APR PY 2007 VL 125 IS 4 BP 469 EP 480 PG 12 WC Ophthalmology SC Ophthalmology GA 155AC UT WOS:000245548900003 ER PT J AU Price, R Ashwell, ZR Chang, MW Boninger, ML Koontz, AM Sisto, SA AF Price, Robert Ashwell, Zachary R. Chang, Michael W. Boninger, Michael L. Koontz, Alicia M. Sisto, Sue Ann TI Upper-limb joint power and its distribution in spinal cord injured wheelchair users: Steady-state self-selected speed versus maximal acceleration trials SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE biomechanics; kinetics; movement; rehabilitation; wheelchairs ID MECHANICAL ENERGY; FORCE APPLICATION; PUSH-OFF; PROPULSION; BIOMECHANICS; GAIT; ACCURACY; DIAMETER; STROKE; SYSTEM AB Objective: To compare upper-limb joint power magnitude and distribution between the shoulder, elbow, and wrist during maximal acceleration (MAC) versus steady-state, self-selected speed (SSS) manual wheelchair propulsion. Design: Cross-sectional biomechanic study. Setting: Research university and teaching hospital. Participants: Volunteer sample of 13 manual wheelchair users with spinal cord injury below T1. Interventions: Not applicable. Main Outcome Measures: Propulsive joint power magnitude and fractional distribution among upper-limb joints. Results: Wilcoxon signed-rank testing revealed shoulder power was larger for MAC versus SSS (median peak, 101.5W; interquartile range [IQR], 74.6; median peak, 37.7W; IQR, 22.9; respectively) (P <.01). Elbow and wrist power were unchanged. Peak shoulder power fraction was larger for MAC versus SSS (median peak, 1.055; lQR, 110 vs peak,.870; IQR,.252) (P <.01). Peak elbow power fraction was smaller for MAC versus SSS (median peak, -.012; IQR,.144 vs peak,.146; IQR,.206) (P <.05). Peak wrist power fraction was smaller for MAC versus SSS (median peak, -.058; IQR,.057 vs peak, -.010; IQR,.150) (P <.05). Conclusions: Power at the shoulder was larger than at other joints. Peak shoulder joint power and power fraction was larger during MAC versus SSS propulsion. Elbow and wrist power fractions were smaller for MAC versus SSS propulsion. Higher joint power, present under MAC, may predispose manual wheelchair users to injury, particularly at the shoulder. C1 Univ Washington, Dept Rehabil Med, Seattle, WA 98053 USA. Vet Affairs Pittsburgh HealthCare Syst, Human Engn Res Labs, Pittsburgh, PA USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr Hlth Syst, Dept Phys Med & Rehabil, Pittsburgh, PA USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Phys Med & Rehabil, Newark, NJ 07103 USA. Kessler Med Rehabil Res & Educ Corp, W Orange, NJ USA. RP Price, R (reprint author), Univ Washington, Dept Rehabil Med, Box 356490,1959 NE Pacific St, Seattle, WA 98053 USA. EM pricer@u.washington.edu OI Boninger, Michael/0000-0001-6966-919X NR 25 TC 9 Z9 9 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD APR PY 2007 VL 88 IS 4 BP 456 EP 463 DI 10.1016/j.apmr.2007.01.016 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 160CC UT WOS:000245913400010 PM 17398246 ER PT J AU Vagefi, PA Razo, O Deshpande, V McGrath, DJ Lauwers, GY Thayer, SP Warshaw, AL Fernandez-del Castillo, C AF Vagefi, Parsia A. Razo, Oswaldo Deshpande, Vikram McGrath, Deborah J. Lauwers, Gregory Y. Thayer, Sarah P. Warshaw, Andrew L. Fernandez-del Castillo, Carlos TI Evolving patterns in the detection and outcomes of pancreatic neuroendocrine neoplasms - The Massachusetts General Hospital experience from 1977 to 2005 SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the New-England-Surgical-Society CY SEP 15-17, 2006 CL Groton, CT SP New England Surg Soc ID ISLET-CELL-CARCINOMA; ENDOCRINE TUMORS; RESECTION; SURVIVAL; VOLUME AB Objective: To assess changing patterns in the detection and outcomes of pancreatic neuroendocrine neoplasms (PNENs). Design: Retrospective review from May 21,1977, through September 16, 2005. Setting: Massachusetts General Hospital, a tertiary care center. Patients: We evaluated 168 patients (51% male; mean age, 56 years) who underwent surgery for histologically confirmed PNENs. Main Outcome Measures: Surgical outcomes, survival, and changes in presentation of PNENs in 2 time groups: 1977-1999 (77 patients) and 2000-2005 (91 patients). Results: Ninety-eight patients (58.3%) had nonfunctioning PNENs, 86 of which were incidental. Insulinomas were the most common type of functional neoplasm (33.3%), followed by gastrinomas and glucagonomas; 12 patients (7.1%) had multiple endocrine neoplasia type 1. Of the neoplasms, 107 (63.7%) were located in the pancreatic body or tail. A pancreaticoduodenectomy was performed in 37 patients (22.0%), distal pancreatectomy was done in 88 (52.4%), and the rest had either middle segment pancreatectomy or enucleation. There were no operative deaths. We classified 76.8% of neoplasms as benign; of those classified as malignant, 25.6% had liver metastases. Of the patients, 10.1% received adjuvant therapy. Complete follow up was available in 90.5% of patients (mean, 63.3 months). Five- and 10-year actuarial survival rates were 77% and 62%, respectively. Incidentally discovered nonfunctioning neoplasms were significantly more frequent in the last 5 years (60.4% vs 40.3%; P = .007), with a trend toward smaller neoplasms (mean, 4.2 cm vs 5.6 cm; P =. 19) and lesser likelihood of malignancy (21.8% vs 40.0%; P = .08). Conclusions: We report a large single-center experience with PNENs. Increasing numbers of PNENs are being resected, largely owing to the incidental detection of nonfunctioning neoplasms. This may lead to the treatment of smaller and less malignant neoplasms. C1 Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Fernandez-del Castillo, C (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, WAC 336,55 Fruit St, Boston, MA 02114 USA. EM cfernandez@partners.org FU NCI NIH HHS [P01 CA117969]; NIDDK NIH HHS [K08 DK071329] NR 25 TC 101 Z9 103 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 2007 VL 142 IS 4 BP 347 EP 353 DI 10.1001/archsurg.142.4.347 PG 7 WC Surgery SC Surgery GA 156DR UT WOS:000245628800009 PM 17438169 ER PT J AU Sokal, SA Chang, YC Craft, DL Sandberg, WS Dunn, PF Berger, DL AF Sokal, Stizanne A. Chang, Yuchiao Craft, David L. Sandberg, Warren S. Dunn, Peter F. Berger, David L. TI Surgeon profiling - A key to optimum operating room use SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the New-England-Surgical-Society CY SEP 15-17, 2006 CL Groton, CT SP New England Surg Soc ID ANESTHESIA; INDUCTION AB Hypothesis: A high-efficiency Pod, composed of 3 parallel-processing operating rooms (ORs) and a dedicated 3-bed miniature postanesthesia care unit, can be filled with surgeons capable of converting time saved from parallel processing into incremental volume. Design: Statistical and mathematical modeling. Setting: Academic medical center with 52 serial-processing ORs, 1 parallel-processing OR, and a congested postanesthesia care unit. Participants: Elective surgical cases (N = 58 356) performed by a single surgical service without a preoperative intensive care unit bed request from April 1, 2004, through March 31, 2006. Interventions: Results from our parallel-processing OR (n = 1729) were extrapolated to all other cases (n = 56 627) to estimate the duration of key process time intervals as if they were performed using parallel processing. Cases that could yield incremental throughput using parallel processing were labeled "good." Total good case hours per week were then aggregated for each surgeon. Main Outcomes Measures: Surgeons with 4.5 hours per week or more of good case time had a "profile" suitable for a 9-hour block in The Pod every 2 weeks. Results: Of the 352 profiled surgeons, 30 had 4.5 hours per week or more of good case time, more than filling the 15 blocks per week. Conclusions: The high-efficiency OR Pod can fill each of its 3 ORs with case/surgeon combinations that should yield additional throughput. Surgeon profiles based on stringent efficiency targets maximize the throughput potential of The Pod's active ORs and more than compensate for the OR turned miniature postanesthesia care unit. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Decis Support & Qual Management Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Berger, DL (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,Wang 465, Boston, MA 02114 USA. NR 7 TC 11 Z9 11 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 2007 VL 142 IS 4 BP 365 EP 369 DI 10.1001/archsurg.142.4.365 PG 5 WC Surgery SC Surgery GA 156DR UT WOS:000245628800015 PM 17438172 ER PT J AU Stephen, AE Roth, SI Fardo, DW Finkelstein, DM Randolph, GW Gaz, RD Hodin, RA AF Stephen, Antonia E. Roth, Sanford I. Fardo, David W. Finkelstein, Dianne M. Randolph, Gregory W. Gaz, Randall D. Hodin, Richard A. TI Predictors of an accurate preoperative sestamibi scan for single-gland parathyroid adenomas SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the New-England-Surgical-Society CY SEP 15-17, 2006 CL Groton, CT SP New England Surg Soc ID PRIMARY HYPERPARATHYROIDISM; TC-99M-MIBI SCINTIGRAPHY; LOCALIZATION; HYPERCALCEMIA; SENSITIVITY; SURGERY; DISEASE AB Objective: To investigate why some patients with single parathyroid adenomas have negative preoperative sestamibi scans. Design: Retrospective review. Setting: Tertiary care center. Patients: Twenty-one patients with false-negative (FN) scans were compared with 22 patients with true-positive (TP) scans. All patients had single parathyroid adenomas. Interventions: Neck exploration and removal of parathyroid adenomas. Main Outcome Measures: Age; sex; preoperative serum calcium and parathyroid hormone levels; gland weight; location, and pathologic features. Results: There was no significant difference in age or preoperative serum calcium or parathyroid hormone levels. Gland weight was greater in the TP group compared with the FN group (mean SD, 1336 +/- 1603 mg vs 475 +/- 365 mg; P = .04); 13 (62%) of the 21 glands in the FN group were located in the upper position, compared with 6 (27%) of the 22 glands in the TP group (P = .03). Ten of the 22 glands in the TP group consisted predominantly of oxyphil cells, compared with 2 of the 21 glands in the FN group (P = .02). A multivariate logistic regression model yielded the following factors that predicted an accurate scan: higher percentage of oxyphil cells (P = .03), heavier gland (P = .03), female sex (P = .04), and gland location in the lower position (P =. 04). Conclusions: Smaller-volume parathyroid adenomas and those in the upper position are less likely to be localized with sestamibi scans. A TP scan correlates with oxyphil cell predominance, supporting a role for the mitochondrial-rich cell in sestamibi uptake and retention. C1 Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Stephen, AE (reprint author), Massachusetts Gen Hosp, Dept Surg Oncol, Yawkey 7B,55 Fruit St, Boston, MA 02114 USA. EM astephen@partners.org NR 25 TC 29 Z9 29 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 2007 VL 142 IS 4 BP 381 EP 386 DI 10.1001/archsurg.142.4.381 PG 6 WC Surgery SC Surgery GA 156DR UT WOS:000245628800019 PM 17441292 ER PT J AU Denis, CV Wagner, DD AF Denis, Cecile V. Wagner, Denisa D. TI Platelet adhesion receptors and their ligands in mouse models of thrombosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Review DE platelets; animal models; thrombosis; adhesion; bleeding ID VON-WILLEBRAND-FACTOR; PLASMINOGEN-ACTIVATOR INHIBITOR-1; BERNARD-SOULIER-SYNDROME; INTEGRIN TYROSINE PHOSPHORYLATION; IN-VIVO; GLYCOPROTEIN-IB; TISSUE FACTOR; ARTERIAL THROMBOSIS; MICE LACKING; P-SELECTIN AB Platelet adhesion and aggregation at sites of vascular injury are two key events in hemostasis and thrombosis. Because of exciting advances in genetic engineering, the mouse has become an important and frequently used model to unravel the molecular mechanisms underlying the multistep process leading to the formation of a stable platelet plug. In gene-targeted mice, the crucial importance of platelet adhesion receptors such as glycoprotein Ib alpha or the alpha IIb beta 3 integrin has been confirmed and further clarified. Their absence leads to highly impaired thrombus formation, independent of the model used to induce vascular injury. In contrast, the relative contribution of other receptors, such as glycoprotein VI, or of various platelet ligands may be regulated by the severity of injury, the type of vessel injured, and the signaling pathways that are generated. Murine models have also helped improve understanding of the second wave of events that leads to stabilization of the platelet aggregate. Despite the current limitations due to lack of standardization and the virtual absence of thrombosis models in diseased vessels, there is no doubt that the mouse will play a key role in the discovery and characterization of the next generation of antithrombotic agents. This review focuses on key findings about the molecular mechanisms supporting hemostasis and thrombosis that have been obtained with genetically engineered mouse models deficient in various platelet adhesion receptors and ligands. Combination of these models with sophisticated methods allowing direct visualization of platelet-vessel wall interactions after injury greatly contributed to recent advances in the field. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Paris Sud, INSERM, U770, F-94275 Le Kremlin Bicetre, France. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM wagner@cbr.med.harvard.edu RI Denis , Cecile/A-7649-2011 OI Denis , Cecile/0000-0001-5152-9156 FU NHLBI NIH HHS [P01 HL056949, P01 HL56949, R37 HL041002, R37 HL41002] NR 105 TC 71 Z9 74 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD APR PY 2007 VL 27 IS 4 BP 728 EP 739 DI 10.1161/01.ATV.0000259359.52265.62 PG 12 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 148VF UT WOS:000245104100009 PM 17272754 ER PT J AU Shin, JJ Glickstein, LJ Steere, AC AF Shin, Junghee J. Glickstein, Lisa J. Steere, Allen C. TI High levels of inflammatory chemokines and cytokines in joint fluid and synovial tissue throughout the course of antibiotic-refractory Lyme arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SURFACE PROTEIN-A; RHEUMATOID-ARTHRITIS; BORRELIA-BURGDORFERI; T-CELLS; INCREASED EXPRESSION; CEREBROSPINAL-FLUID; PERIPHERAL-BLOOD; METHOTREXATE; CXCR3; MICE AB Objective. To investigate the possible role of chemokines and cytokines in the pathogenesis of Lyme arthritis. Methods. Using cytometric bead array and flow cytometry techniques, chemokine and cytokine levels were determined in 65 synovial fluid (SF) samples and 7 synovial tissue (ST) samples from 17 patients with antibiotic-responsive Lyme arthritis and 35 patients with antibiotic-refractory Lyme arthritis seen during the past 18 years. In the ST samples, expression of chemokine receptors was measured using immunohistochemistry. Results. Before or during antibiotic therapy, when the majority of patients had positive polymerase chain reaction (PCR) results for Borrelia burgdorferi DNA, SF from patients with antibiotic-refractory arthritis contained exceptionally high levels of Th1 chemoattractants and cytokines, particularly CXCL9 and interferon-gamma (IFN gamma). Compared with the patients whose arthritis was responsive to antibiotic treatment, those with antibiotic-refractory arthritis had significantly higher levels of CXCL9 and CXCL10 (both P <= 0.001) and CCL3, CCL4, CXCL8, IFN gamma, tumor necrosis factor a, interleukin-1 beta (IL-1 beta), and IL-6 (all P <= 0.01). During the post-antibiotic period, when the results of PCR for B burgdorferi DNA in SF and ST were uniformly negative, patients with antibiotic-refractory arthritis continued to exhibit high SF and ST levels of these chemokines and cytokines. In addition, synovial samples showed marked expression of the receptors for T cell or macrophage chemokines, CXCR3 and CCR5. Conclusion. Patients with antibiotic-refractory Lyme arthritis have high synovial fluid levels of proinflammatory chemokines and cytokines, especially CXCL9 and IFN gamma, throughout the illness. Thus, even when antibiotic treatment reduces or completely clears the infection in these patients, the inflammatory response in synovium persists. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Shin, JJ (reprint author), Massachusetts Gen Hosp, 55 Fruit St,CNY 149-8301, Boston, MA 02114 USA. EM jjshin@partners.org FU NIAMS NIH HHS [AR-20358] NR 49 TC 63 Z9 64 U1 2 U2 12 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD APR PY 2007 VL 56 IS 4 BP 1325 EP 1335 DI 10.1002/art.22441 PG 11 WC Rheumatology SC Rheumatology GA 159DH UT WOS:000245845100032 PM 17393419 ER PT J AU Kosten, TA Zhang, XY Haile, CN AF Kosten, Therese A. Zhang, Xiang Yang Haile, Colin N. TI Strain differences in maintenance of cocaine self-administration and their relationship to novelty activity responses SO BEHAVIORAL NEUROSCIENCE LA English DT Article DE Lewis inbred rats; Fischer 344 inbred rats; progressive ratio; locomotor activity ID CORTICOTROPIN RELEASING HORMONE; CONDITIONED PLACE PREFERENCE; INBRED RAT STRAINS; LOCOMOTOR-ACTIVITY; FISCHER-344 RATS; FEMALE RATS; DOPAMINE-TRANSPORTER; NUCLEUS ACCUMBENS; LEWIS; ACQUISITION AB The authors previously demonstrated that Fischer 344 (F344) and Lewis inbred rats differ in acquisition of cocaine self-administration. Other studies show that acquisition and maintenance of drug self-administration are predicted by locomotor activity in a novel environment among outbred Sprague-Dawley rats. The present study was designed to determine whether this relationship extended to F344 and Lewis rats. In Experiment 1, F344, Lewis, and Sprague-Dawley rats were trained to self-administer cocaine and tested with several doses under fixed- and progressive-ratio schedules of reinforcement. Self-administered infusions and ineffective active lever presses-those emitted during infusion and time-out periods-were assessed. In Experiment 2, separate sets of rats of each strain were examined for locomotor responses (distance traveled and center time) under novelty conditions. Results show that F344 rats self-administer more cocaine than Lewis or Sprague-Dawley rats under both schedules and emit more ineffective lever presses-a possible measure of craving. Strain comparisons of locomotor responses suggest that center time, not activity, relates to self-administration behavior. Maintenance studies of cocaine self-administration rather than acquisition may better reflect vulnerability to addiction. C1 Michael E DeBakey Vet Affairs Med Ctr, Res Serv Line 151, Houston, TX 77030 USA. Baylor Coll Med, Menninger Dept Psychiat, Houston, TX 77030 USA. RP Kosten, TA (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Res Serv Line 151, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM tkosten@bcm.edu OI Haile, Colin/0000-0001-8293-7291 NR 58 TC 31 Z9 31 U1 1 U2 3 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD APR PY 2007 VL 121 IS 2 BP 380 EP 388 DI 10.1037/0735-7044.121.2.380 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 157CM UT WOS:000245696200016 PM 17469928 ER PT J AU Samuels, JF Bienvenu, OJ Pinto, A Fyer, AJ McCracken, JT Rauch, SL Murphy, DL Grados, MA Greenberg, BD Knowles, JA Placentini, J Cannistraro, PA Cullen, B Riddle, MA Rasmussen, SA Pauls, DL Willour, VL Shugart, YY Liang, KY Hoehn-Saric, R Nestadt, G AF Samuels, Jack F. Bienvenu, O. Joseph Pinto, Anthony Fyer, Abby J. McCracken, James T. Rauch, Scott L. Murphy, Dennis L. Grados, Marco A. Greenberg, Benjamin D. Knowles, James A. Placentini, John Cannistraro, Paul A. Cullen, Bernadette Riddle, Mark A. Rasmussen, Steven A. Pauls, David L. Willour, Virginia L. Shugart, Yin Y. Liang, Kung-yee Hoehn-Saric, Rudolf Nestadt, Gerald TI Hoarding in obsessive-compulsive disorder: results from the OCD collaborative genetics study SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE hoarding; obsessive-compulsive disorder; comorbidity; personality ID FACTOR-ANALYZED SYMPTOM; PERSONALITY-DISORDERS; DIMENSIONS; BEHAVIOR; FAMILY; SCHIZOPHRENIA; RATIONALE; MODEL; LA AB Hoarding behavior occurs frequently in obsessive-compulsive disorder (OCD). Results from previous studies suggest that individuals with OCD who have hoarding symptoms are clinically different than non-hoarders and may represent a distinct clinical group. In the present study, we compared 235 hoarding to 389 non-hoarding participants, all of whom had OCD, collected in the course of the OCD Collaborative Genetics Study. We found that, compared to non-hoarding individuals, boarders were more likely to have symmetry obsessions and repeating, counting, and ordering compulsions; poorer insight; more severe illness; difficulty initiating or completing tasks, and indecision. Hoarders had a greater prevalence of social phobia and generalized anxiety disorder. Hoarders also had a greater prevalence of obsessive-compulsive and dependent personality disorders. Five personality traits were independently associated with hoarding: miserliness, preoccupation with details, difficulty making decisions, odd behavior or appearance, and magical thinking. Hoarding and indecision were more prevalent in the relatives of hoarding than of non-hoarding probands. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. Brown Univ, Sch Med, Butler Hosp, Dept Psychiat & Human Behav, Providence, RI 02906 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Sch Med, Los Angeles, CA 90024 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21287 USA. RP Samuels, JF (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 600 N Wolfe St,Meyer 4-181, Baltimore, MD 21287 USA. EM jacks@jhmi.edu RI Liang, Kung-Yee/F-8299-2011; Pinto, Anthony/D-2718-2017; OI Pinto, Anthony/0000-0002-6078-7242; Samuels, Jack/0000-0002-6715-7905 FU NCRR NIH HHS [RR00052]; NIMH NIH HHS [K23-MH64543, R01 MH50214] NR 51 TC 112 Z9 114 U1 2 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD APR PY 2007 VL 45 IS 4 BP 673 EP 686 DI 10.1016/j.brat.2006.05.008 PG 14 WC Psychology, Clinical SC Psychology GA 149RO UT WOS:000245164500004 PM 16824483 ER PT J AU Walsh, DM Minogue, AM Frigerio, CS Fadeeva, JV Wasco, W Selkoe, DJ AF Walsh, D. M. Minogue, A. M. Frigerio, C. Sala Fadeeva, J. V. Wasco, W. Selkoe, D. J. TI The APP family of proteins: similarities and differences SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT Conference on Neurological Disorder - Molecules, Mechanisms nad Thrrapeutics CY SEP 21-22, 2006 CL Univ Coll Cork, Devere Hall, Cork, IRELAND HO Univ Coll Cork, Devere Hall DE Alzheimer's disease; beta-amyloid-cleaving enzyme (BACE); amyloid precursor protein (APP); amyloid precursor-like protein (APLP); gamma-secretase; therapy ID AMYLOID PRECURSOR PROTEIN; BETA-SECRETASE; GAMMA-SECRETASE; TRANSMEMBRANE DOMAIN; ALZHEIMERS-DISEASE; CONVERTING-ENZYME; ALPHA-SECRETASE; MICE LACKING; CLEAVAGE; APLP2 AB overwhelming evidence indicates that the A beta (amyloid beta-peptide) plays a critical role in the pathogenesis of Alzheimer's disease. A beta is derived from the APP (amyloid precursor protein) by the action of two aspartyl proteases (beta- and gamma-secretases) that are leading candidates for therapeutic intervention. APP is a member of a multigene family that includes APLP1 (amyloid precursor-like protein 1) and APLP2. Both APLPs are processed in a manner analogous to APP, with all three proteins subject to ectodomain shedding and subsequent cleavage by gamma-secretase. Careful study of the APP family of proteins has already revealed important insights about APP. Here, we will review how knowledge of the similarities and differences between APP and the APLPs may prove useful for the development of novel disease-modifying therapeutics. C1 Univ Coll Dublin, Conway Inst, Lab Neurodegenerat Res, Dublin 2, Ireland. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Res Unit, Boston, MA 02129 USA. RP Walsh, DM (reprint author), Univ Coll Dublin, Conway Inst, Lab Neurodegenerat Res, Dublin 2, Ireland. EM dominic.walsh@ucd.ie FU NIA NIH HHS [AG05179]; Wellcome Trust [067660] NR 49 TC 78 Z9 80 U1 0 U2 5 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD APR PY 2007 VL 35 BP 416 EP 420 PN 2 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 157GD UT WOS:000245705800061 PM 17371289 ER PT J AU Georges, GE Maris, MB Maloney, DG Sandmaier, BM Sorror, ML Shizuru, JA Lange, T Agura, ED Bruno, B McSweeney, PA Pulsipher, MA Chauncey, TR Mielcarek, M Storer, BE Storb, R AF Georges, George E. Maris, Michael B. Maloney, David G. Sandmaier, Brenda M. Sorror, Mohamed L. Shizuru, Judith A. Lange, Thoralf Agura, Edward D. Bruno, Benedetto McSweeney, Peter A. Pulsipher, Michael A. Chauncey, Thomas R. Mielcarek, Marco Storer, Barry E. Storb, Rainer TI Nonmyeloablative unrelated donor hematopoietic cell transplantation to treat patients with poor-risk, relapsed, or refractory multiple myeloma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE multiple myeloma; nonmyeloablative conditioning; allogeneic hematopoietic cell transplantation; unrelated donor; graft-versus-tumor effect; chronic graft-versus-host disease; peripheral blood stem cell transplantation ID HIGH-DOSE THERAPY; BONE-MARROW-TRANSPLANTATION; COLONY-STIMULATING FACTOR; VERSUS-HOST-DISEASE; ALLOGENEIC TRANSPLANTATION; HEMATOLOGIC MALIGNANCIES; PROGNOSTIC-FACTORS; LYMPHOCYTE INFUSIONS; RANDOMIZED-TRIAL; CHEMOTHERAPY AB The purpose of this study was to determine long-term outcome of unrelated donor nomnyeloablative hematopoietic cell transplantation (HCT) in patients with poor-risk multiple myeloma. A total of 24 patients were enrolled; 17 patients (71%) had chemotherapy-refractory disease, and 14 (58%) experienced disease relapse or progression after previous autologous transplantation. Thirteen patients underwent planned autologous transplantation followed 43-135 days later with unrelated transplantation, whereas 11 proceeded directly to unrelated transplantation. All 24 patients were treated with fludarabine (90 mg/m(2)) and 2 Gy of total body irradiation before HLA-matched unrelated peripheral blood stem cell transplantation. Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil. The median follow-up was 3 years after allografting. One patient experienced nonfatal graft rejection. The incidences of acute grades II and III and chronic graft-versus-host disease were 54%, 13%, and 75%, respectively. The 3-year nonrelapse mortality (NRM) was 21%. Complete responses were observed in 10 patients (42%); partial responses, in 4 (17%). At 3 years, overall survival (OS) and progression-free survival (PFS) rates were 61% and 33%, respectively. Patients receiving tandem autologous-unrelated transplantation had superior OS and PFS (77% and 51%) compared with patients proceeding directly to unrelated donor transplantation (44% and 11%) (PFS P value =.03). In summary, for patients with poor-risk, relapsed, or refractory multiple myeloma, cytoreductive autologous HCT followed by nonmyeloablative conditioning and unrelated HCT is an effective treatment approach, with low NRM, high complete remission rates, and prolonged disease-free survival. (c) 2007 American Society for Blood and Marrow Transplantation. C1 Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. Univ Washington, Dept Med, Seattle, WA USA. Stanford Univ, Dept Med, Palo Alto, CA 94304 USA. Univ Leipzig, Dept Med, D-7010 Leipzig, Germany. Baylor Univ, Med Ctr, Dept Med, Dallas, TX USA. Univ Turin, Div Ematol, Turin, Italy. Rocky Mt Canc Ctr, Dept Blood & Marrow Transplantat, Denver, CO USA. Univ Utah, Dept Med, Salt Lake City, UT 84112 USA. VA Puget Sound Hlth Care Syst, Dept Med Oncol, Seattle, WA USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Georges, GE (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D1-100,POB 19024, Seattle, WA 98109 USA. EM ggeorges@fhcrc.org FU NCI NIH HHS [P30 CA015704-31S1, P30 CA015704-33S2, K23 CA092058-05, K23 CA092058-03, P30 CA015704-30S1, P30 CA015704-33S1, P30 CA015704-31, CA 78902, P30 CA015704-32, P01 CA018029-30, K23 CA092058, R01 CA109381-03, P01 CA018029-26, P30 CA015704-32S2, P30 CA015704-30, K23 CA092058-02, K23 CA092058-01, P01 CA018029-24, P01 CA018029-28, P01 CA018029-31, P01 CA078902-09, P30 CA015704-32S1, P01 CA018029-27, CA 15704, CA 92058, P01 CA078902, P30 CA015704, P01 CA018029-25, P30 CA015704-34S1, P30 CA015704-33, P01 CA018029-32, CA 18029, P01 CA018029, P30 CA015704-346232, P01 CA018029-270047, P30 CA015704-34, P30 CA015704-31S2, K23 CA092058-04, P01 CA018029-29] NR 50 TC 23 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD APR PY 2007 VL 13 IS 4 BP 423 EP 432 DI 10.1016/j.bbmt.2006.11.011 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 154XC UT WOS:000245540300005 PM 17287157 ER PT J AU Ito, T Fraser, IP Yeo, Y Highley, CB Bellas, E Kohane, DS AF Ito, Taichi Fraser, Iain P. Yeo, Yoon Highley, Christopher B. Bellas, Evangelia Kohane, Daniel S. TI Anti-inflammatory function of an in situ cross-linkable conjugate hydrogel of hyaluronic acid and dexamethasone SO BIOMATERIALS LA English DT Article DE inflammation; hydrogel; cytokine; drug release; adhesion ID PERITONEAL MESOTHELIAL CELLS; PLASMINOGEN-ACTIVATOR INHIBITOR-1; POSTOPERATIVE ABDOMINAL ADHESIONS; RAT GASTROINTESTINAL-TRACT; COLON-SPECIFIC DELIVERY; CHEMICAL-MODIFICATION; POTENTIAL PRODRUGS; PREVENTION; DERIVATIVES; CYTOKINES AB Postoperative peritoneal adhesions cause pelvic pain, infertility, and potentially lethal bowel obstruction. We have designed and synthesized an injectable hydrogel composed of cross-linkable modified hyaluronic acids (HAs) conjugated to dexamethasone (HAX-DEX), and investigated its anti-inflammatory function. HAX-DEX formed a hydrogel in < 1 min by cross-linking reactions between aldehyde groups and hydrazide groups. The hydrogel degraded in media over 5 days, releasing dexamethasone slowly over that time, reducing TNF-alpha and IL-6 production from lipopolysaccharide-stimulated primary mouse macrophages in vitro. HAX-DEX was biocompatible on subcutaneous injection, and caused less inflammation than unmodified cross-linked HA. (c) 2006 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pediat Intens Care,Lab Biomat & Drug Delivery, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Lab Dev Immunol, Boston, MA 02114 USA. MIT, Dept Chem Engn, Cambridge, MA 02142 USA. RP Kohane, DS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pediat Intens Care,Lab Biomat & Drug Delivery, Bartlett Extens 413,55 Fruit St, Boston, MA 02114 USA. EM dkohane@partners.org FU NIGMS NIH HHS [GM073626] NR 41 TC 59 Z9 62 U1 6 U2 47 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD APR PY 2007 VL 28 IS 10 BP 1778 EP 1786 DI 10.1016/j.biomaterials.2006.12.012 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 139MM UT WOS:000244436000005 PM 17204321 ER PT J AU Laframboise, T Harrington, D Weir, BA AF Laframboise, Thomas Harrington, David Weir, Barbara A. TI PLASQ: a generalized linear model-based procedure to determine allelic dosage in cancer cells from SNP array data SO BIOSTATISTICS LA English DT Article DE allelic imbalance; cancer genomics; DNA copy number; expectation-maximization algorithm; generalized linear model; single nucleotide polymorphism array ID POLYMORPHISM; NORMALIZATION; MICROARRAYS; ALGORITHM; SIGNAL AB Human cancer is largely driven by the acquisition of mutations. One class of such mutations is copy number polymorphisms, comprised of deviations from the normal diploid two copies of each autosomal chromosome per cell. We describe a probe-level allele-specific quantitation (PLASQ) procedure to determine copy number contributions from each of the parental chromosomes in cancer cells from single-nucleotide polymorphism (SNP) microarray data. Our approach is based upon a generalized linear model that takes advantage of a novel classification of probes on the array. As a result of this classification, we are able to fit the model to the data using an expectation-maximization algorithm designed for the purpose. We demonstrate a strong model fit to data from a variety of cell types. In normal diploid samples, PLASQ is able to genotype with very high accuracy. Moreover, we are able to provide a generalized genotype in cancer samples (e.g. CCCCT at an amplified SNP). Our approach is illustrated on a variety of lung cancer cell lines and tumors, and a number of events are validated by independent computational and experimental means. An R software package containing the methods is freely available. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Laframboise, T (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM tlafram@broad.mit.edu FU NIAID NIH HHS [2 R01 AI052817] NR 19 TC 37 Z9 39 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD APR PY 2007 VL 8 IS 2 BP 323 EP 336 DI 10.1093/biostatistics/kxl012 PG 14 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 154MP UT WOS:000245512000012 PM 16787995 ER PT J AU Richardson, P AF Richardson, Paul TI Toward a new therapeutic backbone in myeloma SO BLOOD LA English DT Editorial Material ID MULTIPLE-MYELOMA; THALIDOMIDE C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Richardson, P (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 2007 VL 109 IS 7 BP 2672 EP 2673 PG 2 WC Hematology SC Hematology GA 156HP UT WOS:000245639000006 ER PT J AU Alsayed, Y Ngo, H Runnels, J Leleu, X Singha, UK Pitsillides, CM Spencer, JA Kimlinger, T Ghobrial, JM Jia, XY Lu, GW Timm, M Kumar, A Cote, D Veilleux, I Hedin, KE Roodman, GD WitZig, TE Kung, AL Hideshima, T Anderson, KC Lin, CP Ghobrial, IM AF Alsayed, Yazan Ngo, Hai Runnels, Judith Leleu, Xavier Singha, Ujjal K. Pitsillides, Costas M. Spencer, Joel A. Kimlinger, Teresa Ghobrial, Joanna M. Jia, Xiaoying Lu, Ganwei Timm, Michael Kumar, Ashok Cote, Daniel Veilleux, Israel Hedin, Karen E. Roodman, G. David WitZig, Thomas E. Kung, Andrew L. Hideshima, Teru Anderson, Kenneth C. Lin, Charles P. Ghobrial, Irene M. TI Mechanisms of regulation of CXCR4/SDF-1 (CXCL12)-dependent migration and homing in multiple myeloma SO BLOOD LA English DT Article ID CELL-DERIVED FACTOR-1-ALPHA; CHEMOKINE RECEPTORS; CIRCULATING CELLS; CXCR4 ANTAGONIST; PROGENITOR CELLS; T-LYMPHOCYTES; BONE-MARROW; STEM-CELLS; ADHESION; KINASE AB The mechanisms by which multiple myeloma (MM) cells migrate and home to the bone marrow are not well understood. In this study, we sought to determine the effect of the chemokine SDF-1 (CXCL12) and its receptor CXCR4 on the migration and homing of MM cells. We demonstrated that CXCR4 is differentially expressed at high levels in the peripheral blood and is down-regulated in the bone marrow in response to high levels of SDF-1. SDF-1 induced motility, internalization, and cytoskeletal rearrangement in MM cells evidenced by confocal microscopy. The specific CXCR4 inhibitor AMD3100 and the anti-CXCR4 antibody MAB171 inhibited the migration of MM cells in vitro. CXCR4 knockdown experiments demonstrated that SDF-1-dependent migration was regulated by the PI3K and ERK/MAPK pathways but not by p38 MAPK. In addition, we demonstrated that AMD3100 inhibited the homing of MM cells to the bone marrow niches using in vivo flow cytometry, in vivo confocal microscopy, and whole body bioluminescence imaging. This study, therefore, demonstrates that SDF-1/CXCR4 is a critical regulator of MM homing and that it provides the framework for inhibitors of this pathway to be used in future clinical trials to abrogate MM trafficking. C1 Univ Pittsburgh, Inst Canc, Dept Internal Med, Div Hematol Oncol, Pittsburgh, PA 15260 USA. Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Adv Microscopy Progam, Boston, MA USA. Mayo Clin, Coll Med, Rochester, MN USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ghobrial, JM (reprint author), Univ Pittsburgh, Inst Canc, Dept Internal Med, Div Hematol Oncol, Pittsburgh, PA 15260 USA. EM irene_ghobrial@dfci.harvard.edu RI Cote, Daniel/D-5185-2011; Spencer, Joel/A-4590-2013; OI Kung, Andrew/0000-0002-9091-488X FU NIBIB NIH HHS [EB000664, R01 EB000664] NR 50 TC 236 Z9 243 U1 1 U2 19 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 APR 1 PY 2007 VL 109 IS 7 BP 2708 EP 2717 DI 10.1182/blood-2006-07-035857 PG 10 WC Hematology SC Hematology GA 156HP UT WOS:000245639000015 PM 17119115 ER PT J AU Tzachanis, D Li, LQ Lafuente, EM Berezovskaya, A Freeman, GJ Boussiotis, VA AF Tzachanis, Dimitrios Li, Lequn Lafuente, Esther M. Berezovskaya, Alla Freeman, Gordon J. Boussiotis, Vassiliki A. TI Twisted gastrulation (Tsg) is regulated by Tob and enhances TGF-beta signaling in activated T lymphocytes SO BLOOD LA English DT Article ID GROWTH-FACTOR-BETA; BONE MORPHOGENETIC PROTEINS; DEVELOPMENTAL PATHWAY; CELL DIFFERENTIATION; TARGETED DISRUPTION; EXPRESSION PATTERNS; MOUSE EMBRYOGENESIS; BMP ANTAGONIST; GENE-THERAPY; PROLIFERATION AB Quiescent T cells express Tob, an APRO gene family member, which functions as a transcriptional regulator. Subtractive hybridization identified Twisted gastrulation (Tsg) as one of the genes suppressed by Tob. Tsg is a secreted protein that interacts with Drosophila decapentaplegic (Dpp) and its vertebrate orthologs BMP2/4 and regulates morphogenetic effects in embryos. Here, we report the expression and function of Tsg in human T cells. Tsg mRNA was almost undetectable in unstimulated T cells and was up-regulated after activation by TCR/CD3 and either CD28, IL-2, or PMA. Tsg protein had no effect on responses of primary T cells to TCR/CD3 stimulation but had a potent inhibitory effect on proliferation and cytokine production of primed alloreactive CD4(+) cells. Surprisingly, Tsg did not affect phosphorylation of the BMP-specific Smad1 but induced phosphorylation of the TGF-beta-specific Smad2 and mediated DNA binding on Smad3/4 consensus-binding sites, suggesting that it acted downstream of TGF-beta. In vitro association assays revealed a direct interaction of Tsg and TGF-beta proteins. Thus, Tsg functions as an agonist synergizing with TGF-beta to inhibit T-cell activation. Modulation of Tsg signaling may represent a novel target for molecular intervention toward control of aberrant T-cell responses during ongoing graft-versus-host disease (GVHD) and autoimmune diseases. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Beth Israel Deaconess Med Ctr, Dept Hematol & Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hematol & Oncol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Boussiotis, VA (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bldg CNY 149-5102,13th St, Boston, MA 02129 USA. EM vboussiotis@partners.org RI Lafuente, Esther M/K-5684-2014 OI Lafuente, Esther M/0000-0001-8466-1022 FU NCI NIH HHS [CA104596, R01 CA104596]; NIAID NIH HHS [AI 43552, AI 56299, P01 AI056299, R01 AI043552, R21 AI043552, R56 AI043552] NR 51 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 2007 VL 109 IS 7 BP 2944 EP 2952 DI 10.1182/blood-2006-03-006510 PG 9 WC Hematology SC Hematology GA 156HP UT WOS:000245639000047 PM 17164348 ER PT J AU Cutler, C Li, SL Ho, VT Koreth, J Alyea, E Soiffer, RJ Antin, JH AF Cutler, Corey Li, Shuli Ho, Vincent T. Koreth, John Alyea, Edwin Soiffer, Robert J. Antin, Joseph H. TI Extended follow-up of methotrexate-free immunosuppression using sirolimus and tacrolimus in related and unrelated donor peripheral blood stem cell transplantation SO BLOOD LA English DT Article; Proceedings Paper CT Joint Meeting of the American-Society-for-Blood-and-Marrow-Transplantation/Center-for-Interna tional-Blood-and-Marrow-Transplant-Research CY FEB 10-14, 2005 CL Keystone, CO SP Amer Soc Blood & Marrow Transplant, Ctr Int Blood & Marrow Transplant Res ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; HUMAN DENDRITIC CELLS; REGULATORY T-CELLS; MYCOPHENOLATE-MOFETIL; RENAL-TRANSPLANTATION; VENOOCCLUSIVE DISEASE; PROPHYLAXIS REGIMENS; RANDOMIZED-TRIAL; CYCLOSPORINE-A AB We assessed the combination of sirolimus and tacrolimus without methotrexate after myeloablative allogeneic stem cell transplantation from 53 matched related donors (MRDs) and 30 unrelated donors (URDs). All patients received cyclophosphamide and total body irradiation conditioning followed by transplantation of mobilized peripheral blood stem cells. The median time to neutrophil engraftment was 14 days. The median time to platelet engraftment was 12 days. No differences between MRD and URD cohorts was noted. The incidence of grade II-IV and III-IV acute graft-versus-host disease (GVHD) were 20.5% and 4.8%. The cumulative incidence of chronic GVHD was 59.1%. There were no differences in acute or chronic GVHD incidence between MRD and URD cohorts. The omission of methotrexate was associated with low transplant-related toxicity, with 30-day and 100-day treatment-related mortality rates of 0% and 4.8%. Relapse-free survival at 1 and 2 years was 72.3% and 68.5%, respectively. Overall survival at 1 and 2 years was 77.1 % and 72.2%, respectively. There were no differences in relapse-free or overall survival between MRD and URD cohorts. The substitution of sirolimus for methotrexate as GVHD prophylaxis is associated with rapid engraftment, a low incidence of acute GVHD, minimal transplant-related toxicity, and excellent survival. Differences between MRD and URD cohorts are not evident when effective GVHD prophylaxis is used. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cutler, C (reprint author), Dana Farber Canc Inst, 44 Binney St,D1B22, Boston, MA 02115 USA. EM corey_cutler@dfci.harvard.edu FU NHLBI NIH HHS [P01 HL070149] NR 56 TC 125 Z9 130 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 2007 VL 109 IS 7 BP 3108 EP 3114 DI 10.1182/blood-2006-09-046219 PG 7 WC Hematology SC Hematology GA 156HP UT WOS:000245639000069 PM 17138818 ER PT J AU Marlar, RA Potts, RM Welsh, CH AF Marlar, Richard A. Potts, Robyn M. Welsh, Carolyn H. TI A systems biology approach to the diagnosis of venous thrombosis risk SO BLOOD COAGULATION & FIBRINOLYSIS LA English DT Editorial Material DE complex disease; hemostasis; systems biology; thrombophilia C1 Oklahoma City Vet Adm Med Ctr, Lab Serv 113, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA. Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Denver, CO 80202 USA. RP Marlar, RA (reprint author), Oklahoma City Vet Adm Med Ctr, Lab Serv 113, 921 13th St, Oklahoma City, OK 73104 USA. EM Richard-Marlar@ouhsc.edu NR 5 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0957-5235 J9 BLOOD COAGUL FIBRIN JI Blood Coagul. Fibrinolysis PD APR PY 2007 VL 18 IS 3 BP 215 EP 217 DI 10.1097/MBC.0b013e3280116c84 PG 3 WC Hematology SC Hematology GA 158YN UT WOS:000245831700001 PM 17413756 ER PT J AU Burnett-Bowie, SAM Mendoza, N Leder, BZ AF Burnett-Bowie, Sherri-Ann M. Mendoza, Natalia Leder, Benjamin Z. TI Effects of gonadal steroid withdrawal on serum phosphate and FGF-23 levels in men SO BONE LA English DT Article DE fibroblast growth factor 23; phosphate; hypogonadism; homeostasis 1,25 dihydroxyvitamin D ID FIBROBLAST GROWTH FACTOR-23; BONE-MINERAL DENSITY; DOMINANT HYPOPHOSPHATEMIC RICKETS; VITAMIN-D METABOLISM; PRIMARY HYPERPARATHYROIDISM; ONCOGENIC OSTEOMALACIA; PARATHYROID-HORMONE; DIETARY PHOSPHATE; IN-VIVO; FIBROBLAST-GROWTH-FACTOR-23 AB Introduction: Fibroblast growth factor (FGF-23) is a novel phosphaturic factor. Current data suggest that serum phosphate, dietary phosphate and 1,25 dihydroxyvitamin D regulate circulating FGF-23 levels in vivo. We examined if hypogonadism-induced increases in serum phosphate are associated with increases in circulating FGF-23 in healthy men in the absence of dietary manipulation. Materials and methods: 25 healthy men were administered goserelin acetate (GnRH analog) 3.6 ing subcutaneously every 4 weeks for 12 weeks to induce acute testosterone and estrogen deficiency. Subjects consumed an ad libitum diet. Morning fasting blood and urine samples were collected to measure serum phosphate, serum intact FGF-23, PTH, and the maximum tubular reabsorption of phosphate (TP/GFR) at baseline, weeks 4 and 12. The changes in serum FGF-23 and phosphate at weeks 4 and 12 were compared to baseline using paired t-tests. Results: Goserelin therapy decreased mean serum testosterone levels from 543 +/- 160 ng/dL to 33 +/- 15 mg/dL at week 4 (P < 0.001), and to 20 +/- 10 ng/dL at week 12 (p < 0.001). SerUnl Phosphate increased significantly from 3.4 +/- 0.6 mg/dL to 3.9 +/- 0.4 mg/dL at week 4 (p=0.002), and to 4.3 +/- 0.4 mg/dL at week 12(p < 0.001). T-m/GFR increased significantly from 3.2 +/- 0.6 mg/dL to 3.6 +/- 0.5 mg/dL at week 4 (P < 0.004), and to 4.1 +/- 0.6 mg/dL at week 12 (p < 0.001). FGF-23 levels, however, did not change during the 12-week study. Conclusions: Gonadal steroid deprivation increased serum phosphate levels in men but did not affect serum FGF-23 concentrations. The absence of any change in circulating FGF-23 suggests that SUpraphysiologic levels of serum phosphate may be required to stimulate circulating FGF-23 or that FGF-23 production is primarily sensitive to changes in dietary phosphate or 1,25 chhydroxyvitainin D within this physiologic serum phosphate range. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Burnett-Bowie, SAM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 1051,50 Blossom St, Boston, MA 02114 USA. EM sburnett-bowie@partners.org; nmendoza1@partners.org; bzleder@partners.org OI Burnett-Bowie, Sherri-Ann/0000-0002-0064-096X FU NCRR NIH HHS [M01-RR-01066, M01 RR001066, K23-RR-16310, K23 RR016310] NR 51 TC 22 Z9 22 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD APR PY 2007 VL 40 IS 4 BP 913 EP 918 DI 10.1016/j.bone.2006.10.016 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 153GI UT WOS:000245419800014 PM 17157573 ER PT J AU Leverenz, JB Umar, I Wang, Q Montine, TJ McMillan, PJ Tsuang, DW Jin, JH Pan, C Shin, J Zhu, D Zhang, J AF Leverenz, James B. Umar, Imran Wang, Qing Montine, Thomas J. McMillan, Pamela J. Tsuang, Debby W. Jin, Jinghua Pan, Catherine Shin, Jenny Zhu, David Zhang, Jing TI Proteomic identification of novel proteins in cortical Lewy bodies SO BRAIN PATHOLOGY LA English DT Article ID SPORADIC PARKINSONS-DISEASE; ALPHA-SYNUCLEIN; NEURODEGENERATIVE DISEASES; NEUROFILAMENT SUBUNIT; ALZHEIMERS-DISEASE; MASS-SPECTROMETRY; FIBRIL FORMATION; BODY DISEASE; DEMENTIA; PROMOTES AB Lewy body (LB) inclusions are one of the pathological hallmarks of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). One way to better understand the process leading to LB formation and associated pathogenesis responsible for neurodegeneration in PD and DLB is to examine the content of LB inclusions. Here, we performed a proteomic investigation of cortical LBs, obtained by laser capture microdissection from neurons in the temporal cortex of dementia patients with cortical LB disease. Analysis of over 2500 cortical LBs discovered 296 proteins; of those, 17 had been associated previously with brainstem and/or cortical LBs. We validated several proteins with immunohistochemical staining followed by confocal microscopy. The results demonstrated that heat shock cognate 71 kDa protein (also known as HSC70, HSP73, or HSPA10) was indeed not only colocalized with the majority of LBs in the temporal cortex but also colocalized to LBs in the frontal cortex of patients with diffuse LB disease. Our investigation represents the first extensive proteomic investigation of cortical LBs, and it is expected that characterization of the proteins in the cortical LBs may reveal novel mechanisms by which LB forms and pathways leading to neurodegeneration in DLB and/or advanced PD. Further investigation of these novel candidates is also necessary to ensure that the potential proteins in cortical LBs are not identified incorrectly because of incomplete current human protein database. C1 Univ Washington, Harborview Med Ctr, Sch Med, Div Neuropathol,Dept Pathol, Seattle, WA 98104 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98104 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA. VA Puget Sound Hlth Care Syst, Dept Mental Illness, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Dept Parkinsons Dis, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. RP Zhang, J (reprint author), Univ Washington, Harborview Med Ctr, Sch Med, Div Neuropathol,Dept Pathol, Box 359635, Seattle, WA 98104 USA. EM zhangj@u.washington.edu RI Jin, Jinghua/G-6385-2010; Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 FU NIA NIH HHS [AG05136, AG025327]; NIEHS NIH HHS [ES012703]; NINDS NIH HHS [NS048595] NR 57 TC 97 Z9 102 U1 0 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD APR PY 2007 VL 17 IS 2 BP 139 EP 145 DI 10.1111/j.1750-3639.2007.00048.x PG 7 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 149AL UT WOS:000245118600002 PM 17388944 ER PT J AU Vachon, CM Ingle, JN Suman, VJ Scott, CG Gottardt, H Olson, JE Goss, PE AF Vachon, C. M. Ingle, J. N. Suman, V. J. Scott, C. G. Gottardt, H. Olson, J. E. Goss, P. E. TI Pilot study of the impact of letrozole vs. placebo on breast density in women completing 5 years of tamoxifen SO BREAST LA English DT Article DE aromatase inhibitors; breast density; mammographic density ID HORMONAL REPLACEMENT THERAPY; MAMMOGRAPHIC DENSITY; POSTMENOPAUSAL WOMEN; CANCER RISK; AROMATASE INHIBITORS; RANDOMIZED-TRIAL; POLYMORPHISMS; ASSOCIATION; ESTROGEN; ADJUVANT AB Breast density, a strong risk factor for breast cancer, is reduced by the anti-estrogen, tamoxifen (TAM). We examined whether aromatase inhibitor (Al) therapy results in further reductions in breast density among women completing 5 years of TAM. Among a sample of women with early-onset breast cancer who were randomized to letrozole (LET)(n = 56) or placebo (PLAC)(n = 48) after 5 years of TAM, we examine the change in percent density at 9-15 months as well as a per-year change in PD by treatment group. There was no difference in the adjusted mean change (-1.0%, LET; -0.3%, PLAC (P = 0.58)) or the percentage change (-2.7%, LET; -3.0%, PLAC (P = 0.96)) in PD between treatment groups at 9-15 months. Results were similar for longitudinal change (-0.68% per year, LET, -0.12% per year, PLAC (P = 0.23)). Breast density does not appear to be a clinically relevant biomarker in women who already have tow PD following 5 years of TAM. Crown Copyright (C) 2006 Published by Elsevier Ltd. All rights reserved. C1 [Vachon, C. M.; Suman, V. J.; Scott, C. G.; Olson, J. E.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Ingle, J. N.] Coll Med, Mayo Clin, Dept Med Oncol, Rochester, MN USA. [Gottardt, H.] Toronto Sunnybrook Canc Ctr, Clin Trials & Epidemiol, Toronto, ON, Canada. [Goss, P. E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Vachon, CM (reprint author), Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN 55905 USA. EM vachon.celine@mayo.edu OI Scott, Christopher/0000-0003-1340-0647 FU NCI NIH HHS [P50 CA116201] NR 39 TC 22 Z9 22 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD APR PY 2007 VL 16 IS 2 BP 204 EP 210 DI 10.1016/j.breast.2006.10.007 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 320ZM UT WOS:000257273800015 PM 17145182 ER PT J AU Sim, K Lee, NB Chua, HC Mahendran, R Fujii, S Yang, SY Chong, MY Si, TM He, YL Lee, MS Sung, KM Chung, EK Chan, YH Shinfuku, N Tan, CH Sartorius, N Baldessarini, RJ AF Sim, Kang Lee, N. B. Chua, Hong C. Mahendran, Rathi Fujii, Senta Yang, Shu-yu Chong, Mian-Yoon Si, Tianmei He, Yan L. Lee, Min S. Sung, Kil M. Chung, Eun K. Chan, Yiong H. Shinfuku, Naotaka Tan, Chay H. Sartorius, Norman Baldessarini, Ross J. TI Newer antidepressant drug use in East Asian psychiatric treatment settings: REAP (Research on East Asia Psychotropic Prescriptions) Study SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE antidepressant; diagnosis; East Asia; treatment ID SEROTONIN REUPTAKE INHIBITORS; TRICYCLIC ANTIDEPRESSANTS; GENERAL-PRACTICE; PRIMARY-CARE; DEPRESSION; DATABASE; TOLERABILITY; METAANALYSIS; EFFICACY; TRENDS AB Aims Antidepressant use in East Asia is poorly documented. We compared patients given newer and older antidepressants to test the hypothesis, suggested in the literature, that use of newer antidepressants is associated with treatment settings rather than specific diagnostic categories. Methods We compared rates of use of older (pre1990) vs. newer antidepressants among 1898 patients identified as antidepressant treated at 21 centres in five East Asian countries (China, Japan, Korea, Singapore, Taiwan) in 2003. Demographics, treatment setting and clinical factors associated with preferential use of newer drugs were tested in univariate and multivariate analyses. Results Newer antidepressants were included in the treatment regimens of 67.5% (N = 1282/1898) of study subjects. Prescription for newer antidepressants was significantly associated with younger age (z = -4.55, d.f. = 1888, P < 0.001), hospitalization [odds ratio (OR) 1.32, 95% confidence interval (CI) 1.07, 1.64, P < 0.01] and treatment within psychiatric hospitals (OR 1.59, 95% CI 1.27, 2.00, P < 0.001). On multivariate analyses, treatment with newer antidepressants was independently associated with younger age (P < 0.001), country (P < 0.001) and treatment within private hospitals (P < 0.001), but not with sex or diagnosis of affective or anxiety disorders (all P > 0.1). Conclusion Demographic factors and treatment settings appear to influence antidepressant choice more than clinical factors such as diagnosis. C1 Woodbridge Hosp, Inst Mental Hlth, Singapore 539747, Singapore. Kobe Univ, Kobe, Hyogo 657, Japan. Kaohsiung Med Univ, Kaohsiung, Taiwan. Beijing Med Univ, Beijing 100083, Peoples R China. Shanghai Mental Hlth Ctr, Shanghai, Peoples R China. Yonsei Univ, Coll Med, Seoul 120749, South Korea. Seoul Natl Hosp, Seoul, South Korea. Natl Univ Singapore, Singapore 117548, Singapore. Univ Geneva, Geneva, Switzerland. Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. Massachusetts Gen Hosp, McLean Div, Psychopharmacol Program, Belmont, MA USA. RP Sim, K (reprint author), Woodbridge Hosp, Inst Mental Hlth, 10 Buangkok View, Singapore 539747, Singapore. EM kang_sim@imh.com.sg NR 28 TC 16 Z9 16 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0306-5251 J9 BRIT J CLIN PHARMACO JI Br. J. Clin. Pharmacol. PD APR PY 2007 VL 63 IS 4 BP 431 EP 437 DI 10.1111/j.1365-2125.2006.02780.x PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 145VV UT WOS:000244894800007 PM 17076698 ER PT J AU Hisatomi, T Sonoda, KH Ishikawa, F Qiao, H Nakamura, T Fukata, M Nakazawa, T Noda, K Miyahara, S Harada, M Kinoshita, S Hafezi-Moghadam, A Ishibashi, T Miller, JW AF Hisatomi, Toshio Sonoda, Koh-hei Ishikawa, Fumihiko Qiao, Hong Nakamura, Takahiro Fukata, Mitsuhiro Nakazawa, Toru Noda, Kousuke Miyahara, Shinsuke Harada, Mine Kinoshita, Shigeru Hafezi-Moghadam, Ali Ishibashi, Tatsuro Miller, Joan W. TI Identification of resident and inflammatory bone marrow derived cells in the sclera by bone marrow and haematopoietic stem cell transplantation SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID DENDRITIC CELLS; CORNEAL STROMA; PHOTORECEPTOR APOPTOSIS; RETINAL-DETACHMENT; GREEN MICE; UVEITIS; MOUSE; POPULATION; PHENOTYPE; MIGRATION AB Aims: To characterise bone marrow derived cells in the sclera under normal and inflammatory conditions, we examined their differentiation after transplantation from two different sources, bone marrow and haematopoietic stem cells (HSC). Methods: Bone marrow and HSC from green fluorescent protein (GFP) transgenic mice were transplanted into irradiated wild-type mice. At 1 month after transplantation, mice were sacrificed and their sclera examined by histology, immunohistochemistry (CD11b, CD11c, CD45), and transmission and scanning electron microscopy. To investigate bone marrow derived cell recruitment under inflammatory conditions, experimental autoimmune uveitis (EAU) was induced in transplanted mice. Results: GFP positive cells were distributed in the entire sclera and comprised 22.4 (2.8)% (bone marrow) and 28.4 (10.9)% (HSC) of the total cells in the limbal zone and 18.1 (6.7)% (bone marrow) and 26.3 (3.4)% (HSC) in the peripapillary zone. Immunohistochemistry showed that GFP (+) CD11c (+), GFP (+) CD11b (+) cells migrated in the sclera after bone marrow and HSC transplantation. Transmission and scanning electron microscopy revealed antigen presenting cells among the scleral fibroblasts. In EAU mice, vast infiltration of GFP (+) cells developed into the sclera. Conclusion: We have provided direct and novel evidence for the migration of bone marrow and HSC cells into the sclera differentiating into macrophages and dendritic cells. Vast infiltration of bone marrow and HSC cells was found to be part of the inflammatory process in EAU. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Angiogenesis Lab, Boston, MA 02114 USA. Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka 812, Japan. RIKEN, Ctr Allergy & Immunol, Res Unit Human Dis Model, Yokohama, Kanagawa, Japan. Kyushu Univ, Grad Sch Med Sci, Dept Med & Biosystem Sci, Fukuoka 812, Japan. Kyoto Prefectural Univ Med, Kyoto 602, Japan. RP Miller, JW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Angiogenesis Lab, 243 Charles St, Boston, MA 02114 USA. EM Joan_Miller@meei.harvard.edu RI 石川, 文彦/L-4488-2014; OI Hisatomi, Toshio/0000-0003-2552-9595; Hafezi-Moghadam, Ali/0000-0002-5336-0697 NR 41 TC 8 Z9 8 U1 1 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD APR PY 2007 VL 91 IS 4 BP 520 EP 526 DI 10.1136/bjo.2006.102046 PG 7 WC Ophthalmology SC Ophthalmology GA 147XH UT WOS:000245037700029 PM 17035278 ER PT J AU Posternak, MA Zimmerman, M AF Posternak, Michael A. Zimmerman, Mark TI Therapeutic effect of follow-up assessments on antidepressant and placebo response rates in antidepressant efficacy trials - Meta-analysis SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Review ID MAJOR DEPRESSIVE DISORDER; EXTENDED-RELEASE XR; BLIND COMPARATIVE TRIAL; DOSE-RESPONSE; OUTPATIENTS; IMIPRAMINE; AMITRIPTYLINE; PAROXETINE; VENLAFAXINE; FLUOXETINE AB Background It remains unclear how much various factors contribute to the placebo response. Aims To estimate the therapeutic impact of follow-up assessments on placebo response in antidepressant trials Method Double-blind, placebo-controlled antidepressant trials that reported weekly changes in Hamilton Rating Scale for Depression (HRSD) scores over 6 weeks were selected. Included studies (n=41) were divided into those that conducted four, five or six follow-up assessments. Reductions in HRSD scores as a function of the different follow-up schedules were compared. Results An extra follow-up visit at week 3 was associated with a 0.86 further reduction in HRSD score; an extra visit at week 5 was associated with a 0.67 further reduction. These effects represented approximately 34-44% of the placebo response that occurred over these time frames. Two additional visits were associated with twice the reduction in HRSD score than one, suggesting that the therapeutic impact of assessment visits Is cumulative and proportional. A comparable therapeutic effect was also found in participants receiving active medication. Conclusions Follow-up assessments in antidepressant treatment trials incur a significant therapeutic effect for participants on placebo, and this represents about 40% of the placebo response. C1 Brown Univ, Sch Med, Rhode Isl Hosp, Dept Psychiat & Human Behav, Providence, RI 02905 USA. RP Posternak, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Depress Clin & Res Program, 50 Staniford St,Suite 401, Boston, MA 02114 USA. EM mposternak@partners.org NR 68 TC 69 Z9 72 U1 1 U2 4 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD APR PY 2007 VL 190 BP 287 EP 292 DI 10.1192/bjp.bp.106.028555 PG 6 WC Psychiatry SC Psychiatry GA 156AI UT WOS:000245619800003 PM 17401033 ER PT J AU Peppercorn, J Blood, E Winer, E Partridge, A AF Peppercorn, Jeffrey Blood, Emily Winer, Eric Partridge, Ann TI Association between pharmaceutical involvement and outcomes in breast cancer clinical trials SO CANCER LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol DE breast cancer; sponsorship; clinical trials; pharmaceutical industry ID CONFLICTS-OF-INTEREST; INDUSTRY SPONSORSHIP; ECONOMIC-ANALYSES; ONCOLOGY; AUTHORS; IMPACT; DRUG AB BACKGROUND. Since 1992, pharmaceutical industry support has surpassed National Institutes of Health funding for clinical research in the United States. In this study, the authors sought to evaluate the impact of this shift in funding from public to private sponsors on the nature of published breast cancer clinical research. METHODS. All published breast cancer clinical trials from 2003, 1998, and 1993 were reviewed from 10 select English-language medical journals to evaluate pharmaceutical involvement over time and the association between sponsorship, trial design, and results. Clinical studies that reported disease-specific outcomes from medical therapy for breast cancer were eligible for analysis. Pharmaceutical involvement was defined as reported pharmaceutical industry funding, provision of drug, and/or authorship for each publication. RESULTS. In total, 140 eligible studies were identified, including 45 studies that were published in 1993, 39 studies that were published in 1998, and 56 studies that were published in 2003. Among those, 67 publications (48%) reported pharmaceutical industry involvement, 36 publications (26%) had at least > 1 pharmaceutical industry author, And 100 publications (71%) were considered positive. Pharmaceutical involvement was identified in 44% of the studies published in 1993, in 38% of the studies published in 1998, and in 58% of the studies published in 2003. Pharmaceutical authorship was reported in 22% of the 1993 studies, in 21% of the 1998 studies, and in 34% of the 2003 studies. For studies that were published in 2003, those that reported pharmaceutical involvement were more likely to be positive (84% vs 54%; P = .02; Fisher exact test), to be single-arm studies (66% vs 33%; P = .03), and to evaluate metastatic disease (72% vs 46%; P = .06). CONCLUSIONS. Pharmaceutical involvement in published clinical breast cancer research may affect study design, focus, and results. Further research is warranted, including analysis of unpublished studies, to evaluate the impact of increasing pharmaceutical industry involvement on clinical research. C1 Univ N Carolina, Div Hematol Oncol, Sch Med, Chapel Hill, NC 27599 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Peppercorn, J (reprint author), Univ N Carolina, Div Hematol Oncol, Sch Med, CB 7305, Chapel Hill, NC 27599 USA. EM jpepper@med.unc.edu NR 25 TC 69 Z9 70 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD APR 1 PY 2007 VL 109 IS 7 BP 1239 EP 1246 DI 10.1002/cncr.22528 PG 8 WC Oncology SC Oncology GA 150PP UT WOS:000245229000003 PM 17326054 ER PT J AU D'Amico, AV McLeod, DG Carroll, PR Cullen, J Chen, MH AF D'Amico, Anthony V. McLeod, David G. Carroll, Peter R. Cullen, Jennifer Chen, Ming-Hui TI Time to an undetectable prostate-specific antigen (PSA) after androgen suppression therapy for postoperative or postradiation PSA recurrence and prostate cancer-specific mortality SO CANCER LA English DT Article DE prostate cancer; prostate-specific antigen; mortality; hormonal therapy ID DATABASE AB BACKGROUND. For men receiving androgen-suppression therapy (AST) for a rising postoperative or postradiation prostate-specific antigen (PSA) recurrence, whether the time to an undetectable (u) PSA was significantly associated with prostate cancer-specific mortality (PCSM) was evaluated. METHODS. The study cohort comprised 585 men with a rising PSA and negative bone scan after surgery (n = 415) or radiation therapy (n = 170) that were treated with AST and achieved a uPSA. Gray's regression was used to evaluate whether the time to a uPSA after AST was significantly associated with the time to PCSM after the uPSA adjusting for known prognostic factors. RESULTS. The median time (interquartile range) to achieve a uPSA was 4.6 (range, 2.8-7.8) months. There were 23 deaths, 4 of which were from prostate cancer. An increasing time to a uPSA (adjusted hazard ratio [HR]: 9.2, 95% confidence interval [CI]: 3.8, 22.1; P < .0001), a decreasing PSA doubling time (DT) (HR: 0.58, 95% CI: 0.43, 0.80; P = .0007), and Gleason score 8 to 10 cancers (HR: 8.6, 95% CI: 1.04, 77; P = .05) were significantly associated with a shorter time to PCSM. CONCLUSIONS. Despite achieving a uPSA after AST, the risk of PCSM increased significantly as the time to the uPSA lengthens, especially in men with a short pre-AST PSA DT and high-grade prostate cancer. These men should be considered for randomized studies evaluating immediate vs delayed chemotherapy after the achievement of the uPSA. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Walter Reed Army Med Ctr, Dept Urol, Ctr Prostate Dis Res, Bethesda, MD USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. Walter Reed Army Med Ctr, Ctr Prostate Dis Res, Dept Stat, Bethesda, MD USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02215 USA. EM adamico@lroc.harvard.edu NR 21 TC 11 Z9 13 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD APR 1 PY 2007 VL 109 IS 7 BP 1290 EP 1295 DI 10.1002/cncr.22550 PG 6 WC Oncology SC Oncology GA 150PP UT WOS:000245229000009 PM 17315162 ER PT J AU Wang, YZ Armstrong, SA AF Wang, Yingzi Armstrong, Scott A. TI Genome-wide SNP analysis in cancer: Leukemia shows the way SO CANCER CELL LA English DT Editorial Material ID TYROSINE KINASE; MUTATIONS; FLT3; REARRANGEMENTS; MLL AB The application of novel genetic/genomic technologies to the study of acute leukemia has frequently been a proving ground for such approaches in cancer. Recent development of high-resolution single-nucleotide polymorphism (SNP) arrays allows detailed assessment of the genomes in cancer cells. A recent study by Mullighan et al. uses SNP arrays to assess copy number alterations in a large group of childhood acute lymphoblastic leukemias and demonstrates frequent mutation of genes encoding transcription factors important for B cell development. These studies not only provide information about the multistep development of leukemia, but also demonstrate the potential for this approach in other cancers. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Armstrong, SA (reprint author), Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. EM scott.armstrong@childrens.harvard.edu NR 10 TC 18 Z9 18 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD APR PY 2007 VL 11 IS 4 BP 308 EP 309 DI 10.1016/j.ccr.2007.03.017 PG 2 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 157PH UT WOS:000245732000003 PM 17418407 ER PT J AU Carrasco, DR Sukhdeo, K Protopopova, M Sinha, R Enos, M Carrasco, DE Zheng, M Mani, M Henderson, J Pinkus, GS Munshi, N Horner, J Ivanova, EV Protopopov, A Anderson, KC Tonon, G DePinho, RA AF Carrasco, Daniel R. Sukhdeo, Kumar Protopopova, Marina Sinha, Raktim Enos, Miriam Carrasco, Daniel E. Zheng, Mei Mani, Mala Henderson, Joel Pinkus, Geraldine S. Munshi, Nikhil Horner, James Ivanova, Elena V. Protopopov, Alexei Anderson, Kenneth C. Tonon, Giovanni DePinho, Ronald A. TI The differentiation and stress response factor XBP-1 drives multiple myeloma pathogenesis SO CANCER CELL LA English DT Article ID UNFOLDED PROTEIN RESPONSE; PLASMA-CELL DIFFERENTIATION; RESOLUTION GENOMIC PROFILES; TRANSCRIPTION FACTOR XBP-1; C-MYC; GENE-EXPRESSION; MESSENGER-RNA; C/EBP-BETA; B-CELLS; GROWTH AB Multiple myeloma. (MM) evolves from a highly prevalent premalignant condition termed MGUS. The factors underlying the malignant transformation of MGUS are unknown. We report a MGUS/MM phenotype in transgenic mice with E mu-directed expression of the XBP-1 spliced isoform (XBP-1 s), a factor governing unfolded protein/ER stress response and plasma-cell development. E mu-XPB-1s elicited elevated serum Ig and skin alterations. With age, E mu-xbp-ls transgenics develop features diagnostic of human MM, including bone lytic lesions and subendothelial Ig deposition. Furthermore, transcriptional profiles of E mu-xbp-1s lymphoid and MM cells show aberrant expression of known human MM dysregulated genes. The similarities of this model with the human disease, coupled with documented frequent XBP-1 s overexpression in human MM, serve to implicate XBP-1 s dysregulation in MM pathogenesis. C1 Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Appl Canc Sci, Belfer Fdn Inst Innovat Canc Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Carrasco, DR (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. EM ruben_carrasco@dfci.harvard.edu; ron_depinho@dfci.harvard.edu OI Sukhdeo, Kumar /0000-0001-8725-6081 FU NCI NIH HHS [R01 CA050947, P01 CA078378, U01 CA084313] NR 39 TC 202 Z9 214 U1 4 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD APR PY 2007 VL 11 IS 4 BP 349 EP 360 DI 10.1016/j.ccr.2007.02.015 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 157PH UT WOS:000245732000007 PM 17418411 ER PT J AU Beer, TM Javle, MM Ryan, CW Garzotto, M Lam, GN Wong, A Henner, WD Johnson, CS Trump, DL AF Beer, Tomasz M. Javle, Milind M. Ryan, Christopher W. Garzotto, Mark Lam, Gilbert N. Wong, Alvin Henner, W. David Johnson, Candace S. Trump, Donald L. TI Phase I study of weekly DN-101, a new formulation of calcitriol, in patients with cancer SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE calcitriol; vitamin D; pulse dosing; phase I ID INDEPENDENT PROSTATE-CANCER; HIGH-DOSE CALCITRIOL; BREAST-TUMOR CELLS; VITAMIN-D ANALOG; ANTITUMOR-ACTIVITY; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; ORAL CALCITRIOL; CARCINOMA; TRIAL; DEXAMETHASONE AB DN-101 is a new, high-dose, oral formulation of calcitriol under investigation for the treatment of cancer. We sought to evaluate the tolerability and pharmacokinetics (PK) of weekly doses of DN-101 in patients with advanced cancer. Patients who completed a previously reported single dose escalation study of DN-101 [Beer et al. (2005) Clin Cancer Res 11:7794-7799] were eligible for this continuation weekly dosing study. Cohorts of 3-10 patients were treated at doses of 15, 30, 45, 60, and 75 mu g calcitriol. Once 45 mu g was established as the maximum tolerated dose (MTD), this cohort was expanded to include 18 patients. Dose limiting toxicity (DLT) was defined as >= grade 2 hypercalcemia or >= grade 3 persistent treatment-related toxicities. Thirty-seven patients were recruited. DLT of transient reversible grade 2 hypercalcemia (serum calcium of 11.6-12.5 mg/dL) occurred in two of six patients treated with 60 mu g of DN-101. No DLT was observed in the 18 patients who received DN-101 weekly at 45 mu g. Overall, DN-101 was well tolerated. The most frequent adverse events were fatigue (27%), hypercalcemia (19%, including five grade 1, two grade 2, and no grade 3 or 4 events), and grade 1 nausea (16%). PK parameters following repeat dosing were comparable to those for the initial dose (n = 4). The MTD for weekly DN-101 was established as 45 mu g. The DLTs observed were two episodes of rapidly reversible grade 2 hypercalcemia in two of the six patients treated at 60 mu g weekly. Repeat doses of DN-101 at 45 mu g weekly are well tolerated and this dose is suitable for studies of weekly DN-101 in cancer patients. C1 Oregon Hlth Sci Univ, Dept Med, Div Hematol & Med Oncol, Portland, OR 97239 USA. Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. Oregon Hlth Sci Univ, Div Urol, Portland, OR 97201 USA. Portland VA Med Ctr, Urol Sect, Portland, OR USA. MicroConstants Inc, San Diego, CA USA. Novacea Inc, San Francisco, CA USA. Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, Buffalo, NY 14263 USA. RP Beer, TM (reprint author), Oregon Hlth Sci Univ, Dept Med, Div Hematol & Med Oncol, Mail Code CR-145,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM beert@ohsu.edu NR 34 TC 26 Z9 27 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD APR PY 2007 VL 59 IS 5 BP 581 EP 587 DI 10.1007/s00280-006-0299-1 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 137LE UT WOS:000244293300003 PM 17066293 ER PT J AU Schumacher, FR Feigelson, HS Cox, DG Haiman, CA Albanes, D Buring, J Calle, EE Chanock, SJ Colditz, GA Diver, WR Dunning, AM Freedman, ML Gaziano, JM Giovannucci, E Hankinson, SE Hayes, RB Henderson, BE Hoover, RN Kaaks, R Key, T Kolonel, LN Kraft, P Le Marchand, L Ma, J Pike, MC Riboli, E Stampfer, MJ Stram, DO Thomas, G Thun, MJ Travis, R Virtamo, J Andriole, G Gelmann, E Willett, WC Hunter, DJ AF Schumacher, Fredrick R. Feigelson, Heather Spencer Cox, David G. Haiman, Christopher A. Albanes, Demetrius Buring, Julie Calle, Eugenia E. Chanock, Stephen J. Colditz, Graham A. Diver, W. Ryan Dunning, Alison M. Freedman, Matthew L. Gaziano, John M. Giovannucci, Edward Hankinson, Sue E. Hayes, Richard B. Henderson, Brian E. Hoover, Robert N. Kaaks, Rudolf Key, Timothy Kolonel, Laurence N. Kraft, Peter Le Marchand, Loic Ma, Jing Pike, Malcolm C. Riboli, Elio Stampfer, Meir J. Stram, Daniel O. Thomas, Gilles Thun, Michael J. Travis, Ruth Virtamo, Jarmo Andriole, Gerald Gelmann, Edward Willett, Walter C. Hunter, David J. TI A common 8q24 variant in prostate and breast cancer from a large nested case-control study SO CANCER RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; BASE-LINE CHARACTERISTICS; GROWTH-FACTOR-I; LIFE-STYLE; GENES; POPULATIONS; PREDICTORS; CARCINOMA; COHORT; HEALTH AB Two recent studies independently identified polymorphisms in the 8q24 region, including a single nucleotide polymorphism (rsl447295), strongly associated with prostate cancer risk. Here, we replicate the overall association in a large nested case-control study from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium using 6,637 prostate cancer cases and 7,361 matched controls. We also examine whether this polymorphism is associated with breast cancer among 2,604 Caucasian breast cancer cases and 3,118 matched controls. The rs1447295 marker was strongly associated with prostate cancer among Caucasians (P = 1.23 x 10(-13)). When we exclude the Multiethnic Cohort samples, previously reported by Freedman et al., the association remains highly significant (P = 8.64 X 10(-13)). Compared with wild-type homozygotes, carriers with one copy of the minor allele had an ORAC = 1.34 (99% confidence intervals, 1.19-1.50) and carriers with two copies of the minor allele had an ORAA = 1.86 (99% confidence intervals, 1.30-2.67). Among African Americans, the genotype association was statistically significant in men diagnosed with prostate cancer at an early age (P = 0.011) and nonsignificant for those diagnosed at a later age (P = 0.924). This difference in risk by age at diagnosis was not present among Caucasians. We found no statistically significant difference in risk when tumors were classified by Gleason score, stage, or mortality. We found no association between rs1447295 and breast cancer risk (P = 0.590). Although the gene responsible has yet to be identified, the validation of this marker in this large sample of prostate cancer cases leaves little room for the possibility of a false-positive result. C1 Harvard Univ, Channing Lab, Brigham & Womens Hosp, Dept Med,Med Sch, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. Harvard Univ, Div Prevent Med, Brigham & Womens Hosp, Dept Med,Med Sch, Boston, MA 02115 USA. Harvard Univ, Div Aging, Brigham & Womens Hosp, Dept Med,Med Sch, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Amer Canc Soc, Dept Epidemiol & Surveillance Res, Natl Home Off, Atlanta, GA 30329 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. NCI, Core Genotyping Facil, Gaithersburg, MD USA. Univ Cambridge, Dept Oncol, Cambridge, England. Int Agcy Res Canc, Hormones & Canc Grp, F-69372 Lyon, France. Int Agcy Res Canc, Unit Nutr & Canc, F-69372 Lyon, France. Univ Oxford, Epidemiol Unit, Canc Res United Kingdom, Oxford, England. Univ Hawaii, Ctr Canc Res, Honolulu, HI 96822 USA. Fdn Jean Dausset, Ctr Etude Polymorphisme Humain, Paris, France. Natl Publ Hlth Inst, Canc Prevent Unit, Helsinki, Finland. Washington Univ, Sch Med, Div Urol, St Louis, MO USA. Columbia Univ, Coll Phys & Surg, Milstein Hosp, Div Hematol & Oncol, New York, NY USA. RP Hunter, DJ (reprint author), Harvard Univ, Channing Lab, Brigham & Womens Hosp, Dept Med,Med Sch, 181 Longwood Ave, Boston, MA 02115 USA. EM dhunter@hsph.harvard.edu RI Cox, David/A-2023-2009; Albanes, Demetrius/B-9749-2015; Colditz, Graham/A-3963-2009; OI Cox, David/0000-0002-2152-9259; Colditz, Graham/0000-0002-7307-0291; Dunning, Alison Margaret/0000-0001-6651-7166; Hayes, Richard/0000-0002-0918-661X FU NCI NIH HHS [R01 CA097193, T32-CA-09001, UO1-CA98216, UO1-CA98233, UO1-CA98710, UO1-CA98758] NR 20 TC 102 Z9 105 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2007 VL 67 IS 7 BP 2951 EP 2956 DI 10.1158/0008-5472.CAN-06-3591 PG 6 WC Oncology SC Oncology GA 156BM UT WOS:000245622900010 PM 17409400 ER PT J AU Chai, JJ Lu, XD Godfrey, V Fletcher, C Roberts, CWM Van Dyke, T Weissman, BE AF Chai, Jingjing Lu, Xiangdong Godfrey, Virginia Fletcher, Christopher Roberts, Charles W. M. Van Dyke, Terry Weissman, Bernard E. TI Tumor-specific cooperation of retinoblastoma protein family and Snf5 inactivation SO CANCER RESEARCH LA English DT Article ID MALIGNANT RHABDOID TUMOR; INTERMEDIATE FILAMENT PROTEINS; ATYPICAL TERATOID/RHABDOID TUMOR; CENTRAL-NERVOUS-SYSTEM; CHOROID-PLEXUS TUMORS; CELL-LINES; TARGETED DISRUPTION; MUTATIONAL ANALYSIS; HSNF5/INI1 GENE; CANCER AB Malignant rhabdoid tumors (MRT) are rare aggressive cancers that occur in young children. Seventy-five percent of sporadic MRTs harbor inactivating SNF5 mutations, and mice heterozygous for an Snf5-null allele develop MRTs with partial penetrance. The diagnosis of choroid plexus carcinomas (CPC) in addition to MRTs in families with a single mutant SNF5 allele prompted us to assess the role of SNF5 loss in CPC in genetically engineered mice. With high frequency, TgT(121) mice develop CPCs that are initiated by inactivation of retinoblastoma protein (pRb) and related proteins p107 and p130. However, CPC penetrance and latency were not significantly affected by SnF5 heterozygosity, consistent with recent evidence that CPCs in SNF5 families were, in many cases, misdiagnosed MRTs. Surprisingly, although the CPC phenotype was unaffected, TgT(121);Snf5(+/-) mice developed MRTs with increased penetrance and decreased latency compared with TgT(121);Snf5(+/-) littermates. MRTs expressed the T-121 protein with a concomitant increase in mitotic activity. The predominant appearance of TgT(121);Snf5(+/-) MRTs in the spinal cord led to the discovery that these tumors likely arose from a subset of spinal cord neural progenitor cells expressing T-121 rather than from transdifferentiation of CPC. Significantly, the target cell type(s) for the MRT is unknown. Hence, this study not only shows that pRb(f) and SNF5 inactivation cooperate to induce MRTs but also provides new insight into the MRT target population. C1 Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27514 USA. Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27514 USA. Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA. Univ N Carolina, Dept Pediat, Chapel Hill, NC 27514 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Boston, MA 02115 USA. RP Weissman, BE (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, CB 7259,Room 32-048, Chapel Hill, NC 27514 USA. EM weissman@med.unc.edu FU NCI NIH HHS [R01CA113794, R01CA046283, R01CA091048] NR 56 TC 11 Z9 12 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2007 VL 67 IS 7 BP 3002 EP 3009 DI 10.1158/0008-5472.CAN-06-4207 PG 8 WC Oncology SC Oncology GA 156BM UT WOS:000245622900016 PM 17409406 ER PT J AU Kuruppu, D Brownell, AL Zhu, AJ Yu, MX Wang, XK Kulu, Y Fuchs, BC Kawasaki, H Tanabe, KK AF Kuruppu, Darshini Brownell, Anna-Liisa Zhu, Aijun Yu, Meixiang Wang, Xukui Kulu, Yakup Fuchs, Bryan C. Kawasaki, Hiroshi Tanabe, Kenneth K. TI Positron emission tomography of herpes simplex virus 1 oncolysis SO CANCER RESEARCH LA English DT Article ID HERPES-SIMPLEX-VIRUS; DIFFUSE LIVER METASTASES; LONG-TERM SURVIVAL; MALIGNANT GLIOMA; GENE-THERAPY; THYMIDINE-KINASE; REPLICATION; CANCER; MUTANT; EXPRESSION AB Viral oncolysis, the destruction of cancer cells by replicating viruses, is under clinical investigation for cancer therapy. Lytic viral replication in cancer cells both destroys the cells and liberates progeny virion to infect adjacent cancer cells. The safety and efficacy of this approach are dependent on selective and robust viral replication in cancer cells rather than in normal cells. Methods to detect and quantify viral replication in tissues have relied on organ sampling for molecular analyses. Preclinical and clinical studies of viral oncolysis will benefit significantly from development of a noninvasive method to repetitively measure viral replication. We have shown that positron emission tomography (PET) allows for in vivo detection of herpes simplex virus (HSV)-1 replication in tumor cells using 9-(4-[F-18]-fluoro-3-[hydroxymethyl]butyl)guanine ([F-18]FHBG) as the substrate for HSV thymidine kinase (HSV-TK). As expected, phosphorylated [F-18]FHBG is initially trapped within HSV-1-infected tumor cells and is detectable as early as 2 h following virus administration. MicroPET images reveal that [F-18]FHBG accumulation in HSV-1-infected tumors peaks at 6 h. However, despite progressive accumulation of HSV-I titers and HSV-TK protein in the tumor as -viral oncolysis proceeds, tumor cell degradation resulting from viral oncolvsis increases over time, which limits intracellular retention of [F-18]FHBG. These observations have important consequences with regard to strategies to use [F-18]FHBG PET for monitoring sites of HSV-TK expression during viral oncolvsis. C1 Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. EM ktanabe@partners.org FU NCI NIH HHS [2R01CA076183]; NIBIB NIH HHS [5R01EB001850] NR 38 TC 22 Z9 24 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2007 VL 67 IS 7 BP 3295 EP 3300 DI 10.1158/0008-5472.CAN-06-4062 PG 6 WC Oncology SC Oncology GA 156BM UT WOS:000245622900048 PM 17409438 ER PT J AU Jaff, MR AF Jaff, Michael R. TI Carotid stent restenosis - A problem in search of a cure? SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Vasc Ultrasound Core Lab, Boston, MA 02114 USA. RP Jaff, MR (reprint author), Massachusetts Gen Hosp, Vasc Ultrasound Core Lab, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD APR 1 PY 2007 VL 69 IS 5 BP 683 EP 684 DI 10.1002/ccd.21175 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 155KO UT WOS:000245576500010 PM 17390301 ER PT J AU Mitchell, JA Subramanian, R White, CJ Soukas, PA Almagor, Y Stewart, RE Rosenfield, K AF Mitchell, Jason A. Subramanian, Rajesh White, Christopher J. Soukas, Peter A. Almagor, Yaron Stewart, Richard E. Rosenfield, Kenneth TI Predicting blood pressure improvement in hypertensive patients after renal artery stent placement: Renal fractional flow reserve SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE peripheral vascular disease; renovascular hypertension; renal stent ID RENOVASCULAR HYPERTENSION; BALLOON ANGIOPLASTY; STENOSIS; REVASCULARIZATION AB Background: Renal stent placement improves or cures hypertension in only 60-70% of patients with renal artery stenosis (RAS) and uncontrolled hypertension. There is a need to better identify patients who are likely to respond to percutaneous renal revascularization. We investigated whether an abnormal renal fractional flow reserve (FFR) would predict blood pressure improvement in patients undergoing renal artery stent placement. Methods: We prospectively enrolled 17 patients with unilateral RAS and medically refractory hypertension (BP > 140/90 mm Hg). Renal FFR was measured at maximal hyperemia induced by papaverine followed by renal stent placement. Blood pressure improvement was defined as a blood pressure of <= 140/90 mm Hg or an absolute decrease in diastolic blood pressure by 15 mm Hg on the same or less number of medications. Patients not meeting the above criteria were nonresponders. Results: Renal stent placement was successful in all patients. The average follow-up was 10 2 months. In patients with an abnormal renal FFR (<0.80) blood pressure improved at 90 days in 86% compared with 30% in the normal renal FFR group (P = 0.04). Translesional pressure gradients (resting, peak, or hyperemic) alone failed to differentiate blood pressure responders from nonresponders. Conclusions: Renal FFR is a promising tool to identify patients likely to benefit following renal stent placement. This finding was independent of translesional pressure gradients, which did not predict blood pressure improvement. The ability to segregate patients with RAS and coexisting hypertension from those with renovascular hypertension may help clinicians select patients most likely to benefit from revascularization. (C) 2007 Wiley-Liss, Inc. C1 Alton Ochsner Med Fdn & Ochsner Clin, Dept Cardiol, New Orleans, LA 70121 USA. David Grant Med Ctr, Dept Cardiol, Travis AFB, CA USA. Memphis Heart Clin, Dept Cardiol, Southaven, MI USA. St Elizabeths Med Ctr, Div Cardiovasc Med, Boston, MA USA. Shaare Zedek Med Ctr, Dept Cardiol, Jerusalem, Israel. Univ N Texas, Hlth Sci Ctr, Dept Internal Med Cardiol, Ft Worth, TX USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP White, CJ (reprint author), Alton Ochsner Med Fdn & Ochsner Clin, Dept Cardiol, 1516 Jefferson Highway, New Orleans, LA 70121 USA. EM cwhite@ochsner.org RI White, Christopher/J-6686-2012 OI White, Christopher/0000-0001-8618-7539 NR 16 TC 51 Z9 55 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD APR 1 PY 2007 VL 69 IS 5 BP 685 EP 689 DI 10.1002/ccd.21095 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 155KO UT WOS:000245576500011 PM 17351955 ER PT J AU Patel, KB Gupta, H Nath, H Aqel, RA Zoghbi, GJ Soto, B Perry, GJ Lloyd, SG AF Patel, Kashyap B. Gupta, Himanshu Nath, Hrudaya Aqel, Raed A. Zoghbi, Gilbert J. Soto, Benigno Perry, Gilbert J. Lloyd, Steven G. TI Origin of all three major coronary arteries from the right sinus of valsalva: Clinical, angiographic, and magnetic resonance imaging findings and incidence in a select referral population SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE imaging (CT/MR); angiography coronary; anomalous coronaries ID ANOMALOUS AORTIC ORIGIN; 2 SEPARATE OSTIA; MYOCARDIAL-INFARCTION; CT ANGIOGRAPHY; CIRCUMFLEX; VISUALIZATION; ADULTS; RARE AB Objective: We sought to determine the incidence and imaging features by coronary angiography and cardiac magnetic resonance imaging (MRI) of anomalies in which the right, circumflex, and left anterior descending coronary arteries arise separately from the right sinus of Valsalva. Background: The anomalous origin of all major coronary arteries from separate ostia in the right sinus of Valsalva has been reported as exceedingly rare, with mainly isolated cases reported. A knowledge of the origin and proximal courses of aberrant arteries is critical for patient management. Methods: 42 consecutive patients without other congenital heart disease referred to our institution for MRI evaluation of anomalous coronary artery over a six year period were evaluated. Analysis of angiograms and MRI was done to determine the anatomic origin and proximal pathway of coronary arteries (determined by conventional angiography and MRI) and degree of any stenosis (by angiography). Results: Seven of the 42 patients (17%) in this referral population had the described anatomy. Both conventional angiography and MRI depicted the origin and proximal courses of these arteries. In all patients, the circumflex passed behind the aorta. In three, the left anterior descending passed through the ventricular septum; in four, it passed anterior to the pulmonary trunk. Conclusions: This series is the largest ever reported on this complex anatomical variant and the first to give a systematic analysis of the anatomy by angiography and MRI. This constellation of multiple anomalous coronary arterial origins and proximal courses may not be as rare as previously reported. Published 2007 Wiley-Liss, Inc.(dagger) C1 Univ Alabama, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. Univ Alabama, Dept Radiol, Birmingham, AL USA. Birmingham VA Med Ctr, Div Cardiol, Birmingham, AL USA. RP Lloyd, SG (reprint author), D-101 Cardiovasc MRI,1530 3rd Ave S, Birmingham, AL 35294 USA. EM sglloyd@uab.edu NR 30 TC 8 Z9 9 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD APR 1 PY 2007 VL 69 IS 5 BP 711 EP 718 DI 10.1002/ccd.21078 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 155KO UT WOS:000245576500017 PM 17330267 ER PT J AU Gnainsky, Y Kushnirsky, Z Bilu, G Hagai, Y Genina, O Volpin, H Bruck, R Spira, G Nagler, A Kawada, N Yoshizato, K Reinhardt, DP Libermann, TA Pines, M AF Gnainsky, Y. Kushnirsky, Z. Bilu, G. Hagai, Y. Genina, O. Volpin, H. Bruck, R. Spira, G. Nagler, A. Kawada, N. Yoshizato, K. Reinhardt, D. P. Libermann, T. A. Pines, M. TI Gene expression during chemically induced liver fibrosis: effect of halofuginone on TGF-beta signaling SO CELL AND TISSUE RESEARCH LA English DT Article DE collagen; cytoglobin/STAP; fibrillin; acid phosphatase; osteopontin; fibrosis; liver; rat (Wistar male) ID HEPATIC STELLATE CELLS; HEPATOCELLULAR-CARCINOMA; I SYNTHESIS; SMAD3; COLLAGEN; GROWTH; ACTIVATION; INHIBITOR; RATS; TRANSCRIPTION AB Hepatic fibrosis is associated with the activation of stellate cells (HSCs), the major source of extracellular matrix (ECM) proteins. Transforming growth factor-beta (TGF-beta), signaling via Smad3, is the most profibrogenic cytokine and the major promoter of ECM synthesis. Halofuginone, an inhibitor of liver fibrosis, inhibits TGF-beta-dependent Smad3 phosphorylation in human HSCs in culture. We have used transcriptional profiling to evaluate the effect of halofuginone on gene expression during the progression of thioacetamide (TAA)-induced liver fibrosis in the rat and have focused on genes that are associated with TGF-beta. TAA treatment causes alterations in the expression of 7% of liver genes. Halofuginone treatment prevents the changes in the expression of 41% of these genes and results in the inhibition of HSC activation and collagen synthesis. During the early stages of the disease, halofuginone affects genes involved in alcohol, lipid, protein, and phosphate metabolism and cell adhesion and, at later stages, in the cell cycle (cell development, differentiation, cell proliferation, and apoptosis). The activation of TGF-beta-dependent genes, such as tartrate-resistant acid phosphatase, its putative substrate osteopontin, stellate cell activation-association protein, and fibrillin-1, during chemically induced fibrosis is prevented by halofuginone. This study thus highlights the role of TGF-beta signaling in liver fibrosis and especially its potential for pharmacological intervention. Halofuginone, which has demonstrated efficacy and tolerance in animals and humans, could become an effective and novel therapy for liver fibrosis. C1 Agr Res Org, Volcani Ctr, Inst Anim Sci, IL-50250 Bet Dagan, Israel. Agr Res Org, Volcani Ctr, Genom & Bioinformat Ctr, IL-50250 Bet Dagan, Israel. E Wolfson Med Ctr, Dept Gastroenterol, Holon, Israel. Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. Technion Israel Inst Technol, Bruce Rappaport Fac Med, Dept Anat & Cell Biol, IL-31096 Haifa, Israel. Chaim Sheba Med Ctr, Div Hematol, IL-52621 Tel Hashomer, Israel. Osaka City Univ, Grad Sch Med, Dept Hepatol, Osaka 558, Japan. Hiroshima Univ, Grad Sch Sci, Dev Biol Lab, CLUSTER Project, Hiroshima, Japan. Hiroshima Univ, Grad Sch Sci, 21st Century COE PRogram, Dept Biol Sci, Hiroshima, Japan. McGill Univ, Fac Med, Dept Anat & Cell Biol, Montreal, PQ, Canada. McGill Univ, Fac Dent, Dept Anat & Cell Biol, Montreal, PQ, Canada. Beth Israel Deaconess Med Ctr, BIDMC Genom Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Pines, M (reprint author), Agr Res Org, Volcani Ctr, Inst Anim Sci, POB 6, IL-50250 Bet Dagan, Israel. EM pines@agri.huji.ac.il RI Libermann, Towia/F-9866-2010; Reinhardt, Dieter/A-3102-2008; OI Reinhardt, Dieter/0000-0001-6535-9872; Libermann, Towia/0000-0002-4006-8179 FU NCI NIH HHS [R21 CA108303]; NIDDK NIH HHS [U01 DK58739] NR 42 TC 39 Z9 43 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD APR PY 2007 VL 328 IS 1 BP 153 EP 166 DI 10.1007/s00441-006-0330-1 PG 14 WC Cell Biology SC Cell Biology GA 145TO UT WOS:000244888100015 PM 17180598 ER PT J AU Karmpaliotis, D Kirtane, JJ Ruisi, CP Polonsky, T Malhotra, A Talmor, D Kosmidou, I Jarolim, P de Lemos, JA Sabatine, MS Gibson, CM Morrow, D AF Karmpaliotis, Dimitri Kirtane, Jay J. Ruisi, Christopher P. Polonsky, Tainar Malhotra, Atul Talmor, Daniel Kosmidou, Ioanna Jarolim, Petr de Lemos, James A. Sabatine, Marc S. Gibson, C. Michael Morrow, David TI Diagnostic and prognostic utility of brain natriuretic peptide in subjects admitted to the ICU with hypoxic respiratory failure due to noncardiogenic and cardiogenic pulmonary edema SO CHEST LA English DT Article DE ARDS; brain natrinretic peptide; cardiogenic pulmonary edema; respiratory failure; Swan-Ganz catheter ID CRITICALLY-ILL PATIENTS; END-EXPIRATORY PRESSURE; ACUTE LUNG INJURY; MECHANICALLY VENTILATED PATIENTS; INTENSIVE-CARE-UNIT; DISTRESS-SYNDROME; ARTERY CATHETERS; CONSENSUS-CONFERENCE; CONTROLLED-TRIAL; WEDGE PRESSURE AB Background: Brain natriuretic peptide (BNP) is useful in diagnosing congestive heart failure (CHF) in patients presenting in the emergency department with acute dyspnea. We prospectively tested the utility of BNP for discriminating ARDS vs cardiogenic pulmonary edema (CPE). Methods: We enrolled ICU patients with acute hypoxemic respiratory failure and bilateral pulmonary infiltrates who were undergoing right-heart catheterization (RHC) to aid in diagnosis. Patients with acute coronary syndrome, end-stage renal disease, recent coronary artery bypass graft surgery, or preexisting left ventricular ejection fraction <= 30% were excluded. BNP was measured at RHC. Two intensivists independently reviewed the records to determine the final diagnosis. Results: Eighty patients were enrolled. Median BNP was 325 pg/mL (interquartile range [IQR], 82 to 767 pg/mL) in acute lung injury/ARDS patients, vs 1,260 pg/mL (IQR, 541 to 2,020 pg/mL) in CPE patients (p = 0.0001). The correlation between BNP and pulmonary capillary wedge pressure was modest (r = 0.27, p = 0.02). BNP offered good discriminatory performance for the final diagnosis (C-statistic, 0.80). At a cut point <= 200 pg/mL, BNP provided specificity of 91% for ARDS. At a cut point >= 1,200 pg/mL, BNP had a specificity of 92% for CPE. Higher levels of BNP were associated with a decreased odds for ARDS (odds ratio, 0.4 per log increase; p = 0.007) after adjustment for age, history of CHIT, and right atrial pressure. BNP was associated with in-hospital mortality (p = 0.03) irrespective of the final diagnosis and independent of APACHE (acute physiology and chronic health evaluation) II score. C onclusion: In ICU patients with hypoxemic respiratory failure, BNP appears useful in excluding CPE and identifying patients with a high probability of ARDS, and was associated with mortality in patients with both ARDS and CPE. Larger studies are necessary to validate these findings. C1 Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Div Pulm & Crit Care, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Cardiovasc Div, Boston, MA 02115 USA. Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Emory Univ, Sch Med, Dept Med, Atlanta, GA USA. SW Texas State Univ, Dallas, TX USA. RP Karmpaliotis, D (reprint author), Piedmont Hosp, Fuqua Heart Ctr, 95 Collier Rd NW Suite 2075, Atlanta, GA 30309 USA. EM dkarmpaliotis@cardioga.com FU NHLBI NIH HHS [R01 HL073146, R01 HL073146-03]; NIA NIH HHS [K23 AG024837, K23 AG024837-04] NR 38 TC 60 Z9 66 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD APR PY 2007 VL 131 IS 4 BP 964 EP 971 DI 10.1373/chest.06-1247 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 158DE UT WOS:000245770600007 PM 17426196 ER PT J AU Fagenholz, PJ Gutman, JA Murray, AF Noble, VE Thomas, SH Harris, NS AF Fagenholz, Peter J. Gutman, Jonathan A. Murray, Alice F. Noble, Vicki E. Thomas, Stephen H. Harris, N. Stuart TI Chest ultrasonography for the diagnosis and monitoring of high-altitude pulmonary edema SO CHEST LA English DT Article DE acute mountain sickness; high-altitude pulmonary edema; hypoxia; mountaineering; pulmonary edema; ultrasound ID EXTRAVASCULAR LUNG WATER; ACUTE MOUNTAIN-SICKNESS; COMET-TAIL ARTIFACT; ULTRASOUND SIGN; EXERCISE; PRESSURE; FEATURES; FLUID AB Background: The comet-tail technique of chest ultrasonography has been described for the diagnosis of cardiogenic pulmonary edema. This is the first report describing its use for the diagnosis and monitoring of high-altitude pulmonary edema (HAPE), the leading cause of death from altitude illness. Methods: Eleven consecutive patients presenting to the Himalayan Rescue Association clinic in Pheriehe, Nepal (4,240 m) with a clinical diagnosis of HAPE underwent one to three chest ultrasound examinations using the comet-tail technique to determine the presence of extravascular lung water (EVLW). Seven patients with no evidence of HAPE or other altitude illness served as control subjects. All examinations were read by a blinded observer. Results: HAFE patients had higher comet-tail score (CTS) [mean +/- SD, 31 +/- 11 vs 0.86 +/- 0.83] and lower oxygen saturation (O(2)Sat) [61 +/- 9.2% vs; 87 +/- 2.8%] than control subjects (p < 0.001 for both). Mean CTS was higher (35 +/- 11 vs 12 +/- 6.8, p < 0.001) and O(2)Sat was lower (60 +/- 11% vs 84 +/- 1.6%, p = 0.002) at hospital admission than at discharge for the HAVE patients with follow-up ultrasound examinations. Regression analysis showed CTS was predictive of O(2)Sat (p < 0.001), and for every 1-point increase in CTS O(2)Sat fell by 0.67% (95% confidence interval, 0.41 to 0.93%, p < 0.001). Conclusions: The comet-tail technique effectively recognizes and monitors the degree of pulmonary edema in HAPE. Reduction in CTS parallels improved oxygenation and clinical status in HAPE. The feasibility of this technique in remote locations and rapid correlation with changes in EVLW make it a valuable research tool. C1 Massachusetts Gen Hosp, Dept Emergency Med, Clin 115, Boston, MA 02140 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Royal Infirm Edinburgh NHS Trust, Emergency Dept, Edinburgh, Midlothian, Scotland. RP Harris, NS (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Clin 115, 55 Fruit St, Boston, MA 02140 USA. EM nsharris@partners.org NR 27 TC 71 Z9 75 U1 1 U2 4 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD APR PY 2007 VL 131 IS 4 BP 1013 EP 1018 DI 10.1378/chest.06-1864 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 158DE UT WOS:000245770600015 PM 17426204 ER PT J AU Wasfi, YS Margolis, ML AF Wasfi, Yasinine S. Margolis, Mitchell L. TI A 45-year-old man with severe dysphagia and pulmonary infiltrates SO CHEST LA English DT Editorial Material ID SARCOIDOSIS C1 Philadelphia Vet Affairs Med Ctr, Pulm Sect, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Pulm Allergy & Crit Care Div, Philadelphia, PA 19104 USA. RP Margolis, ML (reprint author), Philadelphia Vet Affairs Med Ctr, Pulm Sect, Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM Mitchell.Margolis@med.va.gov NR 10 TC 3 Z9 3 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD APR PY 2007 VL 131 IS 4 BP 1256 EP 1259 DI 10.1378/chest.06-0977 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 158DE UT WOS:000245770600051 PM 17426240 ER PT J AU Nichols, JH Christenson, RH Clarke, W Gronowski, A Hammett-Stabler, CA Jacobs, E Kazmierczak, S Lewandrowski, K Price, C Sacks, DB Sautter, RL Shipp, G Sokoll, L Watson, ID Winter, W Zucker, ML AF Nichols, James H. Christenson, Robert H. Clarke, William Gronowski, Ann Hammett-Stabler, Catherine A. Jacobs, Ellis Kazmierczak, Steve Lewandrowski, Kent Price, Christopher Sacks, David B. Sautter, Robert L. Shipp, Gregg Sokoll, Lori Watson, Ian D. Winter, William Zucker, Marcia L. TI Executive summary. The National Academy of Clinical Biochemistry Laboratory Medicine Practice Guideline: Evidence-based practice for point-of-care testing SO CLINICA CHIMICA ACTA LA English DT Article DE point-of-care testing; evidence-based medicine; practice guidelines AB Background: Point-of-care testing (POCT) is clinical laboratory testing conducted close to the site of patient care. POCT has the potential to provide faster test results and therapeutic intervention with improved patient outcomes. However, when over-utilized or used inappropriately POCT results can be misleading and increase healthcare costs. Methods: The National Academy of Clinical Biochemistry developed evidence-based Laboratory Medicine Practice Guidelines for POCT. Results: These Laboratory Medicine Practice Guidelines systematically review the scientific literature relating POCT to clinical outcomes and offer recommendations to improve the clinical utility of POCT. Conclusions: These guidelines will be useful to clinicians considering the addition of POCT, to those that question current practices in POCT, and to clinicians seeking evidence-based support for POCT in clinical management. These guidelines represent the most comprehensive systematic review of the POCT literature to date and will help define future research that is needed to add to our current POCT knowledge base. (c) 2007 Elsevier B.V. All rights reserved. C1 Tufts Univ, Sch Med, Baystate Hlth, Springfield, MA 01199 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Washington Univ, St Louis, MO USA. Univ N Carolina, Chapel Hill, NC USA. New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Oxford, Oxford, England. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Carolinas Med Ctr, Charlotte, NC USA. Nanosphere, Northbrook, IL USA. Univ Hosp Aintree, Liverpool, Merseyside, England. Univ Florida, Gainesville, FL USA. ITC, Edison, NJ USA. RP Nichols, JH (reprint author), Tufts Univ, Sch Med, Baystate Hlth, 759 Chestnut St, Springfield, MA 01199 USA. EM james.nichols@bhs.org OI Watson, Ian D/0000-0003-2294-3715; Sacks, David/0000-0003-3100-0735 NR 3 TC 47 Z9 50 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD APR PY 2007 VL 379 IS 1-2 BP 14 EP 28 DI 10.1016/j.cca.2006.12.025 PG 15 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 157QC UT WOS:000245734200002 PM 17270169 ER PT J AU Jeske, WP McDonald, MK Hoppensteadt, DA Bau, EC Mendes, A Dietrich, CP Walenga, JM Coyne, E AF Jeske, Walter P. McDonald, Meredith K. Hoppensteadt, Debra A. Bau, Elaine C. Mendes, Aline Dietrich, Carl P. Walenga, Jeanine M. Coyne, Erwin TI Isolation and characterization of heparin from tuna skins SO CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS LA English DT Article DE heparin; anticoagulant; fish skin ID SHRIMP PENAEUS-BRASILIENSIS; HIGH ANTICOAGULANT ACTIVITY; MOLECULAR-WEIGHT HEPARINS; CHONDROITIN SULFATES; MUCOPOLYSACCHARIDES; PENTASACCHARIDE; THERAPY; HAGFISH AB This study characterized heparin isolated from tuna skins. Glycosaminoglycans were isolated from tuna skin after digestion using anion exchange resin. Heparin was eluted from the resin by sodium chloride gradient and was further fractionated by acetone fractionation. Anticoagulant activity was determined using the activated partial thromboplastin time and Heptest assays. Potency was determined using amidolytic antifactor IIa and antifactor Xa assays. The presence of heparin in the extracted tuna skin glycosaminoglycans was confirmed using C-13-nuclear magnetic resonance. The activated partial thromboplastin time and Heptest clotting times were doubled at concentrations of about 4 and 1 mu g/mL, respectively. The clotting time prolongation and antiprotease activity induced by tuna heparin was readily neutralized by 25 mu g/mL protamine sulfate. These results demonstrate that biologically active heparin with properties similar to clinical grade heparin can be derived from tuna skin, a raw material with other-wise relatively little economic value. C1 Loyola Univ, Ctr Med, Cardiovasc Inst, Maywood, IL 60153 USA. Loyola Univ, Ctr Med, Dept Pathol, Maywood, IL 60153 USA. Univ Fed Sao Paulo, Dept Bioquim, Sao Paulo, Brazil. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, Hines, IL 60141 USA. RP Jeske, WP (reprint author), Loyola Univ, Ctr Med, Cardiovasc Inst, 2160 S 1st Ave, Maywood, IL 60153 USA. EM wjeske@lumc.edu NR 28 TC 2 Z9 3 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1076-0296 J9 CLIN APPL THROMB-HEM JI Clin. Appl. Thromb.-Hemost. PD APR PY 2007 VL 13 IS 2 BP 137 EP 145 DI 10.1177/1076029606298982 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 148YN UT WOS:000245113400004 PM 17456622 ER PT J AU Kriangkum, J Taylor, BJ Treon, SP Mant, MJ Reiman, T Belch, AR Pilarski, LM AF Kriangkum, Jitra Taylor, Brian J. Treon, Steven P. Mant, Michael J. Reiman, Tony Belch, Andrew R. Pilarski, Linda M. TI Molecular characterization of Waldenstrom's macroglobulinemia reveals frequent occurrence of two B-cell clones having distinct IgH VDJ sequences SO CLINICAL CANCER RESEARCH LA English DT Article ID V-H GENES; SOMATIC MUTATION; LYMPHOMA; IMMUNOGLOBULIN; HYPERMUTATION; RECEPTOR; ORIGINS; MYELOMA AB Purpose: Malignant B lineage cells in Waldenstrom's macroglobulinemia (WM) express a unique clonotypic IgM VDJ. The occurrence of biclonal B cells and their clonal relationships were characterized. Experimental Design: Bone marrow and blood from 20 WM patients were analyzed for clonotypic VDJ sequences, clonal B-cell frequencies, and the complementary determining region 3 profile. Results: Two different clonotypic VDJ sequences were identified in 4 of 20 WM. In two cases, partner clones had different VDJ rearrangements, with one clonotypic signature in bone marrow and a second in blood. For both cases, the bone marrow clone was hypermutated, whereas the blood clone was germ line or minimally mutated. In two other cases, partner clones shared a common VDJ rearrangement but had different patterns of somatic mutations. They lacked intraclonal diversity and were more abundant in bone marrow than in blood. VDJ mutation profiles suggested they arose from a common IgM progenitor. Single-cell analysis in one case indicated the partner clones were reciprocally expressed, following rules of allelic exclusion. Conclusions: The existence of two B-cell clones having distinct VDJ sequences is common in WM, suggesting that frequent transformation events may occur. In two cases, the partner clones had distinct tissue distributions in either blood or bone marrow, were of different immunoglobulin isotypes, and in one case exhibited differential response to therapy. The contributions of each clone are unknown. Their presence suggests that WM may involve a background of molecular and cellular events leading to emergence of one or more malignant clones. C1 Cross Canc Inst, Dept Oncol, Edmonton, AB T6G 1Z2, Canada. Univ Alberta, Dept Med, Edmonton, AB, Canada. Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02115 USA. RP Pilarski, LM (reprint author), Cross Canc Inst, Dept Oncol, 11560 Univ Ave, Edmonton, AB T6G 1Z2, Canada. EM lpilarsk@ualberta.ca NR 31 TC 14 Z9 14 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2007 VL 13 IS 7 BP 2005 EP 2013 DI 10.1158/1078-0432.CCR-06-2788 PG 9 WC Oncology SC Oncology GA 156PG UT WOS:000245660800009 PM 17404080 ER PT J AU Ryan, CJ Halabi, S Ou, SS Vogelzang, NJ Kantoff, P Small, EJ AF Ryan, Charles J. Halabi, Susan Ou, San-San Vogelzang, Nicholas J. Kantoff, Philip Small, Eric J. CA Canc Leukemia Grp B TI Adrenal androgen levels as predictors of outcome in prostate cancer patients treated with ketoconazole plus antiandrogen withdrawal: Results from a cancer and leukemia group B study SO CLINICAL CANCER RESEARCH LA English DT Article ID FLUTAMIDE WITHDRAWAL; DOSE KETOCONAZOLE; TESTOSTERONE; COMBINATION; CARCINOMA; RECEPTORS; THERAPY AB Purpose: Adrenal androgens activate the androgen receptor and stimulate prostate cancer growth. Ketoconazole is used as an inhibitor of adrenal androgen synthesis in men with androgen-independent prostate cancer. This study analyzes the relationship between pretreatment androgen levels and outcome following ketoconazole treatment. Experimental Design: Baseline levels of three adrenal androgens (androstenedione, dehydroepiandrostenedione, and dehydroepiandrostenedione-sulfate) and testosterone were measured. Regression models (logistic and proportional hazard) were used to assess the prognostic significance of these levels in predicting overall survival and prostate-specific antigen (PSA) response defined by Consensus Criteria. Results: In 103 patients with available levels, PSA response rate was 28% and median response duration was 4.8 months. The median baseline androstenedione level was 0.64 ng/mL and was 0.88 ng/mL versus 0.53 ng/mL for those with and without a PSA response, respectively (P = 0.034). In univariate analysis, elevation of baseline androstenedione levels was predictive of PSA response [odds ratio, 2.26; 95% confidence interval (95% CI), 1.03-4.96; P = 0.043]. In multivariate analysis, both the uppermost and the middle tertile of baseline androstenedione level were associated with an improved overall survival compared with those in the lower tertile (hazard ratio, 0.59; 95% Cl, 0.36-0.98; P = 0.40; hazard ratio, 0.53; 95% Cl, 0,32-0.90; P = 0.018, respectively). A linear correlation was observed among all androgen levels. Conclusions: Higher androstenedione levels predict likelihood of response to ketoconazole and improved survival compared with patients with lower levels. These data suggest that therapy with ketoconazole is less effective in patients with low levels of androgen at baseline. C1 Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Duke Univ, Med Ctr, Ctr Stat, Canc & Leukemia Grp B, Durham, NC USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ryan, CJ (reprint author), Univ Calif San Francisco, Ctr Comprehens Canc, 3rd Floor,1600 Divisadero, San Francisco, CA 94143 USA. EM ryanc@medicine.ucsf.edu FU NCI NIH HHS [CA31946] NR 18 TC 58 Z9 59 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2007 VL 13 IS 7 BP 2030 EP 2037 DI 10.1158/1078-0432.CCR-06-2344 PG 8 WC Oncology SC Oncology GA 156PG UT WOS:000245660800012 PM 17404083 ER PT J AU Cahill, DP Levine, KK Betensky, RA Codd, PJ Romany, CA Reavie, LB Batchelor, TT Futreal, PA Stratton, MR Curry, WT Iafrate, AJ Louis, DN AF Cahill, Daniel P. Levine, Kymberly K. Betensky, Rebecca A. Codd, Patrick J. Romany, Candice A. Reavie, Linsey B. Batchelor, Tracy T. Futreal, P. Andrew Stratton, Michael R. Curry, William T. Iafrate, A. John Louis, David N. TI Loss of the mismatch repair protein MSH6 in human glioblastomas is associated with tumor progression during temozolomide treatment SO CLINICAL CANCER RESEARCH LA English DT Article ID NERVOUS-SYSTEM TUMORS; BASE EXCISION-REPAIR; COLON-CANCER; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; MICROSATELLITE INSTABILITY; METHYLATING AGENTS; HUMAN-CELLS; MUTS-ALPHA; DEFICIENT; MUTATIONS AB Purpose: Glioblastomas are treated by surgical resection followed by radiotherapy [X-ray therapy (XRT)] and the alkylating chemotherapeutic agent temozolomide. Recently, inactivating mutations in the mismatch repair gene MSH6 were identified in two glioblastomas recurrent post-temozolomide. Because mismatch repair pathway inactivation is a known mediator of alkylator resistance in vitro, these findings suggested that MSH6 inactivation was causally linked to these two recurrences. However, the extent of involvement of MSH6 in glioblastoma is unknown. We sought to determine the overall frequency and clinical relevance of MSH6 alterations in glioblastomas. Experimental Design: The MSH6 gene was sequenced in 54 glioblastomas. MSH6 and O-6- methylguanine methyltransferase (MGMT) immunohistochemistry was systematically scored in a panel of 46 clinically well-characterized glioblastomas, and the corresponding patient response to treatment evaluated. Results: MSH6 mutation was not observed in any pretreatment glioblastoma (0 of 40), whereas 3 of 14 recurrent cases had somatic mutations (P = 0.015). MSH6 protein expression was detected in all pretreatment (17 of 17) cases examined but, notably, expression was lost in 7 of 17 (41%) recurrences from matched post-XRT + temozolomide cases (P = 0.016). Loss of MSH6 was not associated with O-6-methylguanine methyltransferase status. Measurements of in vivo tumor growth using three-dimensional reconstructed magnetic resonance imaging showed that MSH6-negative glioblastomas had a markedly increased rate of growth while under temozolomide treatment (3.17 versus 0.04 cc/mo for MSH6-positive tumors; P = 0.020). Conclusions: Loss of MSH6 occurs in a subset of post -XRT + temozolomide glioblastoma recurrences and is associated with tumor progression during temozolomide treatment, mirroring the alkylator resistance conferred by MSH6 inactivation in vitro. MSH6 deficiency may therefore contribute to the emergence of recurrent glioblastomas during temozolomide treatment. C1 Massachusetts Gen Hosp, Pathol Serv, Mol Pathol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Biostat, Boston, MA USA. Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton, England. RP Louis, DN (reprint author), Massachusetts Gen Hosp, Pathol Serv, Mol Pathol Unit, 55 Fruit St,Warren 2, Boston, MA 02114 USA. EM dlouis@partners.org OI Cahill, Daniel/0000-0003-2552-6546 FU Wellcome Trust [077012] NR 37 TC 147 Z9 150 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2007 VL 13 IS 7 BP 2038 EP 2045 DI 10.1158/1078-0432.CCR-06-2149 PG 8 WC Oncology SC Oncology GA 156PG UT WOS:000245660800013 PM 17404084 ER PT J AU Raponi, M Harousseau, JL Lancet, JE Lowenberg, B Stone, R Zhang, Y Rackoff, W Wang, YX Atkins, D AF Raponi, Mitch Harousseau, Jean-Luc Lancet, Jeffrey E. Loewenberg, Bob Stone, Richard Zhang, Yi Rackoff, Wayne Wang, Yixin Atkins, David TI Identification of molecular predictors of response in a study of tipifarnib treatment in relapsed and refractory acute myelogenous leukemia SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 18-21, 2002 CL ORLANDO, FL SP Amer Soc Clin Oncol ID FARNESYL TRANSFERASE INHIBITOR; CHRONIC MYELOID-LEUKEMIA; KAPPA-B ACTIVATION; GENE-EXPRESSION; BREAST-CANCER; FARNESYLTRANSFERASE INHIBITORS; HEMATOLOGIC MALIGNANCIES; PROTEIN TRANSFERASE; PHASE-II; IN-VIVO AB Purpose: Microarray technology was used to identify gene expression markers that predict response to the orally available farnesyltransferase inhibitor tipifarnib (Zarnestra, R115777) in acute myelogenous leukemia (AML). Experimental Design: Gene expression profiles from 58 bone marrow samples from a cohort of relapsed and refractory AML patients were analyzed on the Affymetrix U133A gene chip that contains similar to 22,000 genes. Results: Supervised statistical analysis identified eight gene expression markers that could predict patient response to tipifarnib. The most robust gene was the lymphoid blast crisis oncogene (AKAP13), which predicted response with an overall accuracy of 63%. This gene provided a negative predictive value of 93% and a positive predictive value of 31% (increased from 18%). AKAP13 was overexpressed in patients who were resistant to tipifarnib. When overexpressed in the HL60 and THP1 cell lines,AKAP13 increased the resistance to tipifarnib by approximately 5- to 7-fold, Conclusion: Diagnostic gene expression signatures may be used to select a group of AML patients that might respond to tipifarnib. C1 Veridex LLC, San Diego, CA 92121 USA. CHRU Hotel Dieu, Serv Hematol Clin, Nantes, France. Univ S Florida, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Erasmus Univ, Med Ctr, Dept Hematol, Rotterdam, Netherlands. Dana Farber Canc Inst, Adult Leukemia Program, Boston, MA 02115 USA. Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ USA. RP Raponi, M (reprint author), Veridex LLC, 3210 Merryfield Row, San Diego, CA 92121 USA. EM mraponi1@vrxus.jnj.com NR 42 TC 34 Z9 36 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2007 VL 13 IS 7 BP 2254 EP 2260 DI 10.1158/1078-0432.CCR-06-2609 PG 7 WC Oncology SC Oncology GA 156PG UT WOS:000245660800039 PM 17404110 ER PT J AU Bruce, B Khanna, G Ren, L Landberg, G Jirstrom, K Powell, C Borczuk, A Keller, ET Wojno, KJ Meltzer, P Baird, K McClatchey, A Bretscher, A Hewitt, SM Khanna, C AF Bruce, Benjamin Khanna, Gaurav Ren, Ling Landberg, Goran Jirstrom, Karin Powell, Charles Borczuk, Alain Keller, Evan T. Wojno, Kirk J. Meltzer, Paul Baird, Kristin McClatchey, Andrea Bretscher, Anthony Hewitt, Stephen M. Khanna, Chand TI Expression of the cytoskeleton linker protein ezrin in human cancers SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE ezrin; merlin; immunohistochemistry; tissue microarray; biomarker; prognosis ID NF2 TUMOR-SUPPRESSOR; C-TERMINAL DOMAIN; ERM PROTEINS; TISSUE MICROARRAY; STROMAL CELLS; METASTASIS; MERLIN; BINDING; HEMANGIOBLASTOMA; TUMORIGENESIS AB Expression of the metastasis-associated protein, ezrin, in over 5,000 human cancers and normal tissues was analyzed using tissue microarray immunohistochemistry. Ezrin staining was compared between cancers and their corresponding normal tissues, between cancers of epithelial and mesenchymal origin, in the context of the putative inhibitor protein, merlin, and against clinicopathological data available for breast, lung, prostate cancers and sarcomas. Ezrin was found in most cancers and normal tissues at varying levels of intensity. In general ezrin was expressed at higher levels in sarcomas than in carcinomas. By normalizing the expression of ezrin in each cancer using ezrin expression found in the corresponding normal tissue, significant associations between ezrin were found in advancing histological grade in sarcomas (P = 0.02) and poor outcome in breast cancer (P = 0.025). Clinicopathologic associations were not changed by simultaneous assessment of ezrin and merlin in each patient sample for the cancer types examined. These data support a role for ezrin in the biology of human cancers and the need for additional studies in breast cancer and sarcoma patients that may validate ezrin as a marker of cancer progression and as a potential target for cancer therapy. C1 NCI, Ctr Canc Res, Tumor & Metastasis Biol Sect, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Bethesda, MD USA. Lund Univ, Malmo Univ Hosp, S-20502 Malmo, Sweden. Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI 48109 USA. NHGRI, Canc Genet Branch, Bethesda, MD USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Dept Pathol, Charlestown, MA USA. Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY USA. Natl Canc Inst, Ctr Canc Res, Pathol Lab, Tissue Army Res Program, Bethesda, MD USA. RP Khanna, C (reprint author), NCI, Ctr Canc Res, Tumor & Metastasis Biol Sect, Bethesda, MD 20892 USA. EM khannac@mail.nih.gov RI Keller, Evan/M-1446-2016; OI Keller, Evan/0000-0002-7592-7535; POWELL, CHARLES/0000-0003-3509-891X; Hewitt, Stephen/0000-0001-8283-1788 FU Intramural NIH HHS; NCI NIH HHS [1P50 CA69568, P01 CA093900] NR 33 TC 70 Z9 89 U1 1 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD APR PY 2007 VL 24 IS 2 BP 69 EP 78 DI 10.1007/s10585-006-9050-x PG 10 WC Oncology SC Oncology GA 162QM UT WOS:000246103400001 PM 17370041 ER PT J AU Young, MRI Neville, BW Chi, AC Lathers, DMR Gillespie, MB Day, TA AF Young, M. Rita I. Neville, Brad W. Chi, Angela C. Lathers, Deanne M. R. Gillespie, M. Boyd Day, Terry A. TI Autocrine motility-stimulatory pathways of oral premalignant lesion cells SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE ceramide; oral cancer; IL-10; migration; PP-2A; premalignant lesions ID PROTEIN PHOSPHATASE-2A; CERAMIDE PRODUCTION; CARCINOMA-CELLS; TUMOR-CELLS; HL-60 CELLS; ACTIVATION; CANCER; PHOSPHORYLATION; INTERLEUKIN-10; INDUCTION AB Patients with premalignant oral lesions have varying levels of risk of developing oral squamous cell carcinoma (OSCC), whose aggressiveness requires increased motility. Not known is if and how premalignant oral lesion cells acquire the increased motility characteristic of OSCC. This was addressed by immunohistochemical analysis of banked premalignant lesion tissues and by functional analyses using cultures established from premalignant oral lesions and OSCC. These studies showed premalignant oral lesion cells and OSCC to be more motile than normal keratinocytes. Concomitantly, levels of ceramide were reduced. The activity of the protein phosphatase PP-2A, which restricts motility and which can be activated by ceramide, was also diminished. This was due to IL-10 released from premalignant lesion cells. Treatment with a membrane-permeable ceramide restored PP-2A activity and blocked migration. These studies show an autocrine motility-stimulatory pathway that is mediated in premalignant lesion cells by IL-10 through its reduction of ceramide levels and inhibition of PP-2A activity. C1 Ralph H Johnson Vet Affairs Hosp, Ralph H Johnson VA Med Ctr, Res Serv 151, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Stomatol, Charleston, SC 29425 USA. RP Young, MRI (reprint author), Ralph H Johnson Vet Affairs Hosp, Ralph H Johnson VA Med Ctr, Res Serv 151, 109 Bee St, Charleston, SC 29401 USA. EM rita.young@va.gov FU NCI NIH HHS [CA97813, CA85266] NR 29 TC 4 Z9 4 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD APR PY 2007 VL 24 IS 2 BP 131 EP 139 DI 10.1007/s10585-007-9063-0 PG 9 WC Oncology SC Oncology GA 162QM UT WOS:000246103400007 PM 17370039 ER PT J AU Leykum, LK El-Serag, HB Cornell, J Papadopoulos, KP AF Leykum, Luci K. El-Serag, Hashem B. Cornell, John Papadopoulos, Kyriakos P. TI Screening for hepatocellular carcinoma among veterans with hepatitis C on disease stage, treatment received, and survival SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; UNITED-STATES; LIVER-CANCER; MANAGEMENT AB Background & Aims: The incidence of hepatocellular carcinoma (HCC) is increasing. Despite recommendations for HCC screening from the American Association for the Study of Liver Disease, the National Cancer Institute does not recommend screening. The question of whether screening is of benefit is an important one. The purpose of this study was to examine the determinants of screening, as well as the impact of screening on disease stage, treatment received, and survival in a US veteran population. Methods: Patients with hepatitis C and HCC who receive care in the South Texas Veteran Health Care System were identified using the Veterans Affairs national hepatitis C registry. Screening status was determined by chart review. Potential determinants of screening were assessed. Screened and unscreened patients were compared on the basis of disease stage at diagnosis, treatment: received, and survival. Results: Seventy-two patients were identified and included in the analysis, of whom only 16 (22%) were screened. Patients seen by a hepatologist before diagnosis were more likely to be screened. All screened patients were diagnosed with early stage disease, compared with 22% of unscreened patients (P <.001). Screened patients were 10 times more likely to have received potentially curative treatment (95% confidence interval, 2.91-31.35). Log-rank test of equality of survivor functions was statistically significant for differences between screened and unscreened groups (P = .0005). Conclusions: Our findings support the American Association for the Study of Liver Disease screening recommendations, and suggest that screening is underused. C1 Univ Texas, Ctr Hlth Sci, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Univ Texas, Ctr Hlth Sci, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Leykum, LK (reprint author), Univ Texas, Ctr Hlth Sci, S Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd,Ambulatory Care 11C6, San Antonio, TX 78229 USA. EM Leykum@uthscsa.edu NR 17 TC 38 Z9 39 U1 0 U2 1 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 APR PY 2007 VL 5 IS 4 BP 508 EP 512 DI 10.1016/j.cgh.2007.01.014 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 162BR UT WOS:000246062000021 PM 17382601 ER PT J AU Link, JM Rich, CM Korat, M Burrows, GG Offner, H Vandenbark, AA AF Link, Jason M. Rich, Cathleen M. Korat, Maya Burrows, Gregory G. Offner, Halina Vandenbark, Arthur A. TI Monomeric DR2/MOG-35-55 recombinant TCR ligand treats relapses of experimental encephalomyelitis in DR2 transgenic mice SO CLINICAL IMMUNOLOGY LA English DT Article DE recombinant TCR ligand; experimental autoimmune; encephalomyelitis; minimum effective dose; multiple sclerosis; HLA-DR2; myelin oligodendrocyte glycoprotein; autoimmunity ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; T-CELL-RECEPTOR; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; PROTEOLIPID PROTEIN; MULTIPLE-SCLEROSIS; DENDRITIC CELLS; PEPTIDE; TOLERANCE; THERAPY; AMELIORATION AB Treatment of human autoimmune diseases such as multiple sclerosis (MS) will likely require agents that can prevent or reverse the inflammatory process that results in clinical relapses and disease progression. We evaluated the ability of a newly designed monomeric recombinant TCR ligand (RTL342M) containing HLA-DR2 peptide-binding domains covalently linked to MOG-35-55 peptide to prevent and treat both the initial episode and subsequent relapses of experimental autoimmune encephalomyelitis (EAE) in HLA-DR2 transgenic mice. Single doses of RTL342M given either i.v. or s.c. to HLA-DR2 mice produced a rapid (within 24 h) and dose-dependent reversal of clinical signs of paralytic EAE, and even a single dose <= 2 mu g could produce a significant treatment effect. Multiple daily doses were even more effective than the same total amount of RTL given as a single dose. By establishing the minimal effective dose, we determined that RTLs may be 50 times more potent than molar equivalent doses of myelin peptide alone. RTL342M given prior to induction of EAE prevented disease in most mice, and the remainder could be successfully retreated with RTL. Most important for clinical application, RTL342M was highly effective for treating EAE relapses when given periodically prior to the relapse or even after relapses had occurred. These data demonstrate the rapid and potent clinical effects of RTL342M at disease onset and during relapses in EAE and establish important principles governing the application of this novel approach as a possible therapy for patients with MS. (c) 2006 Elsevier Inc. All rights reserved. C1 Portland VA Med Ctr, Neuroimmunol Res R&D 31, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. RP Link, JM (reprint author), Portland VA Med Ctr, Neuroimmunol Res R&D 31, SW US Vet Hosp Rd, Portland, OR 97239 USA. EM linkja@ohsu.edu OI Link, Jason/0000-0002-6892-0431 FU NIAID NIH HHS [AI43960]; NINDS NIH HHS [NS46877, NS41965, NS47661] NR 28 TC 14 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD APR PY 2007 VL 123 IS 1 BP 95 EP 104 DI 10.1016/j.clim.2006.12.002 PG 10 WC Immunology SC Immunology GA 150XJ UT WOS:000245252600013 PM 17257899 ER PT J AU Lipsky, BA AF Lipsky, B. A. TI Empirical therapy for diabetic foot infections: are there clinical clues to guide antibiotic selection? SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Editorial Material DE antibiotic therapy; diabetic foot infections; empirical therapy; foot infections; guidelines; treatment ID RESISTANT STAPHYLOCOCCUS-AUREUS; LOWER-EXTREMITY INFECTIONS; ULCERS; BACTERIOLOGY; MULTICENTER; PREVALENCE; PATHOGENS; TRIAL AB Initial antibiotic therapy for diabetic foot infections is usually empirical. Several principles may help to avoid selecting either an unnecessarily broad or inappropriately narrow regimen. First, clinically severe infections require broad-spectrum therapy, while less severe infections may not. Second, aerobic Gram-positive cocci, particularly Staphylococcus aureus (including methicillin-resistant S. aureus (MRSA) for patients at high-risk) should always be covered. Third, therapy should also be targeted at aerobic Gram-negative pathogens if the infection is chronic or has failed to respond to previous antibiotic therapy. Fourth, anti-anaerobe agents should be considered for necrotic or gangrenous infections on an ischaemic limb. Parenteral therapy is needed for severe infections, but oral therapy is adequate for most mild or moderate infections. C1 VA Puget Sound Hlth Care Syst, Primary Care Clin, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. RP Lipsky, BA (reprint author), VA Puget Sound Hlth Care Syst, Primary Care Clin, 1660 S Columbian Way, Seattle, WA 98108 USA. EM Benjamin.lipsky@med.va.gov OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 20 TC 27 Z9 27 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1198-743X J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PD APR PY 2007 VL 13 IS 4 BP 351 EP 353 DI 10.1111/j.1469-0691.2007.01697.x PG 3 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 143JT UT WOS:000244718200001 PM 17359317 ER PT J AU Hwang, RW Herndon, JH AF Hwang, Raymond W. Herndon, James H. TI The business case for patient safety SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Review ID PHYSICIAN ORDER ENTRY; TOTAL HIP-ARTHROPLASTY; ADVERSE DRUG EVENTS; INTENSIVE-CARE UNIT; WRONG-SITE SURGERY; HOSPITALIZED-PATIENTS; HEALTH-CARE; RESOURCE UTILIZATION; MEDICAL ERRORS; NOSOCOMIAL INFECTIONS AB Recent trends have focused attention on improving patient safety in the United States healthcare system. Lapses in patient safety create undue, often preventable, morbidity. These include adverse drug events, adverse surgical events and nosocomial infections. From an organizational perspective, these events are both inefficient and expensive. Many safe practices and quality enhancing improvements, such as computer provider order entry, proper infection surveillance, telemedicine intensive care, and registered nurse staffing are in fact cost-effective. However, in order to fully achieve higher quality, better adverse event reporting and a culture of safety must first be developed. Increased provider recognition, models of success, public awareness and consumer demand are propelling improvements. As we will outline in this review of the current literature, the business case for patient safety is a compelling one, offering substantial economic incentives for achieving the necessary goal of improved patient outcomes. RP Herndon, JH (reprint author), Massachusetts Gen Hosp, Harvard Combined Orthopaed Residency Program, 55 Fruit St, Boston, MA 02114 USA. EM jherndon@partners.org NR 114 TC 2 Z9 2 U1 11 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD APR PY 2007 IS 457 BP 21 EP 34 DI 10.1097/BLO.0b013e3180342816 PG 14 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 155KF UT WOS:000245575600006 PM 17259896 ER PT J AU Shervin, N Rubash, HE Katz, JN AF Shervin, Nina Rubash, Harry E. Katz, Jeffrey N. TI Orthopaedic procedure volume and patient outcomes - A systematic literature review SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Review ID TOTAL HIP-REPLACEMENT; CORONARY ANGIOPLASTY VOLUME; SHORT-TERM MORTALITY; HOSPITAL VOLUME; SURGICAL-VOLUME; SHOULDER ARTHROPLASTY; PROVIDER VOLUME; KNEE REPLACEMENT; ELDERLY-PATIENTS; SURGEON VOLUME AB The association between greater hospital procedure volumes and improved patient outcomes has been well established with respect to a variety of procedures and treatments. However, this association in orthopaedics has not been summarized systematically. We reviewed existing literature on associations between hospital and surgeon procedure volume and patient outcomes in orthopaedic surgery. The patient outcomes examined were mortality, hip dislocation, infection, revision, complications, functional outcome, and satisfaction. Of the 26 articles reviewed, most examined outcomes after primary joint arthroplasties (predominantly hip arthroplasties) with a relatively limited number of studies examining revision arthroplasties, hip fractures, spine, or general orthopaedics. No studies evaluated any other subspecialties. We found an association between higher hospital volumes and lower rates of mortality and hip dislocation. We also found an association between higher surgeon volume and lower rates of hip dislocation. All other associations were negative or inconclusive. In addition, surgeon volume had a greater effect on patients than hospital volume for primary and revision joint arthroplasties, whereas hospital volume was more strongly related to outcome than surgeon volume for the other procedures examined. Our findings suggest the need for additional studies in the various subspecialties to establish more definitive conclusions. C1 Massachusetts Gen Hosp, Harvard Combined Orthopaed Residency Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Sect Clin Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Shervin, N (reprint author), 1 Longfellow Pl,Unit 2524, Boston, MA 02114 USA. EM nshervin@partners.org FU NIAMS NIH HHS [P60 AR47782, K24 AR02123] NR 42 TC 90 Z9 91 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD APR PY 2007 IS 457 BP 35 EP 41 DI 10.1097/BLO.0b013e3180375514 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 155KF UT WOS:000245575600007 PM 17415062 ER PT J AU Warner, JJP Herndon, JH Cole, BJ AF Warner, Jon J. P. Herndon, James H. Cole, Brian J. TI An academic compensation plan for an orthopaedic department SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID PRACTICE EXPENSES; SYSTEMS AB The academic orthopaedic department has the primary goal of providing clinical services, educating orthopaedic surgeons, providing advancements through research and technology development, and creating and maintaining the administrative infrastructure that monitors and enables the department's overall mission. Simultaneous reductions in revenues and increases in the cost to practice medicine pose the greatest challenge to maintaining the academic orthopaedic department. Fundamental differences exist between the private practice and academic orthopaedic surgeon. Most importantly, while their value systems may differ, appropriate incentives (tangible and intangible) must exist to promote growth and retention in a non-private practice setting. A proper compensation plan must consider revenue and nonrevenue-generating activities within the context of the academic orthopaedic department to maintain the department's mission. This article discusses these issues and provides an overview of solutions available to structure an appropriate compensation plan that encourages academic and clinical productivity yet remains sensitive to divergent goals and values of the department's members. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Shoulder Serv, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Rush Univ, Med Ctr, Dept Orthoped, Chicago, IL 60612 USA. Rush Univ, Med Ctr, Dept Anat & Cell Biol, Chicago, IL 60612 USA. RP Warner, JJP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Shoulder Serv, 55 Fruit St,Yawkey Bldg,Suite 3G, Boston, MA 02114 USA. EM jwarner@partners.org NR 27 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD APR PY 2007 IS 457 BP 64 EP 72 DI 10.1097/BLO.0b013e31803372f5 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 155KF UT WOS:000245575600011 ER PT J AU Hariri, S Prestipino, AL Rubash, HE AF Hariri, Sanaz Prestipino, Ann L. Rubash, Harry E. TI The hospital-physician relationship - Past, present, and future SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID CAREER SATISFACTION AB The traditional hospital-physician relationship in the United States was an implicit symbiotic collaboration sheltered by financial success. The health care economic challenges of the 1980s and 1990s unmasked the weaknesses of this relationship as hospitals and doctors often found themselves in direct competition in the struggle to maintain revenue. We recount and examine the history of the largely implicit American hospital-physician relationship and propose a means of establishing formal, explicit hospital-physician collaborations focused on delivering quality patient care and ensuring economic viability for both parties. We present the process of planning a joint hospital-physician ambulatory surgery center (ASC) at a not-for-profit academic institution as an example of a collaboration to negotiate a model embraced by both parties. However, the ultimate success of this new center, as measured in quality of patient care and economic viability, has yet to be determined. C1 Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Anesthesia Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harvard Combined Orthoped Surg Program, Boston, MA 02114 USA. RP Rubash, HE (reprint author), Massachusetts Gen Hosp, Surg Serv, 55 Fruit St,YCOC,Suite 3700, Boston, MA 02114 USA. EM hrubash@partners.org NR 29 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD APR PY 2007 IS 457 BP 78 EP 86 DI 10.1097/BLO.0b013e31803372a7 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 155KF UT WOS:000245575600013 ER PT J AU Wilens, TE Biederman, J Spencer, TJ Adler, LA AF Wilens, Timothy E. Biederman, Joseph Spencer, Thomas J. Adler, Lenard A. TI ADHD: Prevalence, diagnosis, and issues of comorbidity SO CNS SPECTRUMS LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; DEFICIT HYPERACTIVITY DISORDER; CONTROLLED CLINICAL-TRIAL; PLACEBO-CONTROLLED TRIAL; SALTS EXTENDED-RELEASE; FILM-COATED TABLETS; DOUBLE-BLIND; YOUNG-ADULTS; PSYCHIATRIC COMORBIDITY; DRIVING PERFORMANCE AB Attention-deficit/hyperactivity disorder (ADHD) is a lifelong condition that begins in childhood and continues with adult manifestations related to the core symptoms. Approximately 50% to 75% of children with ADHD continue to meet criteria for the disorder as adolescents and adults. Adults with the disorder increasingly present to primary care physicians, psychiatrists, and other practitioners for diagnosis and treatment. Understanding the diagnosis of ADHD in adults requires knowledge of age-dependent decline of symptoms over time. Retrospective recall of symptoms and impairment are valid methods of diagnosing the disorder. ADHD is also a brain disorder with a strong neurobiologic basis, complex etiology, and genetic component. Genetic and environmental vulnerabilities give rise to abnormalities in the brain and subsequent behavioral and cognitive deficits, which may produce the symptoms associated with ADHD. Magnetic resonance imaging studies of ADHD have provided evidence that abnormalities in the brain are caused by the disorder itself rather than treatment of the disorder. Psychiatric comorbidity is common among patients with ADHD and tends to complicate treatment. Acute and long-term use of long-acting stimulant formulations (methylphenidate and amphetamine compounds) have shown robust efficacy and tolerability consistent with the treatment response established in children with ADHID. Non-stimulant medications have demonstrated efficacy as well, and may be preferred in patients with tic and substance use disorders. In this expert roundtable supplement, Timothy E. Wilens, MID, reviews the epidemiology and clinical presentation of adult ADHD. Next, Joseph Biederman, MID, provides an overview of recent advances in the neurobiology of ADHD. Thomas J. Spencer, MID, reviews stimulant treatment of adult ADHID, and Lenard A. Adler concludes with a discussion of non-stimulant trials in adult ADHD. C1 [Wilens, Timothy E.; Biederman, Joseph; Spencer, Thomas J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Wilens, Timothy E.; Spencer, Thomas J.] Massachusetts Gen Hosp, Subst Abuse Serv, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Biederman, Joseph] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Adler, Lenard A.] NYU, Sch Med, Adult ADHD Program, New York, NY USA. RP Wilens, TE (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 81 TC 1 Z9 1 U1 7 U2 23 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD APR PY 2007 VL 12 IS 4 SU 6 BP 3 EP + PG 12 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 241QA UT WOS:000251669700001 ER PT J AU Duda, JE AF Duda, John E. TI History and prevalence of involuntary emotional expression disorder SO CNS SPECTRUMS LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; TRAUMATIC BRAIN-INJURY; PSEUDOBULBAR AFFECT; PATHOLOGICAL LAUGHTER; MULTIPLE-SCLEROSIS; STROKE; INCONTINENCE; DISEASE; DIAGNOSIS; LABILITY AB The syndrome now known as involuntary emotional expression disorder (IEED) is a condition characterized by uncontrollable episodes of laughing and/or crying. It has been known for more than a century, but confusing and conflicting terminology may have hampered the progress of physicians in recognizing this condition. IEED is associated with various neurological disorders and neurodegenerative diseases, including amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease and other dementias, and neurological injuries such as stroke and traumatic brain injury. It is hoped that better defined terminology for IEED may help in the future diagnosis of this debilitating condition, the establishment of accurate prevalence rates for IEED in the varying underlying conditions, and also in removing blame and stigma from sufferers by providing reassurance about the nature of their condition. C1 Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Duda, JE (reprint author), Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. EM john.duda@med.va.gov NR 49 TC 3 Z9 4 U1 1 U2 3 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD APR PY 2007 VL 12 IS 4 SU 5 BP 6 EP 10 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 170WT UT WOS:000246697600002 PM 17426669 ER PT J AU Biederman, J Wilens, TE Spencer, TJ Adler, LA AF Biederman, Joseph Wilens, Timothy E. Spencer, Thomas J. Adler, Lenard A. TI Diagnosis and treatment of adults with attention-deficit/hyperactivity disorder SO CNS SPECTRUMS LA English DT Editorial Material ID DEFICIT HYPERACTIVITY DISORDER; CONTROLLED CLINICAL-TRIAL; PLACEBO-CONTROLLED TRIAL; SALTS EXTENDED-RELEASE; FILM-COATED TABLETS; DOUBLE-BLIND; YOUNG-ADULTS; PSYCHIATRIC COMORBIDITY; DRIVING PERFORMANCE; TIC DISORDERS AB Attention-deficit/hyperactivity disorder (ADHD) is a lifelong condition that begins in childhood and continues with adult manifestations related to the core symptoms. Approximately 50% to 75% of children with ADHD continue to meet criteria for the disorder as adolescents and adults. Adults with the disorder increasingly present to primary care physicians, psychiatrists, and other practitioners for diagnosis and treatment. Understanding the diagnosis of ADHD in adults requires knowledge of age-dependent decline of symptoms over time. Retrospective recall of symptoms and impairment are valid methods of diagnosing the disorder. ADHD is also a brain disorder with a strong neurobiologic basis, complex etiology, and genetic component. Genetic and environmental vulnerabilities give rise to abnormalities in the brain and subsequent behavioral and cognitive deficits, which may produce the symptoms associated with ADHD. Magnetic resonance imaging studies of ADHD have provided evidence that abnormalities in the brain are caused by the disorder itself rather than treatment of the disorder. Psychiatric comorbidity is common among patients with ADHD and tends to complicate treatment. Acute and long-term use of long-acting stimulant formulations (methylphenidate and amphetamine compounds) have shown robust efficacy and tolerability consistent with the treatment response established in children with ADHD. Non-stimulant medications have demonstrated efficacy as well, and may be preferred in patients with tic and substance use disorders. In this expert roundtable supplement, Timothy E. Wilens, MID, reviews the epidemiology and clinical presentation of adult ADHD. Next, Joseph Biederman, MID, provides an overview of recent advances in the neurobiology of ADHD. Thomas J. Spencer, MID, reviews stimulant treatment of adult ADHD, and Lenard A. Adler concludes with a discussion of non-stimulant trials in adult ADHD. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Subst Abuse Serv, Boston, MA 02114 USA. NYU, Sch Med, Adult ADHD Program, New York, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 82 TC 3 Z9 3 U1 4 U2 7 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD APR PY 2007 VL 12 IS 4 BP A1 EP A14 PG 14 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 165VU UT WOS:000246335000001 ER PT J AU Barnato, AE Kahn, JM Rubenfeld, GD McCauley, K Fontaine, D Frassica, JJ Hubmayr, R Jacobi, J Brower, RG Chalfin, D Sibbald, W Asch, DA Kelley, M Angus, DC AF Barnato, Amber E. Kahn, Jeremy M. Rubenfeld, Gordon D. McCauley, Kathleen Fontaine, Dorrie Frassica, Joseph J. Hubmayr, Rolf Jacobi, Judith Brower, Roy G. Chalfin, Donald Sibbald, William Asch, David A. Kelley, Mark Angus, Derek C. TI Prioritizing the organization and management of intensive care services in the United States: The PrOMIS Conference SO CRITICAL CARE MEDICINE LA English DT Article DE intensive care units; critical care; organization; organization and administration; health priorities ID CRITICALLY ILL; WORKFORCE REQUIREMENTS; TRAUMA CENTERS; MORTALITY; LIFE; SHORTAGE; OUTCOMES; SYSTEM; END; EPIDEMIOLOGY AB Objective., Adult critical care services are a large, expensive part of U.S. health care. The current agenda for response to workforce shortages and rising costs has largely been determined by members of the critical care profession without input from other stakeholders. We sought to elicit the perceived problems and solutions to the delivery of critical care services from a broad set of U.S. stakeholders. Design. A consensus process involving purposive sampling of identified stakeholders, preconference Web-based survey, and 2-day conference. Setting: Participants represented healthcare providers, accreditation and quality-oversight groups, federal sponsoring institutions, healthcare vendors, and institutional and individual payers. Subjects. We identified 39 stakeholders for the field of critical care medicine. Thirty-six (92%) completed the preconference survey and 37 (95%) attended the conference. Interventions, None. Measurements and Main Results., Participants expressed moderate to strong agreement with the concerns identified by the critical care professionals and additionally expressed consternation that the critical care delivery system was fragmented, variable, and not patient-centered. Recommended solutions included regionalizing the adult critical care system into "tiers" defined by explicit triage criteria and professional competencies, achieved through voluntary hospital accreditation, supported through an expanded process of competency certification, and monitored through process and outcome surveillance; implementing mechanisms for improved communication across providers and settings and between providers and patients/families; and conducting market research and a public education campaign regarding critical care's promises and limitations. Conclusions. This consensus conference confirms that agreement on solutions to complex healthcare delivery problems can be achieved and that problem and solution frames expand with broader stakeholder participation. This process can be used as a model by other specialties to address priority setting in an era of shifting demographics and increasing resource constraints. C1 Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. Univ Pittsburgh, CRISMA Lab, Dept Crit Care Med, Pittsburgh, PA USA. Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Div Pulm Allergy & Crit Care, Philadelphia, PA 19104 USA. Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. Baystate Med Ctr, Harvard MIT Div Hlth Sci & Technol, Div Pediat Crit Care, Springfield, MA 01199 USA. Mayo Clin Coll Med, Dept Internal Med, Div Pulm & Crit Care Med, Rochester, MN USA. Methodist Hosp Clarian Hlth Partners, Indianapolis, IN USA. Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD USA. Montefiore Med Ctr, Dept Crit Care Med, New York, NY USA. Albert Einstein Coll Med, New York, NY USA. Sunnybrook & Womens Hlth Sci Ctr, Toronto, ON, Canada. Univ Toronto, Dept Med, Toronto, ON, Canada. Univ Penn, Ctr Hlth Equity Res & Promot, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Henry Ford Hlth Syst, Detroit, MI USA. RP Angus, DC (reprint author), Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. EM angusdc@ccm.upmc.edu RI Angus, Derek/E-9671-2012; OI Frassica, Joseph/0000-0001-6453-6726; Asch, David/0000-0002-7970-286X NR 52 TC 59 Z9 61 U1 1 U2 2 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 APR PY 2007 VL 35 IS 4 BP 1003 EP 1011 DI 10.1097/01.CCM.0000259535.06205.B4 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 151PJ UT WOS:000245302400001 PM 17334242 ER PT J AU Stengrevics, S Anderson, C Bethune, C Carroll, D Cierpial, C Donahue, V Griffith, C Haldeman, S Silva, J Snydeman, C Tubridy, A AF Stengrevics, S. Anderson, C. Bethune, C. Carroll, D. Cierpial, C. Donahue, V Griffith, C. Haldeman, S. Silva, J. Snydeman, C. Tubridy, A. TI Cardiac nursing practice group: Uniting cardiac nurses with a shared vision SO CRITICAL CARE NURSE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. EM sstengrevics@partners.org NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CRITICAL CARE NURSES PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 0279-5442 J9 CRIT CARE NURSE JI Crit. Care Nurse PD APR PY 2007 VL 27 IS 2 BP 97 EP 97 PG 1 WC Critical Care Medicine; Nursing SC General & Internal Medicine; Nursing GA 151PY UT WOS:000245304100049 ER PT J AU Haldeman, S Ciehial, C Silva, J AF Haldeman, S. Ciehial, C. Silva, J. TI Improving safety for the anticoagulated patient: Falls and medication administration SO CRITICAL CARE NURSE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. EM SHaldeman@Partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CRITICAL CARE NURSES PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 0279-5442 J9 CRIT CARE NURSE JI Crit. Care Nurse PD APR PY 2007 VL 27 IS 2 BP 108 EP 108 PG 1 WC Critical Care Medicine; Nursing SC General & Internal Medicine; Nursing GA 151PY UT WOS:000245304100106 ER PT J AU Collins, J Collage, J Jeffries, M AF Collins, J. Collage, J. Jeffries, M. TI Sweet success: Implementing a comprehensive hospital-wide teaching plan to educate the diabetes mellitus inpatient SO CRITICAL CARE NURSE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jcollins7@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CRITICAL CARE NURSES PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 0279-5442 J9 CRIT CARE NURSE JI Crit. Care Nurse PD APR PY 2007 VL 27 IS 2 BP 124 EP 124 PG 1 WC Critical Care Medicine; Nursing SC General & Internal Medicine; Nursing GA 151PY UT WOS:000245304100186 ER PT J AU Yaffe, K AF Yaffe, Kristine TI Metabolic syndrome and cognitive decline SO CURRENT ALZHEIMER RESEARCH LA English DT Article; Proceedings Paper CT Workshop on Exploring the Links between Obesity and Alzheimers Disease CY JUN 20-21, 2006 CL Bethesda, MD DE metabolic syndrome; cognition; dementia; insulin resistance ID CARDIOVASCULAR RISK-FACTORS; TYPE-2 DIABETES-MELLITUS; C-REACTIVE PROTEIN; ALZHEIMER-DISEASE; OLDER WOMEN; BLOOD-PRESSURE; ELDERLY-WOMEN; LATE-LIFE; DEMENTIA; INFLAMMATION AB Over 33% of women and 20% of men aged 65 and older will develop dementia during their lifetime, and many more will develop a milder form of cognitive impairment. Given the anticipated exponential increase in both the incidence and prevalence of cognitive impairment in the next century, it is critical to identify preventative strategies to thwart this critical public health issue. The metabolic syndrome is comprised of five cardiovascular risk factors that include abdominal obesity, hypertriglyceridemia, low high density lipoprotein (HDL) levels, hypertension, and hyperglycemia. The prevalence of the metabolic syndrome, similar to that for cognitive disorders, increases dramatically with age. While several of the individual components of the metabolic syndrome have been linked to risk of developing dementia and cognitive impairment, few studies have looked at the components of the metabolic syndrome as a whole. We found, in two separate studies involving elders of different ethnicities, that the metabolic syndrome is a risk factor for accelerated cognitive aging. This was especially true for elders with the metabolic syndrome and with elevated serum level of inflammation. Several possible mechanisms may explain the association between the metabolic syndrome and cognitive decline including micro- and macro-vascular disease, inflammation, adiposity and insulin resistance. If metabolic syndrome is associated with increased risk of developing cognitive impairment, regardless of mechanism, then early identification and treatment of these individuals might offer avenues for disease course modification. C1 Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, Box 181,4150 Clement St, San Francisco, CA 94121 USA. EM Kristine.yaffe@ucsf.edu FU NIDDK NIH HHS [DK070713] NR 39 TC 52 Z9 54 U1 3 U2 9 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD APR PY 2007 VL 4 IS 2 BP 123 EP 126 DI 10.2174/156720507780362191 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 156BH UT WOS:000245622400006 PM 17430234 ER PT J AU Cohen, A Horton, ES AF Cohen, Allison Horton, Edward S. TI Progress in the treatment of type 2 diabetes: new pharmacologic approaches to improve glycemic control SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Review DE DPP-4 inhibitors; GIP; GLP-1; incretin mimetics; oral antidiabetic drugs; rimonabant; type 2 diabetes ID DIPEPTIDYL-PEPTIDASE-IV; METFORMIN-TREATED PATIENTS; GLUCAGON-LIKE PEPTIDE-1; CANNABINOID-1 RECEPTOR BLOCKER; ORAL ANTIHYPERGLYCEMIC THERAPY; SULFONYLUREA DRUGS INCREASE; RANDOMIZED CONTROLLED-TRIAL; CARDIOVASCULAR RISK-FACTORS; ACUTE MYOCARDIAL-INFARCTION; BLOOD-GLUCOSE CONTROL AB Background: Type 2 diabetes mellitus (T2DM) is a leading cause of morbidity and mortality that places a substantial economic and health burden on the public. Successful management of T2DM requires strict control of glycemia as well as other risk factors to prevent disease progression. Despite the availability of multiple classes of oral antidiabetic drugs and insulin, the majority of patients fail to attain or maintain tight glycemic control over time, raising their risk of serious microvascular and macrovascular complications. Scope: This review briefly outlines current standards of diabetes treatment and explores several new and investigational approaches. It is based on MEDLINE literature searches (1966-August 2006) and on abstracts from the American Diabetes Association Scientific Sessions (2002-2006) and the European Association for the Study of Diabetes Annual Meetings (1998-2006). Articles concerning basic science, preclinical, and clinical trial results were selected for this review based on their originality and relevance. Findings: Medical professional societies and other specialist groups have proposed a series of practical steps to enable more patients with T2DM to reach treatment goals. Among their most important recommendations is a call for new drugs to stabilize or reverse the progressive pancreatic islet-cell dysfunction that characterizes the disease. New modalities, such as incretin mimetics and DPP-4 inhibitors, are now emerging from clinical development and will provide patients with more treatment options. Conclusions: It appears likely that early and aggressive treatment with multiple drug combinations will become more common in the management of T2DM. The new treatment modalities discussed here offer hope for improved outcomes and for meeting the considerable public health challenges posed by this complex condition. However, long-term studies are needed to determine durability of treatment effects, as well as the ultimate role of these new agents in the management of patients with T2DM. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. RP Cohen, A (reprint author), Joslin Diabet Ctr, 1 Joslin Pl,Clin Res 3rd Floor,Room 348, Boston, MA 02215 USA. EM allison.cohen@joslin.harvard.edu NR 89 TC 35 Z9 35 U1 1 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0300-7995 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD APR PY 2007 VL 23 IS 4 BP 905 EP 917 DI 10.1185/030079907X182068 PG 13 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 162JF UT WOS:000246082400026 PM 17407648 ER PT J AU Hurlbut, GD Kankel, MW Lake, RJ Artavanis-Tsakonas, S AF Hurlbut, Gregory D. Kankel, Mark W. Lake, Robert J. Artavanis-Tsakonas, Spyros TI Crossing paths with Notch in the hyper-network SO CURRENT OPINION IN CELL BIOLOGY LA English DT Review ID ELEGANS VULVAL DEVELOPMENT; GROWTH-FACTOR RECEPTOR; SIGNALING PATHWAYS; DROSOPHILA EYE; STEM-CELLS; BRANCHING MORPHOGENESIS; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; MAPK ACTIVATION; SONIC-HEDGEHOG AB The development of complex and diverse metazoan morphologies is coordinated by a surprisingly small number of evolutionarily conserved signaling mechanisms. These signals can act in parallel but often appear to function as an integrated hyper-network. The nodes defining this complex molecular circuitry are poorly understood, but the biological significance of pathway cross-talk is profound. The importance of such large-scale signal integration is exemplified by Notch and its ability to cross-talk with all the major pathways to influence cell differentiation, proliferation, survival and migration. The Notch pathway is; thus, a useful paradigm to illustrate the complexity of pathway cross-talk: its pervasiveness, context dependency, and importance in development and disease. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc,Dept Cell Biol, Charlestown, MA USA. Univ Paris Sud 11, Fac Sci Orsay, Paris, France. Coll France, F-75231 Paris, France. RP Artavanis-Tsakonas, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc,Dept Cell Biol, Charlestown, MA USA. EM tsakonas@helix.mgh.harvard.edu NR 115 TC 152 Z9 157 U1 1 U2 6 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD APR PY 2007 VL 19 IS 2 BP 166 EP 175 DI 10.1016/j.ceb.2007.02.012 PG 10 WC Cell Biology SC Cell Biology GA 154YD UT WOS:000245543500009 PM 17317139 ER PT J AU Ganem, NJ Storchova, Z Pellman, D AF Ganem, Neil J. Storchova, Zuzana Pellman, David TI Tetraploidy, aneuploidy and cancer SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID KINETOCHORE-MICROTUBULE ATTACHMENT; SPINDLE ASSEMBLY CHECKPOINT; CYTOKINESIS FAILURE; MAMMALIAN-CELLS; CHROMOSOMAL INSTABILITY; AURORA-B; P53; PROGRESSION; POLYPLOIDY; PROTEIN AB Aneuploidy is one of the most obvious differences between normal and cancer cells. However, there remains debate over how aneuploid cells arise and whether or not they are a cause or consequence of tumorigenesis. One proposed route to aneuploid cancer cells is through an unstable tetraploid intermediate. Supporting this idea, recent studies demonstrate that tetraploidy promotes chromosomal aberrations and tumorigenesis in vivo. These tetraploid cells can arise by a variety of mechanisms, including mitotic slippage, cytokinesis failure, and viral-induced cell fusion. Furthermore, new studies suggest that there might not be a ploidy-sensing checkpoint that permanently blocks the proliferation of tetraploid cells. Therefore, abnormal division of tetraploid cells might facilitate genetic changes that lead to aneuploid cancers. C1 Harvard Univ, Sch Med, Childrens Hosp, Dana Farber Canc Inst,Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. RP Pellman, D (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Dana Farber Canc Inst,Dept Pediat Oncol, Boston, MA 02115 USA. EM david_pellman@dfci.harvard.edu FU NCI NIH HHS [R01CA98537]; NIGMS NIH HHS [5T32GM008704] NR 53 TC 344 Z9 357 U1 2 U2 23 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD APR PY 2007 VL 17 IS 2 BP 157 EP 162 DI 10.1016/j.gde.2007.02.011 PG 6 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 162LW UT WOS:000246089900013 PM 17324569 ER PT J AU Ng, SYM Yoshida, T Georgopoulos, K AF Ng, Samuel Yao-Ming Yoshida, Toshimi Georgopoulos, Katia TI Ikaros and chromatin regulation in early hematopoiesis SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID COMMON LYMPHOID PROGENITORS; STEM-CELLS; HISTONE DEACETYLASE; REMODELING COMPLEX; LINEAGE COMMITMENT; BONE-MARROW; IDENTIFICATION; DIFFERENTIATION; CANCER AB Hematopoiesis is the developmental process by which all blood and immune cells are generated. A decade-old scheme has supported an early and complete separation of the erythro-myeloid from the lymphoid lineages. Recent advances have redrawn this map, separating lymphoid and myeloid from erythroid programs early in development. Subsequently, the fate restriction of both the lympho-myeloid and the erythro-megalkaryocyte progenitors is dependent on lkaros and its associated chromatin regulators. Genetic studies of this family of nuclear factors are now providing unique insight into the functional molecular signatures that bestow plasticity to the hematopoietic stem cell and its early progeny. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Georgopoulos, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM katia.georgopoulos@cbrc2.mgh.harvard.edu FU NIAID NIH HHS [5R01 AI042254, 5T32 AI07529, 4R37 AI33062, 5R01 AI038342, R37 AI033062] NR 29 TC 46 Z9 47 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 2007 VL 19 IS 2 BP 116 EP 122 DI 10.1016/j.coi.2007.02.014 PG 7 WC Immunology SC Immunology GA 152IL UT WOS:000245355400002 PM 17307348 ER PT J AU Anawalt, BD AF Anawalt, Bradley D. TI Update on the development of male hormonal contraceptives SO CURRENT OPINION IN INVESTIGATIONAL DRUGS LA English DT Review DE androgen; gonadotropin; gonadotropin-releasing hormone antagonist; male contraception; progestin; spermatogenesis; testosterone ID TESTOSTERONE-INDUCED AZOOSPERMIA; NORMAL MEN; CHINESE MEN; SPERMATOGENIC SUPPRESSION; NORETHISTERONE ENANTHATE; LEVONORGESTREL IMPLANTS; CYPROTERONE-ACETATE; YOUNG MEN; ANTAGONIST; UNDECANOATE AB Efficacy trials have shown that male hormonal contraceptives can be effective, safe and reversible. A combination of a long-acting injectable testosterone plus a progestin is most likely to be the first commercially available male hormonal contraceptive. Some potential daily oral or transdermal testosterone plus progestin formulations are also being investigated. In addition, researchers have discovered promising novel drugs such as selective androgen receptor modulators and oral gonadotropin-releasing hormone antagonists that may prove useful in male hormonal contraceptive regimens. This review briefly summarizes some of the more recent findings in the development of male hormonal contraceptives. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Anawalt, BD (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM bradley.anawalt@va.gov NR 42 TC 0 Z9 0 U1 0 U2 0 PU THOMSON REUTERS (SCIENTIFIC) LTD PI LONDON PA 77 HATTON GARDEN, LONDON, EC1N 8JS, ENGLAND SN 1472-4472 EI 2040-3429 J9 CURR OPIN INVEST DR JI Curr. Opin. Investig. Drugs PD APR PY 2007 VL 8 IS 4 BP 318 EP 323 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 151AQ UT WOS:000245261100007 PM 17458182 ER PT J AU Schacter, DL Wig, GS Stevens, WD AF Schacter, Daniel L. Wig, Gagan S. Stevens, W. Dale TI Reductions in cortical activity during priming SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Review ID INFERIOR TEMPORAL CORTEX; BRAIN ACTIVITY; EXPLICIT MEMORY; NEURAL MECHANISMS; FUSIFORM CORTEX; VISUAL MEMORY; REPETITION; FMRI; REPRESENTATIONS; COMPONENTS AB Priming is a nonconscious form of memory in which an encounter with a stimulus influences the subsequent identification, production or classification of the same or a related stimulus. Neuroimaging studies have revealed that behavioral priming is typically accompanied by reduced activity in several cortical regions. We review recent studies that have concerned two key issues. First, specificity effects produced by changes between study and test in either the physical features of stimuli or the behavioral response reveal cortical sensitivity to the perceptual, conceptual and stimulus-to-decision mapping properties of primed items. Second, correlations between behavioral priming and activity reductions are robust across a range of tasks and procedures in prefrontal regions but not in posterior regions. On the basis of these recent studies, we suggest that the reduction in cortical activity during priming involves at least two different mechanisms. C1 Harvard Univ, Dept Psychol, Boston, MA 02138 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Schacter, DL (reprint author), Harvard Univ, Dept Psychol, Boston, MA 02138 USA. EM dls@wjh.harvard.edu OI Schacter, Daniel/0000-0002-2460-6061 FU NIA NIH HHS [AG08441]; NIMH NIH HHS [MH060941] NR 46 TC 155 Z9 159 U1 2 U2 14 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD APR PY 2007 VL 17 IS 2 BP 171 EP 176 DI 10.1016/j.conb.2007.02.001 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 165RX UT WOS:000246324300007 PM 17303410 ER PT J AU Yang, YG Sykes, M AF Yang, Yong-Guang Sykes, Megan TI Tolerance in xenotransplantation SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE pig; tolerance; xenotransplantation ID GENE-KNOCKOUT PIGS; LONG-TERM SURVIVAL; T-CELL TOLERANCE; THYMIC LOBE TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; CARDIAC XENOGRAFT SURVIVAL; DONOR-SPECIFIC TRANSFUSION; PORCINE ENDOTHELIAL-CELLS; HUMAN NK CELLS; MIXED CHIMERISM AB Purpose of review This review assesses recent progress in the induction of xenograft tolerance, with a focus on the strategies showing promise in preclinical large animal models. Recent findings True xenograft tolerance has been limited to rodent models. In large animal models, T cell costimulatory blockers have been widely used as a key component of immunosuppression in controlling xenograft rejection. Despite significant improvements in xenograft survival, blocking T cell costimulation has not yet shown the ability to achieve tolerance in primates. Development of an effective, nontoxic recipient conditioning regimen allowing donor marrow cell engraftment will be essential to the translation of the mixed chimerism approach to clinical xenotransplantation. Costimulatory blockade has been shown to promote this type of tolerance in rodent xenograft models. Thymic xenotransplantation with Gal-transferase knockout source pigs, for the first time, permitted porcine kidney xenograft survival in nonhuman primates for several months without rejection. Summary Tolerance induction is likely to be critical for clinical success of xenotransplantation. With further investigation, induction of xenotransplantation tolerance may be achieved in nonhuman primates and ultimately in humans. C1 Harvard Univ, Sch Med, Transplantat Biol Res Ctr, Massachusetts Gen Hosp,Bone Marrow Transplantat S, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Sch Med, Transplantat Biol Res Ctr, Massachusetts Gen Hosp,Bone Marrow Transplantat S, MGH E Bldg 149-5102,13th St, Boston, MA 02129 USA. EM megan.sykes@tbrc.mgh.harvard.edu NR 82 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1087-2418 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD APR PY 2007 VL 12 IS 2 BP 169 EP 175 DI 10.1097/MOT.0b013e3280146483 PG 7 WC Transplantation SC Transplantation GA 155JT UT WOS:000245574400011 ER PT J AU Myaskovsky, L Switzer, GE Crowley-Matoka, M Unruh, M DiMartini, AF Dew, MA AF Myaskovsky, Larissa Switzer, Galen E. Crowley-Matoka, Megan Unruh, Mark DiMartini, Andrea F. Dew, Mary Amanda TI Psychosocial factors associated with ethnic differences in transplantation SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE psychosocial issues; racial/ethnic differences; transplantation ID CADAVER KIDNEY-TRANSPLANT; ORGAN DONATION; AFRICAN-AMERICANS; LIVER-TRANSPLANTATION; RACIAL-DIFFERENCES; EDUCATION-PROGRAM; UNITED-STATES; HEALTH-CARE; WILLINGNESS; ATTITUDES AB Purpose of review Ethnic minorities in the United States are overrepresented among patients in need of organ transplantation. This review highlights how psychosocial factors are associated with ethnic differences in the use of transplantation to treat end-stage organ disease. Recent findings Recent empirical work has examined ethnic group differences in deceased organ donation, living organ donation, willingness to undergo transplantation, and choosing living versus deceased organ transplantation. There are marked differences, however, in the extent of available research across types of transplantation, with the bulk of research focusing on kidney transplantation. Summary Psychosocial factors, including mistrust of the medical system, perceived discrimination, social support and coping, and transplant knowledge and attitudes, are associated with ethnic differences in solid organ donation and transplantation. Recent research demonstrates that ethnic minorities are less willing to donate organs for a variety of psychosocial reasons. There is a paucity of research focused on ethnic minority groups other than African-Americans and considering end-organ diseases aside from kidney failure. Finally, studies of ethnic differences in transplantation are often limited by cross-sectional designs. Longitudinal research would better indicate whether known ethnic differences in psychosocial factors predict differences in physical or mental health outcomes after donation and transplantation. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Anthropol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Epidemiol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Psychol, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Dept Anthropol, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Dept Epidemiol, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Dept Psychol, Pittsburgh, PA USA. RP Myaskovsky, L (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C 151C-U, Pittsburgh, PA 15240 USA. EM myaskovskyl@upmc.edu NR 55 TC 6 Z9 6 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1087-2418 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD APR PY 2007 VL 12 IS 2 BP 182 EP 187 DI 10.1097/MOT.0b013e32805b7192 PG 6 WC Transplantation SC Transplantation GA 155JT UT WOS:000245574400013 ER PT J AU Newton, AW Vandeven, AM AF Newton, Alice W. Vandeven, Andrea M. TI Update on child maltreatment SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE child abuse; child sexual abuse; neglect; shaken baby syndrome; traumatic brain injury ID SHAKEN-BABY-SYNDROME; SUDDEN-INFANT-DEATH; ABUSE FATALITIES; YOUNG-CHILDREN; UNITED-STATES; SEXUAL-ABUSE; RISK-FACTORS; HEAD-INJURY; ADOLESCENTS; NEGLECT AB Purpose of review Recent literature regarding assessment, management and prevention of child maltreatment will be considered. Unexplained infant and child death will also be reviewed. Recent findings Controversies in the evaluation of unexpected infant death and inflicted traumatic brain injury are ongoing. Evidence continues to accumulate describing the serious long-term sequelae of child maltreatment. Studies have examined the earliest beginnings of these adverse outcomes commencing in childhood. Despite sustained efforts to develop a variety of training and intervention programs, the deployment of these efforts has been hampered by the lack of evidence that they make any difference in improving recognition of child abuse or in preventing recurrent maltreatment. There is a great need in the child abuse field for more formal, rigorous assessment of all manner of intervention programs. Summary Efforts to improve the recognition of and management of child abuse need to be sustained. As our understanding of child maltreatment continues to grow, evidence-based interventions will likely improve outcomes for abused children and their families. General pediatricians are often the first to notice signs and symptoms of possible child maltreatment; collaboration with hospital-based Child Protection Teams is critical when considering the possibility of abuse or neglect. C1 Harvard Univ, Childrens Hosp, Massachusetts Gen Hosp, Dept Pediat,Child Protect Program,Med Sch, Cambridge, MA 02138 USA. Childrens Hosp, Div Gen Pediat, Boston, MA USA. RP Newton, AW (reprint author), Childrens Hosp, Child Protect Program, 300 Longwood Ave, Boston, MA 02115 USA. EM alice.newton@childrens.harvard.edu NR 43 TC 11 Z9 11 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD APR PY 2007 VL 19 IS 2 BP 223 EP 229 DI 10.1097/MOP.0b013e32809f9543 PG 7 WC Pediatrics SC Pediatrics GA 154RZ UT WOS:000245526500018 PM 17496770 ER PT J AU Pielop, JA Phillips, R Rosen, T AF Pielop, Josie A. Phillips, Rhea Rosen, Ted TI Actinobacillus actinomycetemcomitans isolated from a case of cutaneous botryomycosis SO CUTIS LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; INFECTION; MYCETOMA AB Cutaneous botryomycosis is an uncommon chronic skin infection that appears as a localized suppurative plaque or nodule with superficial crusting or ulceration. Although clinically suggestive of a deep fungal or atypical mycobacterial infection, botryomycosis is bacterial in origin. Staphylococcus aureus is the most frequent organism cultured; however, gram-negative bacilli including Pseudomonas aeruginosa, Proteus species, and Escherichia coli also have been isolated from botryomycotic infections.(1) Histologic examination reveals characteristic granules with basophilic centers composed of clumped nonfilamentous bacteria surrounded by an eosinophilic periphery (Splendore-Hoeppli phenomenon). Foreign bodies, impaired host immunity, and virulent organisms are possible pathogenic factors. C1 Baylor Coll Med, Dept Dermatol, Houston, TX 77030 USA. Michael E DeBakey Vet Adm Med Ctr, Houston, TX USA. RP Rosen, T (reprint author), Baylor Coll Med, Dept Dermatol, 1 Baylor Plaza FB840, Houston, TX 77030 USA. EM vampireted@aol.com NR 22 TC 1 Z9 1 U1 0 U2 0 PU QUADRANT HEALTHCOM INC PI PARSIPPANY PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA SN 0011-4162 J9 CUTIS JI Cutis PD APR PY 2007 VL 79 IS 4 BP 293 EP 296 PG 4 WC Dermatology SC Dermatology GA 160VI UT WOS:000245970000007 PM 17500377 ER PT J AU Adams, DS Masi, A Levin, M AF Adams, Dany S. Masi, Alessio Levin, Michael TI H+ pump-dependent changes in membrane voltage are an early mechanism necessary and sufficient to induce Xenopus tail regeneration SO DEVELOPMENT LA English DT Article DE regeneration; Xenopus; tail; ion pump; H+ flow ID LEFT-RIGHT ASYMMETRY; APPLIED ELECTRIC-FIELD; SPINAL-CORD HEMISECTION; CELL-CYCLE PROGRESSION; LIMB REGENERATION; NERVE REGENERATION; GAP-JUNCTIONS; HUMAN KERATINOCYTES; POTASSIUM CHANNELS; GUINEA-PIG AB In many systems, ion flows and long-term endogenous voltage gradients regulate patterning events, but molecular details remain mysterious. To establish a mechanistic link between biophysical events and regeneration, we investigated the role of ion transport during Xenopus tail regeneration. We show that activity of the V-ATPase H+ pump is required for regeneration but not wound healing or tail development. The V-ATPase is specifically upregulated in existing wound cells by 6 hours post-amputation. Pharmacological or molecular genetic loss of V-ATPase function and the consequent strong depolarization abrogates regeneration without inducing apoptosis. Uncut tails are normally mostly polarized, with discrete populations of depolarized cells throughout. After amputation, the normal regeneration bud is depolarized, but by 24 hours post-amputation becomes rapidly repolarized by the activity of the V-ATPase, and an island of depolarized cells appears just anterior to the regeneration bud. Tail buds in a nonregenerative 'refractory' state instead remain highly depolarized relative to uncut or regenerating tails. Depolarization caused by V-ATPase loss-of-function results in a drastic reduction of cell proliferation in the bud, a profound mispatterning of neural components, and a failure to regenerate. Crucially, induction of H+ flux is sufficient to rescue axonal patterning and tail outgrowth in otherwise non-regenerative conditions. These data provide the first detailed mechanistic synthesis of bioelectrical, molecular and cell-biological events underlying the regeneration of a complex vertebrate structure that includes spinal cord, and suggest a model of the biophysical and molecular steps underlying tail regeneration. Control of H+ flows represents a very important new modality that, together with traditional biochemical approaches, may eventually allow augmentation of regeneration for therapeutic applications. C1 Harvard Univ, Sch Dent Med, Ctr Regenerat & Dev Biol, Forsyth Inst, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. RP Levin, M (reprint author), Harvard Univ, Sch Dent Med, Ctr Regenerat & Dev Biol, Forsyth Inst, 140 The Fenway, Boston, MA 02115 USA. EM mlevin@forsyth.org OI Masi, Alessio/0000-0002-0361-0950 FU NCRR NIH HHS [C06 RR 11244, P41 RR 001395]; NIDCR NIH HHS [K22 DE 016633, K22 DE016633, K22 DE016633-03]; NIGMS NIH HHS [GM 06227] NR 98 TC 115 Z9 118 U1 1 U2 13 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD APR 1 PY 2007 VL 134 IS 7 BP 1323 EP 1335 DI 10.1242/dev.02812 PG 13 WC Developmental Biology SC Developmental Biology GA 144YM UT WOS:000244832500009 PM 17329365 ER PT J AU Pellock, BJ Buff, E White, K Hariharan, IK AF Pellock, Brett J. Buff, Eugene White, Kristin Hariharan, Iswar K. TI The Drosophila tumor suppressors Expanded and Merlin differentially regulate cell cycle exit, apoptosis, and Wingless signaling SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Merlin; Expanded; Wingless; Hippo; apoptosis; tumor suppressor; cell cycle ID MORPHOGENETIC FURROW; PROMOTES APOPTOSIS; IMAGINAL DISKS; PROLIFERATION ARREST; GENETIC MOSAICS; EYE DEVELOPMENT; PROTEIN-KINASE; GROWTH; HIPPO; POLARITY AB Mutations that inactivate either merlin (mer) or expanded (ex) result in increased cell growth and proliferation in Drosophila. Both Mer and Ex are members of the Band 4.1 protein superfamily, and, based on analyses of mer ex double mutants, they are proposed to function together in at least a partially redundant manner upstream of the Hippo (Hpo) and Warts (Wts) proteins to regulate cell growth and division. By individually analyzing ex and mer mutant phenotypes, we have found important qualitative and quantitative differences in the ways Mer and Ex function to regulate cell proliferation and cell survival. Though both mer and ex restrict cell and tissue growth, ex clones exhibit delayed cell cycle exit in the developing eye, while mer clones do not. Conversely, loss of mer substantially compromises normal developmental apoptosis in the pupal retina, while loss of ex has only mild effects. Finally, ex has a role in regulating Wingless protein levels in the eye that is not obviously shared by either mer or hpo. Taken together, our data suggest that Mer and Ex differentially regulate multiple downstream pathways. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Hariharan, IK (reprint author), Univ Calif Berkeley, Dept Mol & Cell Biol, 361 LSA, Berkeley, CA 94720 USA. EM ikh@berkeley.edu RI White, Kristin/D-7936-2013 FU NCI NIH HHS [P01 CA095281, CA95281]; NIGMS NIH HHS [GM55568, R01 GM055568, GM61672, R01 GM061672] NR 72 TC 75 Z9 76 U1 2 U2 9 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 APR 1 PY 2007 VL 304 IS 1 BP 102 EP 115 DI 10.1016/j.ydbio.2006.12.021 PG 14 WC Developmental Biology SC Developmental Biology GA 151LC UT WOS:000245290600010 PM 17258190 ER PT J AU Walker, AK Boag, PR Blackwell, TK AF Walker, Amy K. Boag, Peter R. Blackwell, T. Keith TI Transcription reactivation steps stimulated by oocyte maturation in C-elegans SO DEVELOPMENTAL BIOLOGY LA English DT Article DE oocyte; germ cell; oocyte maturation; meiosis; C. elegans; transcription; CTD; CTD phosphatase; FCP-1; ubiquitylation ID RNA-POLYMERASE-II; ANAPHASE-PROMOTING COMPLEX; EMBRYONIC GERM LINEAGE; CAENORHABDITIS-ELEGANS; GENE-EXPRESSION; MEIOTIC MATURATION; SACCHAROMYCES-CEREVISIAE; FCP1 PHOSPHATASE; TERMINAL DOMAIN; CELL LINEAGE AB Developing oocytes produce materials that will support early embryonic development then cease transcription before fertilization. Later, a distinct transcription program is established in the embryo. Little is understood about how these global gene regulation transitions are effected. We have investigated in C elegans how oocyte transcription is influenced by maturation, a process that releases meiotic arrest and prepares for fertilization. By monitoring transcription-associated phosphorylation of the RNA polymerase II (Pol II) C-terminal domain (CTD), we find that oocyte transcription shuts down independently of maturation. Surprisingly, maturation signals then induce CTD phosphorylation that is associated specifically with transcription initiation steps and accumulates to high levels when expression of the CTD phosphatase FCP-1 is inhibited. This CTD phosphorylation is also uncovered when a ubiquitylation pathway is blocked, or when maturation is stimulated precociously. CTD phosphorylation is similarly detected during embryonic mitosis, when transcription is also largely silenced. We conclude that oocyte maturation signals induce abortive transcription events in which FCP-1 may recycle phosphorylated Pol II and that analogous processes may occur during mitosis. Our findings suggest that maturation signals may initiate preparations for embryonic transcription, possibly as part of a broader program that begins the transition from maternal to zygotic gene expression. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Stem Cell Inst, Dept Pathol, Joslin Diabet Ctr,Med Sch,Sect Dev & Stem Cell Bi, Boston, MA 02215 USA. RP Blackwell, TK (reprint author), Harvard Univ, Stem Cell Inst, Dept Pathol, Joslin Diabet Ctr,Med Sch,Sect Dev & Stem Cell Bi, 1 Joslin Pl, Boston, MA 02215 USA. EM keith.blackwell@joslin.harvard.edu FU NIGMS NIH HHS [GM63826, R01 GM063826] NR 58 TC 17 Z9 17 U1 1 U2 2 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 APR 1 PY 2007 VL 304 IS 1 BP 382 EP 393 DI 10.1016/j.ydbio.2006.12.039 PG 12 WC Developmental Biology SC Developmental Biology GA 151LC UT WOS:000245290600031 PM 17291483 ER PT J AU Fiorina, P Jurewicz, M Tanaka, K Behazin, N Augello, A Vergani, A Von Adrian, U Smith, NR Sayegh, MH Abdi, R AF Fiorina, Paolo Jurewicz, Mollie Tanaka, Katsunori Behazin, Negin Augello, Andrea Vergani, Andrea Von Adrian, Uli Smith, Neal R. Sayegh, Mohamed H. Abdi, Reza TI Characterization of donor dendritic cells and enhancement of dendritic cell efflux with cc-chemokine ligand 21 - A novel strategy to prolong islet allograft survival SO DIABETES LA English DT Article ID IN-VIVO DEPLETION; CD8(+) T-CELLS; RECEPTOR EXPRESSION; DIABETES-MELLITUS; LYMPHOID ORGANS; TRANSPLANTATION; REJECTION; IMMUNOGENICITY; ANTIGEN; RAT AB Dendritic cells (DCs) are the most potent antigen-presenting cells, yet little data are available on the differential characteristics of donor and recipient DCs (dDCs and rDCs, respectively) during the process of islet allograft rejection. DTR-GFP-DC mice provide a novel tool to monitor DC trafficking and characteristics during allograft rejection. We show rapid migration of dDCs to recipient lymphoid tissues as early as 3 h post-islet allotransplantation. Compared with rDCs, dDCs express different patterns of chemokine receptors, display differential proliferative capacity, and exhibit a higher level of maturity; these findings could be attributed to the effects of injury that dDCs undergo during islet cell preparation and engraftment. Intriguingly, we detected dDCs in the spleen of recipients long after rejection of islet allografts. Given that dDCs express high levels of CCR7, islets were cultured before transplant with the ligand for CCR7 (CCL21). This novel method, which enabled us to enhance the efflux of dDCs from islet preparations, resulted in a prolongation of islet allograft survival in immunocompetent recipients. This study introduces dDCs and rDCs as two distinct types of DCs and provides novel data with clinical implications to use chemokine-based DC-depleting strategies to prolong islet allograft survival. C1 Harvard Univ, Sch Med, Transplantat Res Ctr, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Transplantat Res Ctr, Brigham & Womens Hosp, Boston, MA 02115 USA. Ist Sci San Raffaele, Dept Med, Milan, Italy. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA USA. RP Abdi, R (reprint author), Harvard Univ, Sch Med, Transplantat Res Ctr, Childrens Hosp, 221 Longwood Ave, Boston, MA 02115 USA. EM rabdi@rics.bwh.harvard.edu RI von Andrian, Ulrich/A-5775-2008; Augello, Andrea/C-7321-2013 OI Augello, Andrea/0000-0001-5959-7989 NR 45 TC 25 Z9 26 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 2007 VL 56 IS 4 BP 912 EP 920 DI 10.2337/db06-1445 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 157CW UT WOS:000245697200002 PM 17287465 ER PT J AU Lachin, JM Christophi, CA Edelstein, SL Ehrmann, DA Hamman, RF Kahn, SE Knowler, WC Nathan, DM AF Lachin, John M. Christophi, Costas A. Edelstein, Sharon L. Ehrmann, David A. Hamman, Richard F. Kahn, Steven E. Knowler, William C. Nathan, David M. CA DPP Res Grp TI Factors associated with diabetes onset during metformin versus placebo therapy in the Diabetes Prevention Program SO DIABETES LA English DT Article ID LIFE-STYLE INTERVENTION; ORAL GLUCOSE-TOLERANCE; BETA-CELL FUNCTION; INSULIN-SECRETION; MELLITUS; SENSITIVITY; RISK AB In the Diabetes Prevention Program, treatment of subjects with impaired glucose tolerance with metformin > 3.2 years reduced the risk of developing type 2 diabetes by 30% compared with placebo. This study describes the mechanisms of this effect. In proportional hazards regression models with 2,155 subjects, changes in weight, the insulinogenic index (IGR), fasting insulin, and proinsulin were predictive of diabetes, though to different degrees within each group. The mean change in weight, fasting insulin, and proinsulin, but not IGR, differed between groups during the study. The 1.7-kg weight loss with metformin versus a 0.3-kg gain with placebo alone explained 64% of the beneficial metformin effect on diabetes risk. Adjustment for weight, fasting insulin, proinsulin, and other metabolic factors combined explained 81% of the beneficial metformin effect, but it remained nominally significant (P = 0.034). After the addition of changes in fasting glucose, 99% of the group effect was explained and is no longer significant. Treatment of high-risk subjects with metformin results in modest weight loss and favorable changes in insulin sensitivity and proinsulin, which contribute to a reduction in the risk of diabetes apart from the associated reductions in fasting glucose. C1 George Washington Univ, Ctr Biostat, Diabet Prevent Program Coordinating Ctr, Rockville, MD 20852 USA. Univ Chicago, Chicago, IL 60637 USA. Univ Colorado, Sch Med, Denver, CO USA. VA PUget Sound Hlth Care Syst, Dept Internal Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. NIDDKD, Phoenix, AZ 85016 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lachin, JM (reprint author), George Washington Univ, Ctr Biostat, Diabet Prevent Program Coordinating Ctr, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. EM dppmail@biostat.bsc.gwu.edu OI Lachin, John/0000-0001-9838-2841; Kahn, Steven/0000-0001-7307-9002 FU Intramural NIH HHS; NIDDK NIH HHS [U01 DK048489, U01 DK048489-06] NR 24 TC 30 Z9 32 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 2007 VL 56 IS 4 BP 1153 EP 1159 DI 10.2337/db06-0918 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 157CW UT WOS:000245697200030 PM 17395752 ER PT J AU Grant, R Adams, AS Trinacty, CM Zhang, F Kleinman, K Soumerai, SB Meigs, JB Ross-Degnan, D AF Grant, Richard Adams, Alyce S. Trinacty, Connie Mah Zhang, Fang Kleinman, Ken Soumerai, Stephen B. Meigs, James B. Ross-Degnan, Dennis TI Relationship between patient medication adherence and subsequent clinical inertia in type 2 diabetes glycemic management SO DIABETES CARE LA English DT Article ID PRIMARY-CARE PHYSICIANS; BLOOD-GLUCOSE CONTROL; ANTIRETROVIRAL THERAPY; PHARMACY RECORDS; COMPLICATIONS; INTERVENTION; VALIDATION; PREVENTION; MELLITUS; OUTCOMES AB OBJECTIVE - Clinical inertia has been identified as a critical barrier to glycemic control in type 2 diabetes. We assessed the relationship between patients' initial medication adherence and subsequent regimen intensification among patients with persistently elevated AlC levels. RESEARCH DESIGN AND METHODS - We analyzed an inception cohort of 2,065 insured patients with type 2 diabetes who were newly started on hypoglycemic therapy and were followed for at least 3 years between 1992 and 2001. Medication adherence was assessed by taking the ratio of medication days dispensed (from pharmacy records) to medication days prescribed (as documented in the medical record) for the first prescribed hypoglycemic drug. Adherence was measured for the period between medication initiation and the next elevated AlC result measured at least 3 months later; intensification was defined as a dose increase or the addition of a second hypoglycemic agent. RESULTS - Patients were aged (mean +/- SD) 55.4 +/- 12.2 years; 53% were men, and 19% were black. Baseline medication adherence was 79.8 +/- 19.3%. Patients in the lowest quartile of adherence were significantly less likely to have their regimens increased within 12 months of their first elevated AlC compared with patients in the highest quartile (27 vs. 37%, respectively, with increased regimens if AlC is elevated, P < 0.001). In multivariate models adjusting for patient demographic and treatment factors, patients in the highest adherence quartile had 53% greater odds of medication intensification after an elevated AlC (95% CI 1.11-1.93, P = 0.01). CONCLUSIONS - Among insured diabetic patients with elevated A I C, level of medication adherence predicted subsequent medication intensification. Poor patient self-management behavior increases therapeutic clinical inertia. C1 Massachusetts Gen Hosp, Dept Med, Gen Med Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Univ, Polgrim Hlth Care, Boston, MA USA. RP Grant, R (reprint author), Div Gen Internal Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM rgrant@partners.org OI Grant, Richard/0000-0002-6164-8025 FU NIDDK NIH HHS [K23 DK067452] NR 29 TC 117 Z9 119 U1 1 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 2007 VL 30 IS 4 BP 807 EP 812 DI 10.2337/dc06-2170 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 157DA UT WOS:000245697600007 PM 17259469 ER PT J AU Fogli-Cawley, JJ Dwyer, JT Saltzman, E McCullough, ML Troy, LM Meigs, JB Jacques, PF AF Fogli-Cawley, Jeanene J. Dwyer, Johanna T. Saltzman, Edward McCullough, Marjorie L. Troy, Lisa M. Meigs, James B. Jacques, Paul F. TI The 2005 Dietary Guidelines for Americans and insulin resistance in the Framingham Offspring Cohort SO DIABETES CARE LA English DT Article ID MAJOR CHRONIC DISEASE; FOOD FREQUENCY QUESTIONNAIRE; HOMEOSTASIS MODEL ASSESSMENT; HEALTHY EATING INDEX; METABOLIC SYNDROME; FOR-AMERICANS; RISK-FACTORS; GLUCOSE; ADHERENCE; QUALITY AB OBJECTIVE - The aim of this study was to examine the relationship between a diet consistent with the 2005 Dietary Guidelines for Americans (DGA), as assessed by the 2005 Dietary Guidelines for Americans Adherence Index (DGAI), and measures of insulin resistance in the Framingham Heart Study Offspring Cohort. RESEARCH DESIGN AND METHODS - We examined cross-sectional associations between DGAI score and degree of insulin resistance as measured by the homeostasis model assessment of insulin resistance (HOMA-IR) and fasting insulin in 3,082 participants in the Framingham Offspring Cohort fifth examination (January 1991-June 1995). RESULTS - Participants in the highest quintile category of the DGAI score had significantly lower HOMA-IR than those in the lowest quintile category after adjusting for age, sex, and waist circumference (6.4 compared with 6.7, P = 0.04). We observed a significant interaction between DGAI score and sex, and upon stratification, the association appeared to be largely confined to women (5.9 compared with 6.6, P < 0.001). No association was apparent in men (7.2 compared with 7.1, P = 0.30). Similar associations were evident between the DGAI score and fasting insulin. CONCLUSIONS - Consumption of a diet consistent with the 2005 DGA may be an effective means to limit insulin resistance in women. C1 Tufts Univ, Jean Mayer US Dept Agr Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. Beth Israel Deaconess Med Ctr, Gen Clin Res Ctr, Boston, MA 02215 USA. Tufts Univ, New England Med Ctr Hosp, Boston, MA 02111 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Amer Canc Soc, Atlanta, GA 30329 USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jacques, PF (reprint author), Tufts Univ, Jean Mayer US Dept Agr Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA. EM paul.jacques@tufts.edu OI Dwyer, Johanna/0000-0002-0783-1769 FU NHLBI NIH HHS [N01-HC-25195] NR 30 TC 20 Z9 21 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 2007 VL 30 IS 4 BP 817 EP 822 DI 10.2337/dc06-1927 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 157DA UT WOS:000245697600009 PM 17259479 ER PT J AU Khaodhiar, L Dinh, T Schomacker, KT Panasyuk, SV Freeman, JE Lew, R Vo, T Panasyuk, AA Lima, C Giurini, JM Lyons, TE Veves, A AF Khaodhiar, Lalita Dinh, Thanh Schomacker, Kevin T. Panasyuk, Svetlana V. Freeman, Jenny E. Lew, Robert Vo, Tiffany Panasyuk, Alexander A. Lima, Christina Giurini, John M. Lyons, Thomas E. Veves, Aristidis TI The use of medical hyperspectral technology to evaluate microcirculatory chaves in diabetic foot ulcers and to predict clinical outcomes SO DIABETES CARE LA English DT Article ID SKIN MICROCIRCULATION; STANDARD TREATMENT; TRIAL; MANAGEMENT AB OBJECTIVE - Foot ulceration is a serious complication of diabetes, and new techniques that can predict wound healing may prove very helpful. We tested the ability of medical hyperspectral technology (FIT), a novel diagnostic scanning technique that can quantify tissue oxy- and deoxyhemoglobin to predict diabetic foot ulcer healing. RESEARCH DESIGN AND METHODS - Ten type I diabetic patients with 21 foot ulcer sites, 13 type I diabetic patients without ulcers, and 14 nondiabetic control subjects were seen up to 4 times over a 6-month period. HT measurements of oxyhemoglobin (HT-oxy) and deoxyhemoglobin (HT-deoxy) were performed at or near the ulcer area and on the upper and lower extremity distant from the ulcer. An HT healing index for each site was calculated from the HT-oxy and -deoxy values. RESULTS - Hyperspectral tissue oxygenation measurements observed changes in tissue immediately surrounding the ulcer when comparing ulcers that heal and ulcers that do not heal (P < 0.001). The sensitivity, specificity, and positive and negative predictive values of the HT index for predicting healing were 93, 86, 93, and 86%, respectively, when evaluated on images taken at the first visit. Changes in HT-oxy among the three risk groups were noted for the metatarsal area of the foot (P < 0.05) and the palm(P < 0.01). Changes in HT-deoxy and the HT healing index were noted for the palm only (P < 0.05 and P < 0.01, respectively). CONCLUSIONS - FIT has the capability to identify microvascular abnormalities and tissue oxygenation in the diabetic foot and predict ulcer healing. FIT can assist in the management of foot ulceration. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Microcirculat Lab, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Joslin Beth Israel Deaconess Foot Ctr, Boston, MA 02215 USA. HyperMed Inc, Waltham, MA USA. Boston Univ, Dept Biostat, Boston, MA 02215 USA. RP Veves, A (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Microcirculat Lab, 321A,West Campus,1 Deaconess Rd, Boston, MA 02215 USA. EM aveves@caregroup.harvard.edu FU NIDDK NIH HHS [R41 DK69871] NR 17 TC 71 Z9 73 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 2007 VL 30 IS 4 BP 903 EP 910 DI 10.2337/dc06-2209 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 157DA UT WOS:000245697600023 PM 17303790 ER PT J AU Wilson, M Weinrebi, J Hoo, GWS AF Wilson, Mark Weinrebi, Jane Hoo, Guy W. Soo TI Intensive insulin therapy in critical care - A review of 12 protocols SO DIABETES CARE LA English DT Review ID BLOOD-GLUCOSE CONTROL; ACUTE MYOCARDIAL-INFARCTION; ILL PATIENTS; DIABETES-MELLITUS; INFUSION PROTOCOL; GLYCEMIC CONTROL; PERIOPERATIVE MANAGEMENT; STRESS HYPERGLYCEMIA; INPATIENT MANAGEMENT; HOSPITAL MORTALITY AB OBJECTIVE - To review performance characteristics of 12 insulin infusion protocols. RESEARCH DESIGN AND METHODS - We systematically identify and compare 12 protocols and then apply the protocols to generate insulin recommendations in the management of a patient with hyperglycemia. The main focus involves a comparison of insulin doses and patterns of insulin administration. RESULTS - There is great variability in protocols. Areas of variation include differences in initiation and titration of insulin, use of bolus dosing, requirements for calculation in adjustment of the insulin infusion, and method of insulin protocol adjustments. Insulin recommendations for a sample patient are calculated to highlight differences between protocols, including the patterns and ranges of insulin dose recommended (range 27-115 units [mean +/- SD 66.7 +/- 27.9]), amount recommended for glucose readings >200 mg/dl, and adjustments nearing target glucose. CONCLUSIONS - The lack of consensus in the delivery of intravenous insulin infusions is reflected in the wide variability of practice noted in this survey. This mandates close attention to the choice of a protocol. One protocol may not suffice for all patients. C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare syst, Endocrine Sect, W Los Angeles Healthcare Ctr,David Geffen Sch Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare syst, Pulm & Crit Care Sect, W Los Angeles Healthcare Ctr,David Geffen Sch Med, Los Angeles, CA 90073 USA. RP Hoo, GWS (reprint author), W Los Angeles Healthcare Ctr, Pulm & Crit Care Sect 111Q, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM guy.soohoo@med.va.gov NR 55 TC 91 Z9 97 U1 1 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 2007 VL 30 IS 4 BP 1005 EP 1011 DI 10.2337/dc06-1964 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 157DA UT WOS:000245697600042 PM 17213376 ER PT J AU Maryniuk, MD AF Maryniuk, Melinda D. TI Overcoming lifelong habits: Making medical nutrition therapy and physical activity work for all patients SO DIABETES EDUCATOR LA English DT Article ID ADULTS C1 Joslin Diabet Ctr, Boston, MA 02215 USA. RP Maryniuk, MD (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM cadre@cadre-diabetes.org NR 16 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD APR PY 2007 VL 33 SU 4 BP 82S EP 86S DI 10.1177/0145721707302058 PG 5 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 166PF UT WOS:000246390400002 PM 17485415 ER PT J AU Shiotani, A Opekun, AR Graham, DY AF Shiotani, Akiko Opekun, Antone R. Graham, David Y. TI Visualization of the small intestine using capsule endoscopy in healthy subjects SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE capsule endoscopy; small bowel prep; polyethylene glycol; visualization; clinical trial ID SMALL-BOWEL; METOCLOPRAMIDE; STOMACH; LAVAGE AB The actual extent of lumen visualized by capsule endoscopy has not been studied systematically. Volunteers were randomized to receive a bowel preparation (prep) consisting of an isotonic solution containing polyethylene glycol and simethicone. The prep (200 ml) was given 30 min before the capsule. The capsule was taken with 100 ml of prep and 100 ml of water; 100 ml of prep was given 45 and 75 min later. The control administration was 100 ml of water and no simethicone. Forty percent of all frames taken in the small bowel were examined and individually scored for circumference, bubbles, debris, and lighting. Nine volunteers were studied twice. Only 50% of the circumference is seen normally. The prep improved the circumference to 62.5% as well as decreasing luminal debris and bubbles and improving the lighting. We conclude that the prep solution improved small bowel visualization, however, improvements are still needed to optimize visualization. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. RP Graham, DY (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Room 3A-320,111D,2002 Holcombe Blvd, Houston, TX 77030 USA. EM dgraham@bcm.tmc.edu FU NIDDK NIH HHS [DK 56338, DK 53659] NR 23 TC 28 Z9 30 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD APR PY 2007 VL 52 IS 4 BP 1019 EP 1025 DI 10.1007/s10620-006-9558-6 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 149FG UT WOS:000245131900025 PM 17380402 ER PT J AU Podar, K Anderson, KC AF Podar, Klaus Anderson, Kenneth C. TI The role of c-Jun in the pathogenesis of multiple myeloma SO DRUGS OF THE FUTURE LA English DT Review ID PROTEASOME INHIBITOR PS-341; CHRONIC MYELOGENOUS LEUKEMIA; PROGRAMMED CELL-DEATH; LUNG-CANCER CELLS; IN-VITRO; TRANSCRIPTION FACTOR; INDUCED APOPTOSIS; OXIDATIVE STRESS; SYMPATHETIC NEURONS; THERAPEUTIC TARGET AB Multiple myeloma (MM) is characterized by clonal proliferation of malignant plasma cells in the bone marrow (BM), associated with bone loss, renal disease and immunodeficiency. The median survival of patients with MM is 4-5 years. Although primarily associated with tumor growth and survival, several studies have demonstrated that c-Jun also induces cell growth inhibition and apoptosis. Several compounds have been reported to induce c-Jun N-terminal kinase (JNK) activity in MM. However, effects on c-Jun, the most prominent molecule downstream of JNK, have only recently been investigated in more detail. For example, adaphostin and bortezornib trigger inhibition of MM cell proliferation and apoptosis, at least in part via robust upregulation of c-Jun and downstream caspase-dependent c-ABL cleavage. This mechanism may not be restricted to MM, but may also be important in a broad range of malignancies, including erythroleukemia and solid tumors, Moreover, c-Jun. upregulation and subsequent c-ABL cleavage may not only be drug-induced, but may also represent a physiological defense mechanism of normal cells against malignant transformation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Podar, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM klaus_podar@dfci.harvard.edu NR 88 TC 0 Z9 0 U1 2 U2 2 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0377-8282 J9 DRUG FUTURE JI Drug Future PD APR PY 2007 VL 32 IS 4 BP 353 EP 359 DI 10.1358/dof.2007.032.04.1090691 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 177OW UT WOS:000247163400007 ER PT J AU Mraz, T Neuzil, P Mandysova, E Niederle, P Reddy, VY AF Mraz, Tomas Neuzil, Petr Mandysova, Eva Niederle, Petr Reddy, Vivek Y. TI Role of echocardiography in percutaneous occlusion of the left atrial appendage SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE left atrial appendage thrombus; percutaneous intervention; echocardiography; atrial fibrillation ID FIBRILLATION; PLAATO; STROKE AB Percutaneous occlusion of the left atrial appendage (LAA) is a modern alternative for the treatment of patients with atrial fibrillation (AF) and with a high risk of stroke who are not eligible for long-term anticoagulation therapy. Echocardiography plays a significant role in selecting patients, guiding the procedure, and in the postprocedural follow-up. Objectives and methods: To test the role of transesophagoeal echocardiography (TEE) and intracardiac echocardiography (ICE) in facilitating and shortening the procedure. Results: ICE represents a more convenient approach in patients who are not under generally anesthesia and helps to facilitate transseptal puncture. On the other hand, TEE, having the ability to rotate the image plane, helps to better determine the position of the occluder. Conclusions: Echocardiographic guidance of this procedure is essential. Which approach will be preferred will depend on the development of these two methods. C1 Hosp Na Homolce, Dept Cardiol, Prague 15030 5, Czech Republic. Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Mraz, T (reprint author), Hosp Na Homolce, Dept Cardiol, Roentgenova 2, Prague 15030 5, Czech Republic. EM mrazt@seznam.cz NR 7 TC 10 Z9 13 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0742-2822 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD APR PY 2007 VL 24 IS 4 BP 401 EP 404 DI 10.1111/j.1540-8175.2007.00404.x PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 148DZ UT WOS:000245056000012 PM 17381650 ER PT J AU Wu, SV Yuan, PQ Wang, LX Peng, YL Chen, CY Tache, Y AF Wu, S. Vincent Yuan, Pu-qing Wang, Lixin Peng, Yen L. Chen, Chih-Yen Tache, Yvette TI Identification and characterization of multiple corticotropin-releasing factor type 2 receptor isoforms in the rat esophagus SO ENDOCRINOLOGY LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAY; MESSENGER-RIBONUCLEIC-ACID; ACTIVATED PROTEIN-KINASE; CENTRAL-NERVOUS-SYSTEM; FACTOR CRF RECEPTOR; HORMONE-RECEPTOR; UROCORTIN-II; CARDIOVASCULAR-SYSTEM; SKELETAL-MUSCLE; PHARMACOLOGICAL CHARACTERIZATION AB The rat esophagus shares some cellular features with skin squamous epithelium and striated muscle that express high levels of corticotropin-releasing factor type 2 (CRF2) receptors or their cognate ligand urocortin (Ucn) 1, 2, and 3. We investigated the expression and cell signaling of CRF2 receptors and ligands in the rat esophagus and lower esophageal sphincter (LES) by RT-PCR and quantitative PCR in normal and corticosterone-treated whole esophageal tissue, laser capture microdissected layers, and isolated esophageal cells. The expression of CRF2 receptor protein and intracellular cAMP and ERK1/2 responses to CRF agonists and CRF2 antagonist were determined in cultured esophageal cells and HEK-293 cells transfected with CRF2b receptors. CRF2 was abundantly expressed in the mucosa and longitudinal muscle layers of the esophagus and LES, whereas CRF1 expression was scarce. CRF2b wild-type transcript was predominantly expressed in the esophagus, and in addition, several new CRF2 splice variants including six CRF2a isoforms were identified. Expression of Ucn 1, Ucn 2, and to a smaller extent Ucn 3, but not CRF mRNA, was detected in the esophagus and LES. Ucn 1 and Ucn 2 stimulated dose-dependent cAMP production and ERK1/ 2 phosphorylation in the esophageal cells, whereas CRF and CRF1 agonist, cortagine, had less potent effects. In addition, Ucn 2-stimulated cAMP and ERK responses were blocked by the CRF2 antagonist, astressin(2)-B. These data established the presence of a prominent CRF2 signaling system in the esophagus and LES- encompassing multiple CRF2 receptor variants and Ucn, suggesting a functional role in secretomotor activity and epithelial and muscle cell proliferation. C1 Univ Calif Los Angeles, Ctr Ulcer Res & Educ, Digest Dis Res Ctr, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Ctr Neurovisceral Sci & Womens Hlth, David Geffen Sch Med, Div Digest Dis,Dept Med, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan. Taipei Vet Gen Hosp, Div Gastroenterol, Taipei 112, Taiwan. RP Wu, SV (reprint author), Univ Calif Los Angeles, Ctr Ulcer Res & Educ, Digest Dis Res Ctr, David Geffen Sch Med, Los Angeles, CA 90095 USA. EM vwu@ucla.edu FU NIDDK NIH HHS [DK 33061, DK 41301] NR 67 TC 34 Z9 35 U1 0 U2 0 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 APR PY 2007 VL 148 IS 4 BP 1675 EP 1687 DI 10.1210/en.2006-0565 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 147GZ UT WOS:000244992700027 PM 17218420 ER PT J AU da Silveira, EB Barkun, AN AF da Silveira, E. B. Barkun, A. N. TI EUS-first versus ERC-first for patients with intermediate probability of bile duct stones: is one strategy superior to the other? SO ENDOSCOPY LA English DT Editorial Material ID LAPAROSCOPIC CHOLECYSTECTOMY C1 Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Gastroenterol, Portland, OR USA. McGill Univ, Div Gastroenterol & Epidemiol, Ctr Hlth, Montreal, PQ, Canada. RP Barkun, AN (reprint author), 1650 Cedar Ave,Room D7-148, Montreal, PQ H3G 1A4, Canada. EM alan.barkun@muhc.mcgill.ca NR 8 TC 3 Z9 3 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD APR PY 2007 VL 39 IS 4 BP 357 EP 358 DI 10.1055/s-2007-966255 PG 2 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 159TS UT WOS:000245890500014 PM 17427072 ER PT J AU Weisskopf, MG Hu, H Sparrow, D Lenkinski, RE Wright, RO AF Weisskopf, Marc G. Hu, Howard Sparrow, David Lenkinski, Robert E. Wright, Robert O. TI Proton magnetic resonance spectroscopic evidence of glial effects of cumulative lead exposure in the adult human hippocampus SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE bone lead; choline; glia; hippocampus; myoinositol; N-acetylaspartate; neuronal viability; proton MRS ID MILD COGNITIVE IMPAIRMENT; BLOOD LEAD; ELDERLY-MEN; NEURONAL CELLS; BONE LEAD; H-1 MRS; CHILDREN; PERFORMANCE; TOXICITY; MYOINOSITOL AB BACKGROUND: Exposure to lead is known to have adverse effects on cognition in several different populations. Little is known about the underlying structural and functional correlates of such exposure in humans. OBJECTIVES: We assessed the association between cumulative exposure to lead and levels of different bra-in metabolite ratios in vivo using magnetic resonance spectroscopy (MRS). METHODS: We performed MRS on 15 men selected from the lowest quintile of patella bone lead within the Department of Veterans Affairs' Normative Aging Study (NAS) and 16 from the highest to assess in the hippocampal levels of the metabolites N-acetylaspartate, myoinositol, and choline, each expressed as a ratio with creatine. Bone lead concentrations-indicators of cumulative lead exposure-were previously measured using K-X-ray fluorescence spectroscopy. MRS was performed on the men from 2002 to 2004. RESULTS: A 20-mu g/g bone and 15-mu g/g bone higher patella and tibia bone lead concentration-the respective interquartile ranges within the whole NAS-were associated with a 0.04 [95% confidence interval (0), 0.00-0.08; p = 0.04] and 0.04 (95% Cl, 0.00-0.08; p = 0.07) higher myoinositol-to-creatine ratio in the hippocampus. After accounting for patella bone lead declines over time, analyses adjusted for age showed that the effect of a 20-mu g/g bone higher patella bone lead level doubled (0.09; 95% Cl, 0.01-0.17; p = 0.03). CONCLUSIONS: Cumulative lead exposure is associated with an increase in the myinositol-to-creatine ratio. These data suggest that, as assessed with MRS, glial effects may be more sensitive than neuronal effects as an indicator of cumulative exposure to lead in adults. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Landmark Ctr,Dept Environm Hlth, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. RP Weisskopf, MG (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Landmark Ctr,Dept Environm Hlth, 401 Pk Dr,POB 15697, Boston, MA 02215 USA. EM mweissko@hsph.harvard.edu RI Lenkinski, Robert/F-9045-2014; OI Lenkinski, Robert/0000-0001-7371-5048 FU NCRR NIH HHS [M01 RR 02635, M01 RR002635]; NIA NIH HHS [R01 AG 13006, R01 AG 14345, R01 AG 18436, R01 AG013006, R01 AG014345, R01 AG018436]; NIAAA NIH HHS [R01 AA 08941]; NIEHS NIH HHS [K01 ES012653, 2R44 ES 03918-02, ES 00002, K01 ES 012653, K01 ES012653-05, K23 ES 000381, K23 ES000381, P30 ES000002, R01 ES 005257, R01 ES005257, R01 ES005257-15] NR 38 TC 21 Z9 21 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 2007 VL 115 IS 4 BP 519 EP 523 DI 10.1289/ehp.9645 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 153DV UT WOS:000245412800030 PM 17450218 ER PT J AU Diehm, N Baumgartner, I Jaff, M Do, DD Minar, E Schmidli, J Diehm, C Biamino, G Vermassen, F Scheinert, D van Sambeek, MRHM Schillinger, M AF Diehm, Nicolas Baumgartner, Iris Jaff, Michael Do, Dai-Do Minar, Erich Schmidli, Juerg Diehm, Curt Biamino, Giancarlo Vermassen, Frank Scheinert, Dierk van Sambeek, Marc R. H. M. Schillinger, Martin TI A call for uniform reporting standards in studies assessing endovascular treatment for chronic ischaemia of lower limb arteries SO EUROPEAN HEART JOURNAL LA English DT Review DE study endpoints; clinical success; functional outcome; study guidelines; peripheral arterial disease; balloon angioplasty; stent; debulking ID SUPERFICIAL FEMORAL-ARTERY; PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; LOWER-EXTREMITY ISCHEMIA; BELOW-THE-KNEE; BALLOON ANGIOPLASTY; FEMOROPOPLITEAL ANGIOPLASTY; INTEROBSERVER VARIATION; DISEASE; BRACHYTHERAPY; STENT AB Endovascular therapy is a rapidly evolving field for the treatment of patients with peripheral arterial disease, and a magnitude of studies reporting on various modern revascularization concepts have been recently published. Thus, studies assessing the efficacy of endovascular therapy of peripheral arteries do not operate with uniformly defined endpoints, rendering a direct comparison of studies difficult. The purpose of this consensus statement is to highlight differences in the terminology used in the current literature and to propose some standardized criteria that must be considered when reporting results of endovascular revascularization for chronic ischaemia of lower limb arteries. C1 Univ Bern, Inselspital, Dept Clin & Intervent Angiol, Swiss Cardiovasc Ctr, CH-3010 Bern, Switzerland. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Sect Vasc Med, Boston, MA USA. Univ Vienna, Dept Angiol, Vienna Gen Hosp, A-1010 Vienna, Austria. Univ Bern, Inselspital, Dept Cardiovasc Surg, Swiss Cardiovasc Ctr, CH-3010 Bern, Switzerland. Univ Heidelberg, Klinikum Karlsbad Langensteinbach, Dept Internal & Vasc Med, D-6900 Heidelberg, Germany. Univ Hosp Heart Ctr, Dept Clin & Intervent Angiol, Leipzig, Germany. State Univ Ghent Hosp, Dept Vasc Surg, B-9000 Ghent, Belgium. Erasmus Univ, Med Ctr, Dept Vasc Surg, Rotterdam, Netherlands. RP Baumgartner, I (reprint author), Univ Bern, Inselspital, Dept Clin & Intervent Angiol, Swiss Cardiovasc Ctr, Freiburgstr, CH-3010 Bern, Switzerland. EM iris.baumgartner@insel.ch NR 39 TC 92 Z9 95 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD APR PY 2007 VL 28 IS 7 BP 798 EP 805 DI 10.1093/eurheartj/ehl545 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 167IW UT WOS:000246446400009 PM 17317699 ER PT J AU Ray, KK Cannon, CP Morrow, DA Kirtane, AJ Buros, J Rifai, N McCabe, CH Gibson, CM Braunwald, E AF Ray, Kausik K. Cannon, Christopher P. Morrow, David A. Kirtane, Ajay J. Buros, Jacqueline Rifai, Nader McCabe, Carolyn H. Gibson, C. Michael Braunwald, Eugene TI Synergistic relationship between hyperglycaemia and inflammation with respect to clinical outcomes in non-ST-elevation acute coronary syndromes: analyses from OPUS-TIMI 16 and TACTICS-TIMI 18 SO EUROPEAN HEART JOURNAL LA English DT Article DE diabetes; C-reactive protein; glucose; inflammation; acute coronary syndrome ID C-REACTIVE PROTEIN; PLASMINOGEN-ACTIVATOR INHIBITOR-1; VASCULAR ENDOTHELIAL-CELLS; MYOCARDIAL-INFARCTION; DIABETES-MELLITUS; SOLUBLE CD40L; BLOOD-GLUCOSE; PLASMA-LEVELS; END-PRODUCTS; ROSIGLITAZONE AB Aims To investigate the relationship between diabetes and inflammation and the potentially synergistic relationship between hyperglycaemia and inflammation on clinical outcomes in non ST-elevation ACS. Methods and results The principal analysis was conducted in 2200 patients in OPUS-TIMI 16 with C-reactive protein data available and then validated in the invasive arem of TACTICS-TIMI 18 (n = 929). In addition, two further inflammatory markers [monocyte chemoattractant protein-1 (MCP-1) and von Willebrand factor (vWF)] were assessed in OPUS-TIMI 16. Diabetic patients had higher C-reactive protein and MCP-1 levels vs. non-diabetic patients in OPUS-TIMI 16 (9 vs. 7.8 mg/L, P = 0.002, and 190.6 vs. 170.8 pg/mL, P = 0.04, respectively), higher C-reactive protein levels in TACTICS-TIMI 18 (6.6 vs. 5.2 mg/L, P = 0.0005), and as expected higher glucose levels in both trials. Stratifying by the median C-reactive protein and diabetes in OPUS-TIMI 16, diabetic patients with C-reactive protein greater than or equal to the median were the highest risk group vs. non-diabetic patients with C-reactive protein less than the median (adjusted HR 1.63, 95% CI 1.20-2.23, P = 0.002). Directionaily, similar findings were observed for MCP-1 and vWF in OPUS-TIMI 16 and for C-reactive protein in TACTICS-TIMI 18. After adjustment for diabetes, the risk associated with a 1 mmol/L increase in glucose was greater among those with a C-reactive protein greater than or equal to the median (HR 1.07, 95% CI 1.03-1.11) vs. those with a C-reactive protein less than the median (HR 1.02, 95% CI 0.97-1.06). After multivariabie adjustment, the synergistic relationship between glucose and C-reactive protein and clinical outcomes remained statistically significant (P = 0.01). A similar pattern was observed in TACTICS-TIMI 18. Conclusion Among ACS patients, diabetes was associated with both greater inflammation and higher glucose levels and patients with both hyperglycaemia and inflammation had worse outcomes. Better control of both inflammation and hyperglycaemia should be assessed in future ACS trials as a means to reduce the cardiovascular risk among diabetics. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Cardiovasc Div,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. RP Cannon, CP (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Dept Med, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM cpcannon@partners.org OI Buros, Jacqueline/0000-0001-9588-4889 NR 29 TC 25 Z9 25 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD APR PY 2007 VL 28 IS 7 BP 806 EP 813 DI 10.1093/eurheartj/ehm010 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 167IW UT WOS:000246446400010 PM 17403721 ER PT J AU Higgins, JP Higgins, JA Williams, G AF Higgins, John P. Higgins, Johanna A. Williams, Gethin TI Stress-induced abnormalities in myocardial perfusion imaging that are not related to perfusion but are of diagnostic and prognostic importance SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Review DE lung/heart ratio; stunning; right ventricular uptake; SPECT MPI; diagnosis; prognosis ID CORONARY-ARTERY-DISEASE; TRANSIENT ISCHEMIC DILATION; LEFT-VENTRICULAR CAVITY; EMISSION COMPUTED-TOMOGRAPHY; SESTAMIBI LUNG UPTAKE; REGIONAL WALL-MOTION; TL-201 SCINTIGRAPHY; EJECTION FRACTION; PULMONARY UPTAKE; GATED SPECT AB Introduction Certain stress-induced ancillary findings on myocardial perfusion scintigraphy increase the likelihood that the patient has coronary artery disease (CAD); furthermore, among CAD patients, they indicate more severe and extensive disease, placing these patients at higher risk for future cardiac events. Indeed, in studies with no obvious perfusion defect yet with serious CAD-for example, balanced ischemia-it can be these high-risk findings that necessitate invasive intervention. Discussion Besides reversible perfusion defects, such findings include increased pulmonary radiotracer uptake, transient cavity dilatation, increased end-diastolic or end-systolic volume, decreased post-stress ejection fraction, and increased right ventricular tracer uptake on stress images. The pathophysiology underlying these findings is clearly different as they do not always occur together, and each independently predicts more severe and extensive CAD. In the current review, these findings are defined and their significance in diagnosing patients with suspected or known CAD is discussed. C1 VA Boston Healthcare Syst, Cardiol Sect, Boston, MA 02132 USA. Harvard Univ, Sch Med, Boston, MA 02132 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Higgins, JP (reprint author), VA Boston Healthcare Syst, Cardiol Sect, 2C-120,1400 VFW Pkwy, Boston, MA 02132 USA. EM John.Higgins@va.gov NR 72 TC 13 Z9 15 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD APR PY 2007 VL 34 IS 4 BP 584 EP 595 DI 10.1007/s00259-006-0293-1 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 146RE UT WOS:000244951300019 PM 17103165 ER PT J AU Keles, A Grunes, B DiFuria, C Gagari, E Srinivasan, V Darendeliler, MA Muller, R Kent, R Stashenko, P AF Keles, Ahmet Grunes, Brandon DiFuria, Catherine Gagari, Eleni Srinivasan, Vasanth Darendeliler, Mehmet A. Muller, Ralph Kent, Ralph, Jr. Stashenko, Philip TI Inhibition of tooth movement by osteoprotegerin vs. pamidronate under conditions of constant orthodontic force SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article DE orthodontics; osteoclasts; osteoprotegerin; resorption; tooth movement ID KAPPA-B LIGAND; BONE-RESORPTION; PERIODONTAL TISSUES; OSTEOCLAST INDUCTION; RECEPTOR ACTIVATOR; GROWTH-FACTOR; H+-ATPASE; IN-VIVO; RATS; BISPHOSPHONATES AB The undesired movement of anchor teeth, and relapse of previously moved teeth, are major clinical problems in orthodontics. Dental implants are increasingly used to preserve anchorage, but these are costly and require invasive surgical procedures. An alternative strategy for maintaining anchorage may be the use of biological inhibitors of osteoclastic bone resorption. In the present study, we investigated the relative efficacy of pamidronate vs. osteoprotegerin (OPG) in inhibiting bone resorption and tooth movement, using a new orthodontic model in mice in which maxillary molars are moved for prolonged periods by near-constant, clinically relevant forces. Osteoclast influx to compression sites was initiated on day 3, was maximal on day 4, and persisted until at least day 12 after force application. Tooth movement paralleled osteoclast numbers. Minimal osteoclast apoptosis was observed, suggesting that recruitment, rather than programmed cell death, is a critical regulatory mechanism under conditions of constant force. Osteoclasts were reduced at compression sites by both OPG (95%) and pamidronate (70%); tooth movement was more dramatically inhibited by OPG (77% vs. 34%). Our findings indicate that constant orthodontic force regulates the recruitment, activation, and viability of osteoclasts, and that OPG could have clinical utility in preventing undesired tooth movement. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Forsyth Inst, Clin Res Collaborat, Boston, MA 02115 USA. Tufts Sch Dent Med, Dept Oral Pathol, Boston, MA USA. Univ Sydney, Dept Orthodont, Sydney, NSW 2006, Australia. ETH, Dept Mech & Proc Engn, Inst Biomech, Zurich, Switzerland. Univ Zurich, Zurich, Switzerland. RP Stashenko, P (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM pstashenko@forsyth.org RI Muller, Ralph/A-1198-2008 OI Muller, Ralph/0000-0002-5811-7725 FU NIDCR NIH HHS [DE-07378] NR 25 TC 17 Z9 20 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD APR PY 2007 VL 115 IS 2 BP 131 EP 136 DI 10.1111/j.1600-0722.2007.00433.x PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 160KV UT WOS:000245940300007 PM 17451503 ER PT J AU Buckley, TC Holohan, DR Mozley, SL Walsh, K Kassel, J AF Buckley, Todd C. Holohan, Dana R. Mozley, Susannah L. Walsh, Kate Kassel, Jon TI The effect of nicotine and attention allocation on physiological and self-report measures of induced anxiety in PTSD: A double-blind placebo-controlled trial SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE PTSD; nicotine; attention ID POSTTRAUMATIC-STRESS-DISORDER; FAGERSTROM TOLERANCE QUESTIONNAIRE; CIGARETTE-SMOKING; PSYCHOMETRIC EVALUATION; SMOKERS; DEPENDENCE; VETERANS; AROUSAL; ADULT; MOOD AB Rates of smoking among populations with psychiatric disorders are more than twice as high as among the general population, yet there are few controlled studies of the mechanisms of this relationship. This trial examined the effect of nicotine by way of cigarette smoking on both self-report and autonomic parameters of anxiety among individuals with PTSD who were also heavy smokers. Half of the participants were randomized to an anxiety-eliciting condition, whereas the other half were assigned to a condition of neutral emotional content. Within each of these conditions, participants were randomized into a nicotine condition (high-yield nicotine cigarette) or a placebo condition (denicotinized cigarette). The final layer of randomization involved assigning participants to either an attention-demanding task or a no task condition. We examined the interactive effects of nicotine and attentional demand on parameters of anxious responding. Nicotine exerted an anxiolytic effect relative to placebo on self-report measures; however, nicotine did not interact with attentional demand in producing this effect. In contrast to the findings on the self-report measures of distress, nicotine enhanced autonomic reactivity to trauma cues, thereby suggesting a decoupling of self-reported anxiety and autonomic arousal associated with responding to trauma-relevant cues. The implications for understanding smoking and psychiatric comorbidity are discussed. C1 VA Boston Healthcare Syst, Dept Psychol, Boston, MA USA. Boston Univ, Dept Psychol, Sch Med, Boston, MA 02215 USA. Virginia Vet Affairs Med Ctr, Dept Psychol, Salem, VA USA. Univ Illinois, Dept Psychol, Chicago, IL 60680 USA. RP Buckley, TC (reprint author), Blackstone Ctr Cognit & Behav Therapy, 169 W Main St, Hopkinton, MA 01748 USA. EM Blackstoneccbt@aol.com FU NIDA NIH HHS [K01-DA016273, R03 DA15113] NR 55 TC 12 Z9 12 U1 6 U2 7 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD APR PY 2007 VL 15 IS 2 BP 154 EP 164 DI 10.1037/1064-1297.15.2.154 PG 11 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 156FN UT WOS:000245633600004 PM 17469939 ER PT J AU Walkley, C AF Walkley, Carl TI Control of self-renewal and differentiation of hematopoietic stem cells by negative cell-cycle regulators SO EXPERIMENTAL HEMATOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Recent Advances in Radiation Effects, Hematopoiesis and Malignancy in honor of Eugene P Cronkite CY MAY 10-13, 2006 CL Brookhaven Natl Lab, Upton, NY HO Brookhaven Natl Lab ID CD34(+) CELLS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Walkley, C (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM walkley@bloodgroup.tch.harvard.edu OI Walkley, Carl/0000-0002-4784-9031 NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD APR PY 2007 VL 35 IS 4 SU 1 BP 94 EP 95 DI 10.1016/j.exphem.2007.01.016 PG 2 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 155LA UT WOS:000245577700015 PM 17379093 ER PT J AU Anderson, KC AF Anderson, Kenneth C. TI Targeted therapy of multiple myeloma based upon tumor-microenvironmental interactions SO EXPERIMENTAL HEMATOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Recent Advances in Radiation Effects, Hematopoiesis and Malignancy in honor of Eugene P Cronkite CY MAY 10-13, 2006 CL Brookhaven Natl Lab, Upton, NY HO Brookhaven Natl Lab ID OVERCOMES DRUG-RESISTANCE; PROTEASOME INHIBITOR PS-341; BONE-MARROW MICROENVIRONMENT; IN-VIVO MODEL; DONOR LYMPHOCYTE INFUSION; LENALIDOMIDE PLUS DEXAMETHASONE; HISTONE DEACETYLASE INHIBITION; GROWTH-FACTOR SECRETION; NEWLY-DIAGNOSED MYELOMA; NECROSIS-FACTOR-ALPHA AB Multiple myeloma (MM) remains incurable, but recent advances in genomics and proteomics have allowed for advances in our understanding of disease pathogenesis, identified novel therapeutic targets, allowed for molecular classification, and provided the scientific rationale for combining targeted therapies to increase tumor cell cytotoxicity and abrogate drug resistance. Besides these advances, recognition of the role of the bone marrow (BM) milieu in conferring growth, survival, and drug resistance in MM cells, both in laboratory and animal models, has allowed for the establishment of a new treatment paradigm targeting the tumor cell and its microenvironment to overcome drug resistance and improve patient outcomes in MM. In particular, thalidomide, bortezomib, and lenalidamide all overcome conventional drug resistance, not only by directly inducing tumor cell cytotoxicity, but by inhibiting adhesion of MM cells to BM. This abrogates constitutive and MM-binding-induced transcription and secretion of cytokines, inhibits angiogenesis, and augments host anti-MM immunity. These three drugs have rapidly translated from bench to bedside and in treatment protocols of MM, first in patients with relapsed refractory disease, and then alone and in combination in newly diagnosed patients. Promising novel targeted agents include the novel proteasome inhibitor NPI-0052 and the heat shock protein inhibitor KOS-953. Importantly, gene-array, proteomic, and cell-signaling studies have not only helped to identify in vivo mechanisms of action and drug resistance to novel agents, but also aided in the design of promising combination-therapy protocols. (c) 2007 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM Kenneth_anderson@dfci.harvard.edu FU NCI NIH HHS [CA10070, CA 50947, CA 78373] NR 133 TC 85 Z9 91 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD APR PY 2007 VL 35 IS 4 SU 1 BP 155 EP 162 DI 10.1016/j.exphem.2007.01.024 PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 155LA UT WOS:000245577700023 PM 17379101 ER PT J AU Stone, RM AF Stone, Richard M. TI Novel therapeutic agents in acute myeloid leukemia SO EXPERIMENTAL HEMATOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Recent Advances in Radiation Effects, Hematopoiesis and Malignancy in honor of Eugene P Cronkite CY MAY 10-13, 2006 CL Brookhaven Natl Lab, Upton, NY HO Brookhaven Natl Lab ID INTERNAL TANDEM DUPLICATION; TYROSINE KINASE INHIBITOR; MYELOGENOUS LEUKEMIA; PHASE-I; GEMTUZUMAB OZOGAMICIN; CELL TRANSPLANTATION; FLT3 ANTAGONIST; AML 10; PKC412; CHEMOTHERAPY AB Acute myeloid leukemia (AML) is an intrinsically resistant disease. Prognosis is poor for the majority of AML patients, based on age and/or adverse biologic features. Standard therapy for AML is highly toxic and poorly tolerated, particularly by the group of older patients for whom few useful therapies exist. Allogeneic hematopoietic stem cell transplantation is an important option for patients with high-risk AML during first remission, as well as for any patient in second or subsequent remission. Use of reduced intensity conditioning transplantations has made allogeneic stem cell transplantation available for a wider group of individuals, but the impact of this novel procedure on the natural history of AML is unknown. The major thrust of novel therapeutics in AML is development of so-called targeted therapies, which are based on exploitation of newly understood pathophysiological events critical for leukemogenesis. Such events include unbridled proliferation, failure to differentiate, stromal cell-mediated survival factors, and failure to undergo normal programmed cell death. Therapies developed to deal with these problems include inhibitors of ras physiology and activated tyrosine kinases, such as fms-like tyrosine kinase 3; histone deacetylase inhibitors, and DNA-hypomethylating agents, which promote transcription of silenced genes; angiogenesis inhibitors; and anti-bcl-2 agents, respectively. Challenges in therapeutic development include the likelihood that only a subset of AML patients will respond to any of these therapies, based on the patient's intrinsic pathophysiology as well as the fact that many of these agents will only work in conjunction with chemotherapy or other viable antileukemic therapies. (c) 2007 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Dana Farber Canc Inst, Dept Med Oncol, Adult Leukemia Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Stone, RM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Adult Leukemia Program, 44 Binney St,M1B-17, Boston, MA 02115 USA. EM rstone@partners.org NR 42 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD APR PY 2007 VL 35 IS 4 SU 1 BP 163 EP 166 DI 10.1016/j.exphem.2007.01.025 PG 4 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 155LA UT WOS:000245577700024 PM 17379102 ER PT J AU Chi, AS Wen, PY AF Chi, Andrew S. Wen, Patrick Y. TI Inhibiting kinases in malignant gliomas SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE malignant glioma; protein kinase inhibitor; signal transduction; targeted molecular therapy ID GROWTH-FACTOR RECEPTOR; BRAIN-TUMOR CONSORTIUM; HIGH-GRADE GLIOMA; CELL LUNG-CANCER; PHASE-II TRIAL; RECURRENT GLIOBLASTOMA-MULTIFORME; NEURAL STEM-CELLS; IN-VIVO; MONOCLONAL-ANTIBODY; SIGNALING PATHWAYS AB Advances in the understanding of glioma pathogenesis have led to increasing interest in the development of targeted molecular agents, and especially kinase inhibitors, for treatment of malignant gliomas. Protein kinases are a large family of enzymes that function as key regulators of cellular signaling pathways governing diverse functions, such as cell proliferation, growth, differentiation, invasion, angiogenesis and apoptosis in malignant gliomas. Preliminary clinical results with kinase inhibitors suggest that they are generally well-tolerated but have shown only modest activity. However, valuable information was obtained from these early clinical trials that will help the future development of these agents. This article reviews the important protein kinases in malignant gliomas, summarizes the existing clinical development of kinase inhibitors and discusses strategies to improve their effectiveness. C1 Dana Farber Brigham & Womens Canc Ctr, Ctr NeuroOncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div NeuroOncol,Dept Neurol, Boston, MA 02115 USA. RP Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr NeuroOncol, Shields Warren 430D,44 Binney St, Boston, MA 02115 USA. EM pwen@partners.org NR 231 TC 29 Z9 31 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD APR PY 2007 VL 11 IS 4 BP 473 EP 496 DI 10.1517/14728222.11.4.473 PG 24 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 149EB UT WOS:000245128700007 PM 17373878 ER PT J AU Podar, K Richardson, PG Chauhan, D Anderson, KC AF Podar, Klous Richardson, Poul G. Chauhan, Dharminder Anderson, Kenneth C. TI Targeting the vascular endothelial growth factor pathway in the treatment of multiple myeloma SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE angiogenesis; bone marrow microenvironment; combination/metronomic therapy; multiple myeloma; vascular endothelial growth factor ID PROTEASOME INHIBITOR PS-341; BONE-MARROW ANGIOGENESIS; OVERCOMES DRUG-RESISTANCE; TYROSINE KINASE INHIBITOR; FACTOR-INDUCED MIGRATION; TUMOR ANGIOGENESIS; FACTOR VEGF; FACTOR EXPRESSION; IN-VITRO; PERMEABILITY FACTOR AB Multiple myeloma is a clonal plasma cell malignancy within the bone marrow associated with bone loss, renal disease and immunodeficiency. Despite new insights into the pathogenesis of multiple myeloma and novel targeted therapies, the median survival remains 3-5 years. It is now well established that the intimate relation between the tumor cells and components of the microenvironment plays a key role in multiple myeloma pathogenesis. Specifically, tumor cells impact the bone marrow and thereby cause immune suppression and lytic bone lesions; conversely, components of the bone marrow provide signals that influence the behavior of multiple myeloma cells, including tumor cell growth, survival, migration and drug resistance. Important contributing effectors are tumor cell-stroma cell and cell-extracellular matrix contacts, the bone marrow vasculature, and a variety of cytokines and growth factors in the bone marrow milieu. C1 Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Podar, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM klaus_podar@dfci.harvard.edu NR 214 TC 9 Z9 10 U1 0 U2 0 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD APR PY 2007 VL 7 IS 4 BP 551 EP 566 DI 10.1586/14737140.7.4.551 PG 16 WC Oncology SC Oncology GA 160GJ UT WOS:000245928600015 PM 17428175 ER PT J AU Jansen, PL Kever, M Rosch, R Krott, E Jansen, M Alfonso-Jaume, A Dooley, S Klinge, U Lovett, DH Mertens, PR AF Jansen, Petra Lynen Kever, Mona Rosch, Raphael Krott, Ellen Jansen, Marc Alfonso-Jaume, Alexandra Dooley, Steven Klinge, Uwe Lovett, David H. Mertens, Peter R. TI Polymeric meshes induce zonal regulation of matrix metalloproteinase-2 gene expression by macrophages and fibroblasts SO FASEB JOURNAL LA English DT Article DE polymers; wound healing; cell-specific gene regulation; transgene ID GLOMERULAR MESANGIAL CELLS; GELATINASE-A TRANSCRIPTION; Y-BOX PROTEIN-1; IV COLLAGENASE; ENHANCER; YB-1; MMP-2; ACTIVATION; INHIBITION; HERNIA AB Matrix metalloproteinase-2 (MMP-2) is a key regulator in wound healing that orchestrates tissue remodeling. In the present study the spatial and temporal distribution of MMP-2 gene transcription, protein synthesis, and enzymatic activity were analyzed following polymeric mesh (polyglactin, polypropylene) implantation in transgenic reporter mice harboring MMP-2 regulatory sequences -1686/+423 or -1241/+423. Polymers induced MMP-2 promoter activity in macrophages within the foreign body granuloma via sequences -1686/+423 with concomitantly up-regulated protein synthesis and enzymatic activity. Macrophages distant from mesh filaments exhibited low MMP-2 expression levels. Fibroblasts surrounding mesh material displayed strong MMP-2 gene transcription independent of the included promoter sequences, whereas fibroblasts without close contact to mesh material had low MMP-2 synthesis rates due to silencing activity of sequences -1686/+1241. In vitro studies support a cellular crosstalk concept, as macrophages trans-repressed MMP-2 gene transcription in fibroblasts. The zonal and cell-specific regulation of MMP-2 gene transcription illuminates an intimate cellular crosstalk in foreign body reaction that may provide a new approach for mesh modification. C1 Univ Hosp, Interdisciplinary Ctr Clin Res BIOMAT, D-52074 Aachen, Germany. Univ Hosp, RWTH Aachen, Dept Surg, Aachen, Germany. William Middleton Mem Univ Wisconsin, Dept Med, Madison, WI USA. Univ Hosp, Dept Med 2, Mannheim, Germany. Univ Calif San Francisco, Dept Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. Univ Hosp, Dept Nephrol & Clin Immunol, Aachen, Germany. RP Jansen, PL (reprint author), Univ Hosp, Interdisciplinary Ctr Clin Res BIOMAT, Pauwelsstr 30, D-52074 Aachen, Germany. EM plynen@ukaachen.de FU NIDDK NIH HHS [DK039776] NR 48 TC 19 Z9 20 U1 2 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 4 BP 1047 EP 1057 DI 10.1096/fj.06-6755com PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156LS UT WOS:000245650400009 PM 17215487 ER PT J AU Argraves, KM Wilkerson, BA Hunter, AW Gazzolo, PJ Argraves, WS Obeid, LM Drake, CJ AF Argraves, Kelley M. Wilkerson, Brent A. Hunter, Andrew W. Gazzolo, Patrick J. Argraves, W. Scott Obeid, Lina M. Drake, Christopher J. TI Sphingolipid signaling in the regulation of vascular network assembly SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Med Univ S Carolina, Dept Med, Dept Biochem, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Dept Vet Affairs, Charleston, SC 29401 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A35 EP A35 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708500163 ER PT J AU Auluck, PK Barnett, SM Eichler, FS Hedley-Whyte, ET AF Auluck, Pavan Kumar Barnett, Sarah M. Eichler, Florian S. Hedley-Whyte, E. Tessa TI Neonatal adrenoleukodystrophy with long-term survival SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners Neurol Program, Boston, MA 02114 USA. RI Auluck, Pavan/A-1160-2010 NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A401 EP A401 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708503237 ER PT J AU Ayasolla, KR Singh, AK Singh, I AF Ayasolla, Kamesh R. Singh, Avtar K. Singh, Inderjit TI Differential effects of aluminum and lithium on LPS and A beta-(25-35) induced iNOS gene expression in glia and in Tau hyper-phosphorylation, and on neurite inhibition. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Dept Pathol, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A1039 EP A1040 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708702343 ER PT J AU Brandauer, J Graham, TE Rockil, KSC Wason, C Goodyear, LJ Kahn, BB AF Brandauer, Josef Graham, Timothy E. Roeckil, Katja S. C. Wason, Christopher Goodyear, Laurie J. Kahn, Barbara B. TI Acute exercise increases serum retinol binding protein 4 concentrations SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A928 EP A928 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708701366 ER PT J AU Cardozo, C Zhao, JA Wu, Y Zhao, WD Zhang, YF Wecht, JM Wen, XL Zeman, R Bauman, WA AF Cardozo, Christopher Zhao, Jingbo A. Wu, Yong Zhao, Weidong Zhang, Yuanfei Wecht, Jill M. Wen, Xialing Zeman, Richard Bauman, William A. TI Differential skeletal muscle gene expression after SCI as compared to denervation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 James J Peters VA Med Ctr, Ctr Excellence Med Consequences SCI, Bronx, NY USA. New York Med Coll, Dept Cell Biol, Basis Sci Bldg, Valhalla, NY 10595 USA. RI Zeman, Richard/A-9295-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A1307 EP A1307 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708704466 ER PT J AU Carlson, BA Shrimali, RK Irons, R Park, JM Hatfield, DL AF Carlson, Bradley A. Shrimali, Rajeev K. Irons, Robert Park, Jin Mo Hatfield, Dolph L. TI Targeted removal of the selenocysteine tRNA ([Ser]Sec) gene (trsp) in mouse macrophages SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIH, NCI, LCP, CCR, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Harvard Med Sch, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A717 EP A718 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708505579 ER PT J AU Cheong, JMK Cabral, CB Yu, YM Tompkins, RG Kelleher, JK AF Cheong, Jennifer M. K. Cabral, Carolina B. Yu, Yong-Ming Tompkins, Ronald G. Kelleher, Joanne K. TI Burn injury results in increased cholesterol synthesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A1073 EP A1073 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708702497 ER PT J AU Danial, NN AF Danial, Nika Nelly TI Dual role of the pro-apoptotic BAD in insulin secretion and beta-cell survival SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A91 EP A91 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708500438 ER PT J AU Davidson, A Selleck, R Thisse, B Thisse, C Song, HD Song, AH Zhou, Y Chen, Z Wingert, R AF Davidson, Alan Selleck, Rori Thisse, Bernard Thisse, Christine Song, Huai-Dong Song, Anhua Zhou, Yi Chen, Zhu Wingert, Rebecca TI Nephron development in zebrafish SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. IGBMC, Strasbourg, France. Shanghei Second Med Univ, Rui Jin Hosp, Shanghei Inst Hematol, Shanghei 200025, Peoples R China. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A141 EP A141 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708501107 ER PT J AU Enkhbaatar, P Murakami, K Yu, YM Lin, F Cox, R Traber, L Herndon, D Traber, D AF Enkhbaatar, Perenlei Murakami, Kazunori Yu, Yong-Ming Lin, Flourence Cox, Robert Traber, Lillian Herndon, David Traber, Daniel TI L-arginine attenuates acute lung injury following smoke inhalation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Univ Texas, Med Branch, Galveston, TX 77550 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Shriners Burns Children, Boston, MA 02114 USA. Shriners Hosp Children, Galveston, TX 77555 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A9 EP A9 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708500042 ER PT J AU Frosch, MP Prada, CM Betensky, RA Garcia-Alloza, M Greenberg, SM Bacskai, BJ AF Frosch, Matthew P. Prada, Claudia M. Betensky, Rebecca A. Garcia-Alloza, Monica Greenberg, Steven M. Bacskai, Brian J. TI Effect of passive immunotherapy on the rate of progression of cerebral amyloid angiopathy (CAA) in transgenic mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Massachusetts Gen Hosp, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Pathol, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A73 EP A74 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708500349 ER PT J AU Hasak, SL Ochoa, CD Quinn, DA Hales, C AF Hasak, Stephen Lawler Ochoa, Cristhiaan D. Quinn, Deborah A. Hales, Charles TI Thrombospondin-1 in pulmonary artery smooth muscle cell growth inhibition SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A1435 EP A1435 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708705502 ER PT J AU Heo, JI Lee, MS Choi, EM Jeong, YJ Kim, JK Lee, SW Han, JA Kim, JI AF Heo, Jee In Lee, Mi-Suk Choi, Eun-Mi Jeong, Yu-Jin Kim, Jun-Kyung Lee, Sam W. Han, Jeong A. Kim, Jong-Il TI DNAJB9, a novel target gene of p53, binds to p53 and inhibits the transcriptional activity SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Hallym Univ, Coll Med, Chunchon, South Korea. Kangwon Natl Univ, Coll Med, Chunchon, South Korea. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Seoul Natl Univ, Coll Med, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A661 EP A661 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708505317 ER PT J AU Kaur, M Paintlia, A Contreras, M Khan, M Singh, I Singh, A AF Kaur, Manjeet Paintlia, Ajaib Contreras, Miguel Khan, Mushfiquddin Singh, Inderjit Singh, Avtar TI Peroxisomal proliferation prevents loss of oligodendrocyte progenitors and hypomyelination in periventricular leukomalacia-like brain SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Med Univ S Carolina, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Dept Pathol & Lab Med, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A990 EP A990 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708702094 ER PT J AU Koh, HJ Hirshman, MF Peter, LE Li, YF Fujii, N Goodyear, LJ AF Koh, Ho-Jin Hirshman, Michael F. Peter, Lauren E. Li, Yangfeng Fujii, Nobuharu Goodyear, Laurie J. TI LKB1 regulates contraction-stimulated glucose transport in mouse skeletal muscle SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A1208 EP A1208 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708704006 ER PT J AU Kucik, DF Wu, X Gupta, K AF Kucik, Dennis F. Wu, Xing Gupta, Kiran TI ICAM-1 diffusion enhances leukocyte adhesion under flow conditions SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Univ Alabama, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Pathol & Lab Med, Birmingham, AL 35233 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A126 EP A127 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708501037 ER PT J AU Lawlor, MW Plotkin, SR Hasserjian, RP Hedley-Whyte, ET AF Lawlor, Michael William Plotkin, Scott R. Hasserjian, Robert P. Hedley-Whyte, E. Tessa TI Precursor B lymphoblastic lymphoma restricted to the central nervous system: A case report SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A391 EP A391 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708503190 ER PT J AU Lee, YH Miron, A Drapkin, R Kindelberger, DW Jarboe, E Folkins, AK Carlson, J McKeon, FD Crum, CP AF Lee, Yonghee Miron, Alexander Drapkin, Ronnie Kindelberger, David W. Jarboe, Elke Folkins, Ann K. Carlson, Joseph McKeon, Frank D. Crum, Christopher P. TI A multi-step model of pelvic serous carcinogenesis that originates in the distal fallopian tube from a novel precursor lesion. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Pochon Cha Univ, Songnam, South Korea. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A77 EP A77 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708500364 ER PT J AU McMullen, ME Takahashi, M Davis, A Stahl, G AF McMullen, Meghan E. Takahashi, Minoru Davis, Alvin Stahl, Gregory TI C1 inhibitor regulates the activation of the mannose binding lectindependent lectin pathway following ischernia-reperfusion SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A1145 EP A1145 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708703262 ER PT J AU McMullen, ME Hart, ML Walsh, MC Buras, J Takahashi, K Stahl, G AF McMullen, Meghan E. Hart, Melanie L. Walsh, Mary C. Buras, Jon Takahashi, Kazue Stahl, Gregory TI Mannose binding lectin binds IgM to activate the lectin complement pathway in vitro and in vivo SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Northeastern Univ, New England Inflammat & Tissue Protect Inst Conso, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A1144 EP A1144 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708703260 ER PT J AU Mulvaney, JM Brooks, VL Roberts, D Chapleau, MW Goldman, RK AF Mulvaney, J. M. Brooks, V. L. Roberts, D. Chapleau, M. W. Goldman, R. K. TI Gain of baroreflex control of heart rate decreases during late pregnancy in rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Oregon Hlth & Sci Univ, Portland, OR 97239 USA. Univ Iowa, VAMC, Iowa City, IA 52242 USA. Portland VA Med Ctr, Portland, OR 97207 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A512 EP A512 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708504210 ER PT J AU Munson, KB AF Munson, Keith Bennett TI Analysis of the gastric H,K ATPase for ion pathways and inhibitor binding sites SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A535 EP A535 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708504316 ER PT J AU Newburg, DS Meng, D Young, C Baker, A Tonkonogy, SL Sartor, RB Walker, WA Nanthakumar, NN AF Newburg, David S. Meng, Di Young, Cheryl Baker, Amy Tonkonogy, Susan L. Sartor, R. Balfour Walker, W. Allan Nanthakumar, N. Nanda TI ERK and JNK mediate signaling by bacterial symbionts via a TLR-4 sentinel to induce fut2-dependent fucosylation of colonic epithelium SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Univ N Carolina, Ctr Gastrointestinal Biol & Dis, Chapel Hill, NC 27599 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A1008 EP A1008 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708702188 ER PT J AU Ochoa, CD Hasak, SL Yu, LY Hales, C Quinn, DA AF Ochoa, Cristhiaan D. Hasak, Stephen L. Yu, Lunyin Hales, Charles Quinn, Deborah A. TI Thrombospondin-1 in hypoxic pulmonary vascular remodeling SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A1434 EP A1435 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708705501 ER PT J AU Pastor-Soler, N Smolak, C Brown, D Breton, S AF Pastor-Soler, Nuria Smolak, Christy Brown, Dennis Breton, Sylvie TI Protein kinase A (PKA) regulates vacuolar H+-ATPase (V-ATPase) recycling in epididymal clear cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Univ Pittsburgh, Sch Med, Dept Med & Cell Biol & Physiol, Pittsburgh, PA 15261 USA. Massachusetts Gen Hosp, Harvard Med Sch, Dept Med, Program Membrane Biol & Nephrol Div, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A1337 EP A1337 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708705050 ER PT J AU Paunescu, TG Tyszkowski, R Brown, D AF Paunescu, Teodor G. Tyszkowski, Robert Brown, Dennis TI V-ATPase expression in the mouse olfactory epithelium SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Massachusetts Gen Hosp, Harvard Med Sch, Div Nephrol, Program Membrane Biol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A535 EP A535 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708504317 ER PT J AU Puigserver, P AF Puigserver, Pere TI Control of nutrient and energy homeostasis through the PGC-1 pathway SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A153 EP A153 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708501167 ER PT J AU Reisner, AT Xu, D Convertino, V Ryan, K Mukkamala, R AF Reisner, Andrew Tomas Xu, Da Convertino, Victor Ryan, Kathy Mukkamala, Ramakrishna TI Cardiac output estimated from an arterial blood pressure waveform by the "long-time interval" algorithm is a superior predictor of lower-body negative pressure level SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Michigan State Univ, Engn Bldg 2120, E Lansing, MI 48824 USA. USA, Inst Surg Res, Ft Sam Houston, TX 78234 USA. RI Xu, Da/A-6423-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A1261 EP A1261 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708704251 ER PT J AU Romero, VA Fernandez-Vina, M Encinales, L Almeciga, I Awad, C Collazos, V Clavijo, OP Zuniga, J Yunis, EJ AF Romero, Viviana A. Fernandez-Vina, Marcelo Encinales, Liliana Almeciga, Ingrid Awad, Carlos Collazos, Vilma Clavijo, Olga P. Zuniga, Joaquin Yunis, Edmond J. TI Tuberculin anergy mediated by humoral immunity SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Lab Med, Houston, TX 77030 USA. Hosp Santa Clara, Bogota, Colombia. Hosp La Tebaida, Armenia, Colombia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A403 EP A403 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708503245 ER PT J AU Rumawas, ME McKeown, NM Rogers, G Dwyer, JT Meigs, JM Jacques, PF AF Rumawas, Marcella E. McKeown, Nicola M. Rogers, Gail Dwyer, Johanna T. Meigs, James M. Jacques, Paul F. TI Mediterranean-style dietary pattern is associated with surrogate measures of insulin resistance in the Framingham Offspring Cohort SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Tufts Univ, USDA, HNRCA, JM, Boston, MA 02111 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A6 EP A6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708500028 ER PT J AU Sarmasik, A Wang, G Wang, KZQ Anton, PE Galson, DL AF Sarmasik, Aliye - Wang, Guangqing - Wang, Kent Z. Q. Anton, Philip E. Galson, Deborah L. TI Membrane recruitment of tee kinase by RANKL activates NFATc1 in osteoclasts SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Univ Pittsburgh, Sch Med, Dept Med, VA Pittsburgh Healthcare Syst,R&D, Pittsburgh, PA 15240 USA. Duquesne Univ, Dept Biol Sci, Pittsburgh, PA 15282 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A249 EP A250 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708502044 ER PT J AU Shivakodi, R Theva, M Meng, D Walker, WA Nanthakumar, NN AF Shivakodi, Rupak Theva, Meena Meng, Di Walker, W. Allan Nanthakumar, N. Nanda TI Salmonella typhimurium bind specific glycoconjugate receptors on human intestinal epithelium during infection SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Depauw Univ, Sci Fellow Program, Greencastle, IN 46135 USA. Boston Univ, Human Physiol Program, Boston, MA 02215 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A587 EP A588 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708504568 ER PT J AU Springer, TA AF Springer, Timothy A. TI Integrin allostery and bidirectional signal transmission across the plasma membrane SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 CBR Inst Biomed Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A151 EP A151 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708501160 ER PT J AU Stone, JR Bedri, S Cizek, SM Rastarhuyeva, I AF Stone, James R. Bedri, Shahinaz Cizek, Stephanie M. Rastarhuyeva, Iryna TI Regulation of the nuclear protein kinase CK1 alpha LS by mitogenic levels of hydrogen peroxide SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A181 EP A181 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708501296 ER PT J AU Subramanian, BK Kuo, F Yoganathan, S Kotyla, T Wilson, T Nicolosi, R AF Subramanian, Balaji Karthick Kuo, Fonghsu Yoganathan, Subbiah Kotyla, Timothy Wilson, Thomas Nicolosi, Robert TI A nanoemulsion preparation of aspirin enhances its antiinflammatory effect in CD-1 mice. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Univ Massachusetts, Lowell, MA 01854 USA. Forsyth Inst, Boston, MA 02115 USA. Univ Massachusetts, Dept Clin Lab & Nutr Sci, Lowell, MA 01854 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A442 EP A442 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708503429 ER PT J AU Taha, AY Hout, PSP Lopez, SR Prayitno, NR Kang, JX Burnham, WM Ma, DWL AF Taha, Ameer Y. Hout, Pedro S. P. Lopez, Sandra R. Prayitno, Nita R. Kang, Jing X. Burnham, W. McIntyre Ma, David W. L. TI Fat-1 transgenic mice endogenously synthesizing. high levels of n-3 PUFA are resistant to pentylenetetrazol induced seizures SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Univ Toronto, Toronto, ON M5G 1A8, Canada. Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A322 EP A322 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708502399 ER PT J AU Tanguay, RL Mathew, LK Sengupta, S Peterson, RT AF Tanguay, Robert L. Mathew, Lijoy K. Sengupta, Sumitra Peterson, Randall T. TI Regenerative pathways probed using chemical genetics in zebrafish SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Oregon State Univ, Corvallis, OR 97331 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A626 EP A627 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708505145 ER PT J AU Taylor, EB Kramer, HF Fujii, NL Yu, HY Roeckl, KSC Witczak, CA Sano, H Peter, LE Hirshman, MF Lienhard, GE Goodyear, LJ AF Taylor, Eric B. Kramer, Henning F. Fujii, Nobuharu L. Yu, Haiyan Roeckl, Katja S. C. Witczak, Carol A. Sano, Hiroyuki Peter, Lauren E. Hirshman, Michael F. Lienhard, Gustav E. Goodyear, Laurie J. TI Fiber type-specific regulation of the Akt substrate of 160 kDa (AS160) in mouse skeletal muscle SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Dartmouth Coll Sch Med, Hanover, NH 03755 USA. RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A1207 EP A1207 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708704003 ER PT J AU Volpato, GP Searles, R Scherrer-Crosbie, M Bloch, KD Ichinose, F Zapol, WM AF Volpato, Gian Paolo Searles, Robert Scherrer-Crosbie, Marielle Bloch, Kenneth D. Ichinose, Fumito Zapol, Warren M. TI Impact of body temperature on cardiovascular responses during hydrogen sulfide (H2S) breathing SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A1400 EP A1400 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708705342 ER PT J AU Wall, DM McCormick, BA AF Wall, Daniel M. McCormick, Beth A. TI Identification of the Salmonella typhimurium SipA functional domain required for intestinal inflammation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A587 EP A587 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708504567 ER PT J AU Witczak, CA Fujii, N Hirshman, MF Goodyear, LJ AF Witczak, Carol A. Fujii, Nobuharu Hirshman, Michael F. Goodyear, Laurie J. TI CaMKK alpha regulates glucose uptake independent of AMPK and Akt signaling in mouse skeletal muscle SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Joslin Diabet Ctr, Boston, MA 02215 USA. RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A836 EP A836 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708700476 ER PT J AU Wu, Y Zhao, WD Zhao, JB Zhang, YF Bauman, WA Cardozo, C AF Wu, Yong Zhao, Weidong Zhao, Jingbo Zhang, Yuanfei Bauman, William A. Cardozo, Christopher TI Evidence from DNA microarray analysis of skeletal muscle that testosterone reverses multiple glucocorticoid-induced defects in IGF-1 signaling networks. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 James J Peters VA Med Ctr, Ctr Excellence Med Consequences SCI, Bronx, NY USA. Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A1304 EP A1304 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708704451 ER PT J AU Yin, HN Chai, JK Yu, YM Shen, CA Wu, YQ Yao, YM Liu, H Liang, LM Tompkins, RG Sheng, ZY AF Yin, Hui-Nan Chai, Jia-Ke Yu, Yong-Ming Shen, Chuan-An Wu, Yan-Qiu Yao, Yong-Ming Liu, Hui Liang, Li-Ming Tompkins, Ronald G. Sheng, Zhi-Yong TI Regulation of IGF-I signal pathways by androgen in skeletal muscle of glucocorticoid-treated rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Gen Hosp PLA, Affiliated Hosp 1, Burns Inst, Dept Burns & Plast Surg, Beijing, Peoples R China. Massachusetts Gen Hosp, Shriners Burns Inst, Dept Surg, Boston, MA 02214 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A336 EP A336 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708502461 ER PT J AU Yu, BL Raher, MJ Ichinose, F Liu, R Bloch, KD Zapol, WM AF Yu, Binglan Raher, Michael J. Ichinose, Fumito Liu, Rong Bloch, Kenneth D. Zapol, Warren M. TI Nitrc oxide breathing prevents vasoconstriction after tetrameric hemoglobin infusion SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A525 EP A525 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708504270 ER PT J AU Yu, LY Quinn, DA Garg, HG Hales, CA AF Yu, Lunyin Quinn, Deborah A. Garg, Hari G. Hales, Charles A. TI Overexpression of RhoA diminishes inhibitory effect of heparin on pulmonary artery smooth muscle cell proliferation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Harvard Univ, Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A1435 EP A1435 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708705503 ER PT J AU Yu, YM Bischoff, D Cabral, C Lin, FM Carter, EA Kelleher, JK Tompkins, RG Fischman, AJ AF Yu, Yong-Ming Bischoff, David Cabral, Carolina Lin, Florence Min Carter, Edward A. Kelleher, Joanne K. Tompkins, Ronald G. Fischman, Alan J. TI Combined stable isotope and positron emission tomography for in vivo metablic investigation - Validation in an animal model SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Massachusetts Gen Hosp, Shriners Burns Hosp, Dept Pediat, Burn Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A699 EP A699 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708505490 ER PT J AU Yuan, JY Degterev, A Huang, ZH Jagtap, P Cuny, G Moskowitz, M AF Yuan, Junying Degterev, Alexei Huang, Zhihong Jagtap, Prakash Cuny, Greg Moskowitz, Michael TI Studying mechanisms of cell death: from apoptosis to necrosis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A38 EP A38 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708500180 ER PT J AU Zhao, JB Zhao, WD Wu, Y Zhang, YF Bauman, W Cardozo, C AF Zhao, Jingbo Zhao, Weidong Wu, Yong Zhang, Yuanfei Bauman, William Cardozo, Christopher TI Attenuation by nandrolone of chronic but not acute denervation atrophy. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 VA Med Ctr, Ctr Excellence Med Consequences SCI, Bronx, NY USA. Mt Sinai Sch Med, New York, NY USA. James J Peters Med Ctr, Bronx, NY 10468 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A1305 EP A1305 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708704457 ER PT J AU Savidge, TC Newman, P Pothoulakis, C Ruhl, A Neunlist, M Bourreille, A Hurst, R Sofroniew, MV AF Savidge, Tor C. Newman, Paul Pothoulakis, Charalabos Ruhl, Anne Neunlist, Michel Bourreille, Arnaud Hurst, Roger Sofroniew, Michael V. TI Enteric glia regulate intestinal barrier function and inflammation via release of S-nitrosoglutathione SO GASTROENTEROLOGY LA English DT Article ID BLOOD-BRAIN-BARRIER; NITRIC-OXIDE; CROHNS-DISEASE; BOWEL-DISEASE; PROTEIN ZO-1; PERMEABILITY; GLUTATHIONE; CELLS; MICE; NITROSYLATION AB Background & Aims: Barrier functions across epithelia and endothelia are essential for homeostatic tissue regulation. Astroglia interact with cerebral endothelia to maintain the blood-brain barrier. Whether similar interactions between astrocyte-like enteric glia and epithelia regulate intestinal barrier function is not known. Methods: Fluorescent permeability markers were used to measure intestinal barrier function in vivo after conditional ablation of enteric glia in transgenic mice. Enteric glial cell regulation of epithelial barrier integrity then was modeled in vitro using coculture. Glial-derived barrier-inducing factors were characterized using size-exclusion chromatography and mass spectrometry. Epithelial barrier integrity was assessed by transepithelial resistance readings and by quantitative measurement of tight-junction-associated protein expression by quantitative polymerase chain reaction and Western blot. Results: We show that ablation of enteric glial cells in transgenic mice causes intestinal mucosal barrier dysfunction, resulting in inflammation. Glial-derived s-nitrosoglutathione (GSNO) was identified as a potent inducer of mucosal barrier function in vitro and in vivo and of attenuated tissue inflammation after ablation of enteric glia in transgenic mice. GSNO regulation of mucosal barrier function was associated directly with an increased expression of perijunctional. F-actin and tight-junction-associated proteins zonula occludens-1 and occludin. GSNO also significantly restored mucosal barrier function in colonic biopsy specimens from patients with Crohn's disease, a well-described inflammatory permeability disorder associated with enteric glial-cell disruption. Conclusions: Enteric glia therefore share the ability of astrocytes to regulate tight-junction integrity, and cellular interactions comparable with those maintaining blood-brain barrier function also regulate epithelial permeability at mucosal surfaces. C1 Univ Texas, Med Branch, Div Gastroenterol, Galveston, TX 77555 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA USA. Beth Israel Deaconess Med Ctr, Gastrointestinal Neuropeptide Ctr, Div Gastroenterol, Boston, MA 02215 USA. Tech Univ Munich, Dept Human Biol, D-8000 Munich, Germany. INSERM, U539, Nantes, France. CHU Nantes, Hotel Dieu, Inst Malad Appareil Digest, F-44035 Nantes 01, France. Univ W England, Bristol BS16 1QY, Avon, England. Univ Calif Los Angeles, Sch Med, Dept Neurobiol, Los Angeles, CA 90024 USA. RP Savidge, TC (reprint author), Univ Texas, Med Branch, Div Gastroenterol, Galveston, TX 77555 USA. EM tcsavidg@utmb.edu RI Hurst, Roger/B-9460-2014; Bourreille, Arnaud/K-2398-2015; Neunlist, Michel/K-2388-2015 OI Hurst, Roger/0000-0002-4097-1368; FU NICHD NIH HHS [HD12437, HD31852]; NIDDK NIH HHS [DK40561, DK33506]; NINDS NIH HHS [NS42039] NR 58 TC 168 Z9 171 U1 3 U2 17 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2007 VL 132 IS 4 BP 1344 EP 1358 DI 10.1053/j.gastro.2007.01.051 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 161MZ UT WOS:000246020900023 PM 17408650 ER PT J AU Cario, E Gerken, G Podolsky, DK AF Cario, E. Gerken, G. Podolsky, D. K. TI Toll-like receptor 2 controls mucosal inflammation by regulating epithelial barrier function SO GASTROENTEROLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; CHRONIC INTESTINAL INFLAMMATION; PROINFLAMMATORY GENE-EXPRESSION; PROTEIN-KINASE-C; NF-KAPPA-B; ULCERATIVE-COLITIS; BOWEL-DISEASE; PHOSPHOINOSITIDE 3-KINASE; BACTERIAL LIGANDS; IMMUNE-RESPONSE AB Background & Aims: Toll-like receptors (TLRs) represent a class of transmembrane pattern recognition receptors essential for microbial recognition and control of innate immune responses. Commensal bacteria play an important role in maintaining tolerance and active stability of the intestinal epithelial barrier by suppressing intestinal inflammation, yet the mechanisms of action are unknown. The aim of this study was to determine the functional relevance of TLR2 to control tight junction (TJ)-associated intestinal epithelial barrier integrity to balance mucosal homeostasis against inflammatory stress-induced damage. Methods: TLR2 ligand (synthetic Pam(3)Cys-SK4 [PCSK])-induced activation of signaling cascades and TJ-associated distribution was assessed by using Western blotting and confocal microscopy combined with functional transfection and inhibitor studies in model intestinal epithelial cell (IEC) lines (IEC-6, Caco-2) or primary IEC cultured short-term ex vivo. DSS colitis was induced by standard protocol in wild-type, TLR2-/-, and MyD88-/- mice. Spontaneous apoptosis was assessed by terminal deoxinucleotidyl-transferase-mediated dUTP-biotin nick end-labeling. Results: Data from in vitro and ex vivo models of intestinal epithelial cells revealed that TLR2 stimulation effectively preserves TJ-associated barrier assembly against stress-induced damage through promotion of PI3K/Akt-mediated cell survival via MyD88. Furthermore, in vivo studies underscored that TLR2-mediated TJ regulation critically determines susceptibility to intestinal injury and inflammation. Inflammatory stress in mice deficient of TLR2 or MyD88 induced early TJ-associated disruption interrelated with anti-apoptotic failure of the intestinal epithelial barrier. Oral treatment of colitis with the TLR2 ligand PCSK significantly suppressed mucosal inflammation and apoptosis by efficiently restoring TJ-associated integrity of the intestinal epithelium in vivo. Conclusion: TLR2 may provide a target to pharmacologically modulate mucosal injury and intestinal inflammation. C1 Univ Hosp, Inst Grp 1, Div Gastroenterol & Hepatol, D-45147 Essen, Germany. Univ Duisburg Gesamthsch, Sch Med, Essen, Germany. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Gastrointestinal Unit, Boston, MA 02114 USA. RP Cario, E (reprint author), Univ Hosp, Inst Grp 1, Div Gastroenterol & Hepatol, Virchowstr 171, D-45147 Essen, Germany. EM elke.cario@uni-due.de RI Huang, Sheng-Chieh/F-4655-2011 FU NIDDK NIH HHS [DK60049, R01 DK060049, DK41557, DK43351] NR 55 TC 331 Z9 346 U1 7 U2 41 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2007 VL 132 IS 4 BP 1359 EP 1374 DI 10.1053/j.gastro.2007.02.056 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 161MZ UT WOS:000246020900024 PM 17408640 ER PT J AU O'Leary, JG Friedman, LS AF O'Leary, Jacqueline G. Friedman, Lawrence S. TI Predicting surgical risk in patients with cirrhosis: From art to science SO GASTROENTEROLOGY LA English DT Editorial Material ID DISEASE MELD SCORE; LIVER-DISEASE; HEPATOCELLULAR-CARCINOMA; ABDOMINAL OPERATIONS; MODEL; MORTALITY; SURGERY; RESECTION C1 Newton Wellesley Hosp, Dept Med, Newton, MA 02462 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Baylor Univ, Med Ctr, Dept Internal Med, Div Hepatol, Dallas, TX USA. RP Friedman, LS (reprint author), Newton Wellesley Hosp, Dept Med, 2014 Washington St, Newton, MA 02462 USA. EM lfriedman@partners.org NR 13 TC 12 Z9 14 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2007 VL 132 IS 4 BP 1609 EP 1611 DI 10.1053/j.gastro.2007.03.016 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 161MZ UT WOS:000246020900045 PM 17428482 ER PT J AU Handschin, C Kobayashi, YM Chin, S Seale, P Campbell, KP Spiegelman, BM AF Handschin, Christoph Kobayashi, Yvonne M. Chin, Sherry Seale, Patrick Campbell, Kevin P. Spiegelman, Bruce M. TI PGC-1 alpha regulates the neuromuscular junction program and ameliorates Duchenne muscular dystrophy SO GENES & DEVELOPMENT LA English DT Article DE PGC-1; neuromuscular junction; GA-binding protein; Duchenne muscular dystrophy; transcriptional regulation ID GA-BINDING-PROTEIN; MDX MOUSE MUSCLE; SKELETAL-MUSCLE; MITOCHONDRIAL BIOGENESIS; GENE-EXPRESSION; TRANSCRIPTIONAL ACTIVATION; OXIDATIVE-PHOSPHORYLATION; GAMMA COACTIVATOR-1; SYNAPTIC EXPRESSION; SUBUNIT GENE AB The coactivator PGC-1 alpha mediates key responses of skeletal muscle to motor nerve activity. We show here that neuregulin-stimulated phosphorylation of PGC-1 alpha and GA-binding protein (GABP) allows recruitment of PGC-1 alpha to the GABP complex and enhances transcription of a broad neuromuscular junction gene program. Since a subset of genes controlled by PGC-1 alpha and GABP is dysregulated in Duchenne muscular dystrophy (DMD), we examined the effects of transgenic PGC-1 alpha in muscle of mdx mice. These animals show improvement in parameters characteristic of DMD, including muscle histology, running performance, and plasma creatine kinase levels. Thus, control of PGC-1 alpha levels in skeletal muscle could represent a novel avenue to prevent or treat DMD. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Univ Zurich, Inst Physiol, CH-8057 Zurich, Switzerland. Univ Zurich, Zurich Ctr Integrat Human Physiol, CH-8057 Zurich, Switzerland. Univ Iowa, Howard Hughes Med Inst, Iowa City, IA 52242 USA. Univ Iowa, Dept Mol Physiol & Biophys, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA. Univ Iowa, Dept Neurol, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA. Univ Iowa, Dept Internal Med, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu RI Handschin, Christoph/E-6886-2015 OI Handschin, Christoph/0000-0003-0603-1097 FU NIDDK NIH HHS [DK54477, DK61562, R01 DK054477, R01 DK061562, R56 DK054477] NR 52 TC 172 Z9 174 U1 0 U2 13 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 1 PY 2007 VL 21 IS 7 BP 770 EP 783 DI 10.1101/gad.1525107 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 152XZ UT WOS:000245396900005 PM 17403779 ER PT J AU Mittal, V Rosen, J Govind, R Degenholtz, H Shingala, S Hulland, S Rhee, Y Kastango, KB Mulsant, BH Castle, N Rubin, FH Nace, D AF Mittal, Vikas Rosen, Jules Govind, Rahul Degenholtz, Howard Shingala, Sunil Hulland, Shelley Rhee, Yongjoo Kastango, Karl B. Mulsant, Benoit H. Castle, Nick Rubin, Fred H. Nace, David TI Perception gap in quality-of-life ratings: An empirical investigation of nursing home residents and Caregivers SO GERONTOLOGIST LA English DT Article DE adaptation-level theory; job satisfaction; perception gap; quality of life ID PATIENT HEALTH; CARE AB Purpose: Several studies have previously documented the existence of a perception gap-the extent to which quality-of-life ratings provided by nursing home residents and caregivers diverge. In this study we use Helson's adaptation-level theory to investigate three types of antecedents: (a) focal factors, (b) background factors, and (c) residual factors. Design and Methods: We calculated the perception gap for 11 quality-of-life domains. Caregivers rated both job satisfaction and their perception of quality of life of residents in the unit where they provided service. Concurrently, residents from these units completed quality-of-life interviews. We computed the perception gap by subtracting the residents' ratings from the caregivers' ratings for each quality-of-life domain. We conducted a hierarchical linear model using 3,850 observations to predict the perception gap. Results: Caregivers perceive quality of life to be lower than residents do across all domains fairly consistently. Caregiver demographics do not directly predict the perception gap. However, satisfaction with work, pay, and promotion were significant predictors (p < .05), and satisfaction with supervisor was a marginally significant predictor (p < . 10), of the perception gap. As satisfaction with these job dimensions increased, the perception gap decreased. Additional models show that several caregiver demographics directly influence job-satisfaction dimensions, though they did not influence the perception gap. Implications: Jobsatisfaction dimensions, rather than caregiver characteristics, are the appropriate predictors of the perception gap. However, caregiver demographics exert their influence indirectly by means of job satisfaction. A key finding is that higher job satisfaction leads to a smaller perception gap. Helson's adaptation-level theory appears to be a useful approach for understanding the antecedents of the perception gap. C1 Univ Pittsburgh, Katz Grad Sch Business, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. VA Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RAND Corp, Pittsburgh, PA USA. Univ Pittsburgh, Dept Internal Med, Pittsburgh, PA 15260 USA. Univ Mississippi, Sch Business, Oxford, MS USA. RP Rosen, J (reprint author), 3811 Ohara St, Pittsburgh, PA 15213 USA. EM rosenji@upmc.edu RI Nace, David/D-2638-2014; OI Degenholtz, Howard/0000-0003-1986-7360 FU AHRQ HHS [HS11976]; NIMH NIH HHS [MH01613, MH52247] NR 27 TC 4 Z9 4 U1 1 U2 13 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD APR PY 2007 VL 47 IS 2 BP 159 EP 168 PG 10 WC Gerontology SC Geriatrics & Gerontology GA 226SJ UT WOS:000250608500002 PM 17440121 ER PT J AU Moskowitz, MA AF Moskowitz, Michael A. TI Pathophysiology of headache - Past and present SO HEADACHE LA English DT Article; Proceedings Paper CT 25th Symposium of the New England Center for Headache CY JUL-AUG -, 2006 CL Stamfort, CT ID CORTICAL SPREADING DEPRESSION; FAMILIAL HEMIPLEGIC MIGRAINE; GENE-RELATED PEPTIDE; FUNCTIONAL MRI; SUBSTANCE-P; MECHANISMS; RECEPTOR; NOCICEPTORS; BLOCKADE; ARTERIES C1 Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. Harvard Mit Div Hlth Sci & Technol, Cambridge, MA USA. RP Moskowitz, MA (reprint author), Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, 149 13th St,Room 6403, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 NR 28 TC 50 Z9 56 U1 0 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0017-8748 J9 HEADACHE JI Headache PD APR PY 2007 VL 47 SU 1 BP S58 EP S63 DI 10.1111/j.1526-4610.2007.00678.x PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 156LW UT WOS:000245651000009 PM 17425711 ER PT J AU Emmons, KM Barbeau, EM Gutheil, C Stryker, JE Stoddard, AM AF Emmons, Karen M. Barbeau, Elizabeth M. Gutheil, Caitlin Stryker, Jo Ellen Stoddard, Anne M. TI Social influences, social context, and health behaviors among working-class, multi-ethnic adults SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE disparities; social context; health behaviors ID UNITED-STATES; PHYSICAL-ACTIVITY; VEGETABLE CONSUMPTION; CANCER PREVENTION; US ADULTS; INTERVENTION; SUPPORT; SMOKING; FRUIT; MORTALITY AB Little research has explored the relationship between social influences (e.g., social networks, social support, social norms) and health as related to modifying factors that may contribute to health disparities. This is a cross-sectional analysis of fruit and vegetable intake and physical activity, using baseline data from two cancer prevention studies with working-class, multi-ethnic adults. Several social influence and social contextual variables were associated with fruit and vegetable intake and physical activity in both samples. Fruit and vegetable consumption was associated with social norms and social networks, although different contextual variables also were related to intake across the two samples. Physical activity was associated with social networks, social norms, and competing demands. By examining how key social influence and contextual mediating variables relate to health behaviors, we can learn more about the types of interventions that might be needed to promote sustained health behavior change in this population. C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. New England Res Inst, Watertown, MA 02172 USA. RP Emmons, KM (reprint author), Harvard Univ, Sch Publ Hlth, 44 Binney St, Boston, MA 02115 USA. EM Karen_M_Emmons@dfci.harvard.edu FU NCI NIH HHS [5 P01 CA 75308] NR 58 TC 51 Z9 51 U1 2 U2 12 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD APR PY 2007 VL 34 IS 2 BP 315 EP 334 DI 10.1177/1090198106288011 PG 20 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 155AL UT WOS:000245549800003 PM 16740510 ER PT J AU Jaradat, AK Biggs, PJ AF Jaradat, Adnan K. Biggs, Peter J. TI Measurement of the leakage radiation from linear accelerators in the backward direction for 4, 6, 10, 15, and 18 MV X-ray energies SO HEALTH PHYSICS LA English DT Article DE X rays; accelerators; medical; medical radiation; radiation protection ID IONIZATION-CHAMBER; MEDICAL ACCELERATOR; NEUTRON SOURCES; RECOMBINATION; SPECTRA AB The x-ray leakage from the housing of a therapy x-ray source is regulated to be < 0.1% of the useful beam exposure at I m from the source. It is to be expected that the machine leakage in the backward direction would be less because the gantry and stand contain significant amounts of additional metal to attenuate the x rays. A reduction in head leakage in this direction will have a direct effect on the thickness of the shielding wall behind the linear accelerator. However, no reports have been published to date on measurements in this area. The x-ray leakage in the backward direction has been measured from linacs having energies of 4, 6, 10, 15, and 18 MV using a 100 cm(3) ionization chamber and Al2O3 dosimeters. The leakage was measured at nine different positions over the rear wall using a 3 X 3 matrix with a 1-m separation between adjacent horizontal and vertical points with either the leftmost or rightmost column aligned with the target and isocenter. In general, the leakage is less than the canonical value, hint the exact value depends on energy, gantry angle, and measurement position. There is significantly greater attenuation directly behind the gantry stand for all energies. Leakage at 10 MV for some positions exceeded 0.1%. Additionally, neutron leakage measurements were made for 10, 15, and 18 MV x-ray beams, using track-etch detectors. The average neutron leakage was less than 0.1% except for 18 MV, where neutron leakage was more than 0.1% of the useful beam at some positions. Health Phys. 92(4):387-395; 2007. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Massachusetts, Dept Phys, Lowell, MA USA. RP Biggs, PJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM pjbiggs@partners.org NR 24 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD APR PY 2007 VL 92 IS 4 BP 387 EP 395 DI 10.1097/01.HP.0000252308.89839.7d PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 145ZP UT WOS:000244904600009 PM 17351504 ER PT J AU Danik, SB Mansour, M Singh, J Reddy, VY Ellinor, PT Milan, D Heist, EK d'Avita, A Ruskin, JN Mela, T AF Danik, Stephan B. Mansour, Moussa Singh, Jagmeet Reddy, Vivek Y. Ellinor, Patrick T. Milan, David Heist, E. Kevin d'Avila, Andre Ruskin, Jeremy N. Mela, Theofanie TI Increased incidence of subacute lead perforation noted with one implantable cardioverter-defibrillator SO HEART RHYTHM LA English DT Article DE defibrillator; right ventricular lead; lead dislodgement; lead revision; cardiac perforation ID CHAMBER PACEMAKER IMPLANTATION; DUAL-CHAMBER; EARLY COMPLICATIONS; THERAPY; SYSTEMS; HEART AB BACKGROUND The rapid evolution of implantable cardioverter-defibrillator (ICD) leads has resulted in thinner active fixation leads. White these advances have made the leads more versatile, new configurations may be associated with unforeseen complications. OBJECTIVE The purpose of this study was to determine the incidence of perforation and dislodgement of defibrillator leads in a single center in the year 2005. METHODS ALL patients who underwent percutaneous ICD implantation at the Massachusetts General Hospital using an endocardial right ventricular Lead were included in this study. The specific leads analyzed were the Riata (1580/1581 and 1590/1591, St. Jude Medical, St Paul, Minnesota, USA;) and Sprint Fidelis (6949-65, Medtronic, Minneapolis, Minnesota, USA.). Information was collected retrospectively. RESULTS A total, of 130 Riata Leads and ill Sprint Fidelis Leads were implanted at the Massachusetts General Hospital during this time period. A total of five lead perforations occurred in patients implanted with the Riata lead as compared with none with the Sprint Fidelis lead (3.8% vs. 0%, respectively; P <.05). Two of the five patients with perforation required pericardiocentesis for tamponade. Clinical symptoms of perforation developed 1-10 days after implant. Moreover, there were five additional Lead revisions in the Riata group, which were likely due to dislodgement and/or microperforation, as compared with none in the Sprint Fidelis group (7.7% vs. 0%, respectively; P <.005). CONCLUSIONS In 2005, at one institution, there were significantly more cardiac perforations and lead revisions with the Riata lead as compared with the Sprint Fidelis right ventricular defibrillator lead. Further data are required to determine whether certain lead characteristics are responsible for this observation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Danik, SB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, 55 Fruit St,Gray Bigelow 109, Boston, MA 02114 USA. EM sdanik@partners.org RI d'Avila, Andre/F-8009-2010 OI d'Avila, Andre/0000-0001-8769-1411 NR 20 TC 71 Z9 73 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD APR PY 2007 VL 4 IS 4 BP 439 EP 442 DI 10.1016/j.hrthm.2006.12.044 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 156NR UT WOS:000245656700004 PM 17399630 ER PT J AU Mayer, EL Burstein, HJ AF Mayer, Erica L. Burstein, Harold J. TI Chemotherapy for metastatic breast cancer SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID PROSPECTIVE RANDOMIZED-TRIAL; PHASE-III TRIAL; SINGLE-AGENT CHEMOTHERAPY; QUALITY-OF-LIFE; TERM-FOLLOW-UP; COMBINATION CHEMOTHERAPY; PROGNOSTIC FACTORS; 1ST-LINE THERAPY; COMPLETE RESPONDERS; CYTOTOXIC THERAPY AB Gytotoxic chemotherapy is a mainstay of treatment for advanced breast cancer. Treatment of metastatic (also called stage IV, advanced, or recurrent) breast cancer is not considered curative. Rather, the goals of treatment with chemotherapy are to prolong survival, alleviate or prevent tumor-related symptoms or complications, and improve quality of life. While the purpose of chemotherapy is to prevent or alleviate symptoms, chemotherapy paradoxically carries considerable toxicities that cause substaritial symptoms in patients, notoriously including fatigue, nausea, vomiting, diarrhea, hair loss, mucositis, neutropemia, and neuropathy. Balancing the benefits and the side effects of chemotherapy is further complicated by the natural history of advanced breast cancer, which can be quite prolonged and typically involves multiple lines of chemotherapy, especially in patients whose tumors respond to treatment. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM hburstein@partners.org FU NCI NIH HHS [T32 CA009172] NR 70 TC 39 Z9 39 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2007 VL 21 IS 2 BP 257 EP + DI 10.1016/j.hoc.2007.03.001 PG 17 WC Oncology; Hematology SC Oncology; Hematology GA 179XC UT WOS:000247322700005 PM 17512448 ER PT J AU Schmocker, C Weylandt, KH Kahlke, L Wang, JD Lobeck, H Tiegs, G Berg, T Kang, JX AF Schmoecker, Christoph Weylandt, Karsten H. Kahlke, Lena Wang, Jingdong Lobeck, Hartmut Tiegs, Gisa Berg, Thomas Kang, Jing X. TI Omega-3 fatty acids alleviate chemically induced acute hepatitis by suppression of cytokines SO HEPATOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; TRANSGENIC MICE; FATTY-ACIDS; TNF-ALPHA; LIPOPOLYSACCHARIDE; EXPRESSION; INTERLEUKIN-1; MECHANISMS; ENDOTOXIN; DISEASE AB Cytokines such os tumor necrosis factor alpha (TNF-alpha) are key factors in liver inflammation. M has been Supplementation with essential omega-3 polyunsatrated fatty acids (n-3 PUFA) demonstrated to lower TNF-alpha and IL-1 production in mononuclear cells. An inflammation-dampening effect has been observed with increased omega-3 fatty acid supplementation in several inflammatory diseases. In this study, we used the transgenic fat-1 mouse, expressing a Caenorhabdits elegans desaturase endogenously forming n-3 PUFA from n-6 PUFA, to analyze the effect of an increased n-3 PUFA tissue status in the macrophage-dependent acute D-galactosamine/lipopolysaccaride (D-GaIN/LPS) hepatitis model. We show less severe inflammatory liver injury in fat-1 mice with a balanced n-6/n-3 PUFA ratio as evidenced by reduced serum alanine aminotransferase levels and less severe histological liver damage. This decreased inflammatory response was associated with decreased plasma TNF-alpha levels and with reduced hepatic gene expression of TNF-alpha, IL-1 beta, IFN-gamma and IL-6 in fat-1 mice, leading to a decreased rate of apoptosis in livers from fat-1 animals, as measured by DAPI-staining. Conclusion: The results of this study offer evidence for an inflammation dampening effect of omega-3 polyunsaturated fatty acids in the context of liver inflammation. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Med Berlin, Charite, Dept Gastroenterol & Hepatol, Berlin, Germany. Klinikum Ernst Von Bergmann, Dept Pathol, Potsdam, Germany. Univ Erlangen Nurnberg, Inst Expt & Clin Pharmacol & Toxicol, D-8520 Erlangen, Germany. RP Kang, JX (reprint author), Massachusetts Gen Hosp, 149-13th St,Room 4433, Charlestown, MA 02129 USA. EM jxkang@partners.org OI Berg, Thomas/0000-0003-0003-6241 FU NCI NIH HHS [R01CA-113605] NR 24 TC 89 Z9 97 U1 1 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD APR PY 2007 VL 45 IS 4 BP 864 EP 869 DI 10.1002/hep.21626 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 154MS UT WOS:000245512300005 PM 17393517 ER PT J AU O'Leary, JG Chan, JL McMahon, CM Chung, RT AF O'Leary, Jacqueline G. Chan, Jessica L. McMahon, Cory M. Chung, Raymond T. TI Atorvastatin does not exhibit antiviral activity against HCV at conventional doses: A pilot clinical trial SO HEPATOLOGY LA English DT Article ID CHRONIC HEPATITIS-C; VIRUS-RNA REPLICATION; INTERFERON; GERANYLGERANYLATION; COMBINATION; THERAPY AB Cholesterol biosynthesis is an integral part of HCV RNA replication. Not only does HCV RNA replicate on lipid rafts, but it also requires cholesterol intermediates to replicate. In addition, it has been shown in vitro that several HMG-CoA reductase inhibitors can decrease HCV RNA replication by ! I log. Therefore, we designed a clinical trial to evaluate the effect of atorvastatin on HCV RNA levels. In this prospective clinical trial, where patients served as their own control, 10 HCV-infected patients who required treatment for high cholesterol were given 20 mg atorvastatin per day. Although serum cholesterol and LDL predictably decreased significantly, there was no statistically significant change in week 4 and week 12 HCV RNA levels compared to pretreatment HCV RNA levels by the paired Student t test. It is unclear whether the addition of an HMG-CoA reductase inhibitor to interferon or a more potent inhibitor of cholesterol biosynthesis may be required to inhibit HCV RNA replication in vivo. In conclusion, atorvastatin, and likely all HMG-CoA reductase inhibitors, does not inhibit HCV RNA replication in vivo at conventional doses. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gastrointestinal Unit, Boston, MA 02114 USA. RP Chung, RT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gastrointestinal Unit, GRJ 825,55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org NR 12 TC 81 Z9 83 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD APR PY 2007 VL 45 IS 4 BP 895 EP 898 DI 10.1002/hep.21554 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 154MS UT WOS:000245512300009 PM 17393518 ER PT J AU Hasserjian, RP Goodman, HJB Lachmann, HJ Muzikansky, A Hawkins, PN AF Hasserjian, R. P. Goodman, H. J. B. Lachmann, H. J. Muzikansky, A. Hawkins, P. N. TI Bone marrow findings correlate with clinical outcome in systemic AL amyloidosis patients SO HISTOPATHOLOGY LA English DT Article DE amyloid; bone marrow; light chain; myeloma; plasma cell ID IMMUNOGLOBULIN LIGHT-CHAINS; DIAGNOSTIC EVALUATION; PLASMA-CELLS; P COMPONENT; TRANSPLANTATION AB Aims Bone marrow sampling is a key investigation in the work-up of amyloid light chain (AL) amyloidosis, but the relationship between bone marrow findings and the varied phenotype and clinical outcome of AL amyloidosis is unclear. The aim was to determine if bone marrow pathological parameters at diagnosis were related to clinical behaviour in AL amyloidosis patients. Methods and results Bone marrow findings, clinical features and outcome of 80 patients referred with a diagnosis of systemic AL amyloidosis were evaluated; six patients were subsequently excluded due to re-categorization as other forms of amyloidosis. At latest follow-up (median 66 months), 11 of the 18 patients with no identifiable bone marrow neoplastic cells (61%) versus only seven of the 56 patients with neoplastic plasma cells or non-Hodgkin's lymphoma (13%) were alive (P = 0.0046). However, neither the quantity of the neoplastic cells nor the serum light chain levels were correlated with amyloid burden or patient survival. Conclusions Identification of a neoplastic population in the bone marrow of AL amyloidosis patients by histology and immunohistochemistry correlates with poor outcome; however, the neoplastic cell burden is not prognostically significant, suggesting that additional factors are important in determining disease behaviour in AL amyloidosis. C1 Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. UCL Royal Free & Univ Coll, Sch Med, Natl Amyloidosis Ctr, London, England. RP Hasserjian, RP (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Lab, WRN 244,55 Fruit St, Boston, MA 02114 USA. EM rhasserjian@partners.org RI Hawkins, Philip/C-5573-2008; OI Lachmann, Helen/0000-0001-8378-2498 FU Medical Research Council [G7900510] NR 18 TC 11 Z9 12 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD APR PY 2007 VL 50 IS 5 BP 567 EP 573 DI 10.1111/j.1365-2559.2007.02658.x PG 7 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 150QC UT WOS:000245230300005 PM 17394492 ER PT J AU Ogino, S Kawasaki, T Ogawa, A Kirkner, GJ Loda, M Fuchs, CS AF Ogino, Shuji Kawasaki, Takako Ogawa, Akiyo Kirkner, Gregory J. Loda, Massimo Fuchs, Charles S. TI Cytoplasmic localization of p27 (cyclin-dependent kinase inhibitor 1B/KIP1) in colorectal cancer: inverse correlations with nuclear p27 loss, microsatellite instability, and CpG island methylator phenotype SO HUMAN PATHOLOGY LA English DT Article DE colon cancer; CIMP; p27; cyclin-dependent kinase inhibitor; MSI ID ALTERED SUBCELLULAR-LOCALIZATION; UBIQUITIN-PROTEASOME PATHWAY; PROGNOSTIC-SIGNIFICANCE; P27(KIP1) EXPRESSION; COLON-CANCER; CIMP; TUMORS; ADENOCARCINOMA; DEGRADATION; PROFILES AB Cytoplasmic mislocalization of p27 (CDKN IB/KIP1) is caused by activated AKTI and has been associated with poor prognosis in various cancers. CIMP in colorectal cancer is characterized by extensive promoter methylation and is associated with MSI-MSI-H and BRAF mutations. We have recently shown a positive correlation between MSI/CIMP and loss of nuclear p27. However, no study has examined cytoplasmic p27 mislocalization in relation to CIMP and MSI in colorectal cancer. Using MethyLight assays, we quantified DNA metbylation in 8 CIMP-specific gene promoters (CACNAIG, CDKN2A (p16), CRABP1, IGF2, MLHI, NEUROGI, RUNX3, and SOCSI) in 853 colorectal cancer samples obtained from 2 large prospective cohorts. We assessed expressions of nuclear and cytoplasmic p27 and nuclear p53 by immunohistochemistry. Cytoplasmic p27 expression was inversely associated with loss of nuclearp27 (P <.0001), CIMP-high (P <.0001), MSI-H (P <.0001), and BRAF mutations (P <.0001). The inverse association of cytoplasmic p27 with CIMP-high (or MSI-H) was independent of MSI (or CIMP) status. In addition, the inverse association of cytoplasmic p27 with CIMP-high was independent of KRAS/BRAF status. BRAF and CDKN2A (p16) methylation were not correlated with cytoplasmic p27 after stratification by CIMP status. The inverse associations of cytoplasmic p27 with MSI-H and CIMP-high were much more pronounced in p53-negative than p53-positive tumors. In conclusion, cytoplasmic p27 expression is inversely associated with MSI-H and CIMP-high, particularly in p53-negative tumors, suggesting interplay of functional losses of p27 and p53 in the development of various molecular Subtypes of colorectal cancer. (c) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Ogino, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU NCI NIH HHS [P01 CA055075-13, P01 CA055075-14, P01 CA087969, P01 CA055075, P01 CA087969-05, P01 CA087969-06, P01 CA55075-13, P01 CA87969-03] NR 35 TC 19 Z9 19 U1 2 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD APR PY 2007 VL 38 IS 4 BP 585 EP 592 DI 10.1016/j.humpath.2006.09.014 PG 8 WC Pathology SC Pathology GA 151VV UT WOS:000245319800008 PM 17239930 ER PT J AU Ogino, S Kawasaki, T Ogawa, A Kirkner, GJ Loda, M Fuchs, CS AF Ogino, Shuji Kawasaki, Takako Ogawa, Akiyo Kirkner, Gregory J. Loda, Massimo Fuchs, Charles S. TI TGFBR2 mutation is correlated with CpG island methytator phenotype in microsatellite instability-high colorectal cancer SO HUMAN PATHOLOGY LA English DT Article DE colon cancer; CIMP; MSI; TGF; RUNX3 ID INTESTINAL EPITHELIAL-CELLS; DNA METHYLATION ANALYSIS; II RECEPTOR GENE; COLON-CANCER; BETA RECEPTOR; GROWTH; RUNX3; EXPRESSION; INACTIVATION; TUMORS AB The transforming growth factor-beta receptor type 2 gene (TGFBR2) is mutated in most microsatellite instability-high (MSI-H) colorectal cancers. Promoter methylation of RUNX3 (runt-related transcription factor 3; encoding a transcription factor downstream of the TGF-beta pathway) is observed in colorectal cancer with CpG island methylator phenotype (CIMP), which is characterized by extensive promoter methylation and is associated with MSI-H and BRAF mutations. However, no study to date has examined interrelationship between TGFBR2 mutation, RUNX3 methylation, and CIMP in colorectal cancer. Using 144 MSI-H colorectal cancers derived from 2 large prospective cohort studies, we analyzed a mononucleotide repeat of TGFBR2 and quantified DNA methylation (by MethyLight technology) in 8 CIMP-specific promoters (RUNX3, CACNAlG [calcium channel, voltage-dependent, T type alpha-IG subunit], CDKN2A [p16], CRABP1 [cellular retinoic acid binding protein 1], IGF2 [insulin-like growth factor 2], MLH1, NEUROGI [neurogenin 1], and SOCS1 [suppressor of cytokine signaling 1]). Among the 144 MSI-H rumors, the presence of TGFBR2 mutation (overall 72% frequency) was correlated positively with CIMP-high (with > 6/8 methylated promoters; P <.0001), RUNX3 methylation (P=.0004), BRAF mutation (P=.0006), and right colon (P=.05); inversely with KRAS mutation (P=.006); but not significantly with sex, tumor differentiation, and p53 status (assessed by immunohistochemistry). After stratification by sex, location, tumor differentiation, RUNX3 status, KRAS/BRAF status, or p53 status, CIMP-high was persistently correlated with TGFBR2 mutation. In contrast, RUNX3, KRAS, or BRAF status was no longer correlated with TGFBR2 mutation after stratification by CIMP status. In conclusion, TGFBR2 mutation is associated with CIMP-high and indirectly with RUNX3 methylation. Our findings emphasize the importance of analyzing global epigenomic status (for which CIMP status is a surrogate marker) when correlating a single epigenetic event (eg, RUNX-3 methylation) with any other molecular or clinicopathologic variables. (c) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Ogino, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU NCI NIH HHS [P01 CA55075-13, P01 CA87969-03] NR 35 TC 28 Z9 28 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD APR PY 2007 VL 38 IS 4 BP 614 EP 620 DI 10.1016/j.humpath.2006.10.005 PG 7 WC Pathology SC Pathology GA 151VV UT WOS:000245319800012 PM 17270239 ER PT J AU Seifer, DB MacLaughlin, DT Cuckle, HS AF Seifer, David B. MacLaughlin, David T. Cuckle, Howard S. TI Serum mullerian-inhibiting substance in Down's syndrome pregnancies SO HUMAN REPRODUCTION LA English DT Article DE antenatal screening; Down's syndrome; marker; MIS; ovarian reserve ID FOLLICLE-STIMULATING-HORMONE; ANTIMULLERIAN HORMONE; OVARIAN RESERVE; TRISOMIC PREGNANCY; MENOPAUSE; MARKER; WOMEN; AGE; IMMUNOASSAY; ANEUPLOIDY AB To examine whether maternal serum levels of mullerian-inhibiting substance (MIS) differ in Down's syndrome and unaffected pregnancies. METHODS: Case-control study was conducted using stored serum from an antenatal screening programme. Sera from 25 Down's syndrome pregnancies were retrieved from -20 degrees C storage together with 125 unaffected controls individually matched for maternal age, weeks of gestation and duration of storage. Results were expressed in multiples of the gestation-specific median value (MoM) in controls. RESULTS: The median value in Down's syndrome pregnancies was 0.83 MoM (P = 0.77, two-tail Wilcoxon rank sum test). Among unaffected pregnancies, there was a statistically significant correlation between MIS and pregnancy-associated plasma protein-A (P < 0.05). MIS levels were elevated in pregnancies where assisted reproduction techniques had been used. CONCLUSION: There is no evidence for a substantial reduction in maternal serum MIS levels in Down's syndrome pregnancies. This study provides useful information regarding serum MIS levels in pregnancy. C1 Univ Leeds, Sch Med, Leeds LS2 9JT, W Yorkshire, England. Maimonides Hosp, Brooklyn, NY 11219 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Cuckle, HS (reprint author), Leeds Screening Ctr, Gemini Pk,Sheepscar Way, Leeds LS7 3JB, W Yorkshire, England. EM h.s.cuckle@leeds.ac.uk OI Seifer, David/0000-0003-3950-9341 NR 27 TC 9 Z9 9 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD APR PY 2007 VL 22 IS 4 BP 1017 EP 1020 DI 10.1093/humrep/del497 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 162TB UT WOS:000246111300016 PM 17218369 ER PT J AU Goodfriend, TL AF Goodfriend, Theodore L. TI Treating resistant hypertension with a neglected old drug SO HYPERTENSION LA English DT Editorial Material ID HEART-FAILURE; SPIRONOLACTONE; CANRENONE; TURNOVER C1 William S Middleton Mem Vet Adm Med Ctr, Res Serv, Madison, WI 53705 USA. Univ Wisconsin, Sch Med & Publ Hlth, Dept Med & Pharmacol, Madison, WI 53706 USA. RP Goodfriend, TL (reprint author), William S Middleton Mem Vet Adm Med Ctr, Res Serv, 2500 Overlook Terr, Madison, WI 53705 USA. EM Theodore.goodfriend@med.va.gov NR 14 TC 14 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD APR PY 2007 VL 49 IS 4 BP 763 EP 764 DI 10.1161/01.HYP.0000259806.91169.01 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 148VG UT WOS:000245104300006 PM 17309945 ER PT J AU Newton-Cheh, C Guo, CY Gona, P Larson, MG Benjamin, EJ Wang, TJ Kathiresan, S O'Donnell, CJ Musone, SL Camargo, AL Drake, JA Levy, D Hirschhorn, JN Vasan, RS AF Newton-Cheh, Christopher Guo, Chao-Yu Gona, Philimon Larson, Martin G. Benjamin, Emelia J. Wang, Thomas J. Kathiresan, Sekar O'Donnell, Christopher J. Musone, Stacy L. Camargo, Amy L. Drake, Jared A. Levy, Daniel Hirschhorn, Joel N. Vasan, Ramachandran S. TI Clinical and genetic correlates of aldosterone-to-renin ratio and relations to blood pressure in a community sample SO HYPERTENSION LA English DT Article DE aldosterone; renin; hypertension, essential; blood pressure; genetics; population; risk factors ID HORMONE REPLACEMENT THERAPY; HYPERALDOSTERONISM TYPE-II; TRAIT LINKAGE ANALYSIS; ESSENTIAL-HYPERTENSION; SERUM ALDOSTERONE; ACTIVE RENIN; POSTMENOPAUSAL WOMEN; ANGIOTENSIN SYSTEM; PLASMA-ALDOSTERONE; SODIUM-INTAKE AB Aldosterone: renin ratio (ARR) is used to screen for hyperaldosteronism. Data regarding correlates of ambulatory ARR in the community and its relation to hypertension incidence are limited. We defined clinical correlates of ARR, determined its heritability, tested for association and linkage, and related ARR to blood pressure (BP) progression in nonhypertensive individuals among 3326 individuals from the Framingham Heart Study (53% women; mean age: 59 years). Ambulatory morning ARR (serum aldosterone and plasma renin concentrations) were related to clinical covariates, genetic variation across the REN locus, a 10-cM linkage map, and among nonhypertensive participants (n = 1773) to progression of >= 1 Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure BP category (optimal: < 120/80 mm Hg, normal: 120 to 129/80 to 84 mm Hg, high normal: 130 to 139/85 to 89 mm Hg, hypertension: >= 140/90 mm Hg), or incident hypertension (systolic BP: >= 140 mm Hg, diastolic BP: >= 90 mm Hg, or use of antihypertensive treatment). ARR was positively associated with age, female sex, untreated hypertension, total/high-density lipoprotein cholesterol ratio, hormone replacement therapy, and beta-blocker use, but negatively associated with angiotensin-converting enzyme inhibitor and diuretic use. ARR was heritable (h(2) = 0.40), had modest linkage to chromosome 11p (logarithm of the odds: 1.89), but was not associated with 17 common variants in REN (n = 1729). On follow-up (mean: 3 years), 607 nonhypertensive individuals (34.2%) developed BP progression, and 283 (16.0%) developed hypertension. Higher baseline logARR was associated with increased risk of BP progression (odds ratio per SD increment: 1.23; 95% CI: 1.11 to 1.37) and hypertension incidence (odds ratio per SD increment: 1.16; 95% CI: 1.00 to 1.33). ARR is a heritable trait influenced by clinical and genetic factors. There is a continuous gradient of increasing risk of BP progression across ARR levels in nonhypertensive individuals. C1 NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Framingham, MA 01702 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Boston Univ, Sch Med, Sect Epidemiol & Prevent Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02215 USA. Childrens Hosp, Boston, MA 02115 USA. RP Newton-Cheh, C (reprint author), NHLBI, Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM cnewtoncheh@partners.org OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N01-HC-25195, 1R01HL67288, 2K24 HL04334, K23HL074077, K23HL080025] NR 63 TC 108 Z9 110 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD APR PY 2007 VL 49 IS 4 BP 846 EP 856 DI 10.1161/01.HYP.0000258554.87444.91 PG 11 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 148VG UT WOS:000245104300023 PM 17296870 ER PT J AU Syed, Z Leeds, D Curtis, D Nesta, F Levine, RA Guttag, J AF Syed, Zeeshan Leeds, Daniel Curtis, Dorothy Nesta, Francesca Levine, Robert A. Guttag, John TI A framework for the analysis of acoustical cardiac signals SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE auscultation; automated diagnosis; cardiac screening; heart murmurs AB Skilled cardiologists perform cardiac auscultation, acquiring and interpreting heart sounds, by implicitly carrying out a sequence of steps. These include discarding clinically irrelevant beats, selectively tuning in to particular frequencies and aggregating information across time to make a diagnosis. In this paper, we formalize a series of analytical stages for processing heart sounds, propose algorithms to enable computers to approximate these steps, and investigate the effectiveness of each step in extracting relevant information from actual patient data. Through such reasoning, we provide insight into the relative difficulty of the various tasks involved in the accurate interpretation of heart sounds. We also evaluate the contribution of each analytical stage in the overall assessment of patients. We expect our framework and associated software to be useful to educators wanting to teach cardiac auscultation, and to primary care physicians, who can benefit from presentation tools for computer-assisted diagnosis of cardiac disorders. Researchers may also employ the comprehensive processing provided by our framework to develop more powerful, fully automated auscultation applications. C1 MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Syed, Z (reprint author), MIT, Comp Sci & Artificial Intelligence Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM zhs@csail.mit.edu NR 25 TC 24 Z9 25 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD APR PY 2007 VL 54 IS 4 BP 651 EP 662 DI 10.1109/TBME.2006.889189 PG 12 WC Engineering, Biomedical SC Engineering GA 150BV UT WOS:000245191500008 PM 17405372 ER PT J AU Han, X Fischl, B AF Han, Xiao Fischl, Bruce TI Atlas renormalization for improved brain MR image segmentation across scanner platforms SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE brain atlas; brain imaging; computational neuroanatomy; magnetic resonance imaging (MRI) segmentation ID INTENSITY SCALE; CEREBRAL-CORTEX; STANDARDIZATION; REGISTRATION; TRANSFORMATIONS; RECONSTRUCTION; TOOL AB Atlas-based approaches have demonstrated the ability to automatically identify detailed brain structures from 3-D magnetic resonance (MR) brain images. Unfortunately, the accuracy of this type of method often degrades when processing data acquired on a different scanner platform or pulse sequence than the data used for the atlas training. In this paper, we improve the performance of an atlas-based whole brain segmentation method by introducing an intensity renormalization procedure that automatically adjusts the prior atlas intensity model to new input data. Validation using manually labeled test datasets has shown that the new procedure improves the segmentation accuracy (as measured by the Dice coefficient) by 10% or more for several structures including hippocampus, amygdala, caudate, and pallidum. The results verify that this new procedure reduces the sensitivity of the whole brain segmentation method to changes in scanner platforms and improves its accuracy and robustness, which can thus facilitate multicenter or multisite neuroanatomical imaging studies. C1 Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Cambridge, MA 02129 USA. MIT, AI Lab, Cambridge, MA 02139 USA. RP Fischl, B (reprint author), CMS Inc, St Louis, MO 63132 USA. EM xiao.han@cmsrtp.com; fischl@nmr.mgh.harvard.edu FU NCRR NIH HHS [P41-RR14075, R01 RR16594-01A1, U24 RR021382]; NIBIB NIH HHS [R01 EB001550, U54 EB005149] NR 25 TC 106 Z9 109 U1 3 U2 9 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD APR PY 2007 VL 26 IS 4 BP 479 EP 486 DI 10.1109/TMI.2007.893282 PG 8 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 155SU UT WOS:000245599200006 PM 17427735 ER PT J AU Segonne, F Pacheco, J Fischl, B AF Segonne, Florent Pacheco, Jenni Fischl, Bruce TI Geometrically accurate topology-correction of cortical surfaces using nonseparating loops SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE homotopy; human cerebral cortex; nonseparating loop; Reeb graph; segmentation; topology ID HUMAN CEREBRAL-CORTEX; IMAGE SEGMENTATION; COORDINATE SYSTEM; BRAIN; ALGORITHM; RECONSTRUCTION; DISEASE; MODELS; MRI AB In this paper, we focus on the retrospective topology correction of surfaces. We propose a technique to accurately correct the spherical topology of cortical surfaces. Specifically, we construct a mapping from the original surface onto the sphere to detect topological defects as minimal nonhomeomorphic regions. The topology of each defect is then corrected by opening and sealing the surface along a set of nonseparating loops that are selected in a Bayesian framework. The proposed method is a wholly self-contained topology correction algorithm, which determines geometrically accurate, topologically correct solutions based on the magnetic resonance imaging (MRI) intensity profile and the expected local curvature. Applied to real data, our method provides topological corrections similar to those made by a trained operator. C1 ENPC, CERTIS Lab, F-77455 Champs Sur Marne, France. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Computat Core,Athinoula A Martinos Ctr Biomed Ima, Charlestown, MA 02129 USA. MIT, CSAIL, Cambridge, MA 02139 USA. RP Segonne, F (reprint author), ENPC, CERTIS Lab, 19 Rue Nobel Cite Descartes, F-77455 Champs Sur Marne, France. EM florent.segonne_ieeetmi@m4x.org FU NCRR NIH HHS [U24 RR021382, P41-RR14075, R01 RR16594-01A1]; NIBIB NIH HHS [R01 EB001550, U54 EB005149]; NINDS NIH HHS [R01 NS052585-01]; PHS HHS [BIRN002] NR 64 TC 323 Z9 324 U1 0 U2 8 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD APR PY 2007 VL 26 IS 4 BP 518 EP 529 DI 10.1109/TMI.2006.887364 PG 12 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 155SU UT WOS:000245599200010 PM 17427739 ER PT J AU Yu, P Grant, PE Qi, Y Han, X Segonne, F Pienaar, R Busa, E Pacheco, J Makris, N Buckner, RL Golland, P Fischl, B AF Yu, Peng Grant, P. Ellen Qi, Yuan Han, Xiao Segonne, Florent Pienaar, Rudolph Busa, Evelina Pacheco, Jenni Makris, Nikos Buckner, Randy L. Golland, Polina Fischl, Bruce TI Cortical surface shape analysis based on spherical wavelets SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE folding; MRI; multiscale; neurodevelopment ID MODELS; SEGMENTATION AB In vivo quantification of neuroanatomical shape variations is possible due to recent advances in medical imaging and has proven useful in the study of neuropathology and neurodevelopment. In this paper, we apply a spherical wavelet transformation to extract shape features of cortical surfaces reconstructed from magnetic resonance images (MRIs) of a set of subjects. The spherical wavelet transformation can characterize the underlying functions in a local fashion in both space and frequency, in contrast to spherical harmonics that have a global basis set. We perform principal component analysis (PCA) (in these wavelet shape features to study patterns of shape variation within normal population from coarse to fine resolution. In addition, we study the development of cortical folding in newborns using the Gompertz model in the wavelet domain, which allows us to characterize the order of development of large-scale and finer folding patterns independently. Given a limited amount of training data, we use a regularization framework to estimate the parameters of the Gompertz model to improve the prediction performance on new data. We develop an efficient method to estimate this regularized Gompertz model based on the Broyden-Fletcher-Goldfarb-Shannon (BFGS) approximation. Promising results are presented using both PCA and the folding development model in the wavelet domain. The cortical folding development model provides quantitative anatomic information regarding macroscopic cortical folding development and may be of potential use as a biomarker for early diagnosis of neurologic deficits in newborns. C1 Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, HMS, MGH, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. RP Fischl, B (reprint author), Harvard Univ, MIT, Div Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM pengyu@mit.edu; ellen@nmr.mgh.harvard.edu; alanqi@csail.mit.edu; xiao.han@cmsrtp.com; segonne@csail.mit.edu; rudolph@nmr.mgh.harvard.edu; evelina@nmr.mgh.harvard.edu; jpacheco@nmr.mgh.harvard.edu; nikos@nmr.mgh.harvard.edu; buckner@nmr.mgh.harvard.edu; polina@csail.mit.edu RI Yu, Peng/A-2877-2010 FU NCRR NIH HHS [U24 RR021382, P41 RR013218, P41 RR014075, P41-RR14075, R01 RR016594, R01 RR16594-01A1]; NIA NIH HHS [P01 AG003991, P01 AG03991, P50 AG005681, P50 AG05681]; NIBIB NIH HHS [R01 EB001550, U54 EB005149]; NINDS NIH HHS [K23 NS042758, K23 NS42758, R01 NS051826, R01-NS051826]; PHS HHS [BIRN002] NR 36 TC 52 Z9 54 U1 2 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD APR PY 2007 VL 26 IS 4 BP 582 EP 597 DI 10.1109/TMI.2007.892499 PG 16 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 155SU UT WOS:000245599200015 PM 17427744 ER PT J AU Haxhinasto, S Benoist, C Mathis, D AF Haxhinasto, Sokol Benoist, Christophe Mathis, Diane TI Regulatory T-cell differentiation - Committed to control: a precocious choice? SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Editorial Material ID FOXP3 C1 Brigham & Womens Hosp, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Haxhinasto, S (reprint author), Brigham & Womens Hosp, Joslin Diabet Ctr, Sect Immunol & Immunogenet, 1 Joslin Pl, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu NR 9 TC 2 Z9 2 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD APR-MAY PY 2007 VL 85 IS 3 BP 175 EP 176 DI 10.1038/sj.icb.7100041 PG 2 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 167CH UT WOS:000246427900001 PM 17310224 ER PT J AU Sundrud, MS Rao, A AF Sundrud, Mark S. Rao, Anjana TI Regulatory T-cell gene expression - ChIP'ing away at foxp3 SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Editorial Material ID LINEAGE C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. CBR Inst Biomed Res, Boston, MA USA. RP Sundrud, MS (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM arao@cbr.med.harvard.edu NR 17 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD APR-MAY PY 2007 VL 85 IS 3 BP 177 EP 178 DI 10.1038/sj.icb.7100051 PG 2 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 167CH UT WOS:000246427900002 PM 17353928 ER PT J AU Ayash-Rashkovsky, M Chenine, AL Steele, LN Lee, SJ Song, RJ Ong, H Rasmussen, RA Hofmann-Lehmann, R Else, JG Augostini, P McClure, HM Secor, WE Ruprecht, RM AF Ayash-Rashkovsky, Mila Chenine, Agnes-Laurence Steele, Lisa N. Lee, Sandra J. Song, Ruijiang Ong, Helena Rasmussen, Robert A. Hofmann-Lehmann, Regina Else, James G. Augostini, Peter McClure, Harold M. Secor, W. Evan Ruprecht, Ruth M. TI Coinfection with Schistosoma mansoni reactivates viremia in rhesus macaques with chronic simian-human immunodeficiency virus clade C infection SO INFECTION AND IMMUNITY LA English DT Article ID CHRONIC IMMUNE ACTIVATION; POLYMERASE CHAIN-REACTION; BLOOD MONONUCLEAR-CELLS; HIV-1 RNA; T-CELLS; HELMINTH INFECTION; LONGITUDINAL DATA; ADULT MACAQUES; MACACA MULATTA; INDIVIDUALS AB We tested the hypothesis that helminth parasite coinfection would intensify viremia and accelerate disease progression in monkeys chronically infected with an R5 simian-human immunodeficiency virus (SHIV) encoding a human immunodeficiency virus type 1 (IHV-1) clade C envelope. Fifteen rhesus monkeys with stable SHIV-1157ip infection were enrolled into a prospective, randomized trial. These seropositive animals had undetectable viral RNA and no signs of immunodeficiency. Seven animals served as virus-only controls; eight animals were exposed to Schistosoma mansoni cercariae. From week 5 after parasite exposure onward, coinfected animals shed eggs in their feces, developed eosinophilia, and had significantly higher mRNA expression of the T-helper type 2 cytokine interleukin-4 (P = 0.001) than animals without schistosomiasis. Compared to virus-only controls, viral replication was significantly increased in coinfected monkeys (P = 0.012), and the percentage of their CD4(+) CD29(+) memory cells decreased over time (P = 0.05). Thus, S. mansoni coinfection significantly increased viral replication and induced T-cell subset alterations in monkeys with chronic SHIV clade C infection. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Div Parasit Dis, Atlanta, GA USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Univ Zurich, Vetsuisse Fac, Clin Lab, CH-8006 Zurich, Switzerland. Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB809, Boston, MA 02115 USA. EM ruth_ruprecht@dfci.harvard.edu RI Hofmann-Lehmann, Regina/C-6528-2009 FU NCRR NIH HHS [P51 RR000165]; NIAID NIH HHS [P01 AI048240, P01 AI 48240, R56 AI062515, R56 AI 062515] NR 44 TC 26 Z9 27 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2007 VL 75 IS 4 BP 1751 EP 1756 DI 10.1128/IAI.01703-06 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 153GY UT WOS:000245421400024 PM 17283092 ER PT J AU Fasching, CE Grossman, T Corthesy, B Plaut, AG Weiser, JN Janoff, EN AF Fasching, Claudine E. Grossman, Tracy Corthesy, Blaise Plaut, Andrew G. Weiser, Jeffrey N. Janoff, Edward N. TI Impact of the molecular form of immunoglobulin A on functional activity in defense against Streptococcus pneumoniae SO INFECTION AND IMMUNITY LA English DT Article ID PNEUMOCOCCAL CAPSULAR POLYSACCHARIDES; LINKED-IMMUNOSORBENT-ASSAY; SECRETORY IGA; POLYMERIC IGA; OPSONOPHAGOCYTIC ASSAY; CONJUGATE VACCINE; ANTIBODY AVIDITY; ANTIGEN-BINDING; POLYMORPHONUCLEAR LEUKOCYTES; NEISSERIA-MENINGITIDIS AB Antibodies of the immunoglobulin A (IgA) class react with capsular polysaccharides of Streptococcus pneumoniae and support complement-dependent opsonophagocytosis (OPC) of the organism by phagocytes. We characterized the biologic impact of the molecular forms of human monoclonal capsule-specific IgA (monomeric IgA [mIgA], polymeric IgA [pIgA], and secretory IgA [SIgA]) on OPC and susceptibility to cleavage by IgA1 protease. The efficiency of SIgA in support of OPC of S. pneumoniae was comparable to that of pIgA, and both forms exceeded that of mIgA by a fivefold margin. This structure-function relationship was associated with three factors. First, the avidities, or functional affinities, of both pIgA and SIgA for pneumococcal capsules exceeded those of mIgA. Second, both pIgA and SIgA required less complement to achieve similar levels of bacterial OPC than did mIgA, indicating that secretory component does not hinder the effect of complement. Third, both pIgA and SIgA mediated agglutination of the organism, whereas mIgA did not. All three forms of capsule-specific IgA showed comparable susceptibilities to cleavage and functional inhibition by bacterial IgA1 protease, demonstrating that secretory component does not prevent the proteolytic degradation of IgA1 by IgA1 protease. IgA1 cleavage results in formation of identical Fab fragments for each of the molecular forms, thereby abolishing the contribution of multivalence of pIgA and SIgA. In summary, the polymeric forms of IgA (both pIgA and SIgA) provide a substantial advantage in binding, agglutination, and OPC of the organism. C1 Univ Colorado, Hlth Sci Ctr, Div Infect Dis, Colorado CFAR,Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. Univ Minnesota, Vet Affairs Med Ctr, Div Infect Dis & Int Med, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Dent, Minneapolis, MN 55455 USA. CHU Vaudois, Div Immunol & Allergie, CH-1011 Lausanne, Switzerland. Tufts Univ, Sch Med, Div Gastroenterol, Boston, MA 02111 USA. Tufts Univ, Sch Med, New England Med Ctr Hosp, GRASP Digest Dis Ctr, Boston, MA 02111 USA. Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Denver Vet Affairs Med Ctr, Hlth Sci Ctr, Denver, CO USA. RP Janoff, EN (reprint author), Univ Colorado, Hlth Sci Ctr, Div Infect Dis, Colorado CFAR,Denver Vet Affairs Med Ctr, 4200 E 9th Ave,Room 1813, Denver, CO 80262 USA. EM Edward.Janoff@uchsc.edu RI Medecine, Bibliotheque/A-5279-2012; OI Weiser, Jeffrey/0000-0001-7168-8090 FU NIAID NIH HHS [AI 38446, AI 44231, AI 48796, R01 AI038446, R01 AI044231, R01 AI048796, R21 AI044231]; NICHD NIH HHS [HD 41361, R01 HD041361]; NIDCR NIH HHS [DE 015072, R01 DE 15844, R01 DE015844, R21 DE015072]; NIDDK NIH HHS [P30 DK 34928, P30 DK034928] NR 60 TC 17 Z9 19 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2007 VL 75 IS 4 BP 1801 EP 1810 DI 10.1128/IAI.01758-06 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 153GY UT WOS:000245421400031 PM 17261616 ER PT J AU Paul, E Nelde, A Verschoor, A Carroll, MC AF Paul, Elahna Nelde, Annette Verschoor, Admar Carroll, Michael C. TI Follicular exclusion of autoreactive B cells requires Fc gamma RIIb SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE autoimmunity; Fc receptors; lupus; rodent; tolerance ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; DENDRITIC CELLS; MICE; RECEPTORS; TOLERANCE; LOCALIZATION; AUTOANTIBODIES; AUTOIMMUNITY; ELIMINATION; EXPRESSION AB In non-autoimmune mice, the 3H9 transgenic Ig heavy chain can pair with endogenous Ig lambda 1 light chains to generate B cells with specificity for DNA. These autoreactive cells are actively regulated in vivo, as indicated by the exclusion of lambda 1 cells from the splenic B cell follicle and the absence of auto-antibody production. To study the role of Fc gamma receptor IIb (Fc gamma RIIb) in peripheral B cell tolerance, Fc gamma RIIb(-/-) mice were crossed with C57BL/6 mice bearing a site-directed knock-in of the 3H9 transgene. 3H9Fc gamma RIIb(-/-) mice become autoreactive, lose the follicular exclusion of anti-DNA B cells and instead have lambda 1 B cells located within splenic germinal centers. They have increased frequencies of splenic auto-antibody-producing cells and elevated titers of IgG anti-DNA auto-antibody. The data implicate an Fc gamma RIIb-dependent checkpoint that can exclude autoreactive B cells from splenic follicles. By restricting their participation in germinal center reactions, this putative checkpoint helps attenuate the production of potentially pathogenic auto-antibodies. The data further suggest that this Fc gamma RIIb-dependent regulation is B cell autonomous. C1 Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Pediat Nephrol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. CBR Inst Biomed Res, Boston, MA USA. RP Paul, E (reprint author), Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. EM epaul@partners.org FU NIAID NIH HHS [P01AI52343] NR 33 TC 19 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD APR PY 2007 VL 19 IS 4 BP 365 EP 373 DI 10.1093/intimm/dxm002 PG 9 WC Immunology SC Immunology GA 152HP UT WOS:000245352800003 PM 17307801 ER PT J AU Zhang, ZL Hinrichs, DJ Lu, HY Chen, H Zhong, WW Kolls, JK AF Zhang, Zili Hinrichs, David J. Lu, Huiying Chen, Hong Zhong, Wenwei Kolls, Jay K. TI After interleukin-12p4O, are interleukin-23 and interleukin-17 the next therapeutic targets for inflammatory bowel disease? SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Review DE CD4(+) T cells; Crohn's disease; inflammatory bowel disease; interleukin-17; interleukin-23; ThIL-17 cells; ulcerative colitis ID HUMAN COLONIC MYOFIBROBLASTS; IL-17-PRODUCING T-CELLS; ACTIVE CROHNS-DISEASE; NF-KAPPA-B; INDUCED COLITIS; AUTOIMMUNE ENCEPHALOMYELITIS; NEUTROPHIL RECRUITMENT; STIMULATING FACTOR; CYTOKINE RECEPTOR; EPITHELIAL-CELLS AB Inflammatory bowel disease (IBD), typified by Crohn's disease and ulcerative colitis, is a common disorder characterized by recurrent and serious inflammation of the gastrointestinal tract. Recent immunologic advances have established that T cells and inflammatory cytokines play a pivotal role in the gastrointestinal inflammation of IBD. However, many cytokines not only elicit inflammation but also protect host against microbial invasion. Hence, suppression of these dual-purpose cytokines often exposes the patients to significant risk of infection. Recent research on Interleukin (IL)-23, IL-17, and IL-17 producing T cells has become the vanguard of further understanding the contribution of cytokines to autoimmune and inflammatory diseases. IL-23 is a newly discovered member of the IL-12-related cytokine family, and is primarily involved in the differentiation of pathogenic T cells characterized by their production of IL-17. IL-17 is a potent inflammatory mediator implicated in a number of autoimmune diseases. The discovery of this IL-23/IL-17-mediated inflammatory axis is having a profound impact on the elucidation of T cell-mediated pathogenesis as well as development of novel therapeutic targets. In this review, we discuss the current literature and present our recent studies on the role of IL-23 and IL-17 in the pathogenesis of IBD. Controlling the expression/production of IL-23 and IL-17 is an approach that would allow the development of a novel treatment strategy with more anti-inflammatory efficacy and potentially with less suppressive effects on host defenses. (c) 2007 Published by Elsevier B.V. C1 Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. RP Kolls, JK (reprint author), Childrens Hosp Pittsburgh, 3705 5th Ave,Suite 3765, Pittsburgh, PA 15213 USA. EM jkolls@lsuhsc.edu NR 63 TC 47 Z9 48 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD APR PY 2007 VL 7 IS 4 BP 409 EP 416 DI 10.1016/j.intimp.2006.09.024 PG 8 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 149KI UT WOS:000245145400001 PM 17321463 ER PT J AU Alonso, A AF Alonso, Anne TI Reflections on the writing group SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Ctr Psychoanalyt Studies, Boston, MA 02114 USA. RP Alonso, A (reprint author), Harvard Univ, Sch Med, Dept Psychiat, 17 Lakeview Ave, Cambridge, MA 02138 USA. EM Annealonso@aol.com NR 0 TC 0 Z9 0 U1 0 U2 1 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0020-7284 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD APR PY 2007 VL 57 IS 2 BP 219 EP 223 DI 10.1521/ijgp.2007.57.2.219 PG 5 WC Psychology, Clinical SC Psychology GA 150NU UT WOS:000245224300005 PM 17419671 ER PT J AU Monroy, A Kojima, K Ghanem, MA Paz, AC Kamil, S Vacanti, CA Eavey, RD AF Monroy, Angelo Kojima, Koji Ghanem, Marcielle A. Paz, Ana Cristina Kamil, Syed Vacanti, Charles A. Eavey, Roland D. TI Tissue engineered cartilage "bioshell" protective layer for subcutaneous implants SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the American-Society-of-Pediatric-Otolaryngology CY MAY 20-22, 2006 CL Chicago, IL SP Amer Soc Pediat Otolaryngol DE tissue engineered cartilage; microtia reconstruction; external ear malformations ID DENSITY POLYETHYLENE IMPLANTS; AURICULAR RECONSTRUCTION; IN-VITRO; AURICLE; SHAPE; EAR AB Objective: One current technique to reconstruct an ear for microtia involves the use of a high density polyethylene auricular implant; however, the implant can extrude if not covered in a temporoparietal fascia flap. Theoretically, an autologous tissue engineered cartilage "bioshell" protective coating around a permanent biocompatible implant might reduce potential extrusion to avoid the flap requirement. We hypothesized that if Subjected to intentional exposure, a bioshell coating over an implant would provide enhanced wound heating. Methods: Six sheets of high density polyethylene and six sheets of 24 carat pure gold wire-mesh measuring 19 mm x 25 mm were implanted subcutaneously in an immunocompetent swine model. Half of each implant group were coated with chondrocytes (50-70 million cells/cm(3)) which were suspended in Pluronic F-127 30% hydrogel; the remaining implants without chondrocytes were used as controls. At 10 weeks postimplantation, partial implant exposure via excision of overlying skin was performed to simulate extrusion and the sites were allowed to heat secondarily. Results: All (6/6) of bioshell implants achieved wound closure after exposure by the seventh post-operative day; controls achieved closure at approximately 10 days. Bioshell neocartilage was evaluated and confirmed histologically using hematoxylin and eosin and safranin O stains. Histochemically, neocartilage approximated native cartilage with 60% glycosaminoglycans content. Conclusion: A 'proof-of-principle' tissue engineered bioshell around subcutaneous high density polyethylene and gold implants generated an elastic neocartilage coating, elicited a tow inflammatory reaction, and was associated with 30% faster wound heating. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Lab Tissue Engn & Regenerat Med, Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med,Sch Med, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Dept Otolaryngol, Worcester, MA 01605 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Pediat Otolaryngol Serv, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Kojima, K (reprint author), Harvard Univ, Lab Tissue Engn & Regenerat Med, Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med,Sch Med, 75 Francis St Thorn 1334, Boston, MA 02115 USA. EM kojima@zeus.bwh.harvard.edu; amarcielte@gmail.com NR 15 TC 14 Z9 16 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD APR PY 2007 VL 71 IS 4 BP 547 EP 552 DI 10.1016/j.ijporl.2006.11.025 PG 6 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 153FR UT WOS:000245418000005 PM 17240459 ER PT J AU Landis, DM Luo, WX Song, J Bellon, JR Punglia, RS Wong, JS Killoran, JH Gelman, R Harris, JR AF Landis, Daniel M. Luo, Weixiu Song, Jun Bellon, Jennifer R. Punglia, Rinaa S. Wong, Julia S. Killoran, Joseph H. Gelman, Rebecca Harris, Jay R. TI Variability among breast radiation oncologists in delineation of the postsurgical lumpectomy cavity SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE partial breast irradiation; interobserver variability; radiation therapy target definition ID LOW-DOSE-RATE; RANDOMIZED-TRIAL; CONSERVING SURGERY; PHASE-I/II; FOLLOW-UP; CANCER; IRRADIATION; BRACHYTHERAPY; RADIOTHERAPY; THERAPY AB Purpose: Partial breast irradiation (PBI) is becoming more widely used. Accurate determination of the surgical lumpectomy cavity volume is more critical with PBI than with whole breast radiation therapy. We examined the interobserver variability in delineation of the lumpectomy cavity among four academic radiation oncologists who specialize in the treatment of breast cancer. Methods and Materials: Thirty-four lumpectomy cavities in 33 consecutive patients were evaluated. Each physician contoured the cavity and a 1.5-cm margin was added to define the planning target volume (PTV). A cavity visualization score (CVS) was assigned (1-5). To eliminate bias, the physician of record was eliminated from the analysis in all cases. Three measures of variability of the PTV were developed: average shift of the center of mass (COM), average percent overlap between the PTV of two physicians (PVO), and standard deviation of the PTV. Results: Of variables examined, pathologic resection volume was significantly correlated with CVS, with larger volumes more easily visualized. Shift of the COM decreased and PVO increased significantly as CVS increased. For CVS 4 and 5 cases, the average COM shift was 3 mm and 2 mm, respectively, and PVO was 77% and 87%, respectively. In multiple linear regression, pathologic diameter >4 cm and CVS >= 3 were significantly associated with smaller COM shift. When CVS was omitted from analysis, PVO was significantly larger with pathologic diameter >= 5 cm, days to planning <36, and older age. Conclusions Even among radiation oncologists who specialize in breast radiotherapy, there can be substantial differences in delineation of the postsurgical radiotherapy target volume. Large treatment margins may be prudent if the cavity is not clearly defined. (c) 2006 Elsevier Inc. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Joint Ctr Radiat Therapy,Residency Training Progr, Boston, MA USA. Swedish Canc Inst, Seattle, WA USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Landis, DM (reprint author), Northwest Hosp, Swedish Canc Inst, 150N 115th St G-16, Seattle, WA 98133 USA. EM Daniel.Landis@swedish.org NR 27 TC 100 Z9 105 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 1 PY 2007 VL 67 IS 5 BP 1299 EP 1308 DI 10.1016/j.ijrobp.2006.11.026 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 155HC UT WOS:000245567500003 PM 17275202 ER PT J AU DeLaney, TF Kepka, L Goldberg, SI Hornicek, FJ Gebhardt, MC Yoon, SS Springfield, DS Raskin, KA Harmon, DC Kirsch, DG Mankin, HJ Rosenberg, AE Nielsen, GP Suit, HD AF DeLaney, Thomas F. Kepka, Lucyna Goldberg, Saveli I. Hornicek, Francis J. Gebhardt, Mark C. Yoon, Sam S. Springfield, Dempsey S. Raskin, Kevin A. Harmon, David C. Kirsch, David G. Mankin, Henry J. Rosenberg, Andrew E. Nielsen, G. Petur Suit, Herman D. TI Radiation therapy for control of soft-tissue sarcomas resected with positive margins SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 16-20, 2005 CL Denver, CO SP Amer Soc Therapeut Radiol & Oncol DE soft-tissue sarcoma; positive margins; radiotherapy ID PROGNOSTIC-FACTORS; SURGICAL MARGINS; POSTOPERATIVE RADIOTHERAPY; EXTREMITY; ADULT; SURGERY; TRIAL AB Purpose: Positive margins (PM) remain after surgery in some soft-tissue sarcoma (STS) patients. We investigated the efficacy of radiation therapy (RT) in STS patients with PM. Methods and Materials: A retrospective chart review was performed on 154 patients with STS at various anatomic sites with PM, defined as tumor on ink, who underwent RT with curative intent between 1970 and 2001. Local control (LC), disease-free survival (DFS), and overall survival (OS) rates were evaluated by univariate (log-rank) and multivariate analysis of prognostic and treatment factors. Results: At 5 years, actuarial LC, DFS, and OS rates were: 76%, 46.7%, and 65.2%, respectively. LC was highest with extremity lesions (p < 0.01), radiation dose > 64 Gy (p < 0.05), microscopically (vs. grossly visible) positive margin (p = 0.03), and superficial lesions (p 0.05). Patients receiving > 64 Gy had higher 5-year LC, DFS, and OS rates of 85%, 52.1%, and 67.8% vs. 66.1%, 41.8%, and 62.9% if <= 64 Gy, p < 0.04. OS was worse in patients with G2/G3 tumors with local failure (LF), p < 0.001. Other known prognostic factors, including grade, stage, size, and age (> 50), also significantly influenced OS. By multivariate analysis, the best predictors of LC were site (extremity vs. other), p < 0.01 and dose (> 64 vs. <= 64 Gy), p < 0.05; the best predictors for OS were size, p < 0.001, gross vs. microscopic PM, p < 0.05, and LF, p < 0.01. Conclusion: Local control is achieved in most PM STS patients undergoing RT. Doses > 64 Gy, superficial location, and extremity site are associated with improved LC. OS is worse in patients with tumors with lesions > 5 cm, grossly positive margins, and after local failure. (c) 2007 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Orthopaed, Boston, MA 02215 USA. Marie Curie Sklodowska Mem Canc Ctr, Dept Radiat Oncol, Warsaw, Poland. Inst Oncol, Warsaw, Poland. RP DeLaney, TF (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Francis H Burr Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. EM tdelaney@partners.org NR 15 TC 57 Z9 63 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 1 PY 2007 VL 67 IS 5 BP 1460 EP 1469 DI 10.1016/j.ijrobp.2006.11.035 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 155HC UT WOS:000245567500024 PM 17394945 ER PT J AU Craft, D Suss, P Bortfeld, T AF Craft, David Suess, Philipp Bortfeld, Thomas TI The tradeoff between treatment plan quality and required number of monitor units in intensity-modulated radiotherapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 24-28, 2005 CL Seattle, WA SP Amer Assoc Physicists Med DE IMRT complexity; monitor units; multi-objective optimization; slim of positive gradients ID FLUENCE MAP OPTIMIZATION; RADIATION-THERAPY; CONFORMAL RADIOTHERAPY; MULTILEAF COLLIMATORS; 2ND CANCERS; IMRT; DELIVERY; IMPACT; COMPENSATION; SEGMENTS AB Purpose: To provide a mathematical approach for quantifying the tradeoff between intensity-modulated radiotherapy (IMRT) complexity and plan quality. Methods and Materials: We solve a multi-objective program that includes IMRT complexity, measured as the number of monitor units (MU) needed to deliver the plan using a multileaf collimator, as an objective. Clinical feasibility of plans is ensured by the use of hard constraints in the formulation. Optimization output is a Pareto surface of treatment plans, which allows the tradeoffs between IMRT complexity, tumor coverage, and tissue sparing to be observed. Paraspinal and lung cases are presented. Results: Although the amount of possible MU reduction is highly dependent on the difficulty of the underlying treatment plan (difficult plans requiring a high degree of intensity modulation are more sensitive to MU reduction), in some cases the number of MU can be reduced more than twofold with a < 1% increase in the objective function. Conclusions: The largely increased number of MU and irradiation time in IMRT is sometimes unnecessary. Tools like the one presented should be considered for integration into daily clinical practice to avoid this problem. (c) 2007 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Fraunhofer Inst Techno & Wirtschaftsmath, Dept Optimizat, Kaiserslautern, Germany. RP Craft, D (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM dcraft@partners.org FU NCI NIH HHS [1 R01 CA103904-01A1] NR 32 TC 36 Z9 36 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 1 PY 2007 VL 67 IS 5 BP 1596 EP 1605 DI 10.1016/j.ijrobp.2006.11.034 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 155HC UT WOS:000245567500040 PM 17394954 ER PT J AU Seliem, RM Chikwava, K Swerdlow, SH Young, RH Ferry, JA AF Seliem, Rania M. Chikwava, Kudakwashe Swerdlow, Steven H. Young, Robert H. Ferry, Judith A. TI Classical Hodgkin's lymphoma presenting as a testicular mass: Report of a case SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE testis; lymphoma; Hodgkin's lymphoma ID LARGE-CELL LYMPHOMA; EPSTEIN-BARR-VIRUS; PRIMARY FOLLICULAR LYMPHOMA; THE-LITERATURE; MALIGNANT-LYMPHOMA; GROUP EXPERIENCE; T-CELL; B-CELL; TESTIS; DISEASE AB Hodgkin's lymphoma almost always presents with lymphadenopathy. Presentation with extranodal disease is quite unusual, although Hodgkin's lymphoma is known to occasionally involve extranodal sites. However, no well-documented cases of testicular Hodgkin's lymphoma have been described. We report the case of a 52-year-old man who presented with a left testicular mass; orchiectomy revealed morphologic and immunophenotypic features typical of classical Hodgkin's lymphoma, nodular sclerosis type. C1 Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Pittsburgh, Sch Med, Dept Pathol, Div Hematopathol, Pittsburgh, PA USA. RP Ferry, JA (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Warren 2,55 Fruit St, Boston, MA 02114 USA. EM jferry@partners.org NR 39 TC 3 Z9 3 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD APR PY 2007 VL 15 IS 2 BP 207 EP 212 DI 10.1177/1066896906299071 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 148XK UT WOS:000245110500025 PM 17478785 ER PT J AU Burstein, HJ Overmoyer, B Gelman, R Silverman, P Savoie, J Clarke, K Dumadag, L Younger, J Ivy, P Winer, EP AF Burstein, Harold J. Overmoyer, Beth Gelman, Rebecca Silverman, Paula Savoie, Jennifer Clarke, Kathryn Dumadag, Leda Younger, Jerry Ivy, Percy Winer, Eric P. TI Rebeccamycin analog for refractory breast cancer: A randomized phase II trial of dosing schedules SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE breast cancer; rebeccamycin; rebeccamycin analog; phase II ID NSC-655649 AB Rebeccamycin analog (NSC 655649) is a synthetic antibiotic cytotoxic agent thought to inhibit topoisomerase function. We sought to determine the response rate to rebeccamycin analog among patients with refractory advanced breast cancer using two different treatment schedules. Eligible patients had measurable disease, central venous access, and one or two prior chemotherapy regimens for advanced cancer, or recurrence within 12 months of adjuvant chemotherapy. Patients were randomized to rebeccamycin analog on one of two treatment schedules: arm 1, 500 mg/m2 IV bolus every 21 days; arm 2, 140 mg/m2 IV bolus daily x5 days, every 21 days. The primary study endpoint was response rate; a two stage accrual design evaluated each schedule separately. Forty-two women entered the trial, 21 on each arm. Prior chemotherapy regimens for metastatic breast cancer were: 0, n=4; 1, n=21; 2, n=17. Prior treatments (including adjuvant therapy) anthracyclines: 88%, taxanes 67%, 5FU-based therapy, 50%. There were 5 partial responses (overall response rate 12%), two in arm 1 and 3 in arm 2, all in patients with prior anthracycline-based adjuvant chemotherapy. Median time to progression was 2.1 months (range 1-14+ months). An additional 9 patients had stable disease as best response. Grade 3 or 4 toxicity rates were: anemia 5%, neutropenia 33%, thrombocytopenia 12%, RBC transfusion 14%, nausea/vomiting 10%. Toxicity profiles were similar between the treatment arms. Rebeccamycin analog is reasonably well tolerated on two different treatment schedules for advanced breast cancer, with modest clinical activity in this heavily pretreated population. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Hosp Cleveland, Ireland Canc Ctr, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NCI, Bethesda, MD 20892 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM hburstein@partners.org NR 8 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD APR PY 2007 VL 25 IS 2 BP 161 EP 164 DI 10.1007/s10637-006-9007-6 PG 4 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 119WW UT WOS:000243046100009 PM 16969707 ER PT J AU Framme, C Alt, C Schnell, S Sherwood, M Brinkmann, R Lin, CP AF Framme, Carsten Alt, Clemens Schnell, Susanne Sherwood, Margaret Brinkmann, Ralf Lin, Charles P. TI Selective targeting of the retinal pigment epithelium in rabbit eyes with a scanning laser beam SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID DIODE-LASER; TIME REGIMEN; PHOTOCOAGULATION; INJURY; RPE; THRESHOLD; DAMAGE; NANOSECOND; EXPOSURE; LESIONS AB PURPOSE. Selective targeting of the retinal pigment epithelium (RPE) with repetitive laser pulses that minimize thermal damage to the adjacent photoreceptors is a promising new therapeutic modality for RPE-related retinal diseases. The selectivity of an alternative, more versatile scanning approach was examined in vivo by using a broad range of scanning parameters. METHODS. Acousto-optic deflectors repeatedly scanned the focus of a continuous wave (cw)-laser across the retina of Dutch belted rabbits, producing microsecond irradiation at each RPE cell. Two irradiation patterns forming separated lines (SEP) or interlaced lines (INT), different dwell times (2.5-75 mu s), and repetition numbers (10 and 100 scans with 100-Hz repetition rate) were tested. Thresholds were evaluated by fundus imaging and angiography. Histology was performed for selected parameters. RESULTS. Selective RPE cell damage was obtained with moderate laser power. The angiographic threshold power decreased with pulse duration, number of exposures, and applying the INT pattern. Ophthalmoscopic thresholds, indicating onset of thermal coagulation, were higher than twice the angiographic threshold for most tested parameters. Histology confirmed selective RPE cell damage for SEP irradiation with 7.5 and 15 mu s; slower scan speeds or closed lines caused photoreceptor damage. CONCLUSIONS. A cw-laser scanner can be set up as a highly compact and versatile device. Selective RPE damage is feasible with dwell times up to 15 mu s. Greatest selectivity is achieved with short exposure times and separated scan tines. Interlaced fines and long exposure times facilitate heat conduction into photoreceptors. A scanner is an attractive alternative for pulsed selective targeting, because both selective targeting and thermal photocoagulation can be realized. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Med Laser Ctr Lubeck, Lubeck, Germany. Univ Regensburg, Eye Hosp, Regensburg, Germany. Tufts Univ, Dept Biomed Engn, Medford, MA USA. Univ Appl Sci Hamburg, Hamburg, Germany. RP Lin, CP (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, CPZN-8240,185 Cambridge St, Boston, MA 02114 USA. EM lin@helix.mgh.harvard.edu RI Brinkmann, Ralf/E-6701-2012 FU NEI NIH HHS [EY 12106] NR 30 TC 14 Z9 15 U1 0 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2007 VL 48 IS 4 BP 1782 EP 1792 DI 10.1167/iovs.06-0797 PG 11 WC Ophthalmology SC Ophthalmology GA 153CB UT WOS:000245408200045 PM 17389512 ER PT J AU Moore, CM Biederman, J Wozniak, J Mick, E Aleardi, M Wardrop, M Dougherty, M Harpold, T Paul, H Randall, E Lyoo, IK Renshaw, PF AF Moore, Constance M. Biederman, Joseph Wozniak, Janet Mick, Eric Aleardi, Megan Wardrop, Megan Dougherty, Meghan Harpold, Terri Paul, Hammerness Randall, Edin Lyoo, In Kyoon Renshaw, Perry F. TI Mania, glutamate/glutamine and risperidone in pediatric bipolar disorder: A proton magnetic resonance spectroscopy study of the anterior cingulate cortex SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE mania; glutamate/glutamine; bipolar disorder; proton magnetic resonance spectroscopy; anterior cingulate cortex ID DEFICIT HYPERACTIVITY DISORDER; IN-VIVO; CONVENTIONAL NEUROLEPTICS; QUANTITATIVE-ANALYSIS; PREFRONTAL CORTEX; MOOD DISORDERS; HUMAN BRAIN; GLUTAMATE; ACTIVATION; CHILDREN AB Background: The purpose of this study was to investigate the anterior cingulate cortex (ACC) glutamate/glutamine (Glx) to creatine ratio (Glx/Cr) in two groups of children with Bipolar Disorder (BPD): those exhibiting manic symptoms requiring treatment and those being stably treated with the atypical antipsychotic risperidone. Atypical antipsychotics have been shown to increase serum glutamate levels and ACC Glx/Cr in subjects with schizophrenia. In this study, we hypothesized that the children with BPD in need of treatment would have lower Glx/Cr compared with the children with BPD being stably treated with risperidone. Methods: Proton MR spectra were acquired, at 1.5 T, from the ACC of eighteen subjects with a DSM-IV diagnosis of BPD: ten (11.10 +/- 3.48 years; five female) were manic and not medicated with any antipsychotic and eight (10.88 +/- 2.99 years; one female) were medicated with the atypical antipsychotic risperidone. Results: Children with BPD exhibiting manic symptoms requiring treatment had lower Glx/Cr than children with BPD being stably treated with the atypical antipsychotic risperidone. The children treated with risperidone also had significantly lower YMRS and CGI-Mania scores than the children not treated with risperidone. Both YMRS and CGI-Mania scores correlated negatively with ACC Glx/Cr levels. Limitations: The cross-sectional design, small sample size, the use of Glx rather than glutamate or glutamine and the use of Cr ratios rather than absolute concentrations are limitations of this study. Conclusions: Children with mania have lower Glx/Cr levels than children with BPD being stably treated with the atypical antipsychotic risperidone. Mania may be associated with reduced glutamate/glutamine levels in the ACC: other imaging studies have shown mania associated with hypometabolism in the ACC. These reductions in glutamate/glutamine may be increased following successful treatment with glutamatergic agents. (c) 2006 Elsevier B.V. All rights reserved. C1 McLean Hosp, Brain Imaging Ctr, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA 02114 USA. RP Moore, CM (reprint author), McLean Hosp, Brain Imaging Ctr, Belmont, MA 02478 USA. EM const@mclean.harvard.edu OI Mick, Eric/0000-0001-8505-8145 FU NIMH NIH HHS [K01 MH001798, K01 MH001978, MH01798] NR 33 TC 29 Z9 31 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD APR PY 2007 VL 99 IS 1-3 BP 19 EP 25 DI 10.1016/j.jad.2006.08.023 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 149NS UT WOS:000245154300003 PM 17005256 ER PT J AU Henin, A Biederman, J Mick, E Hirshfeld-Becker, DR Sachs, GS Wu, Y Yan, L Ogutha, J Nierenberg, AA AF Henin, Aude Biederman, Joseph Mick, Eric Hirshfeld-Becker, Dina R. Sachs, Gary S. Wu, Yelena Yan, Leslie Ogutha, Jacqueline Nierenberg, Andrew A. TI Childhood antecedent disorders to bipolar disorder in adults: A controlled study SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE bipolar disorder; childhood disorders; adult; mood disorders; ADHD ID DEFICIT HYPERACTIVITY DISORDER; ADOLESCENT MANIA; REFERRED CHILDREN; CONDUCT DISORDER; JUVENILE MANIA; ONSET; COMORBIDITY; PHENOMENOLOGY; UNIPOLAR; PARENTS AB Objective: The aim of the study was to examine antecedent childhood psychiatric disorders in adult patients with bipolar disorder. Method: Using structured diagnostic interviews, childhood psychiatric diagnoses of 83 referred patients with diagnosed DSM-IV bipolar disorder were compared to those of 308 adults without mood disorders. Results: Patients with bipolar disorder had significantly higher rates of childhood disruptive behavior disorders (ADHD, oppositional-defiant disorder, and conduct disorder), childhood anxiety disorders (separation anxiety and overanxious disorder), and enuresis, compared to patients without mood disorders. The presence of these childhood disorders was associated with an earlier age of onset of bipolar illness. Limitations: The retrospective nature of the study may have affected both the rates of disorders recalled, as well as the ages of onset of disorders. Different referral sources for bipolar and comparison participants may have also impacted findings. Conclusions: Bipolar disorder in adults is frequently preceded by childhood disruptive behavior and anxiety disorders. These childhood disorders may be important markers of risk for adult bipolar disorder. (c) 2006 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Bipolar Clin, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Res Program, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Henin, A (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, 185 Alewife Brook Pkwy,Suite 2000, Cambridge, MA 02138 USA. EM ahenin@partners.org OI Mick, Eric/0000-0001-8505-8145 NR 42 TC 41 Z9 44 U1 3 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD APR PY 2007 VL 99 IS 1-3 BP 51 EP 57 DI 10.1016/j.jad.2006.09.001 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 149NS UT WOS:000245154300007 PM 17045657 ER PT J AU Williams, BR Baker, PS Allman, RM Roseman, JM AF Williams, Beverly Rosa Baker, Patricia Sawyer Allman, Richard M. Roseman, Jeffrey M. TI Bereavement among African American and White older adults SO JOURNAL OF AGING AND HEALTH LA English DT Article DE African American and White older adults; geriatric bereavement events; spousal loss; nonspousalfiamily loss; friendship loss ID SOCIAL SUPPORT; LATE-LIFE; FICTIVE KIN; FAMILY; DEATH; AGE; FRIENDSHIPS; NETWORKS; PATTERNS; WOMEN AB Purpose: The authors examined epidemiology and sociodemographic predictors of spousal, nonspousal family, and friendship bereavement among African American and White community-dwelling older adults using longitudinal data from 839 participants of the University of Alabama at Birmingham Study of Aging, a prospective cohort study of a random sample of Alabama Medicare beneficiaries. Method: Authors calculated cumulative incidences of each type of loss and used logistic regression to identify factors significantly and independently associated with loss. Results: Of participants, 71% reported at least one loss; 50% reported nonspousal family loss, and 37% reported friendship loss. For married participants, the cumulative incidence of spousal loss was 8.1%. Female sex and income < $12,000 were predictors of spousal loss. Female sex and education >= 12 years were predictors of friendship loss. Higher educated African American women were at greater risk of nonspousal family loss. Discussion: Future research should examine bereavement burden and identify health outcomes of multiple losses. C1 Univ Alabama, Birmingham Atlanta VA Geriatr Res Educ & Clin Ctr, GRECC, Birmingham VA Med Ctr, Birmingham, AL 35233 USA. RP Williams, BR (reprint author), Univ Alabama, Birmingham Atlanta VA Geriatr Res Educ & Clin Ctr, GRECC, Birmingham VA Med Ctr, 700 W 19th St, Birmingham, AL 35233 USA. EM beverly.williams3@va.gov FU NIA NIH HHS [R01 AG015062, R01 AG15062] NR 60 TC 13 Z9 13 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0898-2643 J9 J AGING HEALTH JI J. Aging Health PD APR PY 2007 VL 19 IS 2 BP 313 EP 333 DI 10.1177/0898264307299301 PG 21 WC Gerontology; Health Policy & Services SC Geriatrics & Gerontology; Health Care Sciences & Services GA 147NQ UT WOS:000245010100009 PM 17413138 ER PT J AU Quijano, LM Stanley, MA Petersen, NJ Casado, BL Steinberg, EH Cully, JA Wilson, NL AF Quijano, Louise M. Stanley, Melinda A. Petersen, Nancy J. Casado, Banghwa Lee Steinberg, Esther H. Cully, Jeffrey A. Wilson, Nancy L. TI Healthy IDEAS: A depression intervention delivered by community-based case managers serving older adults SO JOURNAL OF APPLIED GERONTOLOGY LA English DT Article DE depression; community-based; case managers; evidence-based ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY-CARE PATIENTS; LATE-LIFE DEPRESSION; BEHAVIORAL ACTIVATION; DISORDERS; FRAMEWORK; SELECTION; SYMPTOMS; SCREENER; OUTCOMES AB This study evaluated an evidence-based intervention for depression delivered by case managers in three community-based service agencies to high-risk, diverse older adults. Case managers were trained to provide screening and assessment, education, referral and linkage, and behavioral activation. Outcomes addressed depression, general health status, social and physical activation, and mental health services use at baseline and 6 months. Participants (n = 94) were predominantly women (79%) and Hispanic (44%), with a mean age of 72 years. Mean Geriatric Depression Scale-15 scores differed significantly between baseline and 6 months (9.0 versus 5.5). At 6 months, significantly more participants knew how to get help for depression (68% versus 93%), reported that increasing activity helped them feel better (72% versus 89%), and reported reduced pain (16% versus 45%). The authors conclude that nonspecialty providers can be trained to successfully implement an evidence-based self-management intervention for depression with frail, high-risk, and diverse older adults. C1 Baylor Coll Med, Ctr Qual Care & Utilizat Studies, Michael E DeBakey Vet Affairs Med Ctr, Huffington Ctr Aging, Houston, TX 77030 USA. Univ Maryland, Baltimore, MD 21201 USA. Sheltering Arms Senior Serv, Houston, TX USA. RP Wilson, NL (reprint author), Baylor Coll Med, Ctr Qual Care & Utilizat Studies, Michael E DeBakey Vet Affairs Med Ctr, Huffington Ctr Aging, 1 Baylor Plaza M-320, Houston, TX 77030 USA. EM nwilson@bcm.edu NR 32 TC 46 Z9 46 U1 4 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0733-4648 J9 J APPL GERONTOL JI J. Appl. Gerontol. PD APR PY 2007 VL 26 IS 2 BP 139 EP 156 DI 10.1177/0733464807299354 PG 18 WC Gerontology SC Geriatrics & Gerontology GA 157WM UT WOS:000245752100002 ER PT J AU Muratoglu, OK Rubash, HE Bragdon, CR Burroughs, BR Huang, A Harris, WH AF Muratoglu, Orhun K. Rubash, Harry E. Bragdon, Charles R. Burroughs, Brian R. Huang, Anna Harris, William H. TI Simulated normal gait wear testing of a highly cross-linked polyethylene tibial insert SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total knee; wear; backside wear; polyethylene ID TOTAL KNEE ARTHROPLASTY; MOLECULAR-WEIGHT POLYETHYLENE; HAP-PAUL-AWARD; KINEMATICS; OSTEOLYSIS; REPLACEMENT; PERFORMANCE; DESIGN AB Polyethylene wear can compromise long-term performance of total knees. We investigated articular and backside wear rate of tibial inserts made from conventional vs highly cross-linked polyethylenes. The inserts were tested on a knee simulator at a frequency of 1.1 Hz using normal gait kinematics with a 7 degrees posterior slope for 7 million cycles. Gravimetrically, the combined articular and backside wear rate was 23 +/- 6 and 4.6 +/- 2 mm(3) per million cycles for the conventional and cross-linked inserts, respectively. We independently measured articular surface wear rates, which were 15 +/- 4 and 5 +/- 2 mm(3) per million cycles for conventional and cross-linked inserts, respectively. Electron beam cross-linked and subsequently melted polyethylene reduced the wear rate of polyethylene on articular and backside surfaces in a cruciate-retaining total knee design when tested on a knee simulator under simulated normal gait. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, GRJ 1206, Boston, MA 02114 USA. NR 24 TC 37 Z9 38 U1 1 U2 4 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD APR PY 2007 VL 22 IS 3 BP 435 EP 444 DI 10.1016/j.arth.2006.07.014 PG 10 WC Orthopedics SC Orthopedics GA 162AC UT WOS:000246057500016 PM 17400100 ER PT J AU Medrano, MS Ding, YP Wang, XG Lu, P Coburn, J Hu, LT AF Medrano, Melisa S. Ding, Yanpeng Wang, Xing-Guo Lu, Peng Coburn, Jenifer Hu, Linden T. TI Regulators of expression of the oligopeptide permease A proteins of Borrelia burgdorferi SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LYME-DISEASE SPIROCHETE; ESCHERICHIA-COLI; SURFACE-PROTEINS; BINDING-PROTEIN; FACTOR-H; DIPEPTIDE PERMEASE; RESPONSE REGULATOR; INFECTION; MICE; TRANSMISSION AB Borrelia burgdorferi undergoes an infectious cycle that requires adaptation to different hosts and marked differences in environment. B. burgdorferi copes with its different environments by regulating the expression of proteins required for survival in specific settings. The B. burgdorferi oligopeptide permease (Opp) is one of only a few transporters encoded by the B. burgdorferi genome. Opp proteins in other bacteria serve multiple environmental adaptation functions. B. burgdorferi appears to broaden the usage of this transporter by utilizing five different substrate binding proteins (OppA proteins) that interact with the integral membrane components of the transporter. Expression of the OppA proteins is individually regulated and may play different roles in adaptation to host environments. Very little is known about the mechanisms used by B. burgdorferi to regulate the expression of different OppA proteins. Here we show that the alternative sigma factors, RpoS and RpoN, regulate the expression of oppA5 but not that of other oppA genes. Using a reporter assay with Escherichia coli and gel shift binding assays, we also show that the B. burgdorferi BosR/Fur homologue interacts with the oppA4 promoter and that another candidate transcription factor, EbfC, interacts with the oppA5 promoter. Binding to the promoters was confirmed by gel shift assays. Expression of BosR/Fur in its different hosts does appear to parallel the expression of oppA4. A better understanding of the factors involved in gene regulation in B. burgdorferi will help to identify coregulated proteins that may cooperate to allow the organism to survive in a specific environment. C1 Tufts Univ, New England Med Ctr, Sch Med, Tupper Res Inst,Div Geog Med & Infect Dis, Boston, MA 02111 USA. Hubei Univ, Sch Life Sci, Wuhan, Peoples R China. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Univ Kentucky, Dept Mol & Cellular Biochem, Lexington, KY USA. Univ Kentucky, Ctr Struct Biol, Lexington, KY USA. RP Hu, LT (reprint author), Tufts Univ, New England Med Ctr, Sch Med, Tupper Res Inst,Div Geog Med & Infect Dis, Box 41,750 Washington St, Boston, MA 02111 USA. EM lhu@tufts-nemc.org RI Hu, Linden/L-6314-2016 OI Hu, Linden/0000-0003-1659-5558 FU NIAID NIH HHS [R01 AI044240-02, R01 AI044240-05, R01 AI050043, R01 AI44240, R01 AI51407, F31 AI52495, R01 AI044240, R01 AI044240-04, R01 AI051407, F31 AI052495, R01 AI044240-01A2, R01 AI044240-03, R01 AI50043]; NIDDK NIH HHS [P30 DK39428] NR 28 TC 30 Z9 32 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 2007 VL 189 IS 7 BP 2653 EP 2659 DI 10.1128/JB.01760-06 PG 7 WC Microbiology SC Microbiology GA 159CC UT WOS:000245842000009 PM 17237172 ER PT J AU Truong-Bolduc, QC Hooper, DC AF Truong-Bolduc, Que Chi Hooper, David C. TI The transcriptional regulators NorG and MgrA modulate resistance to both quinolones and beta-lactams in Staphylococcus aureus SO JOURNAL OF BACTERIOLOGY LA English DT Article ID PENICILLIN-BINDING PROTEIN-4; MULTIDRUG-RESISTANCE; EFFLUX PUMP; TRANSPORTER; EXPRESSION; AUTOLYSIS; GENES AB MgrA is a known regulator of the expression of several multidrug transporters in Staphylococcus aureus. We identified another regulator of multiple efflux pumps, NorG, by its ability, like that of MgrA, to bind specifically to the promoter of the gene encoding the NorA efflux pump. NorG is a member of the family of the GntR-like transcriptional regulators, and it binds specifically to the putative promoters of the genes encoding multidrug efflux pumps NorA, NorB, NorC, and AbcA. Overexpression of norG produces a threefold increase in norB transcripts associated with a fourfold increase in the level of resistance to quinolones. In contrast, disruption of norG produces no change in the level of transcripts of norA, norB, and norC but causes an increase of at least threefold in the transcript level of abcA, associated with a fourfold increase in resistance to methicillin, cefotaxime, penicillin G, and nafcillin. Overexpression of cloned abcA caused an 8- to 128-fold increase in the level of resistance to all four beta-lactam antibiotics. Furthermore, MgrA and NorG have opposite effects on norB and abcA expression. MgrA acts as an indirect repressor for norB and a direct activator for abcA, whereas NorG acts as a direct activator for norB and a direct repressor for abcA. C1 Harvard Univ, Div Infect Dis, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Med Serv, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hooper, DC (reprint author), Harvard Univ, Div Infect Dis, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org FU NIAID NIH HHS [R01 AI023988, R01-AI23988] NR 29 TC 43 Z9 49 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 2007 VL 189 IS 8 BP 2996 EP 3005 DI 10.1128/JB.01819-06 PG 10 WC Microbiology SC Microbiology GA 161QB UT WOS:000246029300006 PM 17277059 ER PT J AU Coufal, M Maxwell, MM Russel, DE Amore, AM Altmann, SM Hollingsworth, ZR Young, AB Housman, DE Kazantsev, AG AF Coufal, Myra Maxwell, Michele M. Russel, Deborah E. Amore, Allison M. Altmann, Stephen M. Hollingsworth, Zane R. Young, Anne B. Housman, David E. Kazantsev, Aleksey G. TI Discovery of a novel small-molecule targeting selective clearance of mutant huntingtin fragments SO JOURNAL OF BIOMOLECULAR SCREENING LA English DT Article DE Huntington's disease; high-throughput screening; huntingtin; protein clearance; toxicity rescue ID DISEASE GENE HOMOLOG; POLYGLUTAMINE AGGREGATION; EMBRYONIC LETHALITY; CELLULAR TOXICITY; MOUSE MODEL; BRAIN; MOTOR; MICE; INACTIVATION; APOPTOSIS AB CAG-triplet repeat extension, translated into polyglutamines within the coding frame of otherwise unrelated gene products, causes 9 incurable neurodegenerative disorders, including Huntington's disease. Although an expansion in the CAG repeat length is the autosomal dominant mutation that causes the fully penetrant neurological phenotypes, the repeat length is inversely correlated with the age of onset. The precise molecular mechanism(s) of neurodegeneration remains elusive, but compelling evidence implicates the protein or its proteolytic fragments as the Cause for the gain of novel pathological function(s). The authors sought to identify small molecules that target the selective clearance of polypeptides containing pathological polyglutamine extension. In a high-throughput chemical screen, they identified compounds that facilitate the clearance of a small huntingtin fragment with extended polyglutamines fused to green fluorescent protein reporter. Identified hits were validated in dose- response and toxicity tests. Compounds have been further tested in an assay for clearance of a larger huntingtin fragment, containing either pathological or normal polyglutamine repeats. In this assay, the authors identified compounds selectively targeting the clearance of mutant but not normal huntingtin fragments. These compounds were subjected to a functional assay, which yielded a lead compound that rescues cells from induced mutant polyglutamine toxicity. C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. MIT, Cambridge, MA 02139 USA. RP Kazantsev, AG (reprint author), Massachusetts Gen Hosp, Bldg 114-3300,16th St, Charlestown, MA 02129 USA. EM akazantsev@partners.org NR 25 TC 15 Z9 15 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0571 J9 J BIOMOL SCREEN JI J. Biomol. Screen PD APR PY 2007 VL 12 IS 3 BP 351 EP 360 DI 10.1177/1087057107299428 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry GA 157WV UT WOS:000245753000006 PM 17379859 ER PT J AU Park, JY Arnaout, MA Gupta, V AF Park, Jun Y. Arnaout, M. Amin Gupta, Vineet TI A simple, no-wash cell adhesion-based high-throughput assay for the discovery of small-molecule regulators of the integrin CD11b/CD18 SO JOURNAL OF BIOMOLECULAR SCREENING LA English DT Article DE integrin; no-wash assay; cell adhesion assay; primary screen ID NEUTROPHIL INHIBITORY FACTOR; MAC-1 CD11B/CD18; BETA-2 INTEGRINS; STRUCTURAL BASIS; INFLAMMATORY RESPONSE; MONOCLONAL-ANTIBODIES; LIGAND-BINDING; SITE FACE; I-DOMAIN; LEUKOCYTE AB The leukocyte-specific integrin CD11b/CD18 plays a key role in the biological function of these cells and represents a validated therapeutic target for inflammatory diseases. Currently, the low affinity interaction between CD11b/CD18 integrin and its respective ligand poses a challenge in the development of cell-based adhesion assays for the high-throughput screening (HTS) environment. Here the authors describe a simple cell-based adhesion assay that can be readily used for HTS for the discovery of functional regulators of CD11b/CD18. The assay consistently produces acceptable Z' values (> 0.5) for HTS. After testing the assay using 2 established blocking antibodies as reference biologicals, the authors performed a proof-of-concept primary screen using a library of 6612 compounds and identified both agonist and antagonist hits. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Nephrol Div,Leukocyte Biol & Inflammat Program, Charlestown, MA 02129 USA. RP Gupta, V (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Nephrol Div,Leukocyte Biol & Inflammat Program, Charlestown, MA 02129 USA. EM vineet_gupta@hms.harvard.edu RI Gupta, Vineet/B-1134-2009; OI Gupta, Vineet/0000-0001-6987-2550 FU NIDDK NIH HHS [K01 DK068253-03, K01 DK068253, DK068253]; NINDS NIH HHS [R03 NS053659, NS053659, R03 NS053659-01] NR 42 TC 16 Z9 16 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0571 J9 J BIOMOL SCREEN JI J. Biomol. Screen PD APR PY 2007 VL 12 IS 3 BP 406 EP 417 DI 10.1177/1087057106299162 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry GA 157WV UT WOS:000245753000012 PM 17438069 ER PT J AU Darouiche, RO Mansouri, MD Zakarevicz, D AlSharif, A Landon, GC AF Darouiche, Rabih O. Mansouri, Mohammad D. Zakarevicz, Devin AlSharif, Atef Landon, Glenn C. TI In vivo efficacy of antimicrobial-coated devices SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID CENTRAL VENOUS CATHETERS; RANDOMIZED CONTROLLED-TRIAL; STAPHYLOCOCCUS-AUREUS; SURGICAL IMPLANTS; 2-STAGE REVISION; MINOCYCLINE; RIFAMPIN; INFECTIONS; COLONIZATION; ANTIBIOTICS AB Background: Since device colonization is a prelude to infection, an anti microbia I-coated device that reduces bacterial colonization can potentially protect against infection. The objective of this animal study was to assess the efficacy of a coating with minocycline and rifampin to prevent colonization of a grit-blasted titanium implant and subsequent osteomyelitis. Methods: Twenty-five rabbits underwent implantation of a titanium-alloy pin, either coated with minocycline and rifampin (thirteen rabbits) or uncoated (twelve rabbits), into the right femoral medullary canal. The implanted devices were inoculated with 500 CFU (colony-forming units) of Staphylococcus aureus prior to wound closure. The rabbits were killed one week later, and the removed device, femoral bone, a specimen obtained by swabbing the track surrounding the device, and blood were cultured. The rates of device colonization, osteomyelitis, and device-related osteomyelitis were compared between the two groups of rabbits. Results: The antimicrobial-coated devices had a significantly lower rate of colonization than the uncoated devices (five of thirteen compared with twelve of twelve, p = 0.0016) and were associated with significantly lower rates of osteomyelitis (six of thirteen compared with twelve of twelve, p = 0.005) and device-related osteomyelitis (five of thirteen compared with twelve of twelve, p = 0.0016). Bacteremia did not develop in any rabbit. Conclusions: Orthopaedic devices coated with minocycline and rifampin significantly protected against device colonization and infection due to Staphylococcus aureus in this in vivo rabbit model. Clinical Relevance: It is possible that orthopaedic devices coated with this unique combination of antimicrobial agents may protect against the development of clinical infection in humans. C1 Baylor Coll Med, Ctr Prostheses Infect, Houston, TX 77030 USA. Kelsey Seybold Clin, Sect Orthoped Surg, Houston, TX 77025 USA. Michael E DeBakey Vet Affairs Med Ctr, Spinal Cord Injury Lab, Houston, TX 77030 USA. RP Darouiche, RO (reprint author), Baylor Coll Med, Ctr Prostheses Infect, 1333 Moursund Ave,Suite A221, Houston, TX 77030 USA. EM rdarouiche@aol.com; mansouri@bcm.tmc.edu; dmzakarevicz@kelsey-seybold.com; alsharif@bcm.tmc.edu; gclandon@kelsey-seybold.com NR 33 TC 60 Z9 61 U1 0 U2 8 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD APR PY 2007 VL 89A IS 4 BP 792 EP 797 DI 10.2106/JBJS.F.00414 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 154PL UT WOS:000245519600014 PM 17403802 ER PT J AU Fitzsimons, MG Agnihotri, AK AF Fitzsimons, Michael G. Agnihotri, Arvind Kumar TI Hyponatremia and cardiopulmonary bypass SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE hyponatremia; sodium; cardiopulmonary bypass ID ANTIDIURETIC-HORMONE; CARBAMAZEPINE C1 Harvard Univ, Dept Anesthesia & Crit Care, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Dept Cardiothorac Surg, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Fitzsimons, MG (reprint author), Harvard Univ, Dept Anesthesia & Crit Care, Sch Med, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM mfitzsimons@partners.org NR 17 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD APR PY 2007 VL 21 IS 2 BP 273 EP 275 DI 10.1053/j.jvca.2006.07.014 PG 3 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 159NM UT WOS:000245872800023 PM 17418748 ER PT J AU Neuzil, P Balak, J Kralovec, S Reddy, VY AF Neuzil, Petr Balak, Jan Kralovec, Stepan Reddy, Vivek Y. TI Substrate-based catheter ablation of epicardial ventricular tachycardia related to an anomalous coronary artery SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE ventricular tachycardia; epicardial mapping; electroanatomical mapping; catheter ablation; coronary artery anomaly; MR imaging ID MYOCARDIAL-INFARCTION AB Delayed enhancement magnetic resonance imaging is known for its ability to identify scarred myocardial tissue. This case report describes the use of MR imaging to define the location and transmural extent of infarcted tissue in a 45-year-old woman with an anomalous right coronary artery and hemodynamically unstable ventricular tachycardia. By demonstrating a predominantly epicardial infarct, MR imaging indicated that the pericardial approach was necessary for successful substrate-based ventricular tachycardia ablation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Na Homolce Hosp, Dept Cardiol, Prague, Czech Republic. RP Reddy, VY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM vreddy@partners.org FU NHLBI NIH HHS [HL68062] NR 11 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD APR PY 2007 VL 18 IS 4 BP 446 EP 448 DI 10.1111/j.1540-8167.2006.00717.x PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 147CS UT WOS:000244981600018 PM 17239137 ER PT J AU Li, HL Yin, R Chen, DD Liu, D Wang, D Yang, QL Dong, YG AF Li, Hong-Liang Yin, Ran Chen, Dandan Liu, Dan Wang, Dong Yang, Qinglin Dong, Yu-Gang TI Long-term activation of adenosine monophosphate-activated protein kinase attenuates pressure-overload-induced cardiac hypertrophy SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE AMPK; NFAT; NF-kappa B; cardiac hypertrophy ID NF-KAPPA-B; AORTIC ENDOTHELIAL-CELLS; IN-VIVO; PROLIFERATION; SURVIVAL; MUSCLE; PEROXYNITRITE; MODULATION; RECEPTOR; PATHWAYS AB Recent in vitro studies suggest that adenosine monophosphate (AMP)-activated protein kinase (AMPK) exerts inhibitory effects on cardiac hypertrophy. However, it is unclear whether long-term activation of AMPK will affect cardiac hypertrophy in vivo. In these reports, we investigate the in vivo effects of long-term AMPK activation on cardiac hypertrophy and the related molecular mechanisms. To examine the effects of AMPK activation in the development of pressure overload-induced cardiac hypertrophy, we administered 5-aminoimidazole 1 carboxamide ribonucleoside (AICAR, 0.5 mg/g body wt), a specific activator of AMPK, to rats with transaortic constriction (TAC) for 7 weeks. We found that long-term AMPK activation attenuated cardiac hypertrophy, and improved cardiac function in rats subjected to TAC. Furthermore, long-term AMPK activation attenuated protein synthesis, diminished calcineurin-nuclear factor of activated T. cells, (NFAT) and nuclear factor kappa B (NF-kappa B) signaling in pressure overload-induced hypertrophic hearts. Our in vitro experiments further proved that activation of AMPK by infection of AdAMPK blocked cardiac hypertrophy and NFAT, NF-kappa B, and MAPK signal pathways. The present study demonstrates for the first time that pharmacological activation of AMPK inhibits cardiac hypertrophy in through blocking signaling transcluction pathways that are involved in cardiac growth. It presents a potential therapy strategy to inhibit pathological cardiac hypertrophy by increasing the activity of AMPK. C1 Sun Yat Sen Univ, Dept Cardiol, Hosp 1, Guangzhou 510080, Guangdong, Peoples R China. Chinese Acad Med Sci, Natl Lab Med Mol Biol, Inst Basic Med Sci, Beijing 100005, Peoples R China. Peking Union Med Coll, Beijing 100005, Peoples R China. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Univ Tennessee, Ctr Hlth Sci, Dept Physiol, Memphis, TN 38163 USA. Morehouse Sch Med, Cardiovasc Res Inst, Atlanta, GA 30310 USA. RP Dong, YG (reprint author), Sun Yat Sen Univ, Dept Cardiol, Hosp 1, 58 Zhongshan Rd 2, Guangzhou 510080, Guangdong, Peoples R China. EM yg.dong@medmail.com.cn NR 36 TC 72 Z9 75 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 1 PY 2007 VL 100 IS 5 BP 1086 EP 1099 DI 10.1002/jcb.21197 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 149NR UT WOS:000245154200002 PM 17266062 ER PT J AU Richardson, JA Amantea, CM Kianmahd, B Tetradis, S Lieberman, JR Hahn, TJ Parhami, F AF Richardson, Jennifer A. Amantea, Christopher M. Kianmahd, Benjamin Tetradis, Sotirios Lieberman, Jay R. Hahn, Theodore J. Parhami, Farhad TI Oxysterol-induced osteoblastic differentiation of pluripotent mesenchyrnal cells is mediated through a PKC- and PKA-dependent pathway SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE oxysterols; marrow stromal cells; osteoblastic differentiation; Runx2; PKC; PKA ID MARROW STROMAL CELLS; TRANSCRIPTION FACTOR; BONE-FORMATION; STEM-CELLS; IN-VITRO; SKELETAL DEVELOPMENT; SIGNALING PATHWAYS; GENE-EXPRESSION; PROTEIN-KINASE; RUNX2 AB Oxysterols form a large family of oxygenated derivatives of cholesterol that are present in circulation, and in human and animal tissues. The discovery of osteoinductive molecules that can induce the lineage-specific differentiation of cells into osteoblastic cells and therefore enhance bone formation is crucial for better management of bone fractures and osteoporosis. We previously reported that specific oxysterols have potent osteoinductive properties and induce the osteoblastic differentiation of pluripotent mesenchymal cells. In the present report we demonstrate that the induction of osteoblastic differentiation by oxysterols is mediated through a protein kinase C (PKC)- and protein kinase A (PKA)-dependent mechanism(s). Furthermore, oxysterol-incluced-osteoblastic differentiation is marked by the prolonged DNA-binding activity of Runx2 in M2-10B4 bone marrow stromal cells (MSCs) and C3H10T1/2 embryonic fibroblastic cells. This increased activity of Runx2 is almost completely inhibited by PKC inhibitors Bisindolylmaleimide and Rottlerin, and only minimally inhibited by PKA inihibitor H-89. PKC- and PKA-dependent mechanisms appear to also regulate other markers of osteoblastic differentiation including alkaline phosphatase (ALP) activity and osteocalcin mRNA expression in response to oxysterols. Finally, osteogenic oxysterols induce osteoblastic differentiation with BMP7 and BMP14 in a synergistic manner as demonstrated by the enhanced Runx2 DNA-binding activity, ALP activity, and osteocalcin mRNA expression. Since Runx2 is an indispensable factor that regulates the differentiation of osteoblastic cells and bone formation in vitro and in vivo, its increased activity in oxysterol-treated cells further validates the potential role of oxysterols in lineage-specific differentiation of pluripotent mesenchymal cells and their potential therapeutic use as bone anabolic factors. C1 Univ Calif Los Angeles, David Geffen Sch Med, Hlth Sci Ctr, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Orthoped Surg, Los Angeles, CA 90095 USA. Ctr Geriatr Res Educ & Clin, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. RP Parhami, F (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Hlth Sci Ctr, Dept Med, BH-307,10833 Conte Ave, Los Angeles, CA 90095 USA. EM fparhami@mednet.ucla.edu FU NHLBI NIH HHS [HL3056]; NIAMS NIH HHS [R01AR050426] NR 49 TC 33 Z9 34 U1 2 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 1 PY 2007 VL 100 IS 5 BP 1131 EP 1145 DI 10.1002/jcb.21112 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 149NR UT WOS:000245154200006 PM 17031848 ER PT J AU Miller, KK Lawson, EA Mathur, V Wexler, TL Meenaghan, E Misra, M Herzog, DB Klibanski, A AF Miller, K. K. Lawson, E. A. Mathur, V. Wexler, T. L. Meenaghan, E. Misra, M. Herzog, D. B. Klibanski, A. TI Androgens in women with anorexia nervosa and normal-weight women with hypothalamic amenorrhea SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HORMONE BINDING GLOBULIN; BONE-MINERAL DENSITY; ORAL-CONTRACEPTIVES; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; STEROID-SECRETION; ADOLESCENT GIRLS; RANDOMIZED TRIAL; DEFICIENT WOMEN; SEX STEROIDS AB Context: Anorexia nervosa and normal-weight hypothalamic amenorrhea are characterized by hypogonadism and hypercortisolemia. However, it is not known whether these endocrine abnormalities result in reductions in adrenal and/or ovarian androgens or androgen precursors in such women, nor is it known whether relative androgen deficiency contributes to abnormalities in bone density and body composition in this population. Objective: Our objective was to determine whether endogenous androgen and dehydroepiandrosterone sulfate (DHEAS) levels: 1) are reduced in women with anorexia nervosa and normal-weight hypothalamic amenorrhea, 2) are reduced further by oral contraceptives in women with anorexia nervosa, and 3) are predictors of weight, body composition, or bone density in such women. Design and Setting: We conducted a cross-sectional study at a general clinical research center. Study Participants: A total of 217 women were studied: 137 women with anorexia nervosa not receiving oral contraceptives, 32 women with anorexia nervosa receiving oral contraceptives, 21 normal-weight women with hypothalamic amenorrhea, and 27 healthy eumenorrheic controls. Main Outcome Measures: Testosterone, free testosterone, DHEAS, bone density, fat-free mass, and fat mass were assessed. Results: Endogenous total and free testosterone, but not DHEAS, were lower in women with anorexia nervosa than in controls. More marked reductions in both free testosterone and DHEAS were observed in women with anorexia nervosa receiving oral contraceptives. In contrast, normal-weight women with hypothalamic amenorrhea had normal androgen and DHEAS levels. Lower free testosterone, total testosterone, and DHEAS levels predicted lower bone density at most skeletal sites measured, and free testosterone was positively associated with fat-free mass. Conclusions: Androgen levels are low, appear to be even further reduced by oral contraceptive use, and are predictors of bone density and fat-free mass in women with anorexia nervosa. Interventional studies are needed to confirm these findings and determine whether oral contraceptive use, mediated by reductions in endogenous androgen levels, is deleterious to skeletal health in such women. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Psychiat, Harris Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Psychiat, Harris Ctr, Bulfinch 457B, Boston, MA 02114 USA. EM KKMiller@Partners.org OI Mathur, Vani/0000-0002-9395-940X FU NCRR NIH HHS [M01 RR001066, M01 RR01066]; NIDDK NIH HHS [R01 DK052625, P30 DK040561, P30 DK040561-12, R01-DK52625] NR 51 TC 51 Z9 54 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2007 VL 92 IS 4 BP 1334 EP 1339 DI 10.1210/jc.2006-2501 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 153WH UT WOS:000245466600025 PM 17284620 ER PT J AU Srouji, SS Pagan, YL D'Amato, F Dabela, A Jimenez, Y Supko, JG Hall, JE AF Srouji, Serene S. Pagan, Yanira L. D'Amato, Fernando Dabela, Amsalu Jimenez, Yarisie Supko, Jeffrey G. Hall, Janet E. TI Pharmacokinetic factors contribute to the inverse relationship between luteinizing hormone and body mass index in polycystic ovarian syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; FOLLICLE-STIMULATING-HORMONE; GLYCOPROTEIN HORMONES; CHARGE HETEROGENEITY; POSTMENOPAUSAL WOMEN; METABOLIC-CLEARANCE; SECRETION; ISOFORMS; DISEASE; PLASMA AB Context: Serum LH levels decrease with increasing body mass index (BMI) in women with polycystic ovarian syndrome (PCOS). Objective: The objective of this study was to determine whether pharmacokinetic factors contribute to the effect of obesity on LH in PCOS. Participants/Interventions/Setting: Twenty-one women with PCOS underwent frequent blood sampling, iv administration of GnRH (75 ng/kg), and sc administration of the NAL-GLU GnRH antagonist (150 mu g/kg) followed by iv recombinant human LH (rhLH; 300 IU) in the General Clinical Research Center at an academic medical center. Main Outcome Measures: Pharmacokinetic parameters were estimated by modeling the LH serum concentration profiles after administration of GnRH and rhLH and related to BMI. Results: Serum levels of LH and rhLH decreased in a distinctly monoexponential fashion in all patients. The apparent biological half-life of rhLH was not influenced by BMI, nor was the total body clearance or apparent volume of distribution. However, the apparent half-life of endogenous LH was inversely related to BMI (r = -0.46; P < 0.04), and the estimated total body clearance of endogenous LH was positively related to BMI ( r = 0.53; P < 0.02). Conclusion: Estimated clearance and apparent half-life of endogenous LH are influenced by BMI in women with PCOS, contributing to the inverse relationship between LH and BMI in this population. The absence of an effect of BMI on the pharmacokinetics of rhLH in these subjects suggests that the effect of obesity on clearance of endogenous LH is the result of alterations in the isoform composition of LH secreted by the pituitary. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Ctr Reprod Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Hall, JE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX 5,55 Fruit St, Boston, MA 02114 USA. EM hall.janet@mgh.harvard.edu FU NCRR NIH HHS [M01 RR1066]; NICHD NIH HHS [K24 HD 01290] NR 43 TC 21 Z9 22 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2007 VL 92 IS 4 BP 1347 EP 1352 DI 10.1210/jc.2006-2716 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 153WH UT WOS:000245466600027 PM 17264175 ER PT J AU Florez, JC Jablonski, KA Sun, MW Bayley, N Kahn, SE Shamoon, H Hamman, RF Knowler, WC Nathan, DM Altshuler, D AF Florez, Jose C. Jablonski, Kathleen A. Sun, Maria W. Bayley, Nick Kahn, Steven E. Shamoon, Harry Hamman, Richard F. Knowler, William C. Nathan, David M. Altshuler, David CA Diabetes Preventio TI Effects of the type 2 diabetes-associated PPARG P12A polymorphism on progression to diabetes and response to troglitazone SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA-2; IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE INTERVENTION; PRO12ALA POLYMORPHISM; PPAR-GAMMA-2 GENE; PREVENTION PROGRAM; INSULIN-SECRETION; GAMMA-GENE; BODY-MASS; POPULATION AB Context: The common P12A polymorphism in PPARG (a target for thiazolidinedione medications) has been consistently associated with type 2 diabetes. Objective: We examined whether PPARG P12A affects progression from impaired glucose tolerance to diabetes, or responses to preventive interventions (lifestyle, metformin, or troglitazone vs. placebo). Patients: This study included 3548 Diabetes Prevention Program participants. Design: We performed Cox regression analysis using genotype at PPARG P12A, intervention, and their interactions as predictors of diabetes incidence. We also genotyped five other PPARG variants implicated in the response to troglitazone and assessed their effect on insulin sensitivity at 1 yr. Results: Consistent with prior cross-sectional studies, P/P homozygotes at PPARG P12A appeared more likely to develop diabetes than alanine carriers (hazard ratio, 1.24; 95% confidence interval, 0.99-1.57; P = 0.07) with no interaction of genotype with intervention. There was a significant interaction of genotype with body mass index and waist circumference (P = 0.03 and 0.002, respectively) with the alanine allele conferring less protection in more obese individuals. Neither PPARG P12A nor five other variants significantly affected the impact of troglitazone on insulin sensitivity in 340 participants at 1 yr. Conclusions: The proline allele at PPARG P12A increases risk for diabetes in persons with impaired glucose tolerance, an effect modified by body mass index. In addition, PPARG P12A has little or no effect on the beneficial response to troglitazone. C1 George Washington Univ, Diabet Prevent Program Coordinating Ctr, Biostat Ctr, Rockville, MD 20852 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. MIT, Cambridge, MA 02139 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. Univ Washington, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA USA. Albert Einstein Coll Med, Div Endocrinol & Metab, Dept Med, Bronx, NY 10461 USA. Univ Colorado Denver & Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. NIDDKD, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ 85014 USA. RP Florez, JC (reprint author), George Washington Univ, Diabet Prevent Program Coordinating Ctr, Biostat Ctr, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. EM jcflorez@partners.org RI Altshuler, David/A-4476-2009; OI Altshuler, David/0000-0002-7250-4107; Shamoon, Harry/0000-0002-5014-5211; Kahn, Steven/0000-0001-7307-9002 FU NIDDK NIH HHS [U01 DK048489, 1 K23 DK65978-03, U01 DK048489-06, K23 DK065978] NR 42 TC 84 Z9 88 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2007 VL 92 IS 4 BP 1502 EP 1509 DI 10.1210/jc.2006-2275 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 153WH UT WOS:000245466600052 PM 17213274 ER PT J AU Aujesky, D Long, JA Fine, MJ Ibrahim, SA AF Aujesky, Drahomir Long, Judith A. Fine, Michael J. Ibrahim, Said A. TI African American race was associated with an increased risk of complications following venous thromboembolism SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE quality; equity; race; anticoagulation; outcomes; venous thromboembolism ID DEEP-VEIN THROMBOSIS; PULMONARY-EMBOLISM MORTALITY; ANTICOAGULATION THERAPY; ANTITHROMBOTIC THERAPY; UNFRACTIONATED HEPARIN; ORAL ANTICOAGULATION; CONTROLLED-TRIAL; UNITED-STATES; DISEASE; METAANALYSIS AB Objective: Limited data exist on the quality of care for patients with venous thromboembolism (VTE), and it is unknown whether the processes and outcomes of care for this illness differ between African Americans and whites. Study Design and Setting: We retrospectively studied 168 patients hospitalized for VTE in two Veterans Affairs hospitals during fiscal years 2000-2002. Patient characteristics, information about processes of care, and medical outcomes at 90 days after the index VTE event were abstracted from medical records. We used logistic regression to explore associations between race, processes of care, and the overall 90-day complication rate (i.e., death, bleeding, or recurrent VTE), adjusting for patient baseline characteristics. Results: Multivariable analysis demonstrated that administration of warfarin within 1 day of starting heparin (odds ratio [OR] 0.20, 95% confidence interval [CI]: 0.05-0.42) and overlap of heparin and warfarin treatment >= 4 days (OR 0.09, 95% CI: 0.02-0.50) were associated with a lower complication rate, and African American race was associated with a higher complication rate (OR 5.2, 95% CI: 1.3-21.6). Race was not significantly associated with the performance of processes of care in multivariable analysis. Conclusion: Although African Americans had an increased risk of complications following VTE, race was not independently associated with the use of processes of care for VTE. (C) 2007 Elsevier Inc. All rights reserved. C1 Univ Lausanne, Clin Epidemiol Ctr, Div Internal Med, Lausanne, Switzerland. Univ Lausanne, Univ Outpatient Clin, Lausanne, Switzerland. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. Univ Penn, Sch Med, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. VA Pittsburgh Healthcare Syst, VA Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. RP Aujesky, D (reprint author), CHU Vaudois, Serv Med Interne, BH 10-622, CH-1011 Lausanne, Switzerland. EM drahomir.aujesky@chuv.ch NR 37 TC 16 Z9 16 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD APR PY 2007 VL 60 IS 4 BP 410 EP 416 DI 10.1016/j.jclinepi.2006.06.023 PG 7 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 148SF UT WOS:000245094200014 PM 17346616 ER PT J AU Benz, EJ AF Benz, Edward J., Jr. TI Introduction of David G. Nathan, MD SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Biographical-Item C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Benz, EJ (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2007 VL 117 IS 4 BP 1107 EP 1111 DI 10.1172/JCI32145 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 153RC UT WOS:000245451700033 PM 17404624 ER PT J AU Nathan, DG AF Nathan, David G. TI Acceptance of the 2006 Kober medal SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID INSTITUTES-OF-HEALTH; CLINICAL-RESEARCH; BIOMEDICAL-RESEARCH C1 Dana Farber Canc Inst, 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 11 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2007 VL 117 IS 4 BP 1111 EP 1113 DI 10.1172/JCI32146 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 153RC UT WOS:000245451700034 ER PT J AU Swiercz, W Cios, K Hellier, J Yee, A Staley, K AF Swiercz, Waldemar Cios, Krzysztof Hellier, Jennifer Yee, Audrey Staley, Kevin TI Effects of synaptic depression and recovery on synchronous network activity SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Article; Proceedings Paper CT International Conference on An Overview of Epilepsy Research - What, Where, When and Why CY MAY 19-20, 2006 CL Chicago, IL SP Ctr Integrat Neurosci & Neuroengn Res DE glutamate; synaptic depression; hippocampus; network; modeling; computational ID RECURRENT COLLATERAL SYNAPSES; READILY RELEASABLE POOL; SPIKING NEURONS; HIPPOCAMPAL SYNAPSES; RAT HIPPOCAMPUS; DYNAMICAL DISEASES; BRAIN SYSTEMS; MODELS; PROBABILITY; VESICLES AB The output of an artificial neural network of spiking neurons linked by glutarnatergic synapses subject to use-dependent depression was compared with physiologic data obtained from rat hippocampal area CA3 in vitro. The authors evaluated how network burst initiation and termination was affected by activity-dependent depression and recovery under a variety of experimental conditions including neuronal membrane depolarization, altered glutamate release probability, the strength of synaptic inhibition, and long-term potentiation and long-term depression of recurrent glutamatergic synapses. The results of computational experiments agreed with the in vitro data and support the idea that synaptic properties, including activity-dependent depression and recovery, play important roles in the timing and duration of spontaneous bursts of network activity. This validated network model is useful for experiments that are not feasible in vitro, and makes possible the investigation of two-dimensional aspects of burst propagation and termination. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Colorado, Hlth Sci Ctr, Dept Comp Sci & Engn, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80202 USA. RP Staley, K (reprint author), Massachusetts Gen Hosp, Dept Neurol, VBK 910,55 Fruit St, Boston, MA 02114 USA. EM kstaley@partners.org FU NINDS NIH HHS [NS 034700, NS034360, NS040109] NR 69 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD APR PY 2007 VL 24 IS 2 BP 165 EP 174 DI 10.1097/WNP.0b013e318033756f PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 156KS UT WOS:000245647400010 PM 17414972 ER PT J AU Abel, GA Lee, SJ Weeks, JC AF Abel, Gregory A. Lee, Stephanie J. Weeks, Jane C. TI Direct-to-consumer advertising in oncology: A content analysis of print media SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol ID PRESCRIPTION DRUG ADVERTISEMENTS; HEALTH-CARE; APPEALS AB Purpose Content analysis of cancer-related direct-to-consumer advertising ( DTCA), with a focus on how benefit and risk/adverse effect information is presented, is essential to understanding its potential impact on oncology outcomes. Methods We reviewed all oncology DTCA appearing in three patient-focused cancer magazines and a sample of selected popular magazines from January 2003 to June 2006. We determined the Flesch reading ease score (FRES) for the text in each advertisement ( a score >= 65 is readable for the average person). We also assessed the proportion, type size, and placement of benefits and risks/adverse effects, as well as the nature and content of advertising appeals. Results Of 284 advertisements identified, 49 were unique. Oncology-related DTCA was rare in the popular magazines, and appeared mostly in those aimed at female readership. About equal amounts of text were devoted to benefits and risks/adverse effects, and all text was difficult to read. The mean FRES for benefit text was 39.71; for risk/adverse effect text, it was 38.22, a difference of 1.49 (95% CI, - 4.02 to 7.00). The largest font size for benefits was 4.60 mm on average; for risks/adverse effects, it was 2.38 mm, a difference of 2.22 mm ( 95% CI, 1.35 to 3.09). Appeals to medication effectiveness were frequent ( 95%) and often made with clinical trial data (61%). Conclusion Oncology print DTCA is prevalent in cancer-related, patient-directed magazines, and infrequent in the popular press. The information presented is considerably difficult to read, raising important questions about the appropriateness of direct-to-consumer marketing for oncologic medications. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Weeks, JC (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, 44 Binney St,Smith 271, Boston, MA 02115 USA. EM jane_weeks@dfci.harvard.edu FU NCI NIH HHS [T32 CA009172] NR 22 TC 17 Z9 17 U1 3 U2 8 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 APR 1 PY 2007 VL 25 IS 10 BP 1267 EP 1271 DI 10.1200/JCO.2006.09.5968 PG 5 WC Oncology SC Oncology GA 156VF UT WOS:000245677300017 PM 17401016 ER PT J AU Henderson, DC Cagliero, E Copeland, PM Louie, PM Borba, CP Fan, XD Freudenreich, O Goff, DC AF Henderson, David C. Cagliero, Enrico Copeland, Paul M. Louie, Pearl M. Borba, Christina P. Fan, Xiaoduo Freudenreich, Oliver Goff, Donald C. TI Elevated hemoglobin A1c as a possible indicator of diabetes mellitus and diabetic ketoacidosis in schizophrenia patients receiving atypical antipsychotics SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID CLOZAPINE TREATMENT; OLANZAPINE TREATMENT; HYPERGLYCEMIA; POPULATION AB Objective: We conducted a retrospective epidemiologic study assessing the incidence of new-onset diabetes mellitus presenting as diabetic ketoacidosis in patients with schizophrenic disorders (ICD-9 295.0-295.9; referred to as "schizophrenia patients" hereafter) treated with atypical antipsychotic agents. Method: The identification of patients and the review of records were achieved by using an electronic database linking administrative and clinical laboratory data between January 1, 1995, and December 31, 2001. The main outcome measure was the incidence of diabetic ketoacidosis or hyperosmolar hyperglycemic syndrome per 10,000 patient years in patients with new-onset or existing diabetes mellitus. We also determined the incidence of diabetic ketoacidosis associated with the use of atypical antipsychotics and calculated the mean hemoglobin A1c (HbA1c) level for all patients. Results: During the 7-year period, 18.4% of schizophrenia patients were diagnosed with diabetes mellitus, compared with 6.6% in the general hospital population (p <.001). After chart review, 23 schizophrenia patients were identified with diabetic ketoacidosis: 11 had diabetes presenting as diabetic ketoacidosis, 8 had diabetic ketoacidosis with known diabetes mellitus, 2 had new-onset diabetes mellitus-hyperosmolar hyperglycemic syndrome, and 2 had hyperosmolar hyperglycemic syndrome with known diabetes mellitus. The incidence of diabetes presenting as diabetic ketoacidosis in schizophrenia patients was more than 10-fold higher than that reported in the general population: 14.93 per 10,000 patient years in schizophrenia patients versus 1.4 per 10,000 patient years in the general population (p <.000001) and versus the 1.98 per 10,000 patient years in the general hospital population (p <.000001). The incidence of diabetic ketoacidosis for each of atypical antipsychotic drugs over the 7-year period was as follows: clozapine, 2.2%; olanzapine, 0.8%; and risperidone, 0.2% (no incidence with ziprasidone or quetiapine). Of the 11 patients with diabetes presenting as diabetic ketoacidosis, the mean HbA1c level at admission was 13.3% +/- 1.9% (10.4%-16.9%). Conclusions: The incidence of diabetes mellitus presenting as diabetic ketoacidosis in schizophrenia patients is higher than in the general hospital population and differs across atypical antipsychotic agents. Elevated HgbA1c levels observed suggests that patients had undiagnosed diabetes mellitus for at least several weeks before the diabetic ketoacidosis episode. C1 Massachusetts Gen Hosp, Schizophrenia Program, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Henderson, DC (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM dchenderson@partners.org NR 38 TC 33 Z9 35 U1 2 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 2007 VL 68 IS 4 BP 533 EP 541 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 159OP UT WOS:000245876000007 PM 17474808 ER PT J AU Michelson, D Adler, LA Amsterdam, JD Dunner, DL Nierenberg, AA Reimherr, FW Schatzberg, AF Kelsey, DK Williams, DW AF Michelson, David Adler, Lenard A. Amsterdam, Jay D. Dunner, David L. Nierenberg, Andrew A. Reimherr, Frederick W. Schatzberg, Alan F. Kelsey, Douglas K. Williams, David W. TI Addition of atomoxetine for depression incompletely responsive to sertraline: A randomized, double-blind, placebo-controlled study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 159th Annual Meeting of the American-Psychiatric-Association CY MAY 20-25, 2006 CL Toronto, CANADA SP Amer Psychiat Assoc ID SEROTONIN TRANSPORTER GENE; ANTIDEPRESSANT RESPONSE; MAJOR DEPRESSION; POLYMORPHISM; PROMOTER; AUGMENTATION; FLUVOXAMINE; EFFICACY; SCALE AB Objective: Despite appropriate treatment with selective serotonin reuptake inhibitors (SSRIs), many depressed patients do not attain remission. Addition of a noradrenergic intervention in patients poorly or partially responsive to SSRIs may improve outcomes, but few well-controlled studies testing this hypothesis have been reported. Method: Patients with major depressive disorder (confirmed by the Structured Clinical Interview for DSM-IV) were treated with sertraline at doses up to 200 mg/day in this study, conducted from June 18, 2003, to January 28, 2005. Patients who continued to experience depressive signs and symptoms after 8 weeks were randomly assigned to have atomoxetine 40 to 120 mg/day or placebo added to sertraline for a further 8 weeks. Results: Of 276 patients starting the study, 146 with persistent depressive symptoms after 8 weeks of sertraline treatment (mean [SD] final sertraline dose: 161.1 [43.4] mg/day) were randomly assigned to addition of atomoxetine or placebo. After 8 additional weeks, there was no difference between treatment groups in mean change in symptom severity or in the proportion of patients whose symptoms remitted (sertraline/ atomoxetine 29/72 [40.3%], sertraline/placebo 28/74 [37.8%], p =.865). Secondary analyses that separated the subgroups with improvements in symptoms that did not reach remission (partial responders) and those with little or no improvement (nonresponders) also showed no effect of atomoxetine. The number of patients discontinuing because of adverse events did not differ between groups. Conclusion: In depressed patients with persistent symptoms after an initial trial of sertraline, addition of atomoxetine did not improve response more than placebo. C1 Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Indiana Univ, Dept Psychiat, Indianapolis, IN 46204 USA. NYU, Dept Psychiat, New York, NY 10016 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Washington, Ctr Anxiety & Depress, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Utah, Hlth Sci Ctr, Mood Disorders Clin, Salt Lake City, UT USA. Univ Utah, Hlth Sci Ctr, Dept Psychiat, Salt Lake City, UT USA. Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA USA. RP Michelson, D (reprint author), Merck Res Labs, POB 1000, N Wales, PA 19454 USA. EM david_michelson@merck.com NR 16 TC 26 Z9 26 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 2007 VL 68 IS 4 BP 582 EP 587 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 159OP UT WOS:000245876000013 PM 17474814 ER PT J AU Henin, A Mick, E Biederman, J Fried, R Wozniak, J Faraone, SV Harrington, K Davis, S Doyle, AE AF Henin, Aude Mick, Eric Biederman, Joseph Fried, Ronna Wozniak, Janet Faraone, Stephen V. Harrington, Kara Davis, Stephanie Doyle, Alysa E. TI Can bipolar disorder-specific neuropsychological impairments in children be identified? SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT Conference on Pediatric Bipolar Disorder CY APR, 2006 CL Chicago, IL DE neuropsychology; bipolar disorder; child; ADHD; processing speed ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; MANIA RATING-SCALE; SUSTAINED ATTENTION; NEUROCOGNITIVE FUNCTION; PSYCHIATRIC-DISORDERS; COGNITIVE FUNCTION; EUTHYMIC PATIENTS; ADOLESCENTS; METAANALYSIS; PERFORMANCE AB This study examined neuropsychological deficits among children with bipolar disorder while attending to its comorbidity with attention-deficit/hyperactivity disorder (ADHD). Seventy-three unmedicated children (ages 6-17 years) with Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) bipolar disorder plus ADHD (BPD + ADHD) were compared with 102 unmedicated children with ADHD without bipolar disorder, and 120 children without bipolar disorder or ADHD. Ninety-four percent of participants were Caucasian, 58% were male, and 42% were female. On average participants were of middle to upper socioeconomic status. Participants were assessed with a comprehensive neuropsychological battery and measures of academic achievement, school failure, and special education placement. Participants with BPD + ADHD and with ADHD were impaired in interference control, verbal learning, and arithmetic achievement and had higher rates of special school services. Across all of the measures of neuropsychological functioning, the only difference observed between youths with BPD + ADHD and youths with ADHD was that youths with BPD + ADHD performed more poorly on one measure of processing speed. Thus, comorbidity with ADHD may account for many of the neuropsychological deficits observed in children with bipolar disorder. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Cambridge, MA 02138 USA. SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY USA. RP Henin, A (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, 185 Alewife Brook Pkwy,Suite 2000, Cambridge, MA 02138 USA. EM ahenin@partners.org OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 NR 74 TC 33 Z9 36 U1 1 U2 7 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD APR PY 2007 VL 75 IS 2 BP 210 EP 220 DI 10.1037/0022-006X.75.2.210 PG 11 WC Psychology, Clinical SC Psychology GA 152XC UT WOS:000245394600002 PM 17469879 ER PT J AU Murphy, CM Taft, CT Eckhardt, CI AF Murphy, Christopher M. Taft, Casey T. Eckhardt, Christopher I. TI Anger problem profiles among partner violent men: Differences in clinical presentation and treatment outcome SO JOURNAL OF COUNSELING PSYCHOLOGY LA English DT Article; Proceedings Paper CT 9th International Family Violence Research Conference CY JUL, 2005 CL Portsmouth, NH DE anger; intimate partner violence; treatment outcome; counseling; subtypes ID COGNITIVE-BEHAVIORAL THERAPY; ABUSE SCREENING-TEST; MARITALLY VIOLENT; SELF-ESTEEM; INTERPERSONAL PROBLEMS; PHYSICAL AGGRESSION; CONSTRUCT-VALIDITY; NONVIOLENT MEN; RISK-FACTORS; PERSONALITY AB Cluster analysis of 139 partner violent men's self-reports on the State-Trait Anger Expression Inventory identified profiles reflecting pathological anger (PA), low anger control (LAC), and normal anger (NA). The PA group self-reported higher pretreatment partner abuse, interpersonal dysfunction, distress, and substance abuse and had lower treatment attendance than the NA and LAC groups. Collateral (victim) partners reported higher pretreatment abuse by the PA and LAC groups than the NA group. At posttreatment and 6-month follow-up, the PA group had the highest levels of physical assault and injury. The LAC group exceeded the NA group in physical assault at posttreatment and psychological aggression at posttreatment and follow-up. The recognition of distinct anger problem profiles may lead to new strategies for research and practice. C1 Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21250 USA. Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Purdue Univ, Dept Psychol Sci, W Lafayette, IN 47907 USA. RP Murphy, CM (reprint author), Univ Maryland Baltimore Cty, Dept Psychol, 1000 Hilltop Circle, Baltimore, MD 21250 USA. EM chmurphy@umbc.edu NR 76 TC 40 Z9 42 U1 6 U2 17 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-0167 J9 J COUNS PSYCHOL JI J. Couns. Psychol. PD APR PY 2007 VL 54 IS 2 BP 189 EP 200 DI 10.1037/0022-0167.54.2.189 PG 12 WC Psychology, Educational; Psychology, Applied SC Psychology GA 153PM UT WOS:000245447400008 ER PT J AU Davis, T Zembowicz, A AF Davis, Tracy Zembowicz, Artur TI Histological evolution of lentiginous melanoma: a report of five new cases SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID MALIGNA TYPE; IN-SITU; NEVUS AB Background: The term lentiginous melanoma was recently used for atypical melanocytic proliferations sharing some histological features with lentigo maligna and associated with a protracted in situ stage before invasion. Lentiginous melanoma was characterized by predominantly single-cell lentiginous growth pattern with focal junctional nests and pagetoid spread, preservation of the dermoepidermal junction, limited cytological atypia, and lack of significant solar elastosis. We report five similar cases. Methods: Histological review of routine sections with clinicopathological correlation. Results: Three patients were male and two were female. The age at presentation ranged from 24 to 66 years. All lesions arose on the truck or proximal extremities. All five cases fulfilled histological criteria proposed for lentiginous melanoma. None of the lesions showed significant solar elastosis. One lesion was followed clinically and histologically for 16 years without intervening treatment. It had three local recurrences before culminating in invasive melanoma. Conclusions: Our observations support recent efforts to distinguish lentiginous melanoma as a distinct clinicopathological entity. Lentiginous melanoma can remain in situ for a long time before invasion and may be considered an analogue of lentigo maligna occurring on non-severely sun-damaged skin. Familiarity with the histological features of this variant is important for its early recognition and treatment. C1 Massachusetts Gen Hosp, Dermatol Unit, Dept Pathol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Zembowicz, A (reprint author), Massachusetts Gen Hosp, Dermatol Unit, Dept Pathol, Warren 820,55 Fruit St, Boston, MA 02114 USA. EM azembowicz@partners.org NR 7 TC 14 Z9 14 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD APR PY 2007 VL 34 IS 4 BP 296 EP 300 DI 10.1111/j.1600-0560.2006.00604.x PG 5 WC Dermatology; Pathology SC Dermatology; Pathology GA 148UE UT WOS:000245099700002 PM 17381799 ER PT J AU York, KM Mlinac, ME Deibler, MW Creed, TA Ganem, I AF York, Kaki M. Mlinac, Michelle E. Deibler, Marla W. Creed, Torrey A. Ganem, Ivonne TI Pediatric behavior management techniques: A survey of predoctoral dental students SO JOURNAL OF DENTAL EDUCATION LA English DT Article DE health behavior; dental education; pediatric dentistry ID DENTISTRY AB Dental schools are increasingly incorporating behavioral management strategies into the curriculum; however, little is known about the efficacy of this instruction. The purposes of this study were to evaluate student exposure to several categories of behavioral management techniques, assess student opportunity to observe faculty use of these techniques, and determine the extent of students' personal use of various behavioral management techniques. Third-year dental students (n=98, (K) over bar age=26.52; s=4.05) were administered a survey assessing their exposure to and willingness to use behavioral management strategies. Results indicated differences between the techniques students recalled being taught and what they indicated they plan to use in their own future clinical practices. Student technique endorsement also varied as a function of student age, gender, ethnicity, and patient age. Despite increasing concerns regarding the use of these techniques, a significant minority of students stated that they were taught to use hand-over-mouth, verbal intimidation, and various forms of active and passive restraint/immobilization. While appreciation for behavioral management strategies within the dental school curriculum was demonstrated by the amount of didactic exposure students received, the need for increased experiential training is evident. Furthermore, student endorsement of controversial techniques appears to reflect the changing view of these techniques within the professional dental community. C1 Temple Univ, Sch Dent, Dept Dent Publ Hlth Sci, Philadelphia, PA 19140 USA. Univ Florida, Dept Med, Gainesville, FL 32611 USA. VA Boston Healthcare Syst, Boston, MA USA. RP Deibler, MW (reprint author), Temple Univ, Sch Dent, Dept Dent Publ Hlth Sci, 3223 N Broad St,Suite 300, Philadelphia, PA 19140 USA. EM marla.deibler@temple.edu NR 9 TC 5 Z9 6 U1 0 U2 1 PU AMER DENTAL EDUCATION ASSOC PI WASHINGTON PA 1400 K STREET, NW, STE 1100, WASHINGTON, DC 20005 USA SN 0022-0337 J9 J DENT EDUC JI J. Dent. Educ. PD APR PY 2007 VL 71 IS 4 BP 532 EP 539 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 217BC UT WOS:000249922400014 PM 17468315 ER PT J AU Dietrich, T Maserejian, NN Joshipura, KJ Krall, EA Garcia, RI AF Dietrich, T. Maserejian, N. N. Joshipura, K. J. Krall, E. A. Garcia, R. I. TI Tobacco use and incidence of tooth loss among US male health professionals SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE periodontitis; smoking; tobacco; tooth loss ID FOOD FREQUENCY QUESTIONNAIRE; ALVEOLAR BONE LOSS; CIGARETTE-SMOKING; RISK-FACTORS; PERIODONTAL-DISEASE; UNITED-STATES; YOUNG-ADULTS; NHANES-III; VALIDITY; REPRODUCIBILITY AB Data on the dose-dependent effects of smoking and smoking cessation on tooth loss are scarce. We hypothesized that smoking has both dose- and time-dependent effects on tooth loss incidence. We used longitudinal data on tobacco use and incident tooth loss in 43,112 male health professionals, between 1986 and 2002. In multivariate Cox models, current smokers of 5 to 14 and 45+ cigarettes daily had a two-fold (HR, 1.94; 95% CI, 1.72, 2.18) and three-fold (HR, 3.05; 95% CI, 2.38, 3.90) higher risk of tooth loss, respectively, compared with never-smokers. Risk decreased with increasing time since cessation, but remained elevated by 20% (95% CI, 16%, 25%) for men who had quit 10+ years before. Current pipe/cigar smokers had a 20% (95% CI, 1.11, 1.30) increased risk of tooth loss compared with never- and former smokers of pipes/cigars. C1 Boston Univ, Goldman Sch Dent Med, Dept Hlth Policy & Hlth Serv Res, Boston, MA 02118 USA. Boston Univ, Goldman Sch Dent Med, Dept Periodontol & Oral Biol, Boston, MA 02118 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Univ Puerto Rico, Sch Dent, Div Dent Publ Hlth, San Juan, PR 00936 USA. VA Boston Healthcare Syst, VA Normat Aging Study, Boston, MA USA. RP Dietrich, T (reprint author), Boston Univ, Goldman Sch Dent Med, Dept Hlth Policy & Hlth Serv Res, 715 Albany St,560 3rd Floor, Boston, MA 02118 USA. EM tdietric@bu.edu OI Dietrich, Thomas/0000-0002-2557-7645 FU NIDCR NIH HHS [K24 DE00419, K24 DE000419, R03 DE016357, R03 DE016357-01A1] NR 33 TC 42 Z9 42 U1 2 U2 6 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD APR PY 2007 VL 86 IS 4 BP 373 EP 377 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 149XA UT WOS:000245179000014 PM 17384035 ER PT J AU McCormick, JK Nadel, ES Brown, DFM Peak, D Nagurney, JT Swap, C Bhatia, K Levine, M Takayesu, K AF McCormick, Jenny K. Nadel, Eric S. Brown, David F. M. Peak, David Nagurney, J. Tobias Swap, Clifford Bhatia, Kriti Levine, Michael Takayesu, Kimo TI Rash and neurological symptoms SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID THROMBOTIC THROMBOCYTOPENIC PURPURA; HEMOLYTIC-UREMIC SYNDROME; VON-WILLEBRAND-FACTOR; FACTOR-CLEAVING PROTEASE; PLASMA-EXCHANGE; ESCHERICHIA-COLI; HIV-INFECTION; PURIFICATION; ASSOCIATION; DEFICIENCY C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP McCormick, JK (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. RI McCormick, John/E-4232-2015 NR 40 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD APR PY 2007 VL 32 IS 3 BP 299 EP 303 DI 10.1016/j.jemermed.2006.12.036 PG 5 WC Emergency Medicine SC Emergency Medicine GA 154UM UT WOS:000245533300014 PM 17394996 ER PT J AU Petrovick, L AF Petrovick, Laurie TI Operation save a life: Massachusetts general hospital trauma center's program to educate drivers on the dangers of driving while intoxicated SO JOURNAL OF EMERGENCY NURSING LA English DT Article C1 Massachusetts Gen Hosp, Div Trauma Emergency Surg & CSurg Crit Care, Boston, MA 02114 USA. RP Petrovick, L (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & CSurg Crit Care, CPZ 810,55 Fruit St, Boston, MA 02114 USA. EM lpetrovick@partners.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-1767 J9 J EMERG NURS JI J. Emerg. Nurs. PD APR PY 2007 VL 33 IS 2 BP 154 EP 157 DI 10.1016/j.jen.2006.11.011 PG 4 WC Emergency Medicine; Nursing SC Emergency Medicine; Nursing GA 152TW UT WOS:000245385800013 PM 17379035 ER PT J AU Kato, N Kitahara, K Rittling, SR Nakashima, K Denhardt, DT Kurosawa, H Ezura, Y Noda, M AF Kato, Norihiko Kitahara, Keiichiro Rittling, Susan R. Nakashima, Kazuhisa Denhardt, David T. Kurosawa, Hisashi Ezura, Yoichi Noda, Masaki TI Osteopontin deficiency enhances anabolic action of EP4 agonist at a sub-optimal dose in bone SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID STEM-CELL NICHE; PROSTAGLANDIN E-2; MICE LACKING; IN-VITRO; HYDROXYAPATITE FORMATION; INHIBITION; KNOCKOUT; RATS; MASS; STIMULATION AB Osteoporosis is one of the most widespread and destructive bone diseases it) our modern world. There is a great need for anabolic agents for bone which could reverse this disease, but few are available for clinical use. Prostaglandin E receptor (EP4) agonist (EP4A) is one of the very few anabolic agents for bone in rat, but its systemic efficacy against bone loss at sub-optimal dose is limited in mice. As osteoblasts are regulated by extracellular matrix proteins, we tested whether deficiency of osteopontin (OPN), a secreted phosphorylated protein, could modulate the effects of EP4A (ONO-AE1-329) treatment at 30 mu g/kg body weight, a sub-optimal dose, for 5 days/week for 4 weeks. OPN deficiency enhanced the anabolic effects of EP4A on bone volume. Histomorphometric analysis indicated that EP4A increased mineral apposition rate as well as bone formation rate in, OPN-deficient but not in wild-type mice. Neither OPN deficiency nor EP4A altered osteoclast parameters. Importantly, OPN deficiency enhanced the direct anabolic action of EP4A locally injected onto the parietal bone in inducing new, bone formation. Combination of OPN deficiency and EP4A treatment caused an increase in mineralized nodule formation in the cultures of bone marrow cells. Finally, OPN deficiency enhanced anabolic action of EP4A in the mice subjected to ovariectomy. These data indicate that OPN deficiency enhances the actions of EP4A at sub-optimal dose. C1 Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Pharmacol, Chiyoda Ku, Tokyo 113, Japan. Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ 08855 USA. Juntendo Univ, Sch Med, Dept Orthoped, Tokyo 113, Japan. 21st Century Ctr Excellence, Program Frontier Res Mol Destruct & Reconstruct T, Tokyo, Japan. Tokyo Med & Dent Univ, Hard Tissue Genome Res Ctr, Tokyo 113, Japan. RP Ezura, Y (reprint author), Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Pharmacol, Chiyoda Ku, 3-10 Kanda Surugadai 2 Chome, Tokyo 113, Japan. EM ezura.mph@mri.tmd.ac.jp; noda.mph@mri.tmd.ac.jp RI Ezura, Yoichi/L-9485-2016 NR 42 TC 8 Z9 8 U1 0 U2 1 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD APR PY 2007 VL 193 IS 1 BP 171 EP 182 DI 10.1677/joe.1.06917 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 159WE UT WOS:000245897500018 PM 17400814 ER PT J AU Holmes, WC AF Holmes, William C. TI Men's childhood sexual abuse histories by one-parent versus two-parent status of childhood home SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID SINGLE-MOTHER; RISK-FACTORS; CHILDREN; HEALTH; DISORDERS; VIOLENCE; BOYS; ASSOCIATION; PREVALENCE; DEPRESSION AB Objectives: To estimate the association between number of parents in the childhood home and childhood sexual abuse (CSA) with adjustment for childhood socioeconomic status (CSES). Methods: Probability sample of 298, 18-49-year-old men from Philadelphia County, number of parents living in childhood home, socioeconomic data and CSA histories were obtained. Results: 197 (66%) men participated. 186 (94%) of these lived with at least one parent; 76 (39%) and 110 (56%) lived with one parent versus two parents, respectively. 22 (29%) of 76 and 18 (16%) of 110 reported CSA histories, respectively (OR 2.08, p = 0.04). Two approaches to adjustment for CSES indicated continued association between parent number and CSA (OR 2.38-2.39, p = 0.05-0.07). Parent number was associated with numerous differences in CSA perpetrator characteristics and abuse experiences. Men from one-parent versus two-parent families reported significantly more non-family and female perpetrators (p = 0.03 and 0.01, respectively) and fondling experiences (p = 0.04). Conclusions: Findings provide additional support for the association between parent number and CSA in boys, suggesting that parent number is not just a proxy for CSES. CSA experiences also differed between one-parent and two-parent homes. Findings generate numerous hypotheses for future study. C1 Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Holmes, WC (reprint author), Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, 733 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM holmeswc@mail.med.upenn.edu FU NIDA NIH HHS [DA015635, R03 DA015635] NR 39 TC 5 Z9 5 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD APR PY 2007 VL 61 IS 4 BP 319 EP 325 DI 10.1136/jech.2005.040188 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 147XG UT WOS:000245037600010 PM 17372292 ER PT J AU Bordeianou, L Hodin, R AF Bordeianou, Liliana Hodin, Richard TI Controversies in the surgical management of sigmoid diverticulitis SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Review DE sigmoid diverticulitis; surgical management; diagnosis; elective surgery ID NATURAL-HISTORY; YOUNG-PATIENTS; DISEASE; COLON; COLECTOMY; COMPLICATIONS; PERITONITIS; RESECTION; FISTULAS; OPERATE AB The timing and appropriateness of surgical treatment of sigmoid diverticular disease remain a topic of controversy. We have reviewed the current literature on this topic, focusing on issues related to the indications and types of surgery. Current evidence would suggest that elective surgery for diverticulitis can be avoided in patients with uncomplicated disease, regardless of the number of recurrent episodes. Furthermore, the need for elective surgey should not be influenced by the age of the patient. Operation should be undertaken in patients with severe attacks, as determined by their clinical and radiological evaluation. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Hodin, R (reprint author), Massachusetts Gen Hosp, Dept Surg, ACC 460,15 Parkman St, Boston, MA 02114 USA. EM rhodin@partners.org NR 35 TC 16 Z9 16 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD APR PY 2007 VL 11 IS 4 BP 542 EP 548 DI 10.1007/s11605-007-0126-y PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 160NQ UT WOS:000245950000022 PM 17436142 ER PT J AU Smith, AK Davis, RB Krakauer, EL AF Smith, A. K. Davis, R. B. Krakauer, E. L. TI Differences in the quality of the patient-physician relationship among terminally ill African American and white patients: Impact on advance care planning and goals of care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Smith, A. K.; Davis, R. B.] Beth Israel Deaconess Med Ctr, Brookline, MA USA. [Krakauer, E. L.] Massachusetts Gen Hosp, 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 4 EP 5 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700015 ER PT J AU Rahilly, CR Scranton, R Lawler, E Gaziano, J AF Rahilly, C. R. Scranton, R. Lawler, E. Gaziano, J. TI Do elderly patients benefit from large reduction in low-density lipoprotein cholesterol? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Rahilly, C. R.] Boston VA Healtcare Syst, Jamaica Plain, MA USA. [Scranton, R.] New England Vet Affairs Healtcare Syst, Boston, MA USA. [Lawler, E.] Boston Univ, Boston, MA 02215 USA. [Gaziano, J.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 5 EP 5 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700016 ER PT J AU Fang, MC Go, AS Chang, Y Borowsky, LH Pomemacki, NK Singer, D AF Fang, M. C. Go, A. S. Chang, Y. Borowsky, L. H. Pomemacki, N. K. Singer, D. TI Is warfarin control more difficult in the oldest patients with atrial fibrillation? The ATRIA study SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Fang, M. C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Go, A. S.] Univ Calif San Francisco, San Francisco & Kaiser Permanente Div Res, San Francisco, CA 94143 USA. [Borowsky, L. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pomemacki, N. K.] Kaiser Permanente Div Res, Oakland, CA 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 6 EP 7 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700022 ER PT J AU Lawrence, V Hazuda, H Cornell, J AF Lawrence, V. Hazuda, H. Cornell, J. TI How elders help themselves recover from major surgery SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Lawrence, V.; Cornell, J.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Hazuda, H.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 6 EP 6 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700020 ER PT J AU Keating, NL Landrum, MB Guadagnoli, E Winer, EP Ayanian, J AF Keating, N. L. Landrum, M. B. Guadagnoli, E. Winer, E. P. Ayanian, J. TI Primary and specialty care before death and hospice enrollment among women with advanced breast cancer SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Keating, N. L.; Landrum, M. B.; Guadagnoli, E.; Ayanian, J.] Harvard Med Sch, Boston, MA USA. [Winer, E. P.] Dana Farber Canc Inst, Boston, MA 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 9 EP 9 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700031 ER PT J AU Smith, AK Earle, CC Davis, RB Mccarthy, EP AF Smith, A. K. Earle, C. C. Davis, R. B. Mccarthy, E. P. TI Racial and ethnic disparities in end-of-life care among patients with advanced cancer SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Smith, A. K.; Davis, R. B.; Mccarthy, E. P.] Beth Israel Deaconess Med Ctr, Brookline, MA USA. [Earle, C. C.] Dana Farber Canc Inst, Boston, MA 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 10 EP 10 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700033 ER PT J AU Fihn, SD Bryson, C Mcdonell, M Diehr, PH Fan, VS AF Fihn, S. D. Bryson, C. Mcdonell, M. Diehr, P. H. Fan, V. S. TI Do primary care providers worry about worrisome results? Effects of feedback on processes and outcomes of care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Fihn, S. D.; Bryson, C.; Fan, V. S.] HSR&D Ctr Excellence, VA Puget Sound, Seattle, WA USA. [Mcdonell, M.] HSR&D VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Diehr, P. H.] Univ Washington, Seattle, WA 98195 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 18 EP 18 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700061 ER PT J AU Kutner, JS Smith, MC Corbin, L Hemphill, L Fairclough, D AF Kutner, J. S. Smith, M. C. Corbin, L. Hemphill, L. Fairclough, D. TI Efficacy of massage therapy for decreasing physical and emotional symptom distress and improving qualityoflife in advanced cancer SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Kutner, J. S.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Smith, M. C.] Florida Atlantic Univ, Boca Raton, FL 33431 USA. [Corbin, L.; Fairclough, D.] Univ Colorado, Hlth Sci Ctr, Aurora, CO USA. [Hemphill, L.] Denver VAMC, Denver, CO 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 20 EP 20 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700068 ER PT J AU Shacter, HE Iqbal, N Akhubue, E Long, JA AF Shacter, H. E. Iqbal, N. Akhubue, E. Long, J. A. TI Glucose control among veterans with poorly controlled diabetes: A guide for potential interventions SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Shacter, H. E.; Iqbal, N.; Long, J. A.] Vet Affairs Med Ctr, CHERP, Philadelphia, PA USA. [Akhubue, E.] Univ Penn, Philadelphia, PA 19104 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 22 EP 22 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700075 ER PT J AU Snyder, C Earle, C Herbert, R Neville, B Frick, K AF Snyder, C. Earle, C. Herbert, R. Neville, B. Frick, K. TI From cancer treatment to primary care: Preventive care for colorectal cancer survivors SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Snyder, C.; Herbert, R.; Frick, K.] Johns Hopkins Univ, Baltimore, MD USA. [Earle, C.; Neville, B.] Dana Farber Canc Inst, Boston, MA 02115 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 22 EP 22 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700073 ER PT J AU Lorenz, K Sherbourne, C Cohen, A Hagenmaier, E Kroenke, K Rubenstein, LV Simon, B Lanto, A Asch, S AF Lorenz, K. Sherbourne, C. Cohen, A. Hagenmaier, E. Kroenke, K. Rubenstein, L. V. Simon, B. Lanto, A. Asch, S. TI How does recall timeframe affect pain screening in routine outpatient care? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Lorenz, K.; Cohen, A.] Vet Adm Greater Los Angeles Hlthcare Syst, Los Angeles, CA USA. [Sherbourne, C.] RAND Hlth, Santa Monica, CA USA. [Hagenmaier, E.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Kroenke, K.] Indiana Univ Purdue Univ, Indianapolis, IN USA. [Simon, B.] Vet Affairs Greater Los Angeles, Los Angeles, CA USA. [Lanto, A.] Vet Affairs Greater Los Angeles HSR&D Ctr Excelle, Sepulveda, CA USA. [Asch, S.] Vet Adm Greater W Lost Angeles Hlthcare Syst, Los Angeles, CA 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 23 EP 23 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700078 ER PT J AU Rodriguez, KL Appelt, CJ Switzer, GE Sonel, AF Arnold, RM AF Rodriguez, K. L. Appelt, C. J. Switzer, G. E. Sonel, A. F. Arnold, R. M. TI Heart failure patients' decision making preferences and perceived involvement in cardiac care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Rodriguez, K. L.; Appelt, C. J.; Sonel, A. F.] Vet Affairs Pittsburg Hlthcare Syst, Pittsburgh, PA USA. [Switzer, G. E.; Arnold, R. M.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 23 EP 23 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700077 ER PT J AU Leykum, L Pugh, J Lawrence, V Parchman, M Noel, P Cornell, J Mcdaniel, R AF Leykum, L. Pugh, J. Lawrence, V. Parchman, M. Noel, P. Cornell, J. Mcdaniel, R. TI Making sense of organizational interventions using complexity science SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Leykum, L.; Lawrence, V.; Parchman, M.; Cornell, J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. [Pugh, J.; Noel, P.] So Texas Vet Hlth Care Syst, San Antonio, TX USA. [Mcdaniel, R.] Univ Texas Austin, Austin, 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 26 EP 27 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700090 ER PT J AU Lopez, L Horng, M Cook, E Hicks, L AF Lopez, L. Horng, M. Cook, E. Hicks, L. TI Lifestyle modification counseling for hypertensive patients: Results from the national health and nutrition examination survey 1999-2004 SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Lopez, L.] Massachusetts Gen Hosp, Inst Hlth Policy, Dept Med, Boston, MA 02114 USA. [Horng, M.; Cook, E.; Hicks, L.] Brigham & Womens Hosp, Boston, MA 02115 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 26 EP 26 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700089 ER PT J AU Adams, AS Trinacty, CM Zhang, F Kleinman, KP Grant, RW Meigs, JB Soumerai, SB Ross-Degnan, D AF Adams, A. S. Trinacty, C. Mah Zhang, F. Kleinman, K. P. Grant, R. W. Meigs, J. B. Soumerai, S. B. Ross-Degnan, D. TI Medication adherence and racial differences in HBA1C control SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Adams, A. S.; Trinacty, C. Mah; Zhang, F.; Kleinman, K. P.; Soumerai, S. B.; Ross-Degnan, D.] Harvard Med Sch, Harvard Pilgrim Hlth Care, Boston, MA USA. [Grant, R. W.; Meigs, J. B.] Massachusetts Gen Hosp, Harvard Med Sch, 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 27 EP 27 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700091 ER PT J AU Mortensen, E Leykum, L Noel, PH Zeber, J Pugh, M Lawrence, V AF Mortensen, E. Leykum, L. Noel, P. Hitchcock Zeber, J. Pugh, M. Lawrence, V. TI Organizational interventions to improve outcomes for patients with COPD SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Mortensen, E.; Leykum, L.; Noel, P. Hitchcock; Zeber, J.; Pugh, M.; Lawrence, V.] So Texas Vet Hlth Care Syst, San Antonio, TX 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 28 EP 28 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700096 ER PT J AU Trinacty, CM Adams, AS Soumerai, B Zhang, F Meigs, JB Piette, JD Ross-Degnan, D AF Trinacty, C. M. Adams, A. S. Soumerai, B. Zhang, F. Meigs, J. B. Piette, J. D. Ross-Degnan, D. TI Racial differences in long-term adherence to hypoglycemic therapy SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Trinacty, C. M.; Adams, A. S.; Soumerai, B.; Zhang, F.; Ross-Degnan, D.] Harvard Med Sch, Harvard Pilgrim Hlth Care, Boston, MA USA. [Meigs, J. B.] Massachusetts Gen Hosp, Gen Med Unit, Boston, MA USA. [Piette, J. D.] Univ Michigan, Ann Arbor, MI 48109 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 31 EP 31 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700107 ER PT J AU Fischer, MA Ferris, TG Vogeli, C Stedman, M Brookhart, MA Weissman, JS AF Fischer, M. A. Ferris, T. G. Vogeli, C. Stedman, M. Brookhart, M. A. Weissman, J. S. TI Impact of electronic prescribing on medication use and cost in community-based practices SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Fischer, M. A.; Stedman, M.; Brookhart, M. A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ferris, T. G.; Vogeli, C.; Weissman, J. S.] Massachusetts Gen Hosp, 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 39 EP 40 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700134 ER PT J AU Groeneveld, PW Matta, A Suh, JJ Olah, JF Yang, F Shea, JA AF Groeneveld, P. W. Matta, A. Suh, J. J. Olah, J. F. Yang, F. Shea, J. A. TI Quality of life for drug eluting stent recipients: Are avoided revascularizations valued? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Groeneveld, P. W.] Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Matta, A.; Suh, J. J.; Olah, J. F.; Yang, F.; Shea, J. A.] Univ Penn, Div Gen Internal Med, Philadelphia, 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 40 EP 40 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700137 ER PT J AU Ling, B Trauth, JM Fine, MJ Mor, MK Abby, R Braddock, CH Bereknyei, S Weissfeld, J Schoen, R Whittle, J AF Ling, B. Trauth, J. M. Fine, M. J. Mor, M. K. Abby, R. Braddock, C. H. Bereknyei, S. Weissfeld, J. Schoen, R. Whittle, J. TI Informed decision making and colorectal cancer screening: Is it occurring in primary care and what is the impact on screening rates? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Ling, B.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Trauth, J. M.; Fine, M. J.; Weissfeld, J.; Schoen, R.] Univ Pittsburgh, Pittsburgh, PA USA. [Mor, M. K.] Univ Pittsburgh, Pittsburgh VA Hlth Care Syst, Sch Med, Pittsburgh, PA USA. [Abby, R.] VA Pittsburg Healthcare Syst, Pittsburgh, PA USA. [Braddock, C. H.; Bereknyei, S.] Stanford Univ, Palo Alto, CA 94304 USA. [Whittle, J.] Med Coll Wisconsin, Milwaukee, WI 53226 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 40 EP 40 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700135 ER PT J AU Siegel, LC Sesso, HD Bowman, TS Gaziano, JM AF Siegel, L. C. Sesso, H. D. Bowman, T. S. Gaziano, J. M. TI A prospective study of physical activity and body mass index on the risk of type 2 diabetes in men SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Siegel, L. C.; Sesso, H. D.; Bowman, T. S.; Gaziano, J. M.] VA Boston Healthcare Syst, Boston, MA 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 42 EP 42 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700142 ER PT J AU Mortensen, E Restrepo, M Copeland, L Anzueto, A Pugh, J AF Mortensen, E. Restrepo, M. Copeland, L. Anzueto, A. Pugh, J. TI Association of lipophilic and hydrophilic ace inhibitor use with pneumonia-related mortality SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Mortensen, E.; Copeland, L.; Pugh, J.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Restrepo, M.; Anzueto, A.] Univ Texas Hlth Sci Ctr San Antonio, Audie L Murphy VA Hosp, San Antonio, TX 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 44 EP 44 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700150 ER PT J AU Ruhnke, GW Norton, DM Cutler, DM AF Ruhnke, G. W. Norton, D. M. Cutler, D. M. TI Community-acquired pneumonia in the elderly: Evidence for marked improvement in 30-day mortality SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Ruhnke, G. W.] Massachusetts Gen Hosp, Boston, MA USA. [Norton, D. M.] Natl Bur Econ Res, Cambridge, MA USA. [Cutler, D. M.] Harvard Univ, Cambridge, MA 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 46 EP 47 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700158 ER PT J AU Groeneveld, PW Yang, F Matta, MA AF Groeneveld, P. W. Yang, F. Matta, M. A. TI Costs and outcomes of drug eluting coronary stents versus bare metal stents among the elderly SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Groeneveld, P. W.] Univ Penn, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Yang, F.; Matta, M. A.] Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 48 EP 48 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700162 ER PT J AU Shlipak, MG Katz, R Fried, L Kestenbaum, B Stevens, L Newman, A Siscovick, DS Samak, MJ AF Shlipak, M. G. Katz, R. Fried, L. Kestenbaum, B. Stevens, L. Newman, A. Siscovick, D. S. Samak, M. J. TI Kidney function loss in black and white elderly persons - A comparison using creatinine and cystatin SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Shlipak, M. G.] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA USA. [Katz, R.; Kestenbaum, B.; Siscovick, D. S.] Univ Washington, Seattle, WA USA. [Fried, L.] VA Pittsburg Healthcare Syst, Pittsburgh, PA USA. [Stevens, L.; Samak, M. J.] Tufts Univ New England Med Ctr, Boston, MA USA. [Newman, A.] Univ Pittsburgh, Pittsburgh, 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 52 EP 53 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700178 ER PT J AU Singh, HS Bibbins-Domingo, K Sadia, A Whooley, MA AF Singh, H. S. Bibbins-Domingo, K. Sadia, A. Whooley, M. A. TI N-terminal pro-B-type natriuretic peptide and inducible ischemia in patients with coronary heart disease from the heart and soul study SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Singh, H. S.; Bibbins-Domingo, K.] Univ Calif San Francisco, San Francisco, CA USA. [Sadia, A.; Whooley, M. A.] San Francisco VA Med Ctr, San Francisco, CA 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 54 EP 54 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700183 ER PT J AU Seal, KH Bertenthal, D Chu, A Gima, KS Marmar, C AF Seal, K. H. Bertenthal, D. Chu, A. Gima, K. S. Marmar, C. TI Va post-deployment screening for mental health disorders among veterans returning from Iraq and Afghanistan - Are we doing a good job? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Seal, K. H.; Marmar, C.] Univ Calif San Francisco, San Francisco, CA USA. [Bertenthal, D.; Chu, A.; Gima, K. S.] San Francisco VA Med Ctr, San Francisco, CA 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 61 EP 61 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700208 ER PT J AU Keyhani, S Ross, J Hebert, P Dellenbaugh, C Penrod, J Siu, AL AF Keyhani, S. Ross, J. Hebert, P. Dellenbaugh, C. Penrod, J. Siu, A. L. TI Does the va provide veterans with better quality preventive care compared to medicare HMO plans? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Keyhani, S.; Ross, J.; Siu, A. L.] James J Peters VAMC, Mt Sinai Sch Med, New York, NY USA. [Hebert, P.] Mt Sinai Sch Med, New York, NY USA. [Dellenbaugh, C.] James J Peters VAMC, Bronx, NY USA. [Penrod, J.] James J Peters VAMC, Mt Sinai Sch Med, Bronx, NY 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 65 EP 66 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700222 ER PT J AU Volpp, K Rosen, A Rosenbaum, P Romano, PS Even-Shoshan, O Canamucio, A Bellini, LM Behringer, T Silber, JH AF Volpp, K. Rosen, A. Rosenbaum, P. Romano, P. S. Even-Shoshan, O. Canamucio, A. Bellini, L. M. Behringer, T. Silber, J. H. TI The impact of the ACGME duty hour rules on mortality rates in teaching hospitals SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Volpp, K.] Univ Penn, Sch Med, Philadelphia VA Med Ctr, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Rosen, A.] Boston Univ, Bedford VA, Boston, MA 02215 USA. [Rosenbaum, P.] Univ Penn Wharton Sch, Philadelphia, PA USA. [Romano, P. S.] Univ Calif Davis, Davis, CA 95616 USA. [Even-Shoshan, O.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Canamucio, A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Bellini, L. M.; Behringer, T.] Univ Penn, Philadelphia, PA 19104 USA. [Silber, J. H.] Childrens Hosp Philadelphia, Wharton Sch, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RI Romano, Patrick/N-4225-2014 OI Romano, Patrick/0000-0001-6749-3979 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 69 EP 69 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700233 ER PT J AU Barrett, TW Mori, M Koudelka, C AF Barrett, T. W. Mori, M. Koudelka, C. TI Perioperative beta-blockers, but not statins, are associated with decreased short term mortality after vascular surgery SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Barrett, T. W.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. [Mori, M.; Koudelka, C.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 76 EP 76 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700255 ER PT J AU Sung, AD Collins, ME Smith, AK Sanders, AM Block, SD Arnold, RM AF Sung, A. D. Collins, M. E. Smith, A. K. Sanders, A. M. Block, S. D. Arnold, R. M. TI Crying, stress and sadness: The experience and attitudes of 3rd year medical students and interns SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Sung, A. D.; Collins, M. E.] Harvard Univ, Boston, MA USA. [Smith, A. K.] Beth Israel Deaconess Med Ctr, Dana Farber Canc Inst, Brookline, MA USA. [Sanders, A. M.; Arnold, R. M.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Block, S. D.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 81 EP 81 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700274 ER PT J AU Massie, F Castiglioni, A Caldwell, JA Wood, A Estrada, CA AF Massie, F. Castiglioni, A. Caldwell, J. A. Wood, A. Estrada, C. A. TI Does performance of physical exam skills during medical school improve with clinical experience? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Massie, F.; Caldwell, J. A.; Wood, A.; Estrada, C. A.] Univ Alabama, Birmingham, AL USA. [Castiglioni, A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 82 EP 83 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700279 ER PT J AU Reddy, S Farnan, JM Yoon, J Leo, T Upadhyay, G Young, M Roberts, C Kondapalli, L Humphrey, HJ Arora, V AF Reddy, S. Farnan, J. M. Yoon, J. Leo, T. Upadhyay, G. Young, M. Roberts, C. Kondapalli, L. Humphrey, H. J. Arora, V. TI Effects of the hidden curriculum on third year medical student participation in and perceptions of unprofessional behaviors SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Reddy, S.; Farnan, J. M.; Yoon, J.; Leo, T.; Kondapalli, L.; Humphrey, H. J.; Arora, V.] Univ Chicago, Chicago, IL 60637 USA. [Upadhyay, G.] Massachusetts Gen Hosp, Boston, MA USA. [Young, M.] Boston Univ, Boston, MA 02215 USA. [Roberts, C.] Columbia Univ, New York, NY 10027 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 83 EP 83 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700281 ER PT J AU Caverzagie, KJ Kogan, JR Shea, JA AF Caverzagie, K. J. Kogan, J. R. Shea, J. A. TI Have we moved beyond assessing medical knowledge? Resident identified learning goals after self-assessment SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Caverzagie, K. J.] Vet Affairs Med Ctr, Philadelphia, PA USA. [Kogan, J. R.] Univ Penn, Huntingdon, PA USA. [Shea, J. A.] Society Directors Res Med Educ, Philadelphia, 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 84 EP 84 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700284 ER PT J AU Salanitro, AH Castiglioni, A Willett, LL Shewchuk, RM Heudebert, GR Milne, C Watson, P Capps, L Caverzagie, KJ Centor, RM AF Salanitro, A. H. Castiglioni, A. Willett, L. L. Shewchuk, R. M. Heudebert, G. R. Milne, C. Watson, P. Capps, L. Caverzagie, K. J. Centor, R. M. TI Housestaff views on successful attending rounds. A multiinstitutional study SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Salanitro, A. H.; Willett, L. L.; Shewchuk, R. M.; Heudebert, G. R.; Centor, R. M.] Univ Alabama, Birmingham, AL USA. [Castiglioni, A.] Vet Affairs Med Ctr, Birmingham, AL USA. [Milne, C.] Univ Utah, Salt Lake City, UT 84112 USA. [Watson, P.] Henry Ford Hosp, Detroit, MI USA. [Capps, L.] Columbia Univ, New York, NY 10027 USA. [Caverzagie, K. J.] Vet Affairs Med Ctr, Philadelphia, 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 84 EP 84 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700285 ER PT J AU Lopez, L Vranceanu, A Betancourt, J Weissman, J AF Lopez, L. Vranceanu, A. Betancourt, J. Weissman, J. TI Physician factors associated with resident physicians' perceptions of their preparedness to deliver cross-cultural care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Lopez, L.; Betancourt, J.; Weissman, J.] Massachusetts Gen Hosp, Inst Hlth Policy, Dept Med, Boston, MA USA. [Vranceanu, A.] Massachusetts Gen Hosp, 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 88 EP 89 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700300 ER PT J AU Gopal, RK Radhakrishnan, P Gateley, A Glasheen, JJ Prochazka, AV AF Gopal, R. K. Radhakrishnan, P. Gateley, A. Glasheen, J. J. Prochazka, A. V. TI Predictors of internal medicine internship burnout: Importance of cognitive factors SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Gopal, R. K.; Prochazka, A. V.] US Dept Vet Affairs, Denver, CO USA. [Radhakrishnan, P.] St Joseph Med Ctr, Phoenix, AZ USA. [Gateley, A.] Univ New Mexico, Albuquerque, NM USA. [Glasheen, J. J.] Univ Colorado, Hlth Sci Ctr, Denver, CO 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 89 EP 89 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700303 ER PT J AU Goldhamer, ME Bates, DW Cook, E Davis, R Cohen, A Singer, D Simon, SR AF Goldhamer, M. E. Bates, D. W. Cook, E. Davis, R. Cohen, A. Singer, D. Simon, S. R. TI Research training in clinical effectiveness: Does academic status in a cohort of trainees impact time to NIH grant funding? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Goldhamer, M. E.] Massachusetts Gen Hosp, Willington, CT USA. [Bates, D. W.] Brigham & Womens Hosp, Watertown, MA USA. [Cook, E.] Harvard Sch Publ Hlth, Boston, MA USA. [Davis, R.; Simon, S. R.] Harvard Univ, Boston, MA USA. [Cohen, A.] Harvard Univ, Brookline, MA USA. [Singer, D.] Massachusetts Gen Hosp, Boston, MA 02114 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 90 EP 90 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700306 ER PT J AU Branch, WT Frankel, RM Gracey, C Haidel, PM Weissmann, P Cantey, P Mitchell, GA Inui, T AF Branch, W. T. Frankel, R. M. Gracey, C. Haidel, P. M. Weissmann, P. Cantey, P. Mitchell, G. A. Inui, T. TI The arthur vining davis foundations faculty development workshops for teaching the human dimensions of care: Longitudinal faculty development enhances the effectiveness of clinical teachers SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Branch, W. T.] Emory Hlthcare, Atlanta, GA USA. [Frankel, R. M.; Mitchell, G. A.; Inui, T.] Indiana Univ Purdue Univ, Indianapolis, IN USA. [Gracey, C.] Houston VA Med Ctr, Rochester, MN USA. [Haidel, P. M.] Houston VA Med Ctr, Houston, TX USA. [Weissmann, P.] Hennepin Cty Med Ctr, Minneapolis, MN USA. [Cantey, P.] Emory Univ, Sch Med, Atlanta, GA 30322 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 93 EP 93 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700315 ER PT J AU Paige, NM Liu, H Goldzweig, CL Wong, E Zhou, A Munjas, B Shekelle, P AF Paige, N. M. Liu, H. Goldzweig, C. L. Wong, E. Zhou, A. Munjas, B. Shekelle, P. TI A systematic review of screening tests for male osteoporosis SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Paige, N. M.; Goldzweig, C. L.; Munjas, B.] VA Greater Los Angels Healthcare Syst, Los Angeles, CA USA. [Liu, H.] Stanford Univ, Sch Med, Div Endocrinol & Metab, Stanford, CA 94305 USA. [Wong, E.] VA Greater Los Angeles Healthcare Syst, Div Endocrinol & Metab, Los Angeles, CA USA. [Zhou, A.] RAND Corp, Santa Monica, CA USA. [Shekelle, P.] RAND Corp, VA Greater Los Angeles Healthcare Syst, Santa Monica, CA 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 99 EP 99 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700334 ER PT J AU An, PG Ashburner, JM Blair, FW Atlas, SJ AF An, P. G. Ashburner, J. M. Blair, F. W. Atlas, S. J. TI Cancer screening in the ambulatory setting by resident physicians SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [An, P. G.; Ashburner, J. M.; Blair, F. W.; Atlas, S. J.] Massachusetts Gen Hosp, 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 101 EP 101 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700343 ER PT J AU Farwell, WR Linder, J Jha, AK AF Farwell, W. R. Linder, J. Jha, A. K. TI Changes in rates of PSA testing among American men SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Farwell, W. R.; Jha, A. K.] VA Boston Healthcare Syst, Boston, MA USA. [Linder, J.] Brigham & Womens Hosp, Boston, MA 02115 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 101 EP 102 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700344 ER PT J AU Huang, AJ Iwaoka-Scott, Y Kim, SE Wong, ST Perez-Stable, EJ Washington, E Sawaya, GF AF Huang, A. J. Iwaoka-Scott, Y. Kim, S. E. Wong, S. T. Perez-Stable, E. J. Washington, E. Sawaya, G. F. TI Preferences for HPV testing among ethnically-diverse older women SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Huang, A. J.] San Francisco VA Med Ctr, San Francisco, CA USA. [Iwaoka-Scott, Y.; Kim, S. E.; Perez-Stable, E. J.; Washington, E.; Sawaya, G. F.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Wong, S. T.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 107 EP 108 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700365 ER PT J AU Mclaughlin-Gavin, CE Jha, AK AF Mclaughlin-Gavin, C. E. Jha, A. K. TI Predictors of impaired fasting glucose in the U. S. population: Opportunities for screening SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Mclaughlin-Gavin, C. E.; Jha, A. K.] VA Boston Healthcare Syst, MAVERIC, Boston, MA 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 107 EP 107 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700363 ER PT J AU Walter, L Lindquist, K Schull, T Nugent, S Casadei, M Partin, M AF Walter, L. Lindquist, K. Schull, T. Nugent, S. Casadei, M. Partin, M. TI Relationship of health status and colorectal cancer screening among elderly veterans SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Walter, L.; Casadei, M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Lindquist, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Schull, T.; Nugent, S.; Partin, M.] Minneapolis VA Med Ctr, Minneapolis, MN 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 109 EP 109 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700370 ER PT J AU Williams, EC Achtmeyer, CE Frey, MS Volpp, B Kivlahan, DR Bradley, KA AF Williams, E. C. Achtmeyer, C. E. Frey, M. S. Volpp, B. Kivlahan, D. R. Bradley, K. A. TI Sustained improvements in documented brief alcohol counseling 2 years after implementation of an electronic clinical reminder SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Williams, E. C.; Kivlahan, D. R.; Bradley, K. A.] Univ Washington, Seattle, WA 98195 USA. [Achtmeyer, C. E.] VA Puget Sound, Seattle, WA USA. [Frey, M. S.] VA Puget Sound, Hlth Serv Res & Dev, Seattle, WA USA. [Frey, M. S.] VA No Calif Healthcare Syst, Martinez, CA 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 110 EP 110 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700373 ER PT J AU Haidet, P Hatem, DS Stein, H Fecile, ML Haley, HA Kimmel, B Mossbarger, DL Inui, TS AF Haidet, P. Hatem, D. S. Stein, H. Fecile, M. L. Haley, H. A. Kimmel, B. Mossbarger, D. L. Inui, T. S. TI The role of relationships in the professional formation of physicians SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Haidet, P.; Kimmel, B.] Houston VAMC, Houston, TX USA. [Hatem, D. S.; Haley, H. A.] Univ Massachusetts, Med Ctr, Worcester, MA USA. [Stein, H.] Univ Oklahoma, Oklahoma City, OK USA. [Fecile, M. L.] Univ Texas Med Branch Galveston, Galveston, TX USA. [Mossbarger, D. L.; Inui, T. S.] Regenstrief Inst Inc, Indianapolis, IN 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 116 EP 116 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700394 ER PT J AU Rodriguez, KL Appelt, CJ Switzer, GE Sonel, AF Arnold, RM AF Rodriguez, K. L. Appelt, C. J. Switzer, G. E. Sonel, A. F. Arnold, R. M. TI "They diagnosed bad heart": A qualitative exploration of patients' knowledge about and experiences with heart failure SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Rodriguez, K. L.; Appelt, C. J.; Sonel, A. F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Switzer, G. E.; Arnold, R. M.] Univ Pittsburgh, Pittsburgh, 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 116 EP 117 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700396 ER PT J AU Singh, H Arora, H Vij, M Rao, R Khan, M Petersen, LA AF Singh, H. Arora, H. Vij, M. Rao, R. Khan, M. Petersen, L. A. TI Communication outcomes of critical imaging results in a computerized notification system SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Singh, H.; Petersen, L. A.] Baylor Coll Med, Houston Ctr Quality Care & Utilizat Studies, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Arora, H.; Rao, R.; Khan, M.] Baylor Coll Med, Houston, TX USA. [Vij, M.] Michaele E DeBakey Vet Affairs Med Ctr, Houston, TX 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 122 EP 122 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700416 ER PT J AU An, PG Rabatin, JS Brown, RL Manwell, LB Linzer, M Schwartz, MD AF An, P. G. Rabatin, J. S. Brown, R. L. Manwell, L. B. Linzer, M. Schwartz, M. D. TI Effects of caring for difficult patients: Data from the MEMO (Minimizing Error, Maximizing Outcome) study SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [An, P. G.] Massachusetts Gen Hosp, Boston, MA USA. [Rabatin, J. S.] Brown Med Sch, Providence, RI USA. [Brown, R. L.; Manwell, L. B.; Linzer, M.] Univ Wisconsin, Madison, WI USA. [Schwartz, M. D.] NYU, Sch Med, New York, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 125 EP 125 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700426 ER PT J AU Gonzales, R Aagaard, E Camargo, CA Ma, O Maselli, J Mackenzie, TD Mcculloch, CE Levin, SK Metlay, JP AF Gonzales, R. Aagaard, E. Camargo, C. A., Jr. Ma, O. Maselli, J. Mackenzie, T. D. Mcculloch, C. E. Levin, S. K. Metlay, J. P. TI Impact of a C-reactive protein-based algorithm on antibiotic treatment of acute cough illness in adults SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Gonzales, R.; Maselli, J.; Mcculloch, C. E.; Levin, S. K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Aagaard, E.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Camargo, C. A., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ma, O.] Oregon Hlth & Sci Univ, Portland, OR USA. [Mackenzie, T. D.] Denver Hlth & Hosp Author, Denver, CO USA. [Metlay, J. P.] Univ Penn, Dept Vet Affairs, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 127 EP 128 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700437 ER PT J AU Aujesky, D Stone, RA Crick, E Fine, MJ AF Aujesky, D. Stone, R. A. Crick, E. Fine, M. J. TI Length of hospital stayand post-discharge mortality in patients with pulmonary embolism: A state-wide perspective SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Aujesky, D.] Univ Lausanne, CH-1015 Lausanne, Switzerland. [Stone, R. A.; Crick, E.; Fine, M. J.] VA Pittsburgh Healthcare Syst, Pittsburgh, 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 129 EP 130 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700444 ER PT J AU Fang, MC Singer, D Chang, Y Borowsky, LH Pomernacki, NK Go, AS AF Fang, M. C. Singer, D. Chang, Y. Borowsky, L. H. Pomernacki, N. K. Go, A. S. TI Linking the quality of anticoagulation control to clinical outcomes in patients with atrial fibrillation: The ATRIA study SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Fang, M. C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Singer, D.; Chang, Y.; Borowsky, L. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pomernacki, N. K.] Kaiser Permanente Div Res, Oakland, CA USA. [Go, A. S.] Univ Calif San Francisco, Kaiser Permanente Div Res, Oakland, CA 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 130 EP 130 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700446 ER PT J AU Singh, H Thomas, EJ Petersen, LA Studdert, D AF Singh, H. Thomas, E. J. Petersen, L. A. Studdert, D. TI Medical errors involving housestaff: A study of closed malpractice claims from 5 insurers SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Singh, H.; Petersen, L. A.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Thomas, E. J.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Studdert, D.] Harvard Sch Publ Hlth, Boston, MA 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 131 EP 131 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700449 ER PT J AU Aggarwal, A Sommers, EA Suen, W Cabral, H Saitz, R Kazis, L AF Aggarwal, A. Sommers, E. A. Suen, W. Cabral, H. Saitz, R. Kazis, L. TI The association of pain characteristics with heavy alcohol use SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Aggarwal, A.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Sommers, E. A.; Cabral, H.; Saitz, R.] Boston Univ, Boston, MA 02215 USA. [Suen, W.] Dana Farber Canc Inst, Boston, MA USA. [Kazis, L.] VA Hosp, CHQOER, Bedford, MA 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 137 EP 137 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700473 ER PT J AU Leykum, L Padgett, C Gustke, D Baruch-Bienen, D Patterson, J AF Leykum, L. Padgett, C. Gustke, D. Baruch-Bienen, D. Patterson, J. TI The association between nurse staffing levels and inpatient falls SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Leykum, L.; Padgett, C.; Gustke, D.; Baruch-Bienen, D.] So Texas Vet Hlth Care Syst, San Antonio, TX USA. [Patterson, J.] Univ Texas Hlth Sci Ctr San Antonio, 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 137 EP 137 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700472 ER PT J AU Metlay, J Hennessy, S Localio, R Leonard, C Haynes, K Cohen, A Kimmel, S Feldman, H Strom, B AF Metlay, J. Hennessy, S. Localio, R. Leonard, C. Haynes, K. Cohen, A. Kimmel, S. Feldman, H. Strom, B. TI The importance of patient medication education and coordination in preventing serious events for older adults on warfarin SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Metlay, J.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Hennessy, S.; Localio, R.; Leonard, C.; Haynes, K.; Cohen, A.; Kimmel, S.; Feldman, H.; Strom, B.] Univ Penn, Philadelphia, PA 19104 USA. RI Cohen, Abigail/K-9180-2013 OI Cohen, Abigail/0000-0002-7425-7218 NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 138 EP 138 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700478 ER PT J AU Woodard, L Urech, T Kuebeler, M Pietz, K Capistrano, L Petersen, LA AF Woodard, L. Urech, T. Kuebeler, M. Pietz, K. Capistrano, L. Petersen, L. A. TI The impact of comorbid medical conditions on the quality of diabetes care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Woodard, L.] Baylor Coll Med, Houston, TX 77030 USA. [Urech, T.; Kuebeler, M.; Pietz, K.; Capistrano, L.; Petersen, L. A.] HSR&D Ctr Excellence, Michael E DeBakey Vet Affair Med Ctr, Houston, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 138 EP 138 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700477 ER PT J AU Rose, AJ Berlowitz, DR Orner, MB Kressin, NR AF Rose, A. J. Berlowitz, D. R. Orner, M. B. Kressin, N. R. TI Understanding uncontrolled hypertension: Is it the patient or the provider? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Rose, A. J.; Berlowitz, D. R.; Orner, M. B.; Kressin, N. R.] US Dept Vet Affairs, Bedford, MA 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 140 EP 140 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700485 ER PT J AU Conigliaro, J Maisto, SA Gordon, A Mcginnis, KA Justice, AC AF Conigliaro, J. Maisto, S. A. Gordon, A. Mcginnis, K. A. Justice, A. C. TI A comparison of the self-administered 30 day TLFB method compared to the phone interview method among clinical samples of HIV plus and HIV-patients SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Conigliaro, J.] Univ Kentucky, Lexington, KY USA. [Maisto, S. A.] Syracuse Univ, Dept Psychol, Syracuse, NY USA. [Gordon, A.] VA Pittsburgh Healtcare Syst, Pittsburgh, PA USA. [Mcginnis, K. A.] Univ Pittsburgh, Pittsburgh, PA USA. [Justice, A. C.] Yale Univ, West Haven, CT USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 143 EP 143 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700495 ER PT J AU Kressin, NR Orner, MB Manze, M Glickman, M Davidson, PK Borzecki, A Berlowitz, DR AF Kressin, N. R. Orner, M. B. Manze, M. Glickman, M. Davidson, P. K. Borzecki, A. Berlowitz, D. R. TI African Americans and beliefs about hypertension, its therapy, and etiology: More worries, fewer benefits, less control SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Kressin, N. R.] Ctr Hlth Qual, Outcomes & Econ Res, VA HSR&D Ctr Excellence, Bedford, MA USA. [Orner, M. B.] US Dept Vet Affairs, Bedford, MA USA. [Manze, M.] Med Ctr, Boston, MA USA. [Glickman, M.; Davidson, P. K.; Borzecki, A.] Boston Univ, Boston, MA 02215 USA. [Berlowitz, D. R.] Boston Univ, Bedford, MA 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 143 EP 143 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700496 ER PT J AU Percac-Lima, S Peters-Lewis, A Atlas, SJ Richter, JM Betancourt, JR Janairo, M Green, AR AF Percac-Lima, S. Peters-Lewis, A. Atlas, S. J. Richter, J. M. Betancourt, J. R. Janairo, M. Green, A. R. TI Barriers to screening colonoscopy in Latino and white non-Latino patients in an urban community health center. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Percac-Lima, S.] Massachusetts Gen Hosp, Chelsea, MA USA. [Peters-Lewis, A.; Atlas, S. J.; Richter, J. M.; Betancourt, J. R.; Janairo, M.; Green, A. R.] Massachusetts Gen Hosp, Boston, MA 02114 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 144 EP 145 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700501 ER PT J AU Dookeran, NM Burgess, J Bowman, C Chen, Y Asch, S Gifford, A AF Dookeran, N. M. Burgess, J. Bowman, C. Chen, Y. Asch, S. Gifford, A. TI HIV testing in adults with alcohol and other substance use disorders. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Dookeran, N. M.; Burgess, J.; Gifford, A.] Boston Univ, Vet Affairs Bedford, Bedford, MA USA. [Bowman, C.; Chen, Y.] VA San Diego, San Diego, CA USA. [Asch, S.] VA Greater Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 150 EP 150 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700519 ER PT J AU Green, AR Carney, D Pallin, D Betancourt, J Ngo, L Iezzoni, LI Banaji, M AF Green, A. R. Carney, D. Pallin, D. Betancourt, J. Ngo, L. Iezzoni, L. I. Banaji, M. TI Implicit bias among physicians and its prediction of thrombolysis decisions for black and white patients. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Green, A. R.] Soc Gen Internal Med, Boston, MA USA. [Carney, D.; Banaji, M.] Harvard Univ, Cambridge, MA USA. [Pallin, D.] Brigham & Womens Hosp, Boston, MA USA. [Betancourt, J.] Massachusetts Gen Hosp, Boston, MA USA. [Ngo, L.] Harvard Med Sch, Beth Israel Med Ctr, Brookline, MA USA. [Iezzoni, L. I.] Harvard Univ, Boston, MA USA. OI Pallin, Daniel/0000-0002-8517-9702 NR 0 TC 0 Z9 0 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 150 EP 151 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700522 ER PT J AU Frank, D Gallagher, TH Cooper, LA Odunlami, B Sellers, S Price, EG Phillips, E Bonham, VL AF Frank, D. Gallagher, T. H. Cooper, L. A. Odunlami, B. Sellers, S. Price, E. G. Phillips, E. Bonham, V. L. TI Physicians' attitudes regarding race-based therapeutics SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Frank, D.] VA Puget Sound, Seattle, WA USA. [Gallagher, T. H.] Univ Washington, Seattle, WA 98195 USA. [Cooper, L. A.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Odunlami, B.; Phillips, E.; Bonham, V. L.] Natl Inst Hlth, Bethesda, MD USA. [Sellers, S.] Univ Wisconsin, Madison, WI 53706 USA. [Price, E. G.] Tulane Univ, New Orleans, LA 70118 USA. RI Price-Haywood, Eboni/L-5527-2014 OI Price-Haywood, Eboni/0000-0003-2901-3852 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 155 EP 156 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700540 ER PT J AU Groeneveld, PW Kwoh, C Mor, MK Geng, M Appelt, CJ Gutierrez, JC Ibrahim, SA AF Groeneveld, P. W. Kwoh, C. Mor, M. K. Geng, M. Appelt, C. J. Gutierrez, J. C. Ibrahim, S. A. TI Racial differences in joint replacement expectations among veterans with osteoarthritis SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Groeneveld, P. W.] Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Kwoh, C.] Univ Pittsburgh, Pittsburgh VA Hlth Care Syst, Philadelphia, PA 19104 USA. [Mor, M. K.] Univ Pittsburgh, Sch Med, Pittsburgh VA Hlth Care Syst, Philadelphia, PA 19104 USA. [Geng, M.; Appelt, C. J.; Ibrahim, S. A.] Pittsburgh VA Hlth Care Syst, Pittsburgh, PA USA. [Gutierrez, J. C.] Philadelphia VA Med Ctr, Philadelphia, 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 158 EP 158 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700548 ER PT J AU Binswanger, I Takahashi, T Dellit, TH Bradley, K Benton, KL Merrill, JO AF Binswanger, I. Takahashi, T. Dellit, T. H. Bradley, K. Benton, K. L. Merrill, J. O. TI Risk of hospitalizations and death among injection drug users seeking care for soft tissue infections SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Binswanger, I.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Takahashi, T.; Bradley, K.] Univ Washington, VA Puget Sound, Seattle, WA 98195 USA. [Dellit, T. H.; Merrill, J. O.] Univ Washington, Seattle, WA 98195 USA. [Benton, K. L.] Univ Colorado, Hlth Sci Ctr, Aurora, CO 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 159 EP 159 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700552 ER PT J AU Pollack, C Chideya, S Cubbin, C Williams, B Dekker, M Braveman, P AF Pollack, C. Chideya, S. Cubbin, C. Williams, B. Dekker, M. Braveman, P. TI Should health studies measure wealth? A systematic review SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Pollack, C.] Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Chideya, S.] CDC, Ctr Dis Control & Prevent, Atlanta, GA USA. [Cubbin, C.; Williams, B.; Dekker, M.; Braveman, P.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Cubbin, C.] Univ Texas Austin, San Francisco, CA 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 160 EP 160 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700554 ER PT J AU Bean-Mayberry, B Yano, E Wang, M Mor, MK Fine, MJ AF Bean-Mayberry, B. Yano, E. Wang, M. Mor, M. K. Fine, M. J. TI Do gender and race affect quality of care in the VA healthcare system? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Bean-Mayberry, B.; Yano, E.; Wang, M.] VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA USA. [Mor, M. K.; Fine, M. J.] Univ Pittsburgh, VA Pittsburgh Ctr Hlth Equity Res & Promot, Pittsburgh, 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 165 EP 166 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700574 ER PT J AU Huang, AJ Grady, DG Blackwell, TL Bauer, DC Sawaya, GF AF Huang, A. J. Grady, D. G. Blackwell, T. L. Bauer, D. C. Sawaya, G. F. TI Persistent hot flashes in older postmenopausal women SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Huang, A. J.] San Francisco VA Med Ctr, San Francisco, CA USA. [Grady, D. G.; Bauer, D. C.; Sawaya, G. F.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Blackwell, T. L.] California Pacific Med Ctr, San Francisco, CA 94143 USA. 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 168 EP 168 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700583 ER PT J AU Rehman, SU Hutchison, FN AF Rehman, S. U. Hutchison, F. N. TI The effectiveness of multidisciplinary primary care morning report SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Rehman, S. U.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Mt Pleasant, MI USA. [Hutchison, F. N.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 188 EP 188 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700650 ER PT J AU Mehrotra, A Keehl-Markowitz, L Ayanian, JZ AF Mehrotra, A. Keehl-Markowitz, L. Ayanian, J. Z. TI Implementation of open access scheduling in primary care: A cautionary tale SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Mehrotra, A.] Univ Pittsburgh, Pittsburgh, PA USA. [Keehl-Markowitz, L.] Massachusetts Gen Hosp, Boston, MA USA. [Ayanian, J. Z.] Harvard Univ, Boston, MA 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 198 EP 198 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700682 ER PT J AU Kressin, NR Orner, MB Berlowitz, DR AF Kressin, N. R. Orner, M. B. Berlowitz, D. R. TI Strategies for improving provider-patient communication about medication adherence: Can behavior change be effected? Does it affect patient outcomes? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Kressin, N. R.] VA HSR&D Ctr Excellence, Outcomes & Econ Res, Ctr Hlth Qaulity, Bedford, MA USA. [Orner, M. B.] US Dept Vet Affairs, Bedford, MA USA. [Berlowitz, D. R.] Boston Univ, Bedford, MA 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 202 EP 202 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700696 ER PT J AU Lu, LC Davis, LG AF Lu, L. C. Davis, L. G. TI Asymptomatic disseminated Coccidioidomycosis presenting with elevated prostatic serum antigen SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Lu, L. C.; Davis, L. G.] Greater Los Angeles VA Med Ctr, Los Angeles, CA 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 239 EP 239 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700833 ER PT J AU Chen, T Haidet, PM AF Chen, T. Haidet, P. M. TI A very deadly rash SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Chen, T.] Baylor Coll Med, Houston, TX USA. [Haidet, P. M.] Houston VA Med Ctr, Houston, TX 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 SU 1 BP 250 EP 250 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 240TQ UT WOS:000251610700872 ER PT J AU Nelson, KM McFarland, L Reiber, G AF Nelson, Karin M. McFarland, Lynne Reiber, Gayle TI Factors influencing disease self-management among veterans with diabetes and poor glycemic control SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the VA-Health-Services-Research-and-Development CY FEB 21-23, 2007 CL Washington, DC DE diabetes; diabetes self-management; veterans ID PHYSICAL-ACTIVITY SCALE; AFFAIRS HEALTH-CARE; QUALITY-OF-LIFE; BEHAVIORAL-APPROACH; EXERCISE BEHAVIOR; CONTROLLED TRIAL; GLUCOSE CONTROL; ELDERLY PASE; OLDER-ADULTS; ADHERENCE AB SPECIFIC AIM: Although the Department of Veterans Affairs (VA) has made significant organizational changes to improve diabetes care, diabetes self-management has received limited attention. The purpose of this study is to assess factors influencing diabetes self-management among veterans with poorly controlled diabetes. METHODS: Surveys were mailed to patients with type 2 diabetes and a HbA1c of 8% or greater who attended 1 of 2 VA Medical Centers in Washington State (n=1,286). Validated survey instruments assessed readiness to change, self-efficacy, provider advice, and diabetes self-care practices. RESULTS: Our response rate was 56% (n=717). Most respondents reported appropriate advice from physicians regarding physical activity, nutrition, and glucose monitoring (73%, 92%, and 98%, respectively), but many were not ready to change self-management behaviors. Forty-five percent reported non-adherence to medications, 42% ate a high-fat diet, and only 28% obtained either moderate or vigorous physical activity. The mean self-efficacy score for diabetes self-care was low and half of the sample reported readiness to change nutrition (52%) or physical activity (51%). Individuals with higher self-efficacy scores were more likely to adhere to medications, follow a diabetic meal plan, eat a lower fat diet, have higher levels of physical activity, and monitor their blood sugars (P <.001 for all). CONCLUSIONS: Although veterans with poor diabetes control receive appropriate medical advice, many were not sufficiently confident or motivated to make and maintain self-management changes. Targeted patient-centered interventions may need to emphasize increasing self-efficacy and readiness to change to further improve VA diabetes outcomes. C1 VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Nelson, KM (reprint author), 1660 S Columbian Way,S-111 GIMC, Seattle, WA 98108 USA. EM Karin.Nelson@va.gov NR 50 TC 39 Z9 40 U1 1 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 IS 4 BP 442 EP 447 DI 10.1007/s11606-006-0053-8 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 148WJ UT WOS:000245107800003 PM 17372790 ER PT J AU Fletcher, RH Lobb, R Bauer, MR Kemp, JA Palmer, RC Kleinman, KP Miroshnik, I Emmons, KM AF Fletcher, Robert H. Lobb, Rebecca Bauer, Mark R. Kemp, James Alan Palmer, Richard C. Kleinman, Ken P. Miroshnik, Irina Emmons, Karen M. TI Screening patients with a family history of colorectal cancer SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE family history; colorectal cancer; genetic; risk ID PRIMARY-CARE PHYSICIANS; RISK; PREFERENCES; POPULATION; INDIVIDUALS; GUIDELINES; RATIONALE; ADHERENCE; ATTITUDES; SERVICES AB OBJECTIVES: To compare screening practices and beliefs in patients with and without a clinically important family history. DESIGN: We mailed a brief questionnaire asking about family history and a second, longer survey asking about knowledge of and beliefs about colorectal cancer to all respondents with a family history and a random sample of respondents without a family history of colorectal cancer. We reviewed electronic medical records for screening examinations and recording of family history. PARTICIPANTS: One thousand eight hundred seventy of 6,807 randomly selected patients ages 35-55 years who had been continuously enrolled in a large multispecialty group practice for at least 5 years. MEASUREMENTS: Recognition of increased risk, screening practices, and beliefs-all according to strength of family history and patient's age. RESULTS: Nineteen percent of respondents reported a family history of colorectal cancer. In 11%, this history was strong enough to warrant screening before age 50 years. However, only 39% (95% CI 36, 42) of respondents under the age of 50 years said they had been asked about family history and only 45% of those with a strong family history of colorectal cancer had been screened appropriately. Forty-six percent of patients with a strong family history did not know that they should be screened at a younger age than average risk people. Medical records mentioned family history of colorectal cancer in 59% of patients reporting a family history. CONCLUSIONS: More efforts are needed to translate information about family history of colorectal cancer into the care of patients. C1 Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Harvard Pilgrim Hlth Care, Boston, MA 02115 USA. Harvard Univ, Harvard Vanguard Med Associates, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Fletcher, RH (reprint author), 208 Boulder Bluff, Chapel Hill, NC 27516 USA. EM Robert_Fletcher@hms.harvard.edu OI Lobb, Rebecca/0000-0003-3503-0675 FU NCI NIH HHS [R21 CA102381, 1 R21 CA102381-01] NR 27 TC 25 Z9 25 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 IS 4 BP 508 EP 513 DI 10.1007/s11606-007-0135-2 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 148WJ UT WOS:000245107800014 PM 17372801 ER PT J AU Ruelaz, AR Diefenbach, P Simon, B Lanto, A Arterburn, D Shekelle, PG AF Ruelaz, Alicia R. Diefenbach, Pamela Simon, Barbara Lanto, Andy Arterburn, David Shekelle, Paul G. TI Perceived barriers to weight management in primary care - Perspectives of patients and providers SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE weight management; primary care; attitudes; beliefs; barriers ID OBESITY; PREVALENCE; OVERWEIGHT; WOMEN AB BACKGROUND: Despite the consequences of overweight and obesity, effective weight management is not occurring in primary care. OBJECTIVE: To identify beliefs about obesity that act as barriers to weight management in primary care by surveying both patients and providers and comparing their responses. DESIGN: Anonymous, cross-sectional, self-administered survey of patients and providers of a Veteran's Administration Primary Care Clinic, distributed at the clinic site. SUBJECTS: Forty-eight Internal Medicine providers and 488 patients. MEASUREMENTS: Beliefs, attitudes, and experiences with weight management as well as demographic characteristics were collected through a questionnaire. RESULTS: Providers and patients differed significantly on many beliefs about weight. Providers were more likely than patients to perceive that patients lack self-control to stay on a diet and that fattening food in society and lack of time for exercise were prime factors in weight gain. They also expressed more interest in helping patients with weight management than patients desiring this. Patients were more likely to state that weight problems should be managed on one's own, talking to a provider is not helpful, providers blame them for their weight problem, and that appointments contain sufficient time for weight discussion. CONCLUSION: Providers and patients emphasize different barriers to weight management. Providers need to be aware of the beliefs that their patients hold to improve weight management discussions and interventions in primary care. C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. VA Hlth Serv Res & Dev Ctr Excellence Study Provi, Los Angeles, CA USA. Grp Hlth Ctr Hlth Studies, Seattle, WA USA. RP Ruelaz, AR (reprint author), Cedars Sinai Med Ctr, MD-8700 Beverly Blvd,8th Floor,Room 8631, Los Angeles, CA 90048 USA. EM ruelaza@cshs.org NR 13 TC 55 Z9 55 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2007 VL 22 IS 4 BP 518 EP 522 DI 10.1007/s11606-007-0125-4 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 148WJ UT WOS:000245107800016 PM 17372803 ER PT J AU Romero, P Zippelius, A Kurth, I Pittet, MJ Touvrey, C Iancu, EM Corthesy, P Devevre, E Speiser, DE Rufer, N AF Romero, Pedro Zippelius, Alfred Kurth, Isabel Pittet, Mikael J. Touvrey, Cedric Iancu, Emanuela M. Corthesy, Patricia Devevre, Estelle Speiser, Daniel E. Rufer, Nathalie TI Four functionally distinct populations of human effector-memory CD8(+) T lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EX-VIVO CHARACTERIZATION; CELL SUBSETS; TELOMERE LENGTH; CHORIOMENINGITIS VIRUS; LINEAGE RELATIONSHIP; REPLICATIVE HISTORY; PROTECTIVE IMMUNITY; CHEMOKINE RECEPTORS; ANTIGEN; EXPRESSION AB In humans, the pathways of memory and effector T cell differentiation remain poorly defined. We have dissected the functional properties of ex vivo effector-memory (EM) CD45RA(-)CCR7(-) T lymphocytes present within the circulating CD8(+) T cell pool of healthy individuals. Our studies show that EM T cells are heterogeneous and are subdivided based on differential CD27 and CD28 expression into four subsets. EM1 (CD27(+)CD28(+)) and EM4 (CD27(-)CD28(+)) T cells express low levels of effector mediators such as granzyme B and perforin and high levels of CD127/IL-7R alpha. EM, cells also have a relatively short replicative history and display strong ex vivo telomerase activity. Therefore, these cells are closely related to central-memory (CD45RA(-)CCR7(+)) cells. In contrast, EM2 (CD27(+)CD28(-)) and EM3 (CD27(-)CD28(-)) cells express mediators characteristic of effector cells, whereby EM3 cells display stronger ex vivo cytolytic activity and have experienced larger numbers of cell divisions, thus resembling differentiated effector (CD45RA(+)CCR7(-)) cells. These data indicate that progressive up-regulation of cytolytic activity and stepwise loss of CCR7, CD28, and CD27 both characterize CD8(+) T cell differentiation. Finally, memory CD8(+) T cells not only include central-memory cells but also EM, cells, which differ in CCR7 expression and may therefore confer memory functions in lymphoid and peripheral tissues, respectively. C1 Swiss Inst Expt Canc Res, CH-1066 Epalinges, Switzerland. Univ Lausanne Hosp, Ludwig Inst Canc Res, Div Clin Oncoimmunol, Lausanne, Switzerland. Univ Zurich Hosp, Dept Internal Med, CH-8091 Zurich, Switzerland. Columbia Univ, Med Ctr, Irving Canc Res Ctr, New York, NY 10032 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02129 USA. RP Rufer, N (reprint author), Swiss Inst Expt Canc Res, 155 Ch Boveresses, CH-1066 Epalinges, Switzerland. EM Nathalie.Rufer@isrec.ch RI Speiser, Daniel/F-2173-2013 NR 43 TC 183 Z9 191 U1 0 U2 10 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 IS 7 BP 4112 EP 4119 PG 8 WC Immunology SC Immunology GA 150EB UT WOS:000245197300016 PM 17371966 ER PT J AU Akbari, O Yang, W Meyer, E Umetsu, DT Wilson, SB AF Akbari, Omid Yang, Wen Meyer, Everett Umetsu, Dale T. Wilson, S. Brian TI A CD1d-dependent antagonist inhibits the activation of iNKT cells and prevents development of allergen-induced airway hyperreactivity SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Akbari, Omid; Meyer, Everett; Umetsu, Dale T.] Harvard Med Sch, Childrens Hosp, Div Immunol, Boston, MA 02115 USA. [Yang, Wen; Wilson, S. Brian] Harvard Med Sch, Massachusetts Gen Hosp, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 39.9 PG 2 WC Immunology SC Immunology GA V44OL UT WOS:000209758200079 ER PT J AU Akbari, O Meyer, EH Freeman, GJ Sharpe, AH DeKruyff, RH Umetsu, DT AF Akbari, Omid Meyer, Everett H. Freeman, Gordon J. Sharpe, Arlene H. DeKruyff, Rosemarie H. Umetsu, Dale T. TI ICOS/ICOSL interaction is required for CD4+NKT cells function and for the induction of airway hyperreactivity SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Akbari, Omid; Meyer, Everett H.; DeKruyff, Rosemarie H.; Umetsu, Dale T.] Harvard Med Sch, Childrens Hosp, Div Immunol, Boston, MA 02115 USA. [Freeman, Gordon J.] Harvard Med Sch, Dana Farber Canc Inst, Adult Oncol, Boston, MA 02115 USA. [Sharpe, Arlene H.] Harvard Med Sch, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 39.4 PG 2 WC Immunology SC Immunology GA V44OL UT WOS:000209758200076 ER PT J AU Aud, D Pai, SY Ho, IC Peng, SL AF Aud, Dee Pai, Sung-Yun Ho, I-Cheng Peng, Stanford L. TI The transcription factor GATA-3 regulates IL-4 responses in B cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Aud, Dee; Peng, Stanford L.] Roche Palo Alto, Palo Alto, CA 94304 USA. [Pai, Sung-Yun] Childrens Hosp Boston, Boston, MA 02115 USA. [Pai, Sung-Yun] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ho, I-Cheng] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 35.23 PG 1 WC Immunology SC Immunology GA V44OL UT WOS:000209758201072 ER PT J AU Barrington, RA Feist, F Mann, W Ketman, K Fu, W Steen, R AF Barrington, Robert A. Feist, Frank Mann, Wolfgang Ketman, Ken Fu, Wei Steen, Robert TI Novel method for deconstructing humoral responses SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Barrington, Robert A.; Feist, Frank; Mann, Wolfgang] Advalytix AG, Concord, MA 01742 USA. [Ketman, Ken] CBR Inst Biomed Res, Boston, MA 02115 USA. [Fu, Wei; Steen, Robert] Biopolymers Facil, Genet, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA B198 PG 1 WC Immunology SC Immunology GA V44OL UT WOS:000209758203308 ER PT J AU Brown, NK McCormick, DJ Brusic, V David, CS Kong, YCM AF Brown, Nicholas Korten McCormick, Daniel J. Brusic, Vladimir David, Chella S. Kong, Yi-chi M. TI A novel H2A(-)E(+) transgenic model susceptible to human but not mouse thyroglobulin in autoimmune thyroiditis: identification of a mouse pathogenic epitope SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Brown, Nicholas Korten; Kong, Yi-chi M.] Wayne State Univ, Sch Med, Immunol & Microbiol, Detroit, MI 48201 USA. [McCormick, Daniel J.; David, Chella S.] Mayo Clin, Coll Med, Rochester, MN 55905 USA. [Brusic, Vladimir] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 129.37 PG 1 WC Immunology SC Immunology GA V44OL UT WOS:000209758201257 ER PT J AU Butte, MJ Keir, ME Phamduy, TB Sharpe, AH Freeman, GJ AF Butte, Manish J. Keir, Mary E. Phamduy, Theresa B. Sharpe, Arlene H. Freeman, Gordon J. TI PD-L1 interacts specifically with B7-1 to regulate T cell function SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Butte, Manish J.; Keir, Mary E.; Phamduy, Theresa B.; Sharpe, Arlene H.] Harvard Med Sch, Dept Pathol, Boston, MA 02115 USA. [Butte, Manish J.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 88.24 PG 1 WC Immunology SC Immunology GA V44OL UT WOS:000209758202091 ER PT J AU Duraiswamy, J Miller, JD Masopust, D Ibegbu, CC Wu, H Freeman, GJ Ahmed, R AF Duraiswamy, Jaikumar Miller, Joseph D. Masopust, David Ibegbu, Chris C. Wu, Hong Freeman, Gordon J. Ahmed, Rafi TI PD-1 expression on memory CD8 and CD4 T-cell subsets in healthy humans SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Duraiswamy, Jaikumar; Miller, Joseph D.; Masopust, David; Ibegbu, Chris C.; Wu, Hong; Ahmed, Rafi] Emory Univ, Emory Vaccine Ctr, Sch Med, Atlanta, GA 30322 USA. [Duraiswamy, Jaikumar; Miller, Joseph D.; Masopust, David; Ibegbu, Chris C.; Wu, Hong; Ahmed, Rafi] Emory Univ, Dept Microbiol & Immunol, Sch Med, Atlanta, GA 30322 USA. [Freeman, Gordon J.] Harvard Med Sch, Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 43.43 PG 2 WC Immunology SC Immunology GA V44OL UT WOS:000209758200233 ER PT J AU Feske, S Osmers, U Kirschner, J Roether, J Picard, C Ehl, S Plogmann, K Fischer, A Rao, A AF Feske, Stefan Osmers, Ute Kirschner, Janbernd Roether, Jens Picard, Capucine Ehl, Stephan Plogmann, Katrin Fischer, Alain Rao, Anjana TI Novel mutations in CRAC channel protein Orai1 cause immunodeficiency associated with non-immunological disease SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Feske, Stefan; Osmers, Ute; Roether, Jens; Rao, Anjana] Harvard Med Sch, CBRI, Boston, MA 02115 USA. [Kirschner, Janbernd; Ehl, Stephan] Univ Freiburg, Dept Pediat, D-79106 Freiburg, Germany. [Picard, Capucine; Fischer, Alain] Hop Necker Enfants Malad, Ctr Etud Deficits Immunitaires, F-75015 Paris, France. [Plogmann, Katrin] Univ Freiburg, Dept Operat Dent & Periodontol, D-79106 Freiburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 89.23 PG 1 WC Immunology SC Immunology GA V44OL UT WOS:000209758202349 ER PT J AU Iwealal, OI Smith, DW Urban, JF Nagler, CR AF Iwealal, Onyinye I. Smith, Donald W. Urban, Joseph F. Nagler, Cathryn R. TI Th2 polarizing helminth infection alters the immune response to an oral Salmonella-OVA vaccine SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Iwealal, Onyinye I.; Smith, Donald W.; Nagler, Cathryn R.] Massachusetts Gen Hosp, Dept Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Urban, Joseph F.] USDA ARS, Nutrient Requirements & Funct Lab, Beltsville Human Nutr Ctr, Beltsville, MD 20705 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 41.5 PG 1 WC Immunology SC Immunology GA V44OL UT WOS:000209758203138 ER PT J AU Koulmanda, M Hoffman, L Qipo, A Shi, H Fan, ZG Flier, JF Strom, TB AF Koulmanda, Maria Hoffman, Lauren Qipo, Andi Shi, Hang Fan, Zhigang Flier, Jeffrey F. Strom, Terry B. TI ARALAST or ANTI-TNF-a TREATMENT PREVENTS AUTOIMMUNE DESTRUCTION OF ISLET GRAFTS IN NONOBESE DIABETIC (NOD) MICE SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Koulmanda, Maria; Hoffman, Lauren; Qipo, Andi; Shi, Hang; Fan, Zhigang; Flier, Jeffrey F.; Strom, Terry B.] Harvard Med Sch, BIDMC, Surg & Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 131.23 PG 1 WC Immunology SC Immunology GA V44OL UT WOS:000209758201318 ER PT J AU Lathers, DMR Kearney, PL Gibbs, K Young, MR AF Lathers, Deanne M. R. Kearney, Patricia L. Gibbs, Kiki Young, M. Rita TI Tumor modulation of T-helper cytokine secretion SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Lathers, Deanne M. R.; Kearney, Patricia L.; Gibbs, Kiki] Ralph H Johnson VAMC, Otolaryngol, Charleston, SC 29401 USA. [Young, M. Rita] Ralph H Johnson VAMC, Med & Otolaryngol, Charleston, SC 29401 USA. [Young, M. Rita] Med Univ South Carolina, Charleston, SC 29401 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 49.6 PG 1 WC Immunology SC Immunology GA V44OL UT WOS:000209758203264 ER PT J AU Lazar-Molnar, E Gacser, A Nosanchuk, JD Freeman, GJ Almo, SC Nathenson, SG AF Lazar-Molnar, Eszter Gacser, Attila Nosanchuk, Joshua D. Freeman, Gordon J. Almo, Steven C. Nathenson, Stanley G. TI The PD-1/PD-L costimulatory pathway plays a key role in Histoplasma capsulatum pathogenesis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Lazar-Molnar, Eszter; Nosanchuk, Joshua D.] Albert Einstein Coll Med, Microbiol & Immunol, Bronx, NY 10461 USA. [Gacser, Attila; Nosanchuk, Joshua D.] Albert Einstein Coll Med, Med, Bronx, NY 10461 USA. [Almo, Steven C.] Albert Einstein Coll Med, Biochem, Bronx, NY 10461 USA. [Nathenson, Stanley G.] Albert Einstein Coll Med, Cell Biol, Bronx, NY 10461 USA. [Freeman, Gordon J.] Harvard Med Sch, Dept Med Oncol, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA B122 PG 1 WC Immunology SC Immunology GA V44OL UT WOS:000209758202171 ER PT J AU Lichtenheld, MG Zuniga-Pflucker, JC Rao, A Pigkin, ME AF Lichtenheld, Mathias Georg Zuniga-Pflucker, Juan Carlos Rao, Anjana Pigkin, Matthew E. TI New Sequence of Strategies to Define Gene Transcriptional Territories in Lymphocytes: The Perforin Example SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Lichtenheld, Mathias Georg; Pigkin, Matthew E.] Univ Miami, Miller Sch Med, Microbiol & Immunol, Miami, FL 33136 USA. [Lichtenheld, Mathias Georg] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. [Zuniga-Pflucker, Juan Carlos] Univ Toronto, Immunol, Toronto, ON M4N 3M5, Canada. [Zuniga-Pflucker, Juan Carlos] Sunnybrook Res Inst, Toronto, ON M4N 3M5, Canada. [Rao, Anjana; Pigkin, Matthew E.] Harvard Med Sch, Pathol, Boston, MA 02115 USA. [Rao, Anjana; Pigkin, Matthew E.] CBR Inst Biomed Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 35.32 PG 1 WC Immunology SC Immunology GA V44OL UT WOS:000209758201055 ER PT J AU Link, JM Meza-Romero, R Afentoulis, M Agotsch, M LaTocha, D Burrows, G Vandenbark, AA AF Link, Jason M. Meza-Romero, Roberto Afentoulis, Michael Agotsch, Marisa LaTocha, Dorian Burrows, Gregory Vandenbark, Arthur A. TI Partial MHC Class II molecules preferentially bind to B cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Link, Jason M.; Afentoulis, Michael; LaTocha, Dorian; Vandenbark, Arthur A.] Portland VA Med Ctr, Portland, OR 97239 USA. [Meza-Romero, Roberto; Agotsch, Marisa; Burrows, Gregory; Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Neurol, Portland, OR 97239 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 93.22 PG 1 WC Immunology SC Immunology GA V44OL UT WOS:000209758202050 ER PT J AU Lu, LR Lkizawa, K Werneck, MBF Cantor, H AF Lu, Linrong Lkizawa, Koichi Werneck, Miriam B. F. Cantor, Harvey TI Definition of a Qa-1-Qdm-dependent interaction between NK cells and activated T cells that inhibits expansion and memory development of pathogenic T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Lu, Linrong; Lkizawa, Koichi; Werneck, Miriam B. F.; Cantor, Harvey] Harvard Med Sch, Dept Pathol, Dana Farber Canc Inst, Canc Immunol & AIDS, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 88.31 PG 1 WC Immunology SC Immunology GA V44OL UT WOS:000209758202112 ER PT J AU Mailloux, AW Lathers, DMR Young, MRI AF Mailloux, Adam William Lathers, Deanne M. R. Young, M. Rita I. TI Lewis Lung Carcinoma-derived CCL22 recruitment of T regulatory cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Mailloux, Adam William] Med Univ South Carolina, Microbiol & Immunol, Charleston, SC 29407 USA. [Lathers, Deanne M. R.] Med Univ South Carolina, Dept Otolaryngol, Charleston, SC 29403 USA. [Lathers, Deanne M. R.; Young, M. Rita I.] Ralph H Johnson VAMC, Res Serv, Charleston, SC 29403 USA. [Young, M. Rita I.] Med Univ South Carolina, Med, Charleston, SC 29403 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA B148 PG 2 WC Immunology SC Immunology GA V44OL UT WOS:000209758200131 ER PT J AU Mingle, B Afshar, R Prioult, G Murakami, H Nagler, C AF Mingle, Bethany Afshar, Roshi Prioult, Guenolee Murakami, Hidehiro Nagler, Cathryn TI Exacerbation of spontaneous colitis in the absence of flora derived TLR4 signals SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Mingle, Bethany; Afshar, Roshi; Nagler, Cathryn] Massachusetts Gen Hosp, DRAI CIID, Charlestown, MA 02129 USA. [Prioult, Guenolee] Nestle Res Ctr, CH-1000 Lausanne, Switzerland. [Murakami, Hidehiro] Ehime Univ, Sch Med, Shigenobu, Ehime 7910295, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 42.2 PG 1 WC Immunology SC Immunology GA V44OL UT WOS:000209758201088 ER PT J AU Mirshahidi, S Whitney, JB Kramer, VG Anderson, KS Ruprecht, RM AF Mirshahidi, Saied Whitney, James B. Kramer, Victor G. Anderson, Karen S. Ruprecht, Ruth M. TI Using Overlapping Synthetic Peptides from Tumor-Associated Protein Antigens for Breast Cancer Vaccine Development SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Mirshahidi, Saied; Whitney, James B.; Kramer, Victor G.; Ruprecht, Ruth M.] Harvard Med Sch, Dana Farber Canc Inst, Canc Immunol & AIDS, Boston, MA 02115 USA. [Anderson, Karen S.] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 41.11 PG 1 WC Immunology SC Immunology GA V44OL UT WOS:000209758203126 ER EF