FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Chou, YF Chen, HH Eijpe, M Yabuuchi, A Chenoweth, JG Tesar, P Lu, J McKay, RDG Geijsen, N AF Chou, Yu-Fen Chen, Hsu-Hsin Eijpe, Maureen Yabuuchi, Akiko Chenoweth, Joshua G. Tesar, Paul Lu, Jun Mckay, Ronald D. G. Geijsen, Niels TI The Growth Factor Environment Defines Distinct Pluripotent Ground States in Novel Blastocyst-Derived Stem Cells SO CELL LA English DT Article ID PRIMORDIAL GERM-CELLS; HUMAN SOMATIC-CELLS; E-CADHERIN; REGULATORY CIRCUITRY; MOUSE EMBRYOS; SELF-RENEWAL; FREE CULTURE; ES CELLS; LINES; DIFFERENTIATION AB Pluripotent stem cell lines can be derived from blastocyst embryos, which yield embryonic stem cell lines (ES cells), as well as the postimplantation epiblast, which gives rise to epiblast stem cell lines (EpiSCs). Remarkably, ES cells and EpiSCs display profound differences in the combination of growth factors that maintain their pluripotent state. Molecular and functional differences between these two stem cell types demonstrate that the tissue of origin and/or the growth factor milieu may be important determinants of the stem cell identity. We explored how developmental stage of the tissue of origin and culture growth factor conditions affect the stem cell pluripotent state. Our findings indicate that novel stem cell lines, with unique functional and molecular properties, can be generated from murine blastocyst embryos. We demonstrate that the culture growth factor environment and cell-cell interaction play a critical role in defining several unique and stable stem cell ground states. C1 [Chou, Yu-Fen; Chen, Hsu-Hsin; Geijsen, Niels] Massachusetts Gen Hosp, Harvard Stem Cell Inst, Ctr Regenerat Med, Boston, MA 02114 USA. [Eijpe, Maureen] Erasmus MC, Dept Cell Biol, NL-3015 GE Rotterdam, Netherlands. [Yabuuchi, Akiko] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Chenoweth, Joshua G.; Mckay, Ronald D. G.] Natl Inst Neurol Disorders & Stroke, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Tesar, Paul] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. [Lu, Jun] Harvard Univ, Broad Inst, Cambridge, MA 02141 USA. [Lu, Jun] MIT, Cambridge, MA 02141 USA. RP Geijsen, N (reprint author), Massachusetts Gen Hosp, Harvard Stem Cell Inst, Ctr Regenerat Med, CPZN-4256,185 Cambridge St, Boston, MA 02114 USA. EM ngeijsen@mgh.harvard.edu RI Tesar, Paul/C-9848-2014 OI Tesar, Paul/0000-0003-1532-3155 FU National Institutes of Health [RO1HD048769-01A1]; Harvard Stem Cell Institute; Dutch Cancer Society (Koningin Wilhelmina Fonds) FX The authors thank Dr. George Daley for his review of our manuscript and help with the blastocyst injections; Dr. Paul Tesar for the EpiSC image; Dr. Roger Tsien for the use of the tdTomato fluorescent reporter; Dr. Keith Orford for critical review of the manuscript; Kelly Shea for providing technical support; and Laura Prickett and Kat Folz-Donahue at the HSCI/MGH Flow Cytometry Core Facility for help with cell purifications. This work was supported by grants from the National Institutes of Health (RO1HD048769-01A1) and the Harvard Stem Cell Institute. M. E. was supported by the Dutch Cancer Society (Koningin Wilhelmina Fonds). NR 56 TC 148 Z9 155 U1 2 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD OCT 31 PY 2008 VL 135 IS 3 BP 449 EP 461 DI 10.1016/j.cell.2008.08.035 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 367EW UT WOS:000260536300016 PM 18984157 ER PT J AU Jin, W Chen, Y Di, GH Miron, P Hou, YF Gao, H Shao, ZM AF Jin, Wei Chen, Ying Di, Gen-hong Miron, Penelope Hou, Yi-feng Gao, Hui Shao, Zhi-ming TI Estrogen Receptor (ER)beta or p53 Attenuates ER alpha-mediated Transcriptional Activation on the BRCA2 Promoter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SPORADIC BREAST-CANCER; GENE-EXPRESSION; MESSENGER-RNA; CARCINOMAS; MUTATIONS; P300; BETA; CBP; SUSCEPTIBILITY; COREGULATORS AB BRCA2 is closely related to the pathogenesis of breast cancer. In the present study, we found that estrogen can activate BRCA2 transcription, which is estrogen receptor (ER) alpha-dependent. During estrogen treatment, ER alpha interacted with CREB-binding protein/p300, p68/p72, and MyoD and formed an activating transcriptional complex that could bind to many Sp1 sites on the BRCA2 promoter and activate its transcription by inducing histone acetylations. MyoD is a new component of ER alpha complex. ER beta or p53 attenuated ER alpha-mediated transcriptional activation by preventing the recruitment of ER alpha transcriptional complex and histone acetylations on the BRCA2 promoter. ER beta interacted with ER alpha and CREB-binding protein/p300 and formed a weak activating transcriptional complex that competed for binding to Sp1 sites with ER alpha transcriptional complex and slightly attenuated BRCA2 transcription. Different from ER beta, p53 interacted with HDAC1 and CtBP1 and formed an inhibiting transcriptional complex that could compete for binding to Sp1 sites with ER alpha transcriptional complex and inhibit BRCA2 transcription more significantly. C1 [Jin, Wei; Chen, Ying; Di, Gen-hong; Hou, Yi-feng; Shao, Zhi-ming] Fudan Univ, Breast Canc Inst, Canc Hosp, Dept Oncol,Shanghai Med Coll,Inst Biomed Sci, Shanghai 200032, Peoples R China. [Jin, Wei; Gao, Hui] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ 08901 USA. [Miron, Penelope] Harvard Univ, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shao, ZM (reprint author), Fudan Univ, Dept Breast Surg, Breast Canc Inst, Canc Hosp Canc Inst, 270 Dong Rd, Shanghai 200032, Peoples R China. EM zhimingshao@yahoo.com FU National Natural Science Foundation of China [30371580, 30572109]; Shanghai Science and Technology Committee [03J14019, 06DJ14004, 06DZ19504]; Cancer Hospital/Cancer Institute of Fudan University [YJ200604]; Shanghai Pujiang Program; [2006CB0D0901] FX This work was supported in part by 973 (Grant 2006CB0D0901), the National Natural Science Foundation of China (Grants 30371580 and 30572109), the Shanghai Science and Technology Committee (Grants 03J14019, 06DJ14004, and 06DZ19504); the Cancer Hospital/Cancer Institute of Fudan University (Grant YJ200604), and the Shanghai Pujiang Program. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 29 TC 20 Z9 22 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 31 PY 2008 VL 283 IS 44 BP 29671 EP 29680 DI 10.1074/jbc.M802785200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 364WS UT WOS:000260366900010 PM 18765668 ER PT J AU Sullivan, MD Ciechanowski, PS Russo, JE Spertus, JA Soine, LA Jordan-Keith, K Caldwell, JH AF Sullivan, Mark D. Ciechanowski, Paul S. Russo, Joan E. Spertus, John A. Soine, Laurie A. Jordan-Keith, Kier Caldwell, James H. TI Angina pectoris during daily activities and exercise stress testing: The role of inducible myocardial ischemia and psychological distress SO PAIN LA English DT Article DE Health status; Quality of life; Coronary heart disease; Depression; Anxiety; Somatization; Symptoms; Chest pain; Visceral pain ID CORONARY-ARTERY-DISEASE; QUALITY-OF-LIFE; RANDOMIZED CONTROLLED TRIAL; CHRONIC REFRACTORY ANGINA; COPING STRATEGIES; CHEST-PAIN; INTERVENTION; INVENTORY; MORTALITY; ANXIETY AB Physicians often consider angina pectoris to be synonymous with myocardial ischemia. However, the relationship between angina and myocardial ischemia is highly variable and we have little insight into the Sources of this variability. We investigated the relationship of inducible myocardial ischemia oil SPECT stress perfusion imaging to angina reported with routine daily activities during the previous four weeks (N = 788) and to angina reported during an exercise stress test (N = 371) in individuals with confirmed or Suspected coronary disease referred for clinical testing. We found that angina experienced during daily lire is more strongly and consistently associated with psychological distress and the personal threat associated with angina than with inducible myocardial ischemia. In multivariable models, the presence of any angina during routine activities over the prior month was significantly associated with age, perceived risk of myocardial infarction, and anxiety when compared to those with no reported angina in the past month. Angina during daily life was not significantly associated with inducible myocardial ischemia oil stress perfusion imaging in bivariate or multivariable models. In contrast, angina experienced during exercise stress testing was significantly related to image and ECG ischemia, though it was also significantly associated with anxiety. These results suggest that angina frequency over the previous four weeks is more strongly associated with personal threat and psychosocial distress than with inducible myocardial ischemia. These results lend support to angina treatment strategies that aim to reduce threat and distress as well as to reduce myocardial ischemia. (C) 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Sullivan, Mark D.; Ciechanowski, Paul S.; Russo, Joan E.; Soine, Laurie A.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Div Consultat Liaison Psychiat, Seattle, WA 98195 USA. [Spertus, John A.] Univ Missouri, Mid Amer Heart Inst, Kansas City, MO 64110 USA. [Jordan-Keith, Kier; Caldwell, James H.] VA Puget Sound Hlth Care Syst, Dept Cardiol, Seattle, WA USA. [Caldwell, James H.] Univ Washington, Dept Med, Div Cardiol, Seattle, WA 98195 USA. [Caldwell, James H.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. RP Sullivan, MD (reprint author), Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Div Consultat Liaison Psychiat, 1959 NE Pacific St,Box 356560, Seattle, WA 98195 USA. EM sullimar@u.washington.edu FU American Heart Association [0450094Z] FX Dr. Sullivan thanks the American Heart Association For the grant that supported this research 0450094Z. The authors have no conflicts of interest to report. NR 55 TC 2 Z9 2 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD OCT 31 PY 2008 VL 139 IS 3 BP 551 EP 561 DI 10.1016/j.pain.2008.06.009 PG 11 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 372IG UT WOS:000260894700010 PM 18694624 ER PT J AU Keating, BJ Tischfield, S Murray, SS Bhangale, T Price, TS Glessner, JT Galver, L Barrett, JC Grant, SFA Farlow, DN Chandrupatla, HR Hansen, M Ajmal, S Papanicolaou, GJ Guo, YR Li, MY DerOhannessian, S de Bakker, PIW Bailey, SD Montpetit, A Edmondson, AC Taylor, K Gai, XW Wang, SS Fornage, M Shaikh, T Groop, L Boehnke, M Hall, AS Hattersley, AT Frackelton, E Patterson, N Chiang, CWK Kim, CE Fabsitz, RR Ouwehand, W Price, AL Munroe, P Caulfield, M Drake, T Boerwinkle, E Reich, D Whitehead, AS Cappola, TP Samani, NJ Lusis, AJ Schadt, E Wilson, JG Koenig, W McCarthy, MI Kathiresan, S Gabriel, SB Hakonarson, H Anand, SS Reilly, M Engert, JC Nickerson, DA Rader, DJ Hirschhorn, JN FitzGerald, GA AF Keating, Brendan J. Tischfield, Sam Murray, Sarah S. Bhangale, Tushar Price, Thomas S. Glessner, Joseph T. Galver, Luana Barrett, Jeffrey C. Grant, Struan F. A. Farlow, Deborah N. Chandrupatla, Hareesh R. Hansen, Mark Ajmal, Saad Papanicolaou, George J. Guo, Yiran Li, Mingyao DerOhannessian, Stephanie de Bakker, Paul I. W. Bailey, Swneke D. Montpetit, Alexandre Edmondson, Andrew C. Taylor, Kent Gai, Xiaowu Wang, Susanna S. Fornage, Myriam Shaikh, Tamim Groop, Leif Boehnke, Michael Hall, Alistair S. Hattersley, Andrew T. Frackelton, Edward Patterson, Nick Chiang, Charleston W. K. Kim, Cecelia E. Fabsitz, Richard R. Ouwehand, Willem Price, Alkes L. Munroe, Patricia Caulfield, Mark Drake, Thomas Boerwinkle, Eric Reich, David Whitehead, A. Stephen Cappola, Thomas P. Samani, Nilesh J. Lusis, A. Jake Schadt, Eric Wilson, James G. Koenig, Wolfgang McCarthy, Mark I. Kathiresan, Sekar Gabriel, Stacey B. Hakonarson, Hakon Anand, Sonia S. Reilly, Muredach Engert, James C. Nickerson, Deborah A. Rader, Daniel J. Hirschhorn, Joel N. FitzGerald, Garret A. TI Concept, Design and Implementation of a Cardiovascular Gene-Centric 50 K SNP Array for Large-Scale Genomic Association Studies SO PLOS ONE LA English DT Article AB A wealth of genetic associations for cardiovascular and metabolic phenotypes in humans has been accumulating over the last decade, in particular a large number of loci derived from recent genome wide association studies (GWAS). True complex disease-associated loci often exert modest effects, so their delineation currently requires integration of diverse phenotypic data from large studies to ensure robust meta-analyses. We have designed a gene-centric 50 K single nucleotide polymorphism (SNP) array to assess potentially relevant loci across a range of cardiovascular, metabolic and inflammatory syndromes. The array utilizes a "cosmopolitan'' tagging approach to capture the genetic diversity across similar to 2,000 loci in populations represented in the HapMap and SeattleSNPs projects. The array content is informed by GWAS of vascular and inflammatory disease, expression quantitative trait loci implicated in atherosclerosis, pathway based approaches and comprehensive literature searching. The custom flexibility of the array platform facilitated interrogation of loci at differing stringencies, according to a gene prioritization strategy that allows saturation of high priority loci with a greater density of markers than the existing GWAS tools, particularly in African HapMap samples. We also demonstrate that the IBC array can be used to complement GWAS, increasing coverage in high priority CVD-related loci across all major HapMap populations. DNA from over 200,000 extensively phenotyped individuals will be genotyped with this array with a significant portion of the generated data being released into the academic domain facilitating in silico replication attempts, analyses of rare variants and cross-cohort meta-analyses in diverse populations. These datasets will also facilitate more robust secondary analyses, such as explorations with alternative genetic models, epistasis and gene-environment interactions. C1 [Keating, Brendan J.; Whitehead, A. Stephen; Reilly, Muredach; Rader, Daniel J.; FitzGerald, Garret A.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. [Tischfield, Sam; Farlow, Deborah N.; de Bakker, Paul I. W.; Patterson, Nick; Chiang, Charleston W. K.; Reich, David; Kathiresan, Sekar; Gabriel, Stacey B.; Hirschhorn, Joel N.] MIT, Broad Inst Harvard, Cambridge, MA 02139 USA. [Tischfield, Sam; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Endocrinol, Program Genom, Boston, MA USA. [Murray, Sarah S.] Scripps Genom Med, La Jolla, CA USA. [Bhangale, Tushar; Nickerson, Deborah A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Price, Thomas S.] MRC SGDP Ctr, Inst Psychiat, London, England. [Glessner, Joseph T.; Grant, Struan F. A.; Gai, Xiaowu; Shaikh, Tamim; Frackelton, Edward; Kim, Cecelia E.; Hakonarson, Hakon] CHOP, Dept Pediat, Div Human Genet, Ctr Applied Genom, Philadelphia, PA USA. [Barrett, Jeffrey C.; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX1 2JD, England. [Chandrupatla, Hareesh R.; Ajmal, Saad; Li, Mingyao; DerOhannessian, Stephanie; Edmondson, Andrew C.; Cappola, Thomas P.; Reilly, Muredach; Rader, Daniel J.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Galver, Luana; Hansen, Mark] Illumina Inc, San Diego, CA USA. [Papanicolaou, George J.; Fabsitz, Richard R.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD USA. [Guo, Yiran] Beijing Genom Inst Shenzhen, Shenzhen, Peoples R China. [de Bakker, Paul I. W.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA USA. [Taylor, Kent] Cedars Sinai Med Ctr, Med Genet Inst, Los Angeles, CA USA. [Wang, Susanna S.; Drake, Thomas; Lusis, A. Jake] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Fornage, Myriam] Univ Texas, Hlth Sci Ctr, Inst Mol Med, Houston, TX USA. [Groop, Leif] Lund Univ, Dept Clin Sci Malmoe, Diabetes & Endocrinol, S-22100 Lund, Sweden. [Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Hall, Alistair S.] Univ Leeds, Leeds Inst Genet, Hlth & Therapeut, Leeds LS2 9JT, W Yorkshire, England. [Hattersley, Andrew T.] Peninsula Med Sch, Inst Biomed & Clin Sci, Diabetes Genet Grp, Exeter, Devon, England. [Chiang, Charleston W. K.; Reich, David; Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Munroe, Patricia] Barts & The London, Dept Clin Pharmacol, London, England. [Ouwehand, Willem] Univ Cambridge, NHS Blood & Transplant, Dept Haematol, Cambridge CB2 1TN, England. [Munroe, Patricia; Caulfield, Mark] Barts & The London, William Harvey Res Inst, London, England. [Boerwinkle, Eric] Univ Texas, Hlth Sci Ctr, Human Genet Ctr, Houston, TX USA. [Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester LE1 7RH, Leics, England. [Schadt, Eric] Merck & Co Inc, Rosetta Inpharmat LLC, Seattle, WA USA. [Wilson, James G.] Univ Mississippi, Med Ctr, VA Med Ctr, University, MS 38677 USA. [Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89069 Ulm, Germany. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiol Div, Boston, MA USA. [Anand, Sonia S.] McMaster Univ, Hamilton Gen Hosp, Hamilton Hlth Sci, Clin Epidemiol & Biostat, Populat Genom Program, Hamilton, ON L8S 4L8, Canada. [Bailey, Swneke D.; Engert, James C.] McGill Univ, Dept Med & Human Genet, Montreal, PQ H3A 2T5, Canada. [Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Cambridge, MA 02138 USA. [McCarthy, Mark I.] Univ Oxford, Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford Ctr Diabetes, Endocrinol & Metabolism, Oxford OX1 2JD, England. [Lusis, A. Jake] Univ Calif Los Angeles, Sch Med, Dept Microbiol, Immunol & Mol Genet, Los Angeles, CA 90024 USA. [Montpetit, Alexandre] Genome Quebec Innovat Ctr, Montreal, PQ, Canada. RP Keating, BJ (reprint author), Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. EM garret@spirit.gcrc.upenn.edu RI FitzGerald, Garret/A-4222-2010; Price, Thomas/B-7372-2008; Guo, Yiran/H-4120-2011; de Bakker, Paul/B-8730-2009; OI Price, Thomas/0000-0001-7356-2109; Guo, Yiran/0000-0002-6549-8589; de Bakker, Paul/0000-0001-7735-7858; Barrett, Jeffrey/0000-0002-1152-370X; Chiang, Charleston/0000-0002-0668-7865 FU National Institute of Health Clinical and Translational Research Award [RR U54 RR023567]; University of Pennsylvania; National Heart, Lung and Blood Institute [N01-HC-65226, U01 HL66642] FX Supported by a National Institute of Health Clinical and Translational Research Award (RR U54 RR023567) to the University of Pennsylvania and National Heart, Lung and Blood Institute (N01-HC-65226). Tushar Bhangale's work was supported by the Program for Genomic Applications supported by the NHLBI (U01 HL66642). NR 39 TC 280 Z9 282 U1 1 U2 22 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 31 PY 2008 VL 3 IS 10 AR e3583 DI 10.1371/journal.pone.0003583 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 432KK UT WOS:000265131700007 PM 18974833 ER PT J AU Zhao, J Sun, BK Erwin, JA Song, JJ Lee, JT AF Zhao, Jing Sun, Bryan K. Erwin, Jennifer A. Song, Ji-Joon Lee, Jeannie T. TI Polycomb Proteins Targeted by a Short Repeat RNA to the Mouse X Chromosome SO SCIENCE LA English DT Article ID INACTIVE-X; XIST RNA; DOMAINS; RECRUITMENT; METHYLATION; TSIX AB To equalize X- chromosome dosages between the sexes, the female mammal inactivates one of her two X chromosomes. X- chromosome inactivation ( XCI) is initiated by expression of Xist, a 17- kb noncoding RNA ( ncRNA) that accumulates on the X in cis. Because interacting factors have not been isolated, the mechanism by which Xist induces silencing remains unknown. We discovered a 1.6- kilobase ncRNA ( RepA) within Xist and identified the Polycomb complex, PRC2, as its direct target. PRC2 is initially recruited to the X by RepA RNA, with Ezh2 serving as the RNA binding subunit. The antisense Tsix RNA inhibits this interaction. RepA depletion abolishes full- length Xist induction and trimethylation on lysine 27 of histone H3 of the X. Likewise, PRC2 deficiency compromises Xist up- regulation. Therefore, RepA, together with PRC2, is required for the initiation and spread of XCI. We conclude that a ncRNA cofactor recruits Polycomb complexes to their target locus. C1 [Zhao, Jing; Sun, Bryan K.; Erwin, Jennifer A.; Lee, Jeannie T.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Zhao, Jing; Sun, Bryan K.; Erwin, Jennifer A.; Song, Ji-Joon; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02493 USA. [Zhao, Jing; Sun, Bryan K.; Erwin, Jennifer A.; Song, Ji-Joon; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Lee, JT (reprint author), Howard Hughes Med Inst, Boston, MA 02115 USA. EM lee@molbio.mgh.harvard.edu RI Song, Ji-Joon/C-1721-2011; OI Sun, Bryan/0000-0002-0740-0125 FU Massachusetts General Hospital Fund for Medical Discovery; NSF predoctoral award; Jane Coffin Childs Fellowship; NIH [R01GM58839] FX We thank R. Spencer and Y. Jeon for unpublished data and technical advice and Y. Ogawa for critical reading of the manuscript. Grant support: Massachusetts General Hospital Fund for Medical Discovery (J.Z.), NSF predoctoral award (J.A.E.), Jane Coffin Childs Fellowship (J.J.S.), and NIH- R01GM58839 (J.T.L.). J.T.L. is an Investigator of the HHMI. The transcript WRepAW for Repeat A has GenBank accession number FJ361197. NR 19 TC 746 Z9 792 U1 7 U2 73 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 31 PY 2008 VL 322 IS 5902 BP 750 EP 756 DI 10.1126/science.1163045 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 368EW UT WOS:000260605200052 PM 18974356 ER PT J AU Ross, JS Nunez-Smith, M Forsyth, BA Rosenbaum, JR AF Ross, Joseph S. Nunez-Smith, Marcella Forsyth, Beverly A. Rosenbaum, Julie R. TI Racial and ethnic differences in personal cervical cancer screening amongst post-graduate physicians: Results from a cross-sectional survey SO BMC PUBLIC HEALTH LA English DT Article ID UNITED-STATES; HEALTH-SERVICES; NATIONAL-SURVEY; HISPANIC WOMEN; CARE; BEHAVIORS; AMERICAN; BREAST; DISPARITIES; POPULATION AB Background: Racial and ethnic disparities in cervical cancer screening have been attributed to socioeconomic, insurance, and cultural differences. Our objective was to explore racial and ethnic differences in adherence to cervical cancer screening recommendations among female post-graduate physicians. Methods: We conducted a cross-sectional survey at one university hospital among a convenience sample of 204 female post-graduate physicians (52% of all potential participants), examining adherence to United States Preventive Services Task Force cervical cancer screening recommendations, perception of adherence to recommendations, and barriers to obtaining care. Results: Overall, 83% of women were adherent to screening recommendations and 84% accurately perceived adherence or non-adherence. Women who self-identified as Asian were significantly less adherent when compared with women who self-identified as white (69% vs. 87%; Relative Risk [RR] = 0.79, 95% Confidence Interval [CI], 0.64-0.97; P < 0.01). Women who self-identified as East Indian were significantly less likely to accurately perceive adherence or non-adherence when compared to women who self-identified as white (64% vs. 88%; RR = 0.73, 95% CI, 0.49-1.09, P = 0.04). Women who self-identified as Asian were significantly more likely to report any barrier to obtaining care when compared with women who self-identified as white (60% vs. 35%; RR = 1.75, 95% CI, 1.24-2.47; P = 0.001) and there was a nonsignificant tendency toward women who self-identified as East Indian being more likely to report any barrier to obtaining care when compared with women who self-identified as white (60% vs. 34%; RR = 1.74, 95% CI, 1.06-2.83; P = 0.06). Conclusion: Among a small group of insured, highly-educated physicians who have access to health care, we found racial and ethnic differences in adherence to cervical cancer screening recommendations, suggesting that culture may play a role in cervical cancer screening. C1 [Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, Bronx, NY USA. [Ross, Joseph S.] James J Peters Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. [Ross, Joseph S.] James J Peters Vet Adm Med Ctr, HSR&D Targeted Res Enhancement Program, Bronx, NY USA. [Nunez-Smith, Marcella] Yale Univ, Sch Med, Dept Internal Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06510 USA. [Forsyth, Beverly A.] Mt Sinai Sch Med, Dept Med, Div Infect Dis, Bronx, NY USA. [Rosenbaum, Julie R.] Yale Univ, Sch Med, Primary Care Internal Med Residency Program, New Haven, CT USA. [Rosenbaum, Julie R.] Waterbury Hosp & Hlth Ctr, Ctr Hlth, Dept Med, New Haven, CT USA. RP Ross, JS (reprint author), Mt Sinai Sch Med, Dept Geriatr & Adult Dev, Bronx, NY USA. EM joseph.ross@mssm.edu; marcella.nunez-smith@yale.edu; beverly.a.forsyth@mssm.edu; julie.rosenbaum@yale.edu NR 29 TC 6 Z9 6 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD OCT 30 PY 2008 VL 8 AR 378 DI 10.1186/1471-2458-8-378 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 379PP UT WOS:000261409000001 PM 18973674 ER PT J AU Rodrigues, GR Walker, RH Bader, B Danek, A Marques, W Tumas, V AF Rodrigues, Guilherme Riccioppo Walker, Ruth H. Bader, Benedikt Danek, Adrian Marques, Wilson, Jr. Tumas, Vitor TI Chorea-Acanthocytosis: Report of Two Brazilian Cases SO MOVEMENT DISORDERS LA English DT Article DE Chorea-acanthocytosis ID PROTEIN; GENE AB Chorea-acanthocytosis (ChAc) is a neurodegenerative disorder characterized by chorea, neuropsychiatric disturbances and acanthocytosis, caused by mutations of VPS13A. This gene produces the protein chorein which is absent in patients with ChAc on Western blot assay. We report the first two Brazilian patients with ChAc confirmed by chorein detection. Patient I is a 36-year-old man with chorea, epilepsy, myopathy. and suicidal ideation. Patient 2 is a 60-year-old woman with a 30 Year history of psychiatric disturbances, epilepsy, choreic movements, and myopathy. Both patients had acanthocytosis, elevated creatine kinase (CK), and absence (of chorein on Western blot analysis. The presence of chorea and neuropsychiatric disturbances associated with elevated CK levels, epilepsy, hyporeflexia, and acanthocytosis suggests the diagnosis of ChAc. Chorein assay of peripheral blood confirms the diagnosis. (C) 2008 Movement Disorder Society C1 [Rodrigues, Guilherme Riccioppo; Marques, Wilson, Jr.; Tumas, Vitor] Ribeirao Preto Sch Med, Dept Neurol, BR-14049900 Ribeirao Preto, Brazil. [Walker, Ruth H.] James J Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY USA. [Walker, Ruth H.] Mt Sinai Sch Med, New York, NY USA. [Bader, Benedikt; Danek, Adrian] Univ Munich, Dept Neurol, D-8000 Munich, Germany. RP Tumas, V (reprint author), Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Neurol Psychiat & Med Psychol, Campus Univ, BR-14049900 Ribeirao Preto, Brazil. EM tumasv@rnp.fmrp.usp.br RI Rodrigues, Guilherme/D-3547-2009; Danek, Adrian/G-7339-2011; Marques, Wilson/G-4240-2012; Tumas, Vitor/C-9949-2014 OI Rodrigues, Guilherme/0000-0002-4296-1016; Danek, Adrian/0000-0001-8857-5383; Marques, Wilson/0000-0002-4589-2749; NR 10 TC 6 Z9 6 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD OCT 30 PY 2008 VL 23 IS 14 BP 2090 EP 2093 DI 10.1002/mds.22305 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 374DA UT WOS:000261021500020 PM 18785241 ER PT J AU Gerberding, JL Romero, JM Ferraro, MJ Pisculli, M Rosenberg, ES Heller, HM Atkins, EH AF Gerberding, Julie L. Romero, Javier M. Ferraro, Mary Jane Pisculli, Mary Rosenberg, Eric S. Heller, Howard M. Atkins, Elisha H. TI A woman with neck pain and fever - Laboratory-acquired infection with B. melitensis, with cervical spinal osteomyelitis and epidural abscess SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BRUCELLOSIS C1 [Gerberding, Julie L.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Romero, Javier M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Ferraro, Mary Jane] Massachusetts Gen Hosp, Clin Microbiol Lab, Boston, MA 02114 USA. [Ferraro, Mary Jane] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Romero, Javier M.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Ferraro, Mary Jane] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Gerberding, JL (reprint author), Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. FU General Electric FX Dr. Romero reports receiving research grant support from General Electric. No other potential conflict of interest relevant to this article was reported. NR 11 TC 3 Z9 3 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 30 PY 2008 VL 359 IS 18 BP 1942 EP 1949 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 366BL UT WOS:000260454500011 PM 18971496 ER PT J AU Faustman, DL AF Faustman, Denise L. TI Immunotherapy on trial for new-onset type 1 diabetes SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CYCLOSPORINE; RESPONSES; PROGRESSION; MELLITUS; THERAPY; IDDM; MICE C1 [Faustman, Denise L.] Massachusetts Gen Hosp, Immunobiol Lab, Boston, MA 02114 USA. [Faustman, Denise L.] Harvard Univ, Sch Med, Boston, MA USA. RP Faustman, DL (reprint author), Massachusetts Gen Hosp, Immunobiol Lab, Boston, MA 02114 USA. NR 14 TC 3 Z9 3 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 30 PY 2008 VL 359 IS 18 BP 1956 EP 1958 DI 10.1056/NEJMe0807425 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 366BL UT WOS:000260454500014 PM 18843119 ER PT J AU Papakostas, GI McGrath, P Stewart, J Charles, D Chen, Y Mischoulon, D Dording, C Fava, M AF Papakostas, George I. McGrath, Patrick Stewart, Jonathan Charles, Dana Chen, Ying Mischoulon, David Dording, Christina Fava, Maurizio TI Psychic and somatic anxiety symptoms as predictors of response to fluoxetine in major depressive disorder SO PSYCHIATRY RESEARCH LA English DT Article DE Depression; Unipolar; SSRI; Clinical; Improvement; Pain ID ATYPICAL DEPRESSION; IMIPRAMINE; PLACEBO; OUTPATIENTS; INHIBITORS; PHENELZINE; REMISSION AB The purpose of this study was to examine whether the presence/severity of psychic and somatic anxiety symptoms predicted clinical response following a 12-week, flexible-dose (20-60 mg daily), open-label trial of fluoxetine for major depressive disorder (MDD). The presence and severity of psychic and somatic anxiety symptoms were assessed with the use of select subscales of the Symptom Questionnaire and the Hopkins Symptom Checklist among 518 outpatients with MDD. With the use of separate logistic regressions, we tested for the relationship between clinical response, baseline Hamilton Depression Rating Scale (HAM-D-17) scores, and subscale scores at baseline entered separately as independent variables Overall completion, response and remission rates for the trial were 64.2%, 55.4%, and 48.9%, respectively. All subscale scores selected for this analysis significantly predicted treatment response to fluoxetine. The presence/severity of psychic and somatic anxiety symptoms of MDD at baseline predicted an increased likelihood of non-response to fluoxetine in MDD. Studies examining whether specific treatment strategies are more effective than the selective serotonin reuptake inhibitors for MDD patients with high levels of co-morbid psychic and somatic anxiety symptoms are warranted. (c) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Papakostas, George I.] Harvard Univ, Dept Psychiat, Depress Clin & Res Program, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. [McGrath, Patrick; Stewart, Jonathan; Chen, Ying] Columbia Univ, New York State Psychiat Inst, Depress Evaluat Serv, New York, NY USA. RP Papakostas, GI (reprint author), Harvard Univ, Dept Psychiat, Depress Clin & Res Program, Massachusetts Gen Hosp,Sch Med, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM gpapakostas@partners.org RI McGrath, Patrick/I-6410-2013; Papakostas, George/I-6905-2013 OI McGrath, Patrick/0000-0001-7217-7321; Papakostas, George/0000-0002-2465-5103 NR 27 TC 20 Z9 21 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD OCT 30 PY 2008 VL 161 IS 1 BP 116 EP 120 DI 10.1016/j.psychres.2008.02.011 PG 5 WC Psychiatry SC Psychiatry GA 373CT UT WOS:000260949300016 PM 18755514 ER PT J AU Sakimoto, T Kim, TI Ellenberg, D Fukai, N Jain, S Azar, DT Chang, JH AF Sakimoto, Tohru Kim, Tae-im Ellenberg, David Fukai, Naomi Jain, Sandeep Azar, Dimitri T. Chang, Jin-Hong TI Collagen XVIII and corneal reinnervation following keratectomy SO FEBS LETTERS LA English DT Article DE Extracellular matrix; Collagen XVIII ID BASEMENT-MEMBRANES; PERIPHERAL-NERVE; SCHWANN-CELLS; REGENERATION; INNERVATION; MICE; TRANSPLANTATION; ANGIOGENESIS; CLEAVAGE; DEFECTS AB The significance of collagen XVIII in the regulation of corneal reinnervation remains largely unknown. We used whole-mount immunoconfocal microscopy to localize collagen XVIII to the nerve basement membrane of wild-type (WT) mouse corneas. Transmission electron microscopy showed corneal nerve disorganization in collagen XVIII knockout mice (col18a1(-/-)). Antibody 2H3-specific neuro. lament colocalized with collagens XVIII and IV and laminin-2 in WT mouse corneas, but did not colocalize with collagen IV and laminin-2 in col18a1(-/-)) mouse corneas. Following keratectomy, col18a1(-/-) mice displayed decreased corneal neurite extension compared to WT mice. Our data indicate that collagen XVIII may play an important role in corneal reinnervation after wounding. (c) 2008 Published by Elsevier B. V. on behalf of the Federation of European Biochemical Societies. C1 [Ellenberg, David; Jain, Sandeep; Azar, Dimitri T.; Chang, Jin-Hong] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA. [Sakimoto, Tohru; Kim, Tae-im; Jain, Sandeep; Azar, Dimitri T.; Chang, Jin-Hong] Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Sakimoto, Tohru; Kim, Tae-im; Jain, Sandeep; Azar, Dimitri T.; Chang, Jin-Hong] Harvard Univ, Schepens Eye Res Inst, Boston, MA 02115 USA. [Fukai, Naomi] Harvard Univ, Sch Dent Med, Sch Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. RP Chang, JH (reprint author), Univ Illinois, Dept Ophthalmol & Visual Sci, 1855 W Taylor St, Chicago, IL 60612 USA. EM changr@uic.edu RI 谭, 德华/D-1910-2009 FU NIH [EY14048, EY10101, EY001792]; Research to Prevent Blindness; Bausch Lomb Japan/MEEI Research; apan Eye Bank Association Overseas Research FX We thank Dr. Bjorn Olsen for providing col18a1-/- mice and Patricia Pearson for TEM imaging. Supported by NIH EY14048 (J. H. C.), EY10101 ( D. T. A.), EY 001792 ( D. T. A.), an unrestricted departmental grant from Research to Prevent Blindness, the Bausch Lomb Japan/MEEI Research Fellowship Award, and the Japan Eye Bank Association Overseas Research Award ( T. S.). NR 30 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 29 PY 2008 VL 582 IS 25-26 BP 3674 EP 3680 DI 10.1016/j.febslet.2008.09.052 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 371BT UT WOS:000260807500018 PM 18840438 ER PT J AU Temereanca, S Brown, EN Simons, DJ AF Temereanca, Simona Brown, Emery N. Simons, Daniel J. TI Rapid Changes in Thalamic Firing Synchrony during Repetitive Whisker Stimulation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE thalamocortical; firing synchrony; somatosensory; barreloid; barrel cortex; whiskers ID RAT BARREL CORTEX; SOMATOSENSORY CORTEX; VENTROBASAL COMPLEX; VISUAL-CORTEX; SPIKE TRAINS; NEURONS; DEFLECTIONS; SYSTEM; RELAY; FREQUENCY AB Thalamic firing synchrony is thought to ensure selective transmission of relevant sensory information to the recipient cortical neurons by rendering them more responsive to temporally correlated input spikes. However, direct evidence for a synchrony code in the thalamus is limited. Here, we directly measure thalamic firing synchrony and its stimulus-induced modulation over time, using simultaneous single unit recordings from individual thalamic barreloids in the rat somatosensory whisker/barrel system. Employing whisker deflections varying in velocity or frequency and a cross-correlation approach, we find systematic changes in both time course and strength of thalamic firing synchrony as a function of stimulus parameters and sensory adaptation. Synchrony develops faster and is greater with higher velocity deflections. Greater firing synchrony reflects stimulus-dependent increases in instantaneous firing rates, greater spike time precision relative to stimulus onset as well as common input that likely arises from divergent trigeminothalamic and corticothalamic neurons. With adaptation, synchrony decreases and takes longer to develop but is more dependent on the cells' common inputs. Rapid, sharp increases in thalamic synchrony mirroring quick increases in whisker velocity occur also during ongoing random, high-frequency whisker vibrations. Together, results demonstrate millisecond by millisecond changes in thalamic near-synchronous firing during complex patterns of ongoing vibrissa movements that may ensure transmission of preferred sensory information in local thalamocortical circuits during whisking and active touch. C1 [Temereanca, Simona; Simons, Daniel J.] Univ Pittsburgh, Sch Med, Dept Neurobiol, Pittsburgh, PA 15261 USA. [Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Brown, Emery N.] Harvard Massachusetts Inst Technol, Dept Brain & Cognit Sci, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Temereanca, Simona] Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, MIT,Med Sch, Charlestown, MA 02129 USA. RP Temereanca, S (reprint author), Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, MIT,Med Sch, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM temerean@nmr.mgh.harvard.edu FU Natinal Institutes of Health [NS19950, HD050627, DA015644, MH59733] FX This work was supported by Natinal Institutes of Health Grants NS19950 (D.J.S), HD050627 (S. T.), DA015644 (E.N.B.), and MH59733 (E.N.B.). Wethank Dr. Harold Kyriazi for expert technical assistance with data recordings and Dr. Robert Haslinger for helpful discussions and technical assistance with data analysis. NR 39 TC 39 Z9 39 U1 0 U2 0 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 OCT 29 PY 2008 VL 28 IS 44 BP 11153 EP 11164 DI 10.1523/JNEUROSCI.1586-08.2008 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 366RZ UT WOS:000260502400007 PM 18971458 ER PT J AU Mody, M Wehner, DT Ahlfors, SP AF Mody, Maria Wehner, Daniel T. Ahlfors, Seppo P. TI Auditory word perception in sentence context in reading-disabled children SO NEUROREPORT LA English DT Article DE dyslexia; magnetoencephalography; N400; phonological mismatch negativity; reading impairment ID MAGNETOENCEPHALOGRAPHY MEG; DEVELOPMENTAL DYSLEXIA; DORSAL STREAM; RECOGNITION; RESPONSES; COMPREHENSION; LOCALIZATION; SENSITIVITY; POTENTIALS; ACTIVATION AB Reading difficulties seem to be related to a phonological deficit that has its origin in poor speech perception. As such, disabled readers may use contextual cues to compensate for their weak speech perception abilities.We compared good and poor readers, 7-13 years old, on auditory perception of words varying in phonological contrast, in congruent versus incongruent sentence contexts. Both groups did worse in the phonologically similar than in the phonologically dissimilar incongruent condition. Magnetoencephalography revealed differential activation between the groups as a function of phonological contrast in left superior temporal gyrus between 200 and 300 ms, suggesting that poor readers may have processed phonologically similar incongruent stimuli as congruent. The results are consistent with a phonological account of reading disability. NeuroReport 19:1567-1571 (C) 2008 Wolters Kluwer Health | Lippincott Williams& Wilkins. C1 [Mody, Maria; Wehner, Daniel T.; Ahlfors, Seppo P.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, MIT, HMS, Charlestown, MA 02129 USA. [Mody, Maria; Wehner, Daniel T.; Ahlfors, Seppo P.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Mody, M (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, MIT, HMS, 149 13th St,Rm 2301, Charlestown, MA 02129 USA. EM maria@nmr.mgh.harvard.edu RI Ahlfors, Seppo/P-3644-2016 FU NIH [DC00159, HDO46171]; NCRR [P41RR14075]; MIND Institute; [DC00038]; [5T32EB001680] FX There was no conflict of interest. The authors thank S. Basho, S. Mosher, C. Sahyoun, D. Von Pechmann, and M. Hamalainen for various aspects of data collection and analysis, and S. Shattuck-Hufnagel, K. Stevens, and C. Perfetfi for helpful comments. Supported by NIH: DC00159 and HDO46171, and in part by NCRR P41RR14075 and the MIND Institute. DTW was also supported by an NIH Training Grant DC00038, and 5T32EB001680 (PI: Bruce Rosen). We thank all the children and parents for their willingness to participate in the study. NR 25 TC 5 Z9 5 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 EI 1473-558X J9 NEUROREPORT JI Neuroreport PD OCT 29 PY 2008 VL 19 IS 16 BP 1567 EP 1571 DI 10.1097/WNR.0b013e328311ca04 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 365VT UT WOS:000260438100003 PM 18815588 ER PT J AU Li, X Sapp, E Valencia, A Kegel, KB Qin, ZH Alexander, J Masso, N Reeves, P Ritch, JJ Zeitlin, S Aronin, N DiFiglia, M AF Li, Xueyi Sapp, Ellen Valencia, Antonio Kegel, Kimberly B. Qin, Zheng-Hong Alexander, Jonathan Masso, Nicholas Reeves, Patrick Ritch, James J. Zeitlin, Scott Aronin, Neil DiFiglia, Marian TI A function of huntingtin in guanine nucleotide exchange on RabII SO NEUROREPORT LA English DT Article DE endosomes; huntingtin; nucleotide exchange factor; RabII ID MEMBRANE; PROTEIN; SPECIFICITY; ENDOSOME; DISEASE; COMPLEX; BRAIN; GEF AB Huntingtin is ubiquitously expressed and enriched in the brain. Deletion of the huntingtin gene in mice is lethal during early embryonic development. The function of huntingtin is, however, not clear. Here, we report that huntingtin is important for the function of RabII, a critical GTPase in regulating membrane traffic from recycling endosomes to the plasma membrane. In huntingtinnull embryonic cells, the levels of RabII on membranes nucleotide exchange activity on RabII were significantly reduced compared with normal embryonic stem cells. In brain membranes, an antibody against huntingtin immunoprecipitated a nucleoticle exchange activity on RabII and huntingtin was coprecipitated with RabII in the presence of guanosine diphosphate. These data suggest a role for huntingtin in a complex that activates RabII. NeuroReport 19:1643-1647 (C) 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [Li, Xueyi] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Cellular Neurobiol, Charlestown, MA 02129 USA. [Li, Xueyi; Sapp, Ellen; Valencia, Antonio; Kegel, Kimberly B.; Qin, Zheng-Hong; Alexander, Jonathan; Masso, Nicholas; Reeves, Patrick; Ritch, James J.; DiFiglia, Marian] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Aronin, Neil] Univ Massachusetts, Sch Med, Dept Med & Cell Biol, Worcester, MA USA. [Zeitlin, Scott] Univ Virginia, Sch Med, Dept Neurosci, Charlottesville, VA 22908 USA. RP Li, X (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Cellular Neurobiol, Charlestown, MA 02129 USA. EM xlil2@partners.org; difiglia@helix.mgh.Harvard.edu FU NIH; DANA Foundation; High Q Foundation; Huntingtin's Disease Society of America; Hereditary Disease Foundation FX This study was supported by grants from NIH (to M. D. and N. A.), DANA Foundation (to M. D. and N. A.), High Q Foundation (to M. D.), and Huntingtin's Disease Society of America (to M. D.). We thank Dr Meiqian Weng for her generous gifts of fresh mouse brains. Xueyi Li is supported by a John J. Wasmuth Postdoctoral Fellowship from the Hereditary Disease Foundation. Authors declared no conflict of interests. NR 16 TC 23 Z9 23 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD OCT 29 PY 2008 VL 19 IS 16 BP 1643 EP 1647 DI 10.1097/WNR.0b013e328315cd4c PG 5 WC Neurosciences SC Neurosciences & Neurology GA 365VT UT WOS:000260438100017 PM 18845944 ER PT J AU Mathew, P Thall, PF Wen, S Bucana, C Jones, D Horne, E Oh, WK Morris, MJ Lee, YC Logothetis, CJ Lin, SH Fidler, IJ AF Mathew, P. Thall, P. F. Wen, S. Bucana, C. Jones, D. Horne, E. Oh, W. K. Morris, M. J. Lee, Y-C Logothetis, C. J. Lin, S-H Fidler, I. J. TI Dynamic change in phosphorylated platelet-derived growth factor receptor in peripheral blood leukocytes following docetaxel therapy predicts progression-free and overall survival in prostate cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE prostate cancer; platelet-derived growth factor receptor; docetaxel; survival ID LOCALLY WEIGHTED REGRESSION; BONE METASTASES; FAMILY; VEGF AB In a placebo-controlled randomised study of the platelet-derived growth factor receptor (PDGFR) inhibitor imatinib mesylate and docetaxel in metastatic prostate cancer with bone metastases (n = 116), no significant differences in progression-free and overall survival were observed. To evaluate pharmacodynamic correlates of outcomes, we assessed the association of plasma platelet-derived growth factor (PDGF) isoform kinetics and PDGFR inhibition with progression-free and overall survival by individual treatment arm. We found that in the docetaxel - placebo arm alone, the probability of decrease in PDGFR phosphorylation (Pr-Decr-pPDGFR) above 0.5 (vs <= 0.5) was associated with a sharp increase in all measured plasma PDGF isoforms (P = 0.006 for AA, 0.002 for BB, 0.045 for AB); a decreased median progression-free survival of 3.3 months vs 6.8 months (hazard ratio (HR) 2.5; P = 0.006 in log-rank test) and an inferior median overall survival of 20 months vs > 30 months (HR 3.1; P = 0.04 in log-rank test). By contrast, in the docetaxel plus imatinib arm, the association of Pr-Decr-pPDGFR > 0.5 with a rise in plasma PDGF isoform concentrations and inferior survival was not observed. The data suggest that dynamic changes in PDGFR phosphorylation in peripheral blood leukocytes predict docetaxel efficacy. Rising plasma PDGF concentrations may explain and/or mark docetaxel resistance. Validation and mechanistic studies addressing these unexpected findings should anticipate a confounding influence of concurrent PDGFR inhibitor therapy. C1 [Mathew, P.; Jones, D.; Horne, E.; Logothetis, C. J.] MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA. [Thall, P. F.; Wen, S.] Dept Biostat, Houston, TX 77030 USA. [Bucana, C.; Fidler, I. J.] MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. [Oh, W. K.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Morris, M. J.] Mem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Oncol Serv, New York, NY 10021 USA. [Lee, Y-C; Lin, S-H] MD Anderson Canc Ctr, Dept Mol Pathol, Houston, TX 77030 USA. RP Mathew, P (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Unit 1374, 1155 Pressler, Houston, TX 77030 USA. EM pmathew@mdanderson.org RI Oh, William/B-9163-2012; OI Oh, William/0000-0001-5113-8147; Morris, Michael J./0000-0002-9454-0096 FU Novartis Pharmaceuticals; National Cancer Institute [5-P50 CA090270-06] FX This study was supported by Novartis Pharmaceuticals and the National Cancer Institute 5-P50 CA090270-06 under an Inter-SPORE collaboration. We acknowledge the assistance of Rebecca Fueger, Cynthia M. Carter, Carol Oborn, Tamara Locke and Sherryl Smith. NR 23 TC 11 Z9 11 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD OCT 28 PY 2008 VL 99 IS 9 BP 1426 EP 1432 DI 10.1038/sj.bjc.6604706 PG 7 WC Oncology SC Oncology GA 366SE UT WOS:000260502900010 PM 18841158 ER PT J AU Jaffer, FA Vinegoni, C John, MC Aikawa, E Gold, HK Finn, AV Ntziachristos, V Libby, P Weissleder, R AF Jaffer, Farouc A. Vinegoni, Claudio John, Michael C. Aikawa, Elena Gold, Herman K. Finn, Aloke V. Ntziachristos, Vasilis Libby, Peter Weissleder, Ralph TI Real-Time Catheter Molecular Sensing of Inflammation in Proteolytically Active Atherosclerosis SO CIRCULATION LA English DT Article DE atherosclerosis; catheters; fluorescence; imaging; inflammation; cathepsins ID IN-VIVO; CARDIOVASCULAR-DISEASE; CYSTEINE PROTEASES; MACROPHAGES; TOMOGRAPHY; PLAQUES; CELLS; POOL AB Background-To enable intravascular detection of inflammation in atherosclerosis, we developed a near-infrared fluorescence ( NIRF) catheter-based strategy to sense cysteine protease activity during vascular catheterization. Methods and Results-The NIRF catheter design was based on a clinical coronary artery guidewire. In phantom studies of NIRF plaques, blood produced only a mild (<30%) attenuation of the fluorescence signal compared with saline, affirming the favorable optical properties of the NIR window. Catheter evaluation in vivo used atherosclerotic rabbits (n=11). Rabbits received an injection of a cysteine protease-activatable NIRF imaging agent (Prosense750; excitation/emission, 750/770 nm) or saline. Catheter pullbacks through the blood-filled iliac artery detected NIRF signals 24 hours after injection of the probe. In the protease agent group, the in vivo peak plaque target-to-background ratio was 558% greater than controls (6.8 +/- 1.9 versus 1.3 +/- 0.3, mean +/- SEM; P<0.05). Ex vivo fluorescence reflectance imaging corroborated these results (target-to-background ratio, 10.3 +/- 1.8 for agent versus 1.8 +/- 0.3 for saline group; P<0.01). In the protease group only, saline flush-modulated NIRF signal profiles further distinguished atheromata from normal segments in vivo (P<0.01). Good correlation between the in vivo and ex vivo plaque target-to-background ratio was present (r=0.82, P<0.01). Histopathological analyses demonstrated strong NIRF signal in plaques only from the protease agent group. NIRF signals colocalized with immunoreactive macrophages and the cysteine protease cathepsin B. Conclusions-An intravascular fluorescence catheter can detect cysteine protease activity in vessels the size of human coronary arteries in real time with an activatable NIRF agent. This strategy could aid in the detection of inflammation and high-risk plaques in small arteries. (Circulation. 2008; 118: 1802-1809.) C1 [Jaffer, Farouc A.; Vinegoni, Claudio; Aikawa, Elena; Ntziachristos, Vasilis; Weissleder, Ralph] Massachusetts Gen Hosp, CMIR, Boston, MA 02129 USA. [Jaffer, Farouc A.; John, Michael C.; Gold, Herman K.; Finn, Aloke V.; Weissleder, Ralph] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA. [Jaffer, Farouc A.; John, Michael C.; Gold, Herman K.; Finn, Aloke V.; Weissleder, Ralph] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02129 USA. [Jaffer, Farouc A.; Libby, Peter] Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr, Boston, MA USA. [Libby, Peter] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Jaffer, FA (reprint author), Massachusetts Gen Hosp, CMIR, 149 13th St,Room 5406, Boston, MA 02129 USA. EM fjaffer@mgh.harvard.edu OI Jaffer, Farouc/0000-0001-7980-384X FU Donald W. Reynolds Foundation [UO1 HL080731, HL-80472]; Siemens Medical Solutions; American College of Cardiology Foundation Career Development; Howard Hughes Medical Institute Career Development; American Heart Association Scientist Development FX This work was supported by the Donald W. Reynolds Foundation ( Drs Weissleder, Libby, and Jaffer), UO1 HL080731 ( Drs Weissleder, Libby, and Jaffer), HL-80472 (Dr Libby), Siemens Medical Solutions ( Dr Weissleder), American College of Cardiology Foundation Career Development Award (Dr Jaffer), Howard Hughes Medical Institute Career Development Award (Dr Jaffer), and American Heart Association Scientist Development Grant (Dr Jaffer). NR 25 TC 104 Z9 107 U1 0 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP 1802 EP 1809 DI 10.1161/CIRCULATIONAHA.108.785881 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 365RT UT WOS:000260426200006 PM 18852366 ER PT J AU Noseworthy, PA Newton-Cheh, C AF Noseworthy, Peter A. Newton-Cheh, Christopher TI Genetic Determinants of Sudden Cardiac Death SO CIRCULATION LA English DT Review DE death, sudden; epidemiology; genetics; heart arrest; tachyarrhythmias ID LONG-QT-SYNDROME; IDIOPATHIC DILATED CARDIOMYOPATHY; RIGHT-VENTRICULAR CARDIOMYOPATHY; CONGESTIVE-HEART-FAILURE; BRUGADA-TYPE ELECTROCARDIOGRAM; ACUTE MYOCARDIAL-INFARCTION; ST-SEGMENT ELEVATION; TORSADES-DE-POINTES; T-WAVE ALTERNANS; HYPERTROPHIC CARDIOMYOPATHY C1 [Newton-Cheh, Christopher] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Massachusetts Gen Hosp,Ctr Human Genet Res, Boston, MA 02114 USA. [Noseworthy, Peter A.; Newton-Cheh, Christopher] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Newton-Cheh, Christopher] MIT, Cambridge, MA 02139 USA. RP Newton-Cheh, C (reprint author), Harvard Univ, Sch Med, Cardiovasc Res Ctr, Massachusetts Gen Hosp,Ctr Human Genet Res, 185 Cambridge St,CPZN 5-242, Boston, MA 02114 USA. EM cnewtoncheh@chgr.mgh.harvard.edu NR 109 TC 38 Z9 39 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP 1854 EP 1863 DI 10.1161/CIRCULATIONAHA.108.783654 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 365RT UT WOS:000260426200012 PM 18955676 ER PT J AU Abtahian, F Olenchock, B Ou, FS Kontos, MC Saucedo, J Mega, JL Scirica, B Peterson, E Cannon, CP Wiviott, SD AF Abtahian, Farhad Olenchock, Benjamin Ou, Fang-Shu Kontos, Michael C. Saucedo, Jorge Mega, Jessica L. Scirica, Benjamin Peterson, Eric Cannon, Christopher P. Wiviott, Stephen D. TI The Impact of Prior Stroke on the Use of Evidence-based Therapies, and In-Hospital Outcomes in MI Patients: A Report of the NCDR ACTION GWTG Registry SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Mega, Jessica L.; Scirica, Benjamin; Cannon, Christopher P.; Wiviott, Stephen D.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Ou, Fang-Shu; Peterson, Eric] Duke Clin Rsch Inst, Durham, NC USA. [Kontos, Michael C.] Virginia Commonwealth Univ, Richmond, VA USA. [Saucedo, Jorge] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Mega, Jessica L.; Scirica, Benjamin; Cannon, Christopher P.; Wiviott, Stephen D.] TIMI Study Grp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S970 EP S970 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503594 ER PT J AU Ahmed, H Neuzil, P d'Avila, A Laragy, M Mares, K Brugge, WR Forcione, DG Ruskin, JN Reddy, VY AF Ahmed, Humera Neuzil, Petr d'Avila, Andre Laragy, Margaret Mares, Karel Brugge, William R. Forcione, David G. Ruskin, Jeremy N. Reddy, Vivek Y. TI Esophageal Temperature Monitoring during Balloon Cryoablation of the Pulmonary Veins SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Ahmed, Humera; d'Avila, Andre; Reddy, Vivek Y.] Univ Miami, Miami, FL USA. [Neuzil, Petr; Mares, Karel] Homolka Hosp, Prague, Czech Republic. [Laragy, Margaret; Brugge, William R.; Forcione, David G.; Ruskin, Jeremy N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI d'Avila, Andre/A-7693-2009; d'Avila, Andre Luiz/F-8009-2010 OI d'Avila, Andre Luiz/0000-0001-8769-1411 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S978 EP S978 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503626 ER PT J AU An, D Toyoda, T Taylor, EB Hirshman, MF Goodyear, LJ AF An, Ding Toyoda, Taro Taylor, Eric B. Hirshman, Michael F. Goodyear, Laurie J. TI Identification Of AS160 As An Insulin, Ischemia, And Exercise Regulated Signaling Protein In The Heart SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [An, Ding; Toyoda, Taro; Taylor, Eric B.; Hirshman, Michael F.; Goodyear, Laurie J.] Joslin Diabet Ctr, Boston, MA 02215 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S485 EP S485 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104501156 ER PT J AU Bailey, D Chatur, S Hafiane, A Haidar, B Juppner, H Bastepe, M Krimbou, L Genest, J AF Bailey, Dana Chatur, Safia Hafiane, Anouar Haidar, Bassam Jueppner, Harald Bastepe, Murat Krimbou, Larbi Genest, Jacques TI Deficiency Of The Stimulatory G Protein alpha-subunit Gs (alpha) Leads To Reduced ApoA-I Mediated Cellular Lipid Efflux and Impaired ABCA1-dependent Nascent HDL Biogenesis Pathway SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Bailey, Dana; Chatur, Safia; Hafiane, Anouar; Haidar, Bassam; Genest, Jacques] McGill Univ, Div Cardiol, Montreal, PQ, Canada. [Jueppner, Harald; Bastepe, Murat] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S558 EP S559 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104501468 ER PT J AU Bamberg, F Ferecik, M Truong, Q Rogers, I Shapiro, M Brady, TJ Nagurney, JT Hoffmann, U AF Bamberg, Fabian Ferecik, Maros Truong, Quynh Rogers, Ian Shapiro, Michael Brady, Thomas J. Nagurney, John T. Hoffmann, Udo TI Characteristics of Atherosclerotic Plaque Burden In Patients With and Without Acute Coronary Syndrome Presenting With Acute Chest Pain to the Emergency Department SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Bamberg, Fabian; Ferecik, Maros; Truong, Quynh; Rogers, Ian; Shapiro, Michael; Brady, Thomas J.; Nagurney, John T.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S597 EP S597 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104501635 ER PT J AU Bezerra, HG Loureiro, R Irlbeck, T Bamberg, F Schlett, CL Rogers, I Brady, T Hoffmann, U Cury, RC AF Bezerra, Hiram G. Loureiro, Ricardo Irlbeck, Thomas Bamberg, Fabian Schlett, Christopher L. Rogers, Ian Brady, Thomas Hoffmann, Udo Cury, Ricardo C. TI Additional Value of Myocardial Perfusion and Function over Coronary Stenosis for the Detection of Patients with Acute Coronary Syndrome by Cardiac CT SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Bezerra, Hiram G.; Loureiro, Ricardo; Irlbeck, Thomas; Bamberg, Fabian; Schlett, Christopher L.; Rogers, Ian; Brady, Thomas; Hoffmann, Udo; Cury, Ricardo C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S936 EP S937 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503462 ER PT J AU Bezerra, HG Loureiro, R Sarwar, A Rocha, J Pflederer, T Marwan, M Petranovic, M Raffel, CO Hoffmann, U McNulty, IA Brady, T Jang, IK Achenbach, S Cury, RC AF Bezerra, Hiram G. Loureiro, Ricardo Sarwar, Ammar Rocha, Jose Pflederer, T. Marwan, M. Petranovic, Milena Raffel, Christopher O. Hoffmann, Udo McNulty, Iris A. Brady, Thomas Jang, I. K. Achenbach, Stephan Cury, Ricardo C. TI Defining the Best Approach for Stenosis Quantification by Dual-Source CT - A Comparative Study Involving Intravascular Ultrasound and Invasive Coronary Angiography SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Bezerra, Hiram G.; Loureiro, Ricardo; Sarwar, Ammar; Rocha, Jose; Petranovic, Milena; Raffel, Christopher O.; Hoffmann, Udo; McNulty, Iris A.; Brady, Thomas; Jang, I. K.; Cury, Ricardo C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pflederer, T.; Marwan, M.; Achenbach, Stephan] Univ Erlangen Nurnberg, Erlangen, Germany. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S845 EP S845 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503098 ER PT J AU Blaha, MJ Budoff, MJ Rivera, JJ Katz, R O'Leary, DH Polak, JF Takasu, J Blumenthal, RS Nasir, K AF Blaha, Michael J. Budoff, Matthew J. Rivera, Juan J. Katz, Ronit O'Leary, Dan H. Polak, Jospeh F. Takasu, Junchiro Blumenthal, Roger S. Nasir, Khurram TI Relationship of Carotid Arterial Compliance and Thoracic Aorta Calcification: Multi-Ethnic Study of Atherosclerosis (MESA) SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Blaha, Michael J.; Rivera, Juan J.; Blumenthal, Roger S.] Johns Hopkins, Baltimore, MD USA. [Budoff, Matthew J.; Takasu, Junchiro] Harbor UCLA, Los Angeles BioMed Rsch Inst, Torrance, CA USA. [Katz, Ronit] Univ Washington, Seattle, WA 98195 USA. [O'Leary, Dan H.] Caritas Carney Hosp, Dorchester, MA USA. [Polak, Jospeh F.] Tufts New England Med Cntr, Boston, MA USA. [Nasir, Khurram] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S1156 EP S1156 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104504587 ER PT J AU Blankstein, R Budoff, M Shaw, LJ Goff, DC Polack, JF Lima, J Blumenthal, RS Nasir, K AF Blankstein, Ron Budoff, Matthew Shaw, Leslee J. Goff, David C., Jr. Polack, Joseph F. Lima, Joao Blumenthal, Roger S. Nasir, Khurram TI Predictors of Coronary Heart Disease Events among Asymptomatic Individuals with Low LDL: The Multi-Ethnic Study of Atherosclerosis SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Blankstein, Ron] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Budoff, Matthew] Harbor UCLA, Med Ctr, Los Angeles, CA USA. [Shaw, Leslee J.] Emory Univ, Sch Med, Atlanta, GA USA. [Goff, David C., Jr.] Wake Forest Univ, Sch Med, Winston Salen, NC USA. [Polack, Joseph F.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Lima, Joao; Blumenthal, Roger S.] Johns Hopkins Univ, Baltimore, MI USA. [Nasir, Khurram] Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S1151 EP S1151 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104504570 ER PT J AU Blankstein, R Soni, AV Sarwar, A Rogers, I Shturman, L Petranovic, M Mamuya, WS Bezerra, H Nasir, K Loureiro, R Okada, D Hoffmann, U Brady, TJ Cury, RC AF Blankstein, Ron Soni, Arland V. Sarwar, Ammar Rogers, Ian Shturman, Leon Petranovic, Milena Mamuya, Wilfred S. Bezerra, Hiram Nasir, Khurram Loureiro, Ricardo Okada, David Hoffmann, Udo Brady, Thomas J. Cury, Ricardo C. TI Adenosine Induced Stress Myocardial Perfusion Imaging using Dual Source Cardiac CT:Initial Clinical Experience SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Blankstein, Ron; Soni, Arland V.; Sarwar, Ammar; Rogers, Ian; Shturman, Leon; Mamuya, Wilfred S.; Bezerra, Hiram; Loureiro, Ricardo; Okada, David; Hoffmann, Udo; Brady, Thomas J.; Cury, Ricardo C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Petranovic, Milena] Harvard Univ, Sch Med, Boston, MA USA. [Nasir, Khurram] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S837 EP S837 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503065 ER PT J AU Blankstein, R Pale, R Nasir, K Shah, AB Bezerra, H Bolen, M Gupta, R Mamuya, WS Abbara, S Brady, TJ Cury, RC AF Blankstein, Ron Pale, Rodrigo Nasir, Khurram Shah, Amar B. Bezerra, Hiram Bolen, Michael Gupta, Rajiv Mamuya, Wilfred S. Abbara, Suhny Brady, Thomas J. Cury, Ricardo C. TI Variability and Predictors of Patient Radiation Dose with Dual Source Cardiac CT: Implications for Future Algorithms to Reduce Patient Radiation Dose SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Nasir, Khurram] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Blankstein, Ron; Pale, Rodrigo; Shah, Amar B.; Bezerra, Hiram; Bolen, Michael; Gupta, Rajiv; Mamuya, Wilfred S.; Abbara, Suhny; Brady, Thomas J.; Cury, Ricardo C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S599 EP S599 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104501644 ER PT J AU Body, SC Collard, CD Shernan, SK Fox, AA Liu, KY Ritchie, MD Perry, TE Muehischlegel, JD Aranki, S Seidman, CE Seidman, JG Donahue, BS Hermann, D Lichtner, P Meitinger, T Estrada, JC Pretorius, M Ellinor, PT Newton-Cheh, C Brown, NJ Roden, DM Darbar, D AF Body, Simon C. Collard, Charles D. Shernan, Stanton K. Fox, Amanda A. Liu, Kuang-Yu Ritchie, Marylyn D. Perry, Tjorvi E. Muehischlegel, Jochen D. Aranki, Sary Seidman, Christine E. Seidman, Jonathan G. Donahue, Brian S. Hermann, Daniel Lichtner, Peter Meitinger, Thomas Estrada, Juan-Carlos Pretorius, Mias Ellinor, Patrick T. Newton-Cheh, Christopher Brown, Nancy J. Roden, Dan M. Darbar, Dawood TI Variation in the 4q25 Chromosomal Locus Predicts New-Onset Atrial Fibrillation after Cardiac Surgery SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Body, Simon C.; Shernan, Stanton K.; Fox, Amanda A.; Liu, Kuang-Yu; Perry, Tjorvi E.; Muehischlegel, Jochen D.; Aranki, Sary; Seidman, Christine E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Collard, Charles D.] Baylor Coll Med, Houston, TX 77030 USA. [Ritchie, Marylyn D.; Donahue, Brian S.; Estrada, Juan-Carlos; Pretorius, Mias; Brown, Nancy J.; Roden, Dan M.; Darbar, Dawood] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Lichtner, Peter; Meitinger, Thomas] Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany. [Ellinor, Patrick T.; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S882 EP S882 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503245 ER PT J AU Bradley, SM Gabriel, EE Aufderheide, TP Barnes, R Christenson, J Davis, DP Stiell, IG Nichol, G AF Bradley, Steven M. Gabriel, Erin E. Aufderheide, Tom P. Barnes, Roxy Christenson, Jim Davis, Daniel P. Stiell, Ian G. Nichol, Graham CA Resuscitation Outcomes Consortium TI Survival Increases with CPR Before Defibrillation of Out-of-Hospital Ventricular Fibrillation or Ventricular Tachycardia: Observations from the Resuscitation Outcomes Consortium SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Bradley, Steven M.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Gabriel, Erin E.; Nichol, Graham] Univ Washington, Seattle, WA 98195 USA. [Aufderheide, Tom P.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Barnes, Roxy] Vancouver Fire Dept, Vancouver, WA USA. [Christenson, Jim] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Davis, Daniel P.] Univ Calif San Diego, San Diego, CA 92103 USA. [Stiell, Ian G.] Univ Ottawa, Ottawa, ON, Canada. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S1445 EP S1445 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104504664 ER PT J AU Briggs, LE Takeda, M Cuadra, AE Wakimoto, H Lu, JT Yasui, K Ikeda, Y Chien, KR Kasahara, H AF Briggs, Laura E. Takeda, Morihiko Cuadra, Adolfo E. Wakimoto, Hiroko Lu, Jonathan T. Yasui, Kenji Ikeda, Yasuhiro Chien, Kenneth R. Kasahara, Hideko TI Perinatal Loss of Nkx2-5 Results in Rapid Conduction and Contraction Defects SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Briggs, Laura E.; Takeda, Morihiko; Cuadra, Adolfo E.; Kasahara, Hideko] Univ Florida, Gainesville, FL USA. [Chien, Kenneth R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yasui, Kenji] Nagoya Univ, Aichi, Japan. [Ikeda, Yasuhiro] Yamaguchi Univ, Sch Med, Ube, Yamaguchi 755, Japan. [Lu, Jonathan T.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Wakimoto, Hiroko] Tokyo Med & Dent Univ, Tokyo, Japan. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S517 EP S517 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104501292 ER PT J AU Brooks, WW Conrad, CH Robinson, KG Bing, OH AF Brooks, Wesley W. Conrad, Chester H. Robinson, Kathleen G. Bing, Oscar H. TI Synergistic Cardiotherapeutic Effect of Phenylbutyrate with Captopril or Losartan in the Treatment of Heart Failure SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Brooks, Wesley W.; Conrad, Chester H.; Robinson, Kathleen G.; Bing, Oscar H.] VA Boston Healthcare Syst, Boston, MA USA. [Brooks, Wesley W.; Conrad, Chester H.; Bing, Oscar H.] Boston Univ, Sch Med, Boston, MA 02118 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S946 EP S946 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503503 ER PT J AU Brouckaert, P Thoonen, R Buys, E Nimmegeers, S Rogge, E Sips, P Bloch, KD de Voorde, JV AF Brouckaert, Peter Thoonen, Robrecht Buys, Emmanuel Nimmegeers, Sofie Rogge, Elke Sips, Patrick Bloch, Kenneth D. de Voorde, Johan Van TI Phenotyping of NO-Insensitive Soluble Guanylate Cyclase beta1H105F Knockin Mice SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Brouckaert, Peter; Thoonen, Robrecht; Sips, Patrick] Univ Ghent, VIB, B-9000 Ghent, Belgium. [Buys, Emmanuel; Bloch, Kenneth D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S284 EP S285 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104500080 ER PT J AU Cawley, SM Buys, E Ichinose, F Brouckaert, P Bloch, KD AF Cawley, Sharon M. Buys, Emannuel Ichinose, Fumito Brouckaert, Peter Bloch, Kenneth D. TI Contractile Defects In Cardiac Myocytes From sGCa1-Deficient Mice SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Cawley, Sharon M.; Buys, Emannuel; Ichinose, Fumito; Bloch, Kenneth D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brouckaert, Peter] Univ Ghent, B-9000 Ghent, Belgium. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S349 EP S349 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104500361 ER PT J AU Chang, KY Figueiredo, JL Kohler, R Francis, S Patel, P McCarthy, J Weissleder, R Plutzky, J Jaffer, F AF Chang, Kiyuk Figueiredo, Jose-Luiz Kohler, Rainer Francis, Sanjeev Patel, Purvish McCarthy, Jason Weissleder, Ralph Plutzky, Jorge Jaffer, Farouc TI Peroxisome Proliferator-Activated Receptor-gamma Activation Reduces Inflammation in Atherosclerosis as Assessed by Serial In Vivo Fluorescence Molecular Imaging SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Chang, Kiyuk; Figueiredo, Jose-Luiz; Kohler, Rainer; Patel, Purvish; McCarthy, Jason; Weissleder, Ralph; Jaffer, Farouc] Massachusetts Gen Hosp, Charlestown, MA USA. [Francis, Sanjeev; Plutzky, Jorge] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S556 EP S556 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104501458 ER PT J AU Chaput, M Handschumacher, MD Guerrero, JL Holmvang, G Dal-Bianco, JP Sullivan, S Johnson, B Vlahakes, GJ Hung, J Levine, RA AF Chaput, Miguel Handschumacher, Mark D. Guerrero, J. L. Holmvang, Godtfred Dal-Bianco, Jacob P. Sullivan, Suzanne Johnson, Benjamin Vlahakes, Gus J. Hung, Judy Levine, Robert A. TI Mitral Leaflet Adaptation to Ventricular Remodeling: Prospective Changes In a Model of Ischemic Mitral Regurgitation SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Chaput, Miguel; Handschumacher, Mark D.; Guerrero, J. L.; Holmvang, Godtfred; Dal-Bianco, Jacob P.; Sullivan, Suzanne; Johnson, Benjamin; Vlahakes, Gus J.; Hung, Judy; Levine, Robert A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S859 EP S859 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503153 ER PT J AU Cubeddu, RJ Cruz-Gonzalez, I Kiernan, TJ Leinbach, RC Truong, QA Rosenfield, K Cadigan, ME Pomerantsev, EV Palacios, IF AF Cubeddu, Roberto J. Cruz-Gonzalez, Ignacio Kiernan, Thomas J. Leinbach, Robert C. Truong, Quynh A. Rosenfield, Kenneth Cadigan, Mary E. Pomerantsev, Eugene V. Palacios, Igor F. TI Increased Mortality after Primary Percutaneous Coronary Intervention for Acute ST Segment Elevation Myocardial Infarction During Off-Hours SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Cubeddu, Roberto J.; Cruz-Gonzalez, Ignacio; Kiernan, Thomas J.; Leinbach, Robert C.; Truong, Quynh A.; Rosenfield, Kenneth; Cadigan, Mary E.; Pomerantsev, Eugene V.; Palacios, Igor F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S1172 EP S1172 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104504653 ER PT J AU Cury, RC Loureiro, R Bezerra, H Petranovic, M Sarwar, A Rocha, J Pflederer, T Marwan, M Raffel, OC Hoffmann, U Brady, T Jang, IK Achenbach, S AF Cury, Ricardo C. Loureiro, Ricardo Bezerra, Hiram Petranovic, Milena Sarwar, Ammar Rocha, Jose Pflederer, Tobias Marwan, Mohamed Raffel, Owen C. Hoffmann, Udo Brady, Thomas Jang, Ik-Kyung Achenbach, Stephan TI Detection, Quantification and Characterization of Coronary Atherosclerotic Plaque by Dual-Source CT - A Comparison to Intravascular Ultrasound SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Cury, Ricardo C.; Loureiro, Ricardo; Bezerra, Hiram; Petranovic, Milena; Sarwar, Ammar; Rocha, Jose; Raffel, Owen C.; Hoffmann, Udo; Brady, Thomas; Jang, Ik-Kyung] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pflederer, Tobias; Marwan, Mohamed; Achenbach, Stephan] Univ Erlangen Nurnberg, Erlangen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S845 EP S845 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503097 ER PT J AU Dal-Blanco, JP Alkawa, E Bischoff, J Guerrero, JL Handschumacher, MD Sullivan, S Johnson, B Titus, JS Iwamoto, Y Wylie-Sears, J Carpentier, A Levine, RA AF Dal-Blanco, Jacob P. Alkawa, Elena Bischoff, Joyce Guerrero, J. L. Handschumacher, Mark D. Sullivan, Suzanne Johnson, Benjamin Titus, James S. Iwamoto, Yoshiko Wylie-Sears, Jill Carpentier, Alain Levine, Robert A. TI Active Adaptation of the Tethered Mitral Valve: Insights Into a Compensatory Mechanism for Ischemic Mitral Regurgitation SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Dal-Blanco, Jacob P.; Guerrero, J. L.; Handschumacher, Mark D.; Sullivan, Suzanne; Johnson, Benjamin; Titus, James S.; Levine, Robert A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Alkawa, Elena; Iwamoto, Yoshiko] Massachusetts Gen Hosp, Charlestown, MA USA. [Bischoff, Joyce; Wylie-Sears, Jill] Childrens Hosp, Boston, MA 02115 USA. [Carpentier, Alain] Pompidou Hosp, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S649 EP S649 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104502063 ER PT J AU Das, S Xiao, CY Quintero, PP Hessler, K Rosenberg, M Kusakari, Y Matsui, T Ellinor, PT Rosenzweig, A AF Das, Saumya Xiao, Chunyang Quintero, Pablo P. Hessler, Katherine Rosenberg, Michael Kusakari, Yoichiro Matsui, Takashi Ellinor, Patrick T. Rosenzweig, Anthony TI The Serum and Glucocorticold Responsive Kinase-1 (SGK-1) is Activated in Human Cardiomyopathy and Mediates Hypertrophy-associated Electrical Remodeling and Left Ventricular Dysfunction SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Das, Saumya; Ellinor, Patrick T.] Mass Gen Hosp, Boston, MA USA. [Xiao, Chunyang] Beth Israel Deaconess Med Cente, Boston, MA USA. [Quintero, Pablo P.; Hessler, Katherine; Rosenberg, Michael; Kusakari, Yoichiro; Matsui, Takashi; Rosenzweig, Anthony] Beth Israel Deaconess Med Cntr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S339 EP S339 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104500317 ER PT J AU DeFilippis, AP Kramer, HJ Katz, R Wong, N Bertoni, A Carr, JJ Budoff, MJ Blumenthal, RS Nasir, K AF DeFilippis, Andrew P. Kramer, Holly J. Katz, Ronlt Wong, Nathan Bertoni, Alain Carr, Jeffrey J. Budoff, Matthew J. Blumenthal, Roger S. Nasir, Khurrarn TI Microalbuminuria is Associated with Progression of Coronary Atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA) SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Kramer, Holly J.] Loyola Univ, Maywood, IL 60153 USA. [Katz, Ronlt] Univ Washington, Seattle, WA 98195 USA. [Wong, Nathan] Univ Calif Irvine, Irvine, CA USA. [Bertoni, Alain; Carr, Jeffrey J.; Budoff, Matthew J.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Nasir, Khurrarn] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Carr, John/A-1938-2012 OI Carr, John/0000-0002-4398-8237 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S1147 EP S1147 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104504556 ER PT J AU Desai, NR Morrow, DA Jiang, ST Bode, C Rifai, N Cannon, CP Gerszten, RE Sabatine, MS AF Desai, Nihar R. Morrow, David A. Jiang, Songtao Bode, Christoph Rifai, Nader Cannon, Christopher P. Gerszten, Robert E. Sabatine, Marc S. CA TIMI Study Grp TI Copeptin Predicts Cardiovascular Death in STEMI Independent of Clinical Factors and NT-proBNP SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Desai, Nihar R.; Morrow, David A.; Cannon, Christopher P.; Sabatine, Marc S.; TIMI Study Grp] Brigham & Womens Hosp, Boston, MA 02115 USA. [Jiang, Songtao] Harvard Clin Rsch Inst, Boston, MA USA. [Bode, Christoph] Univ Freiburg, Freiburg, Germany. [Rifai, Nader] Childrens Hosp, Boston, MA 02115 USA. [Gerszten, Robert E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 SU 2 BP S762 EP S762 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104502522 ER PT J AU Dewland, TA Pellegrini, CN Wang, YF Marcus, GM Varosy, PD AF Dewland, Thomas A. Pellegrini, Cara N. Wang, Yongfei Marcus, Gregory M. Varosy, Paul D. TI Dual Chamber ICD Selection is Associated with Racial and Socioeconomic Disparities and Increased Complication Rates Among Patients Enrolled in the NCDR ICD Registry SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Dewland, Thomas A.; Pellegrini, Cara N.; Marcus, Gregory M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Wang, Yongfei] Yale Univ, Sch Med, New Haven, CT USA. [Varosy, Paul D.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S834 EP S835 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503055 ER PT J AU Dinh, T Doupis, J Greenman, R Lima, C Giurini, JM Gnardellis, C Khaodhiar, L Lyons, TE Veves, A AF Dinh, Thanh Doupis, John Greenman, Robert Lima, Christina Giurini, John M. Gnardellis, Charalambos Khaodhiar, Lalita Lyons, Thomas E. Veves, Aristidis TI Role of Vascular Reactivity and Inflammation In the Development and Healing of Diabetic Foot Ulceration SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Doupis, John] Joslin Diabet Ctr, Boston, MA 02215 USA. [Dinh, Thanh; Greenman, Robert; Lima, Christina; Giurini, John M.; Lyons, Thomas E.; Veves, Aristidis] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Gnardellis, Charalambos] Lab Appl Stat & Informat, Messolonghl, Greece. [Khaodhiar, Lalita] Boston Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S809 EP S809 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104502711 ER PT J AU Duerschmled, D Canult, M Lievens, D Brill, A Cifuni, SM Patten, I Bader, M Wagner, DD AF Duerschmled, Daniel Canult, Matthias Lievens, Dirk Brill, Alexander Cifuni, Stephen M. Patten, Ian Bader, Michael Wagner, Denise D. TI Platelet Serotonin Receptor Stimulation Induces Shedding of the Adhesion Molecule GPIb alpha SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Duerschmled, Daniel; Canult, Matthias; Lievens, Dirk; Brill, Alexander; Cifuni, Stephen M.; Patten, Ian; Wagner, Denise D.] Immune Dis Inst, Boston, MA USA. [Bader, Michael] Max Delbruck Ctr Mol Med, Berlin, Germany. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S477 EP S477 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104501116 ER PT J AU Ennis, C McGuiness, M Vohora, R Ennis, S Rosenthal, L AF Ennis, Cynthia McGuiness, Matthew Vohora, Rishi Ennis, Stephanie Rosenthal, Lawrence TI Factors Associated with Implantable Cardioverter-Defibrillator Implantation SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Ennis, Cynthia; Vohora, Rishi; Rosenthal, Lawrence] U Mass Mem Med Cntr, Worcester, MA USA. [McGuiness, Matthew] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Ennis, Stephanie] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S1484 EP S1484 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104504840 ER PT J AU Ennis, C McGuiness, M Vohora, R Ennis, S Rosenthal, L AF Ennis, Cynthia McGuiness, Matthew Vohora, Rishi Ennis, Stephanie Rosenthal, Lawrence TI Implantable Cardioverter-Defibrillator Underutilization in Primay Prevention Patients SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Ennis, Cynthia; Vohora, Rishi; Rosenthal, Lawrence] U Mass Mem Med Cntr, Worcester, MA USA. [McGuiness, Matthew] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Ennis, Stephanie] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S1464 EP S1464 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104504748 ER PT J AU Feuchtner, G Jodocy, D Cury, RC Friedrich, G Blumenthal, RS Budoff, M Nasir, K AF Feuchtner, Gudrun Jodocy, Daniel Cury, Ricardo C. Friedrich, Guy Blumenthal, Roger S. Budoff, Matt Nasir, Khurram TI Atherosclerotic Plaque Composition Among patients with Stenotic Coronary Artery Disease on Non Invasive Coronary CT Angiography SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Feuchtner, Gudrun; Jodocy, Daniel; Friedrich, Guy] Innsbruck Med Univ, Innsbruck, Austria. [Cury, Ricardo C.; Nasir, Khurram] Boston Massachusetts Gen Hosp, Boston, MA USA. [Blumenthal, Roger S.] Johns Hopkins Univ, Baltimore, MD USA. [Budoff, Matt] Harbor UCLA Med Ctr, Torrance, CA 90509 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S598 EP S598 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104501639 ER PT J AU Finn, A John, MC Nakazawa, G Raghunathan, C Ezell, T Lajoie, S Xu, X Cheng, Q Kolodgie, F Virmani, R Gold, HK AF Finn, Aloke John, Michael C. Nakazawa, Gaku Raghunathan, Chitra Ezell, Tucker Lajoie, Scott Xu, Xin Cheng, Qi Kolodgie, Frank Virmani, Renu Gold, Herman K. TI Differential Healing in Paclitaxel and Sirolimus-Eluting Stents in Combination with Oral PPAR Gamma Agents: The Role of Drug Interaction in Delayed Healing SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [John, Michael C.; Lajoie, Scott; Gold, Herman K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Finn, Aloke; Raghunathan, Chitra; Ezell, Tucker] Emory Univ, Sch Med, Atlanta, GA USA. [Nakazawa, Gaku; Xu, Xin; Cheng, Qi; Kolodgie, Frank; Virmani, Renu] CVPath, Gaithersburg, MD 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S960 EP S960 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503560 ER PT J AU Forman, DE Giugliano, RP Cannon, CP Morrow, DA Qin, J Antman, EM Braunwald, E AF Forman, Daniel E. Giugliano, Robert P. Cannon, Christopher P. Morrow, David A. Qin, Jie Antman, Elliott M. Braunwald, Eugene TI A Simple TIMI Discharge Risk Score Post ACS Predicts CV Mortality at 2 Years SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Forman, Daniel E.; Giugliano, Robert P.; Cannon, Christopher P.; Morrow, David A.; Antman, Elliott M.; Braunwald, Eugene] Brigham & Womens Hosp, Boston, MA 02115 USA. [Qin, Jie] TIMI Study Grp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S1060 EP S1060 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104504209 ER PT J AU Fox, CS Gona, P Hoffmann, U Salton, CJ Massaro, J Levy, D Larson, M D'Agostino, RB O'Donnell, CJ Manning, WJ AF Fox, Caroline S. Gona, Philimon Hoffmann, Udo Salton, Carol J. Massaro, Joseph Levy, Daniel Larson, Martin D'Agostino, Ralph B. O'Donnell, Christopher J. Manning, Warren J. TI Pericardial Fat, Intra-Thoracic Fat, and Left Ventricular Mass: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Fox, Caroline S.; Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Framingham, MA USA. [Gona, Philimon; Massaro, Joseph; Larson, Martin; D'Agostino, Ralph B.] Boston Univ, Framingham, MA USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Salton, Carol J.; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S1152 EP S1152 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104504576 ER PT J AU Frangiskakis, JM Nilles, KM Grimley, SR Gutmann, R Bloom, HL Dudley, SC Ellinor, PT Shalaby, A Weiss, R Saba, S McNamara, DM AF Frangiskakis, J. M. Nilles, Kathy M. Grimley, Sara R. Gutmann, Rebecca Bloom, Heather L. Dudley, Samuel C. Ellinor, Patrick T. Shalaby, Alaa Weiss, Raul Saba, Samir McNamara, Dennis M. TI African-Americans with Congestive Heart Failure Have More Arrhythmias than Caucasians Independent of the SCN5A S1103Y Genotype SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Frangiskakis, J. M.; Nilles, Kathy M.; Grimley, Sara R.; Gutmann, Rebecca; Shalaby, Alaa; McNamara, Dennis M.] Univ Pittsburgh, Med Cntr, Pittsburgh, PA USA. [Bloom, Heather L.] Emory Univ, Sch Med, Atlanta, GA USA. [Bloom, Heather L.] Atlanta VA Med Cntr, Atlanta, GA USA. [Dudley, Samuel C.] Univ Illinois, Chicago, IL USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shalaby, Alaa] Pittsburgh VA Med Cntr, Pittsburgh, PA USA. [Weiss, Raul] Ohio State Univ, Columbus, OH 43210 USA. [Saba, Samir; McNamara, Dennis M.] Barry London, London, England. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S718 EP S718 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104502342 ER PT J AU Gao, G Shang, LL Zhou, A Zhe, J Gaconnet, G Dudley, SC AF Gao, Go Shang, Lijuan L. Zhou, Anyu Zhe, Jiao Gaconnet, Georgia Dudley, Samuel C., Jr. TI The Possible Mechanism of Acquired Sodium Channel mRNA Splicing Variants with Human Heart Failure SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Gao, Go; Shang, Lijuan L.; Zhe, Jiao; Gaconnet, Georgia; Dudley, Samuel C., Jr.] Univ Chicago, Chicago, IL 60637 USA. [Zhou, Anyu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S873 EP S873 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503209 ER PT J AU Georgiopoulou, VV Kalogeropoulos, AP de Rekeneire, N Rodondi, N Smith, AL Hoffmann, U Kanaya, A Newman, AB Kritchevsky, SB Vasan, RS Wilson, PW Harris, TB Butler, J AF Georgiopoulou, Vasiliki V. Kalogeropoulos, Andreas P. de Rekeneire, Nathalie Rodondi, Nicolas Smith, Andrew L. Hoffmann, Udo Kanaya, Alka Newman, Anne B. Kritchevsky, Stephen B. Vasan, Ramachandran S. Wilson, Peter W. Harris, Tamara B. Butler, Javed TI Serum Resistin Concentrations and Risk of New Onset Heart Failure in the Elderly SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Georgiopoulou, Vasiliki V.; Kalogeropoulos, Andreas P.; Smith, Andrew L.; Wilson, Peter W.; Butler, Javed] Emory Univ, Atlanta, GA 30322 USA. [de Rekeneire, Nathalie] EpiCntr, Paris, France. [Rodondi, Nicolas] Univ Lausanne, Lausanne, Switzerland. [Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kanaya, Alka] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Newman, Anne B.] Univ Pittsburgh, Pittsburgh, PA USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Vasan, Ramachandran S.] Boston Univ, Boston, MA 02215 USA. [Harris, Tamara B.] NIA, Bethesda, MD 20892 USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S1021 EP S1021 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104504058 ER PT J AU Gibson, CM Pride, YB Mohanavelu, S Wiviott, SD Antman, EM Braunwald, E AF Gibson, C. Michael Pride, Yuri B. Mohanavelu, Satishkumar Wiviott, Stephen D. Antman, Elliott M. Braunwald, Eugene TI Angiographic and Clinical Outcomes Among Patients with Acute Coronary Syndrome Presenting with Isolated Anterior ST-Segment Depressions SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Gibson, C. Michael; Mohanavelu, Satishkumar; Wiviott, Stephen D.; Antman, Elliott M.; Braunwald, Eugene] Beth Israel Deaconess Med Ctr, TIMI Study Grp, Boston, MA 02215 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S654 EP S654 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104502079 ER PT J AU Go, AS Fang, MC Udaltsova, N Chang, Y Borowsky, LH Pomernacki, NK Singer, DE AF Go, Alan S. Fang, Margaret C. Udaltsova, Natalia Chang, Yuchiao Borowsky, Leila H. Pomernacki, Niela K. Singer, Daniel E. TI Proteinuria and Reduced Glomerular Filtration Rate Independently Increase Risk of Thromboembolism In Atrial Fibrillation: The ATRIA Study SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Go, Alan S.; Udaltsova, Natalia; Pomernacki, Niela K.] Kaiser Permanente No Calif, Oakland, CA USA. [Fang, Margaret C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Chang, Yuchiao; Borowsky, Leila H.; Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S915 EP S915 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503378 ER PT J AU Goebel, JR Doering, LV Shugarman, LR Asch, SM Sherbourne, CD Lanto, AB Evangelista, LS Nyamathi, AM Maliski, SL Lorenz, KA AF Goebel, Joy R. Doering, Lynn V. Shugarman, Lisa R. Asch, Steven M. Sherbourne, Cathy D. Lanto, Andy B. Evangelista, Lorraine S. Nyamathi, Adeline M. Maliski, Sally L. Lorenz, Karl A. TI Heart Failure, the Hidden Problem of Pain SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Goebel, Joy R.] Calif State Univ Long Beach, Long Beach, CA 90840 USA. [Doering, Lynn V.; Asch, Steven M.; Evangelista, Lorraine S.; Nyamathi, Adeline M.; Maliski, Sally L.; Lorenz, Karl A.] Univ Calif Los Angeles, Los Angeles, CA USA. [Shugarman, Lisa R.; Sherbourne, Cathy D.] RAND Corp, Santa Monica, CA USA. [Lanto, Andy B.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S823 EP S824 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503011 ER PT J AU Green, SM Selzer, F Mulukutla, S Lee, A Joon, LS Kelsey, SF Kip, KE Marroquin, OC AF Green, Sandy M. Selzer, Faith Mulukutla, Suresh Lee, Ashley Joon, Lee S. Kelsey, Sherry F. Kip, Kevin E. Marroquin, Oscar C. TI The Effect of Gender and Race on Outcomes in Patients Undergoing PCI for Proximal Coronary Artery Lesions: A Report from the NHLBI Dynamic Registry of PCI SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Green, Sandy M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Selzer, Faith; Mulukutla, Suresh; Lee, Ashley; Joon, Lee S.; Kelsey, Sherry F.; Marroquin, Oscar C.] Univ Pittsburgh, Pittsburgh, PA USA. [Kip, Kevin E.] Univ S Florida, Tampa, FL USA. RI Marroquin, Oscar/F-2214-2015 OI Marroquin, Oscar/0000-0002-0909-0319 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S632 EP S632 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104501774 ER PT J AU Ho, PM Maddox, TM Wang, L Fihn, SD Jesse, RL Peterson, ED Rumsfeld, JS AF Ho, P. Michael Maddox, Thomas M. Wang, Li Fihn, Stephan D. Jesse, Robert L. Peterson, Eric D. Rumsfeld, John S. TI Proton Pump Inhibitors May Attenuate the Benefits of Clopidogrel among ACS Patients: Empirical Evidence from 3,311 ACS Patients SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Ho, P. Michael; Maddox, Thomas M.; Rumsfeld, John S.] Denver Va Med Ctr, Denver, CO USA. [Wang, Li; Fihn, Stephan D.] Puget Sound VA Med Cntr, Seattle, WA USA. [Jesse, Robert L.] Richmond VA Med Cntr, Richmond, VA USA. [Peterson, Eric D.] Duke Clin Rsch Inst, Durham, NC USA. NR 0 TC 3 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S1165 EP S1165 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104504623 ER PT J AU Jacobson, AF AF Jacobson, Arnold F. TI Impact of Right Ventricular Function on Long-term Survival of Patients with Left Ventricular Dysfunction SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Jacobson, Arnold F.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S953 EP S953 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503529 ER PT J AU Januzzi, JL Bajwa, E Khah, U Gong, M Thompson, BT Christiani, D AF Januzzi, James L., Jr. Bajwa, Ednan Khah, Uzma Gong, Michelle Thompson, B. T. Christiani, David TI An Inflammatory Paradox In Acute Respiratory Distress Syndrome? Plasma C-reactive Protein Concentrations are Strongly Associated with Survival In ARDS SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Januzzi, James L., Jr.; Bajwa, Ednan; Khah, Uzma; Gong, Michelle; Thompson, B. T.; Christiani, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S767 EP S767 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104502542 ER PT J AU Jensen, JK Januzzi, JL Atar, D Mickley, H AF Jensen, Jasper K. Januzzi, James L. Atar, Dan Mickley, Hans TI Prevalence and Importance of Cardiac Arrhythmias after Acute Ischemic Stroke SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Jensen, Jasper K.; Mickley, Hans] Odense Univ Hosp, DK-5000 Odense C, Denmark. [Januzzi, James L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Atar, Dan] Aker Univ Hosp, Div Cardiol, Oslo, Norway. [Atar, Dan] Univ Oslo, Fac Med, Oslo, Norway. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S759 EP S759 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104502512 ER PT J AU Koenig, W Bamberg, F Lee, H Truong, QA Nichols, JH Trischler, G Morrow, DA Nagurney, TJ Hoffmann, U AF Koenig, Wolfgang Bamberg, Fabian Lee, Hang Truong, Quynh A. Nichols, John H. Trischler, Gerlinde Morrow, David A. Nagurney, Tobias J. Hoffmann, Udo TI High-Sensitivity Troponin Reliably Excludes Acute Coronary Syndrome In Patients with Acute Chest Pain: Results from the Rule Out Myocardial Infarction by Computed Tomography (ROMICAT) Study SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Koenig, Wolfgang; Trischler, Gerlinde] Univ Ulm, Ulm, Germany. [Bamberg, Fabian; Lee, Hang; Truong, Quynh A.; Nichols, John H.; Nagurney, Tobias J.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Morrow, David A.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S637 EP S637 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104502017 ER PT J AU Kolm, P Jiang, XZ Spertus, JA Maron, DJ O'Rourke, R Teo, KK Zhang, W Boden, WE Weintraub, WS AF Kolm, Paul Jiang, Xiaozhang Spertus, John A. Maron, David J. O'Rourke, Robert Teo, Koon K. Zhang, Wei Boden, William E. Weintraub, William S. TI Baseline Physical Limitation is Related to Death and MI in the COURAGE Trial SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Kolm, Paul; Jiang, Xiaozhang; Zhang, Wei; Weintraub, William S.] Christiana Care Hlth Syst, Newark, DE USA. [Spertus, John A.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Maron, David J.] Vanderbilt Univ Med Cntr, Nashville, TN USA. [O'Rourke, Robert] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Teo, Koon K.] McMaster Univ, Med Ctr, Hamilton, ON, Canada. [Boden, William E.] Buffalo Gen Hosp, Buffalo, NY 14203 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S1162 EP S1162 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104504610 ER PT J AU Kristo, F Anderson, TJ Hardy, GJ Sinha, S Shen, SQ Tager, AM Gerszten, RE AF Kristo, Fjoralba Anderson, Thomas J. Hardy, Gregory J. Sinha, Sumita Shen, Shiqian Tager, Andrew M. Gerszten, Robert E. TI Both leukocyte and non-leukocyte Blt1 contribute to atherogenesis SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Kristo, Fjoralba; Anderson, Thomas J.; Hardy, Gregory J.; Sinha, Sumita; Shen, Shiqian; Tager, Andrew M.; Gerszten, Robert E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S450 EP S450 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104500811 ER PT J AU Lehman, SJ Bamberg, F Schleft, CL Lee, H Shturman, L Donnelly, PM Rogers, IS Brady, TJ Hoffmann, U AF Lehman, Sam J. Bamberg, Fabian Schleft, Christopher L. Lee, Hang Shturman, Leon Donnelly, Patrick M. Rogers, Ian S. Brady, Thomas J. Hoffmann, Udo TI Progression of Coronary Artery Disease as Assessed by Serial 64-Slice Contrast Enhanced Computed Tomography SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Lehman, Sam J.; Bamberg, Fabian; Schleft, Christopher L.; Lee, Hang; Shturman, Leon; Donnelly, Patrick M.; Rogers, Ian S.; Brady, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S776 EP S777 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104502579 ER PT J AU Levine, YC Michel, T AF Levine, Yehoshua C. Michel, Thomas TI Simvastatin Regulates Insulin Signaling in Endothelial Cells via Activation of AMP-Activated Protein Kinase SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Levine, Yehoshua C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Michel, Thomas] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S404 EP S404 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104500606 ER PT J AU Lewis, GD Shah, RV Martinovic, M Bloch, KD Semigran, MJ AF Lewis, Gregory D. Shah, Ravi V. Martinovic, Maryann Bloch, Kenneth D. Semigran, Marc J. TI Pulmonary Vasoconstriction Occurs out of Proportion to Increases in Pulmonary Capillary Wedge Pressure During Exercise in Heart Failure SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Lewis, Gregory D.; Shah, Ravi V.; Martinovic, Maryann; Bloch, Kenneth D.; Semigran, Marc J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S953 EP S954 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503532 ER PT J AU Lipshultz, SE Scully, RE Lipsitz, SR Sallan, SE Silverman, LB Miller, TL Barry, EV Asselin, BL Athale, U Clavell, LA Larsen, E Moghrabi, A Samson, Y Schorin, MA Orav, EJ Colan, SD AF Lipshultz, Steven E. Scully, Rebecca E. Lipsitz, Stuart R. Sallan, Stephen E. Silverman, Lewis B. Miller, Tracie L. Barry, Elly V. Asselin, Barbara L. Athale, Uma Clavell, Luis A. Larsen, Eric Moghrabi, Albert Samson, Yvan Schorin, Marshall A. Orav, E. John Colan, Steven D. TI Dexrazoxane Cardioprotection In Doxorubicin-Treated Children with Acute Lymphoblastic Leukemia: Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium Protocol 95-01 Randomized Controlled SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Lipshultz, Steven E.; Scully, Rebecca E.; Miller, Tracie L.] Univ Miami, Miami, FL USA. [Lipsitz, Stuart R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sallan, Stephen E.; Silverman, Lewis B.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Barry, Elly V.] Genzyme Corp, Cambridge, MA USA. [Asselin, Barbara L.] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Athale, Uma] McMaster Univ, Hamilton, ON, Canada. [Clavell, Luis A.] San Jorge Childrens Hosp, Santurce, PR USA. [Larsen, Eric] Maine Childrens Canc Program, Portland, ME USA. [Moghrabi, Albert] Hop St Justine, Montreal, PQ H3T 1C5, Canada. [Samson, Yvan] Univ Quebec, Ctr Hosp, Quebec City, PQ, Canada. [Schorin, Marshall A.] Inova Fairfax Hosp, Fairfax, VA USA. [Orav, E. John] Brigham & Womens Hosp, Boston, MA 02115 USA. [Colan, Steven D.] Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S1055 EP S1056 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104504193 ER PT J AU Ly, H Hoshino, K Pomerantseva, I Kawase, Y Yoneyama, R Takewa, Y Vooght, C Frangioni, JV Hajjar, RJ AF Ly, Hung Hoshino, Kozo Pomerantseva, Irina Kawase, Yoshiaki Yoneyama, Ryuichi Takewa, Yoshiaki Vooght, Carrie Frangioni, John V. Hajjar, Roger J. TI In Vivo Myocardial Distribution of Adult Stem Cells Immediately Following Intracoronary Delivery In a Swine Model of Myocardial Infarction SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Ly, Hung] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Hoshino, Kozo; Kawase, Yoshiaki; Yoneyama, Ryuichi; Takewa, Yoshiaki; Hajjar, Roger J.] Mt Sinai Sch Med, New York, NY USA. [Pomerantseva, Irina] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vooght, Carrie; Frangioni, John V.] Beth Israel Deaconess Med Cntr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S537 EP S537 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104501375 ER PT J AU Maree, AO Vangjeli, C Jneid, H Cox, D Shields, DC Fitzgerald, DJ AF Maree, Andrew O. Vangjeli, Ciara Jneid, Hani Cox, Dermot Shields, Denis C. Fitzgerald, Desmond J. TI G-Protein Beta3 Subunit Polymorphism (GNB3 825T) Carriage is Associated with Increased Bleeding in the Orbofiban in Patients with Unstable Coronary Syndromes-Thrombolysis in Myocardial Infarction (OPUS-TIMI) 16 SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Maree, Andrew O.] Boston Univ, Med Ctr, Boston, MA USA. [Vangjeli, Ciara; Cox, Dermot] Royal Coll Surgeons Ireland, Dublin 2, Ireland. [Jneid, Hani] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shields, Denis C.; Fitzgerald, Desmond J.] Univ Coll Dublin, Dublin 2, Ireland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S816 EP S816 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104502738 ER PT J AU Marques, J Mendoza, I Mendoza-Britto, I Palacios, I Noya, B Moleiro, F AF Marques, Juan Mendoza, Ivan Mendoza-Britto, Ivan Palacios, Igo Noya, Belkisyole Moleiro, Federico TI A New Epidemic of Myocarditis. Acute Chagas Disease due to Oral Infection in a Major Latin America City. Electrocardiographic Changes in 121 Cases SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Marques, Juan; Mendoza, Ivan; Noya, Belkisyole; Moleiro, Federico] Cent Univ Venezuela, Caracas, Venezuela. [Mendoza-Britto, Ivan] Albert Einstein Hosp, Philadelphia, PA USA. [Palacios, Igo] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S676 EP S676 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104502170 ER PT J AU Marroquin, OC Selzer, F Mulukutla, SR Green, SM Lee, JS Anderson, WD Smith, C Kelsey, SF Kip, KE AF Marroquin, Oscar C. Selzer, Faith Mulukutla, Suresh R. Green, Sandy M. Lee, Joon S. Anderson, William D. Smith, Conrad Kelsey, Sherry F. Kip, Kevin E. TI Incremental Benefit of Drug-Eluting Stents when Used for Proximal Coronary Artery Lesions: A Report from the NHLBI Dynamic Registry SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Marroquin, Oscar C.; Mulukutla, Suresh R.; Lee, Joon S.; Anderson, William D.; Smith, Conrad] Presbyterian Univ Hosp, UPMC, Pittsburgh, PA 15213 USA. [Selzer, Faith; Kelsey, Sherry F.] Univ Pittsburgh, Pittsburgh, PA USA. [Kip, Kevin E.] Univ S Florida, Tampa, FL USA. [Green, Sandy M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Marroquin, Oscar/F-2214-2015 OI Marroquin, Oscar/0000-0002-0909-0319 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S631 EP S632 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104501773 ER PT J AU Mega, JL Wiviott, SD Mohanavolu, S Nicolau, JC McCabe, CH Antman, EM Braunwald, E AF Mega, Jessica L. Wiviott, Stephen D. Mohanavolu, Satishkumar Nicolau, Jose C. McCabe, Carolyn H. Antman, Elliott M. Braunwald, Eugene TI Cardiovascular Outcomes of Women and Men with Acute Coronary Syndromes and Angiographically Confirmed Epicardial Coronary Artery Disease In TRITON-TIMI 38 SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Mega, Jessica L.; Wiviott, Stephen D.; Antman, Elliott M.; Braunwald, Eugene] Brigham & Womens Hosp, Boston, MA 02115 USA. [Mohanavolu, Satishkumar; McCabe, Carolyn H.] TIMI Study Grp, Boston, MA USA. [Nicolau, Jose C.] Univ Sao Paulo, Heart Inst InCor HC, Sao Paulo, Brazil. RI Nicolau, Jose/E-1487-2012 NR 0 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S967 EP S967 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503583 ER PT J AU Mehta, RH Sheng, S O'Brien, SM Gammie, JS Grover, FL Ferguson, TB Peterson, ED AF Mehta, Rajendra H. Sheng, Shubin O'Brien, Sean M. Gammie, James S. Grover, Frederick L. Ferguson, T. Bruce, Jr. Peterson, Eric D. CA Soc Thoracic Surg Natl Cardiac Dat TI Reoperation for Bleeding among 528,279 Patients Undergoing Coronary Artery Bypass Surgery: The Society of Thoracic Surgeons National Database Experience SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Mehta, Rajendra H.; Sheng, Shubin; O'Brien, Sean M.; Peterson, Eric D.] Duke Clin Rsch Inst, Durham, NC USA. [Gammie, James S.] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. [Grover, Frederick L.] Denver VA Med Ctr, Denver, CO USA. [Grover, Frederick L.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Ferguson, T. Bruce, Jr.] E Carolina Univ, Brodie Sch Med, Greenville, NC USA. RI O'Brien, Sean/H-6268-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S940 EP S940 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503477 ER PT J AU Memisoglu, A Wittes, J Iskandrian, AE Kaul, S Porter, TR Senior, R Monaghan, MJ Udelson, JE Walovitch, RC Picard, MH AF Memisoglu, Asli Wittes, Janet Iskandrian, Ami E. Kaul, Sanjiv Porter, Thomas R. Senior, Roxy Monaghan, Mark J. Udelson, James E. Walovitch, Richard C. Picard, Michael H. TI Perfusion Stress Echocardiography with Perflubutane Polymer Microspheres Provides Incremental Predictive Value for Coronary Artery Disease Over Clinical Risk Factors SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Memisoglu, Asli; Walovitch, Richard C.] Acusphere Inc, Watertown, MA USA. [Wittes, Janet] Stat Collaborat, Washington, DC USA. [Iskandrian, Ami E.] Univ Alabama Birmingham, Birmingham, AL USA. [Kaul, Sanjiv] Oregon Hlth & Sci Univ, Portland, OR USA. [Porter, Thomas R.] Univ Nebraska Med Ctr, Omaha, NE USA. [Senior, Roxy] Northwick Pk Hosp & Clin Res Ctr, Harrow, Middx, England. [Monaghan, Mark J.] Kings Coll Hosp London, London, England. [Udelson, James E.] Tufts New England Med Cntr, Boston, MA USA. [Picard, Michael H.] Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 SU 2 BP S934 EP S934 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503451 ER PT J AU Minamishima, S De Yu, J Bougaki, M Adrie, C Minamishima, YA Lefer, DJ Ichinose, F AF Minamishima, Shizuka De Yu, Jia Bougaki, Masahiko Adrie, Christophe Minamishima, Yoji A. Lefer, David J. Ichinose, Fumito TI Hydrogen Sulfide Improves Outcome after Cardiac Arrest and Cardiopulmonary Resuscitation in Mouse SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Minamishima, Shizuka; De Yu, Jia; Bougaki, Masahiko; Adrie, Christophe; Ichinose, Fumito] Massachusetts Gen Hosp, Charlestown, MA USA. [Minamishima, Yoji A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lefer, David J.] Albert Einstein Coll Med, New York, NY USA. RI Minamishima, Yoji/E-5380-2010 OI Minamishima, Yoji/0000-0001-7995-9318 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S1446 EP S1447 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104504672 ER PT J AU Nallamshetty, S Yi, BA Stone, J O'Gara, PT MaCare, CA AF Nallamshetty, Shriram Yi, Byungdoo A. Stone, James O'Gara, Patrick T. MaCare, Calurn A. TI Biatrial Enlargement and Recurrent Cardioembolism in a 55 Year-Old Man with Atrial Fibrillation SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Nallamshetty, Shriram; Yi, Byungdoo A.; Stone, James; MaCare, Calurn A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [O'Gara, Patrick T.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S648 EP S648 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104502060 ER PT J AU Noseworthy, PA Rosenberg, M Ruskin, JN Palacios, IF Mela, T Fifer, MA Das, S AF Noseworthy, Peter A. Rosenberg, Michael Ruskin, Jeremy N. Palacios, Igor F. Mela, Theofanie Fifer, Michael A. Das, Saumya TI Ventricular Arrhythmia Following Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy: Clinical Predictors of Events SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Noseworthy, Peter A.; Ruskin, Jeremy N.; Palacios, Igor F.; Mela, Theofanie; Fifer, Michael A.; Das, Saumya] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rosenberg, Michael] Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S594 EP S594 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104501624 ER PT J AU Owens, DS Budoff, MJ Nasir, K Katz, R Takasu, J Carr, JJ Shavelle, DM Kronmal, RA Probstfield, JL O'Brien, KD AF Owens, David S. Budoff, Matthew J. Nasir, Khurram Katz, Ronit Takasu, Junichiro Carr, J. J. Shavelle, David M. Kronmal, Richard A. Probstfield, Jeffrey L. O'Brien, Kevin D. TI Aortic Valve Calcification Is Prospectively Associated with Primary Cardiovascular Events Independent of Subclinical Coronary Artery Disease Severity: the Multi-Ethnic Study of Atherosclerosis (MESA) SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Owens, David S.; Katz, Ronit; Kronmal, Richard A.; Probstfield, Jeffrey L.; O'Brien, Kevin D.] Univ Washington, Seattle, WA 98195 USA. [Budoff, Matthew J.; Takasu, Junichiro; Shavelle, David M.] Harbor UCLA Med Ctr, Los Angeles BioMed Rsch Inst, Los Angeles, CA USA. [Nasir, Khurram] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Carr, J. J.] Wake Forest Univ, Winston Salem, NC 27109 USA. RI Carr, John/A-1938-2012 OI Carr, John/0000-0002-4398-8237 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S995 EP S995 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503694 ER PT J AU Patel, AM D'Avila, A Neuzil, P Kim, SJ Morgan, D Afonso, V Ruskin, JN Reddy, VY AF Patel, Anshul M. D'Avila, Andre Neuzil, Petr Kim, Steven J. Morgan, Dennis Afonso, Valtino Ruskin, Jeremy N. Reddy, Vivek Y. TI The Effect of Step-Wise Atrial Ablation on the Substrate for Persistent Atrial Fibrillation SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Patel, Anshul M.] St Josephs Hosp, Atlanta, GA USA. [D'Avila, Andre; Reddy, Vivek Y.] Univ Miami, Miami, FL USA. [Neuzil, Petr] Na Homolce Hosp, Prague, Czech Republic. [Kim, Steven J.; Morgan, Dennis; Afonso, Valtino] St Jude Med, St Paul, MN USA. [Ruskin, Jeremy N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI d'Avila, Andre/A-7693-2009; d'Avila, Andre Luiz/F-8009-2010 OI d'Avila, Andre Luiz/0000-0001-8769-1411 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S588 EP S589 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104501601 ER PT J AU Perry, KJ Bloch, KD MacRae, CA Shin, JT AF Perry, Kenneth J. Bloch, Kenneth D. MacRae, Calum A. Shin, Jordan T. TI Paradoxical Augmentation Of BMP-signaling In Vivo Following Loss Of BMPR2 In Zebrafish Is Mediated Through Recruitment Of An Alternative Type 2 Receptor SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Perry, Kenneth J.; MacRae, Calum A.; Shin, Jordan T.] Massachusetts Gen Hosp, Charlestown, MA USA. [Bloch, Kenneth D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S506 EP S506 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104501246 ER PT J AU Pijnappels, DA Stadtfeld, M Zeng, M Yu, E Fujiwara, Y Wang, GW Orkin, SH Jackson-Grusby, L Hochedlinger, K Wu, SM AF Pijnappels, Daniel A. Stadtfeld, Matthias Zeng, Min Yu, Esther Fujiwara, Yuko Wang, Guangwen Orkin, Stuart H. Jackson-Grusby, Laurie Hochedlinger, Konrad Wu, Sean M. TI Derivation and Functional Characterization of Nkx2.5+Cardiac Progenitor Cells from Mouse Induced Pluripotent Stem Cells SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Pijnappels, Daniel A.; Zeng, Min; Yu, Esther] Massachusetts Gen Hosp, Cardiovasc Rsch Cntr, Boston, MA 02114 USA. [Stadtfeld, Matthias; Hochedlinger, Konrad] Massachusetts Gen Hosp, Cntr Regenerat Med, Boston, MA 02114 USA. [Fujiwara, Yuko; Orkin, Stuart H.] Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. [Wang, Guangwen; Jackson-Grusby, Laurie] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Wu, Sean M.] Harvard Stem Cell Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S428 EP S428 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104500714 ER PT J AU Potente, M Guarani, V Baldessari, D Ejaz, S Mostoslavsky, R Fleming, I Mione, M Alt, FW Zeiher, AM Dimmeler, S AF Potente, Michael Guarani, Virginia Baldessari, Danila Ejaz, Sohail Mostoslavsky, Raul Fleming, Ingrid Mione, Marina Alt, Frederick W. Zeiher, Andreas M. Dimmeler, Stefanie TI Signal-Responsive Repression of Notch1 Signaling by the Sirt1 Deacetylase Regulates Sprouting Angiogenesis SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Baldessari, Danila; Mione, Marina] IFOM FIRC Inst Mol Oncol, Milan, Italy. [Mostoslavsky, Raul] Massachusetts Gen Hosp Canc Cntr, Boston, MA USA. [Alt, Frederick W.] CBR Inst BioMed Rsch, Howard Hughes Med Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S460 EP S461 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104501045 ER PT J AU Pride, YB Canto, JG Frederick, PD Gibson, CM AF Pride, Yuri B. Canto, John G. Frederick, Paul D. Gibson, C. Michael TI Outcomes Among Patients with Non-ST-Segment Elevation Myocardial Infarction Presenting to Interventional Hospitals With and Without On-Site Cardiac Surgery: A NRMI 5 Analysis SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Pride, Yuri B.; Gibson, C. Michael] BIDMC, Boston, MA USA. [Canto, John G.] Cntr Cardiovascular Prevent, Watson Clin, Lakeland, FL USA. [Frederick, Paul D.] ICON Lifecycle Sci Grp, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S1163 EP S1163 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104504617 ER PT J AU Raffel, OC Tearney, GJ Chia, S Gauthier, DD Bouma, BE Jang, IK AF Raffel, Owen C. Tearney, Guillermo J. Chia, Stanley Gauthier, Denise DeJoseph Bouma, Brett E. Jang, Ik-Kyung TI Distance From the Coronary Ostium as a Predictor of Vulnerable Plaque Morphology; An In-vivo Optical Coherence Tomography Study SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S627 EP S627 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104501755 ER PT J AU Reddy, VY Doshi, SK d'Avila, A Neuzil, P Kim, YH AF Reddy, Vivek Y. Doshi, Shephal K. d'Avila, Andre Neuzil, Petr Kim, Young-Hoon TI Visually-Guided Ablation of the Pulmonary Venous Antrum Using a Compliant Balloon Catheter SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Reddy, Vivek Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Doshi, Shephal K.] St Johns Hosp, Santa Monica, CA USA. [d'Avila, Andre] Univ Miami, Miami, FL USA. [Neuzil, Petr] Homolka Hosp, Prague, Czech Republic. [Kim, Young-Hoon] Massachusetts Gen Hosp, Seoul, South Korea. RI d'Avila, Andre/A-7693-2009; d'Avila, Andre Luiz/F-8009-2010 OI d'Avila, Andre Luiz/0000-0001-8769-1411 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S923 EP S924 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503410 ER PT J AU Rehman, SR van Kimmenade, RR Januzzi, JL AF Rehman, Shafiq R. van Kimmenade, Roland R. Januzzi, James L. TI Combining Amino-Terminal Pro-B Type Natriuretic Peptide with the Interleukin Receptor Family Member ST2 for Optimal Long-Term Risk Prediction in Acute Dyspnea: Multimarker Results at 4 Years from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Study SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Rehman, Shafiq R.; van Kimmenade, Roland R.; Januzzi, James L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Kimmenade, R.R.J./L-4432-2015 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S871 EP S871 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503200 ER PT J AU Ren, B Mukhopadhyay, A Lanahan, AA Zhuang, ZW Moodie, KL Peterson, RT Simons, M AF Ren, Bin Mukhopadhyay, Arpita Lanahan, Anthony A. Zhuang, Zhen W. Moodie, Karen L. Peterson, Randall T. Simons, Michael TI Recovery of Erk Signaling Restores Defective Angiogenesis and Arteriogenesis in Synectin-Deficient Animals SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Ren, Bin; Lanahan, Anthony A.; Zhuang, Zhen W.; Moodie, Karen L.; Simons, Michael] Dartmouth Med Sch, Lebanon, NH USA. [Mukhopadhyay, Arpita; Peterson, Randall T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S576 EP S576 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104501547 ER PT J AU Rengifo-Moreno, P Cruz-Gonzalez, I Cubeddu, RJ Sanchez-Ledezma, M Ning, MM McNamara, M Buonanno, F Lnglessis-Azuaje, I Demirjian, Z Palacios, IF AF Rengifo-Moreno, Pablo Cruz-Gonzalez, Ignacio Cubeddu, Roberto J. Sanchez-Ledezma, Maria Ning, Mingming McNamara, Maryellen Buonanno, Ferdinando Lnglessis-Azuaje, Ignacio Demirjian, Zareh Palacios, Igor F. TI Efficacy And Safety Of Percutaneous Patent Foramen Ovate Closure In Patients With Thrombophilia SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Rengifo-Moreno, Pablo; Cruz-Gonzalez, Ignacio; Cubeddu, Roberto J.; Sanchez-Ledezma, Maria; Ning, Mingming; McNamara, Maryellen; Buonanno, Ferdinando; Lnglessis-Azuaje, Ignacio; Demirjian, Zareh; Palacios, Igor F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S904 EP S904 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503333 ER PT J AU Rieber, J Hoffmann, U Hetterich, H Bamberg, F Achenbach, S AF Rieber, Johannes Hoffmann, Udo Hetterich, Holger Bamberg, Fabian Achenbach, Stefan TI Impact of Different Post-Processing Techniques on Inter-Observer Agreement for Coronary CTA. Results from a Multicenter Trial SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Hoffmann, Udo; Bamberg, Fabian] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rieber, Johannes; Hetterich, Holger] Dept Cardiol, Munich, Germany. [Achenbach, Stefan] Univ Erlangen Nurnberg, Erlangen, Germany. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S1063 EP S1063 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104504224 ER PT J AU Rivera, JJ Nasir, K Blumenthal, RS Yoon, YE Chang, SA Choi, EK Choi, SI Chun, EJ Choi, DJ Chang, HJ AF Rivera, Juan J. Nasir, Khurram Blumenthal, Roger S. Yoon, Yeonyee E. Chang, Song A. Choi, Eue-Keun Choi, Sang-Il Chun, Eun-Ju Choi, Dong-Joo Chang, Hyuk-Jae TI Traditional Risk Factors & Coronary Plaque Composition Assessed by Non Invasive CT Angiography in Asymptomatic Individuals SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Nasir, Khurram] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rivera, Juan J.; Blumenthal, Roger S.] Johns Hopkins Univ, Baltimore, MD USA. [Yoon, Yeonyee E.; Chang, Song A.; Choi, Eue-Keun; Choi, Sang-Il; Chun, Eun-Ju; Choi, Dong-Joo; Chang, Hyuk-Jae] Seoul Natl Univ, Bundang Hosp, Seoul, South Korea. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S776 EP S776 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104502577 ER PT J AU Rivera, JJ Nasir, K Yoon, Y Chang, SA Choi, EK Choi, SI Chun, EJ Chol, DJ Blumenthal, R Chang, HJ AF Rivera, Juan J. Nasir, Khurram Yoon, Yeonyee Chang, Song A. Choi, Eue-Keun Choi, Sang-Il Chun, Eun-Ju Chol, Dong-Joo Blumenthal, Roger Chang, Hyuk-Jae TI Cardiac CT Assessment of Atherosclerotic Plaque SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Rivera, Juan J.; Blumenthal, Roger] Johns Hopkins Univ, Baltimore, MD USA. [Nasir, Khurram] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yoon, Yeonyee; Chang, Song A.; Choi, Eue-Keun; Choi, Sang-Il; Chun, Eun-Ju; Chol, Dong-Joo; Chang, Hyuk-Jae] Seoul Natl Univ, Bundang Hosp, Seoul, South Korea. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S775 EP S776 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104502575 ER PT J AU Rodriguez, A Maree, A Tarragona, S Fernandez-Pereira, C Rodriguez-Granillo, AM Rodriguez-Granillo, GA Santaera, O Mieres, J Kukreja, N Antoniucci, D Palacios, IF Serruys, PW AF Rodriguez, Alfredo Maree, Andrew Tarragona, Sonia Fernandez-Pereira, Carlos Rodriguez-Granillo, Alfredo M. Rodriguez-Granillo, Gaston A. Santaera, Omar Mieres, Juan Kukreja, Neville Antoniucci, David Palacios, Igor F. Serruys, Patrick W. TI Percutaneous Coronary Intervention with Bare Metal Stents and Oral Sirolimus has Comparable Safety and Efficacy to Treatment with Drug Eluting Stents but with Significant Cost Saving : Long Term Follow Up Results From the Randomized, Controlled ORAR III (Oral Rapamycin in Argentina) Study SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Maree, Andrew] Boston Univ, Boston, MA 02215 USA. [Rodriguez, Alfredo] Otamendi Hosp, Buenos Aires, DF, Argentina. [Tarragona, Sonia] Argentina Minist Hlth, Buenos Aires, DF, Argentina. [Fernandez-Pereira, Carlos] Adrogue Clin, Buenos Aires, DF, Argentina. [Rodriguez-Granillo, Alfredo M.] Cardiovasc Rsch Cntr CECI, Buenos Aires, DF, Argentina. [Rodriguez-Granillo, Gaston A.; Mieres, Juan] Otamendi Hosp, Buenos Aires, DF, Argentina. [Santaera, Omar] Argentina Soc Cardiovasc Intervent CACI, Buenos Aires, DF, Argentina. [Kukreja, Neville; Serruys, Patrick W.] Erasmus Thorax Cntr, Rotterdam, Netherlands. [Antoniucci, David] Careggi Hosp, Florence, Italy. [Palacios, Igor F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S1051 EP S1051 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104504175 ER PT J AU Rogers, IS Moloo, J Chae, CU Blankstein, R Bamberg, F Pena, AJ Seneviratne, SK Truong, QA Nichols, JH Ferencik, M Brown, DF Nagurney, JT Brady, TJ Hoffmann, U AF Rogers, Ian S. Moloo, Jamaluddin Chae, Claudia U. Blankstein, Ron Bamberg, Fabian Pena, Antonio J. Seneviratne, Sujith K. Truong, Quynh A. Nichols, John H. Ferencik, Maros Brown, David F. Nagurney, John T. Brady, Thomas J. Hoffmann, Udo TI Cardiac CT Angiography vs. SPECT Perfusion Imaging for the Evaluation of Patients with Acute Chest Pain SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Rogers, Ian S.; Moloo, Jamaluddin; Chae, Claudia U.; Blankstein, Ron; Bamberg, Fabian; Pena, Antonio J.; Seneviratne, Sujith K.; Truong, Quynh A.; Nichols, John H.; Ferencik, Maros; Brown, David F.; Nagurney, John T.; Brady, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S995 EP S995 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503697 ER PT J AU Rosenfield, KA White, CJ Jones, PG Spertus, JA Cates, CU Ho, KK Jeff, MA Kcroshetz, WJ Caldwell, SP Brindis, RG Anderson, HV AF Rosenfield, K. A. White, C. J. Jones, P. G. Spertus, J. A. Cates, C. U. Ho, K. K. Jeff, M. A. Kcroshetz, W. J. Caldwell, S. P. Brindis, R. G. Anderson, H. V. TI Relationship Between Procedure Indications and Outcomes of Carotid Artery Stenting: Preliminary Results from the CARE Registry SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Rosenfield, K. A.; Jeff, M. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [White, C. J.] Ochsner Clin & Alton Ochsner Med Fdn, New Orleans, LA USA. [Jones, P. G.; Spertus, J. A.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Cates, C. U.] Emory Univ, Atlanta, GA 30322 USA. [Ho, K. K.] Beth Israel Hosp, Boston, MA USA. [Kcroshetz, W. J.] NINDS, Bethesda, MD 20892 USA. [Caldwell, S. P.] Amer Coll Cardiol, Washington, DC USA. [Brindis, R. G.] Kaiser Permanente, Oakland, CA USA. [Anderson, H. V.] Univ Texas HSC, Houston, TX USA. RI White, Christopher/J-6686-2012 OI White, Christopher/0000-0001-8618-7539 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S907 EP S907 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503343 ER PT J AU Schnabel, RB Sullivan, LM Levy, D Pencina, MJ Massaro, JM D'Agostino, RB Newton-Cheh, C Magnani, JW Tadros, TM Kennel, W Wang, TJ Ellinor, PT Wolf, PA Vasan, RS Benjamin, EJ AF Schnabel, Renate B. Sullivan, Lisa M. Levy, Daniel Pencina, Michael J. Massaro, Joseph M. D'Agostino, Ralph B. Newton-Cheh, Christopher Magnani, Jared W. Tadros, Thomas M. Kennel, William Wang, Thomas J. Ellinor, Patrick T. Wolf, Philip A. Vasan, Ramachandran S. Benjamin, Emella J. TI Development of a Risk Score for Incident Atrial Fibrillation in the Community; the Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Schnabel, Renate B.; Pencina, Michael J.; Tadros, Thomas M.; Kennel, William; Wang, Thomas J.; Wolf, Philip A.; Vasan, Ramachandran S.; Benjamin, Emella J.] NHLBI, Framingham Heart Study, Boston, MA USA. [Sullivan, Lisa M.; D'Agostino, Ralph B.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [D'Agostino, Ralph B.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Newton-Cheh, Christopher] Broad Inst Harvard, Cambridge, MA USA. [Newton-Cheh, Christopher] MIT, Cambridge, MA 02139 USA. [Magnani, Jared W.] Boston Univ, Dept Cardiol, Boston, MA 02215 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Rsch Ctr, Boston, MA 02114 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S1089 EP S1090 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104504328 ER PT J AU Schulz, C Leuschen, NV Frohlich, T Lorenz, M Arnold, GJ Massberg, S AF Schulz, Christian Leuschen, Nina V. Froehlich, Thomas Lorenz, Michael Arnold, Georg J. Massberg, Steffen TI Differential Platelet Proteome Analysis Following Specific Activation Of Glycoprotein VI SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Schulz, Christian; Lorenz, Michael; Massberg, Steffen] Tech Univ Munich, Ctr Heart, Munich, Germany. [Leuschen, Nina V.] Univ Cologne, Inst Genet, D-5000 Cologne, Germany. [Froehlich, Thomas; Arnold, Georg J.] Univ Munich, Gene Cntr, Lab Funct Genome Anal, Munich, Germany. [Massberg, Steffen] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Massberg, Steffen] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RI Frohlich, Thomas/C-6735-2011 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S477 EP S477 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104501117 ER PT J AU Schulz, C Schafer, A von Bruhl, ML Pelisek, J Stolla, M Bauersachs, J Massberg, S AF Schulz, Christian Schaefer, Andreas von Bruehl, Marie L. Pelisek, Jaroslav Stolla, Moritz Bauersachs, Johann Massberg, Steffen TI Fractalkine Modulates Recruitment Of Monocytic Cells Following Rupture Of Atherosclerotic Plaque SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Schulz, Christian; von Bruehl, Marie L.; Stolla, Moritz; Massberg, Steffen] Tech Univ Munich, Ctr Heart, Munich, Germany. [Schaefer, Andreas; Bauersachs, Johann] Univ Wurzburg, Univ Klinikum, Med Klin & Poliklin 1, Wurzburg, Germany. [Pelisek, Jaroslav] Tech Univ Munich, Klinikum Rechts Isar, Clin Vasc Surg, Munich, Germany. [Massberg, Steffen] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Massberg, Steffen] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S471 EP S472 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104501093 ER PT J AU Seneviratne, SK Rogers, IS Bamberg, F Shapiro, MD Truong, Q Lehman, SJ Nichols, JH Chae, CU Hoffmann, U AF Seneviratne, Sujith K. Rogers, Ian S. Bamberg, Fabian Shapiro, Michael D. Truong, Quynh Lehman, Sam J. Nichols, John H. Chae, Claudia U. Hoffmann, Udo TI Resting Regional Left Ventricular Function by 64-slice Cardiac CT adds Incremental Value to Coronary Plaque and Stenosis In Predicting Acute Coronary Syndrome in Patients with Acute Chest Pain SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Seneviratne, Sujith K.; Rogers, Ian S.; Bamberg, Fabian; Shapiro, Michael D.; Truong, Quynh; Lehman, Sam J.; Nichols, John H.; Chae, Claudia U.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S993 EP S993 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503688 ER PT J AU Sherwood, MW Morrow, DA Scirica, BM Jiang, S Bode, C Rifai, N Gerszten, RE Cannon, CP Braunwald, E Sabatine, MS AF Sherwood, Matthew W. Morrow, David A. Scirica, Benjamin M. Jiang, Songtao Bode, Christoph Rifai, Nader Gerszten, Robert E. Cannon, Christopher P. Braunwald, Eugene Sabatine, Marc S. TI Baseline Troponin Levels Predict 30 Day CV Mortality in STEMI Independent of Clinical and Electrocardiographic Factors: Analysis from CLARITY-TIMI 28 SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Sherwood, Matthew W.; Morrow, David A.; Scirica, Benjamin M.; Jiang, Songtao; Cannon, Christopher P.; Braunwald, Eugene; Sabatine, Marc S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TMI Study Grp, Boston, MA 02115 USA. [Bode, Christoph] Univ Freiburg, Freiburg, Germany. [Rifai, Nader] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA. [Gerszten, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S636 EP S636 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104502014 ER PT J AU Singer, DE Chang, YC Fang, MC Borowsky, LH Pomernacki, NK Udaltsova, N Go, AS AF Singer, Daniol E. Chang, Yuchiao Fang, Margaret C. Borowsky, Leila H. Pomernacki, Niels K. Udaltsova, Natalia Go, Alan S. TI Warfarin INR-Response Curves in Subgroups of Patients with Nonvalvular Atrial Fibrillation: Should Target Anticoagulation Intensity be Adjusted for Patient Characteristics?: The ATRIA Study SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Singer, Daniol E.; Chang, Yuchiao; Borowsky, Leila H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fang, Margaret C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Pomernacki, Niels K.; Udaltsova, Natalia; Go, Alan S.] Kaiser Permanente, Div Rsch, Oakland, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S757 EP S757 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104502504 ER PT J AU Singh, SM Heist, EK Donaldson, DM Mela, T Ruskin, JN Mansour, MC AF Singh, Sheldon M. Heist, E. Kevin Donaldson, David M. Mela, Theofanie Ruskin, Jeremy N. Mansour, Moussa C. TI Intracardiac Echocardiography From Within the Left Atrium Improves the Accuracy of Image Integration During Catheter Ablation of Atrial Fibrillation SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Singh, Sheldon M.; Heist, E. Kevin; Donaldson, David M.; Mela, Theofanie; Ruskin, Jeremy N.; Mansour, Moussa C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S980 EP S980 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503632 ER PT J AU Singh, TP Givertz, M Semigran, M Costantino, F DeNofrio, D Gauvreau, K AF Singh, Tajinder P. Givertz, Michael Semigran, Marc Costantino, Fred DeNofrio, David Gauvreau, Kimberlee TI Association of Race and Socioeconomic Position with Graft Failure in Heart Transplant Recipients SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Singh, Tajinder P.; Gauvreau, Kimberlee] Childrens Hosp, Boston, MA 02115 USA. [Givertz, Michael] Brigham & Womens Hosp, Boston, MA 02115 USA. [Semigran, Marc] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Costantino, Fred] New Engalnd Organ Bank, Newton, MA USA. [DeNofrio, David] Tufts Mod Cntr, Newton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S801 EP S801 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104502677 ER PT J AU Solis-Martin, J Johnson, B Guerrero, JL Handschumacher, M Sullivan, S Braithwaite, GJC Muratoglu, OK Vlahakes, GJ Levine, RA Hung, J AF Solis-Martin, Jorge Johnson, Benjamin Guerrero, J. Luis Handschumacher, Mark Sullivan, Suzanne Braithwaite, G. J. C. Muratoglu, O. K. Vlahakes, G. J. Levine, Robert A. Hung, Judy TI Polymer Injection Therapy to Reverse Remodel the Papillary Muscles: Efficacy In Reducing Mitral Regurgitation in a Chronic Ischemic Model SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Solis-Martin, Jorge; Johnson, Benjamin; Guerrero, J. Luis; Handschumacher, Mark; Sullivan, Suzanne; Muratoglu, O. K.; Vlahakes, G. J.; Levine, Robert A.; Hung, Judy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Braithwaite, G. J. C.] Cambridge Polymer INC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S647 EP S647 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104502055 ER PT J AU Spreafico, M Peyvandi, F Foco, L Bernardinelli, L Duga, S Asselta, R Ardissino, D Kathiresan, S Merlini, PA Mannucci, PM AF Spreafico, Marta Peyvandi, Flora Foco, Luisa Bernardinelli, Luisa Duga, Stefano Asselta, Rosanna Ardissino, Diego Kathiresan, Sekar Merlini, Piera A. Mannucci, Pier M. TI Factor V Leiden, But Not Prothrombin G20120A, Is Associated With Premature Myocardial Infarction SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Spreafico, Marta; Peyvandi, Flora; Duga, Stefano; Asselta, Rosanna; Mannucci, Pier M.] Univ Milan, Milan, Italy. [Spreafico, Marta; Peyvandi, Flora; Mannucci, Pier M.] Maggiore Hosp, IRCCS, Milan, Italy. [Foco, Luisa; Bernardinelli, Luisa] Univ Pavia, I-27100 Pavia, Italy. [Ardissino, Diego] Univ Parma, I-43100 Parma, Italy. [Kathiresan, Sekar] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Merlini, Piera A.] Osped Niguarda Ca Granda, Milan, Italy. RI Mannucci, Pier/C-3102-2014 NR 0 TC 1 Z9 1 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S956 EP S956 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503543 ER PT J AU Stewart, GC Lipes, MA Anello, MS Pratibhu, PP Gottumukkala, R Winters, GL Towbin, JA Baughman, KL AF Stewart, Garrick C. Lipes, Myra A. Anello, Mary Susan Pratibhu, Parakash P. Gottumukkala, Raju Winters, Gayle L. Towbin, Jeffrey A. Baughman, Kenneth L. TI Parvovirus B19 and Cardiomyopathy - The New Coxsackievirus SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Stewart, Garrick C.; Anello, Mary Susan; Pratibhu, Parakash P.; Winters, Gayle L.; Baughman, Kenneth L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lipes, Myra A.; Gottumukkala, Raju] Joslin Diabet Ctr, Boston, MA 02215 USA. [Towbin, Jeffrey A.] Baylor Coll Med, 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S720 EP S720 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104502352 ER PT J AU Syed, Z Scirica, BM Morrow, DA Mohanavelu, S Stultz, CM Guttag, JV AF Syed, Zeeshan Scirica, Benjamin M. Morrow, David A. Mohanavelu, Satishkumar Stultz, Collin M. Guttag, John V. TI ECG Markers to Predict Cardiovascular Death: Heart Rate Variability, Deceleration Capacity and Morphologic Variability in Non-ST-Elevation ACS from the MERLIN-TIMI 36 Trial SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Syed, Zeeshan; Stultz, Collin M.; Guttag, John V.] MIT, Cambridge, MA 02139 USA. [Scirica, Benjamin M.; Morrow, David A.; Mohanavelu, Satishkumar] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S670 EP S670 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104502146 ER PT J AU Tamehim, N Fitzgerald, ML AF Tamehim, Norimasa Fitzgerald, Michael L. TI The Sphingolipid Synthesis Regulator SPTLC1 is Bound by PARD3 through a Type II PDZ Protein-Protein Interaction SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Tamehim, Norimasa; Fitzgerald, Michael L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S376 EP S377 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104500481 ER PT J AU Thibault, H Raher, MJ Buys, E Cawley, S Derumeaux, G Janssens, S Picard, MH Bloch, KD Scherrer-Crosbie, M AF Thibault, Helene Raher, Michael J. Buys, Emmanuel Cawley, Sharon Derumeaux, Genevieve Janssens, Stefan Picard, Michael H. Bloch, Kenneth D. Scherrer-Crosbie, Marielle TI Nitric Oxide Synthase 3 Predisposes to Adverse Left Ventricular Remodeling in Insulin Resistance SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Thibault, Helene; Raher, Michael J.; Buys, Emmanuel; Cawley, Sharon; Picard, Michael H.; Bloch, Kenneth D.; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Derumeaux, Genevieve] Lyon Hosp, Lyon, France. [Janssens, Stefan] Katholieke Univ Leuven, Louvain, Belgium. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S945 EP S945 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503495 ER PT J AU Truong, QA Bamberg, F Mahabadi, AA Toepker, MH Rogers, IS Seneviratne, S Nichols, JH Lehman, SJ Schlett, CL Brady, TJ Hoffmann, U AF Truong, Quynh A. Bamberg, Fabian Mahabadi, Amir A. Toepker, Michael H. Rogers, Ian S. Seneviratne, Sujith Nichols, John H. Lehman, Sam J. Schlett, Christopher L. Brady, Thomas J. Hoffmann, Udo TI Predictive Value of Left Atrial Volume and Function by MDCT for Acute Coronary Syndrome in Patients with Acute Chest Pain: ROMICAT Substudy SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Truong, Quynh A.; Bamberg, Fabian; Mahabadi, Amir A.; Toepker, Michael H.; Rogers, Ian S.; Seneviratne, Sujith; Nichols, John H.; Lehman, Sam J.; Schlett, Christopher L.; Brady, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S761 EP S761 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104502519 ER PT J AU van Kimmenade, RR Rehman, S Januzzi, JL AF van Kimmenade, Roland R. Rehman, Shafiq Januzzi, James L., Jr. TI Do We Need More than One Biomarker for Risk Prediction in Acute Dyspnea? Concentrations of ST2 Strongly Predict 4 Year Prognosis in Acutely Dyspneic Patients with Very Low NT-proBNP Values SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [van Kimmenade, Roland R.] Univ Hosp Maastricht, Maastricht, Netherlands. [Rehman, Shafiq; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Kimmenade, R.R.J./L-4432-2015 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S866 EP S867 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104503182 ER PT J AU Wang, T Peterson, ED Ou, FS Nallamothu, BK Rumsfeld, JS Roe, MT AF Wang, Tracy Peterson, Eric D. Ou, Fang-Shu Nallamothu, Brahmajee K. Rumsfeld, John S. Roe, Matthew T. TI Do Hospitals that Improve "Direct Arrival" Door to Balloon Times for Primary Percutaneous Coronary Intervention Also Improve "Transfer In" Door to Balloon Times? SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Wang, Tracy; Peterson, Eric D.; Ou, Fang-Shu; Roe, Matthew T.] Duke Univ, Durham, NC USA. [Nallamothu, Brahmajee K.] Univ Michigan, Ann Arbor VA Med Ctr, Ann Arbor, MI 48109 USA. [Rumsfeld, John S.] Univ Colorado, Denver VA Med Ctr, Denver, CO 80202 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S1108 EP S1108 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104504400 ER PT J AU Xu, R Wojcik, J Gervino, EV Hauser, TH Amundsen, CA Powers, C Matthews, BP Warram, JH Doria, A AF Xu, Rui Wojcik, Joanna Gervino, Ernest V. Hauser, Thomas H. Amundsen, Celeste A. Powers, Christine Matthews, Brian P. Warram, James H. Doria, Alessandro TI A Common Allele at the GRB14 Locus is Associated with Increased Cardiovascular Risk in Type 2 Diabetes: Evidence from a Pooled DNA GWA Study SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Xu, Rui; Wojcik, Joanna; Amundsen, Celeste A.; Powers, Christine; Matthews, Brian P.; Warram, James H.; Doria, Alessandro] Joslin Diabet Ctr, Boston, MA 02215 USA. [Gervino, Ernest V.; Hauser, Thomas H.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S622 EP S623 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104501735 ER PT J AU Yalamarti, B Ke, QG Bodyak, N Stillman, I Tamez, H Karumanchi, SA Thadhani, R Kang, PM AF Yalamarti, Bhargavi Ke, Qingen Bodyak, Natalya Stillman, Isaac Tamez, Hector Karumanchi, S. A. Thadhani, Ravi Kang, Peter M. TI Activated Vitamin D Regresses Cardiac Hypertrophy and Attenuates Progression to Heart Failure in Dahl Salt-Sensitive Rats SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Yalamarti, Bhargavi; Ke, Qingen; Bodyak, Natalya; Stillman, Isaac; Karumanchi, S. A.; Thadhani, Ravi; Kang, Peter M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Tamez, Hector] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S335 EP S335 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104500300 ER PT J AU Yen, R Fernandes, V Cushman, M Bahrami, H Nasir, K Tracy, R Bluemke, DA Lima, JA AF Yen, Raymond Fernandes, Veronica Cushman, Mary Bahrami, Hossein Nasir, Khurram Tracy, Russell Bluemke, David A. Lima, Joao A. TI Relationship of Fibrinogen with Regional Left Ventricular Dysfunction In Asymptomatic Individuals Without Clinical Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Yen, Raymond; Fernandes, Veronica; Bluemke, David A.; Lima, Joao A.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Cushman, Mary; Tracy, Russell] Univ Vermont, Colchester, VT USA. [Bahrami, Hossein] Johns Hopkins Sch Med, Baltimore, MD USA. [Nasir, Khurram] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S1103 EP S1104 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104504381 ER PT J AU Zahid, M Good, CB Sonel, AF AF Zahid, Maliha Good, Chester B. Sonel, Ali F. TI Clinical Significance of Borderline Elevated Troponin-1 Levels Across Different Assays SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Zahid, Maliha] Univ Pittsburgh, Pittsburgh, PA USA. [Good, Chester B.; Sonel, Ali F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S636 EP S636 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104502015 ER PT J AU Zhao, XH Cai, JM Underhill, H OiKawa, M Dong, L Ota, H Hatsukami, T Yuan, C AF Zhao, Xihai Cai, Jianming Underhill, Hunter OiKawa, Minako Dong, Li Ota, Hideki Hatsukami, Thomas Yuan, Chun TI Prevalence of Carotid Atherosclerotic Plaque Composition and Surface Disruption for Different Categories of Normalized Wall Index as Measured by Magnetic Resonance Imaging SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Zhao, Xihai; Underhill, Hunter; OiKawa, Minako; Dong, Li; Ota, Hideki; Yuan, Chun] Univ Washington, Seattle, WA 98195 USA. [Cai, Jianming] Peoples Liberat Army Gen Hosp, Beijing, Peoples R China. [Hatsukami, Thomas] VA Puget Sound Healthcare Syst, Seattle, WA USA. RI Ota, Hideki/A-3717-2012 OI Ota, Hideki/0000-0002-7239-3152 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S688 EP S688 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104502220 ER PT J AU Bustos, RI Forget, MA Settleman, JE Hansen, SH AF Bustos, Rodrigo I. Forget, Marie-Annick Settleman, Jeffrey E. Hansen, Steen H. TI Coordination of Rho and Rac GTPase Function via p190B RhoGAP SO CURRENT BIOLOGY LA English DT Article ID ACTIN POLYMERIZATION; ACTIVATING PROTEIN; CELL-ADHESION; RND PROTEINS; KINASE; DOMAIN; PATHWAY; BIOLOGY; BINDING; FAMILY AB The Rac GTPase regulates Rho signaling in a broad range of physiological settings and in oncogenic transformation [1-3]. Here, we report a novel mechanism by which crosstalk between Rac and Rho GTPases is achieved. Activated Rac1 binds directly to p190B Rho GTPase-activating protein (RhoGAP), a major modulator of Rho signaling. p190B colocalizes with constitutively active Rac1 in membrane ruffles. Moreover, activated Rac1 is sufficient to recruit p190B into a detergent-insoluble membrane fraction, a process that is accompanied by a decrease in GTP-bound RhoA from membranes. p19013 is recruited to the plasma membrane in response to integrin engagement [4]. We demonstrate that collagen type 1, a potent inducer of Rac1-dependent cell motility in HeLa cells, counteracts cytoskeletal collapse resulting from overexpression of wild-type p190B, but not that resulting from overexpression of a p19013 mutant specifically lacking the Rac1-binding sequence. Furthermore, this p190B mutant exhibits dramatically enhanced RhoGAP activity, consistent with a model whereby binding of Rac1 relieves autoinhibition of p19013 RhoGAP function. Collectively, these observations establish that activated Rac1, through direct interaction with p190B, modulates subcellular RhoGAP localization and activity, thereby providing a novel mechanism for Rac control of Rho signaling in a broad range of physiological processes. C1 [Bustos, Rodrigo I.; Forget, Marie-Annick; Hansen, Steen H.] Childrens Hosp Boston, GI Cell Biol Lab, Boston, MA 02115 USA. [Bustos, Rodrigo I.; Forget, Marie-Annick; Hansen, Steen H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Settleman, Jeffrey E.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Settleman, Jeffrey E.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Hansen, SH (reprint author), Childrens Hosp Boston, GI Cell Biol Lab, Boston, MA 02115 USA. EM steen.hansen@childrens.harvard.edu FU NIH [CA62142, CA092354]; Roy and Lynne Frank Foundation and Children's Hospital FX We are grateful to Tobias Meyer, Martin A. Schwartz, and Arthur S. Alberts for providing reagents, to Ashley D. Pollock and Jessica Wagner for technical assistance, and to Lynne Coluccio and Scott R. Frank for helpful discussions. This work was funded by R01 NIH CA62142 to J.S., R01 NIH CA092354 to S.H.H., and funds from The Roy and Lynne Frank Foundation and Children's Hospital to S.H.H. NR 26 TC 44 Z9 45 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD OCT 28 PY 2008 VL 18 IS 20 BP 1606 EP 1611 DI 10.1016/j.cub.2008.09.019 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 367KR UT WOS:000260551400033 PM 18948007 ER PT J AU Lee, JT AF Lee, Jeannie T. TI Jeannie T. Lee SO CURRENT BIOLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu FU Howard Hughes Medical Institute NR 0 TC 0 Z9 0 U1 0 U2 1 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 OCT 28 PY 2008 VL 18 IS 20 BP R940 EP R941 DI 10.1016/j.cub.2008.07.087 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 367KR UT WOS:000260551400007 PM 18983954 ER PT J AU Rehman, SU Mueller, T Januzzi, JL AF Rehman, Shafiq U. Mueller, Thomas Januzzi, James L., Jr. TI Characteristics of the Novel Interleukin Family Biomarker ST2 in Patients With Acute Heart Failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE heart failure; ST2; NT-proBNP; mortality ID BRAIN NATRIURETIC PEPTIDE; CRITICALLY-ILL PATIENTS; AMINO-TERMINAL PROBNP; SOLUBLE ST2; SEPTIC SHOCK; MYOCARDIAL-INFARCTION; EMERGENCY-DEPARTMENT; 1-YEAR MORTALITY; RESPONSE GENE; MEMBER ST2 AB Objectives The purpose of this study was to examine the patient-specific characteristics of the interleukin-1 receptor family member ST2 in patients with acute heart failure (HF). Background ST2 signaling is involved in the process of cardiac fibrosis and hypertrophy. Methods In all, 346 patients with acute HF had ST2 measured. Associations between ST2 and demographics, severity/ type of HF, and other biomarkers were examined. Receiver-operator characteristic curves and multivariable Cox proportional hazards analyses evaluated the prognostic ability of ST2. Results The ST2 values correlated with the severity of HF p < 0.001), left ventricular ejection fraction (r = -0.134; p = 0.014), creatinine clearance (r = -0.224; p < 0.001), B-type natriuretic peptide (r = 0.293; p < 0.001), amino terminal B-type natriuretic peptide ( r = 0.413; p < 0.001), and C-reactive protein ( r = 0.429; p < 0.001). ST2 was not associated with age, prior HF, or body mass index. The ST2 levels at presentation were higher among patients who died by 1 year. The area under the receiver-operator characteristic for death at 1 year was 0.71 (p < 0.001). In a multivariable Cox model containing established clinical and biochemical predictors (including natriuretic peptides), ST2 remained a predictor of mortality (hazard ratio: 2.04, 95% confidence interval: 1.30 to 3.24, p = 0.003), and was equally predictive in patients with HF and preserved or impaired systolic function. When both ST2 and natriuretic peptides were elevated, the highest rates of death were observed in cumulative hazard analysis (p < 0.001). In the presence of a low ST2 level, natriuretic peptides did not predict mortality. Conclusions Consistent with its proposed role in a myocardial-specific response to stretch, ST2 has strong clinical and biochemical correlates in patients with acute HF. Prognostically, ST2 is powerful in acute HF and is synergistic with natriuretic peptides for this use. (J Am Coll Cardiol 2008; 52: 1458-65) (C) 2008 by the American College of Cardiology Foundation C1 [Rehman, Shafiq U.; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Rehman, Shafiq U.; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Mueller, Thomas] Konventhosp Barmherzige Brueder, Dept Lab Med, Linz, Austria. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM JJanuzzi@partners.org NR 34 TC 138 Z9 157 U1 1 U2 8 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 OCT 28 PY 2008 VL 52 IS 18 BP 1458 EP 1465 DI 10.1016/j.jacc.2008.07.042 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 363HQ UT WOS:000260258800005 PM 19017513 ER PT J AU Smith, EE Vijayappa, M Lima, F Delgado, P Wendell, L Rosand, J Greenberg, SM AF Smith, E. E. Vijayappa, M. Lima, F. Delgado, P. Wendell, L. Rosand, J. Greenberg, S. M. TI Impaired visual evoked flow velocity response in cerebral amyloid angiopathy SO NEUROLOGY LA English DT Article ID WHITE-MATTER LESIONS; LOBAR INTRACEREBRAL HEMORRHAGE; TRANSCRANIAL DOPPLER; PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; VASOMOTOR REACTIVITY; TRANSGENIC MICE; DEMENTIA; BRAIN; PROGRESSION AB Objective: Animal models of cerebral amyloid angiopathy (CAA) exhibit abnormal vascular reactivity. We determined whether vascular reactivity, measured by transcranial Doppler ultrasound (TCD), is reduced in humans with CAA. Methods: Cases were recruited from an established prospective study of CAA. Healthy controls were recruited from a study of normal aging. Evoked mean flow velocity increase in the posterior cerebral artery (PCA) was measured while subjects viewed a flashing alternating checkerboard stimulus. In a separate but partially overlapping cohort we measured the mean flow velocity increase in the middle cerebral artery (MCA) while subjects inhaled carbon dioxide. Results: The visual evoked mean flow velocity increase was 8.0 +/- 6.1% in CAA (n = 11) compared to 17.4 +/- 5.7% in controls (n = 9, p = 0.002). The PCA pulsatility index, a marker of distal vascular resistance, was higher in CAA (CAA 1.35 +/- 0.35, control 1.04 +/- 0.14, p = 0.03). Among CAA subjects, lower visual evoked mean flow velocity increase was associated with a higher number of hemorrhages seen on MRI (r = -0.87, p = 0.0005) and higher MRI white matter hyperintensity volume (r = -0.67, p = 0.02). The MCA response to carbon dioxide did not differ between CAA and control in 20 subjects (9 CAA, 11 control, p = 0.54). Conclusions: Cerebral amyloid angiopathy (CAA) was associated with decreased vascular reactivity in response to visual stimulation, possibly reflecting the occipital predilection of the disease. The association of posterior cerebral artery (PCA) evoked flow velocity response with elevated PCA pulsatility index and MRI markers of small vessel disease suggests that abnormal PCA evoked flow velocity in CAA is caused by pathology of the distal resistance vessels. Neurology r 2008; 71:1424-1430 C1 [Smith, E. E.; Vijayappa, M.; Lima, F.; Delgado, P.; Wendell, L.; Rosand, J.; Greenberg, S. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Hemorrhag Stroke Res Program, Boston, MA 02114 USA. [Rosand, J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Smith, EE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Hemorrhag Stroke Res Program, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM eesmith@partners.org OI Smith, Eric/0000-0003-3956-1668 FU United States National Institute of Neurological Disorders and Stroke [K23 NS046327]; National Institute of Aging [R01 AG026484] FX Funded by grants from the United States National Institute of Neurological Disorders and Stroke K23 NS046327 (E.E.S.) and the National Institute of Aging R01 AG026484 (S.M.G.). NR 40 TC 50 Z9 50 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 28 PY 2008 VL 71 IS 18 BP 1424 EP 1430 DI 10.1212/01.wnl.0000327887.64299.a4 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 365RS UT WOS:000260426100008 PM 18955685 ER PT J AU Grueneberg, DA Degott, S Pearlberg, J Li, W Davies, JE Baldwin, A Endege, W Doench, J Sawyer, J Hu, Y Boyce, F Xian, J Munger, K Harlow, E AF Grueneberg, Dorre A. Degott, Sebastien Pearlberg, Joseph Li, Wenliang Davies, Joan E. Baldwin, Amy Endege, Wilson Doench, John Sawyer, Jacqueline Hu, Yanhui Boyce, Frederick Xian, Jun Munger, Karl Harlow, Ed TI Kinase requirements in human cells: I. Comparing kinase requirements across various cell types SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer; essential kinases; shRNA screens; fingerprints ID MAMMALIAN-CELLS; GENETIC SCREEN; RNAI SCREEN; EXPRESSION; THERAPY AB shRNA loss-of-function screens were used to identify kinases that were rate-limiting for promoting cell proliferation and survival. Here, we study the differences in kinase requirements among various human cells, including freshly prepared primary cells, isogenic cells, immortalized cells, and cancer cell lines. Closely related patterns of kinase requirements among the various cell types were observed in three cases: (i) in repeat experiments using the same cells, (ii) with multiple populations of freshly prepared primary, epithelial cells isolated from the same tissue source, and (iii) between nearly isogenic cells that differ from each other by the expression of a single gene. Other commonly used cancer cell lines were distinct from one another, even when they were isolated from similar tumor types. Even primary cells of different lineages isolated from the same tissue source showed many differences. The differences in kinase requirements among cell lines observed in this study suggest that the control of proliferation and survival may be significantly different between cell lines and that simple comparisons from any one cell to another may be misleading. Although the regulation of cell proliferation and survival are heavily studied areas, we did not see a bias in these screens toward the identification of previously known and well studied kinases, suggesting that our knowledge of molecular events in these areas is still meager. C1 [Grueneberg, Dorre A.; Degott, Sebastien; Pearlberg, Joseph; Li, Wenliang; Davies, Joan E.; Endege, Wilson; Doench, John; Sawyer, Jacqueline; Hu, Yanhui; Xian, Jun; Harlow, Ed] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Baldwin, Amy; Munger, Karl] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Boyce, Frederick] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Harlow, E (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 240 Longwood Ave, Boston, MA 02115 USA. EM eharlow@hms.harvard.edu RI Li, Wenliang/A-1022-2010; OI Munger, Karl/0000-0003-3288-9935; Doench, John/0000-0002-3707-9889 FU AstraZeneca Pharmaceuticals FX The authors would like to thank L. Bergeron and L. Ronco for their advice and support in the generation of the screening data for lung cancer cell lines. The work in Figures 2, 4, and S7 was supported by a sponsored research agreement from AstraZeneca Pharmaceuticals. NR 25 TC 53 Z9 54 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 28 PY 2008 VL 105 IS 43 BP 16472 EP 16477 DI 10.1073/pnas.0808019105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 372PM UT WOS:000260913500015 PM 18948591 ER PT J AU Bommi-Reddy, A Almeciga, I Sawyer, J Geisen, C Li, WL Harlow, E Kaelin, WG Grueneberg, DA AF Bommi-Reddy, Archana Almeciga, Ingrid Sawyer, Jacqueline Geisen, Christoph Li, Wenliang Harlow, Ed Kaelin, William G., Jr. Grueneberg, Dorre A. TI Kinase requirements in human cells: III. Altered kinase requirements in VHL-/- cancer cells detected in a pilot synthetic lethal screen SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE essential kinases; shRNA screens; VHL; kidney cancer; therapeutics ID RENAL-CARCINOMA CELLS; TUMOR-SUPPRESSOR GENE; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; HIPPEL-LINDAU-DISEASE; CYCLIN D1; GROWTH; PROTEIN; TARGETS; RNAI; PHOSPHORYLATION AB Clear cell renal carcinomas are the most common form of kidney cancer and frequently are linked to biallelic inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene. The VHL gene product, pVHL, has multiple functions including directing the polyubiquitylation of the HIF transcription factor. We screened 100 shRNA vectors, directed against 88 kinases, for their ability to inhibit the viability of VHL-/- renal carcinoma cells preferentially compared with isogenic cells in which pVHL function was restored. shRNAs for "hits" identified in the primary screen were interrogated in secondary screens that included shRNA titration studies. Multiple shRNAs against CDK6, MET, and MAP2K1 (also known as MEK1) preferentially inhibited the viability of 786-O and RCC4 VHL-/- cells compared with their wild-type pVHL-reconstituted counterparts. The sensitivity of pVHL-proficient cells to these shRNAs was not restored upon HIF activation, suggesting that loss of an hypoxia-inducible factor (HIF)-independent pVHL function formed the basis for selectivity. A small-molecule Cdk4/6 inhibitor displayed enhanced activity against VHL-/- renal carcinoma cells, suggesting that in some cases hits from shRNA screens such as described here might translate into therapeutic targets. C1 [Sawyer, Jacqueline; Li, Wenliang; Harlow, Ed; Grueneberg, Dorre A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Bommi-Reddy, Archana; Almeciga, Ingrid; Geisen, Christoph; Kaelin, William G., Jr.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Geisen, Christoph; Kaelin, William G., Jr.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Harlow, E (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM eharlow@hms.harvard.edu; william_kaelin@dfci.harvard.edu FU National Institutes of Health [R21CA104940] FX We thank Donna Neuberg for help with statistical analysis. A.B.-R. was supported by the American Foundation for Urologic Disease and the Tisch Family Fund for research in solid tumors. W.G.K. is a Howard Hughes Medical Institute investigator and was supported by the Murray Foundation. This work is supported by National Institutes of Health Grant R21CA104940 (to W.G.K and A.B-R.). NR 35 TC 83 Z9 86 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 28 PY 2008 VL 105 IS 43 BP 16484 EP 16489 DI 10.1073/pnas.0806574105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 372PM UT WOS:000260913500017 PM 18948595 ER PT J AU Okazaki, M Ferrandon, S Vilardaga, JP Bouxsein, ML Potts, JT Gardella, TJ AF Okazaki, Makoto Ferrandon, Sebastien Vilardaga, Jean-Pierre Bouxsein, Mary L. Potts, John T., Jr. Gardella, Thomas J. TI Prolonged signaling at the parathyroid hormone receptor by peptide ligands targeted to a specific receptor conformation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN-RECEPTOR; FUNCTIONAL SELECTIVITY; BINDING MECHANISM; CANCELLOUS BONE; PTH; RAT; INTERNALIZATION; OSTEOPOROSIS; INTERMITTENT; INFUSION AB The parathyroid hormone receptor (PTHR) is a class B G protein-coupled receptor that plays critical roles in bone and mineral ion metabolism. Ligand binding to the PTHR involves interactions to both the amino-terminal extracellular (N) domain, and transmembrane/extracellular loop, or juxtamembrane (J) regions of the receptor. Recently, we found that PTH(1-34), but not PTH-related protein, PTHrP(1-36), or M-PTH(1-14) (M = Ala/ Aib(1),Aib(3),Gln(10),Har(11),Ala(12),Trp(14),Arg(19)), binds to the PTHR in a largely GTP gamma S-resistant fashion, suggesting selective binding to a novel, high-affinity conformation (R-0), distinct from the GTP gamma S-sensitive conformation (RG). We examined the effects in vitro and in vivo of introducing the M substitutions, which enhance interaction to the J domain, into IPTH analogs extended C-terminally to incorporate residues involved in the N domain interaction. As compared with PTH(1-34), M-PTH(1-28) and M-PTH(1-34) bound to R-0 with higher affinity, produced more sustained cAMP responses in cells, formed more stable complexes with the PTHR in FRET and subcellular localization assays, and induced more prolonged calcemic and phosphate responses in mice. Moreover, after 2 weeks of daily injection in mice, M-PTH(1-34) induced larger increases in trabecular bone volume and greater increases in cortical bone turnover, than did PTH(1-34). Thus, the putative R-0 PTHR conformation can form highly stable complexes with certain PTH ligand analogs and thereby mediate surprisingly prolonged signaling responses in bone and/or kidney PTH target cells. Controlling, via ligand analog design, the selectivity with which a PTH ligand binds to R-0, versus RG, may be a strategy for optimizing signaling duration time, and hence therapeutic efficacy, of PTHR agonist ligands. C1 [Okazaki, Makoto; Ferrandon, Sebastien; Vilardaga, Jean-Pierre; Potts, John T., Jr.; Gardella, Thomas J.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Ferrandon, Sebastien; Vilardaga, Jean-Pierre] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Bouxsein, Mary L.] Harvard Univ, Sch Med, Orthopad Biomech Lab, Beth Israel Deaconess Med Ctr, Boston, MA 02114 USA. RP Potts, JT (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM potts.john@mgh.harvard.edu; gardella@helix.mgh.harvard.edu FU National Institutes of Health [DK-11794] FX We thank Ashok Khatri of the Massachusetts General Hospital BiopolymerCore Facility for peptide synthesis and Dr. Ernestina Schipani of the Massachusetts General Hospital Skeletal Phenotyping Core Facility for bone histology. This work was supported by National Institutes of Health Grant DK-11794. NR 35 TC 52 Z9 52 U1 1 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 28 PY 2008 VL 105 IS 43 BP 16525 EP 16530 DI 10.1073/pnas.0808750105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 372PM UT WOS:000260913500024 PM 18946036 ER PT J AU Morokuma, J Blackiston, D Adams, DS Seebohm, G Trimmer, B Levin, M AF Morokuma, Junji Blackiston, Douglas Adams, Dany S. Seebohm, Guiscard Trimmer, Barry Levin, Michael TI Modulation of potassium channel function confers a hyperproliferative invasive phenotype on embryonic stem cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer; ion channel; melanocyte; neural crest; KCNQ ID HUMAN BREAST-CANCER; NERVOUS-SYSTEM; ELECTRICAL-STIMULATION; PROTEIN-SYNTHESIS; FROG ERYTHROCYTE; PROGENITOR CELLS; XENOPUS-LAEVIS; K+ CURRENT; EXPRESSION; VOLTAGE AB Ion transporters, and the resulting voltage gradients and electric fields, have been implicated in embryonic development and regeneration. These biophysical signals are key physiological aspects of the microenvironment that epigenetically regulate stem and tumor cell behavior. Here, we identify a previously unrecognized function for KCNQ1, a potassium channel known to be involved in human Romano-Ward and Jervell-Lange-Nielsen syndromes when mutated. Misexpression of its modulatory wild-type beta-subunit XKCNE1 in the Xenopus embryo resulted in a striking alteration of the behavior of one type of embryonic stem cell: the pigment cell lineage of the neural crest. Depolarization of embryonic cells by misexpression of KCNE1 non-cell-autonomously induced melanocytes to overproliferate, spread out, and become highly invasive of blood vessels, liver, gut, and neural tube, leading to a deeply hyperpigmented phenotype. This effect is mediated. by the up-regulation of Sox10 and Slug genes, thus linking alterations in ion channel function to the control of migration, shape, and mitosis rates during embryonic morphogenesis. Taken together, these data identify a role for the KCNQ1 channel in regulating key cell behaviors and reveal the molecular identity of a biophysical switch, by means of which neoplastic-like properties can be conferred upon a specific embryonic stem cell subpopulation. C1 [Morokuma, Junji; Blackiston, Douglas; Adams, Dany S.; Levin, Michael] Harvard Univ, Sch Dent Med, Forsyth Inst, Ctr Regenerat & Dev Biol, Boston, MA 02115 USA. [Morokuma, Junji; Blackiston, Douglas; Adams, Dany S.; Levin, Michael] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Seebohm, Guiscard] Univ Tubingen, Inst Physiol 1, D-72076 Tubingen, Germany. [Seebohm, Guiscard] Ruhr Univ Bochum, D-44780 Bochum, Germany. [Trimmer, Barry] Tufts Univ, Dept Biol, Medford, MA 02155 USA. RP Levin, M (reprint author), Harvard Univ, Sch Dent Med, Forsyth Inst, Ctr Regenerat & Dev Biol, 140 Fenway, Boston, MA 02115 USA. EM mlevin@forsyth.org FU NIDCR NIH HHS [5T32DE007327-07, 5K22DE16633, K22 DE016633-04, K22 DE016633, T32 DE007327]; NIGMS NIH HHS [R01-GM07742] NR 70 TC 52 Z9 54 U1 2 U2 12 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 28 PY 2008 VL 105 IS 43 BP 16608 EP 16613 DI 10.1073/pnas.0808328105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 372PM UT WOS:000260913500038 PM 18931301 ER PT J AU Joos, B Fischer, M Kuster, H Pillai, SK Wong, JK Boni, J Hirschel, B Weber, R Trkola, A Gunthard, HF AF Joos, Beda Fischer, Marek Kuster, Herbert Pillai, Satish K. Wong, Joseph K. Boeni, Juerg Hirschel, Bernard Weber, Rainer Trkola, Alexandra Guenthard, Huldrych F. CA Swiss HIV Cohort Study TI HIV rebounds from latently infected cells, rather than from continuing low-level replication SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HIV-1; latent reservoir; structured treatment interruption; viral diversity; coreceptor usage ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; STRUCTURED TREATMENT INTERRUPTIONS; IN-VIVO; PLASMA VIREMIA; INTRINSIC STABILITY; CELLULAR RESERVOIRS; TYPE-1 REPLICATION; VIRAL CONTROL; T-CELLS AB Rapid rebound of plasma viremia in patients after interruption of long-term combination antiretroviral therapy (cART) suggests persistence of low-level replicating cells or rapid reactivation of latently infected cells. To further characterize rebounding virus, we performed extensive longitudinal clonal evolutionary studies of HIV env C2-V3-C3 regions and exploited the temporal relationships of rebounding plasma viruses with regard to pretreatment sequences in 20 chronically HIV-1-infected patients having undergone multiple 2-week structured treatment interruptions (STI). Rebounding virus during the short STI was homogeneous, suggesting mono- or oligoclonal origin during reactivation. No evidence for a temporal structure of rebounding virus in regard to pretreatment sequences was found. Furthermore, expansion of distinct lineages at different STI cycles emerged. Together, these findings imply stochastic reactivation of different clones from long-lived latently infected cells rather than expansion of viral populations replicating at low levels. After treatment was stopped, diversity increased steadily, but pretreatment diversity was, on average, achieved only >2.5 years after the start of STI when marked divergence from preexisting quasispecies also emerged. In summary, our results argue against persistence of ongoing low-level replication in patients on suppressive cART. Furthermore, a prolonged delay in restoration of pretreatment viral diversity after treatment interruption demonstrates a surprisingly sustained evolutionary bottleneck induced by punctuated antiretroviral therapy. C1 [Joos, Beda; Fischer, Marek; Kuster, Herbert; Weber, Rainer; Trkola, Alexandra; Guenthard, Huldrych F.] Univ Zurich Hosp, Div Infect Dis, Dept Med, CH-8091 Zurich, Switzerland. [Joos, Beda; Fischer, Marek; Kuster, Herbert; Weber, Rainer; Trkola, Alexandra; Guenthard, Huldrych F.] Univ Zurich Hosp, Hosp Epidemiol, CH-8091 Zurich, Switzerland. [Pillai, Satish K.; Wong, Joseph K.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Boeni, Juerg] Univ Zurich, Natl Ctr Retroviruses, CH-8028 Zurich, Switzerland. [Hirschel, Bernard] Univ Hosp Geneva, Div Infect Dis, CH-1211 Geneva, Switzerland. RP Joos, B (reprint author), Univ Zurich Hosp, Div Infect Dis, Dept Med, CH-8091 Zurich, Switzerland. EM beda.joos@usz.ch; huldrych.guenthard@usz.ch RI gunthard, huldrych/F-1724-2011; Joos, Beda/D-5547-2009; Kuster, Herbert/A-3912-2013; Infektiologie, USZ/A-6921-2011; SHCS, all/G-4072-2011; SHCS, ch/G-4077-2011; SHCS, only/G-4080-2011; Weber, Rainer/D-5175-2012; Pantaleo, Giuseppe/K-6163-2016; Trkola, Alexandra/K-2115-2012 OI gunthard, huldrych/0000-0002-1142-6723; Joos, Beda/0000-0002-3082-8875; Trkola, Alexandra/0000-0003-1013-876X FU Swiss National Science Foundation (SNF) [3345-65168, 3100AO-103748/1, PP00B-102647, 320000-116035]; Swiss HIV Cohort Study (SHCS) [290]; SNF [33CSC0-10878]; EMDO Foundation; Elizabeth Glaser Pediatric AIDS Foundation; National Institutes of Health [R01 NS51132] FX We thank the participating patients for their commitment; Christine Schneider, Christina Grube, and Roland Hafner for excellent patient care; Esther Beerli, Friederike Burgener, Christine Leemann, Tuyet Trinh Lu, Barbara Niederost, and Barbel Sauer for laboratory support; and Ingrid Nievergelt and Christine Vogtli for administrative assistance. This work was supported by Swiss National Science Foundation (SNF) Grants 3345-65168 and 3100AO-103748/1 (to H.F.G. and A.T.), PP00B-102647 (to A.T.), and 320000-116035 (to H.F.G.); the Swiss HIV Cohort Study (SHCS) (SNF Grant 33CSC0-10878) SHCS Project No. 290 (to H.F.G.); a grant from the EMDO Foundation (to H.F.G., and a research grant from the Kanton of Zurich. A.T. is the Elizabeth Glaser Scientist supported by the Elizabeth Glaser Pediatric AIDS Foundation. J.K.W. was supported by National Institutes of Health Grant R01 NS51132. NR 62 TC 150 Z9 151 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 28 PY 2008 VL 105 IS 43 BP 16725 EP 16730 DI 10.1073/pnas.0804192105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 372PM UT WOS:000260913500058 PM 18936487 ER PT J AU Nathan, DA AF Nathan, David A. TI Glycemic Management of Type 2 Diabetes How Tight Is Right and How to Get There SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID BLOOD-GLUCOSE CONTROL; MYOCARDIAL-INFARCTION; CONSENSUS ALGORITHM; RISK; COMPLICATIONS; MELLITUS; ROSIGLITAZONE; THERAPY; UKPDS; THIAZOLIDINEDIONES C1 Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. RP Nathan, DA (reprint author), Massachusetts Gen Hosp, Ctr Diabet, 50 Staniford St,Ste 340, Boston, MA 02114 USA. EM dnathan@Partners.org NR 23 TC 4 Z9 6 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 27 PY 2008 VL 168 IS 19 BP 2064 EP 2066 DI 10.1001/archinte.168.19.2064 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 364JQ UT WOS:000260332400001 PM 18955633 ER PT J AU Nezam, SMRM Joo, C Tearney, GJ de Boer, JF AF Nezam, S. M. R. Motaghian Joo, C. Tearney, G. J. de Boer, J. F. TI Application of maximum likelihood estimator in nano-scale optical path length measurement using spectral-domain optical coherence phase microscopy SO OPTICS EXPRESS LA English DT Article ID TOMOGRAPHY; INTERFEROMETRY; SUBWAVELENGTH; DYNAMICS; IMAGES AB Spectral-domain optical coherence phase microscopy (SD-OCPM) measures minute phase changes in transparent biological specimens using a common path interferometer and a spectrometer based optical coherence tomography system. The Fourier transform of the acquired interference spectrum in spectral-domain optical coherence tomography (SD-OCT) is complex and the phase is affected by contributions from inherent random noise. To reduce this phase noise, knowledge of the probability density function (PDF) of data becomes essential. In the present work, the intensity and phase PDFs of the complex interference signal are theoretically derived and the optical path length (OPL) PDF is experimentally validated. The full knowledge of the PDFs is exploited for optimal estimation (Maximum Likelihood estimation) of the intensity, phase, and signal-to-noise ratio (SNR) in SD-OCPM. Maximum likelihood (ML) estimates of the intensity, SNR, and OPL images are presented for two different scan modes using Bovine Pulmonary Artery Endothelial (BPAE) cells. To investigate the phase accuracy of SD-OCPM, we experimentally calculate and compare the cumulative distribution functions (CDFs) of the OPL standard deviation and the square root of the Cramer-Rao lower bound (1/2SNR) over 100 BPAE images for two different scan modes. The correction to the OPL measurement by applying ML estimation to SD-OCPM for BPAE cells is demonstrated. (C) 2008 Optical Society of America C1 [Nezam, S. M. R. Motaghian] Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Nezam, SMRM (reprint author), Harvard Univ, Sch Med, 55 Fruit St,BAR 7, Boston, MA 02114 USA. EM rmotaghi@caltech.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU National Institute of Health [NCRR 19768]; CIMIT; Center for the Integration of Medicine and Innovative Technology [DAMD17-02-2-0006] FX This research was supported in part by the National Institute of Health under grant number NCRR 19768, and CIMIT, the Center for the Integration of Medicine and Innovative Technology with funding from the Department of the Army under its Cooperative Agreement DAMD17-02-2-0006. S. M. R. Motaghiannezam is currently with the California Institute of Technology, Pasadena, CA. C. Joo is currently with General Electric Global Research Lab, Niskayuna, NY. J.F. de Boer is currently with VU University, De Boelelaan 1081, T-0.67, Amsterdam, The Netherlands, jfdeboer@few.vu.nl. NR 18 TC 4 Z9 4 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD OCT 27 PY 2008 VL 16 IS 22 BP 17186 EP 17195 DI 10.1364/OE.16.017186 PG 10 WC Optics SC Optics GA 371XL UT WOS:000260865900006 ER PT J AU Horner, BM Eberlin, KR Ferguson, KK Hirsh, EL Randolph, MA Butler, PEM AF Horner, Benjamin M. Eberlin, Kyle R. Ferguson, Kelly K. Hirsh, Erica L. Randolph, Mark A. Butler, Peter E. M. TI Recipient Damage After Musculocutaneous Transplant Rejection SO TRANSPLANTATION LA English DT Article DE Composite; Tissue; Retransplantation; Recipient; Damage ID COMPOSITE TISSUE-TRANSPLANTATION; PRIMARY ALLOGRAFT NEPHRECTOMY; INTERNATIONAL REGISTRY; HAND; RATS; CYCLOSPORINE; TOLERANCE; FK-506 AB Background. In the event of a composite allograft failure, damage to the recipient tissues may make retransplantation impossible. This study aimed to quantify the damage after composite allograft failure to assess whether retransplantation is feasible. Methods. Rats (n=6) in the group I received composite musculocutaneous flap allotransplants (WF-Lew) with immunosuppression allowing healing-in of the allograft before being tapered allowing rejection. At full rejection, the recipient vascular pedicle was examined, biopsies of the recipient tissue bed were taken and graded for damage, and in vitro assays were performed. Groups II (allograft without immunosuppression, n=7), III (isograft with immunosuppression, n=5), and IV (isograft without inummosuppression, n=6) were included to attempt to identify the contributions of the rejection process, inummosuppression, and healing to recipient tissue damage. Results. The vascular pedicle was patent to within 1 mm of the anastomosis in all rejected allografts. Furthermore, it was possible to retransplant after full rejection. There was minimal damage to the recipient tissues at the time of full rejection in group I. In contrast, group II had significantly more damage (P < 0.05) to recipient muscle and skin. This correlated with more severe immune reaction with more than 100 times antibody production in group II compared with group I. Groups III and IV had little recipient tissue damage. Conclusions. These results suggest that it is possible to retransplant after rejection of a musculocutaneous transplant while on immunosuppression. Furthermore, the second transplant will not be limited in form or function by recipient tissue bed damage. C1 [Horner, Benjamin M.; Eberlin, Kyle R.; Randolph, Mark A.] Massachusetts Gen Hosp, Dept Surg, Plast Surg Res Lab, Boston, MA 02114 USA. [Horner, Benjamin M.; Ferguson, Kelly K.; Hirsh, Erica L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,CNY, Boston, MA USA. [Horner, Benjamin M.; Butler, Peter E. M.] UCL, Royal Free Hosp, Dept Plast Surg, London, England. RP Randolph, MA (reprint author), Massachusetts Gen Hosp, Dept Surg, Plast Surg Res Lab, WAC 435, Boston, MA 02114 USA. EM marandolph@partners.org OI Ferguson, Kelly/0000-0001-8467-3250; Butler, Peter/0000-0001-7419-1493 FU Fulbright Commission Postgraduate Award; Royal College of Surgeons of England Research Fellowship; Berkeley Research Fellowship; Plastic Surgery Education Foundation Research Award FX This work was supported by Fulbright Commission Postgraduate Award, Royal College of Surgeons of England Research Fellowship, Berkeley Research Fellowship, Plastic Surgery Education Foundation Research Award (B.H.). NR 20 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT 27 PY 2008 VL 86 IS 8 BP 1104 EP 1110 DI 10.1097/TP.0b013e3181872ac3 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 367LY UT WOS:000260554700014 PM 18946349 ER PT J AU Ganzini, L Goy, ER Dobscha, SK AF Ganzini, Linda Goy, Elizabeth R. Dobscha, Steven K. TI Prevalence of depression and anxiety in patients requesting physicians' aid in dying: cross sectional survey SO BRITISH MEDICAL JOURNAL LA English DT Article ID MENTAL STATUS QUESTIONNAIRE; REDUCING SUICIDAL IDEATION; TERMINALLY-ILL PATIENTS; PRIMARY-CARE PATIENTS; ASSISTED SUICIDE; HASTENED DEATH; OLDER PATIENTS; CANCER; HOPELESSNESS; DESIRE AB Objective To determine the prevalence of depression and anxiety in terminally ill patients pursuing aid in dying from physicians. Design Cross sectional survey. Setting State of Oregon, USA. Participants 58 Oregonians, most terminally ill with cancer or amyotrophic lateral sclerosis, who had either requested aid in dying from a physician or contacted an aid in dying advocacy organisation. Main outcome measures Diagnosis of depression or anxiety according to the hospital anxiety and depression scale and the structured clinical interview for the Diagnostic and Statistical Manual of Mental Disorders. Results 15 study participants met "caseness" criteria for depression, and 13 met criteria for anxiety. 42 patients died by the end of the study; 18 received a prescription fora lethal drug under the Death with Dignity Act, and nine died by lethal ingestion. 15 participants who received a prescription for a lethal drug did not meet criteria for depression; three did. All three depressed participants died by legal ingestion within two months of the research interview. Conclusion Although most terminally ill Oregonians who receive aid in dying do not have depressive disorders, the current practice of the Death with Dignity Act may fail to protect some patients whose choices are influenced by depression from receiving a prescription for a lethal drug. C1 [Ganzini, Linda; Goy, Elizabeth R.; Dobscha, Steven K.] Portland VA Med Ctr, Columbia Ctr Study Chron Comorbid Mental & Phys D, Hlth Serv Res & Dev, Portland, OR 97239 USA. [Ganzini, Linda; Goy, Elizabeth R.; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. RP Ganzini, L (reprint author), Portland VA Med Ctr, Columbia Ctr Study Chron Comorbid Mental & Phys D, Hlth Serv Res & Dev, POB 1034, Portland, OR 97239 USA. EM Linda.Ganzini@va.gov FU Northwest Health Foundation FX Northwest Health Foundation. The funding source had no role in any aspect of the study or this paper. NR 37 TC 50 Z9 50 U1 2 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD OCT 25 PY 2008 VL 337 IS 7676 AR a1682 DI 10.1136/bmj.a1682 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 363WS UT WOS:000260298800034 PM 18842645 ER PT J AU Shen, J Brugge, WR Dimaio, CJ Pitman, MB AF Shen, Jian Brugge, William R. Dimaio, Christopher J. Pitman, Martha B. TI Molecular Analysis of Pancreatic Cyst Fluid SO CANCER CYTOPATHOLOGY LA English DT Meeting Abstract C1 [Shen, Jian; Brugge, William R.; Dimaio, Christopher J.; Pitman, Martha B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2008 VL 114 IS 5 SU S BP 346 EP 347 PG 2 WC Oncology; Pathology SC Oncology; Pathology GA 361PY UT WOS:000260140800008 ER PT J AU Moriarty, AT Darragh, TM Souers, R Fatheree, LA Wilbur, DC AF Moriarty, Ann T. Darragh, Teresa M. Souers, Rhona Fatheree, Lisa A. Wilbur, David C. TI Performance of Herpes Simplex Challenges in Proficiency Testing: Observations from the College of American Pathologists (CAP) Proficiency Testing (PAP PT) Program SO CANCER CYTOPATHOLOGY LA English DT Meeting Abstract C1 [Moriarty, Ann T.] Ameripath Indiana, Indianapolis, IN USA. [Darragh, Teresa M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Souers, Rhona] Coll Amer Pathologists, Northfield, IL USA. [Fatheree, Lisa A.] Coll Amer Pathologists, Indianapolis, IL USA. [Wilbur, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2008 VL 114 IS 5 SU S BP 394 EP 394 PG 1 WC Oncology; Pathology SC Oncology; Pathology GA 361PY UT WOS:000260140800083 ER PT J AU Reyes, CV Jensen, JD AF Reyes, Cesar V. Jensen, Joanne D. TI On-Site Evaluation of Bronchial Brushing cytology SO CANCER CYTOPATHOLOGY LA English DT Meeting Abstract C1 [Reyes, Cesar V.] Morris Hosp, Morris, IL USA. [Reyes, Cesar V.] Vet Affairs Edward Hines Jr Hosp, Morris, IL USA. [Jensen, Joanne D.] Morris Hosp, Hines, IL USA. [Jensen, Joanne D.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2008 VL 114 IS 5 SU S BP 408 EP 408 PG 1 WC Oncology; Pathology SC Oncology; Pathology GA 361PY UT WOS:000260140800103 ER PT J AU Knoepp, SM Mino-Kenudson, M Balassanian, R AF Knoepp, Stewart M. Mino-Kenudson, Mari Balassanian, Ronald TI Distinguishing Squamous Cell Carcinoma from Adenocarcinoma in Lung Fine Needle Aspiration Biopsy. A Cytologic/Histologic Review of 109 Cases SO CANCER CYTOPATHOLOGY LA English DT Meeting Abstract C1 [Knoepp, Stewart M.; Mino-Kenudson, Mari; Balassanian, Ronald] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2008 VL 114 IS 5 SU S BP 409 EP 410 PG 2 WC Oncology; Pathology SC Oncology; Pathology GA 361PY UT WOS:000260140800105 ER PT J AU Theodore, S Cao, SW McLean, P Standaert, D AF Theodore, Shaji Cao Shuwen McLean, Pamela Standaert, David TI Microglial activation and adaptive immune response in a mouse model of Parkinson's disease SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract C1 [Theodore, Shaji; Cao Shuwen; Standaert, David] Univ Alabama, Birmingham, W Midlands, England. [McLean, Pamela] Massachusetts Gen Hosp, Charlestown, MA USA. RI Cao, Shuwen/E-1924-2016 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD OCT 25 PY 2008 VL 203 IS 2 BP 188 EP 189 PG 2 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 377SJ UT WOS:000261270600175 ER PT J AU Offner, H AF Offner, Halina TI Immunoregulatory and neuroprotective effect of sex steroids on EAE and MS SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract C1 [Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. [Offner, Halina] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD OCT 25 PY 2008 VL 203 IS 2 BP 205 EP 206 PG 2 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 377SJ UT WOS:000261270600220 ER PT J AU Lin, HH Murray, M Cohen, T Colijn, C Ezzati, M AF Lin, Hsien-Ho Murray, Megan Cohen, Ted Colijn, Caroline Ezzati, Majid TI Effects of smoking and solid-fuel use on COPD, lung cancer, and tuberculosis in China: a time-based, multiple risk factor, modelling study SO LANCET LA English DT Article ID AIR-POLLUTION; HEALTH SYSTEM; RURAL CHINA; HONG-KONG; MORTALITY; INTERVENTIONS; DISEASE; TOBACCO; BURDEN; CESSATION AB Background Chronic obstructive pulmonary disease (COPD), lung cancer, and tuberculosis are three leading causes of death in China, where prevalences of smoking and solid-fuel use are also high. We aimed to predict the effects of risk-factor trends on COPD, lung cancer, and tuberculosis. Methods We used representative data sources to estimate past trends in smoking and household solid-fuel use and to construct a range of future scenarios. We obtained the aetiological effects of risk factors on diseases from meta-analyses of epidemiological studies and from large studies in China. We modelled future COPD and lung cancer mortality and tuberculosis incidence, taking into account the accumulation of hazardous effects of risk factors on COPD and lung cancer over time, and dependency of the risk of tuberculosis infection on the prevalence of disease. We quantified the sensitivity of our results to methods and data choices. Findings If smoking and solid-fuel use remain at current levels between 2003 and 2033, 65 million deaths from COPD and 18 million deaths from lung cancer are predicted in China; 82% of COPD deaths and 75% of lung cancer deaths will be attributable to the combined effects of smoking and solid-fuel use. Complete gradual cessation of smoking and solid-fuel use by 2033 could avoid 26 million deaths from COPD and 6.3 million deaths from lung cancer; interventions of intermediate magnitude would reduce deaths by 6-31% (COPD) and 8-26% (lung cancer). Complete cessation of smoking and solid-fuel use by 2033 would reduce the projected annual tuberculosis incidence in 2033 by 1.4-52% if 80% DOTS coverage is sustained, 27-62% if 50% coverage is sustained, or 33-71% if 20% coverage is sustained. Interpretation Reducing smoking and solid-fuel use can substantially lower predictions of COPD and lung cancer burden and would contribute to effective tuberculosis control in China. Funding International Union Against Tuberculosis and Lung Disease. C1 [Ezzati, Majid] Harvard Univ, Sch Publ Hlth, Dept Populat & Int Hlth, Boston, MA 02115 USA. [Lin, Hsien-Ho; Murray, Megan; Cohen, Ted] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ezzati, Majid] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Lin, Hsien-Ho] Mennonite Christian Hosp, Community Hlth Soc, Hualien, Taiwan. [Murray, Megan] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Murray, Megan; Cohen, Ted] Brigham & Womens Hosp, Div Social Med & Hlth Inequal, Boston, MA 02115 USA. [Colijn, Caroline] Univ Bristol, Dept Engn Math, Bristol, Avon, England. [Ezzati, Majid] Harvard Univ, Initiat Global Hlth, Cambridge, MA 02138 USA. RP Ezzati, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Populat & Int Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM majid_ezzati@harvard.edu RI Cohen, Ted/G-8101-2011; OI LIN, HSIEN-HO/0000-0002-7481-6016 FU International Union Against Tuberculosis and Lung Disease; World Bank FX This research was funded by the International Union Against Tuberculosis and Lung Disease, through a grant from the World Bank. We thank Cheng-Yuan Chiang, Donald Enarson, Ems Baris, and Ziad Obermeyer for Valuable discussion on methods and models, Colin Mathers for mortality projections, Zheng Zhou for help with data on smoking and fuel use, Jonathan Sinton for discussions on fuels use trends in China, and the Chinese Ministry of Health for tuberculosis prevalence data. We thank the China Health and Nutrition Survey, Jill Boreham, Rachel Huxley, and Zhengming Chen for valuable information and data on risk factor exposure and effects. NR 79 TC 102 Z9 112 U1 3 U2 27 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD OCT 25 PY 2008 VL 372 IS 9648 BP 1473 EP 1483 DI 10.1016/S0140-6736(08)61345-8 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 370ZJ UT WOS:000260801300024 PM 18835640 ER PT J AU Bhattacharya, D Hoover, S Falk, SP Weisblum, B Vestling, M Striker, R AF Bhattacharya, Dipankar Hoover, Spencer Falk, Shaun P. Weisblum, Bernard Vestling, Martha Striker, Rob TI Phosphorylation of yellow fever virus NS5 alters methyltransferase activity SO VIROLOGY LA English DT Article DE Phosphorylation; Methyltransferase; RNA cap; Flavivirus ID RNA CAP; CRYSTAL-STRUCTURE; PROTEINS; SEQUENCE; SUBSTRATE; TRANSCOMPLEMENTATION; HYPERPHOSPHORYLATION; TRANSCRIPTION; METHYLATIONS; REPLICATION AB Serine/threonine phosphorylation of the nonstructural protein 5 (NS5) is conserved feature of flaviviruses, but the kinase(s) responsible and function(s) remain unknown. Mass spectrometry was used to characterize phosphorylated residues of yellow fever virus (YFV) NS5 expressed in mammalian cells. Multiple different phosphopeptides were detected. Mutational and additional mass spectrometry data implicated serine 56 (S56), a conserved residue near the active site in the NS5 methyltransferase domain, as one of the phosphorylation sites. Methyltransferase activity is required to form a methylated RNA cap structure and for translation of the YFV polyprotein. We show the 2'-O methylation reaction requires the hydroxyl side chain of S56, and replacement with a negative charge inhibits enzymatic activity. Furthermore mutational alteration of S56, S56A or S56D, prevents amplification in a viral replicon system. Collectively our data suggest phosphorylation of NS5 S56 may act to shut down capping in the viral life cycle. Published by Elsevier Inc. C1 [Bhattacharya, Dipankar; Hoover, Spencer; Striker, Rob] Univ Wisconsin, Dept Med, Madison, WI 53706 USA. [Falk, Shaun P.; Weisblum, Bernard] Univ Wisconsin, Dept Pharmacol, Madison, WI 53706 USA. [Vestling, Martha] Univ Wisconsin, Dept Chem, Madison, WI 53706 USA. [Striker, Rob] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Striker, R (reprint author), Univ Wisconsin, Dept Med, Madison, WI 53706 USA. EM rtstriker@wisc.edu FU NIH/NIAID Regional Center of Excellence FX This work was sponsored by the NIH/NIAID Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research (RCE) Program. The authors wish to acknowledge membership within and support from the Region V 'Great Lakes' RCE (NIH award 1-U54-AI-057153). We thank the UW Madison Biotechnology mass spectrometry facility and the Human Proteomics Mass Spectrometry Facility supported by the "The Wisconsin Partnership Fund for a Healthy Future" for technical assistance. We also thank Janet Smith and Richard Kuhn for helpful discussions, and Deane Mosher for comments on drafts of this manuscript. NR 35 TC 19 Z9 19 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 25 PY 2008 VL 380 IS 2 BP 276 EP 284 DI 10.1016/j.virol.2008.07.013 PG 9 WC Virology SC Virology GA 361SW UT WOS:000260148400013 PM 18757072 ER PT J AU Chudakova, DA Zeidan, YH Wheeler, BW Yu, J Novgorodov, SA Kindy, MS Hannun, YA Gudz, TI AF Chudakova, Daria A. Zeidan, Youssef H. Wheeler, Brian W. Yu, Jin Novgorodov, Sergei A. Kindy, Mark S. Hannun, Yusuf A. Gudz, Tatyana I. TI Integrin-associated Lyn Kinase Promotes Cell Survival by Suppressing Acid Sphingomyelinase Activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SRC FAMILY KINASES; OLIGODENDROCYTE PROGENITOR MIGRATION; CYTOPLASMIC DOMAIN; CEREBRAL-ISCHEMIA; TYROSINE KINASES; SALVAGE PATHWAY; FACTOR RECEPTOR; BRAIN-INJURY; C-DELTA; CERAMIDE AB Integrins govern cellular adhesion and transmit signals leading to activation of intracellular signaling pathways aimed to prevent apoptosis. Herein we report that attachment of oligodendrocytes (OLs) to fibronectin via alpha(v)beta(3) integrin receptors rendered the cells more resistant to apoptosis than the cells attached to laminin via alpha(6)beta(1) integrins. Investigation of molecular mechanisms involved in alpha(v)beta(3) integrin-mediated cell survival revealed that ligation of the integrin with fibronectin results in higher expression of activated Lyn kinase. Both in OLs and in the mouse brain, Lyn selectively associates with alpha(v)beta(3) integrin, not with alpha(v)beta(5) integrin, leading to suppression of acid sphingomyelinase activity and preventing ceramide-mediated apoptosis. In OLs, knockdown of Lyn with small interfering RNA resulted in OL apoptosis with concomitant accumulation of C-16-ceramide due to activation of acid sphingomyelinase (ASMase) and sphingomyelin hydrolysis. Knocking down ASMase partially protected OLs from apoptosis. In the brain, ischemia/reperfusion (IR) triggered rearrangements in the alpha(v)beta(3) integrin-Lyn kinase complex leading to disruption of Lyn kinase-mediated suppression of ASMase activity. Thus, co-immunoprecipitation studies revealed an increased association of alpha(v)beta(3) integrin-Lyn kinase complex with ionotropic glutamate receptor subunits, GluR2 and GluR4, after cerebral IR. Sphingolipid analysis of the brain demonstrated significant accumulation of ceramide and sphingomyelin hydrolysis. The data suggest a novel mechanism for regulation of ASMase activity during cell adhesion in which Lyn acts as a key upstream kinase that may play a critical role in cerebral IR injury. C1 [Chudakova, Daria A.; Wheeler, Brian W.; Yu, Jin; Kindy, Mark S.; Gudz, Tatyana I.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Kindy, Mark S.; Gudz, Tatyana I.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Novgorodov, Sergei A.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Zeidan, Youssef H.; Novgorodov, Sergei A.; Hannun, Yusuf A.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. RP Gudz, TI (reprint author), Med Univ S Carolina, Dept Neurosci, 114 Doughty St, Charleston, SC 29425 USA. EM gudz@musc.edu FU National Institutes of Health/NCCR COBRE in Lipidomics and Pathobiology [P20 RR 17677-04]; National Institutes of Health [P01-CA97132, AG16583]; National Science Foundation EPSCOR [EPS0132573]; Veterans Affairs Merit Awards FX This work was supported, in whole or in part, by National Institutes of Health/NCCR COBRE in Lipidomics and Pathobiology Grant P20 RR 17677-04 (to T. I. G.) and National Institutes of Health Grant P01-CA97132 (to Y.A.H.). This work was also supported by National Science Foundation EPSCOR Grant EPS0132573 (to M. S. K.), and Veterans Affairs Merit Awards (to T. I. G. and M. S. K.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact.; Supported by National Institutes of Health Grant AG16583. NR 63 TC 23 Z9 24 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 24 PY 2008 VL 283 IS 43 BP 28806 EP 28816 DI 10.1074/jbc.M803301200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 362EB UT WOS:000260179900005 PM 18682390 ER PT J AU Makino, CL Peshenko, IV Wen, XH Olshevskaya, EV Barrett, R Dizhoor, AM AF Makino, Clint L. Peshenko, Igor V. Wen, Xiao-Hong Olshevskaya, Elena V. Barrett, Ronald Dizhoor, Alexander M. TI A Role for GCAP2 in Regulating the Photoresponse GUANYLYL CYCLASE ACTIVATION AND ROD ELECTROPHYSIOLOGY IN GUCA1B KNOCK-OUT MICE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RETINAL RODS; PHOTOTRANSDUCTION CASCADE; CGMP-PHOSPHODIESTERASE; PROTEINS GCAPS; CALCIUM; PHOTORECEPTORS; EXPRESSION; DEGENERATION; CLONING; DOMAIN AB Cyclic GMP serves as the second messenger in visual transduction, linking photon absorption by rhodopsin to the activity of ion channels. Synthesis of cGMP in photoreceptors is supported by a pair of retina-specific guanylyl cyclases, retGC1 and -2. Two neuronal calcium sensors, GCAP1 and GCAP2, confer Ca2+ sensitivity to guanylyl cyclase activity, but the importance and the contribution of each GCAP is controversial. To explore this issue, the gene GUCA1B, coding for GCAP2, was disrupted in mice, and the capacity for knock-out rods to regulate retGC and generate photoresponses was tested. The knock-out did not compromise rod viability or alter outer segment ultrastructure. Levels of retGC1, retGC2, and GCAP-1 expression did not undergo compensatory changes, but the absence of GCAP2 affected guanylyl cyclase activity in two ways; (a) the maximal rate of cGMP synthesis at low [Ca2+] dropped 2-fold and (b) the half-maximal rate of cGMP synthesis was attained at a higher than normal [Ca2+]. The addition of an antibody raised against mouse GCAP2 produced similar effects on the guanylyl cyclase activity in wild type retinas. Flash responses of GCAP2 knockout rods recovered more slowly than normal. Knock-out rods became more sensitive to flashes and to steps of illumination but tended to saturate at lower intensities, as compared with wild type rods. Therefore, GCAP2 regulation of guanylyl cyclase activity quickens the recovery of flash and step responses and adjusts the operating range of rods to higher intensities of ambient illumination. C1 [Peshenko, Igor V.; Olshevskaya, Elena V.; Dizhoor, Alexander M.] Salus Univ, PA Coll Optometry, Basic Sci & Hafter Res Labs, Elkins Pk, PA 19027 USA. [Makino, Clint L.; Wen, Xiao-Hong] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Makino, Clint L.; Wen, Xiao-Hong] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Barrett, Ronald] Wayne State Univ, Dept Anat & Cell Biol, Detroit, MI 48201 USA. RP Dizhoor, AM (reprint author), Salus Univ, PA Coll Optometry, Basic Sci & Hafter Res Labs, 8360 Old York Rd, Elkins Pk, PA 19027 USA. EM adizhoor@salus.edu OI Makino, Clint/0000-0002-6005-9069 FU National Institutes of Health [EY11522, EY011358, EY014104]; Massachusetts Lions Eye Research Fund; Pennsylvania Lions Sight Conservation and Eye Research Foundation; Pennsylvania Department of Health FX This work was supported, in whole or in part, by National Institutes of Health Grants EY11522, EY011358, and EY014104. This work was also supported by the Massachusetts Lions Eye Research Fund, the Pennsylvania Lions Sight Conservation and Eye Research Foundation, and the Pennsylvania Department of Health. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 52 TC 54 Z9 54 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 24 PY 2008 VL 283 IS 43 BP 29135 EP 29143 DI 10.1074/jbc.M804445200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 362EB UT WOS:000260179900041 PM 18723510 ER PT J AU Larade, K Jiang, ZG Zhang, YZ Wang, WF Bonner-Weir, S Zhu, H Bunn, HF AF Larade, Kevin Jiang, Zhigang Zhang, Yongzhao Wang, WenFang Bonner-Weir, Susan Zhu, Hao Bunn, H. Franklin TI Loss of Ncb5or Results in Impaired Fatty Acid Desaturation, Lipoatrophy, and Diabetes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STEAROYL-COA DESATURASE-1; PANCREATIC BETA-CELLS; ENDOPLASMIC-RETICULUM STRESS; COENZYME-A DESATURASE; BREAST-CANCER CELLS; FACTOR-KAPPA-B; CONGENITAL METHEMOGLOBINEMIA; CYTOCHROME-B5 REDUCTASE; GENERALIZED DEFICIENCY; MENTAL-RETARDATION AB Targeted ablation of the novel flavoheme reductase Ncb5or knock-out (KO) results in progressive loss of pancreatic beta-cells and white adipose tissue over time. Lipoatrophy persisted in KO animals in which the confounding metabolic effects of diabetes were eliminated by islet transplantation (transplanted knockout (TKO)). Lipid profiles in livers prepared from TKO animals were markedly deficient in triglycerides and diacylglycerides. Despite enhanced expression of stearoyl-Co-A desaturase-1, levels of palmitoleic and oleic acids (Delta 9 fatty acid desaturation) were decreased in TKO relative to wild type controls. Treatment of KO hepatocytes with palmitic acid reduced cell viability and increased apoptosis, a response blunted by coincubation with oleic acid. The results presented here support the hypothesis that Ncb5or supplies electrons for fatty acid desaturation, offer new insight into the regulation of a crucial step in fatty acid biosynthesis, and provide a plausible explanation for both the diabetic and the lipoatrophic phenotype in Ncb5or(-/-) mice. C1 [Larade, Kevin; Jiang, Zhigang; Zhang, Yongzhao; Bunn, H. Franklin] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Wang, WenFang; Zhu, Hao] Univ Kansas, Med Ctr, Sch Allied Hlth, Kansas City, KS 66160 USA. [Bonner-Weir, Susan] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Bunn, HF (reprint author), CHRB 5-215,75 Francis St, Boston, MA 02115 USA. EM hfbunn@rics.bwh.harvard.edu FU National Institutes of Health [DK067355, AI56374]; Juvenile Diabetes Research Foundation [1-2005-121, 3-2005-232]; American Diabetes Association [7-04-RA-15] FX This work was supported, in whole or in part, by National Institutes of Health Grants DK067355 and AI56374. This work was also supported by Juvenile Diabetes Research Foundation Grants 1-2005-121 and 3-2005-232 and American Diabetes Association Grant 7-04-RA-15. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked " advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 52 TC 20 Z9 20 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 24 PY 2008 VL 283 IS 43 BP 29285 EP 29291 DI 10.1074/jbc.M804645200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 362EB UT WOS:000260179900055 PM 18682384 ER PT J AU Pierce, A Mirzaei, H Muller, F De Waal, E Taylor, AB Leonard, S Van Remmen, H Regnier, F Richardson, A Chaudhuri, A AF Pierce, Anson Mirzaei, Hamid Muller, Florian De Waal, Eric Taylor, Alexander B. Leonard, Shanique Van Remmen, Holly Regnier, Fred Richardson, Arlan Chaudhuri, Asish TI GAPDH Is Conformationally and Functionally Altered in Association with Oxidative Stress in Mouse Models of Amyotrophic Lateral Sclerosis SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE protein oxidation; amyotrophic lateral sclerosis; BisANS; protein unfolding; GAPDH ID MOTOR-NEURON DEGENERATION; COPPER-BINDING-SITE; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; SUPEROXIDE-DISMUTASE; PROTEIN OXIDATION; CREATINE-KINASE; SKELETAL-MUSCLE; TRANSGENIC MICE; SELECTIVE DEGRADATION; HYDROGEN-PEROXIDE AB It is proposed that conformational changes induced in proteins by oxidation can lead to loss of activity or protein aggregation through exposure of hydrophobic residues and alteration in surface hydrophobicity. Because increased oxidative stress and protein aggregation are consistently observed in amyotrophic lateral sclerosis (ALS), we used a 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid (BisANS) photolabeling approach to monitor changes in protein unfolding in vivo in skeletal muscle proteins in ALS mice. We find two major proteins, creatine kinase (CK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), conformationally affected in the ALS G93A mouse model concordant with a 43% and 41% reduction in enzyme activity, respectively. This correlated with changes in conformation and activity that were detected in CK and GAPDH with in vitro oxidation. Interestingly, we found that GAPDH, but not CK, is conformationally and functionally affected in a longer-lived ALS model (H46R/H48Q), exhibiting a 22%, reduction in enzyme activity. We proposed a reaction mechanism for BisANS with nucleophilic amino acids Such as lysine, serine, threonine, and tyrosine, and BisANS was found to be primarily incorporated to lysine residues in GAPDH. We identified the specific BisANS incorporation sites on GAPDH in nontransgenic (NTg), G93A, and H46R/H48Q mice using liquid chromatography-tandem mass spectrometry analysis. Four BisANS-containing sites (K52, K104, K212, and K248) were found in NTg GAPDH, while three out of four of these sites were lost in either G93A or H46R/H48Q GAPDH. Conversely, eight new sites (K2, K63, K69, K114, K183, K251, S330, and K331) were found on GAPDH for G93A, including one common site (K114) for H46R/H48Q, which is not found on GAPDH from NTg mice. These data show that GAPDH is differentially affected structurally and functionally in vivo in accordance with the degree of oxidative stress associated with these two models of ALS. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Pierce, Anson; Muller, Florian; Van Remmen, Holly; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Mirzaei, Hamid; Regnier, Fred] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [De Waal, Eric; Taylor, Alexander B.; Chaudhuri, Asish] Univ Texas San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Leonard, Shanique; Van Remmen, Holly; Richardson, Arlan; Chaudhuri, Asish] Univ Texas San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Van Remmen, Holly; Richardson, Arlan; Chaudhuri, Asish] S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA. [Taylor, Alexander B.] Univ Texas Hlth Sci Ctr San Antonio, Xray Crystallog Core Lab, San Antonio, TX 78229 USA. RP Chaudhuri, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM Chaudhuria@uthscsa.edu RI Pierce, Anson/D-1079-2012 OI Pierce, Anson/0000-0002-1383-0180 FU Veterans Affairs (VA)-Veterans Integrated Service Network; Amyotrophic Lateral Sclerosis Association; VA Merit; MDA 3879; National Institutes of Health [AG025362, AG23843, R37 AG26557]; Department of VA; VA CDA-2 FX We would like to thank Dr. David Borchelt for kindly providing us with the H46R/H48Q mice for use in this study. We would also like to thank Dr. Susan Weintraub and the Mass Spectrometry Core for access to their facility and tlieir assistance in the identification of proteins by MALDI-TOF MS. This work was supported by Veterans Affairs (VA)-Veterans Integrated Service Network, Amyotrophic Lateral Sclerosis Association, and VA Merit grants (A.C.); VA Merit and MDA 3879 (H.V.R.); National Institutes of Health grant AG025362 (F.R. and H.V.R.); National Institutes of Health grants AG23843 and R37 AG26557 (A.R.); a Research Enhancement Award Program grant from the Department of VA (to A.R., H.V.R., and A.C.); and a VA CDA-2 grant (to A.P.). NR 51 TC 44 Z9 45 U1 1 U2 8 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD OCT 24 PY 2008 VL 382 IS 5 BP 1195 EP 1210 DI 10.1016/j.jmb.2008.07.088 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 363LY UT WOS:000260270000009 PM 18706911 ER PT J AU Gillespie, K Kodani, I Dickinson, DP Ogbureke, KUE Camba, AM Wu, MJ Looney, S Chu, TC Qin, HY Bisch, F Sharawy, M Schuster, GS Hsu, SD AF Gillespie, Kevin Kodani, Isamu Dickinson, Douglas P. Ogbureke, Kalu U. E. Camba, Amy M. Wu, Mengjie Looney, Stephen Chu, Tin-Chun Qin, Haiyan Bisch, Frederick Sharawy, Mohamed Schuster, George S. Hsu, Stephen D. TI Effects of oral consumption of the green tea polyphenol EGCG in a murine model for human Sjogren's syndrome, an autoimmune disease SO LIFE SCIENCES LA English DT Article DE Sjogren's syndrome; Green tea; EGCG; Autoimmune disease; Non-obese diabetic mice ID SALIVARY-GLAND; CELLS; PATHOGENESIS; EXPRESSION; THERAPIES AB Significance: Protection of glandular cells from autoimmune-induced damage would be of significant clinical benefit to Sjogren's syndrome (SS) patients. Epigallocatechin-3-gallate (EGCG) possesses anti-apoptotic, anti-inflammatory, and autoantigen-inhibitory properties. Aims: To investigate if EGCG protects against certain autoimmune-induced pathological changes in the salivary glands of the non-obese diabetic (NOD) mouse model for SS. Main methods: Animals were provided with either water or water containing 0.2% EGCG. At the age of 8,16 and 22 weeks, submandibular salivary gland tissue and serum samples were collected for pathological and serological analysis. Key findings: Significant lymphocyte infiltration was observed in the salivary glands of the water-fed group at the age of 16 weeks, while the EGCG group showed reduced lymphocyte infiltration. By 22 weeks of age, water-fed animals demonstrated elevated levels of apoptotic activity within the lymphocytic infiltrates, and high levels of serum total anti-nuclear antibody, compared to EGCG-fed animals. Remarkably, proliferating cell nuclear antigen (PCNA) and Ki-67 levels in the salivary glands of water-fed NOD mice were significantly elevated in comparison to BALB/c control mice; in contrast, PCNA and Ki-67 levels in EGCC-fed NOD animals were similar to BALB/c mice. These results indicate that EGCG protects the NOD mouse submandibular glands from autoimmune-induced inflammation, and reduces serum autoantibody levels. Abnormal proliferation, rather than apoptosis, appears to be a characteristic of the NOD mouse gland that is normalized by EGCG. The evidence suggests that EGCG could be useful in delaying or managing SS-like autoimmune disorders. (C) 2008 Elsevier Inc. All rights reserved. C1 [Dickinson, Douglas P.; Ogbureke, Kalu U. E.; Camba, Amy M.; Looney, Stephen; Qin, Haiyan; Sharawy, Mohamed; Schuster, George S.; Hsu, Stephen D.] Med Coll Georgia, Sch Dent, Dept Oral Biol, Augusta, GA 30912 USA. [Gillespie, Kevin; Bisch, Frederick] USA, Dept Periodontol, Ft Gordon, GA USA. [Kodani, Isamu] Tottori Univ, Fac Med, Tottori Univ Hosp, Dept Oral & Maxillofacial Surg, Yonago, Tottori 683, Japan. [Wu, Mengjie] Zhejiang Univ, Sch Dent, Hosp Stomotol, Hangzhou 310003, Zhejiang, Peoples R China. [Chu, Tin-Chun] Seton Hall Univ, Coll Arts & Sci, Dept Biol Sci, S Orange, NJ USA. [Hsu, Stephen D.] US Dept Vet Affairs, VA Med Ctr, Augusta, GA USA. RP Hsu, SD (reprint author), Med Coll Georgia, Sch Dent, Dept Oral Biol, AD1443, Augusta, GA 30912 USA. EM shsu@mail.mcg.edu RI Dickinson, Douglas/B-9111-2009; OI Chu, Tinchun/0000-0002-6314-1009 FU MCG; US Army Periodontics; Department of Oral Biology; School of Dentistry FX The authors thank Ms. Vera B. Larke for her technical assistance. This study was supported in part by funds from a grant from MCG, a fund from US Army Periodontics, and from Department of Oral Biology, School of Dentistry to S.H. NR 28 TC 34 Z9 37 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD OCT 24 PY 2008 VL 83 IS 17-18 BP 581 EP 588 DI 10.1016/j.lfs.2008.08.011 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 365JJ UT WOS:000260401700001 PM 18809413 ER PT J AU Hoffman, AN Cheng, JP Zafonte, RD Kline, AE AF Hoffman, Ann N. Cheng, Jeffrey P. Zafonte, Ross D. Kline, Anthony E. TI Administration of haloperidol and risperidone after neurobehavioral testing hinders the recovery of traumatic brain injury-induced deficits SO LIFE SCIENCES LA English DT Article DE Antipsychotics; Brain injury; Functional recovery; Water maze ID CONTROLLED CORTICAL IMPACT; WATER MAZE PERFORMANCE; RAT FRONTAL-CORTEX; ISCHEMIA IN-VIVO; ATYPICAL ANTIPSYCHOTICS; SIGMA(1) RECEPTOR; WORKING-MEMORY; DOPAMINERGIC TRANSMISSION; METHYLPHENIDATE TREATMENT; CHOLINERGIC MARKERS AB Aims: Agitation and aggression are common behavioral sequelae of traumatic brain injury (TBI). The management of these symptoms is critical for effective patient care and therefore antipsychotics are routinely administered even though the benefits vs. risks of this approach on functional outcome after TBI are unclear. A recent study from our group revealed that both haloperidol and risperidone impaired recovery when administered prior to testing. However, the results may have been confounded by drug-induced sedation. Hence, the current study reevaluated the behavioral effects of haloperidol and risperidone when provided after daily testing, thus circumventing the potential sedative effect. Main methods: Fifty-four isoflurane-anesthetized mate rats received a cortical impact or sham injury and then were randomly assigned to three TBI and three sham groups that received haloperidol (0.5 mg/kg), risperidone (0.45 nng/kg), or vehicle (1.0 mL/kg). Treatments began 24 h after surgery and were administered (i.p.) every day thereafter for 19 days. Motor and cognitive function was assessed on post-operative days 1-5 and 14-19, respectively. Hippocampal CA(1)/CA(3) neurons and cortical lesion volume were quantified at 3 weeks. Key findings: Only risperidone delayed motor recovery, but both antipsychotics impaired spatial learning relative to vehicle (p<0.05). Neither swim speed nor histological outcomes were affected. No differences were observed between the haloperidol and risperidone groups in any task. Significance: These data support our previous finding that chronic haloperidol and risperidone hinder the recovery of TBI-induced deficits, and augment those data by demonstrating that the effects are not mediated by drug-induced sedation. (C) 2008 Elsevier Inc. All rights reserved. C1 [Kline, Anthony E.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA. [Hoffman, Ann N.; Cheng, Jeffrey P.; Kline, Anthony E.] Univ Pittsburgh, Safar Ctr Resuscitat Res, Pittsburgh, PA 15213 USA. [Kline, Anthony E.] Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA 15213 USA. [Kline, Anthony E.] Univ Pittsburgh, Ctr Neural Basis Cognit, Pittsburgh, PA 15213 USA. [Zafonte, Ross D.] Harvard Univ, Sch Med, Boston, MA 02144 USA. [Zafonte, Ross D.] Spaulding Rehabil Hosp, Boston, MA 02114 USA. [Zafonte, Ross D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kline, AE (reprint author), Univ Pittsburgh, Dept Phys Med & Rehabil, 3471 5th Ave,Suite 201, Pittsburgh, PA 15213 USA. EM klineae@upmc.edu OI Cheng, Jeffrey/0000-0001-8285-3207 FU NIH [HD046700] FX This work was supported, in part, by NIH grant HD046700 (AEK). NR 48 TC 42 Z9 43 U1 2 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD OCT 24 PY 2008 VL 83 IS 17-18 BP 602 EP 607 DI 10.1016/j.lfs.2008.08.007 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 365JJ UT WOS:000260401700004 PM 18801378 ER PT J AU Basu, U Wang, YB Alt, FW AF Basu, Uttiya Wang, Yabin Alt, Frederick W. TI Evolution of Phosphorylation-Dependent Regulation of Activation-Induced Cytidine Deaminase SO MOLECULAR CELL LA English DT Article ID CLASS-SWITCH RECOMBINATION; SINGLE-STRANDED-DNA; ANTIBODY DIVERSIFICATION ENZYME; KINASE-A PHOSPHORYLATION; SOMATIC HYPERMUTATION; B-CELLS; AID; MICRORNA-155; MECHANISMS; REGIONS AB Interaction of activation-induced cytidine deaminase (AID) with replication protein A (RPA) has been proposed to promote AID access to transcribed double-stranded (ds) DNA during immunoglobulin light chain and heavy chain class switch recombination (CSR). Mouse AID (mAID) interaction with RPA and transcription-dependent dsDNA deamination in vitro requires protein kinase A (PKA) phosphorylation at serine 38 (S38), and normal mAID CSR activity depends on S38. However, zebrafish AID (zAID) catalyzes robust CSR in mouse cells despite lacking an S38-equivalent PKA site. Here, we show that aspartate 44 (D44) in zAID provides similar in vitro and in vivo functionality as mAID S38 phosphorylation. Moreover, introduction of a PKA site into a zAID D44 mutant made it PKA dependent for in vitro activities and restored normal CSR activity. Based on these findings, we generated mAID mutants that similarly function independently of S38 phosphorylation. Comparison of bony fish versus amphibian and mammalian AlDs suggests evolutionary divergence from constitutive to PKA-regulated RPA/AID interaction. C1 [Basu, Uttiya; Wang, Yabin; Alt, Frederick W.] Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Basu, Uttiya; Wang, Yabin; Alt, Frederick W.] Immune Dis Inst, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst, 300 Longwood Ave, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu FU National Institutes of Health FX We thank David Schatz, Jayanta Chaudhuri, Andrew Franklin, Jing Wang, Vivian Choi, Abhishek Datta, and Ting Ting Zhang for evaluation of the manuscript. We thank Tasuku Honjo for AID-deficient mice, and Vasco Barrette and Michel Nussenzweig for a retroviral construct expressing WT zebrafish AID. Tiffany Bel and Lisa Aquaviva provided technical assistance in maintenance of AID-deficient mice. U.B. was a fellow of the Irvington Institute of Immunology program of the Cancer Research Institute, and is current y a Special Fellow of the Leukemia and Lymphoma Society of America. This work was supported by a National Institutes of Health grant to F.W.A., who is an investigator of the Howard Hughes Medical Institute. NR 36 TC 23 Z9 26 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD OCT 24 PY 2008 VL 32 IS 2 BP 285 EP 291 DI 10.1016/j.molcel.2008.08.019 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 367IX UT WOS:000260546800016 PM 18951095 ER PT J AU Chen, YI Wang, FN Nelson, AJ Xu, HB Kim, Y Rosen, BR Kwong, KK AF Chen, Y. Iris Wang, Fu-Nien Nelson, Aimee J. Xu, Haibo Kim, Young Rosen, Bruce R. Kwong, Kenneth K. TI Electrical stimulation modulates the amphetamine-induced hemodynamic changes: An fMRI study to compare the effect of stimulating locations and frequencies on rats SO NEUROSCIENCE LETTERS LA English DT Article DE Amphetamine; fMRI; rCBV; Acupuncture; Electroacupuncture; Forepaw stimulation ID INDUCED PLACE PREFERENCE; SOMATOTOPIC ORGANIZATION; SOMATOSENSORY CORTEX; MORPHINE-WITHDRAWAL; DOPAMINE RELEASE; BASAL GANGLIA; MOTOR CORTEX; HUMAN BRAIN; ACUPUNCTURE; ELECTROACUPUNCTURE AB Our previous fMRI and microdialysis measurements showed that electroacupuncture (EA) at LI4 was effective in alleviating excessive cerebral dopamine release induced by D-amphetamine (AMPH) in rats. We now compare the effect of EA in adjusting excess dopamine release at two stimulating frequencies (2 Hz versus 100 Hz at LI4) and at two acupoints (forepaw (LI4) versus hindpaw (ST36), at 2 Hz). fMRI measurements of relative cerebral blood volume (rCBV) were used to monitor the brain activity of "rest", followed by AMPH challenge, 10 min "rest", and then 20 min of EA. Results: EA at LI4 and ST36 significantly attenuated the AMPH-induced rCBV increases in the striatum, S1 cortex, and thalamus. Frequency: EA at 100 Hz induced greater attenuation of rCBV than EA at 2 Hz in the S1, insula, anterior cingulate cortices, dorsolateral striatum, and thalamus. Acupoints: EA at LI4 modulated a broader area in the medial anterior striatum while EA at ST36 modulated a more site-specific area in the dorsolateral striatum. in the thalamus, EA at LI4 showed greater attenuating effect than EA at ST36 did. However, in the insular cortex, EA at ST36 showed stronger attenuation. Conclusion: EA at both LI4 and ST36 was effective in restoring dopamine homeostasis from an excess state, with the most effective response at LI4 with 100 Hz, while the responses to 2 Hz EA at LI4 and ST36 showed slightly different spatial distribution of MR signal. This therefore provided insight into the neurophysiological basis of electroacupuncture effects in cortical and subcortical circuits. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Chen, Y. Iris; Wang, Fu-Nien; Xu, Haibo; Kim, Young; Rosen, Bruce R.; Kwong, Kenneth K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging,Dept Radiol, Charlestown, MA 02129 USA. [Wang, Fu-Nien] Natl Tsing Hua Univ, Dept Biomed Engn & Environm Sci, Hsinchu, Taiwan. [Nelson, Aimee J.] Univ Waterloo, Waterloo, ON N2L 3G1, Canada. [Xu, Haibo] Union Hosp, Wuhan, Peoples R China. RP Chen, YI (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging,Dept Radiol, Room 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM iris@nmr.mgh.harvard.edu FU NIH/NCCAM [P01 AT002048] FX Funding agency: sponsored by NIH/NCCAM grant P01 AT002048. NR 37 TC 4 Z9 4 U1 2 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 24 PY 2008 VL 444 IS 2 BP 117 EP 121 DI 10.1016/j.neulet.2008.08.033 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 366XG UT WOS:000260516300002 PM 18722508 ER PT J AU Kahn, CR AF Kahn, C. Ronald TI Medicine - Can we nip obesity in its vascular bud? SO SCIENCE LA English DT Editorial Material ID ADIPOSE-TISSUE; STEM-CELLS; NEURAL CREST; BROWN; FAT; ORIGIN; PREADIPOCYTES; ADIPOGENESIS; ADIPOCYTES C1 [Kahn, C. Ronald] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu FU NIDDK NIH HHS [R01 DK082659, P30 DK036836] NR 21 TC 21 Z9 21 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 24 PY 2008 VL 322 IS 5901 BP 542 EP 543 DI 10.1126/science.1165667 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363WV UT WOS:000260299100029 PM 18948531 ER PT J AU Pettigrew, LC Kindy, MS Scheff, S Springer, JE Kryscio, RJ Li, Y Grass, DS AF Pettigrew, L. Creed Kindy, Mark S. Scheff, Stephen Springer, Joe E. Kryscio, Richard J. Li, Yizhao Grass, David S. TI Focal cerebral ischemia in the TNFalpha-transgenic rat SO JOURNAL OF NEUROINFLAMMATION LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; BRAIN-INJURY; PROINFLAMMATORY CYTOKINES; INDUCED APOPTOSIS; ARTERY OCCLUSION; FACTOR RECEPTOR; MICE LACKING; TNF-ALPHA; STROKE AB Background: To determine if chronic elevation of the inflammatory cytokine, tumor necrosis factor-alpha (TNF alpha), will affect infarct volume or cortical perfusion after focal cerebral ischemia. Methods: Transgenic (TNF alpha-Tg) rats overexpressing the murine TNF alpha gene in brain were prepared by injection of mouse DNA into rat oocytes. Brain levels of TNF alpha mRNA and protein were measured and compared between TNF alpha-Tg and non-transgenic (non-Tg) littermates. Mean infarct volume was calculated 24 hours or 7 days after one hour of reversible middle cerebral artery occlusion (MCAO). Cortical perfusion was monitored by laser-Doppler flowmetry (LDF) during MCAO. Cortical vascular density was quantified by stereology. Post-ischemic cell death was assessed by immunohistochemistry and regional measurement of caspase-3 activity or DNA fragmentation. Unpaired t tests or analysis of variance with post hoc tests were used for comparison of group means. Results: In TNF alpha-Tg rat brain, the aggregate mouse and rat TNF alpha mRNA level was fourfold higher than in non-Tg littermates and the corresponding TNF alpha protein level was increased fivefold (p <= 0.01). Infarct volume was greater in TNF alpha-Tg rats than in non-Tg controls at 24 hours (p <= 0.05) and 7 days (p <= 0.01). Within the first 10 minutes of MCAO, cortical perfusion measured by LDF was reduced in TNF alpha-Tg rats (p <= 0.05). However, regional vascular density was equivalent between TNF alpha-Tg and non-Tg animals (p = NS). Neural cellular apoptosis was increased in transgenic animals as shown by elevated caspase-3 activity (p = 0.05) and DNA fragmentation (p <= 0.001) at 24 hours. Conclusion: Chronic elevation of TNF alpha protein in brain increases susceptibility to ischemic injury but has no effect on vascular density. TNF alpha-Tg animals are more susceptible to apoptotic cell death after MCAO than are non-Tg animals. We conclude that the TNF alpha-Tg rat is a valuable new tool for the study of cytokine-mediated ischemic brain injury. C1 [Pettigrew, L. Creed; Scheff, Stephen] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. [Pettigrew, L. Creed] Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA. [Pettigrew, L. Creed] Vet Adm Med Ctr, Lexington, KY 40511 USA. [Kindy, Mark S.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Kindy, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Springer, Joe E.] Univ Kentucky, Dept Phys Med & Rehabil, Lexington, KY 40536 USA. [Kryscio, Richard J.] Univ Kentucky, Dept Stat, Lexington, KY 40536 USA. [Kryscio, Richard J.] Univ Kentucky, Sch Publ Hlth, Lexington, KY 40536 USA. [Li, Yizhao] Jinan Great Wall Hosp, Jinan, Shandong, Peoples R China. [Grass, David S.] Xenogen Biosci, Cranbury, NJ USA. RP Pettigrew, LC (reprint author), Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. EM cpetti@uky.edu; kindyms@musc.edu; sscheff@email.uky.edu; joe.springer@uky.edu; kryscio@email.uky.edu; swillia@uky.edu; David.Grass@xenogen.com FU NIH/NINDS [R01 NS047395, R01 NS039588]; Shandong University, China FX Financial support was provided by NIH/NINDS grants R01 NS047395 (LCP) and R01 NS039588 (MSK) and by a Visiting Research Scientist Award provided by Shandong University, China (YL) for training at the University of Kentucky in Lexington, Kentucky. Dr. George Kollias prepared the microinjection construct containing the murine TNF alpha gene and its promoter that was used to make the transgenic animal. Mr. Richard Coffee constructed the animal at Xenogen Biosciences in Cranbury, New Jersey. We thank Mary Louise Holtz, Ph. D., Xaio-Hong Song, M. D., Susan D. Craddock, and Ravikumar Rao for technical contributions to this work and Sherry Chandler Williams, ELS, for editing the manuscript and preparing the illustrations. NR 48 TC 32 Z9 32 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PD OCT 23 PY 2008 VL 5 AR 47 DI 10.1186/1742-2094-5-47 PG 19 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 371YZ UT WOS:000260869900001 PM 18947406 ER PT J AU Chin, L Meyerson, M Aldape, K Bigner, D Mikkelsen, T VandenBerg, S Kahn, A Penny, R Ferguson, ML Gerhard, DS Getz, G Brennan, C Taylor, BS Winckler, W Park, P Ladanyi, M Hoadley, KA Verhaak, RGW Hayes, DN Spellman, PT Absher, D Weir, BA Ding, L Wheeler, D Lawrence, MS Cibulskis, K Mardis, E Zhang, JH Wilson, RK Donehower, L Wheeler, DA Purdom, E Wallis, J Laird, PW Herman, JG Schuebel, KE Weisenberger, DJ Baylin, SB Schultz, N Yao, J Wiedemeyer, R Weinstein, J Sander, C Gibbs, RA Gray, J Kucherlapati, R Lander, ES Myers, RM Perou, CM McLendon, R Friedman, A Van Meir, EG Brat, DJ Mastrogianakis, GM Olson, JJ Lehman, N Yung, WKA Bogler, O Berger, M Prados, M Muzny, D Morgan, M Scherer, S Sabo, A Nazareth, L Lewis, L Hall, O Zhu, YM Ren, YR Alvi, O Yao, JQ Hawes, A Jhangiani, S Fowler, G San Lucas, A Kovar, C Cree, A Dinh, H Santibanez, J Joshi, V Gonzalez-Garay, ML Miller, CA Milosavljevic, A Sougnez, C Fennell, T Mahan, S Wilkinson, J Ziaugra, L Onofrio, R Bloom, T Nicol, R Ardlie, K Baldwin, J Gabriel, S Fulton, RS McLellan, MD Larson, DE Shi, XQ Abbott, R Fulton, L Chen, K Koboldt, DC Wendl, MC Meyer, R Tang, YZ Lin, L Osborne, JR Dunford-Shore, BH Miner, TL Delehaunty, K Markovic, C Swift, G Courtney, W Pohl, C Abbott, S Hawkins, A Leong, S Haipek, C Schmidt, H Wiechert, M Vickery, T Scott, S Dooling, DJ Chinwalla, A Weinstock, GM O'Kelly, M Robinson, J Alexe, G Beroukhim, R Carter, S Chiang, D Gould, J Gupta, S Korn, J Mermel, C Mesirov, J Monti, S Nguyen, H Parkin, M Reich, M Stransky, N Garraway, L Golub, T Protopopov, A Perna, I Aronson, S Sathiamoorthy, N Ren, G Kim, H Kong, SK Xiao, YH Kohane, IS Seidman, J Cope, L Pan, F Van Den Berg, D Van Neste, L Yi, JM Li, JZ Southwick, A Brady, S Aggarwal, A Chung, T Sherlock, G Brooks, JD Jakkula, LR Lapuk, AV Marr, H Dorton, S Choi, YG Han, J Ray, A Wang, V Durinck, S Robinson, M Wang, NJ Vranizan, K Peng, V Van Name, E Fontenay, GV Ngai, J Conboy, JG Parvin, B Feiler, HS Speed, TP Socci, ND Olshen, A Lash, A Reva, B Antipin, Y Stukalov, A Gross, B Cerami, E Wang, WQ Qin, LX Seshan, VE Villafania, L Cavatore, M Borsu, L Viale, A Gerald, W Topal, MD Qi, Y Balu, S Shi, Y Wu, G Bittner, M Shelton, T Lenkiewicz, E Morris, S Beasley, D Sanders, S Sfeir, R Chen, J Nassau, D Feng, L Hickey, E Schaefer, C Madhavan, S Buetow, K Barker, A Vockley, J Compton, C Vaught, J Fielding, P Collins, F Good, P Guyer, M Ozenberger, B Peterson, J Thomson, E AF Chin, L. Meyerson, M. Aldape, K. Bigner, D. Mikkelsen, T. VandenBerg, S. Kahn, A. Penny, R. Ferguson, M. L. Gerhard, D. S. Getz, G. Brennan, C. Taylor, B. S. Winckler, W. Park, P. Ladanyi, M. Hoadley, K. A. Verhaak, R. G. W. Hayes, D. N. Spellman, Paul T. Absher, D. Weir, B. A. Ding, L. Wheeler, D. Lawrence, M. S. Cibulskis, K. Mardis, E. Zhang, Jinghui Wilson, R. K. Donehower, L. Wheeler, D. A. Purdom, E. Wallis, J. Laird, P. W. Herman, J. G. Schuebel, K. E. Weisenberger, D. J. Baylin, S. B. Schultz, N. Yao, Jun Wiedemeyer, R. Weinstein, J. Sander, C. Gibbs, R. A. Gray, J. Kucherlapati, R. Lander, E. S. Myers, R. M. Perou, C. M. McLendon, Roger Friedman, Allan Van Meir, Erwin G Brat, Daniel J Mastrogianakis, Gena Marie Olson, Jeffrey J Lehman, Norman Yung, W. K. Alfred Bogler, Oliver Berger, Mitchel Prados, Michael Muzny, Donna Morgan, Margaret Scherer, Steve Sabo, Aniko Nazareth, Lynn Lewis, Lora Hall, Otis Zhu, Yiming Ren, Yanru Alvi, Omar Yao, Jiqiang Hawes, Alicia Jhangiani, Shalini Fowler, Gerald San Lucas, Anthony Kovar, Christie Cree, Andrew Dinh, Huyen Santibanez, Jireh Joshi, Vandita Gonzalez-Garay, Manuel L. Miller, Christopher A. Milosavljevic, Aleksandar Sougnez, Carrie Fennell, Tim Mahan, Scott Wilkinson, Jane Ziaugra, Liuda Onofrio, Robert Bloom, Toby Nicol, Rob Ardlie, Kristin Baldwin, Jennifer Gabriel, Stacey Fulton, Robert S. McLellan, Michael D. Larson, David E. Shi, Xiaoqi Abbott, Rachel Fulton, Lucinda Chen, Ken Koboldt, Daniel C. Wendl, Michael C. Meyer, Rick Tang, Yuzhu Lin, Ling Osborne, John R. Dunford-Shore, Brian H. Miner, Tracie L. Delehaunty, Kim Markovic, Chris Swift, Gary Courtney, William Pohl, Craig Abbott, Scott Hawkins, Amy Leong, Shin Haipek, Carrie Schmidt, Heather Wiechert, Maddy Vickery, Tammi Scott, Sacha Dooling, David J. Chinwalla, Asif Weinstock, George M. O'Kelly, Michael Robinson, Jim Alexe, Gabriele Beroukhim, Rameen Carter, Scott Chiang, Derek Gould, Josh Gupta, Supriya Korn, Josh Mermel, Craig Mesirov, Jill Monti, Stefano Nguyen, Huy Parkin, Melissa Reich, Michael Stransky, Nicolas Garraway, Levi Golub, Todd Protopopov, Alexei Perna, Ilana Aronson, Sandy Sathiamoorthy, Narayan Ren, Georgia Kim, Hyunsoo Kong, Sek Won Xiao, Yonghong Kohane, Isaac S. Seidman, Jon Cope, Leslie Pan, Fei Van Den Berg, David Van Neste, Leander Yi, Joo Mi Li, Jun Z. Southwick, Audrey Brady, Shannon Aggarwal, Amita Chung, Tisha Sherlock, Gavin Brooks, James D. Jakkula, Lakshmi R. Lapuk, Anna V. Marr, Henry Dorton, Shannon Choi, Yoon Gi Han, Ju Ray, Amrita Wang, Victoria Durinck, Steffen Robinson, Mark Wang, Nicholas J. Vranizan, Karen Peng, Vivian Van Name, Eric Fontenay, Gerald V. Ngai, John Conboy, John G. Parvin, Bahram Feiler, Heidi S. Speed, Terence P. Socci, Nicholas D. Olshen, Adam Lash, Alex Reva, Boris Antipin, Yevgeniy Stukalov, Alexey Gross, Benjamin Cerami, Ethan Wang, Wei Qing Qin, Li-Xuan Seshan, Venkatraman E. Villafania, Liliana Cavatore, Magali Borsu, Laetitia Viale, Agnes Gerald, William Topal, Michael D. Qi, Yuan Balu, Sai Shi, Yan Wu, George Bittner, Michael Shelton, Troy Lenkiewicz, Elizabeth Morris, Scott Beasley, Debbie Sanders, Sheri Sfeir, Robert Chen, Jessica Nassau, David Feng, Larry Hickey, Erin Schaefer, Carl Madhavan, Subha Buetow, Ken Barker, Anna Vockley, Joseph Compton, Carolyn Vaught, Jim Fielding, Peter Collins, Francis Good, Peter Guyer, Mark Ozenberger, Brad Peterson, Jane Thomson, Elizabeth CA Canc Genome Atlas Res Network Tissue Source Sites Genome Sequencing Ctr Canc Genome Characterization Ctr Project Teams TI Comprehensive genomic characterization defines human glioblastoma genes and core pathways SO NATURE LA English DT Article ID NF1 GENE; MISMATCH REPAIR; NEUROFIBROMATOSIS TYPE-1; SOMATIC MUTATIONS; MALIGNANT GLIOMAS; ALKYLATING-AGENTS; HIGH-FREQUENCY; PIK3CA GENE; CELL-LINES; TUMORS AB Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas ( TCGA) pilot project aims to assess the value of large- scale multi- dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas - the most common type of primary adult brain cancer - and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol- 3- OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer. C1 [Chin, L.; Meyerson, M.; Winckler, W.; Verhaak, R. G. W.; Weir, B. A.; Wiedemeyer, R.; Beroukhim, Rameen; Chiang, Derek; Mermel, Craig; Garraway, Levi] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chin, L.; Yao, Jun; Protopopov, Alexei; Perna, Ilana; Ren, Georgia; Xiao, Yonghong] Dana Farber Canc Inst, Ctr Appl Canc Sci, Belfer Inst innovat Canc Sci, Boston, MA 02115 USA. [Chin, L.; Robinson, Jim; Alexe, Gabriele; Carter, Scott] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Meyerson, M.; Getz, G.; Winckler, W.; Verhaak, R. G. W.; Weir, B. A.; Lawrence, M. S.; Lander, E. S.; O'Kelly, Michael; Beroukhim, Rameen; Chiang, Derek; Gould, Josh; Gupta, Supriya; Korn, Josh; Mermel, Craig; Mesirov, Jill; Monti, Stefano; Nguyen, Huy; Parkin, Melissa; Reich, Michael; Stransky, Nicolas; Garraway, Levi; Golub, Todd] Harvard Univ, Cambridge, MA 02142 USA. [Bigner, D.; McLendon, Roger] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Friedman, Allan] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Mikkelsen, T.] Henry Ford Hosp, Dept Neurol Surg, Detroit, MI 48202 USA. [VandenBerg, S.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [Aldape, K.] Univ Texas Houston MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Yung, W. K. Alfred] Univ Texas Houston MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Bogler, Oliver] Univ Texas Houston MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA. [Kahn, A.; Sfeir, Robert; Chen, Jessica; Nassau, David; Feng, Larry; Hickey, Erin] SRA Int, Fairfax, VA 22033 USA. NCI, Ctr Biomed Informat & Informat Technol, Rockville, MD 20852 USA. [Collins, Francis; Good, Peter; Guyer, Mark; Ozenberger, Brad; Peterson, Jane; Thomson, Elizabeth] NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. [Gerhard, D. S.; Barker, Anna; Vockley, Joseph; Compton, Carolyn; Vaught, Jim; Fielding, Peter] NCI, NIH, Bethesda, MD 20892 USA. [Penny, R.; Shelton, Troy; Lenkiewicz, Elizabeth; Morris, Scott; Beasley, Debbie; Sanders, Sheri] Int Genom Consortium, Phoenix, AZ 85004 USA. [Ferguson, M. L.] MLF Consulting, Arlington, MA 02474 USA. [Ding, L.; Mardis, E.; Wilson, R. K.; Wallis, J.; Fennell, Tim; Baldwin, Jennifer; Fulton, Robert S.; McLellan, Michael D.; Larson, David E.; Shi, Xiaoqi; Abbott, Rachel; Fulton, Lucinda; Chen, Ken; Koboldt, Daniel C.; Wendl, Michael C.; Meyer, Rick; Tang, Yuzhu; Lin, Ling; Osborne, John R.; Dunford-Shore, Brian H.; Miner, Tracie L.; Delehaunty, Kim; Markovic, Chris; Swift, Gary; Courtney, William; Pohl, Craig; Abbott, Scott; Hawkins, Amy; Leong, Shin; Haipek, Carrie; Schmidt, Heather; Wiechert, Maddy; Vickery, Tammi; Scott, Sacha; Dooling, David J.; Chinwalla, Asif; Weinstock, George M.] Washington Univ, Sch Med, Dept Genet, Genome Ctr, St Louis, MO 63108 USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21231 USA. [Park, P.; Aronson, Sandy; Sathiamoorthy, Narayan; Kim, Hyunsoo; Kohane, Isaac S.] Harvard Univ, Sch Med, Partners Healthcare Ctr Genet & Genom, Boston, MA 02115 USA. [Park, P.; Kucherlapati, R.; Kohane, Isaac S.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA. [Park, P.; Kong, Sek Won; Kohane, Isaac S.] Childrens Hosp, Informat Program, Boston, MA 02115 USA. [Brennan, C.] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10065 USA. [Taylor, B. S.; Schultz, N.; Sander, C.; Socci, Nicholas D.; Lash, Alex; Reva, Boris; Antipin, Yevgeniy; Stukalov, Alexey; Gross, Benjamin; Cerami, Ethan; Wang, Wei Qing; Gerald, William] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA. [Taylor, B. S.] Weill Cornell Grad Sch Med Sci, Dept Physiol & Biophys, New York, NY 10065 USA. [Ladanyi, M.; Borsu, Laetitia] Mem Sloan Kettering Canc Ctr, Dept Pathol, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. [Spellman, Paul T.; Gray, J.; Jakkula, Lakshmi R.; Lapuk, Anna V.; Marr, Henry; Dorton, Shannon; Han, Ju; Ray, Amrita; Durinck, Steffen; Wang, Nicholas J.; Fontenay, Gerald V.; Conboy, John G.; Parvin, Bahram; Feiler, Heidi S.] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA. [Purdom, E.; Wang, Victoria; Speed, Terence P.] Univ Calif Berkeley, Dept Stat, Berkeley, CA 95720 USA. [Choi, Yoon Gi; Vranizan, Karen; Peng, Vivian; Van Name, Eric; Ngai, John] Univ Calif Berkeley, Dept Mol & Cellular Biol, Berkeley, CA 95720 USA. [Robinson, Mark; Speed, Terence P.] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia. [Southwick, Audrey; Brady, Shannon; Aggarwal, Amita; Chung, Tisha; Sherlock, Gavin] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. [Brooks, James D.] Stanford Univ, Sch Med, Dept Urol, Stanford, CA 94305 USA. [Wheeler, D.; Donehower, L.; Wheeler, D. A.] Baylor Coll Med, Human Genome Sequencing Ctr, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Perou, C. M.; Miller, Christopher A.; Milosavljevic, Aleksandar] Baylor Coll Med, Grad Program Struct & Computat Biol & Mol Biophys, Houston, TX 77030 USA. [Perou, C. M.; Milosavljevic, Aleksandar] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Univ N Carolina, Dept Genet, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Hoadley, K. A.; Topal, Michael D.] Univ N Carolina, Dept Pathol & Lab Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Qi, Yuan] Univ N Carolina, Dept Internal Med, Lineberger Comprehens Canc Ctr, Div Med Oncol, Chapel Hill, NC 27599 USA. [Hayes, D. N.; Herman, J. G.; Schuebel, K. E.; Baylin, S. B.; Yi, Joo Mi] Johns Hopkins Univ, Div Canc Biol, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. [Cope, Leslie] Johns Hopkins Univ, Biometry & Clin Trials Div, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. [Van Neste, Leander] Univ Ghent, Fac Biosci & Engn, Dept Mol Biotechnol, B-9000 Ghent, Belgium. [Van Meir, Erwin G; Mastrogianakis, Gena Marie; Olson, Jeffrey J] Emory Univ, Sch Med, Dept Neurosurg, Atlanta, GA 30322 USA. [Van Meir, Erwin G; Olson, Jeffrey J] Emory Univ, Sch Med, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. [Van Meir, Erwin G; Brat, Daniel J; Olson, Jeffrey J] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA 30322 USA. [Brat, Daniel J] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Laird, P. W.; Weisenberger, D. J.; Pan, Fei; Van Den Berg, David] Univ So Calif, USC Epigenome Ctr, Los Angeles, CA 90089 USA. [Lehman, Norman] Henry Ford Hosp, Dept Pathol, Detroit, MI 48202 USA. [Berger, Mitchel; Prados, Michael] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. [Cibulskis, K.; Sougnez, Carrie] MIT, Eli & Edythe L Broad Inst, Canc Genome Project, Cambridge, MA 02142 USA. [Sougnez, Carrie] MIT, Eli & Edythe L Broad Inst, Med Resequencing Project, Cambridge, MA 02142 USA. [Lander, E. S.] MIT, Dept Biol, Cambridge, MA 02142 USA. [Lander, E. S.] Harvard Univ, Dept Syst Biol, Boston, MA 02115 USA. [Golub, Todd] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Seidman, Jon] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Absher, D.; Myers, R. M.] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA. [Olshen, Adam; Qin, Li-Xuan; Seshan, Venkatraman E.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA. [Villafania, Liliana; Cavatore, Magali; Viale, Agnes] Mem Sloan Kettering Canc Ctr, Genom Core Lab, New York, NY 10065 USA. [Bittner, Michael] Translat Genom Res Inst, Computat Biol Div, Phoenix, AZ 85004 USA. [Zhang, Jinghui; Schaefer, Carl; Madhavan, Subha; Buetow, Ken] NCI, Ctr Biomed Informat & Informat Technol, Rockville, MD 20852 USA. [Weinstein, J.] Univ Texas Houston MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. [Li, Jun Z.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. [Kong, Sek Won] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. RP Chin, L (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM lynda_chin@dfci.harvard.edu; matthew_meyerson@dfci.harvard.edu RI Wendl, Michael/A-2741-2008; Speed, Terence /B-8085-2009; leng, xianwei/F-9073-2011; sander, chris/H-1452-2011; Meyerson, Matthew/E-7123-2012; Sherlock, Gavin/E-9110-2012; Miller, Christopher/A-1060-2009; Kohane, Isaac Kohane/K-3716-2012; Robinson, Mark/A-6432-2015; Laird, Peter/G-8683-2012; Lehman, Norman/A-7351-2015; Chiang, Daisy/C-9481-2011; Reva, Boris/B-6436-2014 OI Van Meir, Erwin G./0000-0003-2444-7707; Lehman, Norman/0000-0001-8394-2607; Bogler, Oliver/0000-0002-3700-0480; Brennan, Cameron/0000-0003-4064-8891; Lash, Alex/0000-0003-3787-1590; Hayes, D. Neil/0000-0001-6203-7771; Sherlock, Gavin/0000-0002-1692-4983; Perou, Charles/0000-0001-9827-2247; Speed, Terence /0000-0002-5403-7998; Miller, Christopher/0000-0003-4266-6700; Kohane, Isaac Kohane/0000-0003-2192-5160; Robinson, Mark/0000-0002-3048-5518; Chiang, Daisy/0000-0002-8205-4285; Reva, Boris/0000-0002-8805-389X FU United States National Institutes of Health [U54HG003067, U54HG003079, U54HG003273, U24CA126543, U24CA126544, U24CA126546, U24CA126551, U24CA126554, U24CA126561, U24CA126563] FX We thank the members of TCGA's External Scientific Committee, the Glioblastoma Disease Working Group (http:// cancergenome.nih.gov/components) and D. N. Louis for discussions; A. Mirick, J. Melone and C. Collins for administrative coordination of TCGA activities; and L. Gaffney for graphic art. This work was supported by the following grants from the United States National Institutes of Health: U54HG003067, U54HG003079, U54HG003273, U24CA126543, U24CA126544, U24CA126546, U24CA126551, U24CA126554, U24CA126561 and U24CA126563. NR 50 TC 2301 Z9 2332 U1 45 U2 311 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD OCT 23 PY 2008 VL 455 IS 7216 BP 1061 EP 1068 DI 10.1038/nature07385 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363FG UT WOS:000260252600035 ER PT J AU Ding, L Getz, G Wheeler, DA Mardis, ER McLellan, MD Cibulskis, K Sougnez, C Greulich, H Muzny, DM Morgan, MB Fulton, L Fulton, RS Zhang, QY Wendl, MC Lawrence, MS Larson, DE Chen, K Dooling, DJ Sabo, A Hawes, AC Shen, H Jhangiani, SN Lewis, LR Hall, O Zhu, YM Mathew, T Ren, YR Yao, JQ Scherer, SE Clerc, K Metcalf, GA Ng, B Milosavljevic, A Gonzalez-Garay, ML Osborne, JR Meyer, R Shi, XQ Tang, YZ Koboldt, DC Lin, L Abbott, R Miner, TL Pohl, C Fewell, G Haipek, C Schmidt, H Dunford-Shore, BH Kraja, A Crosby, SD Sawyer, CS Vickery, T Sander, S Robinson, J Winckler, W Baldwin, J Chirieac, LR Dutt, A Fennell, T Hanna, M Johnson, BE Onofrio, RC Thomas, RK Tonon, G Weir, BA Zhao, XJ Ziaugra, L Zody, MC Giordano, T Orringer, MB Roth, JA Spitz, MR Wistuba, II Ozenberger, B Good, PJ Chang, AC Beer, DG Watson, MA Ladanyi, M Broderick, S Yoshizawa, A Travis, WD Pao, W Province, MA Weinstock, GM Varmus, HE Gabriel, SB Lander, ES Gibbs, RA Meyerson, M Wilson, RK AF Ding, Li Getz, Gad Wheeler, David A. Mardis, Elaine R. McLellan, Michael D. Cibulskis, Kristian Sougnez, Carrie Greulich, Heidi Muzny, Donna M. Morgan, Margaret B. Fulton, Lucinda Fulton, Robert S. Zhang, Qunyuan Wendl, Michael C. Lawrence, Michael S. Larson, David E. Chen, Ken Dooling, David J. Sabo, Aniko Hawes, Alicia C. Shen, Hua Jhangiani, Shalini N. Lewis, Lora R. Hall, Otis Zhu, Yiming Mathew, Tittu Ren, Yanru Yao, Jiqiang Scherer, Steven E. Clerc, Kerstin Metcalf, Ginger A. Ng, Brian Milosavljevic, Aleksandar Gonzalez-Garay, Manuel L. Osborne, John R. Meyer, Rick Shi, Xiaoqi Tang, Yuzhu Koboldt, Daniel C. Lin, Ling Abbott, Rachel Miner, Tracie L. Pohl, Craig Fewell, Ginger Haipek, Carrie Schmidt, Heather Dunford-Shore, Brian H. Kraja, Aldi Crosby, Seth D. Sawyer, Christopher S. Vickery, Tammi Sander, Sacha Robinson, Jody Winckler, Wendy Baldwin, Jennifer Chirieac, Lucian R. Dutt, Amit Fennell, Tim Hanna, Megan Johnson, Bruce E. Onofrio, Robert C. Thomas, Roman K. Tonon, Giovanni Weir, Barbara A. Zhao, Xiaojun Ziaugra, Liuda Zody, Michael C. Giordano, Thomas Orringer, Mark B. Roth, Jack A. Spitz, Margaret R. Wistuba, Ignacio I. Ozenberger, Bradley Good, Peter J. Chang, Andrew C. Beer, David G. Watson, Mark A. Ladanyi, Marc Broderick, Stephen Yoshizawa, Akihiko Travis, William D. Pao, William Province, Michael A. Weinstock, George M. Varmus, Harold E. Gabriel, Stacey B. Lander, Eric S. Gibbs, Richard A. Meyerson, Matthew Wilson, Richard K. TI Somatic mutations affect key pathways in lung adenocarcinoma SO NATURE LA English DT Article ID HUMAN BREAST; MENDELIAN-INHERITANCE; HOMOZYGOUS DELETIONS; COLORECTAL CANCERS; EGFR MUTATIONS; TOBACCO-SMOKE; KRAS MUTATION; NEVER SMOKERS; RECEPTOR GENE; GEFITINIB AB Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well- classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers - including NF1, APC, RB1 and ATM - and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment. C1 [Ding, Li; Mardis, Elaine R.; McLellan, Michael D.; Fulton, Lucinda; Fulton, Robert S.; Wendl, Michael C.; Larson, David E.; Chen, Ken; Dooling, David J.; Osborne, John R.; Meyer, Rick; Shi, Xiaoqi; Tang, Yuzhu; Koboldt, Daniel C.; Lin, Ling; Abbott, Rachel; Miner, Tracie L.; Pohl, Craig; Fewell, Ginger; Haipek, Carrie; Schmidt, Heather; Dunford-Shore, Brian H.; Crosby, Seth D.; Sawyer, Christopher S.; Vickery, Tammi; Sander, Sacha; Robinson, Jody; Weinstock, George M.; Wilson, Richard K.] Washington Univ, Sch Med, Dept Genet, Genome Ctr, St Louis, MO 63108 USA. [Getz, Gad; Cibulskis, Kristian; Sougnez, Carrie; Greulich, Heidi; Lawrence, Michael S.; Winckler, Wendy; Baldwin, Jennifer; Dutt, Amit; Fennell, Tim; Hanna, Megan; Onofrio, Robert C.; Weir, Barbara A.; Zhao, Xiaojun; Ziaugra, Liuda; Zody, Michael C.; Gabriel, Stacey B.; Lander, Eric S.; Meyerson, Matthew] Broad Inst Harvard & MIT, Canc Program, Genome Biol Program, Cambridge, MA 02142 USA. [Wheeler, David A.; Muzny, Donna M.; Morgan, Margaret B.; Sabo, Aniko; Hawes, Alicia C.; Shen, Hua; Jhangiani, Shalini N.; Lewis, Lora R.; Hall, Otis; Zhu, Yiming; Mathew, Tittu; Ren, Yanru; Yao, Jiqiang; Scherer, Steven E.; Clerc, Kerstin; Metcalf, Ginger A.; Ng, Brian; Milosavljevic, Aleksandar; Gonzalez-Garay, Manuel L.; Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Greulich, Heidi; Winckler, Wendy; Dutt, Amit; Hanna, Megan; Johnson, Bruce E.; Tonon, Giovanni; Weir, Barbara A.; Zhao, Xiaojun; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Zhang, Qunyuan; Kraja, Aldi; Province, Michael A.] Washington Univ, Sch Med, Div Stat Genom, Dept Genet, St Louis, MO 63108 USA. [Chirieac, Lucian R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Chirieac, Lucian R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Chirieac, Lucian R.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Thomas, Roman K.] Max Planck Soc, Max Planck Inst Neurol Res, Klaus Joachim Zulch Labs, D-50931 Cologne, Germany. [Thomas, Roman K.] Univ Cologne, Fac Med, D-50931 Cologne, Germany. [Thomas, Roman K.] Univ Cologne, Ctr Integrated Oncol, D-50931 Cologne, Germany. [Thomas, Roman K.] Univ Cologne, Dept Internal Med 1, D-50931 Cologne, Germany. [Giordano, Thomas] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Orringer, Mark B.; Chang, Andrew C.; Beer, David G.] Univ Michigan, Thorac Surg Sect, Dept Surg, Ann Arbor, MI 48109 USA. [Roth, Jack A.; Wistuba, Ignacio I.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Houston, TX 77030 USA. [Spitz, Margaret R.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Wistuba, Ignacio I.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Ozenberger, Bradley; Good, Peter J.] NHGRI, NIH, Bethesda, MD 20892 USA. [Watson, Mark A.] Washington Univ, Dept Pathol & Immunol, St Louis, MO 63108 USA. [Ladanyi, Marc; Broderick, Stephen; Yoshizawa, Akihiko; Travis, William D.; Pao, William] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA. [Ladanyi, Marc; Broderick, Stephen; Yoshizawa, Akihiko; Travis, William D.; Pao, William] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA. [Ladanyi, Marc; Broderick, Stephen; Yoshizawa, Akihiko; Travis, William D.; Pao, William] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. [Ladanyi, Marc; Broderick, Stephen; Yoshizawa, Akihiko; Travis, William D.; Pao, William] Mem Sloan Kettering Canc Ctr, Dept Computat Biol, New York, NY 10065 USA. [Ladanyi, Marc; Pao, William] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. [Varmus, Harold E.] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA. RP Wilson, RK (reprint author), Washington Univ, Sch Med, Dept Genet, Genome Ctr, St Louis, MO 63108 USA. EM matthew_meyerson@dfci.harvard.edu; rwilson@wustl.edu RI Wendl, Michael/A-2741-2008; Chen, Ken/A-1074-2009; Meyerson, Matthew/E-7123-2012; Dutt, Amit/I-1911-2013; OI Dutt, Amit/0000-0002-1119-4774; Chang, Andrew/0000-0001-9506-0425; Giordano, Thomas/0000-0003-0641-8873 FU National Human Genome Research Institute FX We thank A. Lash, M.F. Zakowski, M.G. Kris and V. Rusch for intellectual contributions, and many members of the Baylor Human Genome Sequencing Center, the Broad Institute of Harvard and MIT, and the Genome Center at Washington University for support. This work was funded by grants from the National Human Genome Research Institute to E.S.L., R.A.G. and R.K.W. NR 50 TC 1294 Z9 1335 U1 29 U2 151 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 23 PY 2008 VL 455 IS 7216 BP 1069 EP 1075 DI 10.1038/nature07423 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363FG UT WOS:000260252600036 PM 18948947 ER PT J AU Gavathiotis, E Suzuki, M Davis, ML Pitter, K Bird, GH Katz, SG Tu, HC Kim, H Cheng, EHY Tjandra, N Walensky, LD AF Gavathiotis, Evripidis Suzuki, Motoshi Davis, Marguerite L. Pitter, Kenneth Bird, Gregory H. Katz, Samuel G. Tu, Ho-Chou Kim, Hyungjin Cheng, Emily H. -Y. Tjandra, Nico Walensky, Loren D. TI BAX activation is initiated at a novel interaction site SO NATURE LA English DT Article ID MITOCHONDRIAL-MEMBRANE PERMEABILIZATION; STABILIZED ALPHA-HELICES; BCL-X-L; BH3-ONLY PROTEINS; CELL-DEATH; INTRACELLULAR-LOCALIZATION; PROAPOPTOTIC ACTIVITY; BH3 DOMAINS; APOPTOSIS; FAMILY AB BAX is a pro- apoptotic protein of the BCL- 2 family that is stationed in the cytosol until activated by a diversity of stress stimuli to induce cell death. Anti- apoptotic proteins such as BCL- 2 counteract BAX- mediated cell death. Although an interaction site that confers survival functionality has been defined for anti- apoptotic proteins, an activation site has not been identified for BAX, rendering its explicit trigger mechanism unknown. We previously developed stabilized alpha- helix of BCL- 2 domains ( SAHBs) that directly initiate BAX- mediated mitochondrial apoptosis. Here we demonstrate by NMR analysis that BIM SAHB binds BAX at an interaction site that is distinct from the canonical binding groove characterized for anti- apoptotic proteins. The specificity of the human BIM- SAHB - BAX interaction is highlighted by point mutagenesis that disrupts functional activity, confirming that BAX activation is initiated at this novel structural location. Thus, we have now defined a BAX interaction site for direct activation, establishing a new target for therapeutic modulation of apoptosis. C1 [Suzuki, Motoshi; Tjandra, Nico] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. [Tu, Ho-Chou; Kim, Hyungjin; Cheng, Emily H. -Y.] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA. [Tu, Ho-Chou; Kim, Hyungjin; Cheng, Emily H. -Y.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Gavathiotis, Evripidis; Davis, Marguerite L.; Pitter, Kenneth; Bird, Gregory H.; Katz, Samuel G.; Walensky, Loren D.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Gavathiotis, Evripidis; Suzuki, Motoshi; Davis, Marguerite L.; Pitter, Kenneth; Bird, Gregory H.; Walensky, Loren D.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. [Gavathiotis, Evripidis; Davis, Marguerite L.; Pitter, Kenneth; Bird, Gregory H.; Katz, Samuel G.; Walensky, Loren D.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Gavathiotis, Evripidis; Davis, Marguerite L.; Pitter, Kenneth; Bird, Gregory H.; Katz, Samuel G.; Walensky, Loren D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Tjandra, N (reprint author), NHLBI, Lab Mol Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA. EM tjandran@nhlbi.nih.gov; loren_walensky@dfci.harvard.edu FU National Cancer Institute [5P01CA92625, 5RO1CA50239, 5RO1CA125562]; Burroughs Wellcome Fund Career Award; Culpeper Scholarship in Medical Science; American Society of Hematology Junior Faculty Scholar Award; William Lawrence Children's Foundation; Intramural Research Program of the National Heart, Lung and Blood Institute; Searle Scholars Program FX We thank E. Smith for editorial and graphics assistance, W. Beavers for amino acid analyses, A. Perry for technical assistance, C. Turner and A. Bielecki of the MIT/Harvard Center for Magnetic Resonance for NMR technical advice, and R. Youle for feedback on the manuscript. We acknowledge the indelible contributions of the late S.J. Korsmeyer, who inspired this work. L.D.W. is supported by National Cancer Institute (NCI) grant 5P01CA92625, a Burroughs Wellcome Fund Career Award in the Biomedical Sciences, a Culpeper Scholarship in Medical Science from the Goldman Philanthropic Partnerships, an American Society of Hematology Junior Faculty Scholar Award, and a grant from the William Lawrence Children's Foundation. This research was also supported by NCI grant 5RO1CA50239. N.T. is supported by the Intramural Research Program of the National Heart, Lung and Blood Institute, NIH. E.H.-Y.C. is supported by the Searle Scholars Program and NCI grant 5RO1CA125562. NR 50 TC 374 Z9 384 U1 5 U2 37 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 23 PY 2008 VL 455 IS 7216 BP 1076 EP U6 DI 10.1038/nature07396 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363FG UT WOS:000260252600037 PM 18948948 ER PT J AU Zheng, HW Ying, HQ Yan, HY Kimmelman, AC Hiller, DJ Chen, AJ Perry, SR Tonon, G Chu, GC Ding, ZH Stommel, JM Dunn, KL Wiedemeyer, R You, MJJ Brennan, C Wang, YA Ligon, KL Wong, WH Chin, L DePinho, RA AF Zheng, Hongwu Ying, Haoqiang Yan, Haiyan Kimmelman, Alec C. Hiller, David J. Chen, An-Jou Perry, Samuel R. Tonon, Giovanni Chu, Gerald C. Ding, Zhihu Stommel, Jayne M. Dunn, Katherine L. Wiedemeyer, Ruprecht You, Mingjian J. Brennan, Cameron Wang, Y. Alan Ligon, Keith L. Wong, Wing H. Chin, Lynda DePinho, Ronald A. TI p53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation SO NATURE LA English DT Article ID CANCER STEM-CELLS; SELF-RENEWAL; INITIATING CELLS; C-MYC; TUMORS; GLIOBLASTOMA; EXPRESSION; RECEPTOR; PATHWAYS; BIOLOGY AB Glioblastoma ( GBM) is a highly lethal brain tumour presenting as one of two subtypes with distinct clinical histories and molecular profiles. The primary GBM subtype presents acutely as a high-grade disease that typically harbours mutations in EGFR, PTEN and INK4A/ARF ( also known as CDKN2A), and the secondary GBM subtype evolves from the slow progression of a low- grade disease that classically possesses PDGF and TP53 events(1-3). Here we show that concomitant central nervous system (CNS)- specific deletion of p53 and Pten in the mouse CNS generates a penetrant acute- onset high- grade malignant glioma phenotype with notable clinical, pathological and molecular resemblance to primary GBM in humans. This genetic observation prompted TP53 and PTEN mutational analysis in human primary GBM, demonstrating unexpectedly frequent inactivating mutations of TP53 as well as the expected PTEN mutations. Integrated transcriptomic profiling, in silico promoter analysis and functional studies of murine neural stem cells ( NSCs) established that dual, but not singular, inactivation of p53 and Pten promotes an undifferentiated state with high renewal potential and drives increased Myc protein levels and its associated signature. Functional studies validated increased Myc activity as a potent contributor to the impaired differentiation and enhanced renewal of NSCs doubly null for p53 and Pten (p53(-/-) Pten(-/-)) as well as tumour neurospheres (TNSs) derived from this model. Myc also serves to maintain robust tumorigenic potential of p53(-/-) Pten(-/-) TNSs. These murine modelling studies, together with confirmatory transcriptomic/ promoter studies in human primary GBM, validate a pathogenetic role of a common tumour suppressor mutation profile in human primary GBM and establish Myc as an important target for cooperative actions of p53 and Pten in the regulation of normal and malignant stem/ progenitor cell differentiation, self- renewal and tumorigenic potential. C1 [Zheng, Hongwu; Ying, Haoqiang; Yan, Haiyan; Kimmelman, Alec C.; Chen, An-Jou; Perry, Samuel R.; Tonon, Giovanni; Chu, Gerald C.; Ding, Zhihu; Stommel, Jayne M.; Dunn, Katherine L.; Wiedemeyer, Ruprecht; You, Mingjian J.; Wang, Y. Alan; Ligon, Keith L.; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Perry, Samuel R.; Chu, Gerald C.; Wang, Y. Alan; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Ctr Appl Canc Sci, Belfer Fdn Inst Innovat Canc Sci, Boston, MA 02115 USA. [Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Kimmelman, Alec C.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Chu, Gerald C.; Ligon, Keith L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ligon, Keith L.] Harvard Univ, Sch Med, Div Neuropathol, Boston, MA 02115 USA. [Chin, Lynda] Harvard Univ, Sch Med, Dept Dermatol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Hiller, David J.; Wong, Wing H.] Stanford Univ, Dept Stat, Stanford, CA 94305 USA. [Brennan, Cameron] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10065 USA. [Brennan, Cameron] Weill Cornell Med Coll, Dept Neurosurg, New York, NY 10065 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM ron_depinho@dfci.harvard.edu RI leng, xianwei/F-9073-2011; OI Zheng, Hongwu/0000-0002-5823-4913; Brennan, Cameron/0000-0003-4064-8891 FU Helen Hay Whitney Foundation; Marsha Mae Moeslein Fellowship; American Brain Tumor Association; Leonard B. Holman Research Pathway Fellowship; Damon Runyon Cancer Research Foundation; Ruth L. Kirschstein National Research Service Award Fellowship; Mildred Scheel Fellowship (Deutsche Krebshilfe); Goldhirsh Foundation; NIH [U01 CA84313, RO1CA99041, 5P01CA95616]; Robert A. and Renee E. Belfer Foundation Institute for Innovative Cancer Science FX We thank A. Berns for providing p53 L mice; S. Zhou and S. Jiang for mouse husbandry and care; R. T. Bronson for discussion on pathology analysis; K. Montgomery for discussion on sequencing; and Y.- H. Xiao, B. Feng and J. Zhang for bioinformatic help. H. Z. was supported by Helen Hay Whitney Foundation. H. Ying is a recipient of the Marsha Mae Moeslein Fellowship from the American Brain Tumor Association. A. C. K. is a recipient of the Leonard B. Holman Research Pathway Fellowship. Z. D. is supported by the Damon Runyon Cancer Research Foundation. J. M. S. is supported by a Ruth L. Kirschstein National Research Service Award Fellowship. R. W. is supported by a Mildred Scheel Fellowship ( Deutsche Krebshilfe). Grant support comes from the Goldhirsh Foundation (R.A.D.), and NIH grants U01 CA84313 (R.A.D.), RO1CA99041 ( L. C.) and 5P01CA95616 (R.A.D., L.C., W.H.W., C.B. and K.L.L.). R.A.D. is an American Cancer Society Research Professor supported by the Robert A. and Renee E. Belfer Foundation Institute for Innovative Cancer Science. NR 35 TC 358 Z9 366 U1 4 U2 57 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 23 PY 2008 VL 455 IS 7216 BP 1129 EP U13 DI 10.1038/nature07443 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363FG UT WOS:000260252600049 PM 18948956 ER PT J AU Joshi, PS Molyneaux, BJ Feng, L Xie, XL Macklis, JD Gan, L AF Joshi, Pushkar S. Molyneaux, Bradley J. Feng, Liang Xie, Xiaoling Macklis, Jeffrey D. Gan, Lin TI Bhlhb5 Regulates the Postmitotic Acquisition of Area Identities in Layers II-V of the Developing Neocortex SO NEURON LA English DT Article ID CORTICOSPINAL MOTOR-NEURONS; DEVELOPING CEREBRAL-CORTEX; GREEN FLUORESCENT PROTEIN; MOUSE BARREL CORTEX; COUP-TFI; DIFFERENTIAL EXPRESSION; AXONAL PROJECTIONS; DROSOPHILA EMBRYO; MAMMALIAN CORTEX; SPINAL-CORD AB While progenitor-restricted factors broadly specify area identities in developing neocortex, the downstream regulatory elements involved in acquisition of those identities in postmitotic neurons are largely unknown. Here, we identify Bhlhb5, a transcription factor expressed in layers II-V, as a postmitotic regulator of area identity. Bhlhb5 is initially expressed in a high caudomedial to low rostrolateral gradient that transforms into a sharp border between sensory and rostral motor cortices. Bhlhb5 null mice exhibit aberrant expression of area-specific genes and structural organization in the somatosensory and caudal motor cortices. In somatosensory cortex, Bhlhb5 null mice display postsynaptic disorganization of vibrissal barrels. In caudal motor cortex, Bhlhb5 null mice exhibit anomalous differentiation of corticospinal motor neurons, accompanied by failure of corticospinal tract formation. Together, these results demonstrate Bhlhb5's function as an area-specific transcription factor that regulates the postmitotic acquisition of area identities and elucidate the genetic hierarchy between progenitors and postmitotic neurons driving neocortical arealization. C1 [Molyneaux, Bradley J.; Macklis, Jeffrey D.] Harvard Univ, Sch Med, MGH HMS Ctr Nervous Syst Repair, Dept Neurol, Cambridge, MA 02138 USA. [Molyneaux, Bradley J.; Macklis, Jeffrey D.] Harvard Univ, Sch Med, Program Neurosci, Cambridge, MA 02138 USA. [Macklis, Jeffrey D.] Massachusetts Gen Hosp, Nayef Al Rodhan Labs, Boston, MA 02114 USA. [Macklis, Jeffrey D.] Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02114 USA. [Macklis, Jeffrey D.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Boston, MA 02114 USA. [Joshi, Pushkar S.; Feng, Liang; Xie, Xiaoling; Gan, Lin] Univ Rochester, Dept Ophthalmol, Rochester, NY 14642 USA. [Gan, Lin] Univ Rochester, Ctr Neural Dev & Dis, Rochester, NY 14642 USA. [Gan, Lin] Univ Rochester, Dept Neurobiol & Anat, Rochester, NY 14642 USA. [Molyneaux, Bradley J.; Macklis, Jeffrey D.] Harvard Univ, Sch Med, MGH HMS Ctr Nervous Syst Repair, Dept Neurosurg, Cambridge, MA 02138 USA. RP Macklis, JD (reprint author), Harvard Univ, Sch Med, MGH HMS Ctr Nervous Syst Repair, Dept Neurosurg, Cambridge, MA 02138 USA. EM jeffrey_macklis@hms.harvard.edu; lin_gan@urmc.rochester.edu OI Molyneaux, Bradley/0000-0002-3377-1229 FU NIH [EY013426, EY015551, NS45523, NS49553]; Harvard M.S.T.P; United Sydney Association FX We thank Drs. J. Rubenstein. R. Hevner. S. McConnell. T. Mori, T. Rabbitts, M. Tsai, C. Learry, and K-F. Lee for generous sharing of antibodies and cDNA clones; Y. Yanagawa, V. Cuzon, and H. Yeh for providing GAD67-GFP knockin brains: J. Zhang, A. Majewska, and K. Billmers for technical help with corticospinal tracing. This work was supported by NIH grants EY013426 and EY015551 to L.G.. NIH grants NS45523 and NS49553 to J.D.M., the Research to Prevent Blindness challenge grant to the Department of Ophthalmology at the University of Rochester (L.G.), the Harvard Stem Cell Institute (J.D.M.), the Spastic Paraplegia Foundation (J.D.M.), and the ALS Association (J.D.M.). B.J.M. was supported by the Harvard M.S.T.P. and United Sydney Association. NR 68 TC 83 Z9 85 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD OCT 23 PY 2008 VL 60 IS 2 BP 258 EP 272 DI 10.1016/j.neuron.2008.08.006 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 367JW UT WOS:000260549300009 PM 18957218 ER PT J AU Wiener, CM Muse, VV Mark, EJ Tinsley, A Harris, NL Kanarek, DJ Korzenik, J AF Wiener, Charles M. Muse, Victorine V. Mark, Eugene J. Tinsley, Andrew Harris, Nancy Lee Kanarek, David J. Korzenik, Joshua TI A woman with dyspnea on exertion - Interstitial lymphocytic pneumonitis and histiocytic pneumonia with eosinophils, findings that are consistent with drug or hypersensitivity reactions, possibly due to infliximab SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID LUNG-DISEASE; BRONCHOALVEOLAR LAVAGE; INFECTIOUS-DISEASES; CT C1 [Wiener, Charles M.] Johns Hopkins Univ Hosp, Dept Med, Baltimore, MD 21287 USA. [Wiener, Charles M.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Muse, Victorine V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Muse, Victorine V.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Mark, Eugene J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wiener, CM (reprint author), Johns Hopkins Univ Hosp, Dept Med, Baltimore, MD 21287 USA. NR 16 TC 6 Z9 7 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 23 PY 2008 VL 359 IS 17 BP 1823 EP 1832 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 363DJ UT WOS:000260245800011 PM 18946068 ER PT J AU Goodyear, LJ AF Goodyear, Laurie J. TI The exercise pill - Too good to be true? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CHRONIC ACTIVATION; GLYCOGEN; MUSCLE C1 [Goodyear, Laurie J.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Goodyear, Laurie J.] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. NR 5 TC 57 Z9 60 U1 1 U2 9 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 OCT 23 PY 2008 VL 359 IS 17 BP 1842 EP 1844 DI 10.1056/NEJMcibr0806723 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 363DJ UT WOS:000260245800015 PM 18946072 ER PT J AU Mehta, RH Liang, L Karve, AM Hernandez, AF Rumsfeld, JS Fonarow, GC Peterson, ED AF Mehta, Rajendra H. Liang, Li Karve, Amrita M. Hernandez, Adrian F. Rumsfeld, John S. Fonarow, Gregg C. Peterson, Eric D. TI Association of patient case-mix adjustment, hospital process performance rankings, and eligibility for financial incentives SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE CORONARY SYNDROMES; COOPERATIVE CARDIOVASCULAR PROJECT; ACUTE MYOCARDIAL-INFARCTION; QUALITY-OF-CARE; ELDERLY-PATIENTS; UNSTABLE ANGINA; HEALTH-CARE; DISPARITIES; CRUSADE; PREVENTION AB Context While most comparisons of hospital outcomes adjust for patient characteristics, process performance comparisons typically do not. Objective To evaluate the degree to which hospital process performance ratings and eligibility for financial incentives are altered after accounting for hospitals' patient demographics, clinical characteristics, and mix of treatment opportunities. Design, Setting, and Patients Using data from the American Heart Association's Get With the Guidelines program between January 2, 2000, and March 28, 2008, we analyzed hospital process performance based on the Centers for Medicare & Medicaid Services' defined core measures for acute myocardial infarction. Hospitals were initially ranked based on crude composite process performance and then ranked again after accounting for hospitals' patient demographics, clinical characteristics, and eligibility for measures using a hierarchical model. We then compared differences in hospital performance rankings and pay-for-performance financial incentive categories (top 20%, middle 60%, and bottom 20% institutions). Main Outcome Measures Hospital process performance ranking and pay-for-performance financial incentive categories. Results A total of 148 472 acute myocardial infarction patients met the study criteria from 449 centers. Hospitals for which crude composite acute myocardial infarction performance was in the bottom quintile (n=89) were smaller nonacademic institutions that treated a higher percentage of patients from racial or ethnic minority groups and also patients with greater comorbidities than hospitals ranked in the top quintile (n=90). Although there was overall agreement on hospital rankings based on observed vs adjusted composite scores (weighted kappa, 0.74), individual hospital ranking changed with adjustment (median, 22 ranks; range, 0-214; interquartile range, 9-40). Additionally, 16.5% of institutions (n=74) changed pay-for-performance financial status categories after accounting for patient and treatment opportunity mix. Conclusion Our findings suggest that accounting for hospital differences in patient characteristics and treatment opportunities is associated with modest changes in hospital performance rankings and eligibility for financial benefits in pay-for-performance programs for treatment of myocardial infarction. C1 [Mehta, Rajendra H.; Liang, Li; Karve, Amrita M.; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC 27715 USA. [Mehta, Rajendra H.; Liang, Li; Karve, Amrita M.; Hernandez, Adrian F.; Peterson, Eric D.] Duke Univ, Med Ctr, Durham, NC USA. [Rumsfeld, John S.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. RP Mehta, RH (reprint author), Duke Clin Res Inst, Box 17969, Durham, NC 27715 USA. EM mehta007@dcri.duke.edu RI Hernandez, Adrian F./A-7818-2016 OI Hernandez, Adrian F./0000-0003-3387-9616 FU GlaxoSmithKline; Medtronic; Merck; Pfizer; National Institutes of Health; AHA; American Heart Association Pharmaceutical Roundtable [0675060N]; Elliot Corday (Los Angeles, California) Foundation; Ahmanson (Los Angeles, California) Foundation FX Dr Hernandez reports receiving research support from GlaxoSmithKline, Johnson & Johnson (Scios Inc), Medtronic, Novartis, and Roche Diagnostics; and honoraria from AstraZeneca, Novartis, Sanofi-Aventis, and Thoratec Corporation. Dr Peterson reports receiving research support from Schering Plough, BMS/Sanofi; and serving as the principal investigator for the American Heart Association's (AHA's) Get With the Guidelines Analytical Center. Drs Hernandez and Peterson report detailed listings of financial disclosures at http://www.dcri.duke.edu/research/coi.jsp. Dr Rumsfeld reports receiving an honorariun for participating on the scientific research advisory board of United Healthcare. Dr Fonarow reports receiving research grants from GlaxoSmithKline, Medtronic, Merck, Pfizer, and the National Institutes of Health; consulting for AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Merck, Novartis, Pfizer, Sanofi-Aventis, and Schering Plough; receiving honoraria from AstraZeneca, Abbott, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Merck, Novartis, Pfizer, Sanofi-Aventis, and Schering Plough; and serving as chair of the AHA's Get With the Guidelines Steering Committee. Drs Mehta and Liang and Ms Karve report no disclosures. The Get With the Guidelines program is supported by the AHA in part through an unrestricted education grant from Merck-Schering Plough. Dr Hernandez reports receiving support from an American Heart Association Pharmaceutical Roundtable grant 0675060N. Dr Fonarow reports receiving support from the Elliot Corday (Los Angeles, California) and Ahmanson (Los Angeles, California) Foundations. NR 30 TC 40 Z9 40 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 22 PY 2008 VL 300 IS 16 BP 1897 EP 1903 DI 10.1001/jama.300.16.1897 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 362UR UT WOS:000260223100019 PM 18940976 ER PT J AU Ross, JS Detsky, AS AF Ross, Joseph S. Detsky, Allan S. TI Comparison of the US and Canadian health care systems - A tale of 2 Mount Sinai's SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID UNITED-STATES; COUNTRIES C1 [Detsky, Allan S.] Mt Sinai Hosp, Dept Med, Toronto, ON M5G 1X5, Canada. [Detsky, Allan S.] Univ Toronto, Univ Hlth Network, Toronto, ON, Canada. [Detsky, Allan S.] Univ Toronto, Dept Med & Hlth Policy, Toronto, ON, Canada. [Detsky, Allan S.] Univ Toronto, Dept Management, Toronto, ON, Canada. [Detsky, Allan S.] Univ Toronto, Dept Evaluat, Toronto, ON, Canada. [Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA. [Ross, Joseph S.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Ross, Joseph S.] James J Peters Vet Adm Med Ctr, HSR&D Res Enhancement Award Program, Bronx, NY USA. [Ross, Joseph S.] James J Peters Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. RP Detsky, AS (reprint author), Mt Sinai Hosp, Dept Med, 427-600 Univ Ave, Toronto, ON M5G 1X5, Canada. EM adetsky@mtsinai.on.ca NR 13 TC 6 Z9 6 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 22 PY 2008 VL 300 IS 16 BP 1934 EP 1936 DI 10.1001/jama.300.16.1934 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 362UR UT WOS:000260223100026 PM 18940983 ER PT J AU Loeffler, JS Halperin, EC AF Loeffler, Jay S. Halperin, Edward C. TI Selling a medical school's name - Ethical and practical dilemmas SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Loeffler, Jay S.] Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Halperin, Edward C.] Univ Louisville, Sch Med, Louisville, KY 40292 USA. RP Loeffler, JS (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, 100 Blossom St,Cox 347, Boston, MA 02114 USA. EM jloeffler@partners.org NR 10 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 22 PY 2008 VL 300 IS 16 BP 1937 EP 1938 DI 10.1001/jama.300.16.1937 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 362UR UT WOS:000260223100027 PM 18940984 ER PT J AU van Zundert, B Peuscher, MH Hynynen, M Chen, A Neve, RL Brown, RH Constantine-Paton, M Bellingham, MC AF van Zundert, Brigitte Peuscher, Marieke H. Hynynen, Meri Chen, Adam Neve, Rachael L. Brown, Robert H., Jr. Constantine-Paton, Martha Bellingham, Mark C. TI Neonatal Neuronal Circuitry Shows Hyperexcitable Disturbance in a Mouse Model of the Adult-Onset Neurodegenerative Disease Amyotrophic Lateral Sclerosis SO JOURNAL OF NEUROSCIENCE LA English DT Article DE action potential; brainstem; dendrite; EPSP; IPSP; motor neuron; interneuron; locomotor activity; sodium channel; synaptic transmission; superior colliculus ID PROTEIN-KINASE-C; RAT HYPOGLOSSAL MOTONEURONS; PERSISTENT NA+ CURRENT; MOTOR-NEURONS; SPINAL MOTONEURONS; CORTICAL HYPEREXCITABILITY; PHOSPHATASE EXPRESSION; SUPERIOR COLLICULUS; RECEPTOR CURRENTS; CALCIUM CURRENTS AB Distinguishing the primary from secondary effects and compensatory mechanisms is of crucial importance in understanding adult-onset neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Transgenic mice that overexpress the G93A mutation of the human Cu-Zn superoxide dismutase 1 gene (hSOD1(G93A) mice) are a commonly used animal model of ALS. Whole-cell patch-clamp recordings from neurons in acute slice preparations from neonatal wild-type and hSOD1(G93A) mice were made to characterize functional changes in neuronal activity. Hypoglossal motoneurons (HMs) in postnatal day 4 (P4)-P10 hSOD1(G93A) mice displayed hyperexcitability, increased persistent Na+ current (PCNa), and enhanced frequency of spontaneous excitatory and inhibitory transmission, compared with wild-type mice. These functional changes in neuronal activity are the earliest yet reported for the hSOD1(G93A) mouse, and are present 2-3 months before motoneuron degeneration and clinical symptoms appear in these mice. Changes in neuronal activity were not restricted to motoneurons: superior colliculus interneurons also displayed hyperexcitability and synaptic changes (P10-P12). Furthermore, in vivo viral-mediated GFP (green fluorescent protein) overexpression in hSOD1(G93A) HMs revealed precocious dendritic remodeling, and behavioral assays revealed transient neonatal neuromotor deficits compared with controls. These findings underscore the widespread and early onset of abnormal neural activity in this mouse model of the adult neurodegenerative disease ALS, and suggest that suppression of PCNa and hyperexcitability early in life might be one way to mitigate or prevent cell death in the adult CNS. C1 [Bellingham, Mark C.] Univ Queensland, Sch Biomed Sci, Brisbane, Qld 4072, Australia. [van Zundert, Brigitte; Peuscher, Marieke H.; Constantine-Paton, Martha; Bellingham, Mark C.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [van Zundert, Brigitte; Hynynen, Meri; Chen, Adam; Brown, Robert H., Jr.] Massachusetts Gen Hosp, Dept Neurol, Day Lab Neuromuscular Res, Charlestown, MA 02429 USA. [Neve, Rachael L.] Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. RP Bellingham, MC (reprint author), Univ Queensland, Sch Biomed Sci, Brisbane, Qld 4072, Australia. EM mark.bellingham@uq.edu.au RI Bellingham, Mark/G-1697-2011 OI Bellingham, Mark/0000-0001-9189-4430 FU National Institutes of Health [EY06039]; Pierre L. de Bourgknecht ALS Research Foundation; National Institute of Neurological Disorders and Stroke; National Institute on Aging; ALS Association; Angel Fund; Project ALS; Al-Athel ALS Foundation; ALS Therapy Alliance (CVS Pharmacy); Motor Neuron Disease Research Institute of Australia; National Health and Medical Research Council of Australia FX This work was supported by National Institutes of Health Grant EY06039 (M.C.-P.); The Pierre L. de Bourgknecht ALS Research Foundation (B.v.Z., R. H. B.); the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, the ALS Association, the Angel Fund, Project ALS, the Al-Athel ALS Foundation (R. H. B.), and the ALS Therapy Alliance (CVS Pharmacy) (R. H. B., M. C. B.); and The Motor Neuron Disease Research Institute of Australia and the National Health and Medical Research Council of Australia (M.C.B.). We thank A.J. Berger, J. Sebe, and R. Power for advice on hypoglossal motoneuron electrophysiological experiments and J. Durand for advice on the behavioral studies. B.v.Z. and M.C.B. performed all the electrophysiological experiments and analysis of electrophysiological data. M. H. P. performed all the HM structural analyses using HSV-GFP p1003, which was constructed and packaged by R.L.N. Behavioral testing was performed and analyzed by M. H. and A. C. B.v.Z., R. H. B., M.C.-P., and M. C. B all contributed to the experimental design and the writing of this manuscript. NR 69 TC 95 Z9 95 U1 1 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 22 PY 2008 VL 28 IS 43 BP 10864 EP 10874 DI 10.1523/JNEUROSCI.1340-08.2008 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 363KH UT WOS:000260265700010 PM 18945894 ER PT J AU Famous, KR Kumaresan, V Sadri-Vakili, G Schmidt, HD Mierke, DF Cha, JHJ Pierce, RC AF Famous, Katie R. Kumaresan, Vidhya Sadri-Vakili, Ghazaleh Schmidt, Heath D. Mierke, Dale F. Cha, Jang-Ho J. Pierce, R. Christopher TI Phosphorylation-Dependent Trafficking of GluR2-Containing AMPA Receptors in the Nucleus Accumbens Plays a Critical Role in the Reinstatement of Cocaine Seeking SO JOURNAL OF NEUROSCIENCE LA English DT Article DE relapse; addiction; psychostimulant; glutamate; CNQX; Pep2-EVKI ID INDUCED PLACE PREFERENCE; PRIMING-INDUCED REINSTATEMENT; GLUTAMATE TRANSMISSION; SYNAPTIC PLASTICITY; BEHAVIORAL SENSITIZATION; NMDA RECEPTOR; DRUG-SEEKING; RATS; ANTAGONIST; SHELL AB A growing body of evidence indicates that enhanced AMPA-mediated glutamate transmission in the core of the nucleus accumbens is critically involved in cocaine priming-induced reinstatement of drug seeking, an animal model of relapse. However, the extent to which increased glutamate transmission in the other major subregion of the nucleus accumbens, the shell, contributes to the reinstatement of cocaine seeking remains unclear. In the present experiments, administration of the AMPA/kainate receptor antagonist CNQX (0, 0.03, or 0.3 mu g) into either the core or the shell of the nucleus accumbens before a systemic cocaine priming injection (10 mg/kg, i.p.) dosedependently attenuated the reinstatement of drug seeking. Cocaine priming-induced reinstatement of cocaine seeking also was associated with increases in GluR2-pSer880 in the nucleus accumbens shell. The phosphorylation of GluR2 by PKC at Ser880 plays an important role in the trafficking of GluR2-containing AMPA receptors from the plasma membrane. The current results showed that administration of a cell-permeable peptide that disrupts GluR2 trafficking (Pep2-EVKI) into either the accumbens core or shell attenuated cocaine-induced reinstatement of drug seeking. Together, these findings indicate that changes in AMPA receptor-mediated glutamate transmission in both the nucleus accumbens core and shell are necessary for the reinstatement of drug seeking induced by a priming injection of cocaine. The present results also demonstrate that the reinstatement of cocaine seeking is associated with increases in the phosphorylation-dependent trafficking of GluR2-containing AMPA receptors in the nucleus accumbens. C1 [Famous, Katie R.; Kumaresan, Vidhya; Schmidt, Heath D.; Pierce, R. Christopher] Boston Univ, Sch Med, Dept Pharmacol, Boston, MA 02118 USA. [Pierce, R. Christopher] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Sadri-Vakili, Ghazaleh; Cha, Jang-Ho J.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA 02129 USA. [Mierke, Dale F.] Dartmouth Coll, Dept Chem, Hanover, NH 03755 USA. RP Pierce, RC (reprint author), Univ Penn, Dept Psychiat, Sch Med, 125 S 31st St, Philadelphia, PA 19104 USA. EM rcpierce@mail.med.upenn.edu FU National Institutes of Health (NIH) [R01 DA22339, R01 DA15214, K02 DA18678]; National Research Service Award (NRSA) from the NIH [F30 DA19304]; NIH Training [T32 GM008541-7]; Glendorn Foundation; [R01 DA18428]; [DA16824] FX This work was supported by National Institutes of Health (NIH) Grants R01 DA22339, R01 DA15214, K02 DA18678 (R.C.P.), and R01 DA18428 (D.F.M.). K.R.F. was partially supported by a National Research Service Award (NRSA) from the NIH (F30 DA19304), as well as NIH Training Grant T32 GM008541-7. H. D. S. was also partially supported by a NRSA from the NIH (DA16824). J.-H.J.C. and G.S.V. received support from the Glendorn Foundation. We thank Audrey Pierce for administrative assistance and Dr. Marina Wolf for comments on previous versions of this manuscript. NR 59 TC 68 Z9 68 U1 2 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 OCT 22 PY 2008 VL 28 IS 43 BP 11061 EP 11070 DI 10.1523/JNEUROSCI.1221-08.2008 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 363KH UT WOS:000260265700029 PM 18945913 ER PT J AU Hebert, PL Sisk, JE Wang, JJ Tuzzio, L Casabianca, JM Chassin, MR Horowitz, C McLaughlin, MA AF Hebert, Paul L. Sisk, Jane E. Wang, Jason J. Tuzzio, Leah Casabianca, Jodi M. Chassin, Mark R. Horowitz, Carol McLaughlin, Mary Ann TI Cost-Effectiveness of Nurse-Led Disease Management for Heart Failure in an Ethnically Diverse Urban Community SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID RANDOMIZED-TRIAL; SF-12; CARE; QUALITY; HEALTH; POPULATION; UTILITY; TRENDS; RISK AB Background: Randomized, controlled trials have shown that nurse-led disease management for patients with heart failure can reduce hospitalizations. Less is known about the cost-effectiveness of these interventions. Objective: To estimate the cost-effectiveness of a nurse-led disease management intervention over 12 months, implemented in a randomized, controlled effectiveness trial. Design: Cost-effectiveness analysis conducted alongside a randomized trial. Data Sources: Medical costs from administrative records, and self-reported quality of life and nonmedical costs from patient surveys. Participants: Patients with systolic dysfunction recruited from ambulatory clinics in Harlem, New York. Time Horizon: 12 months. Perspective: Societal and payer. Intervention: 12-month program that involved 1 face-to-face encounter with a nurse and regular telephone follow- up. Outcome Measures: Quality of life as measured by the Health Utilities Index Mark 3 and EuroQol-5D and cost-effectiveness as measured by the incremental cost-effectiveness ratio ( ICER). Results of Base-Case Analysis: Costs and quality of life were higher in the nurse-managed group than the usual care group. The ICERs over 12 months were $17 543 per EuroQol-5D-based quality-adjusted life-year ( QALY) and $15 169 per Health Utilities Index Mark 3-based QALY ( in 2001 U. S. dollars). Results of Sensitivity Analysis: From a payer perspective, the ICER ranged from $3673 to $4495 per QALY. Applying national prices in place of New York City prices yielded a societal ICER of $13 460 to $ 15 556 per QALY. Cost-effectiveness acceptability curves suggest that the intervention was most likely cost-effective for patients with less severe ( New York Heart Association classes I to II) heart failure. Limitation: The trial was conducted in an ethnically diverse, inner-city neighborhood; thus, results may not be generalizable to other communities. Conclusion: Over 12 months, the nurse-led disease management program was a reasonably cost-effective way to reduce the burden of heart failure in this community. C1 Univ Washington, Sch Publ Hlth & Community Med, Vet Adm Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Mt Sinai Sch Med, New York, NY USA. Fordham Univ, Bronx, NY 10458 USA. Joint Commiss, Oak Brook Terrace, IL USA. RP Hebert, PL (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM Paul.Hebert2@va.gov FU Agency for Healthcare Research and Quality [R01 HS10402-01] FX Grant Support: Dr. Sisk was supported by a grant from the Agency for Healthcare Research and Quality (R01 HS10402-01). NR 39 TC 48 Z9 50 U1 4 U2 17 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 21 PY 2008 VL 149 IS 8 BP 540 EP W105 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 367XJ UT WOS:000260585600003 PM 18936502 ER PT J AU Eikelboom, JW Hankey, GJ Thom, J Bhatt, DL Steg, PG Montalescot, G Johnston, SC Steinhubl, SR Mak, KH Easton, JD Hamm, C Hu, TF Fox, KAA Topol, EJ AF Eikelboom, John W. Hankey, Graeme J. Thom, Jim Bhatt, Deepak L. Steg, P. Gabriel Montalescot, Gilles Johnston, S. Claiborne Steinhubl, Steven R. Mak, Koon-Hou Easton, J. Donald Hamm, Christian Hu, Tingfei Fox, Keith A. A. Topol, Eric J. CA CHARISMA Investigators TI Incomplete Inhibition of Thromboxane Biosynthesis by Acetylsalicylic Acid Determinants and Effect on Cardiovascular Risk SO CIRCULATION LA English DT Article DE aspirin; aspirin resistance; atherosclerosis ID LOW-DOSE ASPIRIN; ST-SEGMENT ELEVATION; MYOCARDIAL-INFARCTION; PLATELET-FUNCTION; PRIMARY PREVENTION; RANDOMIZED-TRIALS; CHARISMA TRIAL; THERAPY; DISEASE; CLOPIDOGREL AB Background -Incomplete inhibition of platelet thromboxane generation, as measured by elevated urinary 11-dehydro thromboxane B(2) concentrations, has been associated with an increased risk of cardiovascular events. We aimed to determine the external validity of this association in aspirin-treated patients enrolled in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) trial and to determine whether there are any modifiable factors or interventions that lower urinary 11-dehydro thromboxane B2 concentrations that could thereby reduce cardiovascular risk. Methods and Results -Urinary 11-dehydro thromboxane B2 concentrations were measured in 3261 aspirin-treated patients at least 1 month after they had been randomly assigned to placebo or clopidogrel. Baseline urinary 11-dehydro thromboxane B2 concentrations in the highest quartile were associated with an increased risk of stroke, myocardial infarction, or cardiovascular death compared with the lowest quartile (adjusted hazard ratio 1.66, 95% CI 1.06 to 2.61, P = 0.03). Increasing age, female sex, history of peripheral artery disease, current smoking, and oral hypoglycemic or angiotensin-converting enzyme inhibitor therapy were independently associated with higher urinary concentrations of 11-dehydro thromboxane B2, whereas aspirin dose >= 150 mg/d, history of treatment with nonsteroidal antiinflammatory drugs, history of hypercholesterolemia, and statin treatment were associated with lower concentrations. Randomization to clopidogrel (versus placebo) did not reduce the hazard of cardiovascular events in patients in the highest quartile of urinary 11-dehydro thromboxane B2 levels. Conclusions -In aspirin-treated patients, urinary concentrations of 11-dehydro thromboxane B2 are an externally valid and potentially modifiable determinant of stroke, myocardial infarction, or cardiovascular death in patients at risk for atherothrombotic events. (Circulation. 2008; 118: 1705-1712.) C1 [Hankey, Graeme J.] Royal Perth Hosp, Dept Neurol, Stroke Unit, Perth, WA 6000, Australia. [Eikelboom, John W.] McMaster Univ, Hamilton, ON, Canada. [Thom, Jim] Royal Perth Hosp, Dept Haematol, Perth, WA 6000, Australia. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hu, Tingfei] Cleveland Clin, Cleveland, OH 44106 USA. [Steg, P. Gabriel] Univ Paris 07, INSERM, AP HP, U698, Paris, France. [Montalescot, Gilles] Hop La Pitie Salpetriere, Inst Cardiol, APHP, Paris, France. [Montalescot, Gilles] Hop La Pitie Salpetriere, INSERM, U856, Paris, France. [Johnston, S. Claiborne] UCSF Neurol, San Francisco, CA USA. [Steinhubl, Steven R.] Weis Ctr Res, Geisinger Clin, Danville, PA 17822 USA. [Mak, Koon-Hou] Gleneagles Med Ctr, Singapore, Singapore. [Easton, J. Donald] Brown Univ, Providence, RI 02912 USA. [Hamm, Christian] Kerckhoff Heart Ctr, Bad Nauheim, Germany. [Fox, Keith A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. [Topol, Eric J.] Scripps Res Inst, La Jolla, CA 92037 USA. [Topol, Eric J.] Scripps Clin, La Jolla, CA 92037 USA. RP Hankey, GJ (reprint author), Royal Perth Hosp, Dept Neurol, Stroke Unit, 197 Wellington St, Perth, WA 6000, Australia. EM gjhankey@cyllene.uwa.edu.au RI Walker, Philip/F-3034-2010; Hankey, Graeme /H-4968-2014; OI Hankey, Graeme /0000-0002-6044-7328; Eikelboom, John/0000-0003-4126-1285; Topol, Eric/0000-0002-1478-4729 NR 35 TC 122 Z9 126 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 OCT 21 PY 2008 VL 118 IS 17 BP 1705 EP 1712 DI 10.1161/CIRCULATIONAHA.108.768283 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 362HQ UT WOS:000260189200004 PM 18838564 ER PT J AU Bell, BD Giovagnoli, AR AF Bell, Brian D. Giovagnoli, Anna R. TI Memory after temporal lobe epilepsy surgery Risk and reward SO NEUROLOGY LA English DT Editorial Material ID LOBECTOMY C1 [Bell, Brian D.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol, Madison, WI 53792 USA. [Bell, Brian D.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Giovagnoli, Anna R.] Ist Nazl Neurol Carlo Besta, Dept Clin Neurosci, Neuropsychol Lab, Milan, Italy. RP Bell, BD (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol, 600 Highland Ave, Madison, WI 53792 USA. EM bell@neurology.wisc.edu NR 6 TC 2 Z9 2 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 21 PY 2008 VL 71 IS 17 BP 1302 EP 1303 DI 10.1212/01.wnl.0000326065.70180.03 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 362IJ UT WOS:000260191100002 PM 18784375 ER PT J AU Grimm, SA McCannel, CA Omuro, AMP Ferreri, AJM Blay, JY Neuwelt, EA Siegal, T Batchelor, T Jahnke, K Shenkier, TN Hall, AJ Graus, F Herrlinger, U Schiff, D Raizer, J Rubenstein, J Laperriere, N Thiel, E Doolittle, N Iwamoto, FM Abrey, LE AF Grimm, S. A. McCannel, C. A. Omuro, A. M. P. Ferreri, A. J. M. Blay, J. -Y. Neuwelt, E. A. Siegal, T. Batchelor, T. Jahnke, K. Shenkier, T. N. Hall, A. J. Graus, F. Herrlinger, U. Schiff, D. Raizer, J. Rubenstein, J. Laperriere, N. Thiel, E. Doolittle, N. Iwamoto, F. M. Abrey, L. E. TI Primary CNS lymphoma with intraocular involvement International PCNSL Collaborative Group Report SO NEUROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; HIGH-DOSE METHOTREXATE; RADIATION-THERAPY; CHEMOTHERAPY; RADIOTHERAPY; EXPERIENCE; BIOPSY AB Objective: To describe the demographics, diagnostic details, therapeutic management, and outcome in patients with primary CNS lymphoma (PCNSL) with ocular involvement. Methods: A retrospective study of 221 patients was assembled from 16 centers in seven countries. Only HIV-negative, immunocompetent patients with brain and ocular lymphoma were included; none had systemic lymphoma. Results: Median age at diagnosis was 60. Fifty-seven percent were women. Median Eastern Cooperative Oncology Group performance status was 2. Ocular disturbance and behavioral/cognitive changes were the most common presenting symptoms. Diagnosis of lymphoma was made by brain biopsy (147), vitrectomy (65), or CSF cytology (11). Diagnosis of intraocular lymphoma was made by vitrectomy/choroidal/retinal biopsy (90) or clinical ophthalmic examination (141). CSF cytology was positive in 23%. Treatment information was available for 176 patients. A total of 102 received dedicated ocular therapy (ocular radiotherapy 79, intravitreal methotrexate 22, and both 1) in addition to treatment for their brain lymphoma. Sixty-nine percent progressed at a median of 13 months; sites of progression included brain 52%, eyes 19%, brain and eyes 12%, and systemic 2%. Patients treated with local ocular therapy did not have a statistically significant decreased risk of failing in the eyes (p = 0.7). Median progression free survival and overall survival for the entire cohort were 18 and 31 months. Conclusion: This is the largest reported series of primary CNS lymphoma (PCNSL) with intraocular involvement. Progression free and overall survival was similar to that reported with PCNSL. Dedicated ocular therapy improved disease control but did not affect overall survival. Neurology (R) 2008; 71: 1355-1360 C1 [Abrey, L. E.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. [McCannel, C. A.] Mayo Clin, Rochester, MN USA. [Omuro, A. M. P.] Grp Hosp Pitie Salpetriere, F-75634 Paris, France. [Neuwelt, E. A.; Doolittle, N.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Siegal, T.] Hadassah Hebrew Univ Hosp, Jerusalem, Israel. [Batchelor, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jahnke, K.; Thiel, E.] Charite Univ Med Berlin, D-13353 Berlin, Germany. [Shenkier, T. N.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Hall, A. J.] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Hall, A. J.] Royal Victorian Eye & Ear Hosp, Melbourne, Vic 3002, Australia. [Graus, F.] Inst Invest Biomed August Pi & Sunyer, Hosp Clin, Barcelona, Spain. [Herrlinger, U.] Univ Tubingen, D-72074 Tubingen, Germany. [Schiff, D.] Univ Virginia, Charlottesville, VA USA. [Raizer, J.] NW Mem Hosp, Chicago, IL 60611 USA. [Rubenstein, J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Laperriere, N.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. RP Abrey, LE (reprint author), Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10021 USA. EM abreyl@mskcc.org RI Ferreri, Andres Jose Maria/A-6662-2013; Blay, Jean-Yves/N-3966-2016; OI Ferreri, Andres Jose Maria/0000-0001-9606-6124; Blay, Jean-Yves/0000-0001-7190-120X; McCannel, Colin/0000-0003-0774-6414 FU NCI NIH HHS [K23 CA100291, R13 CA124293] NR 20 TC 68 Z9 73 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 21 PY 2008 VL 71 IS 17 BP 1355 EP 1360 DI 10.1212/01.wnl.0000327672.04729.8c PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 362IJ UT WOS:000260191100010 PM 18936428 ER PT J AU Koulmanda, M Bhasin, M Hoffman, L Fan, ZG Qipo, AD Shi, H Bonner-Weir, S Putheti, P Degauque, N Libermann, TA Auchincloss, H Flier, JS Strom, TB AF Koulmanda, Maria Bhasin, Manoj Hoffman, Lauren Fan, Zhigang Qipo, Andi Shi, Hang Bonner-Weir, Susan Putheti, Prabhakar Degauque, Nicolas Libermann, Towia A. Auchincloss, Hugh, Jr. Flier, Jeffrey S. Strom, Terry B. TI Curative and beta cell regenerative effects of alpha 1-antitrypsin treatment in autoimmune diabetic NOD mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autoimmunity; type 1 diabetes; inflammation ID REGULATORY T-CELLS; INSULIN-RESISTANCE; PANCREATIC-ISLETS; MESSENGER-RNA; TGF-BETA; TYPE-1; ONSET; INFLAMMATION; REJECTION; APOPTOSIS AB Invasive insulitis is a destructive T cell-dependent autoimmune process directed against insulin-producing beta cells that is central to the pathogenesis of type 1 diabetes mellitus (T1DM) in humans and the clinically relevant nonobese diabetic (NOD) mouse model. Few therapies have succeeded in restoring long-term, drug-free euglycemia and immune tolerance to beta cells in overtly diabetic NOD mice, and none have demonstrably enabled enlargement of the functional beta cell mass. Recent studies have emphasized the impact of inflammatory cytokines on the commitment of antigen-activated T cells to various effector or regulatory T cell phenotypes and insulin resistance and defective insulin signaling. Hence, we tested the hypothesis that inflammatory mechanisms trigger insulitis, insulin resistance, faulty insulin signaling, and the loss of immune tolerance to islets. We demonstrate that treatment with alpha 1-antitrypsin (AAT), an agent that dampens inflammation, does not directly inhibit T cell activation, ablates invasive insulitis, and restores euglycemia, immune tolerance to beta cells, normal insulin signaling, and insulin responsiveness in NOD mice with recent-onset T1DM through favorable changes in the inflammation milieu. Indeed, the functional mass of beta cells expands in AAT-treated diabetic NOD mice. C1 [Koulmanda, Maria; Hoffman, Lauren; Fan, Zhigang; Qipo, Andi; Shi, Hang; Auchincloss, Hugh, Jr.; Strom, Terry B.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Bhasin, Manoj; Putheti, Prabhakar; Degauque, Nicolas; Libermann, Towia A.; Flier, Jeffrey S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Bhasin, Manoj; Libermann, Towia A.] Beth Israel Deaconess Med Ctr, Genom Ctr, Boston, MA 02115 USA. [Koulmanda, Maria; Fan, Zhigang; Qipo, Andi; Putheti, Prabhakar; Degauque, Nicolas; Strom, Terry B.] Beth Israel Deaconess Med Ctr, Transplant Res Ctr, Boston, MA 02115 USA. [Hoffman, Lauren; Shi, Hang; Flier, Jeffrey S.] Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02115 USA. [Bonner-Weir, Susan] Joslin Diabet Ctr, Boston, MA 02115 USA. RP Strom, TB (reprint author), Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. EM strom@bidmc.harvard.edu RI Libermann, Towia/F-9866-2010; OI Degauque, Nicolas/0000-0003-2990-3513; Libermann, Towia/0000-0002-4006-8179 NR 41 TC 101 Z9 109 U1 0 U2 6 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 OCT 21 PY 2008 VL 105 IS 42 BP 16242 EP 16247 DI 10.1073/pnas.0808031105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 368BX UT WOS:000260597400033 PM 18852471 ER PT J AU Cohen, T Colijn, C Murray, M AF Cohen, Ted Colijn, Caroline Murray, Megan TI Modeling the effects of strain diversity and mechanisms of strain competition on the potential performance of new tuberculosis vaccines SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE bacillus Calmette-Guerin; mathematical model; strain replacement ID MYCOBACTERIUM-TUBERCULOSIS; BEIJING GENOTYPE; RESISTANT TUBERCULOSIS; IMPERFECT VACCINES; CLINICAL ISOLATE; IMMUNE-RESPONSE; VACCINATION; EVOLUTION; VIRULENCE; POLYMORPHISM AB While bacillus Calmette-Guerin vaccination plays an important role in reducing the morbidity of tuberculosis (TB) infection during childhood, new tuberculosis vaccines are necessary to disrupt the transmission of disease and improve global control of this pathogen. Growing evidence of the presence of meaningful Mycobacterium tuberculosis strain diversity, coupled with the possibility that new vaccines may differentially protect against infection or disease with circulating M. tuberculosis strains, suggest that these vaccines may have complicated effects on disease dynamics. We use a mathematical model to explore the potential effects of strain diversity on the performance of vaccines and find that vaccines offer great promise for improving tuberculosis control, but the expected benefits of mass vaccination will be eroded if strain replacement with M. tuberculosis variants that are not effectively targeted by vaccines occurs. Determining the likelihood of strain replacement will require additional knowledge of the strain specificities of current vaccine candidates, and an improved understanding of the mechanisms of strain interaction, which are responsible for maintaining the diversity of M. tuberculosis within communities. C1 [Cohen, Ted; Murray, Megan] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Cohen, Ted; Colijn, Caroline; Murray, Megan] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Colijn, Caroline] Univ Bristol, Dept Engn Math, Bristol BS8 1TR, Avon, England. [Murray, Megan] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Cohen, T (reprint author), Brigham & Womens Hosp, Div Global Hlth Equ, 75 Francis St, Boston, MA 02115 USA. EM tcohen@hsph.harvard.edu RI Cohen, Ted/G-8101-2011 FU National Institutes of Health [K08 AI055985-06] FX We thank Gary Schoolnik and Barun Mathema for comments on an early draft and Hana Akselrod for assistance with manuscript preparation. This work was supported by National Institutes of Health Grant K08 AI055985-06 NR 49 TC 18 Z9 18 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 OCT 21 PY 2008 VL 105 IS 42 BP 16302 EP 16307 DI 10.1073/pnas.0808746105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 368BX UT WOS:000260597400043 PM 18849476 ER PT J AU Sorror, ML Storer, BE Sandmaier, BM Maris, M Shizuru, J Maziarz, R Agura, E Chauncey, TR Pulsipher, MA McSweeney, PA Wade, JC Bruno, B Langston, A Radich, J Niederwieser, D Blume, KG Storb, R Maloney, DG AF Sorror, Mohamed L. Storer, Barry E. Sandmaier, Brenda M. Maris, Michael Shizuru, Judith Maziarz, Richard Agura, Edward Chauncey, Thomas R. Pulsipher, Michael A. McSweeney, Peter A. Wade, James C. Bruno, Benedetto Langston, Amelia Radich, Jerald Niederwieser, Dietger Blume, Karl G. Storb, Rainer Maloney, David G. TI Five-Year Follow-Up of Patients With Advanced Chronic Lymphocytic Leukemia Treated With Allogeneic Hematopoietic Cell Transplantation After Nonmyeloablative Conditioning SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT Tandem Bone Marrow Transplantation Meeting CY FEB 16, 2007 CL Keystone, CO SP Amer Soc Bone Marrow Transplant ID VERSUS-HOST-DISEASE; MINIMAL RESIDUAL DISEASE; BONE-MARROW-TRANSPLANTATION; TREATMENT-RELATED MORTALITY; VARIABLE-REGION MUTATIONS; HEAVY-CHAIN GENE; GENOMIC ABERRATIONS; CLINICAL-EFFICACY; ZAP-70 EXPRESSION; CD38 EXPRESSION AB Purpose We reported encouraging early results of allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning in 64 patients who had advanced chronic lymphocytic leukemia (CLL). Here, we have extended the follow-up to a median of 5 years and have included data on an additional 18 patients. Patients and Methods Eighty-two patients, age 42 to 72 years, who had fludarabine-refractory CLL were conditioned with 2 Gy total-body irradiation alone or combined with fludarabine followed by HCT from related (n = 52) or unrelated (n = 30) donors. Results Complete remission (CR) and partial remission were achieved in 55% and 15% of patients, respectively. Higher CR rates were noted after unrelated HCT (67% v 48%). The 5-year incidences of nonrelapse mortality (NRM), progression/relapse, overall survival, and progression-free survival were 23%, 38%, 50%, and 39%, respectively. Among 25 patients initially reported in CR, 8% relapsed and 8% died as a result of NRM, whereas 84% have remained alive and in CR. Among 14 responding patients who were tested and who had molecular eradication of their disease, two died as a result of NRM, two relapsed, and 10 have remained negative. At 5 years, 76% of living patients were entirely well, whereas 24% continued to receive immunosuppression for chronic graft-versus-host disease; the median performance status in each group was 100% and 90%, respectively. Lymphadenopathy >= 5 cm, but not cytogenetic abnormalities at HCT, predicted relapse. In a risk-stratification model, patients who had lymphadenopathy less than 5 cm and no comorbidities had a 5-year OS of 71%. Conclusion Nonmyeloablative HCT resulted in a median survival of 5 years for patients who had fludarabine-refractory CLL with sustained remissions and in the continued resolution of chronic graft-versus-host disease in surviving patients. C1 [Sorror, Mohamed L.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Stanford Univ, Stanford, CA 94305 USA. Univ Leipzig, Leipzig, Germany. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Baylor Univ, Baylor, TX USA. Univ Utah, Salt Lake City, UT USA. Univ Colorado, Boulder, CO 80309 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Turin, Turin, Italy. Emory Univ, Atlanta, GA 30322 USA. RP Sorror, ML (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D1-100,POB 19024, Seattle, WA 98109 USA. EM msorror@fhcrc.org FU NCI NIH HHS [CA15704, CA18029, CA78902, P01 CA018029, P01 CA078902] NR 51 TC 169 Z9 173 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 20 PY 2008 VL 26 IS 30 BP 4912 EP 4920 DI 10.1200/JCO.2007.15.4757 PG 9 WC Oncology SC Oncology GA 361FT UT WOS:000260113600013 PM 18794548 ER PT J AU Baer, MR George, SL Caligiuri, MA Sanford, BL Bothun, SM Mrozek, K Kolitz, JE Powell, BL Moore, JO Stone, RM Anastasi, J Bloomfield, CD Larson, RA AF Baer, Maria R. George, Stephen L. Caligiuri, Michael A. Sanford, Ben L. Bothun, Sandra M. Mrozek, Krzysztof Kolitz, Jonathan E. Powell, Bayard L. Moore, Joseph O. Stone, Richard M. Anastasi, John Bloomfield, Clara D. Larson, Richard A. TI Low-Dose Interleukin-2 Immunotherapy Does Not Improve Outcome of Patients Age 60 Years and Older With Acute Myeloid Leukemia in First Complete Remission: Cancer and Leukemia Group B Study 9720 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 12th International Symposium on Acute Leukemias CY FEB 16-20, 2008 CL Munich, GERMANY ID COLONY-STIMULATING FACTOR; ACUTE MYELOGENOUS LEUKEMIA; PHASE-III TRIAL; RECOMBINANT INTERLEUKIN-2; ELDERLY-PATIENTS; ONCOLOGY-GROUP; IN-VIVO; CHEMOTHERAPY; CELLS; AML AB Purpose Cancer and Leukemia Group B (CALGB) 9720 evaluated subcutaneous low-dose recombinant interleukin-2 (rIL-2) maintenance immunotherapy as a strategy for prolonging remission in older patients with acute myeloid leukemia (AML). Patients and Methods AML patients age 60 years and older in first complete remission after induction and consolidation chemotherapy were randomly assigned to no further therapy or a 90-day regimen of 14-day cycles of low-dose rIL-2, aimed at expanding natural killer (NK) cells, followed by 3-day higher doses aimed at activating cytotoxicity of expanded NK cells to lyse residual AML cells. All randomly assigned patients were included in an intention-to-treat analysis. Results A total of 163 (64%) of 254 patients who completed induction and consolidation chemotherapy on CALGB 9720 were randomly assigned to rIL-2 (n = 81) or no further therapy (n = 82); the most common reasons for lack of random assignment were patient refusal and relapse. Fifteen patients randomly assigned to rIL-2 never initiated it because of refusal, intercurrent medical problems, or relapse, and 24 patients initiated rIL-2 but stopped early because of toxicity or relapse. Grade 4 toxicities during rIL-2 therapy included thrombocytopenia (65%) and neutropenia (64%), and grade 3 toxicities included anemia (33%), infection (24%) and malaise/fatigue (14%). Forty-two patients (52%) randomly assigned to rIL-2 completed the full 90-day course. Patients in both arms had similar distributions of both disease-free (combined median = 6.1 months; P = .47) and overall survival (combined median = 14.7 months; P = .61) after random assignment. Moreover, the 42 patients who completed all planned therapy did not show prolongation of disease-free or overall survival. Conclusion Low-dose rIL-2 maintenance immunotherapy is not a successful strategy in older AML patients. C1 [Baer, Maria R.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. N Shore Univ Hosp, Manhasset, NY USA. Duke Univ, Med Ctr, CALGB Stat Ctr, Durham, NC USA. Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Chicago, Chicago, IL 60637 USA. RP Baer, MR (reprint author), Univ Maryland, Greenebaum Canc Ctr, 22 S Greene St, Baltimore, MD 21201 USA. EM mbaer@umm.edu RI Mrozek, Krzysztof/A-3142-2008; OI Larson, Richard/0000-0001-9168-3203 FU NCI NIH HHS [CA02599, CA03927, CA31946, CA31983, CA32291, CA33601, CA35279, CA41287, CA47577, CA77658, U10 CA033601] NR 32 TC 62 Z9 66 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 20 PY 2008 VL 26 IS 30 BP 4934 EP 4939 DI 10.1200/JCO.2008.17.0472 PG 6 WC Oncology SC Oncology GA 361FT UT WOS:000260113600016 PM 18591543 ER PT J AU Chen, RC Lin, NU Golshan, M Harris, JR Bellon, JR AF Chen, Ronald C. Lin, Nancy U. Golshan, Mehra Harris, Jay R. Bellon, Jennifer R. TI Internal Mammary Nodes in Breast Cancer: Diagnosis and Implications for Patient Management - A Systematic Review SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID EXTENDED RADICAL-MASTECTOMY; RECEIVING ADJUVANT CHEMOTHERAPY; POSITIVE AXILLARY NODES; SENTINEL LYMPH-NODES; HIGH-RISK; RANDOMIZED-TRIAL; CLINICAL-RELEVANCE; DRAINAGE PATTERNS; TUMOR LOCATION; RADIATION-THERAPY AB The management of internal mammary nodes (IMNs) in breast cancer is controversial. Surgical series from the 1950s showed that one third of breast cancer patients had IMN involvement, with a higher risk in patients with medial tumors and/or positive axillary nodes. IMN metastasis has similar prognostic importance as axillary nodal involvement. However, after three randomized trials showed no survival benefit from extended mastectomy compared with radical or modified radical mastectomy, IMN dissection was largely abandoned. Recently, lymphoscintigraphy studies have renewed interest in IMN evaluation. Approximately one fifth of internal mammary sentinel nodes are pathologic, although most centers do not perform IMN biopsies because of concerns about morbidity and lack of established survival benefit. In addition, results from randomized trials testing the value of postmastectomy irradiation and a meta-analysis of 78 randomized trials have provided high levels of evidence that local-regional tumor control is associated with long-term survival improvements. This benefit was limited to trials that used systemic therapy, which was not routinely administered in the earlier surgical studies, although the contribution from IMN treatment is unclear. IMN irradiation has also been shown to cause increased cardiac morbidity. Before mature results from current randomized trials assessing the benefit of IMN irradiation become available, lymphoscintigraphy may be used to help guide decisions regarding systemic and local-regional treatment. However, even in patients with visualized primary IMN drainage, the potential benefit of treatment should be balanced against the risk of added morbidity. C1 Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Bellon, Jennifer R.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Bellon, JR (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM jbellon@lroc.harvard.edu NR 88 TC 102 Z9 110 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 20 PY 2008 VL 26 IS 30 BP 4981 EP 4989 DI 10.1200/JCO.2008.17.4862 PG 9 WC Oncology SC Oncology GA 361FT UT WOS:000260113600023 PM 18711171 ER PT J AU Nanda, A Mamon, HJ Fuchs, CS AF Nanda, Akash Mamon, Harvey J. Fuchs, Charles S. TI Sign of Leser-Trelat in Newly Diagnosed Advanced Gastric Adenocarcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ERUPTIVE SEBORRHEIC KERATOSES; ACANTHOSIS NIGRICANS; YOUNG WOMAN; TRIPE PALMS; MALIGNANCIES C1 [Nanda, Akash] Harvard Radiat Oncol Program, Boston, MA USA. [Mamon, Harvey J.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Fuchs, Charles S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Nanda, A (reprint author), Harvard Radiat Oncol Program, Boston, MA USA. NR 20 TC 1 Z9 3 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 20 PY 2008 VL 26 IS 30 BP 4992 EP 4993 DI 10.1200/JCO.2008.17.9143 PG 2 WC Oncology SC Oncology GA 361FT UT WOS:000260113600025 PM 18809604 ER PT J AU Ajani, AE Reid, CM Duffy, SJ Andrianopoulos, N Lefkovits, J Black, A New, G Lew, R Shaw, JA Yan, BP Gurvitch, R Al-Fiadh, A Brennan, AL Clark, DJ AF Ajani, Andrew E. Reid, Christopher M. Duffy, Stephen J. Andrianopoulos, Nick Lefkovits, Jeffrey Black, Alexander New, Gishel Lew, Robert Shaw, James A. Yan, Bryan P. Gurvitch, Ronen Al-Fiadh, Ali Brennan, Angela L. Clark, David J. TI Outcomes after percutaneous coronary intervention in contemporary Australian practice: insights from a large multicentre registry SO MEDICAL JOURNAL OF AUSTRALIA LA English DT Article ID DRUG-ELUTING STENTS; BARE-METAL STENTS; RANDOMIZED CONTROLLED-TRIAL; AMERICAN-HEART-ASSOCIATION; COLLEGE-OF-CARDIOLOGY; LATE THROMBOSIS; ARTERY-DISEASE; SLOW-RELEASE; DOUBLE-BLIND; TASK-FORCE AB Objective: To examine short-and medium-term outcomes of percutaneous coronary interventions (PCIs), with a focus on comparing drug-eluting stents (DESs) with bare-metal stents (BMSs). Design, setting and participants: Retrospective analysis of data from the Melbourne Interventional Group (MIG) registry, a large multicentre Australian registry. The study cohort consisted of 6364 consecutive patients undergoing 7167 PCIs between April 2004 and August 2007. Main outcome measures; Clinical events including death, myocardial infarction.(MI), target lesion revascularisation (TLR), target vessel revascularisation (TVR) and major adverse cardiac events (MACE) (a composite of death, MI and TVR), at 30 days and at 12 months. Results: The cohort was predominantly male (74%), with a mean age of 64.7 years (SD, 12.0 years). DESs were used in 3482 (51.4%) of PCIs. In the overall cohort, rates of clinical events were low at 30 days: mortality (1.9%), MI (2.4%), TLR (2.0%), TVR (2.4%) and MACE (5.7%). At 12 months, event rates were: mortality (5.2%), MI (6.0%), TLR (5.8%), TVR (8.2%) and MACE (16.2%). Patients receiving DESs had similar mortality rates to those receiving BMSs (4.0% v 6.0%; P = 0.62 [propensity score-adjusted]); late thrombosis rates were also similar in the two groups (0.8% v 1.1%; P = 0.38). The proportion of patients receiving DESs fell significantly over time, from 54.9% in the first 24 months to 44.7% in the last 15 months of the study period (P < 0.01). Independent predictors of 12-month mortality included diabetes, renal failure, ST-segment-elevation MI and cardiogenic shock. Conclusion: Our clinical event rates were comparable with international registry outcomes. Rates of mortality and stent thrombosis were no higher in patients with DESs than those with BMSs. Although DESs were used in about half the procedures (preferentially for higher-risk lesions), recent trends suggest their use is in decline. C1 [Ajani, Andrew E.] Univ Melbourne, Melbourne, Vic, Australia. [Lew, Robert] Frankston Hosp, Melbourne, Vic, Australia. [New, Gishel] Box Hill Hosp, Melbourne, Vic, Australia. [Black, Alexander] Geelong Hosp, Geelong, Vic, Australia. [Duffy, Stephen J.; Shaw, James A.] Alfred Hosp, Melbourne, Vic, Australia. [Yan, Bryan P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yan, Bryan P.] Harvard Univ, Sch Med, Boston, MA USA. [Al-Fiadh, Ali; Clark, David J.] Austin Hosp, Melbourne, Vic 3084, Australia. [Reid, Christopher M.; Andrianopoulos, Nick; Brennan, Angela L.] Monash Univ, Dept Epidemiol & Prevent Med, Ctr Cardiovasc Res & Educ Therapeut, Melbourne, Vic 3004, Australia. [Ajani, Andrew E.] Royal Melbourne Hosp, Melbourne, Vic, Australia. RP Ajani, AE (reprint author), Royal Melbourne Hosp, Melbourne, Vic, Australia. EM andrew.ajani@mh.org.au RI Yan, Bryan/C-3390-2008; Shaw, James/F-1522-2010; Yan, Bryan/P-5928-2015 FU AstraZeneca; BIOTRONIK; Boston Scientific; Johnson Johnson; Medtronic; Pfizer; Sanofi-Aventis; Schering-Plough; Servier; St Jude Medical and Terumo; National Health and Medical Research Council Centre FX The MIG acknowledges funding from AstraZeneca, BIOTRONIK, Boston Scientific, Johnson & Johnson, Medtronic, Pfizer, Sanofi-Aventis, Schering-Plough, Servier, St Jude Medical and Terumo. These companies do not have access to the data and do not have the right to review articles before publication. The work of Stephen Duffy and Catherine Farrington is supported by a National Health and Medical Research Council Centre of Clinical Research Excellence grant to the Alfred and Baker Medical Unit. NR 30 TC 15 Z9 16 U1 1 U2 2 PU AUSTRALASIAN MED PUBL CO LTD PI PYRMONT PA LEVEL 2, 26-32 PYRMONT BRIDGE RD, PYRMONT, NSW 2009, AUSTRALIA SN 0025-729X J9 MED J AUSTRALIA JI Med. J. Aust. PD OCT 20 PY 2008 VL 189 IS 8 BP 423 EP 428 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 380CE UT WOS:000261442500003 PM 18928433 ER PT J AU Lutskiy, MI Park, JY Remold, SK Remold-O'Donnell, E AF Lutskiy, Maxim I. Park, Jun Y. Remold, Susanna K. Remold-O'Donnell, Eileen TI Evolution of Highly Polymorphic T Cell Populations in Siblings with the Wiskott-Aldrich Syndrome SO PLOS ONE LA English DT Article AB Population level evolutionary processes can occur within a single organism when the germ line contains a mutation that confers a cost at the level of the cell. Here we describe how multiple compensatory mutations arose through a within-individual evolutionary process in two brothers with the immune deficiency Wiskott-Aldrich Syndrome (WAS). As a result, both brothers have T lymphocyte populations that are highly polymorphic at the locus of the germ line defect, and no single allele achieves fixation. WASP, the gene product affected in this disease, is specific to white blood cells where it is responsible for regulating actin cytoskeleton dynamics in a wide range of cellular responses. The brothers inherited a rare allele predicted to result in truncated WASP lacking the carboxy-terminal VCA domains, the region that directly catalyzes actin filament generation. Although the brothers' T cell populations are highly polymorphic, all share a corrective effect relative to the inherited allele in that they restore the VCA domain. This indicates massive selection against the truncated germ line allele. No single somatic allele becomes fixed in the circulating T cell population of either brother, indicating that a regulated step in maturation of the affected cell lineage is severely compromised by the germ line allele. Based on the finding of multiple somatic mutations, the known maturation pathway for T-lineage cells and the known defects of T cells and precursor thymocytes in mice with truncated WASP, we hypothesize that the presence of truncated WASP (WASP Delta VCA) confers an extreme disadvantage in early developing thymocytes, above and beyond the known cost of absence of full-length WASP, and that the disadvantage likely occurs through dominant negative competition of WASP Delta VCA with N-WASP, a protein that otherwise partially compensates for WASP absence in developing thymocytes. C1 [Lutskiy, Maxim I.; Park, Jun Y.; Remold-O'Donnell, Eileen] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Lutskiy, Maxim I.; Remold-O'Donnell, Eileen] Harvard Univ, Sch Med, Dept Pediat, Boston, MA USA. [Remold, Susanna K.] Univ Louisville, Dept Biol, Program Dis Evolution, Louisville, KY 40292 USA. RP Lutskiy, MI (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. EM remold@cbrinstitute.org FU National Institutes of Health [HL59561, AI39574, HL081407]; National Science Foundation [DEB-0452163]; Jeffrey Modell Foundation FX This work was supported by National Institutes of Health grants HL59561, AI39574 and HL081407, National Science Foundation grant DEB-0452163, and the Jeffrey Modell Foundation. NR 42 TC 15 Z9 15 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 20 PY 2008 VL 3 IS 10 AR e3444 DI 10.1371/journal.pone.0003444 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 432IB UT WOS:000265125600006 PM 18941616 ER PT J AU Leleu, X Roccaro, AM Moreau, AS Dupire, S Robu, D Gay, J Hatjiharissi, E Burwik, N Ghobrial, IM AF Leleu, Xavier Roccaro, Aldo M. Moreau, Anne-Sophie Dupire, Sophie Robu, Daniela Gay, Julie Hatjiharissi, Evdoxia Burwik, Nicholas Ghobrial, Irene M. TI Waldenstrom Macroglobulinemia SO CANCER LETTERS LA English DT Review DE Waldenstrom Macroglobulinemia; novel therapy; transplantation ID CONSENSUS PANEL RECOMMENDATIONS; CHRONIC LYMPHOCYTIC-LEUKEMIA; 2ND INTERNATIONAL WORKSHOP; IGM MONOCLONAL GAMMOPATHY; MARGINAL ZONE LYMPHOMA; EXTENDED RITUXIMAB THERAPY; MULTIPLE-MYELOMA CELLS; NON-HODGKIN-LYMPHOMA; OF-THE-LITERATURE; PROGNOSTIC-FACTORS AB In the past years, new developments have occurred both in the understanding of the biology of Waldenstrom Macroglobulinemia (WM) and in therapeutic options for WM. WM is a B-cell disorder characterized primarily by bone marrow infiltration with lymphoplasmacytic cells, along with demonstration of an IgM monoclonal gammopathy. Despite advances in therapy, WM remains incurable, with 5-6 years median overall survival of patients in symptomatic WM. Therapy is postponed for asymptomatic patients, and progressive anemia is the most common indication for initiation of treatment. The main therapeutic options include alkylating agents, nucleoside analogues, and rituximab. Studies involving combination chemotherapy are ongoing, and preliminary results are encouraging. No specific agent or regimen has been shown to be superior to another for treatment of WM. As such, novel therapeutic agents are needed for the treatment of WM. In ongoing efforts, we and others have sought to exploit advances made in the understanding of the biology of WM so as to better target therapeutics for this malignancy. These efforts have led to the development of several novel agents including the proteasome inhibitor bortezomib, and several Akt/mTor inhibitors, perifosine and Rad001, and immunomodulatory agents such as thalidomide and lenalidomide. Studies with monoclonal antibodies are ongoing and promising including the use of alemtuzumab, SGN-70, and the APRIL/BLYS blocking protein TACI-Ig atacicept. Other agents currently being tested in clinical trials include the PKC inhibitor enzastaurin, the natural product resveratrol, as well as the statin simvastatin. This report provides an update of the current preclinical studies and clinical efforts for the development of novel agents in the treatment of WM. (c) 2008 Published by Elsevier Ireland Ltd. C1 [Leleu, Xavier; Roccaro, Aldo M.; Moreau, Anne-Sophie; Hatjiharissi, Evdoxia; Burwik, Nicholas; Ghobrial, Irene M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Leleu, Xavier; Roccaro, Aldo M.; Moreau, Anne-Sophie; Hatjiharissi, Evdoxia; Burwik, Nicholas; Ghobrial, Irene M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Leleu, Xavier; Moreau, Anne-Sophie; Dupire, Sophie; Robu, Daniela; Gay, Julie] CHRU, Hop Huriez, Serv Malad Sang, Lille, France. [Roccaro, Aldo M.] Univ Bari, Sch Med, Dept Internal Med & Oncol, Bari, Italy. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM Irene_ghobrial@dfcri.harvard.edu OI Roccaro, Aldo/0000-0002-1872-5128 FU International Waldenstrom Macroglobulinemia Foundation (IWMF); Franco-American Fulbright Foundation FX Supported in part by International Waldenstrom Macroglobulinemia Foundation (IWMF) grant, XL is supported by a grant from the Franco-American Fulbright Foundation. NR 104 TC 12 Z9 14 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 EI 1872-7980 J9 CANCER LETT JI Cancer Lett. PD OCT 18 PY 2008 VL 270 IS 1 BP 95 EP 107 DI 10.1016/j.canlet.2008.04.040 PG 13 WC Oncology SC Oncology GA 357LL UT WOS:000259847200010 PM 18555588 ER PT J AU Hao, ZY Duncan, GS Seagal, J Su, YW Hong, C Haight, J Chen, NJ Elia, A Wakeham, A Li, WY Liepa, J Wood, GA Casola, S Rajewsky, K Mak, TW AF Hao, Zhenyue Duncan, Gordon S. Seagal, Jane Su, Yu-Wen Hong, Claire Haight, Jillian Chen, Nien-Jung Elia, Andrew Wakeham, Andrew Li, Wanda Y. Liepa, Jennifer Wood, Geoffrey A. Casola, Stefano Rajewsky, Klaus Mak, Talk W. TI Fas Receptor Expression in Germinal-Center B Cells Is Essential for T and B Lymphocyte Homeostasis SO IMMUNITY LA English DT Article ID LYMPHOPROLIFERATIVE SYNDROME; NEGATIVE SELECTION; IMMUNE-RESPONSES; CLONAL SELECTION; GENE; ANTIGEN; MICE; CD28; AUTOIMMUNITY; MUTATIONS AB Fas is highly expressed in activated and germinal center (GC) B cells but can potentially be inactivated by misguided somatic hypermutation. We employed conditional Fas-deficient mice to investigate the physiological functions of Fas in various B cell subsets. B cell-specific Fas-deficient mice developed fatal lymphoproliferation due to activation of B cells and T cells. Ablation of Fas specifically in GC B cells reproduced the phenotype, indicating that the lymphoproliferation initiates in the GC environment. B cell-specific Fas-deficient mice also showed an accumulation of IgG1(+) memory B cells expressing high amounts of CD80 and the expansion of CD28-expressing CD4(+) Th cells. Blocking T cell-B cell interaction and GC formation completely prevented the fatal lymphoproliferation. Thus, Fas-mediated selection of GC B cells and the resulting memory B cell compartment is essential for maintaining the homeostasis of both T and B lymphocytes. C1 [Hao, Zhenyue; Duncan, Gordon S.; Su, Yu-Wen; Hong, Claire; Haight, Jillian; Chen, Nien-Jung; Elia, Andrew; Wakeham, Andrew; Li, Wanda Y.; Liepa, Jennifer; Mak, Talk W.] Univ Hlth Network, Ontario Canc Inst, Campbell Family Inst Canc Res, Toronto, ON M5G 2C1, Canada. [Seagal, Jane; Rajewsky, Klaus] Immune Dis Inst Biomed Res, Boston, MA 02115 USA. [Seagal, Jane; Rajewsky, Klaus] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Wood, Geoffrey A.] Univ Guelph, Dept Pathobiol, Guelph, ON N1G 2W1, Canada. [Casola, Stefano] IFOM FIRC Inst Mol Oncol Fdn, Milan, Italy. [Mak, Talk W.] Univ Toronto, Dept Immunol, Toronto, ON M5G 2C1, Canada. [Mak, Talk W.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2C1, Canada. RP Hao, ZY (reprint author), Univ Hlth Network, Ontario Canc Inst, Campbell Family Inst Canc Res, Toronto, ON M5G 2C1, Canada. EM zhenyuehao@gmail.com; tmak@uhnres.utoronto.ca RI Su, Yu-Wen/E-8804-2010 FU Terry Fox Cancer Foundation; Canadian Institutes of Health Research,; Leukemia and Lymphoma Society; Deutsche Forschungsgemeinschaft [SFB 243]; National Institutes of Health (USA) FX We thank various Mak lab members for technical assistance, T. Calzascia for help with Th 17 cell differentiation, Toronto Centre for Phenogenomics for help with histology, and M. Saunders for scientific editing. This work was supported by grants to T.W.M. from the Terry Fox Cancer Foundation, Canadian Institutes of Health Research, and Leukemia and Lymphoma Society; to Z.H. from Canadian Institutes of Health Research; and to K.R. from the Deutsche Forschungsgemeinschaft through SFB 243 and the National Institutes of Health (USA). NR 41 TC 104 Z9 105 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD OCT 17 PY 2008 VL 29 IS 4 BP 615 EP 627 DI 10.1016/j.immuni.2008.07.016 PG 13 WC Immunology SC Immunology GA 364DP UT WOS:000260316700014 PM 18835195 ER PT J AU Hasler, U Leroy, V Jeon, US Bouley, R Dimitrov, M Kim, JA Brown, D Kwon, HM Martin, PY Feraille, E AF Hasler, Udo Leroy, Valeeie Jeon, Un Sil Bouley, Richard Dimitrov, Mitko Kim, Jeong Ah Brown, Dennis Kwon, H. Moo Martin, Pierre-Yves Feraille, Eric TI NF-kappa B modulates aquaporin-2 transcription in renal collecting duct principal cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INDUCED NEPHROTIC SYNDROME; ENHANCER-BINDING PROTEIN; WATER CHANNEL EXPRESSION; DOWN-REGULATION; NULL MICE; ACTIVATION; MECHANISM; GENE; HYPERTONICITY; PERMEABILITY AB Renal tubulo-interstitial inflammation is frequently associated with polyuria and urine concentration defects. This led us to investigate the effects of the major pro-inflammatory nuclear factor kappa B (NF-kappa B) pathway on aquaporin 2 (AQP2) expression by the collecting duct. Using immortalized collecting duct principal cells (mpkCCD(c14)), we found that, acting independently of vasopressin, activation of NF-kappa B by lipopolysaccharide (LPS) decreased AQP2 mRNA and protein levels in a time-and dose-dependent manner but did not decrease AQP2 mRNA stability. Consistently, constitutively active I kappa B kinase beta decreased AQP2 expression. The LPS-induced decrease in AQP2 mRNA levels was confirmed in rat kidney slices and was reproduced both under conditions of elevated cAMP concentration and V-2 receptor antagonism. Computer analysis of the AQP2 promoter revealed two putative kappa B elements. Mutation of either kappa B element abolished the LPS-induced decrease of luciferase activity in cells expressing AQP2 promoter-luciferase plasmid constructs. Chromatin immunoprecipitation revealed that LPS challenge decreased p65, increased p50 and p52, and had no effect on RelB and c-Rel binding to kappa B elements of the AQP2 promoter. RNA-mediated interference silencing of p65, p50, and p52 confirmed controlled AQP2 transcription by these NF-kappa B subunits. We additionally found that hypertonicity activated NF-kappa B in mpkCCD(c14) cells, an effect that may counteract the Tonicity-responsive enhancer binding protein (TonEBP)-dependent increase in AQP2 gene transcription. Taken together, these findings indicate that NF-kappa B is an important physiological regulator of AQP2 transcription. C1 [Hasler, Udo; Leroy, Valeeie; Dimitrov, Mitko; Martin, Pierre-Yves; Feraille, Eric] Fdn Rech Med, Serv Nephrol, CH-1211 Geneva 4, Switzerland. [Hasler, Udo; Leroy, Valeeie; Dimitrov, Mitko; Martin, Pierre-Yves; Feraille, Eric] Univ Geneva, CH-1211 Geneva, Switzerland. [Jeon, Un Sil; Kim, Jeong Ah; Kwon, H. Moo] Univ Maryland, Dept Med, Baltimore, MD 21201 USA. [Bouley, Richard; Brown, Dennis] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Bouley, Richard; Brown, Dennis] Massachusetts Gen Hosp, MGH Ctr Syst Biol, Program Membrane Biol, Boston, MA USA. [Bouley, Richard; Brown, Dennis] Massachusetts Gen Hosp, Div Nephrol, Boston, MA USA. RP Feraille, E (reprint author), Fdn Rech Med, Serv Nephrol, 64 Ave Roseraie, CH-1211 Geneva 4, Switzerland. EM Eric.Feraille@medecine.unige.ch RI Dimitrov, Mitko/C-9822-2009; Lee-Kwon, Whaseon/D-6021-2011 FU National Institutes of Health [R01-DK-42479, DK38452]; Swiss National Foundation [31-67878.02, 31-109473]; Elsie de Reuter Foundation; Ernest Boninchi Foundation; Fondation pour la Recherche Medicale FX This work was supported, in whole or in part, by National Institutes of Health Grants R01-DK-42479 (to H. M. K.) and DK38452 (to D. B). This work was also supported in part by Swiss National Foundation Grants 31-67878.02 and 31-109473, a Carlos and Elsie de Reuter Foundation grant, a Ernest Boninchi Foundation grant (to E. F.), and a Fondation pour la Recherche Medicale grant (to U. H.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 54 TC 31 Z9 32 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 17 PY 2008 VL 283 IS 42 BP 28095 EP 28105 DI 10.1074/jbc.M708350200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 359EN UT WOS:000259969300012 PM 18703515 ER PT J AU Humbert, M Rasmussen, RA Song, RJ Ong, H Sharma, P Chenine, AL Kramer, VG Siddappa, NB Xu, WD Else, JG Novembre, FJ Strobert, E O'Neil, SP Ruprecht, RM AF Humbert, Michael Rasmussen, Robert A. Song, Ruijiang Ong, Helena Sharma, Prachi Chenine, Agnes L. Kramer, Victor G. Siddappa, Nagadenahalli B. Xu, Weidong Else, James G. Novembre, Francis J. Strobert, Elizabeth O'Neil, Shawn P. Ruprecht, Ruth M. TI SHIV-1157i and passaged progeny viruses encoding R5 HIV-1 clade C env cause AIDS in rhesus monkeys SO RETROVIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 SUBTYPE-C; PERINATAL TRANSMISSION; BIOLOGICAL PHENOTYPE; MACACA-NEMESTRINA; CHALLENGE VIRUSES; ANTIBODY-RESPONSE; CORECEPTOR SWITCH; ENVELOPE PROTEIN; MACAQUES AB Background: Infection of nonhuman primates with simian immunodeficiency virus (SIV) or chimeric simian-human immunodeficiency virus (SHIV) strains is widely used to study lentiviral pathogenesis, antiviral immunity and the efficacy of AIDS vaccine candidates. SHIV challenges allow assessment of anti-HIV-1 envelope responses in primates. As such, SHIVs should mimic natural HIV-1 infection in humans and, to address the pandemic, encode HIV-1 Env components representing major viral subtypes worldwide. Results: We have developed a panel of clade C R5-tropic SHIVs based upon env of a Zambian pediatric isolate of HIV-1 clade C, the world's most prevalent HIV-1 subtype. The parental infectious proviral clone, SHIV-1157i, was rapidly passaged through five rhesus monkeys. After AIDS developed in the first animal at week 123 post-inoculation, infected blood was infused into a sixth monkey. Virus reisolated at this late stage was still exclusively R5 tropic and mucosally transmissible. Here we describe the long-term follow-up of this initial cohort of six monkeys. Two have remained non-progressors, whereas the other four gradually progressed to AIDS within 123-270 weeks post-exposure. Two progressors succumbed to opportunistic infections, including a case of SV40 encephalitis. Conclusion: These data document the disease progression induced by the first mucosally transmissible, pathogenic R5 non-clade B SHIV and suggest that SHIV-1157i-derived viruses, including the late-stage, highly replication-competent SHIV-1157ipd3N4 previously described ( Song et al., 2006), display biological characteristics that mirror those of HIV-1 clade C and support their expanded use for AIDS vaccine studies in nonhuman primates. C1 [Humbert, Michael; Rasmussen, Robert A.; Song, Ruijiang; Ong, Helena; Chenine, Agnes L.; Kramer, Victor G.; Siddappa, Nagadenahalli B.; Xu, Weidong; Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Humbert, Michael; Rasmussen, Robert A.; Song, Ruijiang; Chenine, Agnes L.; Siddappa, Nagadenahalli B.; Xu, Weidong; O'Neil, Shawn P.; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Sharma, Prachi; Else, James G.; Novembre, Francis J.; Strobert, Elizabeth] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA. [O'Neil, Shawn P.] New England Reg Primate Res Ctr, Southborough, MA 01772 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM michael_humbert@dfci.harvard.edu; robert_rasmussen@dfci.harvard.edu; rsong@adarc.org; helena_ong@dfci.harvard.edu; psharm9@emory.edu; achenine@hivresearch.org; victor_kramer@dfci.harvard.edu; nb_siddappa@dfci.harvard.edu; wxu@health.usf.edu; jelse@emory.edu; fnovembr@rmy.emory.edu; eliz@rmy.emory.edu; Shawn.O'Neil@pfizer.com; ruth_ruprecht@dfci.harvard.edu OI Byrareddy, Siddappa /0000-0002-7423-1763 FU NIH [P01 AI048240, RR-00165] FX The authors thank Susan Sharp for assistance in the preparation of this manuscript. This work was supported by NIH grant P01 AI048240 to RAR, JGE and RMR and NIH grant RR-00165 providing base grant support to the Yerkes National Primate Research Center. NR 45 TC 47 Z9 47 U1 2 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD OCT 17 PY 2008 VL 5 AR 94 DI 10.1186/1742-4690-5-94 PG 12 WC Virology SC Virology GA 372DM UT WOS:000260881900001 PM 18928523 ER PT J AU George, RE Sanda, T Hanna, M Frohling, S Luther, W Zhang, JM Ahn, Y Zhou, WJ London, WB McGrady, P Xue, LQ Zozulya, S Gregor, VE Webb, TR Gray, NS Gilliland, DG Diller, L Greulich, H Morris, SW Meyerson, M Look, AT AF George, Rani E. Sanda, Takaomi Hanna, Megan Frohling, Stefan Luther, William, II Zhang, Jianming Ahn, Yebin Zhou, Wenjun London, Wendy B. McGrady, Patrick Xue, Liquan Zozulya, Sergey Gregor, Vlad E. Webb, Thomas R. Gray, Nathanael S. Gilliland, D. Gary Diller, Lisa Greulich, Heidi Morris, Stephan W. Meyerson, Matthew Look, A. Thomas TI Activating mutations in ALK provide a therapeutic target in neuroblastoma SO NATURE LA English DT Article ID ANAPLASTIC LYMPHOMA KINASE; HIGH-RISK NEUROBLASTOMA; EML4-ALK FUSION GENE; CELL LUNG-CANCER; GEFITINIB; IDENTIFICATION; INHIBITOR; TRANSPLANTATION; TRANSFORMATION; PLEIOTROPHIN AB Neuroblastoma, an embryonal tumour of the peripheral sympathetic nervous system, accounts for approximately 15% of all deaths due to childhood cancer(1). High- risk neuroblastomas are rapidly progressive; even with intensive myeloablative chemotherapy, relapse is common and almost uniformly fatal(2,3). Here we report the detection of previously unknown mutations in the ALK gene, which encodes a receptor tyrosine kinase, in 8% of primary neuroblastomas. Five non- synonymous sequence variations were identified in the kinase domain of ALK, of which three were somatic and two were germ line. The most frequent mutation, F1174L, was also identified in three different neuroblastoma cell lines. ALK complementary DNAs encoding the F1174L and R1275Q variants, but not the wild- type ALK cDNA, transformed interleukin-3-dependent murine haematopoietic Ba/F3 cells to cytokine-independent growth. Ba/F3 cells expressing these mutations were sensitive to the small- molecule inhibitor of ALK, TAE684 (ref. 4). Furthermore, two human neuroblastoma cell lines harbouring the F1174L mutation were also sensitive to the inhibitor. Cytotoxicity was associated with increased amounts of apoptosis as measured by TdT-mediated dUTP nick end labelling ( TUNEL). Short hairpin RNA (shRNA)- mediated knockdown of ALK expression in neuroblastoma cell lines with the F1174L mutation also resulted in apoptosis and impaired cell proliferation. Thus, activating alleles of the ALK receptor tyrosine kinase are present in primary neuroblastoma tumours and in established neuroblastoma cell lines, and confer sensitivity to ALK inhibition with small molecules, providing a molecular rationale for targeted therapy of this disease. C1 [George, Rani E.; Sanda, Takaomi; Luther, William, II; Ahn, Yebin; Diller, Lisa; Look, A. Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Hanna, Megan; Greulich, Heidi; Meyerson, Matthew] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hanna, Megan; Greulich, Heidi; Meyerson, Matthew] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Zhang, Jianming; Zhou, Wenjun; Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Hanna, Megan; Greulich, Heidi; Meyerson, Matthew] Harvard & MIT, Broad Inst, Cambridge, MA 02142 USA. [Frohling, Stefan; Gilliland, D. Gary] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [London, Wendy B.; McGrady, Patrick] Univ Florida, Childrens Oncol Grp Stat & Data Ctr, Gainesville, FL 32601 USA. [Xue, Liquan; Morris, Stephan W.] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA. [Xue, Liquan; Morris, Stephan W.] St Jude Childrens Hosp, Dept Oncol, Memphis, TN 38105 USA. [Webb, Thomas R.] St Jude Childrens Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USA. [Zozulya, Sergey; Gregor, Vlad E.] ChemBridge Res Labs Inc, San Diego, CA 92127 USA. RP Look, AT (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu; thomas_look@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; Webb, Thomas/J-4511-2013; OI Zozulya, Sergey/0000-0002-1179-2993 FU National Institutes of Health; Friends for Life Neuroblastoma Fund; Children's Oncology Group; Alex's Lemonade Stand Foundation; NCI [CA69129]; Cancer Center Core [CA21765]; American Lebanese Syrian Associated Charities; St. Jude Children's Research Hospital FX We thank J. Elechko and L. Moreau for technical assistance, A. Azarova for help with cell culture and cell growth assays, Q. Jiang and X. Cui for assistance during ALK small-molecule inhibitor development, and A. Kung for Ba/F3 cells and retroviral vectors. Weacknowledge the Children's Oncology Group for provision of neuroblastoma tumour and matched normal DNAs, and tumour touch prep slides. We thank J. Maris for neuroblastoma cell lines. We thank Abbott Molecular International for the Vysis LSI ALK Dual Color, Break Apart Rearrangement Probe. This work was supported by grants from the National Institutes of Health (R.E.G.), the Friends for Life Neuroblastoma Fund (R.E.G.), the Children's Oncology Group (R.E.G.), Alex's Lemonade Stand Foundation (M.H. and M.M.), NCI CA69129 (L.X. and S.W.M.), Cancer Center Core grant CA21765 (T.R.W., L.X. and S.W.M.), the American Lebanese Syrian Associated Charities and St. Jude Children's Research Hospital (T.R.W., L.X. and S.W.M.). NR 27 TC 408 Z9 420 U1 3 U2 31 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 16 PY 2008 VL 455 IS 7215 BP 975 EP 978 DI 10.1038/nature07397 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 360DW UT WOS:000260038300052 PM 18923525 ER PT J AU Blumenthal, D AF Blumenthal, David TI Election 2008 - Primum non nocere - The McCain plan for health insecurity SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID INSURANCE C1 [Blumenthal, David] Massachusetts Gen Hosp, Partners Healthcare Syst, Inst Hlth Policy, Boston, MA 02114 USA. RP Blumenthal, D (reprint author), Massachusetts Gen Hosp, Partners Healthcare Syst, Inst Hlth Policy, Boston, MA 02114 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 16 PY 2008 VL 359 IS 16 BP 1645 EP 1647 DI 10.1056/NEJMp0806563 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 360EY UT WOS:000260041400001 PM 18815391 ER PT J AU Rosenbaum, L AF Rosenbaum, Lisa TI Becoming a physician: Living unlabeled - Diagnosis and disorder SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Rosenbaum, Lisa] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rosenbaum, L (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 16 PY 2008 VL 359 IS 16 BP 1650 EP 1653 DI 10.1056/NEJMp0804984 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 360EY UT WOS:000260041400003 PM 18923169 ER PT J AU Dinulos, JGH Zembowicz, A Burnett, MM Harris, NL AF Dinulos, James G. H. Zembowicz, Artur Burnett, Melissa M. Harris, Nancy Lee TI A girl with recurrent oral lesions and cutaneous bullae - Dermatitis due to zinc deficiency (acrodermatitis enteropathica-like syndrome) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ERYTHEMA MULTIFORME; EPIDERMOLYSIS-BULLOSA; DISEASE; CLASSIFICATION C1 [Dinulos, James G. H.] Dartmouth Hitchcock Med Ctr, Dept Med, Lebanon, NH 03766 USA. [Dinulos, James G. H.] Dartmouth Hitchcock Med Ctr, Dept Pediat, Lebanon, NH 03766 USA. [Dinulos, James G. H.] Dartmouth Med Sch, Dept Med, Hanover, NH USA. [Dinulos, James G. H.] Dartmouth Med Sch, Dept Pediat, Hanover, NH USA. [Zembowicz, Artur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Zembowicz, Artur] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Dinulos, JGH (reprint author), Dartmouth Hitchcock Med Ctr, Dept Med, Lebanon, NH 03766 USA. FU SkinMedica; Barrier Pharmaceuticals; Connetics; Novartis; Merck FX Dr. Dinulos reports receiving consulting fees from SkinMedica, Barrier Pharmaceuticals, and Connetics and lecture fees from Novartis. Dr. Zembowicz reports receiving consulting fees from Merck. No other potential conflict of interest relevant to this article was reported. NR 20 TC 2 Z9 2 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 16 PY 2008 VL 359 IS 16 BP 1718 EP 1724 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 360EY UT WOS:000260041400012 PM 18923175 ER PT J AU DaSilva, AF Becerra, L Pendse, G Chizh, B Tully, S Borsook, D AF DaSilva, Alexandre F. Becerra, Lino Pendse, Gautam Chizh, Boris Tully, Shannon Borsook, David TI Colocalized Structural and Functional Changes in the Cortex of Patients with Trigeminal Neuropathic Pain SO PLOS ONE LA English DT Article AB Background: Recent data suggests that in chronic pain there are changes in gray matter consistent with decreased brain volume, indicating that the disease process may produce morphological changes in the brains of those affected. However, no study has evaluated cortical thickness in relation to specific functional changes in evoked pain. In this study we sought to investigate structural (gray matter thickness) and functional (blood oxygenation dependent level - BOLD) changes in cortical regions of precisely matched patients with chronic trigeminal neuropathic pain (TNP) affecting the right maxillary (V2) division of the trigeminal nerve. The model has a number of advantages including the evaluation of specific changes that can be mapped to known somatotopic anatomy. Methodology/Principal Findings: Cortical regions were chosen based on sensory (Somatosensory cortex (SI and SII), motor (MI) and posterior insula), or emotional (DLPFC, Frontal, Anterior Insula, Cingulate) processing of pain. Both structural and functional (to brush-induced allodynia) scans were obtained and averaged from two different imaging sessions separated by 2-6 months in all patients. Age and gender-matched healthy controls were also scanned twice for cortical thickness measurement. Changes in cortical thickness of TNP patients were frequently colocalized and correlated with functional allodynic activations, and included both cortical thickening and thinning in sensorimotor regions, and predominantly thinning in emotional regions. Conclusions: Overall, such patterns of cortical thickness suggest a dynamic functionally-driven plasticity of the brain. These structural changes, which correlated with the pain duration, age-at-onset, pain intensity and cortical activity, may be specific targets for evaluating therapeutic interventions. C1 [DaSilva, Alexandre F.; Becerra, Lino; Pendse, Gautam; Tully, Shannon; Borsook, David] Harvard Univ, Med Sch, Mclean Hosp, Brain Imag Ctr, PAIN Grp, Boston, MA USA. [Becerra, Lino; Borsook, David] Harvard Univ, Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Chizh, Boris] GSK Addenbrooks Hosp, Cambridge, England. RP DaSilva, AF (reprint author), Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. EM adasilva@umich.edu FU NINDS [R01 NS042721, 1K24NS064050]; GSK; NIDCR [K12-DE014528] FX This work was primarily supported by NINDS R01 NS042721 and 1K24NS064050 (DB), as well as in part from an investigator initiated grant from GSK (DB). Additional support was provided by NIDCR K12-DE014528 (AFMD). NR 86 TC 65 Z9 67 U1 1 U2 18 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 OCT 16 PY 2008 VL 3 IS 10 AR e3396 DI 10.1371/journal.pone.0003396 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 432GT UT WOS:000265122200001 PM 18923647 ER PT J AU Wyller, VB Saul, JP Barbieri, R de Lange, C Hopp, E Norum, IB Thaulow, E AF Wyller, Vegard Bruun Saul, J. Philip Barbieri, Riccardo de Lange, Charlotte Hopp, Einar Norum, Ingvild B. Thaulow, Erik TI Autonomic Heart Rate Control at Rest and During Unloading of the Right Ventricle in Repaired Tetralogy of Fallot in Adolescents SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID BODY NEGATIVE-PRESSURE; RATE-VARIABILITY; NERVOUS ACTIVITY; SURGICAL REPAIR; MODULATION; RESPONSES; OUTFLOW; TILT AB Arrhythmias in patients with repaired tetralogy of Fallot (ToF) might be due in part to altered autonomic heart rate control caused by altered right ventricle hemodynamics. This study investigated autonomic heart rate control in adolescents with ToF at rest and during unloading of the right ventricle. A total of 17 patients with ToF and 56 healthy controls aged 12 to 18 years underwent orthostatic stress with lower body negative pressure of -20 mm Hg. Heart rate, blood pressure, and stroke volume were recorded noninvasively. Indices of heart rate variability were computed in time and frequency domains. All patients with ToF also underwent cardiac magnetic resonance imaging, demonstrating pulmonary regurgitation and right ventricular dilation. At rest, heart rate variability indices of vagal heart rate control were nonsignificantly lower in the patients with ToF compared with controls. During lower body negative pressure, heart rate increased more in controls than patients with ToF (p <= 0.001). Further, most heart rate variability indices decreased in controls, but increased in patients with ToF (p <= 0.01 or p <= 0.001 for all variables), suggesting vagal activation in the patients with ToF. In conclusion, adolescents after ToF repair have fairly normal heart rate control at rest despite altered right ventricular hemodynamics. During unloading of the right ventricle, however, vagal heart rate control increases in the patients with ToF and decreases in the controls. (C) 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;102:1085-1089) C1 [Wyller, Vegard Bruun; Norum, Ingvild B.; Thaulow, Erik] Univ Oslo, Rikshosp, Div Pediat, Univ Hosp, N-0027 Oslo, Norway. [Saul, J. Philip] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. [de Lange, Charlotte; Hopp, Einar] Univ Oslo, Rikshosp, Univ Hosp, Dept Radiol, N-0027 Oslo, Norway. RP Wyller, VB (reprint author), Univ Oslo, Rikshosp, Div Pediat, Univ Hosp, N-0027 Oslo, Norway. EM brwylle@online.no OI Barbieri, Riccardo/0000-0001-9381-3833 FU National Institutes of Health, Bethesda, Maryland [U01-HL068281-06, R01-HL084502] FX Dr. Saul was supported by Grant U01-HL068281-06 from the National Institutes of Health, Bethesda, Maryland. Dr. Barbieri was supported by Grant R01-HL084502 from the National Institutes of Health, Bethesda, Maryland. NR 21 TC 0 Z9 0 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 15 PY 2008 VL 102 IS 8 BP 1085 EP 1089 DI 10.1016/j.amjcard.2008.05.065 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 360YN UT WOS:000260094800022 PM 18929714 ER PT J AU Kavvoura, FK McQueen, MB Khoury, MJ Tanzi, RE Bertram, L Ioannidis, JPA AF Kavvoura, Fotini K. McQueen, Matthew B. Khoury, Muin J. Tanzi, Rudolph E. Bertram, Lars Ioannidis, John P. A. TI Evaluation of the Potential Excess of Statistically Significant Findings in Published Genetic Association Studies: Application to Alzheimer's Disease SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Alzheimer disease; bias (epidemiology); genetic markers; genetics; meta-analysis; publication bias ID GENOME-WIDE ASSOCIATION; PUBLICATION BIAS; RANDOMIZED-TRIALS; CLINICAL-TRIALS; METAANALYSIS; EPIDEMIOLOGY; REPLICATION; HETEROGENEITY; LOCI; INCONSISTENCY AB The authors evaluated whether there is an excess of statistically significant results in studies of genetic associations with Alzheimer's disease reflecting either between-study heterogeneity or bias. Among published articles on genetic associations entered into the comprehensive AlzGene database (www. alzgene. org) through January 31, 2007, 1,348 studies included in 175 meta-analyses with 3 or more studies each were analyzed. The number of observed studies (O) with statistically significant results (P = 0.05 threshold) was compared with the expected number (E) under different assumptions for the magnitude of the effect size. In the main analysis, the plausible effect size of each association was the summary effect presented in the respective meta-analysis. Overall, 19 meta-analyses (all with eventually nonsignificant summary effects) had a documented excess of O over E: Typically single studies had signi. cant effects pointing in opposite directions and early summary effects were dissipated over time. Across the whole domain, O was 235 (17.4%), while E was 164.8 (12.2%) (P < 10(-6)). The excess showed a predilection for meta-analyses with nonsignificant summary effects and between-study heterogeneity. The excess was seen for all levels of statistical significance and also for studies with borderline P values (P = 0.05 -0.10). The excess of signi. cant findings may represent significance-chasing biases in a setting of massive testing. C1 [Kavvoura, Fotini K.; Ioannidis, John P. A.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Clin & Mol Epidemiol Unit, GR-45110 Ioannina, Greece. [McQueen, Matthew B.] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Natl Off Publ Hlth Genom, Atlanta, GA USA. [Tanzi, Rudolph E.; Bertram, Lars] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Genet & Aging Res Unit, Charlestown, MA USA. [Ioannidis, John P. A.] Fdn Res & Technol Hellas, Biomed Res Inst, Ioannina, Greece. [Ioannidis, John P. A.] Tufts Univ, Sch Med, Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies,Dept Med, Boston, MA 02111 USA. RP Ioannidis, JPA (reprint author), Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Clin & Mol Epidemiol Unit, GR-45110 Ioannina, Greece. EM jioannid@cc.uoi.gr RI Ioannidis, John/G-9836-2011; Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X FU European Union; European Social Fund; Greek Ministry of Development; Cure Alzheimer Fund FX Author affiliations: Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece (Fotini K. Kavvoura, John P. A. Ioannidis); Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado (Matthew B. McQueen); National Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, Georgia (Muin J. Khoury); Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts (Rudolph E. Tanzi, Lars Bertram); Biomedical Research Institute, Foundation for Research and Technology - Hellas, Ioannina, Greece (John P. A. Ioannidis); Institute for Clinical Research and Health Policy Studies, Department of Medicine, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts (John P. A. Ioannidis).; Dr F. K. Kavvoura was supported by a PENED (Programma Enisxusis Ereunitikou Dunamikou) grant cofinanced by the European Union - European Social Fund (75%) and the Greek Ministry of Development - General Secretariat of Research and Technology (25%). The AlzGene database is sponsored by a grant from the Cure Alzheimer Fund. NR 50 TC 26 Z9 27 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 15 PY 2008 VL 168 IS 8 BP 855 EP 865 DI 10.1093/aje/kwn206 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 359DF UT WOS:000259965800001 PM 18779388 ER PT J AU Janne, PA AF Jaenne, Pasi A. TI Gefitinib first or gefitinib second - Is timing everything in the treatment of EGFR mutant non-small cell lung cancer? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID RECEPTOR GENE-MUTATIONS; PROSPECTIVE PHASE-II C1 [Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Jaenne, Pasi A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Jaenne, Pasi A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 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 OCT 15 PY 2008 VL 178 IS 8 BP 783 EP 785 DI 10.1164/rccm.200806-910ED PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 358QM UT WOS:000259932600003 PM 18832554 ER PT J AU Liao, KP Gaut, J Huang, AJ Cohen, G AF Liao, Katherine P. Gaut, Joseph Huang, Ambrose J. Cohen, George TI A 20-Year-Old Man With Right Leg Pain Following Orofacial Surgery SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article ID COMPARTMENT SYNDROME; LITHOTOMY POSITION C1 [Liao, Katherine P.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Gaut, Joseph; Huang, Ambrose J.; Cohen, George] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Liao, KP (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St,PBB-B3, Boston, MA 02115 USA. EM kliao@partners.org NR 12 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD OCT 15 PY 2008 VL 59 IS 10 BP 1527 EP 1532 DI 10.1002/art.24121 PG 6 WC Rheumatology SC Rheumatology GA 362RN UT WOS:000260214900023 PM 18821652 ER PT J AU New, AS Triebwasser, J Charney, DS AF New, Antonia S. Triebwasser, Joseph Charney, Dennis S. TI The case for shifting borderline personality disorder to Axis I SO BIOLOGICAL PSYCHIATRY LA English DT Review DE Axis I; Axis II; borderline personality disorder; nosology; specificity; validity ID POSITRON-EMISSION-TOMOGRAPHY; CHILDHOOD SEXUAL-ABUSE; IMPULSIVE AGGRESSIVE-BEHAVIOR; DEPRESSED-PATIENTS; PREFRONTAL CORTEX; BIPOLAR DISORDER; RISK-FACTORS; FOLLOW-UP; ANTERIOR CINGULATE; LIFE EVENTS AB Through reviewing what is known about the nature, course, and heritability of borderline personality disorder (BPD), we argue for a reconceptualization of this disorder that would lead to its placement on Axis I. Borderline personality disorder is a prevalent and disabling condition, and yet the empirical research into its nature and treatment has not been commensurate with the seriousness of the illness. We not only review empirical evidence about the etiology, phenomenology, and course of the disorder in BPD but we also address fundamental misconceptions about BPD that we believe have contributed to misunderstanding and stigmatization of the disease. Finally, we suggest future directions for research that might permit the identification of core features of this disorder, with a focus on the importance of naturalistic assessments and of assessments through the course of development. C1 [New, Antonia S.; Triebwasser, Joseph; Charney, Dennis S.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [New, Antonia S.; Triebwasser, Joseph] Bronx Vet Affairs Med Ctr, New York, NY USA. RP New, AS (reprint author), Mt Sinai Sch Med, Dept Psychiat, Box 1217, New York, NY 10029 USA. EM antonia.new@mssm.edu FU Veterans Administration (VA) [9001-03-0051] FX Dr. New gratefully acknowledges the support of the Veterans Administration (VA) for ber VA Merit Award (VA Project #: 9001-03-0051). NR 100 TC 33 Z9 34 U1 2 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 OCT 15 PY 2008 VL 64 IS 8 BP 653 EP 659 DI 10.1016/j.biopsych.2008.04.020 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 357TE UT WOS:000259868600003 PM 18550033 ER PT J AU Yanik, GA Ho, VT Levine, JE White, ES Braun, T Antin, JH Whitfield, J Custer, J Jones, D Ferrara, JLM Cooke, KR AF Yanik, Gregory A. Ho, Vincent T. Levine, John E. White, Eric S. Braun, Thomas Antin, Joseph H. Whitfield, Joel Custer, Joseph Jones, Dawn Ferrara, James L. M. Cooke, Kenneth R. TI The impact of soluble tumor necrosis factor receptor etanercept on the treatment of idiopathic pneumonia syndrome after allogeneic hematopoietic stem cell transplantation SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; DIFFUSE ALVEOLAR HEMORRHAGE; RESPIRATORY-DISTRESS-SYNDROME; SEVERE APLASTIC-ANEMIA; RHEUMATOID-ARTHRITIS; LUNG INJURY; INTERSTITIAL PNEUMONITIS; MOLECULAR-CLONING; CONTROLLED-TRIAL AB Idiopathic pneumonia syndrome (IPS) refers to a diffuse, noninfectious, acute lung injury after hematopoietic stem cell transplantation. Historically, IPS is associated with respiratory failure and mortality rates exceeding 50%. Preclinical studies have implicated tumor necrosis factor-alpha as an important effector molecule in the development of disease. We studied the tumor necrosis factor-alpha inhibitor, etanercept, combined with corticosteroids in treating 15 patients (median age, 18 years; range, 1-60 years) with IPS. Eight of 15 patients required mechanical ventilation at therapy onset. Etanercept was administered subcutaneously at a dose of 0.4 mg/kg (maximum 25 mg) twice weekly, for a maximum of 8 doses. Therapy was well tolerated with no infectious pulmonary complications noted. Ten of 15 patients had a complete response, defined as the ability to discontinue supplemental oxygen support during study therapy. The median time to complete response was 7 days (range, 3-18 days), with a day 28 survival of 73%. IPS onset was associated with elevations of several inflammatory proteins in the bronchoalveolar lavage fluid and plasma, and response to therapy correlated with reductions in pulmonary and systemic inflammation. The combination of etanercept and corticosteroids is safe and is associated with high response rates and improved survival in patients with IPS. C1 [Yanik, Gregory A.] Univ Michigan, Med Ctr, Canc Ctr 5303, Blood & Marrow Transplantat Program,Dept Pediat, Ann Arbor, MI 48109 USA. [Yanik, Gregory A.; Levine, John E.; Whitfield, Joel; Jones, Dawn; Ferrara, James L. M.; Cooke, Kenneth R.] Univ Michigan, Blood & Marrow Transplantat Program, Dept Internal Med, Ann Arbor, MI 48109 USA. [Ho, Vincent T.; Antin, Joseph H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [White, Eric S.] Univ Michigan, Dept Internal Med, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA. [Braun, Thomas] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Custer, Joseph] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. RP Yanik, GA (reprint author), Univ Michigan, Med Ctr, Canc Ctr 5303, Blood & Marrow Transplantat Program,Dept Pediat, 1500 E Med Ctr Dr,SPC 5941, Ann Arbor, MI 48109 USA. EM gyanik@umich.edu; kenneth.cooke@uhhospitals.org OI Levine, John/0000-0002-9133-0800; White, Eric/0000-0003-4060-8443 FU Orphan Products Division of the Food and Drug Administration; Leukemia & Lymphoma Society; Burroughs Wellcome Fund; Immunex Corporation, Seattle, WA; Robert Wood Johnson Harold Amos Medical Faculty Development Program FX This work was supported by grants from the Orphan Products Division of the Food and Drug Administration, the Leukemia & Lymphoma Society, the Burroughs Wellcome Fund, and Immunex Corporation, Seattle, WA(now Amgen, Thousand Oaks, CA). K. R. C. is an Amy Strelzer-Manasevit Scholar of the National Marrow Program, a Fellow of the Robert Wood Johnson Harold Amos Medical Faculty Development Program, a Clinical Scholar of the Leukemia & Lymphoma Society, and the recipient of a Clinical Scientist in Translational Research Award from the Burroughs Wellcome Fund. NR 48 TC 42 Z9 45 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 OCT 15 PY 2008 VL 112 IS 8 BP 3073 EP 3081 DI 10.1182/blood-2008-03-143412 PG 9 WC Hematology SC Hematology GA 357SH UT WOS:000259866100019 PM 18664626 ER PT J AU Kindler, T Cornejo, MG Scholl, C Liu, JN Leeman, DS Haydu, JE Frohling, S Lee, BH Gilliland, DG AF Kindler, Thomas Cornejo, Melanie G. Scholl, Claudia Liu, Jianing Leeman, Dena S. Haydu, J. Erika Froehling, Stefan Lee, Benjamin H. Gilliland, D. Gary TI K-Ras(G12D)-induced T-cell lymphoblastic lymphoma/leukemias harbor Notch1 mutations and are sensitive to gamma-secretase inhibitors SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ONCOGENIC K-RAS; MOLECULAR-GENETICS; SIGNALING PATHWAYS; SOMATIC ACTIVATION; HYPERACTIVE RAS; TRANSGENIC MICE; DIFFERENTIATION; EXPRESSION; THYMOCYTE AB To study the impact of oncogenic K-Ras on T-cell leukemia/lymphoma development and progression, we made use of a conditional K-Ras(G12D) murine knockin model, in which oncogenic K-Ras is expressed from its endogenous promoter. Transplantation of whole bone marrow cells that express oncogenic K-Ras into wild-type recipient mice resulted in a highly penetrant, aggressive T-cell leukemia/lymphoma. The lymphoblasts were composed of a CD4/CD8 double-positive population that aberrantly expressed CD44. Thymi of primary donor mice showed reduced cellularity, and immunophenotypic analysis demonstrated a block in differentiation at the double-negative 1 stage. With progression of disease, approximately 50% of mice acquired Notch1 mutations within the PEST domain. Of note, primary lymphoblasts were hypersensitive to gamma-secretase inhibitor treatment, which is known to impair Notch signaling. This inhibition was Notch-specific as assessed by down-regulation of Notch1 target genes and intracellular cleaved Notch. We also observed that the oncogenic K-Ras-induced T-cell disease was responsive to rapamycin and inhibitors of the RAS/MAPK pathway. These data indicate that patients with T-cell leukemia with K-Ras mutations may benefit from therapies that target the NOTCH pathway alone or in combination with inhibition of the PI3K/AKT/MTOR and RAS/MAPK pathways. C1 [Kindler, Thomas; Cornejo, Melanie G.; Scholl, Claudia; Liu, Jianing; Leeman, Dena S.; Haydu, J. Erika; Froehling, Stefan; Lee, Benjamin H.; Gilliland, D. Gary] Brigham & Womens Hosp, Div Hematol, Dept Med, Boston, MA 02115 USA. [Lee, Benjamin H.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Gilliland, D. Gary] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Gilliland, D. Gary] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Kindler, T (reprint author), Johannes Gutenberg Univ Mainz, Dept Med 3, Langenbeckstr 1, D-55131 Mainz, Germany. EM thomas.kindler@ukmainz.de RI Kindler, Thomas/K-5995-2013 FU National Institutes of Health [CA66996, CA105423]; Leukemia & Lymphoma Society; German Research Foundation FX The authors thank members of the Gilliland laboratory for support and helpful discussions, and Drs David A. Tuveson and Tyler E. Jacks for providing us with the conditional murine K-RasG12D model.; This work was supported by National Institutes of Health grants CA66996 and CA105423 (D.G.G.) and the Leukemia & Lymphoma Society (D.G.G.). T.K. is a fellow of the German Research Foundation. D.G.G. is a Doris Duke Charitable Foundation Distinguished Clinical Scientist and an Investigator of the Howard Hughes Medical Institute. NR 55 TC 46 Z9 47 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 OCT 15 PY 2008 VL 112 IS 8 BP 3373 EP 3382 DI 10.1182/blood-2008-03-147587 PG 10 WC Hematology SC Hematology GA 357SH UT WOS:000259866100054 PM 18663146 ER PT J AU Lee, SJ Kukreja, M Wang, T Giralt, SA Szer, J Arora, M Woolfrey, AE Cervantes, F Champlin, RE Gale, RP Halter, J Keating, A Marks, DI McCarthy, PL Olavarria, E Stadtmauer, EA Abecasis, M Gupta, V Khoury, HJ George, B Hale, GA Liesveld, JL Rizzieri, DA Antin, JH Bolwell, BJ Carabasi, MH Copelan, E Ilhan, O Litzow, MR Schouten, HC Zander, AR Horowitz, MM Maziarz, RT AF Lee, Stephanie J. Kukreja, Manisha Wang, Tao Giralt, Sergio A. Szer, Jeffrey Arora, Mukta Woolfrey, Ann E. Cervantes, Francisco Champlin, Richard E. Gale, Robert Peter Halter, Joerg Keating, Armand Marks, David I. McCarthy, Philip L. Olavarria, Eduardo Stadtmauer, Edward A. Abecasis, Manuel Gupta, Vikas Khoury, H. Jean George, Biju Hale, Gregory A. Liesveld, Jane L. Rizzieri, David A. Antin, Joseph H. Bolwell, Brian J. Carabasi, Matthew H. Copelan, Edward Ilhan, Osman Litzow, Mark R. Schouten, Harold C. Zander, Axel R. Horowitz, Mary M. Maziarz, Richard T. TI Impact of prior imatinib mesylate on the outcome of hematopoietic cell transplantation for chronic myeloid leukemia SO BLOOD LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; MARROW TRANSPLANTATION; CHRONIC-PHASE; BONE-MARROW; FOLLOW-UP; THERAPY; ERA; MULTICENTER; INTERFERON; FAILURE AB Imatinib mesylate (IM, Gleevec) has largely supplanted allogeneic hematopoietic cell transplantation (HCT) as first line therapy for chronic myeloid leukemia (CML). Nevertheless, many people with CML eventually undergo HCT, raising the question of whether prior IM therapy impacts HCT success. Data from the Center for International Blood and Marrow Transplant Research on 409 subjects treated with IM before HCT (IM+) and 900 subjects who did not receive IM before HCT (IM-) were analyzed. Among patients in first chronic phase, IM therapy before HCT was associated with better survival but no statistically significant differences in treatment-related mortality, relapse, and leukemia-free survival. Better HLA-matched donors, use of bone marrow, and transplantation within one year of diagnosis were also associated with better survival. A matched-pairs analysis was performed and confirmed a higher survival rate among first chronic phase patients receiving IM. Among patients transplanted with advanced CML, use of IM before HCT was not associated with treatment-related mortality, relapse, leukemia-free survival, or survival. Acute graft-versus-host disease rates were similar between IM+ and IM- groups regardless of leukemia phase. These results should be reassuring to patients receiving IM before HCT. C1 [Lee, Stephanie J.; Woolfrey, Ann E.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Kukreja, Manisha; Wang, Tao; Horowitz, Mary M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Giralt, Sergio A.; Champlin, Richard E.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Szer, Jeffrey] Royal Melbourne Hosp, Parkville, Vic 3050, Australia. [Arora, Mukta] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Cervantes, Francisco] Hosp Clin Barcelona, Barcelona, Spain. [Gale, Robert Peter] Ctr Adv Studies Leukemia, Los Angeles, CA USA. [Halter, Joerg] Univ Basel Hosp, CH-4031 Basel, Switzerland. [Keating, Armand; Gupta, Vikas] Princess Margaret Hosp Children, Toronto, ON, Canada. [Marks, David I.] Bristol Childrens Hosp, Bristol, Avon, England. [McCarthy, Philip L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Olavarria, Eduardo] Hammersmith Hosp, London, England. [Stadtmauer, Edward A.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Abecasis, Manuel] Inst Portugues Oncol Francisco Gentil, Lisbon, Portugal. [Khoury, H. Jean] Emory Univ, Sch Med, Atlanta, GA USA. [George, Biju] Christian Med Coll & Hosp, Vellore 632004, Tamil Nadu, India. [Hale, Gregory A.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Liesveld, Jane L.] Univ Rochester, Med Ctr, Rochester, NY 14627 USA. [Rizzieri, David A.] Duke Univ, Med Ctr, Durham, NC USA. [Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bolwell, Brian J.; Copelan, Edward] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Carabasi, Matthew H.] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Ilhan, Osman] Ibni Sinai Hosp, Ankara, Turkey. [Litzow, Mark R.] Mayo Clin, Rochester, MN USA. [Schouten, Harold C.] Univ Hosp Maastricht, Maastricht, Netherlands. [Zander, Axel R.] Univ Hosp Eppendorf, Hamburg, Germany. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Lee, SJ (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D5-290, Seattle, WA 98109 USA. EM sjlee@fhcrc.org RI Halter, Joerg/C-9487-2012; OI Szer, Jeff/0000-0001-6783-2301 FU Novartis; National Cancer Institute [U24CA76518]; National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute; Office of Naval Research; Health Resources and Services Administration; AABB; Aetna; American International Group; American Society for Blood and Marrow Transplantation; Amgen; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US; Baxter International; Bayer HealthCare Pharmaceuticals; BioOne Corporation; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Bristol-Myers Squibb Company; Cangene Corporation; Celgene Corporation; CellGenix; Cerus Corporation; Cubist Pharmaceuticals; Cylex; CytoTherm; DOR BioPharma; Dynal Biotech, an Invitrogen company; EKR Therapeutics; Enzon Pharmaceuticals; Gambro BCT; Gamida Cell; Genzyme Corporation; Gift of Life Bone Marrow Foundation; GlaxoSmithKline; Histogenetics; HKS Medical Information Systems; Hospira; Infectious Diseases Society of America; Kiadis Pharma; Kirin Brewery; Merck Company; Medical College of Wisconsin; MGI Pharma; Millennium Pharmaceuticals; Miller Pharmacal Group; Milliman USA; Miltenyi Biotec; MultiPlan; National Marrow Donor Program; Nature Publishing Group; Oncology Nursing Society; Osiris Therapeutics; Pall Life Sciences; PDL BioPharma; Pfizer; Pharmion Corporation; Roche Laboratories; Schering Plough Corporation; Society for Healthcare Epidemiology of America; StemCyte; StemSoft Software; SuperGen; Sysmex; Teva Pharmaceutical Industries; Marrow Foundation; THERAKOS; University of Colorado Cord Blood Bank; ViaCell; Vidacare Corporation; ViraCor Laboratories; ViroPharma; Wellpoint FX This work was supported by Novartis (research grant). The CIBMTR is supported by Public Health Service Grant U24CA76518 from the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and the National Heart, Lung, and Blood Institute; Office of Naval Research; Health Resources and Services Administration; and grants from the following: AABB; Aetna; American International Group; American Society for Blood and Marrow Transplantation; Amgen; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US; Baxter International; Bayer HealthCare Pharmaceuticals; BioOne Corporation; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Bristol-Myers Squibb Company; Cangene Corporation; Celgene Corporation; CellGenix; Cerus Corporation; Cubist Pharmaceuticals; Cylex; CytoTherm; DOR BioPharma; Dynal Biotech, an Invitrogen company; EKR Therapeutics; Enzon Pharmaceuticals; Gambro BCT; Gamida Cell; Genzyme Corporation; Gift of Life Bone Marrow Foundation; GlaxoSmithKline; Histogenetics; HKS Medical Information Systems; Hospira; Infectious Diseases Society of America; Kiadis Pharma; Kirin Brewery; Merck & Company; Medical College of Wisconsin; MGI Pharma; Millennium Pharmaceuticals; Miller Pharmacal Group; Milliman USA; Miltenyi Biotec; MultiPlan; National Marrow Donor Program; Nature Publishing Group; Oncology Nursing Society; Osiris Therapeutics; Pall Life Sciences; PDL BioPharma; Pfizer; Pharmion Corporation; Roche Laboratories; Schering Plough Corporation; Society for Healthcare Epidemiology of America; StemCyte; StemSoft Software; SuperGen; Sysmex; Teva Pharmaceutical Industries; Marrow Foundation; THERAKOS; University of Colorado Cord Blood Bank; ViaCell; Vidacare Corporation; ViraCor Laboratories; ViroPharma; and Wellpoint.; The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, or any other agency of the U. S. Government. NR 24 TC 72 Z9 78 U1 0 U2 3 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 OCT 15 PY 2008 VL 112 IS 8 BP 3500 EP 3507 DI 10.1182/blood-2008-02-141689 PG 8 WC Hematology SC Hematology GA 357SH UT WOS:000259866100067 PM 18664621 ER PT J AU Ford, JM Roach, BJ Hoffman, RS Mathalon, DH AF Ford, Judith M. Roach, Brian J. Hoffman, Ralph S. Mathalon, Daniel H. TI The dependence of P300 amplitude on gamma synchrony breaks down in schizophrenia SO BRAIN RESEARCH LA English DT Article DE Schizophrenia; EEG; Phase synchrony; Power ID SINGLE-TRIAL ANALYSIS; AUDITORY ODDBALL PARADIGM; EVOKED-RESPONSES; WAVELET ANALYSIS; EEG ACTIVITY; METAANALYSIS; VARIABILITY; STIMULI; HUMANS AB Introduction: Auditory P300 amplitude reduction in schizophrenia is canonical and may be explained by poor synchronization or reduced power of the underlying neural activity. We asked if patients have reduced synchrony and power, and whether together with P300 amplitude, they make unique or overlapping contributions to the discrimination between patients and controls. We also asked whether people who have large P300s have higher power and greater synchrony of neural activity, and if the relationships between P300 and power and synchrony are different in patients and healthy controls. Methods: We recorded EEG data from 22 controls and 21 patients with schizophrenia (DSM-IV) while they performed an auditory target detection task. We used wavelet analyses of the single trial data to estimate total power and synchrony of delta, theta, alpha, beta, and gamma activity in a 50ms window around the peak of the P300 to the target. We measured P300 amplitude from the average of the single trials, in a 50ms window around its peak. Results and conclusions: P300 amplitude and delta and theta synchrony were reduced in patients; delta power and synchrony better distinguished between groups than P300 amplitude. In healthy controls, but not patients, gamma synchrony predicted P300 amplitude. In patients, P300 and gamma synchrony are affected by independent factors; the relationship between them is attenuated by an additional pathophysiological process. (c) Published by Elsevier B.V. C1 [Ford, Judith M.; Roach, Brian J.; Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Ford, Judith M.; Roach, Brian J.; Mathalon, Daniel H.] San Francisco VA Med Ctr, Psychiat Serv, San Francisco, CA 94121 USA. [Hoffman, Ralph S.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. RP Ford, JM (reprint author), Univ Calif San Francisco, Dept Psychiat, 4150 Clement St, San Francisco, CA 94121 USA. EM judith.ford@ucsf.edu OI Roach, Brian/0000-0002-3264-1465; Mathalon, Daniel/0000-0001-6090-4974 FU VA Schizophrenia Biological Research Center; National Institute of Mental Health [MH40052, MH S8262, MH067967]; National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD) FX This work was supported by the VA Schizophrenia Biological Research Center and grants from National Institute of Mental Health (MH40052, MH S8262, MH067967), and the National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD). NR 33 TC 39 Z9 39 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 OCT 15 PY 2008 VL 1235 SI SI BP 133 EP 142 DI 10.1016/j.brainres.2008.06.048 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 371UZ UT WOS:000260858400014 PM 18621027 ER PT J AU Saad, AG Yeap, BY Thunnissen, FBJM Pinkus, GS Pinkus, JL Loda, M Sugarbaker, DJ Johnson, BE Chirieac, LR AF Saad, Ali G. Yeap, Beow Y. Thunnissen, Frederik B. J. M. Pinkus, Geraldine S. Pinkus, Jack L. Loda, Massimo Sugarbaker, David J. Johnson, Bruce E. Chirieac, Lucian R. TI Immunohistochemical Markers Associated With Brain Metastases in Patients With Nonsmall Cell Lung Carcinoma SO CANCER LA English DT Article DE epidermal growth factor receptor; Ki-67 labeling index; overall survival; tumor markers; vascular endothelial growth factor ID ENDOTHELIAL GROWTH-FACTOR; FACTOR RECEPTOR; COMPUTED-TOMOGRAPHY; ONCOLOGY-GROUP; TUMOR-GROWTH; CANCER; EXPRESSION; ANGIOGENESIS; PROLIFERATION; CHEMOTHERAPY AB BACKGROUND. To the authors' knowledge, there are no reliable markers able to identify patients with nonsmall cell lung cancer (NSCLC) that will develop metastases to the brain. The authors investigated associations between immunohistochemical markers and the development of brain metastases in patients with NSCLC. METHODS. This was a hospital-based, case-control Study of patients who were newly diagnosed with NSCLC between 1989 and 2003, developed brain metastases, and had pathology material available from both the primary NSCLC and the brain metastases. These patients were compared with a control group of patients who had NSCLC and no evidence of brain metastases. NSCLC was examined for expression levels of Ki-67, caspase-3, vascular endothelial growth factor A (VEGF-A), VEGF-C, E-cadherin, and epidermal growth factor receptor (EGFR) in 54 surgical pathology specimens using immunohistochemistry, and associations were evaluated between those markers and the development of brain metastases. RESULTS. Brain metastases developed after a median of 12.5 months (range, 1.7-89.4 months) after the diagnosis of NSCLC. A significantly increased risk of developing brain metastases was associated with patients with NSCLC who had primary tumors with high Ki-67 levels (adjusted odds ratio [OR] of 12.2; 95% confidence interval [95% CI], 2.4-70.4 [P < .001]), low caspase-3 expression (adjusted OR of 43; 95% CI, 5.3 to > 100 [P < .001]), high VEGF-C expression (adjusted OR of 14.6; 95% Cl, 2.0 to > 100 [P < .001]), and low E-cadherin (adjusted OR of 3.6; 95% Cl, 0.9-16.4 [P = .05]). No significant risk was associated with VEGF-A or EGFR expression. High Ki-67 expression also was associated with a shorter overall survival (P = .04). CONCLUSIONS. The results of the current study indicated that patients with NSCLC who had high Ki-67 expression, low caspase-3 expression, high VEGF-C expression, and low E-cadherin expression in their tumors may benefit from close surveillance because they may have an increased risk of developing brain metastases. Cancer 2008; 113:2129-38. (C) 2008 American Cancer Society. C1 [Saad, Ali G.; Pinkus, Geraldine S.; Pinkus, Jack L.; Loda, Massimo; Chirieac, Lucian R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Saad, Ali G.; Yeap, Beow Y.; Pinkus, Geraldine S.; Pinkus, Jack L.; Loda, Massimo; Sugarbaker, David J.; Johnson, Bruce E.; Chirieac, Lucian R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Yeap, Beow Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Thunnissen, Frederik B. J. M.] Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Amsterdam, Netherlands. [Sugarbaker, David J.] Brigham & Womens Hosp, Dept Gen Thorac Surg, Boston, MA 02115 USA. [Johnson, Bruce E.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Johnson, Bruce E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Chirieac, LR (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM lchirieac@partners.org OI Thunnissen, Erik/0000-0001-5355-8508 FU National Institutes of Health [CA90578, CA074386, CA092824]; Brigham and Women's Hospital FX Supported by CA90578, CA074386, and CA092824 from the National Institutes of Health and by the International Mesothelioma Program from Brigham and Women's Hospital. NR 55 TC 33 Z9 34 U1 1 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 OCT 15 PY 2008 VL 113 IS 8 BP 2129 EP 2138 DI 10.1002/cncr.23826 PG 10 WC Oncology SC Oncology GA 362LA UT WOS:000260198000018 PM 18720359 ER PT J AU Haas, JS Earle, CC Orav, JE Brawarsky, P Keohane, M Neville, BA Williams, DR AF Haas, Jennifer S. Earle, Craig C. Orav, John E. Brawarsky, Phyllis Keohane, Marie Neville, Bridget A. Williams, David R. TI Racial Segregation and Disparities in Breast Cancer Care and Mortality SO CANCER LA English DT Article DE race; ethnicity; breast cancer; segregation ID RESIDENTIAL SEGREGATION; CLAIMS DATA; LUNG-CANCER; OLDER WOMEN; MEDICARE BENEFICIARIES; SOCIOECONOMIC-STATUS; GEOGRAPHIC-VARIATION; CARCINOMA TREATMENT; CONSERVING SURGERY; ETHNIC DISPARITIES AB BACKGROUND. Questions have existed as to whether residential segregation is a mediator of racial/ethnic disparities in breast cancer care and breast cancer mortality, or has a differential effect by race/ethnicity. METHODS. Data from the Surveillance, Epidemiology, and End Results-Medicare database on white, black, and Hispanic women aged 66 to 85 years with breast cancer were examined for the receipt of adequate breast cancer care. RESULTS. Blacks were less likely than whites to receive adequate breast cancer care (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.71-0.86). Individuals, both black and white, who lived in areas with greater black segregation were less likely to receive adequate breast cancer care (OR, 0.73; 95% CI, 0.64-0.82). Black segregation was a mediator of the black/white disparity in breast cancer care, explaining 8.9% of the difference. After adjustment, adequate care for Hispanics did not significantly differ from whites, but individuals, both Hispanic and white, who lived in areas with greater Hispanic segregation were less likely to receive adequate breast cancer care (OR, 0.73; 95% CI, 0.61-0.89). Although Blacks experienced greater breast cancer mortality than whites, black segregation did not substantially mediate the black-white disparity in survival, and was not significantly associated with mortality (hazards ratio, 1.03; 95% CI, 0.87-1.21). Breast cancer mortality did not differ between Hispanics and whites. CONCLUSIONS. Among seniors, segregation mediates some of the black-white disparity in breast cancer care, but not mortality. Individuals who live in more segregated areas are less likely to receive adequate breast cancer care. Cancer 2008; 113:2166-72. (C) 2008 American Cancer Society. C1 [Haas, Jennifer S.; Orav, John E.; Brawarsky, Phyllis; Keohane, Marie] Brigham & Womens Hosp, Div Gen Med & Primary Care, Dept Med, Boston, MA 02120 USA. [Haas, Jennifer S.; Orav, John E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Earle, Craig C.; Neville, Bridget A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Williams, David R.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Haas, JS (reprint author), Brigham & Womens Hosp, Div Gen Med & Primary Care, Dept Med, 1620 Tremont St, Boston, MA 02120 USA. EM jhaas@partners.org FU National Cancer Institute [R01 CA112451] FX Supported by the National Cancer Institute (R01 CA112451).; We thank Joan Warren, PhD for her helpful comments on an earlier version of this article. We thank Philip J. Ethington, PhD for sharing methods for creating measures of residential segregation in municipal areas. NR 46 TC 37 Z9 37 U1 2 U2 9 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 2008 VL 113 IS 8 BP 2166 EP 2172 DI 10.1002/cncr.23828 PG 7 WC Oncology SC Oncology GA 362LA UT WOS:000260198000023 PM 18798230 ER PT J AU Spain, P Carpenter, WR Talcott, JA Clark, JA Do, YK Hamilton, RJ Galanko, JA Jackman, A Godley, PA AF Spain, Pamela Carpenter, William R. Talcott, James A. Clark, Jack A. Do, Young Kyung Hamilton, Robert J. Galanko, Joseph A. Jackman, Anne Godley, Paul A. TI Perceived Family History Risk and Symptomatic Diagnosis of Prostate Cancer The North Carolina Prostate Cancer Outcomes Study SO CANCER LA English DT Article DE prostatic neoplasms; diagnosis; treatment; African Americans/psychology; European continental ancestry group/psychology; attitude to health; socioeconomic factors; access to healthcare ID AFRICAN-AMERICAN MEN; COMMON OUTCOMES; RELATIVE RISK; OLDER MEN; KNOWLEDGE; SURVIVAL; ANTIGEN; SERVICES; BEHAVIOR; BELIEFS AB BACKGROUND. Prostate cancer (PrCA) is the most common cancer and the second leading cause of cancer death among US men. African American (AA) men remain at significantly greater risk of PrCA diagnosis and mortality than other men. Many factors contribute to the experienced disparities. METHODS. Guided by the Health Belief Model, the authors surveyed a population of AA and Caucasian men newly diagnosed with PrCA to describe racial differences in perceived risk of PrCA and to examine whether 1) perceived high risk predicts greater personal responsibility for prostate care; and 2) greater personal responsibility for prostate care predicts earlier, presymptomatic diagnosis. Multivariate general linear modeling was performed. RESULTS. The authors found that men with a PrCA family history appreciated their increased risk, but AA men with a family history were less likely to appreciate their increased risk. Nevertheless, neither reporting a PrCA family history nor perceived increased risk significantly predicted screening and preventive behaviors. Furthermore, higher physician trust predicted increased likelihood to have regular prostate exams and screening, indicating that the racial differences in seeking prostate care may be mediated through physician trust. Expressed personal responsibility for screening and more frequent preventive behaviors were associated with more frequent screening diagnoses, fewer symptomatic diagnoses, and less frequent advanced cancers. CONCLUSIONS. Together, these results indicate that appreciating greater risk for PrCA is not sufficient to ensure that men will intend, or be able, to act. Increased trust in physicians may be a useful, central marker that efforts to reduce disparities in access to medical care are succeeding. Cancer 2008;113:2180-7. (C) 2008 American Cancer Society. C1 [Spain, Pamela] RTI Int, Hlth & Social Org Res, Res Triangle Pk, NC 27709 USA. [Spain, Pamela; Jackman, Anne; Godley, Paul A.] Univ N Carolina, Cecil G Sheps Ctr Hlth Serv Res, Chapel Hill, NC USA. [Carpenter, William R.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Carpenter, William R.; Do, Young Kyung] Univ N Carolina, Dept Hlth Policy & Adm, Chapel Hill, NC 27599 USA. [Talcott, James A.] Massachusetts Gen Hosp, Ctr Canc, Ctr Outcomes Res, Boston, MA USA. [Talcott, James A.] Harvard Univ, Sch Med, Boston, MA USA. [Clark, Jack A.] Edith Nourse Rogers Mem Vet Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Clark, Jack A.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Hamilton, Robert J.] Univ Toronto, Dept Urol Surg, Toronto, ON, Canada. [Galanko, Joseph A.; Godley, Paul A.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. [Godley, Paul A.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. RP Spain, P (reprint author), RTI Int, Hlth & Social Org Res, POB 12194, Res Triangle Pk, NC 27709 USA. EM pspain@rti.org RI Carpenter, William/E-5125-2013; OI Clark, Jack/0000-0002-7424-1670; Hamilton, Robert/0000-0002-6715-5934 FU Agency for Healthcare Research and Quality [5-P01-HS010861]; National Center on Minority Health and Health Disparities [1 P60 MD0024-01]; National Cancer Institute [1 U01 CA114629-01, R25T CA 57726]; NIH [P30 DK 034987]; Department of Defense [PC040795] FX Supported by Agency for Healthcare Research and Quality Grant 5-P01-HS010861, National Center on Minority Health and Health Disparities Grant 1 P60 MD0024-01, and National Cancer Institute Grant 1 U01 CA114629-01.; Dr. Carpenter is supported by a training grant from the National Cancer Institute (R25T CA 57726). Dr. Galanko is supported by NIH Grant P30 DK 034987.; Dr. Godley is supported by Department of Defense Grant PC040795. NR 30 TC 11 Z9 11 U1 2 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 OCT 15 PY 2008 VL 113 IS 8 BP 2180 EP 2187 DI 10.1002/cncr.23801 PG 8 WC Oncology SC Oncology GA 362LA UT WOS:000260198000025 PM 18798229 ER PT J AU Krull, KR Gioia, G Ness, KK Ellenberg, L Recklitis, C Leisenring, W Huang, S Stovall, M Robison, LL Zeltzer, L AF Krull, Kevin R. Gioia, Gerard Ness, Kirsten K. Ellenberg, Leah Recklitis, Christopher Leisenring, Wendy Huang, Sujuan Stovall, Marilyn Robison, Leslie L. Zeltzer, Lonnie TI Reliability and Validity of the Childhood Cancer Survivor Study Neurocognitive Questionnaire SO CANCER LA English DT Article DE Childhood Cancer Survivor Study; neurocognitive; questionnaire; late effects ID ACUTE LYMPHOBLASTIC-LEUKEMIA; QUALITY-OF-LIFE; TEMPORAL-LOBE EPILEPSY; FRONTAL-LOBE; NEUROPSYCHOLOGICAL PERFORMANCE; CHILDREN; MEMORY; DEPRESSION; ONCOLOGY; SEQUELAE AB BACKGROUND. Up to 40% of childhood cancer survivors may experience neurocognitive impairment in I or more specific domains. As such, regular monitoring has been recommended for patients exposed to cranial irradiation and/or antimetabolite chemotherapy. This study reports the results of a questionnaire developed to identify those survivors who may be experiencing neurocognitive problems. METHODS. Participants for this study were 7121 members of the Childhood Cancer Survivor Study cohort (6739 survivors and 382 siblings). These participants completed a new neurocognitive questionnaire designed to assess functions commonly affected by cancer therapy, as well as a standard measure of emotional functioning. A measure of cognitive and emotional functioning was also completed on a subset of the patients roughly 7 years before the current questionnaire. Responses to the questionnaires among subgroups of survivors were then analyzed to examine the reliability and validity of the new neurocognitive questionnaire. RESULTS. Four reliable factors were identified that assessed task efficiency, emotional regulation, organization, and memory skills. These neurocognitive factors accurately discriminated survivors who were at "high risk" for neurocognitive dysfunction, because of neurologic abnormalities or a history of intensive focal cranial irradiation, from healthy "low-risk" survivors and siblings. CONCLUSIONS. The questionnaire demonstrated excellent reliability, as well as construct and discriminative validity. It appears to be a practical and efficient tool for monitoring neurocognitive outcomes in adult survivors of pediatric cancer. Cancer 2008; 113:2188-97. (C) 2008 American Cancer Society. C1 [Krull, Kevin R.; Ness, Kirsten K.; Huang, Sujuan; Robison, Leslie L.] St Jude Childrens Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. [Gioia, Gerard] Childrens Natl Med Ctr, Dept Psychiat, Washington, DC 20010 USA. [Ellenberg, Leah] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Recklitis, Christopher] Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02115 USA. [Leisenring, Wendy] Fred Hutchinson Canc Res Ctr, Dept Biostat, Seattle, WA 98104 USA. [Stovall, Marilyn] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [Zeltzer, Lonnie] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. RP Krull, KR (reprint author), St Jude Childrens Hosp, Dept Epidemiol & Canc Control, 332 N Lauderdale St,MS 735, Memphis, TN 38105 USA. EM kevin.krull@stjude.org OI Zeltzer, Lonnie/0000-0001-9306-9450 FU NCI NIH HHS [U24 CA055727, U24 CA055727-14, U24-CA55727] NR 56 TC 30 Z9 30 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD OCT 15 PY 2008 VL 113 IS 8 BP 2188 EP 2197 DI 10.1002/cncr.23809 PG 10 WC Oncology SC Oncology GA 362LA UT WOS:000260198000026 PM 18792068 ER PT J AU Wang, JH Cai, Y Yu, WD Ren, CX Spencer, DM Ittmann, M AF Wang, Jianghua Cai, Yi Yu, Wendong Ren, Chengxi Spencer, David M. Ittmann, Michael TI Pleiotropic Biological Activities of Alternatively Spliced TMPRSS2/ERG Fusion Gene Transcripts SO CANCER RESEARCH LA English DT Article ID HUMAN PROSTATE-CANCER; TMPRSS2-ERG FUSION; EXPRESSION; ERG; TUMORIGENESIS; ANGIOGENESIS; ABERRATIONS; PROGRESSION; METASTASIS; EPITHELIUM AB TMPRSS2/ERG gene fusions are found in the majority of prostate cancers; however, there is significant heterogeneity in the 5' region of the alternatively spliced fusion gene transcripts. We have found that there is also significant heterogeneity within the coding exons as well. There is variable inclusion of a 72-bp exon and other novel alternatively spliced isoforms. To assess the biological significance of these alternatively spliced transcripts, we expressed various transcripts in primary prostatic epithelial cells (PrEC) and in an immortalized PrEC line, PNT1a. The fusion gene transcripts promoted proliferation, invasion, and motility with variable activities that depended on the structure of the 5' region encoding the TMPRSS2/ERG fusion and the presence of the 72-bp exon. Cotransfection of different isoforms further enhanced biological activity, mimicking the situation in vivo, in which multiple isoforms are expressed. Finally, knockdown of the fusion gene in VCaP cells resulted in inhibition of proliferation in vitro and tumor progression in an in vivo orthotopic mice model. Our results indicate that TMPRSS2/ERG fusion isoforms have variable biological activities promoting tumor initiation and progression and are consistent with our previous clinical observations indicating that certain TMPRSS2/ERG fusion isoforms are significantly correlated with more aggressive disease. [Cancer Res 2008; 68(20):8516-24] C1 [Wang, Jianghua; Cai, Yi; Yu, Wendong; Ren, Chengxi; Ittmann, Michael] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. [Spencer, David M.] Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. [Wang, Jianghua; Cai, Yi; Yu, Wendong; Ren, Chengxi; Ittmann, Michael] Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA. RP Ittmann, M (reprint author), Baylor Coll Med, Dept Pathol, 1 Baylor Plaza, Houston, TX 77030 USA. EM mittmann@bcm.tmc.edu FU Department of Defense Prostate Cancer Research [DAMD W81XWH-08-1-0055]; National Cancer Institute [P50CA058204]; Department of Veterans Affairs; Michael E. DeBakey Veterans Affairs Medical Center FX Grant support: This work was supported by grants from the Department of Defense Prostate Cancer Research program (DAMD W81XWH-08-1-0055), the National Cancer Institute to the Baylor Prostate Cancer Specialized Program of Research Excellence (P50CA058204), and the Department of Veterans Affairs Merit Review program (M. Ittmann) and by the use of the facilities of the Michael E. DeBakey Veterans Affairs Medical Center. NR 35 TC 87 Z9 93 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 OCT 15 PY 2008 VL 68 IS 20 BP 8516 EP 8524 DI 10.1158/0008-5472.CAN-08-1147 PG 9 WC Oncology SC Oncology GA 364GE UT WOS:000260323400038 PM 18922926 ER PT J AU Chin, LJ Ratner, E Leng, SG Zhai, RH Nallur, S Babar, I Muller, RU Straka, E Su, L Burki, EA Crowell, RE Patel, R Kulkarni, T Homer, R Zelterman, D Kidd, KK Zhu, Y Christiani, DC Belinsky, SA Slack, FJ Weidhaas, JB AF Chin, Lena J. Ratner, Elena Leng, Shuguang Zhai, Rihong Nallur, Sunitha Babar, Imran Muller, Roman-Ulrich Straka, Eva Su, Li Burki, Elizabeth A. Crowell, Richard E. Patel, Rajeshvari Kulkarni, Trupti Homer, Robert Zelterman, Daniel Kidd, Kenneth K. Zhu, Yong Christiani, David C. Belinsky, Steven A. Slack, Frank J. Weidhaas, Joanne B. TI A SNP in a let-7 microRNA Complementary Site in the KRAS 3 ' Untranslated Region Increases Non-Small Cell Lung Cancer Risk SO CANCER RESEARCH LA English DT Article ID TARGET SITES; POLYMORPHISMS; EXPRESSION; GENES; ASSOCIATION; SUPPRESSION; HAPLOTYPES; GENOTYPES; MIR-125A; SURVIVAL AB Lung cancer is the leading cause of cancer deaths worldwide, yet few genetic markers of lung cancer risk useful for screening exist. The let-7 family-of-microRNAs (miRNA) are global genetic regulators important in controlling lung cancer oncogene expression by binding to the 3' untrauslated regions of their target mRNAs. The purpose of this study was to identify single nucleotide polymorphisms (SNP) that could modify let-7 binding and to assess the effect of such SNPs on target gene regulation and risk for non-small cell lung cancer (NSCLC). let-7 complementary sites (LCS) were sequenced in the KRAS 3' untranslated region from 74 NSCLC cases to identify mutations and SNPs that correlated with NSCLC. The allele frequency of a previously unidentified SNP at LCS6 was characterized in 2,433 people (representing 46 human populations). The frequency of the variant allele is 18.1% to 20.3% in NSCLC patients and 5.8% in world populations. The association between the SNP and the risk for NSCLC was defined in two independent case-control studies. A case-control study of lung cancer from New Mexico showed a 2.3-fold increased risk (confidence interval, 1.1-4.6; P = 0.02) for NSCLC cancer in patients who smoked <40 pack-years. This association was validated in a second independent case-control study. Functionally, the variant allele results in KRAS overexpression in vitro. The LCS6 variant allele in a KRAS miRANA complementary site is significantly associated with increased risk for NSCLC among moderate smokers and represents a new paradigm for let-7 miRNAs in lung cancer susceptibility. [Cancer Res 2008;68(20):8535-40] C1 [Ratner, Elena; Nallur, Sunitha; Muller, Roman-Ulrich; Patel, Rajeshvari; Kulkarni, Trupti; Weidhaas, Joanne B.] Yale Univ, Dept Therapeut Radiol, New Haven, CT 06520 USA. [Chin, Lena J.; Babar, Imran; Slack, Frank J.] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA. [Straka, Eva; Kidd, Kenneth K.] Yale Univ, Dept Genet, New Haven, CT 06520 USA. [Homer, Robert] Yale Univ, Dept Pathol, New Haven, CT 06520 USA. [Zelterman, Daniel; Zhu, Yong] Yale Univ, Dept Epidemiol, New Haven, CT 06520 USA. [Zhai, Rihong; Su, Li; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulmonary & Crit Care Unit,Dept Med, Boston, MA USA. [Crowell, Richard E.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA. [Leng, Shuguang; Burki, Elizabeth A.; Belinsky, Steven A.] Lovelace Resp Res Inst, Lung Canc Program, Albuquerque, NM USA. RP Weidhaas, JB (reprint author), Yale Univ, Dept Therapeut Radiol, 333 Cedar St, New Haven, CT 06520 USA. EM frank.slack@yale.edu; joanne.weidhaas@yale.edu RI Paranjape, Trupti/E-4338-2012; OI Weidhaas, Joanne/0000-0002-5096-3281; Slack, Frank/0000-0001-8263-0409 FU Connecticut Department of Public Health; Shannon Foundation; Flight Attendant Medical Research Institute [R01 CA122676, U01 CA097356, CA074386, CA090578, CA092824, ES00002] FX Grant support: Connecticut Department of Public Health (FJ. Slack and J.B. Weidhaas), Shannon Foundation funds (J.B. Weidhaas), grant R01 CA122676 (Y. Zhu), grant U01 CA097356 (S. Belinsky), grants CA074386, CA090578, CA092824, and ES00002 (D. Christiani), and a grant from the Flight Attendant Medical Research Institute (R. Zhai). NR 36 TC 366 Z9 401 U1 3 U2 30 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 OCT 15 PY 2008 VL 68 IS 20 BP 8535 EP 8540 DI 10.1158/0008-5472.CAN-08-2129 PG 6 WC Oncology SC Oncology GA 364GE UT WOS:000260323400040 PM 18922928 ER PT J AU Chen, YM Chen, PL Chen, CF Jiang, XZ Riley, DJ AF Chen, Yumay Chen, Phang-Lang Chen, Chi-Fen Jiang, Xianzhi Riley, Daniel J. TI Never-in-mitosis related kinase 1 functions in DNA damage response and checkpoint control SO CELL CYCLE LA English DT Article DE checkpoint control; radiation; S-phase; mitosis; chromosome breaks ID POLYCYSTIC KIDNEY-DISEASE; NIMA-RELATED KINASES; PROTEIN-KINASE; ASPERGILLUS-NIDULANS; FAMILY KINASE; CHROMATIN CONDENSATION; ATAXIA-TELANGIECTASIA; MITOTIC PROGRESSION; MURINE MODELS; NEK2 KINASE AB Nek1, the first mammalian ortholog of the fungal protein kinase never in mitosis A, is involved early in the DNA damage sensing/repair pathway after ionizing radiation. Here we extend this finding by showing that Nek1 localizes to nuclear foci of DNA damage in response to many different types of damage in addition to IR. Untransformed cells established from kat2J/Nek1(-/-) mice fail to arrest properly at G(1)/S and M-phase checkpoints in response to DNA damage. G(1)-S-phase checkpoint control can be rescued by ectopically overexpressing wild-type Nek1. In Nek1(-/-) murine cells and in human cells with Nek1 expression silenced by siRNA, the checkpoint kinases Chk1 and Chk2 fail to be activated properly in response to ionizing or UV radiation. In cells without functional Nek1, DNA is not repaired properly, double-stranded DNA breaks persist long after low dose IR, and excessive numbers of chromosome breaks are observed. These data show that Nek1 is important for efficient DNA damage checkpoint control and for proper DNA damage repair. C1 [Chen, Yumay; Riley, Daniel J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. [Chen, Phang-Lang; Chen, Chi-Fen; Jiang, Xianzhi] Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92717 USA. [Riley, Daniel J.] S Texas Vet Hlth Care Syst, Renal Res Div, Audie L Murphy Div, San Antonio, TX USA. RP Chen, YM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, MC 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM cheny@uthscsa.edu RI Jiang, Xianzhi/A-5427-2013 OI Jiang, Xianzhi/0000-0002-4645-154X FU PKD foundation; American Society of Nephrology; National Kidney Foundation; NIH [R01-DK067339, P50-DK061597, R01-DK61626]; George M. O'Brien Kidney Research Center; Veterans Administration Renal Research FX This work was supported by grants from the PKD foundation, the American Society of Nephrology, the National Kidney Foundation, and the NIH (R01-DK067339) to Y. C.; a George M. O'Brien Kidney Research Center grant from the NIH to Y. C. (P50-DK061597), Hanna E. Abboud, Program Director); and a grant from the NIH to D. J. R. (R01-DK61626). We thank Huai-Chin Chiang and Sergio Garcia for technical support, and a Veterans Administration Renal Research Excellence Award to the South Texas Veterans Health Care System, Audie L. Murphy Division, for help with core services, equipment, and institutional NR 42 TC 34 Z9 34 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD OCT 15 PY 2008 VL 7 IS 20 BP 3194 EP 3201 DI 10.4161/cc.7.20.6815 PG 8 WC Cell Biology SC Cell Biology GA 363JI UT WOS:000260263200015 PM 18843199 ER PT J AU Coleman, RE Guise, TA Lipton, A Roodman, GD Berenson, JR Body, JJ Boyce, BF Calvi, LM Hadji, P McCloskey, EV Saad, F Smith, MR Suva, LJ Taichman, RS Vessella, RL Weilbaecher, KN AF Coleman, Robert E. Guise, Theresa A. Lipton, Allan Roodman, G. David Berenson, James R. Body, Jean-Jacques Boyce, Brendan F. Calvi, Laura M. Hadji, Peyman McCloskey, Eugene V. Saad, Fred Smith, Matthew R. Suva, Larry J. Taichman, Russell S. Vessella, Robert L. Weilbaecher, Katherine N. TI Advancing Treatment for Metastatic Bone Cancer: Consensus Recommendations from the Second Cambridge Conference SO CLINICAL CANCER RESEARCH LA English DT Review ID KAPPA-B LIGAND; BREAST-CANCER; PROSTATE-CANCER; ZOLEDRONIC ACID; SKELETAL COMPLICATIONS; RECEPTOR ACTIVATOR; MULTIPLE-MYELOMA; TUMOR BURDEN; SOLID TUMORS; LUNG-CANCER AB Purpose: Summarize current knowledge, critical gaps in knowledge, and recommendations to advance the field of metastatic bone cancer. Experimental Design: A multidisciplinary consensus conference was convened to review recent progress in basic and clinical research, assess critical gaps in current knowledge, and prioritize recommendations to advance research in the next 5 years. The program addressed three principal topics: biology of metastasis, preserving normal bone health, and optimizing bone-targeted therapies. Results: A variety of specific recommendations were identified as important to advance research and clinical care over the next 5 years. Conclusions: Priorities for research in bone biology include characterizing components of the stem cell niche in bone, developing oncogenic immunocompetent animal models of bone metastasis, and investigating the unique contribution of the bone microenvironment to tumor growth and dormancy. Priorities for research in preserving normal bone health include developing methods to measure and characterize disseminating tumor cells, assessing outcomes from the major prevention trials currently in progress, and improving methodologies to assess risks and benefits of treatment. Priorities for optimizing bone-targeted therapies include advancing studies of serum proteomics and genomics to reliably identify patients who will develop bone metastases, enhancing imaging for early detection of bone metastases and early response evaluation, and developing new tests to evaluate response to bone-directed treatments. C1 [Coleman, Robert E.] Univ Sheffield, Canc Res Ctr, Weston Pk Hosp, Acad Unit Clin Oncol, Sheffield S10 2SJ, S Yorkshire, England. [McCloskey, Eugene V.] Univ Sheffield, Metab Bone Ctr, Sheffield S10 2SJ, S Yorkshire, England. [Guise, Theresa A.] Univ Virginia, Dept Internal Med, Div Endocrinol, Charlottesville, VA USA. [Lipton, Allan] Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Med & Oncol, Hershey, PA 17033 USA. [Roodman, G. David] Vet Adm Pittsburgh Healthcare Syst, Dept Med, Pittsburgh, PA USA. [Berenson, James R.] Inst Myeloma & Bone Canc Res, West Hollywood, CA USA. [Body, Jean-Jacques] Univ Libre Bruxelles, CHU Brugmann, Brussels, Belgium. [Boyce, Brendan F.; Calvi, Laura M.] Univ Rochester, Sch Med & Dent, Div Endocrinol Metab, New York, NY USA. [Hadji, Peyman] Univ Hosp Giessen & Marburg GmbH, Dept Endocrinol, Marburg, Germany. [Saad, Fred] Univ Montreal, Hop Notre Dame, Ctr Hosp, Dept Urol Oncol, Montreal, PQ, Canada. [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Dept Genitourinary Med Oncol, Boston, MA USA. [Suva, Larry J.] Univ Arkansas Med Sci, Ctr Orthopaed Res, Little Rock, AR 72205 USA. [Taichman, Russell S.] Univ Michigan, Sch Dent, Dept Periodont & Oral Med, Ann Arbor, MI 48109 USA. [Vessella, Robert L.] Univ Washington, Seattle, WA 98195 USA. [Weilbaecher, Katherine N.] Washington Univ, Sch Med, Div Mol Oncol, St Louis, MO USA. RP Coleman, RE (reprint author), Univ Sheffield, Canc Res Ctr, Weston Pk Hosp, Acad Unit Clin Oncol, Whitham Rd, Sheffield S10 2SJ, S Yorkshire, England. EM r.e.coleman@sheffield.ac.uk OI Taichman, Russell S./0000-0002-7890-0020; Calvi, Laura Maria/0000-0001-6969-239X FU Novartis Pharmaceuticals; Amgen FX The consensus conference was supported by educational grants provided by Novartis Pharmaceuticals, Amgen, Inc., and Merck & Co. Editorial assistance was provided by InforMEDical Communications, Inc., Carlisle, MA. NR 50 TC 35 Z9 36 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 15 PY 2008 VL 14 IS 20 BP 6387 EP 6395 DI 10.1158/1078-0432.CCR-08-1572 PG 9 WC Oncology SC Oncology GA 364TZ UT WOS:000260359600006 PM 18927277 ER PT J AU Sabo, E Meitner, PA Tavares, R Corless, CL Lauwers, GY Moss, SF Resnick, MB AF Sabo, Edmond Meitner, Patricia A. Tavares, Rosemarie Corless, Christopher L. Lauwers, Gregory Y. Moss, Steven F. Resnick, Murray B. TI Expression Analysis of Barrett's Esophagus - Associated High-Grade Dysplasia in Laser Capture Microdissected Archival Tissue SO CLINICAL CANCER RESEARCH LA English DT Article ID GELATINASE-ASSOCIATED LIPOCALIN; SQUAMOUS-CELL CARCINOMA; BREAST-CANCER PATIENTS; GENE-EXPRESSION; EPIDERMAL DIFFERENTIATION; NEOPLASTIC PROGRESSION; TOPOISOMERASE-I; GASTRIC-CANCER; UP-REGULATION; ADENOCARCINOMA AB Purpose: Identifying genes differentially expressed in nonclysplastic BE (NDBE) from those expressed in high-grade clysplasia (HGD) should be of value in improving our understanding of this transition and may yield new diagnostic and/or prognostic markers. The aim of this study was to determine the differential transcriptome of HGD compared with NDBE through gene microarray analysis of epithelial cells microdissected from archival tissue specimens. Experimental Design: Laser capture microdissection was used to isolate epithelial cells from adjacent inflammatory and stromal cells. Epithelial mRNA was extracted from areas of NDBE and HGD in matched biopsies from 11 patients. mRNA was reverse transcribed and applied on Affymetrix cDNA microarray chips customized for formalin-exposed tissue. For a subset of these genes, differential gene expression was confirmed by real-time PCR and immunohistochemistry. Results: There were 131 genes overexpressed by at least 2.5-fold in HGD versus NDBE and 16 genes that were underexpressed by at least 2.5-fold. Among the overexpressed genes are several previously shown to be increased in the neoplastic progression of BE, as well as novel genes such as lipocalin-2, S100A9, matrix metallopeptidase 12, secernin 1, and topoisomerase II alpha. Genes decreased in dysplastic epithelium include MUC5AC, trefoil factor 1 (TFF1), meprin A, and CD13. Real-time PCR validated the changes in expression in 24 of 28 selected genes. Immunohistochemistry confirmed increased protein expression for topoisomerase II alpha, S100A9, and lipocalin-2 and decreased expression of TFF1 across the spectrum of BE-associated clysplasia from NDBE through adenocarcinoma. Conclusions: This is the first study to identify epithelial genes differentially expressed in HGD versus NDBE in matched patient samples. The genes identified include several previously implicated in the pathogenesis of BE-associated dysplasia and new candidates for further investigation. C1 [Sabo, Edmond; Meitner, Patricia A.; Tavares, Rosemarie; Resnick, Murray B.] Brown Univ, Rhode Isl Hosp, Dept Pathol, Providence, RI 02903 USA. [Moss, Steven F.] Brown Univ, Rhode Isl Hosp, Dept Med, Providence, RI 02903 USA. [Corless, Christopher L.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Resnick, MB (reprint author), Brown Univ, Rhode Isl Hosp, Dept Pathol, APC12,593 Eddy St, Providence, RI 02903 USA. EM mresnick@lifespan.org FU NIH [P20 RR17695] FX Molecular Pathology Core of the COBRE Center for Cancer Research Development and NIH grant P20 RR17695, awarded by the National Center for Research Resources, Institutional Development Award Program. NR 54 TC 25 Z9 26 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 OCT 15 PY 2008 VL 14 IS 20 BP 6440 EP 6448 DI 10.1158/1078-0432.CCR-08-0302 PG 9 WC Oncology SC Oncology GA 364TZ UT WOS:000260359600012 PM 18927283 ER PT J AU Girnun, GD Chen, L Silvaggi, J Drapkin, R Chirieac, LR Padera, RF Upadhyay, R Vafai, SB Weissleder, R Mahmood, U Naseri, E Buckley, S Li, D Force, J McNamara, K Demetri, G Spiegelman, BM Wong, KK AF Girnun, Geoffrey D. Chen, Liang Silvaggi, Jessica Drapkin, Ronny Chirieac, Lucian R. Padera, Robert F. Upadhyay, Rabi Vafai, Scott B. Weissleder, Ralph Mahmood, Umar Naseri, Elnaz Buckley, Stephanie Li, Danan Force, Jeremy McNamara, Kate Demetri, George Spiegelman, Bruce M. Wong, Kwok-Kin TI Regression of Drug-Resistant Lung Cancer by the Combination of Rosiglitazone and Carboplatin SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-RECEPTOR; GAMMA LIGAND TROGLITAZONE; HUMAN BREAST-CANCER; PPAR-GAMMA; K-RAS; PHASE-II; SOLID TUMORS; COLON-CANCER; MUTATIONS; EGFR AB Purpose: Current therapy for lung cancer involves multimodality therapies. However, many patients are either refractory to therapy or develop drug resistance. KRAS and epidermal growth factor receptor (EGFR) mutations represent some of the most common mutations in lung cancer, and many studies have shown the importance of these mutations in both carcinogenesis and chemoresistance. Genetically engineered murine models of mutant EGFR and KRAS have been developed that more accurately recapitulate human lung cancer, Recently, using cell-based experiments, we showed that platinum-based drugs and the anticliabetic drug rosiglitazone (PPAR gamma ligand) interact synergistically to reduce cancer cell and tumor growth. Here, we directly determined the efficacy of the PPAR gamma/carboplatin combination in these more relevant models of drug resistant non-small cell lung cancer. Experimental Design: Tumorigenesis was induced by activation of either mutant KRAS or EGFR. Mice then received either rosiglitazone or carboplatin monotherapy, or a combination of both drugs. Change in tumor burden, pathology, and evidence of apoptosis and cell growth were assessed. Results: Tumor burden remained unchanged or increased in the mice after monotherapy with either rosiglitazone or carboplatin. In striking contrast, we observed significant tumor shrinkage in mice treated with these drugs in combination. Immunohistochemical analyses showed that this synergy was mediated via both increased apoptosis and decreased proliferation. Importantly, this synergy between carboplatin and rosiglitazone did not increase systemic toxicity. Conclusions: These data show that the PPAR gamma ligand/carboplatin combination is a new therapy worthy of clinical investigation in lung cancers, including those cancers that show primary resistance to platinum therapy or acquired resistance to targeted therapy. C1 [Girnun, Geoffrey D.; Buckley, Stephanie] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. [Girnun, Geoffrey D.; Silvaggi, Jessica; Vafai, Scott B.; Naseri, Elnaz; Spiegelman, Bruce M.] Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02115 USA. [Upadhyay, Rabi; Weissleder, Ralph; Mahmood, Umar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. [Chen, Liang; Drapkin, Ronny; Li, Danan; Force, Jeremy; McNamara, Kate; Demetri, George; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chen, Liang; Li, Danan; Force, Jeremy; McNamara, Kate; Demetri, George] Dana Farber Harvard Ctr Canc, Ludwig Ctr, Boston, MA USA. [Drapkin, Ronny; Chirieac, Lucian R.; Padera, Robert F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Demetri, George; Wong, Kwok-Kin] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Girnun, GD (reprint author), Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Off Bressler Res Bldg 10-039,Lab Bressler Res Bld, Baltimore, MD 21201 USA. EM ggirnun@som.umaryland.edu; kwong1@partners.org RI Drapkin, Ronny/E-9944-2016; OI Drapkin, Ronny/0000-0002-6912-6977; wong, kwok kin/0000-0001-6323-235X FU NIH [K08 AG024004, R01 CA122794, R01 AG2400401, K01 DK064685, R37DK31405]; Sidney Kimmel Foundation; Joan Scarangello Foundation; Cecily and Robert Harris Foundation; University of Maryland/Greenebaum Cancer Center CRF FX NIH grant K08 AG024004, R01 CA122794, R01 AG2400401, the Sidney Kimmel Foundation for Cancer Research, the Joan Scarangello Foundation to Conquer Lung Cancer, the Cecily and Robert Harris Foundation, and the Flight Attendant Medical Research Institute (K.K. Wong); NIH grant K01 DK064685, and the University of Maryland/Greenebaum Cancer Center CRF (G,D. Girnun); NIH MERIT award (B.M. Spiegelman); and R37DK31405 (J. Silvaggi). NR 52 TC 48 Z9 48 U1 1 U2 11 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 OCT 15 PY 2008 VL 14 IS 20 BP 6478 EP 6486 DI 10.1158/1078-0432.CCR-08-1128 PG 9 WC Oncology SC Oncology GA 364TZ UT WOS:000260359600016 PM 18927287 ER PT J AU Kondo, E Maecker, B Weihrauch, MR Wickenhauser, C Zeng, WY Nadler, LM Schultze, JL von Bergwelt-Baildon, MS AF Kondo, Eisei Maecker, Britta Weihrauch, Martin R. Wickenhauser, Claudia Zeng, WanYong Nadler, Lee M. Schultze, Joachim L. von Bergwelt-Baildon, Michael S. TI Cyclin D1-Specific Cytotoxic T Lymphocytes Are Present in the Repertoire of Cancer Patients: Implications for Cancer Immunotherapy SO CLINICAL CANCER RESEARCH LA English DT Article ID CD40-ACTIVATED B-CELLS; INDEPENDENT BINDING; EPITHELIAL-CELLS; IMMUNE-RESPONSE; SELF-TOLERANCE; TUMOR-ANTIGENS; PROTEIN; IDENTIFICATION; EXPRESSION; SELECTION AB Purpose: Cyclin D1, a key cell cycle regulator, is overexpressed in multiple types of cancer. Such tumor-associated genes may be useful targets for cancer immunotherapy. Nevertheless, it had previously been suggested that efficient T cells recognizing cyclin D1 derived epitopes are absent from the repertoire because of thymic deletion. We attempted to induce autologous CTL from healthy donors and patients with cyclin D1-overexpressing tumors using a highly efficient T-cell expansion system based on CD40-activated B cells as antigen-presenting cells. Experimental Design: Cyclin D1-derived, HLA-A*0201-restricted epitopes were predicted by multiple computer algorithms, screened in HLA-A2-binding assays, and used for T-cell stimulation. The generated CTL lines and clones were analyzed by IFN-gamma enzyme-linked immunosorbent spot assay or cytolysis assay. Results: After screening, at least two naturally processed and presented HLA-A*0201 - binding cyclin D1 epitopes were identified. CTL specific for these epitopes could be successfully generated from HLA-A2(+) donors. T cells efficiently recognized target cells pulsed with the cognate peptide and cyclin D1-expressing tumor cell lines in an HLA-A*0201-restricted manner. More importantly, HLA-A*0201 - matched, primary cyclin D1(+) tumor cells were efficiently recognized by cyclin D1-specific CTL. These CTL could be generated from patients with mantle cell lymphoma and cyclin D1(+) colon cancer. Conclusions: These results underscore that cyclin D1 needs to be considered as a target for broad-based antitumor immunotherapy. C1 [Kondo, Eisei; Weihrauch, Martin R.; von Bergwelt-Baildon, Michael S.] Univ Hosp Cologne, Dept Internal Med 1, D-50924 Cologne, Germany. [Kondo, Eisei; Weihrauch, Martin R.; von Bergwelt-Baildon, Michael S.] Univ Hosp Cologne, Max Eder Nachwuchsgrp Deutschen Krebshilfe, D-50924 Cologne, Germany. [Wickenhauser, Claudia] Univ Hosp Cologne, Inst Pathol, D-50924 Cologne, Germany. [Maecker, Britta] Hannover Med Sch, Dept Pediat Hematol Oncol, D-3000 Hannover, Germany. [Zeng, WanYong; Nadler, Lee M.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. [Nadler, Lee M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Nadler, Lee M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Schultze, Joachim L.] Univ Bonn, Lab Genom & Immunoregulat, D-5300 Bonn, Germany. RP von Bergwelt-Baildon, MS (reprint author), Univ Hosp Cologne, Max Eder Nachwuchsgrp, Joseph Stelzmann Str 9,Haus 16, D-50924 Cologne, Germany. EM michael.bergwelt@uk-koeln.de RI Kondo, Eisei/F-2791-2010; Schultze, Joachim/D-7794-2011 OI Kondo, Eisei/0000-0003-0995-9405; Schultze, Joachim/0000-0003-2812-9853 FU Deutsche Krebshilfe; Alexander von Humboldt Stiftung; Kanae Foundation; Deutsche Forschungsgemeinschaft; Multiple Myeloma Research Foundation; NIH [P01-CA-66996, P01-CA-78378]; Leukemia and Lymphoma Society FX The Mildred Scheel Scholarship and Max-Eder Young Investigator Award from Deutsche Krebshilfe (M.S. von Bergwelt-Baildon), the Alexander von Humboldt Stiftung and Kanae Foundation for Life and Socio-Medical Science (E Kondo), the Deutsche Forschungsgemeinschaft and Multiple Myeloma Research Foundation (B. Maecker), NIH grants P01-CA-66996 and P01-CA-78378 (L.M. Nadler), and a Sofja Kovalevskaja Award by the Alexander von Humboldt Foundation and a Translational Research Award by the Leukemia and Lymphoma Society (J.L. Schultze). NR 40 TC 12 Z9 12 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 OCT 15 PY 2008 VL 14 IS 20 BP 6574 EP 6579 DI 10.1158/1078-0432.CCR-08-0825 PG 6 WC Oncology SC Oncology GA 364TZ UT WOS:000260359600027 PM 18927298 ER PT J AU Mudumana, SP Hentschel, D Liu, Y Vasilyev, A Drummond, IA AF Mudumana, Sudha P. Hentschel, Dirk Liu, Yan Vasilyev, Aleksandr Drummond, Iain A. TI odd skipped related1 reveals a novel role for endoderm in regulating kidney versus vascular cell fate SO DEVELOPMENT LA English DT Article DE odd-skipped related; endoderm; pronephros; vasculature; glomerulus; kidney development; zebrafish ID ZEBRAFISH PRONEPHROS; POSTERIOR MESODERM; XENOPUS-LAEVIS; EXPRESSION ANALYSIS; ENDOTHELIAL-CELLS; GENE; DIFFERENTIATION; BMP; HEART; VASCULOGENESIS AB The kidney and vasculature are intimately linked both functionally and during development, when nephric and blood/vascular progenitor cells occupy adjacent bands of mesoderm in zebrafish and frog embryos. Developmental mechanisms that underlie the differentiation of kidney versus blood/vascular lineages remain unknown. The odd skipped related1 (osr1) gene encodes a zinc-finger transcription factor that is expressed in the germ ring mesendoderm and subsequently in the endoderm and intermediate mesoderm, prior to the expression of definitive kidney or blood/vascular markers. Knockdown of osr1 in zebrafish embryos resulted in a complete, segment-specific loss of anterior kidney progenitors and a compensatory increase in the number of angioblast cells in the same trunk region. Histology revealed a subsequent absence of kidney tubules, an enlarged cardinal vein and expansion of the posterior venous plexus. Altered kidney versus vascular development correlated with expanded endoderm development in osr1 knockdowns. Combined osr1 loss of function and blockade of endoderm development by knockdown of sox32/casanova rescued anterior kidney development. The results indicate that osr1 activity is required to limit endoderm differentiation from mesendoderm; in the absence of osr1, excess endoderm alters mesoderm differentiation, shifting the balance from kidney towards vascular development. C1 [Mudumana, Sudha P.; Liu, Yan; Vasilyev, Aleksandr; Drummond, Iain A.] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA 02129 USA. [Hentschel, Dirk] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. RP Drummond, IA (reprint author), Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA 02129 USA. EM idrummon@receptor.mgh.harvard.edu FU National Institute of Health [DK071041]; American Heart Association [0625923T] FX We thank personnel in the Fish facility at MGH for help with fish husbandry, Dr Alan Davidson for the swirl mutant and for comments on this work, Dr Jing Wei Xiong for bonnie and clyde mutants and blood/vascular lineage markers, Randy Peterson and Chetana Sachidanandan for endoderm markers, Sasha Petrova for editing this manuscript, and Dr Tom Schultheiss for critical review of the data. This work was funded by a National Institute of Health grant (DK071041) to I.A.D. and by a postdoctoral fellowship from American Heart Association (0625923T) to S. P. M. NR 79 TC 31 Z9 32 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 OCT 15 PY 2008 VL 135 IS 20 BP 3355 EP 3367 DI 10.1242/dev.022830 PG 13 WC Developmental Biology SC Developmental Biology GA 353LH UT WOS:000259568600005 PM 18787069 ER PT J AU Wang, LB Sewell, WF Kim, SD Shin, JT MacRae, CA Zon, LI Seidman, JG Seidman, CE AF Wang, Libin Sewell, William F. Kim, Sang D. Shin, Jordan T. MacRae, Calum A. Zon, Leonard I. Seidman, J. G. Seidman, Christine E. TI Eya4 regulation of Na(+)/K(+)-ATPase is required for sensory system development in zebrafish SO DEVELOPMENT LA English DT Article DE eya4; Na(+)/K(+)-ATPase; hair cells; myocardium; neuromast; otic vesicle ID SENSORINEURAL HEARING-LOSS; BETA-SUBUNIT GENES; INNER-EAR; EYES ABSENT; ALPHA-SUBUNIT; DILATED CARDIOMYOPATHY; TRANSCRIPTION FACTORS; LATERAL-LINE; K-ATPASE; NA,K-ATPASE AB To investigate the mechanisms by which mutations in the human transcriptional co-activator EYA4 gene cause sensorineural hearing loss that can occur in association with dilated cardiomyopathy, we studied eya4 expression during zebrafish development and characterized eya4 deficiency. eya4 morphant fish embryos had reduced numbers of hair cells in the otic vesicle and lateral line neuromasts with impaired sensory responses. Analyses of candidate genes that are known to be expressed in a temporal and spatial pattern comparable to eya4 focused our analyses on atp1b2b, which encodes the beta 2b subunit of the zebrafish Na(+)/K(+)-ATPase. We demonstrate atp1b2b levels are reduced in eya4 morphant fish and that morpholino oligonucleotides targeting the atp1b2b gene recapitulated the eya4 deficiency phenotypes, including heart failure, decreased sensory hair cell numbers in the otic vesicle and neuromasts, and abnormal sensory responses. Furthermore, atp1b2b overexpression rescued these phenotypes in eya4 morphant fish. We conclude that eya4 regulation of Na(+)/K(+)-ATPase is crucial for the development of mechanosensory cells and the maintenance of cardiac function in zebrafish. C1 [Wang, Libin; Kim, Sang D.; Seidman, J. G.; Seidman, Christine E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Wang, Libin; Zon, Leonard I.; Seidman, J. G.; Seidman, Christine E.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Sewell, William F.] Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. [Sewell, William F.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. [Sewell, William F.] MEEI, Boston, MA 02114 USA. [Shin, Jordan T.; MacRae, Calum A.] Massachusetts Gen Hosp, Dev Biol Lab, Boston, MA 02129 USA. [Shin, Jordan T.; MacRae, Calum A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA. [Zon, Leonard I.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Zon, Leonard I.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Zon, Leonard I.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Seidman, CE (reprint author), Harvard Univ, Sch Med, Dept Genet, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM cseidman@genetics.med.harvard.edu FU Howard Hughes Medical Institute; National Institutes of Health FX We greatly appreciate the scientific comments from David A. Conner and his critical reading of the manuscript. We are grateful to Jost Schonberger for his valuable discussions. We thank Jose Rivera-Feliciano, Jenna Galloway, Sarah Keller, Haobing Wang, Yariv Houvras, Bruce Barut and Susanne Bartlett for their technical assistance. This work was supported by grants from the Howard Hughes Medical Institute (C.E.S.) and the National Institutes of Health (J.G.S. and C.E.S.). NR 46 TC 23 Z9 25 U1 0 U2 3 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 OCT 15 PY 2008 VL 135 IS 20 BP 3425 EP 3434 DI 10.1242/dev.012237 PG 10 WC Developmental Biology SC Developmental Biology GA 353LH UT WOS:000259568600011 PM 18799547 ER PT J AU Khatri, R Schipani, E AF Khatri, Richa Schipani, Ernestina TI About the importance of being desulfated SO GENES & DEVELOPMENT LA English DT Article DE Proteoglycan; desulfation; FGF; chondrocytes ID MULTIPLE SULFATASE DEFICIENCY; ENDOPLASMIC-RETICULUM STRESS; FIBROBLAST-GROWTH-FACTOR; MOLECULAR-MECHANISMS; BONE-DEVELOPMENT; GENETIC-BASIS; AUTOPHAGY; HYPOXIA; BNIP3; CELLS AB Sulfated proteoglycans have important structural and signaling functions in the growth plate. In the October 1, 2008, issue of Genes & Development, Settembre and colleagues (pp. 2645 - 2650) report that lack of SUMF1, a crucial enzyme in the activation of sulfatases, causes a severe chondrodysplasia by augmenting fibroblast growth factor signaling and by hampering the autophagic process, which the investigators show is constitutively on in chondrocytes. The findings highlight the essential role of desulfation in cartilage biology and organogenesis. C1 [Khatri, Richa; Schipani, Ernestina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. RP Schipani, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. EM schipani@helix.mgh.harvard.edu FU NIH [RO1 AR048191-06] FX This work was supported by NIH Grant RO1 AR048191-06 to E. S. NR 37 TC 5 Z9 6 U1 0 U2 0 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 OCT 15 PY 2008 VL 22 IS 20 BP 2750 EP 2754 DI 10.1101/gad.1735508 PG 5 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 360QT UT WOS:000260073200003 PM 18923073 ER PT J AU de Bakker, PIW Ferreira, MAR Jia, XM Neale, BM Raychaudhuri, S Voight, BF AF de Bakker, Paul I. W. Ferreira, Manuel A. R. Jia, Xiaoming Neale, Benjamin M. Raychaudhuri, Soumya Voight, Benjamin F. TI Practical aspects of imputation-driven meta-analysis of genome-wide association studies SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENETIC-ASSOCIATION; SUSCEPTIBILITY LOCI; COMMON VARIANTS; LARGE-SCALE; POPULATION; STRATIFICATION; POWER; REPLICATION; COVERAGE; DISEASE AB Motivated by the overwhelming success of genome-wide association studies, droves of researchers are working vigorously to exchange and to combine genetic data to expediently discover genetic risk factors for common human traits. The primary tools that fuel these new efforts are imputation, allowing researchers who have collected data on a diversity of genotype platforms to share data in a uniformly exchangeable format, and meta-analysis for pooling statistical support for a genotype-phenotype association. As many groups are forming collaborations to engage in these efforts, this review collects a series of guidelines, practical detail and learned experiences from a variety of individuals who have contributed to the subject. C1 [de Bakker, Paul I. W.] Harvard Univ, Sch Med, Partners Healthcare Syst Ctr Genet & Genom, Div Genet,Dept Med,Brigham & Womens Hosp, Boston, MA 02115 USA. [de Bakker, Paul I. W.; Ferreira, Manuel A. R.; Neale, Benjamin M.; Raychaudhuri, Soumya; Voight, Benjamin F.] Harvard & MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Ferreira, Manuel A. R.; Neale, Benjamin M.; Raychaudhuri, Soumya; Voight, Benjamin F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Jia, Xiaoming] Harvard Mit Div Hlth Sci & Technol, Boston, MA 02115 USA. [Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. RP de Bakker, PIW (reprint author), Brigham & Womens Hosp, New Res Bldg,Suite 168,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM pdebakker@rics.bwh.harvard.edu RI Voight, Benjamin/F-1775-2011; de Bakker, Paul/B-8730-2009; Ferreira, Manuel/D-3609-2013 OI de Bakker, Paul/0000-0001-7735-7858; FU NIH [AR007530-23, KAR055688A] FX S.R. is Supported by a T32 NIH training grant (AR007530-23), an NIH K08 grant (KAR055688A), and through the BWH Rheumatology Fellowship program. NR 42 TC 294 Z9 300 U1 0 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 15 PY 2008 VL 17 BP R122 EP R128 DI 10.1093/hmg/ddn288 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 398XG UT WOS:000262764200006 PM 18852200 ER PT J AU McCarroll, SA AF McCarroll, Steven A. TI Extending genome-wide association studies to copy-number variation SO HUMAN MOLECULAR GENETICS LA English DT Article ID STRUCTURAL VARIATION; LINKAGE DISEQUILIBRIUM; LARGE-SCALE; FINE-SCALE; DISEASE; SUSCEPTIBILITY; POLYMORPHISM; MULTIPLE; SCHIZOPHRENIA; CONTRIBUTE AB Appreciating the contribution of human genome copy-number variation (CNV) to clinical phenotypes is one of the compelling genetics challenges of the coming years. It is increasingly possible to pursue such investigations as an extension of genome-wide association studies (GWAS), enabled by innovations in the design and analysis of SNP (single nucleotide polymorphism) arrays and by progress in determining the genomic locations and population-genetic properties of the CNVs that segregate in the human population. Extensions of GWAS to CNV have already resulted in discoveries of both de novo and inherited CNV that are associated with risk of common disease. This review will discuss new approaches, recent findings and the analytical challenges involved in expanding GWAS to appreciate the contribution of CNV to human phenotypes. C1 [McCarroll, Steven A.] MIT & Harvard, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [McCarroll, Steven A.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [McCarroll, Steven A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [McCarroll, Steven A.] Harvard Univ, Sch Med, Boston, MA USA. RP McCarroll, SA (reprint author), MIT & Harvard, Broad Inst, Program Med & Populat Genet, 7 Cambridge Ctr,Room 6145, Cambridge, MA 02142 USA. EM smccarro@broad.mit.edu RI McCarroll, Steven/A-8433-2009 FU Lilly Life Sciences Research Fellowship FX The author Would like to acknowledge support from a Lilly Life Sciences Research Fellowship. NR 37 TC 99 Z9 106 U1 1 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 15 PY 2008 VL 17 BP R135 EP R142 DI 10.1093/hmg/ddn282 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 398XG UT WOS:000262764200008 PM 18852202 ER PT J AU Nery, FC Zeng, J Niland, BP Hewett, J Farley, J Irimia, D Li, YQ Wiche, G Sonnenberg, A Breakefield, XO AF Nery, Flavia C. Zeng, Juan Niland, Brian P. Hewett, Jeffrey Farley, Jonathan Irimia, Daniel Li, Yuqing Wiche, Gerhard Sonnenberg, Arnoud Breakefield, Xandra O. TI TorsinA binds the KASH domain of nesprins and participates in linkage between nuclear envelope and cytoskeleton SO JOURNAL OF CELL SCIENCE LA English DT Article DE Nesprin; Dystonia; Cell migration; Nuclear polarization; DYT1; Vimentin; Actin ID DYSTONIA PROTEIN TORSINA; EARLY-ONSET DYSTONIA; INTERMEDIATE-FILAMENTS; DYT1 DYSTONIA; ENDOPLASMIC-RETICULUM; IDIOPATHIC DYSTONIA; SECRETORY PATHWAY; MEMBRANE PROTEIN; CULTURED-CELLS; MOTOR DEFICITS AB A specific mutation(Delta E) in torsinA underlies most cases of the dominantly inherited movement disorder, early-onset torsion dystonia (DYT1). TorsinA, a member of the AAA+ ATPase superfamily, is located within the lumen of the nuclear envelope ( NE) and endoplasmic reticulum ( ER). We investigated an association between torsinA and nesprin-3, which spans the outer nuclear membrane (ONM) of the NE and links it to vimentin via plectin in fibroblasts. Mouse nesprin-3 alpha co-immunoprecipitated with torsinA and this involved the C-terminal region of torsinA and the KASH domain of nesprin-3 alpha. This association with human nesprin-3 appeared to be stronger for torsinA Delta E than for torsinA. TorsinA also associated with the KASH domains of nesprin-1 and -2 (SYNE1 and 2), which link to actin. In the absence of torsinA, in knockout mouse embryonic fibroblasts (MEFs), nesprin-3 alpha was localized predominantly in the ER. Enrichment of yellow fluorescent protein ( YFP)-nesprin-3 in the ER was also seen in the fibroblasts of DYT1 patients, with formation of YFP-positive globular structures enriched in torsinA, vimentin and actin. TorsinA-null MEFs had normal NE structure, but nuclear polarization and cell migration were delayed in a wound-healing assay, as compared with wild-type MEFs. These studies support a role for torsinA in dynamic interactions between the KASH domains of nesprins and their protein partners in the lumen of the NE, with torsinA influencing the localization of nesprins and associated cytoskeletal elements and affecting their role in nuclear and cell movement. C1 [Nery, Flavia C.; Zeng, Juan; Niland, Brian P.; Hewett, Jeffrey; Farley, Jonathan; Breakefield, Xandra O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Mol Neurogenet Unit, Boston, MA 02114 USA. [Nery, Flavia C.; Zeng, Juan; Niland, Brian P.; Hewett, Jeffrey; Farley, Jonathan; Breakefield, Xandra O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res,Dept Radiol, Boston, MA 02114 USA. [Nery, Flavia C.; Zeng, Juan; Niland, Brian P.; Hewett, Jeffrey; Farley, Jonathan; Breakefield, Xandra O.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. [Irimia, Daniel] Massachusetts Gen Hosp, Dept Surg & Bioengn, BioMEMS Resource Ctr, Boston, MA 02114 USA. [Li, Yuqing] Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. [Li, Yuqing] Univ Alabama, Ctr Neurodegenerat & Expt Therapeut, Birmingham, AL 35294 USA. [Wiche, Gerhard] Univ Vienna, Dept Mol Cell Biol, Max F Perutz Labs, A-1030 Vienna, Austria. [Sonnenberg, Arnoud] Netherlands Canc Inst, Dept Cell Biol, NL-1066 CX Amsterdam, Netherlands. RP Breakefield, XO (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Mol Neurogenet Unit, Boston, MA 02114 USA. EM breakefield@hms.harvard.edu RI Li, Yuqing/G-1596-2011; OI Li, Yuqing/0000-0003-1211-5529; Irimia, Daniel/0000-0001-7347-2082 FU Bachmann-Strauss Foundation; Jack Fasciana Fund for Support of Dystonia Research; NINDS [NS037409]; Fondazione Telethon FX We thank Phyllis Hanson for advice and help with electron microscopy analysis; Brian Burke for advice and for the GFP-KASH constructs for nesprin-1 and -2; John Heuser for electron microscopy; Igor Bagayev, Thomas Wurdinger, Johan Skog and Bakhos Tannous for help with image analysis; D. Cristopher Bragg for advice; Miguel Sena-Esteves for vector generation; Pradeep Bhide and Deirdre McCarthy for help with timed pregnancies and for advice; Ashira Gendelman, Lisa Pike and John Kuster for data analysis; David Corey for his generosity in allowing us to use his confocal microscope; and Suzanne McDavitt for skilled editorial assistance. Funding was provided by the Bachmann-Strauss Foundation, the Jack Fasciana Fund for Support of Dystonia Research and NINDS NS037409. NR 68 TC 98 Z9 106 U1 0 U2 9 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD OCT 15 PY 2008 VL 121 IS 20 BP 3476 EP 3486 DI 10.1242/jcs.029454 PG 11 WC Cell Biology SC Cell Biology GA 358JD UT WOS:000259912100020 PM 18827015 ER PT J AU Kaunitz, JD Yamaguchi, DT AF Kaunitz, Jonathan D. Yamaguchi, Dean T. TI TNAP, TrAP, Ecto-Purinergic Signaling, and Bone Remodeling SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE OSTEOBLAST: OSTEOCLAST; P2Y RECEPTORS; BONE REMODELING COMPARTMENT; BONE LINING CELLS; BICARBONATE; EXTRACELLULAR pH ID RESISTANT ACID-PHOSPHATASE; OSTEOBLAST-LIKE CELLS; UTERINE BICARBONATE SECRETION; STIMULATED ATPASE ACTIVITY; ALKALINE-PHOSPHATASE; CYSTIC-FIBROSIS; CARBONIC-ANHYDRASES; EPITHELIAL-CELLS; EXTRACELLULAR PH; DEFICIENT MICE AB Bone remodeling is a process of continuous resorption and formation/mineralization carried out by osteoclasts and osteoblasts, which, along with osteocytes, comprise the bone multicellular unit (BMU). A key component of the BMU is the bone remodeling compartment (BRC), isolated from the marrow by a canopy of osteoblast-like lining cells. Although much progress has been made regarding the cytokine-dependent and hormonal regulation of bone remodeling, less attention has been placed on the role of extracellular pH (pH(e)). Osteoclastic bone resorption occurs at acidic pH(e). Furthermore, osteoclasts can be regarded as epithelial-like cells, due to their polarized structure and ability to form a seal against bone, isolating the lacunar space. The major ecto-phosphatases of osteoclasts and osteoblasts, acid and alkaline phosphatases, both have ATPase activity with pH optima several units different from neutrality. Furthermore, osteoclasts and osteoblasts express plasma membrane purinergic P2 receptors that, upon activation by ATP, accelerate bone osteoclast resorption and impair osteoblast mineralization. We hypothesize that these ecto-phosphatases help regulate [ATP](e) and localized pH(e) at the sites of bone resorption and mineralization by pH-dependent ATP hydrolysis coupled with P2Y-dependent regulation of osteoclast and osteoblast function. Furthermore, osteoclast cellular HCO(3)(-), formed as a product of lacunar V-ATPase H(+) secretion, is secreted into the BRC, which could elevate BRC pH(e), in turn affecting osteoblast function. We will review the existing data addressing regulation of BRC pH(e), present a hypothesis regarding its regulation, and discuss the hypothesis in the context of the function of proteins that regulate pH(e). J. Cell. Biochem. 105: 655-662, 2008. (c) 2008 Wiley-Liss, Inc. C1 [Kaunitz, Jonathan D.] Univ Calif Los Angeles, Sch Med, Div Gastroenterol, Dept Med, Los Angeles, CA 90073 USA. [Kaunitz, Jonathan D.; Yamaguchi, Dean T.] Univ Calif Los Angeles, Sch Med, Greater Los Angeles Vet Affairs Hlth Syst, Res Serv, Los Angeles, CA 90073 USA. [Kaunitz, Jonathan D.; Yamaguchi, Dean T.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU Medical Service, West Los Angeles Veterans Affairs Medical Center FX We thank Dr. Baruch Frenkel and Dr. Yasutada Akiba for their kind, informed, and helpful advice, the Medical Service, West Los Angeles Veterans Affairs Medical Center for its support, and Jenifer Kugler for her editorial assistance. NR 75 TC 51 Z9 54 U1 0 U2 11 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 OCT 15 PY 2008 VL 105 IS 3 BP 655 EP 662 DI 10.1002/jcb.21885 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 388MH UT WOS:000262023400005 PM 18773425 ER PT J AU Zhang, XY Yu, SB Galson, DL Luo, M Fan, J Zhang, J Guan, YF Xiao, GZ AF Zhang, Xiaoyan Yu, Shibing Galson, Deborah L. Luo, Min Fan, Jie Zhang, Jian Guan, Youfei Xiao, Guozhi TI Activating Transcription Factor 4 Is Critical for Proliferation and Survival in Primary Bone Marrow Stromal Cells and Calvarial Osteoblasts SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE ATF4; OSTEOBLASTS; PROLIFERATION; APOPTOSIS; CELL CYCLE; CYCLIN D1 ID OSTEOCALCIN GENE-EXPRESSION; DNA-BINDING PROTEINS; CYCLIN D1 PROMOTER; RESPONSE ELEMENT; LEUCINE-ZIPPER; TARGETED DISRUPTION; PARATHYROID-HORMONE; ANABOLIC ACTIONS; IN-VITRO; ATF4 AB Activating transcription factor 4 (ATF4) is essential for bone formation. However, the mechanism of its actions in bone is poorly understood. The present study examined the role for ATF4 in the regulation of proliferation and survival of primary mouse bone marrow stromal cells (BMSCs) and osteoblasts. Results showed that Atf4(-/-) cells display a severe proliferative defect as measured by multiple cell proliferation assays. Cell cycle progression of Atf4(-/-) BMSCs was largely delayed with significant G1 arrest. Expression of cyclin D1 was decreased both at the mRNA and protein level. A similar proliferation defect was observed in Atf4(-/-) calvarial periosteal osteoblasts when compared with wt control. Knocking down Atf4 mRNA by small interfering RNA in MC3T3-E1 subclone 4 preosteoblasts markedly reduced expression of cyclin D1 and cell proliferation. In contrast, overexpression of ATF4 increased cyclin D1 expression as well as cell proliferation in AV4(-/-) BMSCs. In addition, apoptosis was significantly increased in Atf4(-/-) BMSCs and calvarial periosteal osteoblasts relative to wt controls. Taken together, these results for the first time demonstrate that ATF4 is a critical regulator of proliferation and survival in BMSCs and osteoblasts in vitro and in vivo. J. Cell. Biochem. 105: 885-895, 2008. (C) 2008 Wiley-Liss, Inc. C1 [Zhang, Xiaoyan; Yu, Shibing; Galson, Deborah L.; Luo, Min; Zhang, Jian; Xiao, Guozhi] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15240 USA. [Zhang, Xiaoyan; Guan, Youfei] Peking Beijing Univ Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100083, Peoples R China. [Fan, Jie] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15240 USA. RP Xiao, GZ (reprint author), VA Pittsburgh Healthcare Syst, Rm 2E-109,151-U, Pittsburgh, PA 15240 USA. EM xiaog@upmc.edu RI Perez , Claudio Alejandro/F-8310-2010; YU, SHIBING/B-7648-2012; Galson, Deborah/E-9370-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X; Galson, Deborah/0000-0002-2045-8807 FU NIH [DK072230]; Department of Defense [W81XWH-07-1-0160]; China National Natural Science Foundation [NNSF 30530340, NNSF 30725033] FX Thanks to Diane George and Dr. Scott Kulich ofthe VA Pittsburgh Healthcare System for assistance in bone histology and the Nucleofector electroporation transfection, respectively. This work was supported by an NIH Grant DK072230 and a Department of Defense Grant W81XWH-07-1-0160 (to GX) and two China National Natural Science Foundation grants NNSF 30530340 and NNSF 30725033 (to Y.G). NR 54 TC 16 Z9 17 U1 0 U2 2 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 OCT 15 PY 2008 VL 105 IS 3 BP 885 EP 895 DI 10.1002/jcb.21888 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 388MH UT WOS:000262023400028 PM 18729081 ER PT J AU Stevceva, L Yoon, V Carville, A Pacheco, B Santosuosso, M Korioth-Schmitz, B Mansfield, K Poznansky, MC AF Stevceva, Liljana Yoon, Victor Carville, Angela Pacheco, Beatriz Santosuosso, Michael Korioth-Schmitz, Birgit Mansfield, Keith Poznansky, Mark C. TI The efficacy of T cell-mediated immune responses is reduced by the envelope protein of the chimeric HIV-1/SIV-KB9 virus in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTIOUS-ANEMIA VIRUS; HUMAN MONOCLONAL-ANTIBODIES; RHESUS-MONKEYS; HIV-1 GP120; MULTIDRUG-RESISTANT; DISEASE PROGRESSION; LYMPHOCYTE RESPONSE; RAPID PROGRESSION; SYNTHETIC PEPTIDE AB Gp120 is a critical component of the envelope of HIV-1. Its role in viral entry is well described. In view of its position on the viral envelope, gp120 is a part of the retrovirus that immune cells encounter first and has the potential to influence antiretroviral immune responses. We propose that high levels of gp120 are present in tissues and may contribute to the failure of the immune system to fully control and ultimately clear the virus. Herein, we show for the first time that lymphoid tissues from acutely HIV-1/SIV (SHIV)-KB9-infected macaques contain deposits of gp120 at concentrations that are high enough to induce suppressive effects on T cells, thus negatively regulating the antiviral CTL response and contributing to virus survival and persistence. We also demonstrate that SHIV-KB9 gp120 influences functional T cell responses during SHIV infection in a manner that suppresses degranulation and cytokine secretion by CTLs. Finally, we show that regulatory T cells accumulate in lymphoid tissues during acute infection and that they respond to gp120 by producing TGF beta, a known suppressant of cytotoxic T cell activity. These findings have significant implications for our understanding of the contribution of non-entry-related functions of HIV-1 gp120 to the pathogenesis of HIV/AIDS. C1 [Stevceva, Liljana; Yoon, Victor; Santosuosso, Michael; Poznansky, Mark C.] Massachusetts Gen Hosp East, Partners AIDS Res Ctr & Infect Dis Med, Boston, MA 02129 USA. [Carville, Angela; Mansfield, Keith] Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Southborough, MA 01772 USA. [Pacheco, Beatriz] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Korioth-Schmitz, Birgit] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Stevceva, L (reprint author), Massachusetts Gen Hosp East, Partners AIDS Res Ctr & Infect Dis Med, Bldg 149,Room 5234, Boston, MA 02129 USA. EM lstevceva@hotmail.com; mpoznansky@partners.org RI Korioth-Schmitz, Birgit/M-7816-2015 OI Korioth-Schmitz, Birgit/0000-0002-5271-9223 FU Public Health Service [R01 AI49757, T32A1007387] FX M.C.P. and L.S. were supported by Public Health Service Grants R01 AI49757 and T32A1007387, respectively. NR 87 TC 11 Z9 11 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2008 VL 181 IS 8 BP 5510 EP 5521 PG 12 WC Immunology SC Immunology GA 359YX UT WOS:000260025300043 PM 18832708 ER PT J AU Gelati, M Aplin, AC Fogel, E Smith, KD Nicosia, RF AF Gelati, Maurizio Aplin, Alfred C. Fogel, Eric Smith, Kelly D. Nicosia, Roberto F. TI The angiogenic response of the aorta to injury and inflammatory cytokines requires macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TUMOR-ASSOCIATED MACROPHAGES; LIPOSOME-MEDIATED DEPLETION; STIMULATING FACTOR-I; RAT AORTA; GENE-THERAPY; CXCR2; MODEL; VIVO; NEOVASCULARIZATION AB The purpose of this study was to define early events during the angiogenic response of the aortic wall to injury. Rat aortic rings produced neovessels in collagen culture but lost this capacity over time. These quiescent rings responded to vascular endothelial growth factor but not to a mixture of macrophage-stimulatory cytokines and chemokines that was angiogenically active on fresh rings. Analysis of cytokine receptor expression revealed selective loss in quiescent rings of the proangiogenic chemokine receptor CXCR2, which was expressed predominantly in aortic macrophages. Pharmacologic inhibition of CXCR2 impaired angiogenesis from fresh rings but had no effect on vascular endothelial growth factor-induced angiogenesis from quiescent explants. Angiogenesis was also impaired in cultures of aortic rings from CXCR2-deficient mice. Reduced CXCR2 expression in quiescent rat aortic rings correlated with marked macrophage depletion. Pharmacologic ablation of macrophages from aortic explants blocked formation of neovessels in vitro and reduced aortic ring-induced angiogenesis in vivo. The angiogenic response of macrophage-depleted rings was completely restored by adding exogenous macrophages. Moreover, angiogenesis from fresh rings was promoted by macrophage CSF (CSF-1) and inhibited with anti-CSF-1 Ab. Thus, aortic angiogenic sprouting following injury is strongly influenced by conditions that modulate resident macrophage numbers and function. C1 [Gelati, Maurizio] Carlo Besta Inst, Lab Neurobiol & Neuroregenerat Med, Milan, Italy. [Aplin, Alfred C.; Smith, Kelly D.; Nicosia, Roberto F.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Fogel, Eric; Nicosia, Roberto F.] Vet Adm Puget Sound Hlth Care Syst, Div Pathol & Lab Med, Seattle, WA 98108 USA. RP Nicosia, RF (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Pathol & Lab Med S Lab 113, 1660 S Columbian Way, Seattle, WA 98108 USA. EM roberto.nicosia@va.gov RI Gelati, Maurizio/H-2110-2016 OI Gelati, Maurizio/0000-0002-4828-9849 FU National Heart, Lung, and Blood Institute [HL52585]; Department of Veterans Affairs Medical Research Service FX Supported by National Heart, Lung, and Blood Institute Grant HL52585 and by a Merit Review Grant from the Department of Veterans Affairs Medical Research Service. NR 48 TC 24 Z9 25 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2008 VL 181 IS 8 BP 5711 EP 5719 PG 9 WC Immunology SC Immunology GA 359YX UT WOS:000260025300065 PM 18832730 ER PT J AU Benn, CL Sun, T Sadri-Vakili, G McFarland, KN DiRocco, DP Yohrling, GJ Clark, TW Bouzou, B Cha, JHJ AF Benn, Caroline L. Sun, Tingting Sadri-Vakili, Ghazaleh McFarland, Karen N. DiRocco, Derek P. Yohrling, George J. Clark, Timothy W. Bouzou, Berengere Cha, Jang-Ho J. TI Huntingtin Modulates Transcription, Occupies Gene Promoters In Vivo, and Binds Directly to DNA in a Polyglutamine-Dependent Manner SO JOURNAL OF NEUROSCIENCE LA English DT Article DE transcription factor; chromatin immunoprecipitation; DNA microarrays; polyglutamine; gene expression; DNA conformation ID DISEASE TRANSGENIC MICE; INTRANUCLEAR INCLUSIONS; REPRESSES TRANSCRIPTION; MEDIATED TRANSCRIPTION; NUCLEAR-LOCALIZATION; STRIATAL CELLS; PROTEIN; EXPRESSION; COMPLEXES; INTERACTS AB Transcriptional dysregulation is a central pathogenic mechanism in Huntington's disease, a fatal neurodegenerative disorder associated with polyglutamine ( polyQ) expansion in the huntingtin (Htt) protein. In this study, we show that mutant Htt alters the normal expression of specific mRNA species at least partly by disrupting the binding activities of many transcription factors which govern the expression of the dysregulated mRNA species. Chromatin immunoprecipitation (ChIP) demonstrates Htt occupation of gene promoters in vivo in a polyQ-dependent manner, and furthermore, ChIP-on-chip and ChIP subcloning reveal that wild-type and mutant Htt exhibit differential genomic distributions. Exon 1 Htt binds DNA directly in the absence of other proteins and alters DNA conformation. PolyQ expansion increases Htt-DNA interactions, with binding to recognition elements of transcription factors whose function is altered in HD. Together, these findings suggest mutant Htt modulates gene expression through abnormal interactions with genomic DNA, altering DNA conformation and transcription factor binding. C1 [Benn, Caroline L.; Sun, Tingting; Sadri-Vakili, Ghazaleh; McFarland, Karen N.; DiRocco, Derek P.; Yohrling, George J.; Cha, Jang-Ho J.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA 02129 USA. [Clark, Timothy W.; Bouzou, Berengere] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Ctr Interdisciplinary Informat, Charlestown, MA 02129 USA. [Yohrling, George J.] Galleon Pharmaceut, Horsham, PA 19044 USA. RP Cha, JHJ (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, 114 16th St, Charlestown, MA 02129 USA. EM cha@helix.mgh.harvard.edu RI McFarland, Karen/H-1890-2011; OI Clark, Timothy/0000-0003-4060-7360 FU National Institutes of Health [NS38106, NS45242] FX This work was supported by the Huntington's Disease Society of America Coalition for the Cure Program, the Glendorn Foundation, National Institutes of Health Grants NS38106 and NS45242, and the Massachusetts General Hospital Fund for Medical Discovery (C. L. B.). Wewould like to acknowledge the expert and generous guidance of Erik Nelson and David Frank (Dana Farber Cancer Institute, Boston, MA) with ChIP subcloning. Human brain samples were generously provided by the Alzheimer's Research Disease Center at Massachusetts General Hospital. We thank Marcy E. MacDonald (Massachusetts General Hospital, Boston, MA) for generously sharing the STHdh striatal cell lines. We are grateful to Eileen M. Denovan-Wright and Geraldine Gomez (Dalhousie University, Halifax, Canada) for help with DNase footprinting assays and helpful discussions. We thank Prianka Chawla, Kelly E. Glajch, Ryan P. Overland, Arjun Vasan, and Samuel Bitoun for technical assistance. We are indebted to Weiguo Zhai and Robert Tjian for helpful discussions regarding the RAP30 and RAP74 chromatin immunoprecipitations. Finally, we especially thank Gillian P. Bates for her insightful comments, constructive discussions, and help with Southern blotting. NR 60 TC 90 Z9 92 U1 0 U2 10 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 OCT 15 PY 2008 VL 28 IS 42 BP 10720 EP 10733 DI 10.1523/JNEUROSCI.2126-08.2008 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 360MC UT WOS:000260060600026 PM 18923047 ER PT J AU Razansky, D Vinegoni, C Ntziachristos, V AF Razansky, Daniel Vinegoni, Claudio Ntziachristos, Vasilis TI Polarization-sensitive optoacoustic tomography of optically diffuse tissues SO OPTICS LETTERS LA English DT Article ID PHOTOACOUSTIC TOMOGRAPHY; IN-VIVO; MICROSCOPY; DICHROISM; LIGHT AB Polarization is indicative of material anisotropy, a property that reveals structural orientation information of molecules inside the material. Herein we investigate whether polarization can be detected optoacoustically in scattering and absorbing tissues. Using a laboratory prototype of polarization-sensitive optoacoustic tomography, we demonstrate high-resolution reconstructions of dichroism. contrast deep in optically diffusive tissue-mimicking phantoms. The technique is expected to enable highly accurate imaging of polarization contrast in tissues, far beyond the current capabilities of pure optical polarization-imaging approaches. (C) 2008 Optical Society of America C1 [Razansky, Daniel; Ntziachristos, Vasilis] Helmholtz Zentrum Munchen, Inst Biol & Med Imaging, D-85764 Neuherberg, Germany. [Razansky, Daniel; Ntziachristos, Vasilis] Tech Univ Munich, Sch Med, D-81675 Munich, Germany. [Razansky, Daniel; Ntziachristos, Vasilis] Tech Univ Munich, Sch Elect Engn, D-81675 Munich, Germany. [Razansky, Daniel; Vinegoni, Claudio; Ntziachristos, Vasilis] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Lab Bioopt & Mol Imaging, Boston, MA 02129 USA. [Razansky, Daniel; Vinegoni, Claudio; Ntziachristos, Vasilis] Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Razansky, D (reprint author), Helmholtz Zentrum Munchen, Inst Biol & Med Imaging, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany. EM daniel.razansky@helmholtz-muenchen.de OI Razansky, Daniel/0000-0001-8676-0964 FU National Institutes of Health (NIH) [R01 EB00438201] FX This study was supported in part by the National Institutes of Health (NIH) grant R01 EB00438201. NR 15 TC 0 Z9 0 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD OCT 15 PY 2008 VL 33 IS 20 BP 2308 EP 2310 DI 10.1364/OL.33.002308 PG 3 WC Optics SC Optics GA 373KP UT WOS:000260970800009 PM 18923605 ER PT J AU Oaklander, AL AF Oaklander, Anne Louise TI RSD/CRPS: The end of the beginning SO PAIN LA English DT Editorial Material ID REGIONAL-PAIN-SYNDROME; REFLEX SYMPATHETIC DYSTROPHY; SYNDROME TYPE-I; SYNDROME TYPE-1; CYTOKINES C1 [Oaklander, Anne Louise] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Oaklander, Anne Louise] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Oaklander, AL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, 275 Charles St,Warren 310 Mailbox, Boston, MA 02114 USA. EM aoaklander@partners.org FU NINDS NIH HHS [K24 NS059892, R01 NS042866, K24 NS059892-01A1, R01NS42866, K24NS059892, R01 NS042866-04] NR 17 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD OCT 15 PY 2008 VL 139 IS 2 BP 239 EP 240 DI 10.1016/j.pain.2008.08.006 PG 2 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 368UT UT WOS:000260648900001 PM 18790569 ER PT J AU Kim, S Mohapatra, G Haber, DA AF Kim, S. Mohapatra, G. Haber, D. A. TI In vitro phosphorylation of BRCA2 by the checkpoint kinase CHEK2 SO BRITISH JOURNAL OF CANCER LA English DT Article DE BRCA1 or 2 (breast cancer gene 1 or 2); CHK2 or CHEK2 (checkpoint kinase 2); IR (ionising radiation); GTG banding (G-bands after trypsin and giemsa); NLS (nuclear localisation signal) ID DNA-DAMAGE CHECKPOINT; CHK2 PROTEIN-KINASE; BREAST-CANCER; PROSTATE-CANCER; MUTATIONS; ATM; P53; SUSCEPTIBILITY; FAMILIES; PATHWAY AB Germline mutations in both BRCA2 and CHEK2 are associated with an increased risk for male breast cancer. To search for potential interactions between the products of these breast cancer susceptibility genes, we undertook systematic mapping of BRCA2 for potential phosphorylation sites by CHEK2. In vitro kinase assays and mass spectrometric analysis identified a 50 amino-acid fragment within the N-terminus of BRCA2 potentially targeted by CHEK2, containing two major phosphopeptides. Inducible overexpression of this peptide, but not a derivative with mutated phosphorylation sites, leads to increased chromosome fragmentation and suppression of cellular proliferation. These results suggest a link between CHEK2 and BRCA2 pathways, which may contribute to the spectrum of cancers associated with germline CHEK2 mutations. C1 [Kim, S.; Haber, D. A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Mohapatra, G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,CNY-7,13 St, Charlestown, MA 02129 USA. EM Haber@helix.mgh.harvard.edu FU NIH [CA84066]; NIH SPORE FX This study was supported in part by NIH CA84066 (DAH) and the NIH SPORE on breast cancer at Massachusetts General Hospital (DAH). NR 32 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD OCT 14 PY 2008 VL 99 IS 8 BP 1302 EP 1306 DI 10.1038/sj.bjc.6604644 PG 5 WC Oncology SC Oncology GA 360BB UT WOS:000260030900018 PM 18797466 ER PT J AU Wiviott, SD Braunwald, E Angiolillo, DJ Meisel, S Dalby, AJ Verheugt, FWA Goodman, SG Corbalan, R Purdy, DA Murphy, SA McCabe, CH Antman, EM AF Wiviott, Stephen D. Braunwald, Eugene Angiolillo, Dominick J. Meisel, Simha Dalby, Anthony J. Verheugt, Freek W. A. Goodman, Shaun G. Corbalan, Ramon Purdy, Drew A. Murphy, Sabina A. McCabe, Carolyn H. Antman, Elliott M. CA Triton-Timi 38 Invest TI Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38 SO CIRCULATION LA English DT Article DE angioplasty; anticoagulants; myocardial infarction; platelets; diabetes mellitus ID ACUTE CORONARY SYNDROMES; ST-SEGMENT-ELEVATION; MYOCARDIAL-INFARCTION; ARTERY-DISEASE; CARDIOVASCULAR OUTCOMES; STENT THROMBOSIS; CLOPIDOGREL; INSULIN; MORTALITY; ASPIRIN AB Background-Patients with diabetes mellitus (DM) are at high risk for recurrent cardiovascular events after acute coronary syndromes, in part because of increased platelet reactivity. The Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38) showed an overall reduction in ischemic events with more intensive antiplatelet therapy with prasugrel than with clopidogrel but with more bleeding. We compared prasugrel with clopidogrel among subjects with DM in TRITON-TIMI 38. Methods and Results-We classified 13 608 subjects on the basis of preexisting history of DM and further according to insulin use. Prespecified analyses of the primary (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and key secondary end points, including net clinical benefit (death, nonfatal myocardial infarction, nonfatal stroke, and nonfatal TIMI major bleeding) were compared by use of the log-rank test. We found that 3146 subjects had a preexisting history of DM, including 776 receiving insulin. The primary end point was reduced significantly with prasugrel among subjects without DM (9.2% versus 10.6%; hazard ratio [HR], 0.86; P=0.02) and with DM (12.2% versus 17.0%; HR, 0.70; P<0.001, P(interaction)=0.09). A benefit for prasugrel was observed among DM subjects on insulin (14.3% versus 22.2%; HR, 0.63; P=0.009) and those not on insulin (11.5% versus 15.3%; HR, 0.74; P=0.009). Myocardial infarction was reduced with prasugrel by 18% among subjects without DM (7.2% versus 8.7%; HR, 0.82; P=0.006) and by 40% among subjects with DM (8.2% versus 13.2%; HR, 0.60; P<0.001, P(interaction)=0.02). Although TIMI major hemorrhage was increased among subjects without DM on prasugrel (1.6% versus 2.4%; HR, 1.43; P=0.02), the rates were similar among subjects with DM for clopidogrel and prasugrel (2.6% versus 2.5%; HR, 1.06; P=0.81, P(interaction)=0.29). Net clinical benefit with prasugrel was greater for subjects with DM (14.6% versus 19.2%; HR, 0.74; P=0.001) than for subjects without DM (11.5% versus 12.3%; HR, 0.92; P=0.16, P(interaction)=0.05). Conclusions-Subjects with DM tended to have a greater reduction in ischemic events without an observed increase in TIMI major bleeding and therefore a greater net treatment benefit with prasugrel compared with clopidogrel. These data demonstrate that the more intensive oral antiplatelet therapy provided with prasugrel is of particular benefit to patients with DM. C1 [Wiviott, Stephen D.; Braunwald, Eugene; Murphy, Sabina A.; McCabe, Carolyn H.; Antman, Elliott M.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, Boston, MA 02115 USA. [Wiviott, Stephen D.; Braunwald, Eugene; Murphy, Sabina A.; McCabe, Carolyn H.; Antman, Elliott M.] Harvard Univ, Sch Med, Boston, MA USA. [Angiolillo, Dominick J.] Univ Florida, Coll Med, Jacksonville, FL USA. [Meisel, Simha] Hillel Yaffe Med Ctr, Hadera, Israel. [Goodman, Shaun G.] Univ Toronto, St Michaels Hosp, Toronto, ON M5B 1W8, Canada. [Goodman, Shaun G.] Canadian Heart Res Ctr, Toronto, ON, Canada. [Dalby, Anthony J.] Millpk Hosp, Johannesburg, South Africa. [Verheugt, Freek W. A.] Univ Nijmegen Hosp, Dept Cardiol, NL-6500 HB Nijmegen, Netherlands. [Corbalan, Ramon] Catholic Univ, Sch Med, Dept Cardiol, Santiago, Chile. [Purdy, Drew A.] Black Hills Cardiovasc Res Grp, Black Hills, SD USA. RP Wiviott, SD (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM swiviott@partners.org RI Verheugt, F.W.A./H-8105-2014 FU Daiichi Sankyo Co, Ltd; Eli Lilly and Co; Sanofi-Aventis; Glaxo Smith Kline; Bristol-Myers Squibb; Novartis; Portola; AstraZeneca; Schering Plough; The Medicines Co FX The TRITON-TIMI 38 trial was supported by Daiichi Sankyo Co, Ltd, and Eli Lilly and Co. Dr Wiviott, Dr Braunwald, C.H. McCabe, S.A. Murphy, and Dr Antman report receiving research grants from Daiichi Sankyo, Eli Lilly, and Sanofi-Aventis. In addition, Dr Wiviott reports receiving consulting or advisory board fees from Sanofi-Aventis and lecture fees from Eli Lilly and Daiichi Sankyo; Dr Braunwald reports receiving consulting or paid advisory board fees from Daiichi Sankyo and Sanofi-Aventis and lecture fees from Eli Lilly and Sanofi-Aventis; Dr Antman reports receiving consulting or advisory board fees from Sanofi-Aventis and lecture fees from Eli Lilly and Sanofi-Aventis. Dr Angiolillo reports research grant support from Glaxo Smith Kline and consulting, speakers bureau, or advisory board fees from Daiichi Sankyo, Eli Lilly, Bristol-Myers Squibb, Sanofi-Aventis, Novartis, and Portola. Dr Goodman reports receiving research grant support, speaker honoraria, or consulting income from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Schering Plough, and The Medicines Co. The other authors report no conflicts. NR 38 TC 384 Z9 401 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 14 PY 2008 VL 118 IS 16 BP 1626 EP 1636 DI 10.1161/CIRCULATIONAHA.108.791061 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 359KX UT WOS:000259986700005 PM 18757948 ER PT J AU Baggish, AL Boucher, CA AF Baggish, Aaron L. Boucher, Charles A. TI Radiopharmaceutical agents for myocardial perfusion imaging SO CIRCULATION LA English DT Review DE isotopes; radioisotopes; myocardial ischemia; nuclear medicine; radiopharmaceuticals ID EMISSION COMPUTED-TOMOGRAPHY; CORONARY-ARTERY-DISEASE; ATTENUATION CORRECTION; PROGNOSTIC VALUE; HUMAN BIODISTRIBUTION; CLINICAL VALIDATION; VASCULAR-SURGERY; CARDIAC RISK; CHEST PAIN; SPECT C1 [Baggish, Aaron L.; Boucher, Charles A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Boucher, CA (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. EM cboucher@partners.org NR 49 TC 22 Z9 24 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 14 PY 2008 VL 118 IS 16 BP 1668 EP 1674 DI 10.1161/CIRCULATIONAHA.108.778860 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 359KX UT WOS:000259986700010 PM 18852377 ER PT J AU Ho, PM Peterson, PN Masoudi, FA AF Ho, P. Michael Peterson, Pamela N. Masoudi, Frederick A. TI Evaluating the evidence - Is there a rigid hierarchy? SO CIRCULATION LA English DT Article DE cardiovascular diseases; epidemiology; research design ID ACUTE MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROMES; VENTRICULAR SYSTOLIC DYSFUNCTION; TO-BALLOON TIME; ESTROGEN PLUS PROGESTIN; BETA-BLOCKER THERAPY; HEART-FAILURE; CLINICAL-TRIALS; POSTMENOPAUSAL ESTROGEN; CARDIOVASCULAR-DISEASE C1 [Ho, P. Michael] Denver Vet Affairs Med Ctr, Denver, CO 80202 USA. [Ho, P. Michael; Peterson, Pamela N.; Masoudi, Frederick A.] Univ Colorado, Denver, CO 80202 USA. [Peterson, Pamela N.; Masoudi, Frederick A.] Denver Hlth Med Ctr, Denver, CO USA. RP Masoudi, FA (reprint author), MC 0960,777 Bannock St, Denver, CO 80204 USA. EM fred.masoudi@uchsc.edu FU Amgen; Oklahoma Foundation for Medical Quality; Colorado Foundation for Medical Care FX Dr Masoudi has served on advisory boards for Takeda, NA; Amgen; and United Healthcare. Dr Masoudi has also received research support from Amgen, has contracts with the Oklahoma Foundation for Medical Quality and the Colorado Foundation for Medical Care, and is an Associate Editor for Journal Watch Cardiology of the Massachusetts Medical Society. The other authors report no conflicts. NR 75 TC 57 Z9 57 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 14 PY 2008 VL 118 IS 16 BP 1675 EP 1684 DI 10.1161/CIRCULATIONAHA.107.721357 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 359KX UT WOS:000259986700011 PM 18852378 ER PT J AU Hu, P Geles, KG Paik, JH DePinho, RA Tjian, R AF Hu, Ping Geles, Kenneth G. Paik, Ji-Hye DePinho, Ronald A. Tjian, Robert TI Codependent Activators Direct Myoblast-Specific MyoD Transcription SO DEVELOPMENTAL CELL LA English DT Article ID MUSCLE PROGENITOR CELLS; SKELETAL-MUSCLE; INSULIN-RECEPTOR; SATELLITE CELLS; SMOOTH-MUSCLE; MYOGENIC DIFFERENTIATION; GENE-TRANSCRIPTION; MAMMALIAN-CELLS; FACTOR FOXO3A; PAX GENES AB Although FoxO and Pax proteins represent two important families of transcription factors in determining cell fate, they had not been functionally or physically linked together in mediating regulation of a common target gene during normal cellular transcription programs. Here, we identify MyoD, a key regulator of myogenesis, as a direct target of FoxO3 and Pax3/7 in myoblasts. Our cell-based assays and in vitro studies reveal a tight codependent partnership between FoxO3 and Pax3/7 to coordinately recruit RNA polymerase II and form a preinitiation complex (PIC) to activate MyoD transcription in myoblasts. The role of FoxO3 in regulating muscle differentiation is confirmed in vivo by observed defects in muscle regeneration caused by MyoD downregulation in FoxO3 null mice. These data establish a mutual interdependence and functional link between two families of transcription activators serving as potential signaling sensors and regulators of cell fate commitment in directing tissue specific MyoD transcription. C1 [Hu, Ping; Geles, Kenneth G.; Tjian, Robert] Univ Calif Berkeley, Howard Hughes Med Inst, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Paik, Ji-Hye; DePinho, Ronald A.] Harvard Univ, Sch Med, Inst Innovat Canc Sci, Dept Med Oncol,Dana Farber Canc Inst,Belfer Fdn, Boston, MA 02115 USA. [Paik, Ji-Hye; DePinho, Ronald A.] Harvard Univ, Sch Med, Inst Innovat Canc Sci, Dept Med,Dana Farber Canc Inst,Belfer Fdn, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Inst Innovat Canc Sci, Dept Genet,Dana Farber Canc Inst,Belfer Fdn, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Ctr Appl Canc Sci,Inst Innovat Canc Sci, Dana Farber Canc Inst,Belfer Fdn, Boston, MA 02115 USA. RP Tjian, R (reprint author), Univ Calif Berkeley, Howard Hughes Med Inst, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. EM jmlim@berkeley.edu RI Hu, Ping/G-2384-2015 FU Damon Runyon Cancer Research Foundation FX We thank M. Haggart for technical assistance, A. Fisher for assistance in large scale cell culture, D. Schichnes for help on microscope usage, and D. King and L. Kohlstaedt for help on peptide synthesis and mass spec. We thank 1. Conboy and M. Carlson for help on satellite cell isolation, M. Marr for help on in vitro transcription assays. and B. Gan for help on isolation of primary myoblasts from knockout mice. We also thank M. Deato, K. Wright, Y. Fong, W. Liu, R. Colemen, F. Herrera, B. Guglielmi, E. Olson, M.E. Buckingham, and M. Rudnicki for critical reading of the manuscript. We thank members of the Tjian laboratory for valuable suggestions and discussions. J.-H.P. is Damon Runyon Fellows supported by the Damon Runyon Cancer Research Foundation. R.T. is an investigator of the Howard Hughes Medical Institute and Director of the Li Ka-Shing Center for Biomedical and Health Sciences. NR 74 TC 70 Z9 73 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD OCT 14 PY 2008 VL 15 IS 4 BP 534 EP 546 DI 10.1016/j.devcel.2008.08.018 PG 13 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 363BP UT WOS:000260241200009 PM 18854138 ER PT J AU Villasenor, J Besse, W Benoist, C Mathis, D AF Villasenor, Jennifer Besse, Whitney Benoist, Christophe Mathis, Diane TI Ectopic expression of peripheral-tissue antigens in the thymic epithelium: Probabilistic, monoallelic, misinitiated SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AIRE; autoimmunity; gene expression; immunological tolerance; T cell tolerance ID PROMISCUOUS GENE-EXPRESSION; ALLELE-SPECIFIC EXPRESSION; CD4(+) T-CELLS; TRANSCRIPTION FACTOR; TH2 CELLS; AIRE; DIFFERENTIATION; SELF; MICE; STOCHASTICITY AB Thymic medullary epithelial cells (MECs) express a broad repertoire of peripheral-tissue antigens (PTAs), many of which depend on the transcriptional regulatory factor Aire. Although Aire is known to be critically important for shaping a self-tolerant T cell repertoire, its role in MEC maturation and function remains poorly understood. Using a highly sensitive and reproducible single-cell PCR assay, we demonstrate that individual Aire-expressing MECs transcribe a subset of PTA genes in a probabilistic fashion, with no signs of preferential coexpression of genes characteristic of particular extrathymic epithelial cell lineages. In addition, Aire-dependent PTA genes in MECs are transcribed morloallelically or biallelically in a stochastic pattern, in contrast to the usually biallelic transcription of these same genes in the relevant peripheral cells or of Aire-independent genes in MECs. Expression of PTA genes in MECs depends on transcriptional regulators and uses transcriptional start sites different from those used in peripheral cells. These findings support the "terminal differentiation" model of Aire function: as MECs mature, they transcribe more and more PTA genes, culminating in a cell population that is both capable of presenting antigens (MHCIIhi, CD80(hi)) and can draw on a large repertoire of antigens to present. C1 Harvard Univ, Sch Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. RP Mathis, D (reprint author), Joslin Diabet Ctr, Sect Immunol & Immunogenet, 1 Joslin Pl,Room 478, Boston, MA 02214 USA. EM cbdm@joslin.harvard.edu FU National Institutes of Health [R01 DK60027, T32 DK07260]; Young Chair funds; Joslin's National Institutes of Diabetes and Digestive and Kidney Diseases FX We thank Jasmine Perez for excellent technical support. This work was supported by National Institutes of Health Grant R01 DK60027 and Young Chair funds (to D.M, and C.B.), and by Joslin's National Institutes of Diabetes and Digestive and Kidney Diseases-funded Diabetes and Endocrinology Research Center core facilities. J.V. and W.B. received support from National Institutes of Health Training Grant T32 DK07260. NR 45 TC 74 Z9 74 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 OCT 14 PY 2008 VL 105 IS 41 BP 15854 EP 15859 DI 10.1073/pnas.0808069105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363BM UT WOS:000260240900040 PM 18836079 ER PT J AU Venanzi, ES Melamed, R Mathis, D Benoist, C AF Venanzi, Emily S. Melamed, Rachel Mathis, Diane Benoist, Christophe TI The variable immunological self: Genetic variation and nongenetic noise in Aire-regulated transcription SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gene expression; immunological tolerance; microarray; thymus; autoimmune regulator ID THYMIC EPITHELIAL-CELLS; CANDIDIASIS-ECTODERMAL DYSTROPHY; AUTOIMMUNE REGULATOR; INSULIN EXPRESSION; IDDM2 LOCUS; NOD MICE; TOLERANCE; ANTIGEN; PROTEIN; SUSCEPTIBILITY AB The Aire transcription factor plays an important role in immunological self-tolerance by mediating the ectopic expression of peripheral self-antigens by thymic medullary epithelial cells (MECs), and the deletion of thymocytes that recognize them. In Aire-deficient humans or mice, central tolerance is incomplete and multiorgan autoimmune disease results. We examined the variability of Aire's effects on ectopic transcription among individual mice of three different inbred strains. Aire's function was, overall, quite similar in the three backgrounds, although generally stronger in C57BL/6 than in BALB/c or NOD mice, and a minority of Aire-regulated genes did show clear differences. Gene expression profiling of wild-type MECs from single mice, or from the two thymic lobes of the same mouse, revealed significantly greater variability in Aire-controlled ectopic gene expression than in Aire-independent transcripts. This "noisy" ectopic expression did not result from parental or early developmental imprinting, but from programming occurring after the formation of the thymic anlage, resulting from epigenetic effects or from the stochastic nature of Aire activity. Together, genetic and nongenetic variability in ectopic expression of peripheral antigens in the thymus make for differences in the portion of self determinants presented for tolerance induction. This variable self may be beneficial in preventing uniform holes in the T-cell repertoire in individuals of a species, but at the cost of variable susceptibility to autoimmunity. C1 [Mathis, Diane; Benoist, Christophe] Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Mathis, D (reprint author), Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. EM cbdm@joslin.harvaid.edu OI Melamed, Rachel/0000-0003-3089-9806 FU National Institutes of Health [R01 DK60027, T32 DK07260]; Young Chair funds; Joslin Diabetes Center's NIDDK FX We thank Vincent Auyeung for the splenic Treg microarray data and Dr. Hamish Scott for the anti-Aire antibody. This work was supported by a National Institutes of Health Grant R01 DK60027, Young Chair funds (to D.M. and C.B.), Joslin Diabetes Center's NIDDK-funded DERC core facilities, and National Institutes of Health Training Grant T32 DK07260 (to E.V.). NR 30 TC 38 Z9 38 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 14 PY 2008 VL 105 IS 41 BP 15860 EP 15865 DI 10.1073/pnas.0808070105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363BM UT WOS:000260240900041 PM 18838677 ER PT J AU Koh, AS Kuo, AJ Park, SY Cheung, P Abramson, J Bua, D Carney, D Shoelson, SE Gozani, O Kingston, RE Benoist, C Mathis, D AF Koh, Andrew S. Kuo, Alex J. Park, Sang Youn Cheung, Peggie Abramson, Jakub Bua, Dennis Carney, Dylan Shoelson, Steven E. Gozani, Or Kingston, Robert E. Benoist, Christophe Mathis, Diane TI Aire employs a histone-binding module to mediate immunological tolerance, linking chromatin regulation with organ-specific autoimmunity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE T cell tolerance; plant homeodomain finger; thymus APS-1; APECED ID THYMIC EPITHELIAL-CELLS; PROMISCUOUS GENE-EXPRESSION; PHD FINGER; H3; PROTEIN; LYSINE-4; METHYLATION; DISEASE; DNA; MECHANISMS AB Aire induces ectopic expression of peripheral tissue antigens WAS) in thymic medullary epithelial cells, which promotes immunological tolerance. Beginning with a broad screen of histone peptides, we demonstrate that the mechanism by which this single factor controls the transcription of thousands of genes involves recognition of the amino-terminal tail of histone H3, but not of other histones, by one of Aire's plant homeodomain (PHD) fingers. Certain posttranslational modifications of H3 tails, notably dimethylation or trimethylation at H3K4, abrogated binding by Aire, whereas others were tolerated. Similar PHD finger-H3 tail-binding properties were recently reported for BRAF-histone deacetylase complex 80 and DNA methyltransferase 3L; sequence alignment, molecular modeling, and biochemical analyses showed these factors and Aire to have structure-function relationships in common. In addition, certain PHD1 mutations underlying the polyendocrine disorder autoimmune polyendocrinopathy-candidiases-ectodermaldystrophy compromised Aire recognition of H3. In vitro binding assays demonstrated direct physical interaction between Aire and nucleosomes, which was in part buttressed by its affinity to DNA. In vivo Aire interactions with chromosomal regions depleted of H3K4me3 were dependent on its H3 tail-binding activity, and this binding was necessary but not sufficient for the up-regulation of genes encoding PTAs. Thus, Aire's activity as a histone-binding module mediates the thymic display of PTAs that promotes self-tolerance and prevents organ-specific autoimmunity. C1 [Koh, Andrew S.; Kingston, Robert E.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Koh, Andrew S.; Kingston, Robert E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Koh, Andrew S.; Park, Sang Youn; Abramson, Jakub; Shoelson, Steven E.; Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. [Koh, Andrew S.; Park, Sang Youn; Abramson, Jakub; Shoelson, Steven E.; Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr, Boston, MA 02215 USA. [Kuo, Alex J.; Cheung, Peggie; Bua, Dennis; Carney, Dylan; Gozani, Or] Stanford Univ, Dept Biol, Stanford, CA 94305 USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM kingston@moibio.mgh.harvard.edu; cbdm@joslin.harvard.edu RI ABRAMSON, JAKUB/K-1348-2012 FU National Institutes of Health (NIH) [P30 DK36836, R01 DK60027, R01 GM48405, R01 GM079641, T32 DK07260]; Genentech; National Research Service [F32 DK774852]; Juvenile Diabetes Research Foundation FX We thank Dr. A. G. W. Matthews for critical suggestions, and the Aire group and Kingston lab for inspiration and helpful discussions. This work was supported by National Institutes of Health (NIH) Grant P30 DK36836 to the Joslin Diabetes Center's Diabetes and Endocrinology Research Center core facilities; NIH Grant R01 DK60027 and Young Chair funds to D.M. and C.B.; NIH Grant R01 GM48405 to R.E.K.; and NIH Grant R01 GM079641 and a Searle Scholar Award to O.G. A.S.K. was supported by NIH Grant T32 DK07260, A.J.K. by a precloctoral fellowship from Genentech, S.Y.P. by National Research Service Award F32 DK774852, and J.A. by a Juvenile Diabetes Research Foundation Advanced Postdoctotal Fellowship. NR 47 TC 99 Z9 104 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 14 PY 2008 VL 105 IS 41 BP 15878 EP 15883 DI 10.1073/pnas.0808470105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363BM UT WOS:000260240900044 PM 18840680 ER PT J AU Diao, HY Iwabuchi, K Li, LJ Onoe, K Van Kaer, L Kon, S Saito, Y Morimoto, J Denhardt, DT Rittling, S Uede, T AF Diao, Hongyan Iwabuchi, Kazuya Li, Lanjuan Onoe, Kazunori Van Kaer, Luc Kon, Shigeyuki Saito, Yoshinari Morimoto, Junko Denhardt, David T. Rittling, Susan Uede, Toshimitsu TI Osteopontin regulates development and function of invariant natural killer T cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE nuclear factor of activated T cells (NFAT); GATA-3; Fas ligand (FasL) ID V-ALPHA-14I NKT CELLS; A-INDUCED HEPATITIS; DENDRITIC CELLS; CONCANAVALIN-A; EXPRESSION; MICE; ACTIVATION; GATA-3; BET; CONTRIBUTES AB Invariant natural killer T (iNKT) cells belong to a subset of lymphocytes bridging innate and acquired immunity. We demonstrated that osteopontin (OPN) is involved in the activation of iNKT cells. In the present work, we examined whether OPN affects development and function of iNKT cells. We found that the number of peripheral iNKT cells was significantly reduced in OPN-deficient mice compared with wild-type mice. Although the number of thymic iNKT cells was not different between WT and OPN-deficient mice, intrathymic iNKT cell maturation was impaired in OPN-deficient mice. iNKT cell function was also significantly altered in OPN-deficient mice, as evidenced by (i) deficient down-regulation of iNKT cell receptor, (h) reduction of IL-4 production while preserving production of IFN-gamma, and (iii) reduction of Fas ligand (FasL) expression, leading to reduced Fas/FasL-dependent cytotoxicity against hepatocytes. Importantly, activation of the transcription factors NFAT2 (nuclear factor of activated T cells 2) and GATA-3 was impaired, whereas activation of T-bet was preserved in iNKT cells of OPN-deficient mice. These data collectively indicate that OPN plays a pivotal role not only in the development, but also in the function of iNKT cells. C1 [Diao, Hongyan; Li, Lanjuan] Hokkaido Univ, Inst Med Genet, Dept Matrix Med, Kita Ku, Sapporo, Hokkaido 0600815, Japan. [Iwabuchi, Kazuya; Onoe, Kazunori] Hokkaido Univ, Inst Med Genet, Div Immunobiol, Sapporo, Hokkaido 0600815, Japan. [Diao, Hongyan] Zhejiang Univ, State Key Lab Diag & Treatment Infect Dis, Affiliated Hosp 1, Coll Med, Hangzhou 310003, Zhejiang, Peoples R China. [Van Kaer, Luc] Vanderbilt Univ, Dept Microbiol & Immunol, Sch Med, Nashville, TN 37232 USA. [Denhardt, David T.] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ 08854 USA. [Rittling, Susan] Forsyth Inst, Boston, MA 02115 USA. RP Diao, HY (reprint author), Hokkaido Univ, Inst Med Genet, Dept Matrix Med, Kita Ku, Kita 15,Nishi 7, Sapporo, Hokkaido 0600815, Japan. EM diao.hy@163.com; toshi@igm.hokudai.ac.jp RI Kon, Shigeyuki/A-3809-2012; uede, toshimitsu/A-4273-2012; Van Kaer, Luc/H-1033-2015 OI Van Kaer, Luc/0000-0001-5275-2309 FU Japan Society for the Promotion of Science [17790315] FX We thank Drs. M. Taniguchi and K. Seino (Research Center for Allergy and Immunology, institute of Physical and Chemical Research, Yokohama, Japan) for TLR2 cells. This work was supported by Japan Society for the Promotion of Science Grant 17790315 (to H.D.). NR 30 TC 19 Z9 22 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 14 PY 2008 VL 105 IS 41 BP 15884 EP 15889 DI 10.1073/pnas.0806089105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363BM UT WOS:000260240900045 PM 18836077 ER PT J AU Lin, B Koizumi, A Tanaka, N Panda, S Masland, RH AF Lin, Bin Koizumi, Amane Tanaka, Nobushige Panda, Satchidananda Masland, Richard H. TI Restoration of visual function in retinal degeneration mice by ectopic expression of melanopsin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GANGLION-CELLS; MOUSE RETINA; RESPONSES; LIGHT; PHOTOPIGMENT; PHOTOTRANSDUCTION; PHOTOSENSITIVITY; PERSISTENCE; DIVERSITY AB The rod and cone cells of the mammalian retina are the principal photoreceptors for image-forming vision. They transmit information by means of a chain of intermediate cells to the retinal ganglion cells, which in turn send signals from the retina to the brain. Loss of photoreceptor cells, as happens in a number of human diseases, leads to irreversible blindness. in a mouse model (rd/rd) of photoreceptor degeneration, we used a viral vector to express in a large number of retinal ganglion cells the light sensitive protein melanopsin, normally present in only a specialized subset of the cells. Whole-cell patch-clamp recording showed photoresponses in these cells even after degeneration of the photoreceptors and additional pharmacological or Cd2+ block of synaptic function. Interestingly, similar responses were observed across a wide variety of diverse types of ganglion cell of the retina. The newly melanopsin-expressing ganglion cells provided an enhancement of visual function in rd/rd mice: the pupillary light reflex (PLR) returned almost to normal; the mice showed behavioral avoidance of light in an open-field test, and they could discriminate a light stimulus from a dark one in a two-choice visual discrimination alley. Recovery of the PLR was stable for at least 11 months. It has recently been shown that ectopic retinal expression of a light sensitive bacterial protein, channelrhodopsin-2, can restore neuronal responsiveness and simple visual abilities in rd/rd mice. For therapy in human photodegenerations, channelrhodopsin-2 and melanopsin have different advantages and disadvantages; both proteins (or modifications of them) should be candidates. C1 [Lin, Bin; Koizumi, Amane; Masland, Richard H.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tanaka, Nobushige; Panda, Satchidananda] Salk Inst Biol Studies, La Jolla, CA 92037 USA. RP Masland, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Thier 429,50 Blossom St, Boston, MA 02114 USA. EM richard_masland@hms.harvard.edu RI Lin, Bin/E-9871-2010; Koizumi, Amane/E-7771-2011; Panda, Satchidananda/J-6891-2012 FU National Institutes of Health [EY 017169, EY016807]; Pew Scholars award FX We thank Aimee Wong and Richard Brown for advice on the testing of mouse visual discriminations and Jeng-Shin Lee and the Harvard vector core for providing the AAV constructs. This work was supported by National Institutes of Health Grants EY 017169 (to R.H.M.) and EY016807 (to S.P.). S.P. was supported by a Pew Scholars award. R.H.M. is a Senior Investigator of Research to Prevent Blindness. NR 28 TC 124 Z9 130 U1 0 U2 11 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 OCT 14 PY 2008 VL 105 IS 41 BP 16009 EP 16014 DI 10.1073/pnas.0806114105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363BM UT WOS:000260240900066 PM 18836071 ER PT J AU Qiu, L Larson, TA Smith, D Vitkin, E Modell, MD Korgel, BA Sokolov, KV Hanlon, EB Itzkan, I Perelman, LT AF Qiu, Le Larson, Timothy A. Smith, Danielle Vitkin, Edward Modell, Mark D. Korgel, Brian A. Sokolov, Konstantin V. Hanlon, Eugene B. Itzkan, Irving Perelman, Lev T. TI Observation of plasmon line broadening in single gold nanorods SO APPLIED PHYSICS LETTERS LA English DT Article ID LIGHT-SCATTERING; PARTICLES; NANOPARTICLES; SPECTROSCOPY; CELLS; SHAPE AB Attempts to realize the important potential of gold nanorods as extremely bright molecular markers have been limited by the broad spectroscopic linewidths usually observed. We identify the origin of this broadening as inhomogeneous broadening due to the extreme sensitivity of the surface plasmon resonance to the nanorod aspect ratio. Using confocal light scattering spectroscopic microscopy, we observed the narrow homogeneously broadened plasmon lines of single gold nanorods and obtained the first quantitative measurements of this homogeneous broadening. We show that homogeneous broadening can be predicted from first principals. (C) 2008 American Institute of Physics. [DOI: 10.1063/1.2995982] C1 [Qiu, Le; Vitkin, Edward; Modell, Mark D.; Hanlon, Eugene B.; Itzkan, Irving; Perelman, Lev T.] Harvard Univ, Biomed Imaging & Spect Lab, BIDMC, Boston, MA 02215 USA. [Larson, Timothy A.; Smith, Danielle; Korgel, Brian A.; Sokolov, Konstantin V.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. [Larson, Timothy A.; Smith, Danielle; Korgel, Brian A.; Sokolov, Konstantin V.] Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA. [Sokolov, Konstantin V.] Univ Texas MD Anderson Canc Ctr, Dept Biomed Engn, Houston, TX 77030 USA. [Sokolov, Konstantin V.] Univ Texas MD Anderson Canc Ctr, Dept Imaging Phys, Houston, TX 77030 USA. [Hanlon, Eugene B.] Dept Vet Affairs, Med Res Serv, Bedford, MA 01730 USA. RP Qiu, L (reprint author), Harvard Univ, Biomed Imaging & Spect Lab, BIDMC, Boston, MA 02215 USA. EM ltperel@bidmc.harvard.edu RI Korgel, Brian/I-5771-2013; OI Sokolov, Konstantin/0000-0002-0198-2005 FU National Science Foundation [BES0116833]; National Institutes of Health [RR017361, CA103830]; Department of Veterans Affairs; Office of Research and Development FX This work was supported by the National Science Foundation (Grant No. BES0116833), National Institutes of Health (Grant Nos. RR017361 and CA103830), and in part by the Department of Veterans Affairs, Office of Research and Development. We thank K. Travis for helpful comments. The electron microscopy studies were conducted at the electron microscope facilities at the Institute of Cellular and Molecular Biology, University of Texas at Austin. NR 20 TC 17 Z9 17 U1 0 U2 11 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0003-6951 EI 1077-3118 J9 APPL PHYS LETT JI Appl. Phys. Lett. PD OCT 13 PY 2008 VL 93 IS 15 AR 153106 DI 10.1063/1.2995982 PG 3 WC Physics, Applied SC Physics GA 361JY UT WOS:000260125100077 ER PT J AU Rigotti, NA Munafo, MR Stead, LF AF Rigotti, Nancy A. Munafo, Marcus R. Stead, Lindsay F. TI Smoking cessation interventions for hospitalized smokers - A systematic review SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 9th Annual Meeting of the Society-for-Research-in-Nicotine-and-Tobacco Europe CY OCT 05, 2007 CL Madrid, SPAIN SP Soc Res Nicotine & Tobacco Europe ID RANDOMIZED CONTROLLED-TRIAL; TRANSDERMAL NICOTINE REPLACEMENT; ACUTE MYOCARDIAL-INFARCTION; CLINICAL-TRIAL; CARDIOVASCULAR-DISEASE; EFFICACY; SURGERY; INPATIENTS; ADMISSION AB Background: A hospital admission provides an opportunity to help people stop smoking. Providing smoking cessation advice, counseling, or medication is now a quality-of-care measure for US hospitals. We assessed the effectiveness of smoking cessation interventions initiated during a hospital stay. Methods: We searched the Cochrane Tobacco Addiction Review Group's register for randomized and quasi-randomized controlled trials of smoking cessation interventions (behavioral counseling and/or pharmacotherapy) that began during hospitalization and had a minimum of 6 months of follow-up. Two authors independently extracted data from each article, with disagreements resolved by consensus. Results: Thirty-three trials met inclusion criteria. Smoking counseling that began during hospitalization and included supportive contacts for more than 1 month after discharge increased smoking cessation rates at 6 to 12 months (pooled odds ratio [OR], 1.65; 95% confidence interval [CI], 1.44-1.90). No benefit was found for interventions with less postdischarge contact. Counseling was effective when offered to all hospitalized smokers and to the subset admitted for cardiovascular disease. Adding nicotine replacement therapy to counseling produced a trend toward efficacy over counseling alone (OR, 1.47; 95% CI, 0.92-2.35). One study added bupropion hydrochloride to counseling, which had a nonsignificant result (OR, 1.56; 95% CI, 0.79-3.06). Conclusions: Offering smoking cessation counseling to all hospitalized smokers is effective as long as supportive contacts continue for more than 1 month after discharge. Adding nicotine replacement therapy to counseling may further increase smoking cessation rates and should be offered when clinically indicated, especially to hospitalized smokers with nicotine withdrawal symptoms. C1 [Rigotti, Nancy A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Munafo, Marcus R.] Univ Bristol, Dept Expt Psychol, Bristol, Avon, England. [Stead, Lindsay F.] Univ Oxford, Oxford, England. [Stead, Lindsay F.] Cochrane Tobacco Addict Review Grp, Oxford, England. RP Rigotti, NA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tobacco Res & Treatment Ctr, 50 Staniford St,Room 914, Boston, MA 02114 USA. EM nrigotti@partners.org OI Munafo, Marcus/0000-0002-4049-993X FU NHLBI NIH HHS [2 K24 HL04440, K24 HL004440, K24 HL004440-10] NR 44 TC 136 Z9 142 U1 1 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 13 PY 2008 VL 168 IS 18 BP 1950 EP 1960 DI 10.1001/archinte.168.18.1950 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 359KA UT WOS:000259984400003 PM 18852395 ER PT J AU Alelu-Paz, R Iturrieta-Zuazo, I Byne, W Haroutunian, V Garcia-Villanueva, M Rabano, A Garcia-Amado, M Prensa, L Gimenez-Amaya, JM AF Alelu-Paz, Raul Iturrieta-Zuazo, Ignacio Byne, William Haroutunian, Vahram Garcia-Villanueva, Mercedes Rabano, Alberto Garcia-Amado, Maria Prensa, Lucia Manuel Gimenez-Amaya, Jose TI A New Antigen Retrieval Technique for Human Brain Tissue SO PLOS ONE LA English DT Article AB Immunohistochemical staining of tissues is a powerful tool used to delineate the presence or absence of an antigen. During the last 30 years, antigen visualization in human brain tissue has been significantly limited by the masking effect of fixatives. In the present study, we have used a new method for antigen retrieval in formalin-fixed human brain tissue and examined the effectiveness of this protocol to reveal masked antigens in tissues with both short and long formalin fixation times. This new method, which is based on the use of citraconic acid, has not been previously utilized in brain tissue although it has been employed in various other tissues such as tonsil, ovary, skin, lymph node, stomach, breast, colon, lung and thymus. Thus, we reported here a novel method to carry out immunohistochemical studies in free-floating human brain sections. Since fixation of brain tissue specimens in formaldehyde is a commonly method used in brain banks, this new antigen retrieval method could facilitate immunohistochemical studies of brains with prolonged formalin fixation times. C1 [Alelu-Paz, Raul; Iturrieta-Zuazo, Ignacio; Garcia-Amado, Maria; Prensa, Lucia; Manuel Gimenez-Amaya, Jose] Univ Autonoma Madrid, Fac Med, Dept Anat Histol & Neurociencia, Madrid, Spain. [Iturrieta-Zuazo, Ignacio; Garcia-Amado, Maria] Univ Navarra, Clin Univ, Lab Neuromorfol Funcion, E-31080 Pamplona, Spain. [Byne, William; Haroutunian, Vahram] Mount Sinai Sch Med, Dept Psychiat, New York, NY USA. [Byne, William; Haroutunian, Vahram] Bronx Vet Affairs Med Ctr, Bronx, NY USA. [Garcia-Villanueva, Mercedes] Hosp Ramon & Cajal, Dept Anat Patol, Madrid, Spain. [Rabano, Alberto] Hosp Alcorcon, Lab Neuropatol, Madrid, Spain. RP Alelu-Paz, R (reprint author), Univ Autonoma Madrid, Fac Med, Dept Anat Histol & Neurociencia, Madrid, Spain. EM josemanuel.gimenezamaya@uam.es RI Garcia-Amado, Maria/K-2705-2014 OI Garcia-Amado, Maria/0000-0001-6778-5680 FU Spanish Ministerio de Educacion y Ciencia [BFU2006-01189] FX This study was supported by a grant from the Spanish Ministerio de Educacion y Ciencia (BFU2006-01189). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 8 Z9 9 U1 0 U2 7 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 OCT 13 PY 2008 VL 3 IS 10 AR e3378 DI 10.1371/journal.pone.0003378 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 432GN UT WOS:000265121600004 PM 18852880 ER PT J AU Kuballa, P Huett, A Rioux, JD Daly, MJ Xavier, RJ AF Kuballa, Petric Huett, Alan Rioux, John D. Daly, Mark J. Xavier, Ramnik J. TI Impaired Autophagy of an Intracellular Pathogen Induced by a Crohn's Disease Associated ATG16L1 Variant SO PLOS ONE LA English DT Article AB The genetic risk factors predisposing individuals to the development of inflammatory bowel disease are beginning to be deciphered by genome-wide association studies. Surprisingly, these new data point towards a critical role of autophagy in the pathogenesis of Crohn's disease. A single common coding variant in the autophagy protein ATG16L1 predisposes individuals to the development of Crohn's disease: while ATG16L1 encoding threonine at amino acid position 300 (ATG16L1*300T) confers protection, ATG16L1 encoding for alanine instead of threonine (ATG16L1*300A, also known as T300A) mediates risk towards the development of Crohn's disease. Here we report that, in human epithelial cells, the Crohn's disease-associated ATG16L1 coding variant shows impairment in the capture of internalized Salmonella within autophagosomes. Thus, we propose that the association of ATG16L1*300A with increased risk of Crohn's disease is due to impaired bacterial handling and lowered rates of bacterial capture by autophagy. C1 [Kuballa, Petric; Huett, Alan; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02115 USA. [Rioux, John D.; Daly, Mark J.] Harvard Univ, Massachusetts Inst Technol, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA. [Rioux, John D.] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada. [Daly, Mark J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA USA. RP Kuballa, P (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02115 USA. EM xavier@molbio.mgh.harvard.edu RI Rioux, John/A-9599-2015 OI Rioux, John/0000-0001-7560-8326 FU Deutsche Forschungsgemeinschaft [KU2511/1-1]; CCIB; National Institutes of Allergy and Infectious Diseases [AI065687, AI067152]; National Institute of Diabetes and Digestive and Kidney Diseases [DK064869, DK062432]; Crohn's and Colitis Foundation of America [SRA512]; [AI062773]; [HL88297] FX PK is supported by a fellowship award from the Deutsche Forschungsgemeinschaft (KU2511/1-1). RJX is supported by the following grants: AI062773, HL88297 and CCIB development funds. JDR is funded by grants from the National Institutes of Allergy and Infectious Diseases (AI065687; AI067152) from the National Institute of Diabetes and Digestive and Kidney Diseases (DK064869; DK062432) and the Crohn's and Colitis Foundation of America (SRA512). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 21 TC 184 Z9 194 U1 2 U2 6 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 OCT 13 PY 2008 VL 3 IS 10 AR e3391 DI 10.1371/journal.pone.0003391 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 432GN UT WOS:000265121600014 PM 18852889 ER PT J AU Yan, BP Kiernan, TJ Clark, DJ Jaff, MR Schainfeld, RM Rosenfield, K AF Yan, Bryan P. Kiernan, Thomas J. Clark, David J. Jaff, Michael R. Schainfeld, Robert M. Rosenfield, Kenneth TI Carotid Duplex Ultrasound Velocity Measurements Versus Intravascular Ultrasound in Detecting Carotid In-Stent Restenosis SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 20th Annual Transcatheter Cardiovascular Therapeutics Conference CY OCT 12-17, 2008 CL Washington, CA SP Cardiovasc Res Fdn C1 [Yan, Bryan P.; Kiernan, Thomas J.; Jaff, Michael R.; Schainfeld, Robert M.; Rosenfield, Kenneth] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Clark, David J.] Austin Hosp, Melbourne, Vic 3084, Australia. RI Yan, Bryan/C-3390-2008; Yan, Bryan/P-5928-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 12 PY 2008 VL 102 IS 8A BP 18I EP 18I PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 360YM UT WOS:000260094700035 ER PT J AU Meliga, E Valgimigli, M Chieffo, A Maree, AO Cook, S Garcia-Garcia, HM D'Amico, M Lombardi, P De Servi, S Marra, S Palacios, I Windecker, S Colombo, A Sheiban, I Serruys, PW AF Meliga, Emanuele Valgimigli, Marco Chieffo, Alaide Maree, Andrew O. Cook, Stephan Garcia-Garcia, Hector M. D'Amico, Maurizio Lombardi, Primiano De Servi, Stefano Marra, Sebastiano Palacios, Igor Windecker, Stephane Colombo, Antonio Sheiban, Imad Serruys, Patrick W. TI Gender Differences In Short And Long Term Clinical Outcomes After Percutaneous Coronary Interventions For Unprotected Left Main Coronary Artery Disease With Drug Eluting Stents Implantation SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 20th Annual Transcatheter Cardiovascular Therapeutics Conference CY OCT 12-17, 2008 CL Washington, CA SP Cardiovasc Res Fdn C1 [Meliga, Emanuele; D'Amico, Maurizio; Lombardi, Primiano; Marra, Sebastiano] San Giovanni Battista Hosp, Intervent Cardiol Dept, Turin, Italy. [Meliga, Emanuele; Garcia-Garcia, Hector M.; Serruys, Patrick W.] Erasmus Univ, Intervent Cardiol Dept, Erasmus MC, Rotterdam, Netherlands. Univ Ferrara, Inst Cardiol, I-44100 Ferrara, Italy. [Chieffo, Alaide; Colombo, Antonio] Ist Sci San Raffaele, Intervent Cardiol Dept, Milan, Italy. [Maree, Andrew O.; Palacios, Igor] Massachusetts Gen Hosp, Intervent Cardiol Dept, Boston, MA 02114 USA. [Maree, Andrew O.; Windecker, Stephane] Univ Hosp Bern, Dept Cardiol, CH-3010 Bern, Switzerland. [De Servi, Stefano] Osped Civile Legnano, Intervent Cardiol Dept, Legnaro, Italy. [Sheiban, Imad] Univ Turin, San Giovanni Battista Hosp, Univ Intervent Cardiol Dept, Turin, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 12 PY 2008 VL 102 IS 8A BP 85I EP 85I PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 360YM UT WOS:000260094700192 ER PT J AU Meliga, E Valgimigli, M Chieffo, A Maree, AO Cook, S Garcia-Garcia, HM D'Amico, M Lombardi, P De Servi, S Marra, S Palacios, I Windecker, S Colombo, A Sheiban, I Serruys, PW AF Meliga, Emanuele Valgimigli, Marco Chieffo, Alaide Maree, Andrew O. Cook, Stephan Garcia-Garcia, Hector M. D'Amico, Maurizio Lombardi, Primiano De Servi, Stefano Marra, Sebastiano Palacios, Igor Windecker, Stephan Colombo, Antonio Sheiban, Imad Serruys, Patrick W. TI Very Long Term Clinical Outcomes After DES Implantation For Unprotected Left Main Coronary Artery Disease In Very High Risk Patients SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 20th Annual Transcatheter Cardiovascular Therapeutics Conference CY OCT 12-17, 2008 CL Washington, CA SP Cardiovasc Res Fdn C1 [Meliga, Emanuele; D'Amico, Maurizio; Lombardi, Primiano; Marra, Sebastiano; Sheiban, Imad] San Giovanni Battista Hosp, Intervent Cardiol Dept, Turin, Italy. [Meliga, Emanuele; Garcia-Garcia, Hector M.; Serruys, Patrick W.] ERASMUS MC, Intervent Cardiol Dept, Thoraxctr, Rotterdam, Netherlands. [Valgimigli, Marco] Univ Ferrara, Inst Cardiol, I-44100 Ferrara, Italy. [Chieffo, Alaide; Colombo, Antonio] Ist Sci San Raffaele, Intervent Cardiol Dept, Milan, Italy. [Maree, Andrew O.; Palacios, Igor] Massachusetts Gen Hosp, Intervent Cardiol Dept, Boston, MA 02114 USA. [Cook, Stephan] Univ Hosp, Dept Cardiol 1, Bern, Switzerland. [De Servi, Stefano] Osped Civile Legnano, Intervent Cardiol Dept, Legnano, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 12 PY 2008 VL 102 IS 8A BP 86I EP 86I PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 360YM UT WOS:000260094700193 ER PT J AU Azmoon, S Lepor, NE Ebrahimi, R Madyoon, H AF Azmoon, Shah Lepor, Norman E. Ebrahimi, Ramin Madyoon, Hooman TI Interpretation of Symptoms in addition to the predictive Value of Coronary Artery Calcium Scores in Assessing Coronary Obstructive Risk SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 20th Annual Transcatheter Cardiovascular Therapeutics Conference CY OCT 12-17, 2008 CL Washington, CA SP Cardiovasc Res Fdn C1 [Azmoon, Shah] NYMC, Valhalla, NY USA. [Lepor, Norman E.; Madyoon, Hooman] Westside Med Imaging, Beverly Hills, CA USA. [Ebrahimi, Ramin] W Los Angeles Vet Affairs Hosp, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 12 PY 2008 VL 102 IS 8A BP 95I EP 95I PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 360YM UT WOS:000260094700216 ER PT J AU Azmoon, S Madyoon, H Ebrahimi, R Lepor, NE AF Azmoon, Shah Madyoon, Hooman Ebrahimi, Ramin Lepor, Norman E. TI Gender Differences in the Assessment of Coronary Artery Stenosis in Patients with Abnormal Coronary Calcium Scores Undergoing 64 Slice CT Angiography SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 20th Annual Transcatheter Cardiovascular Therapeutics Conference CY OCT 12-17, 2008 CL Washington, CA SP Cardiovasc Res Fdn C1 [Azmoon, Shah] NYMC, Valhalla, NY USA. [Madyoon, Hooman; Lepor, Norman E.] Westside Med Coll, Beverly Hills, CA USA. [Ebrahimi, Ramin] W Los Angeles Vet Affairs Hosp, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 12 PY 2008 VL 102 IS 8A BP 98I EP 98I PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 360YM UT WOS:000260094700227 ER PT J AU Pop, A Ansel, G Jaff, M Bresnahan, J Safian, R AF Pop, Andrei Ansel, Gary Jaff, Michael Bresnahan, John Safian, Robert TI Neurologic Outcome of Stroke After Carotid Stenting SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 20th Annual Transcatheter Cardiovascular Therapeutics Conference CY OCT 12-17, 2008 CL Washington, CA SP Cardiovasc Res Fdn C1 [Pop, Andrei; Safian, Robert] William Beaumont Hosp, Royal Oak, MI 48072 USA. [Ansel, Gary] MidWest Cardiol Res Fdn, Columbus, OH USA. [Jaff, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bresnahan, John] Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 12 PY 2008 VL 102 IS 8A BP 101I EP 102I PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 360YM UT WOS:000260094700234 ER PT J AU Kiernan, TJ Yan, BP Cubeddu, RJ Rengifo-Moreno, P Gupta, V Inglessis, I Jaff, MR Schainfeld, RM Palacios, IF AF Kiernan, Thomas J. Yan, Bryan P. Cubeddu, Roberto J. Rengifo-Moreno, Pablo Gupta, Vishal Inglessis, Ignacio Jaff, Michael R. Schainfeld, Robert M. Palacios, Igor F. TI Patent Foramen Ovate, Cryptogenic Stroke and May-Thurner Syndrome : a Retrospective Analysis SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 20th Annual Transcatheter Cardiovascular Therapeutics Conference CY OCT 12-17, 2008 CL Washington, CA SP Cardiovasc Res Fdn C1 [Kiernan, Thomas J.; Yan, Bryan P.; Cubeddu, Roberto J.; Rengifo-Moreno, Pablo; Gupta, Vishal; Inglessis, Ignacio; Jaff, Michael R.; Schainfeld, Robert M.; Palacios, Igor F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Yan, Bryan/C-3390-2008; Yan, Bryan/P-5928-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 12 PY 2008 VL 102 IS 8A BP 112I EP 112I PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 360YM UT WOS:000260094700263 ER PT J AU Finn, AV John, MC Nakazawa, G Raghunathan, C Ezell, T Lajoie, S Xu, X Cheng, Q Kolodgie, F Virmani, R Gold, HK AF Finn, Aloke V. John, Michael C. Nakazawa, Gaku Raghunathan, Chitra Ezell, Tucker Lajoie, Scott Xu, Xin Cheng, Qi Kolodgie, Frank Virmani, Renu Gold, Herman K. TI Differential Healing in Paclitaxel and Sirolimus-Eluting Stents in Combination with Oral PPAR Gamma Agents: The Importance of Drug Interaction in Delayed Healing SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 20th Annual Transcatheter Cardiovascular Therapeutics Conference CY OCT 12-17, 2008 CL Washington, CA SP Cardiovasc Res Fdn C1 [Finn, Aloke V.; Raghunathan, Chitra; Ezell, Tucker] Emory Univ, Atlanta, GA 30322 USA. [John, Michael C.; Lajoie, Scott; Gold, Herman K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nakazawa, Gaku; Xu, Xin; Cheng, Qi; Kolodgie, Frank; Virmani, Renu] CVPath, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 12 PY 2008 VL 102 IS 8A BP 128I EP 128I PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 360YM UT WOS:000260094700303 ER PT J AU Kiernan, TJ Yan, BP Cubeddu, RJ Cruz-Gonzalez, I Rosenfield, K Palacios, I AF Kiernan, Thomas J. Yan, Bryan P. Cubeddu, Roberto J. Cruz-Gonzalez, Ignacio Rosenfield, Kenneth Palacios, Igor TI Coronary Artery Perforations in the Current Era of Percutaneous Coronary Intervention SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 20th Annual Transcatheter Cardiovascular Therapeutics Conference CY OCT 12-17, 2008 CL Washington, CA SP Cardiovasc Res Fdn C1 [Kiernan, Thomas J.; Yan, Bryan P.; Cubeddu, Roberto J.; Cruz-Gonzalez, Ignacio; Rosenfield, Kenneth; Palacios, Igor] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Yan, Bryan/C-3390-2008; Yan, Bryan/P-5928-2015 NR 0 TC 0 Z9 0 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 12 PY 2008 VL 102 IS 8A BP 212I EP 212I PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 360YM UT WOS:000260094700526 ER PT J AU Movahed, MR Ebrahimi, R Jamal, MM Hashemzadeh, M AF Movahed, Mohammad Reza Ebrahimi, Ramin Jamal, M. Mazen Hashemzadeh, Mehrtash TI Significant Decline in the Nationwide Trends in the Mortality in Patients undergoing Percutaneous Coronary Intervention SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 20th Annual Transcatheter Cardiovascular Therapeutics Conference CY OCT 12-17, 2008 CL Washington, CA SP Cardiovasc Res Fdn C1 [Movahed, Mohammad Reza] Univ Arizona, Med Ctr, Tucson, AZ USA. [Movahed, Mohammad Reza] So Arizona VA Hlth Care Syst, Tucson, AZ USA. [Ebrahimi, Ramin] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. [Jamal, M. Mazen] VA Long Beach Hlth Care Syst, Long Beach, CA USA. [Hashemzadeh, Mehrtash] VA Long Beach Healthcare Syst, Long Beach, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 12 PY 2008 VL 102 IS 8A BP 216I EP 217I PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 360YM UT WOS:000260094700540 ER PT J AU Movahed, MR Hashemzadeh, MH Jamal, MM Ebrahimi, R AF Movahed, Mohammad Reza Hashemzadeh, Mehrtash Hashmezadeh Jamal, M. Mazen Ebrahimi, Ramin TI Significant Decline in the Nationwide Trends in the Mortality in Patients undergoing Multi Vessel Percutaneous Coronary Intervention SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 20th Annual Transcatheter Cardiovascular Therapeutics Conference CY OCT 12-17, 2008 CL Washington, CA SP Cardiovasc Res Fdn C1 [Movahed, Mohammad Reza] So Arizona VA Hlth Care Syst, Tucson, AZ USA. [Movahed, Mohammad Reza] Univ Arizona, Med Ctr, Tucson, AZ USA. [Hashemzadeh, Mehrtash Hashmezadeh; Jamal, M. Mazen] VA Long Beach Hlth Care Syst, California, CA USA. [Ebrahimi, Ramin] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 12 PY 2008 VL 102 IS 8A BP 217I EP 217I PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 360YM UT WOS:000260094700541 ER PT J AU Hill, DR Ryan, ET AF Hill, David R. Ryan, Edward T. TI Management of travellers' diarrhoea SO BRITISH MEDICAL JOURNAL LA English DT Review ID NORTH-AMERICAN TRAVELERS; IRRITABLE-BOWEL-SYNDROME; DOUBLE-BLIND; BISMUTH SUBSALICYLATE; ESCHERICHIA-COLI; PLUS LOPERAMIDE; MEXICO; TRIAL; RIFAXIMIN; PLACEBO C1 [Hill, David R.] Hosp Trop Dis, Natl Travel Hlth Network & Ctr, London WC1E 6JB, England. [Hill, David R.] Hosp Trop Dis, London Sch Hyg & Trop Med, London WC1E 6JB, England. [Ryan, Edward T.] Massachusetts Gen Hosp, Travelers Advice & Immunizat Ctr, Boston, MA 02114 USA. [Ryan, Edward T.] Massachusetts Gen Hosp, Trop & Geog Med Ctr, Boston, MA 02114 USA. RP Hill, DR (reprint author), Hosp Trop Dis, Natl Travel Hlth Network & Ctr, London WC1E 6JB, England. EM david.hill@uclh.org NR 34 TC 11 Z9 11 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD OCT 11 PY 2008 VL 337 IS 7674 AR a1746 DI 10.1136/bmj.a1746 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 358FU UT WOS:000259903300036 PM 18838421 ER PT J AU Shipman, C Gysels, M White, P Worth, A Murray, SA Barclay, S Forrest, S Shepherd, J Dale, J Dewar, S Peters, M White, S Richardson, A Lorenz, K Koffman, J Higginson, IJ AF Shipman, Cathy Gysels, Marjolein White, Patrick Worth, Allison Murray, Scott A. Barclay, Stephen Forrest, Sarah Shepherd, Jonathan Dale, Jeremy Dewar, Steve Peters, Marilyn White, Suzanne Richardson, Alison Lorenz, Karl Koffman, Jonathan Higginson, Irene J. TI Improving generalist end of life care: national consultation with practitioners, commissioners, academics, and service user groups SO BRITISH MEDICAL JOURNAL LA English DT Article ID PRIMARY PALLIATIVE CARE; GOLD-STANDARDS-FRAMEWORK; CANCER; DEATH; COMMUNICATION; COUNTRIES; TRENDS; FAMILY; PLACE; DIE AB Objective To identify major concerns of national and local importance in the provision, commissioning, research, and use of generalist end of life care. Design A national consultation and prioritising exercise using a modified form of the nominal group technique. Participants Healthcare practitioners, commissioners, academics, and representatives of user and voluntary groups. Setting Primary and secondary care, specialist palliative care, and academic and voluntary sectors in England and Scotland. Results 74% of those invited ( 210/ 285) participated. The stage of life to which "end of life care" referred was not understood in a uniform way. Perceptions ranged from a period of more than a year to the last few days of life. Prominent concerns included difficulties in prognosis and the availability of adequate support for patients with advanced non- malignant disease. Generalists in both primary and secondary care were usually caring for only a few patients approaching the end of life at any one time at a point in time. It was therefore challenging to maintain skills and expertise particularly as educational opportunities were often limited. End of life care took place among many other competing and incentivised activities for general practitioners in the community. More needs to be known about models of end of life care and how these can be integrated in a generalist's workload. A greater evidence base is needed about the effectiveness and application of current tools such as the gold standards framework and Liverpool care pathway and about models of palliation in patients with diseases other than cancer. Conclusions Definitions of end of life care need clarification and standardisation. A greater evidence base is needed to define models of good practice together with a commitment to provide education and training and adequate resources for service provision. More needs to be known about the context of provision and the influence of competing priorities and incentives. C1 [Shipman, Cathy; Gysels, Marjolein; Koffman, Jonathan; Higginson, Irene J.] Kings Coll London, Dept Palliat Care Policy & Rehabil, Weston Educ Ctr, London SE5 9RJ, England. [Shipman, Cathy; White, Patrick; Peters, Marilyn; White, Suzanne] Kings Coll London, Dept Gen Practice & Primary Care, London SE11 6SP, England. [Worth, Allison; Murray, Scott A.] Univ Edinburgh, Primary Palliat Care Res Grp, Edinburgh EH8 9DX, Midlothian, Scotland. [Barclay, Stephen; Forrest, Sarah] Univ Cambridge, Gen Practice & Primary Care Res Unit, Dept Publ Hlth & Primary Care, Cambridge CB2 2SR, England. [Shepherd, Jonathan; Dale, Jeremy] Univ Warwick, Ctr Primary Hlth Care Studies, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England. [Dewar, Steve] Kings Fund, London W1G 0AN, England. [Richardson, Alison] Kings Coll London, Florence Nightingale Sch Nursing & Midwifery, London SE1 8WA, England. [Lorenz, Karl] Univ Calif Los Angeles, Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Shipman, C (reprint author), Kings Coll London, Dept Palliat Care Policy & Rehabil, Weston Educ Ctr, London SE5 9RJ, England. EM Catherine.shipman@kcl.ac.uk RI green, sam/C-2608-2008; OI Barclay, Stephen/0000-0002-4505-7743; White, Patrick/0000-0002-2047-8787; Dale, Jeremy/0000-0001-9256-3553 FU National Institute of Health Research Service Development and Organisation research and development programme FX National Institute of Health Research Service Development and Organisation research and development programme. NR 42 TC 67 Z9 67 U1 2 U2 12 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD OCT 11 PY 2008 VL 337 IS 7674 AR a1720 DI 10.1136/bmj.a1720 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 358FU UT WOS:000259903300032 PM 18829640 ER PT J AU Sugiana, C Pagliarini, DJ McKenzie, M Kirby, DM Salemi, R Abu-Amero, KK Dahl, HHM Hutchison, WM Vascotto, KA Smith, SM Newbold, RF Christodoulou, J Calvo, S Mootha, VK Ryan, MT Thorburn, DR AF Sugiana, Canny Pagliarini, David J. McKenzie, Matthew Kirby, Denise M. Salemi, Renato Abu-Amero, Khaled K. Dahl, Hans-Henrik M. Hutchison, Wendy M. Vascotto, Katherine A. Smith, Stacey M. Newbold, Robert F. Christodoulou, John Calvo, Sarah Mootha, Vamsi K. Ryan, Michael T. Thorburn, David R. TI Mutation of C20orf7 Disrupts Complex I Assembly and Causes Lethal Neonatal Mitochondrial Disease SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID RESPIRATORY-CHAIN DISORDERS; CYTOCHROME-C-OXIDASE; LEIGH-SYNDROME; ENCODED SUBUNITS; DEFICIENCY; GENE; PROTEIN; ENCEPHALOMYOPATHY; SUPERCOMPLEXES; ENCEPHALOPATHY AB Complex I (NADH:ubiquinone oxidoreductase) is the first and largest multimeric complex of the mitochondrial respiratory chain. Human complex I comprises seven Subunits encoded by mitochondrial DNA and 38 nuclear-encoded subunits that are assembled together in a process that is only partially understood. To date, Mutations causing complex I deficiency have been described in all 14 core subunits, five supernumerary Subunits, and four assembly factors. We describe complex I deficiency caused by mutation of the putative complex I assembly factor C20orf7. A candidate region for a lethal neonatal form of complex I deficiency was identified by homozygosity mapping of an Egyptian family with one affected child and two affected pregnancies predicted by enzyme-based prenatal diagnosis. The region was confirmed by microcell-mediated chromosome transfer, and 11 candidate genes encoding potential mitochondrial proteins were sequenced. A homozygous missense mutation in C20orf7 segregated with disease in the family. We show that C20orf7 is peripherally associated with the matrix face of the mitochondrial inner membrane and that silencing its expression with RNAi decreases complex I activity. C20orf7 patient fibroblasts showed an almost cornplete absence of complex I holoenzyme and were defective at all early stage of complex I assembly, but in a manner distinct from the assembly defects caused by mutations in the assembly factor NDUFAF1. Our results indicate that C20orf7 is crucial in the assembly of complex I and that mutations in C20orf7 cause mitochondrial disease. C1 [Sugiana, Canny; Kirby, Denise M.; Salemi, Renato; Vascotto, Katherine A.; Smith, Stacey M.; Thorburn, David R.] Royal Childrens Hosp, Mitochondrial & Metab Res Grp, Parkville, Vic 3052, Australia. [Dahl, Hans-Henrik M.; Hutchison, Wendy M.] Royal Childrens Hosp, Murdoch Childresn Res Inst, Genet Hearing Res Grp, Parkville, Vic 3052, Australia. [Sugiana, Canny; Thorburn, David R.] Univ Melbourne, Dept Paediat, Parkville, Vic 3052, Australia. [Pagliarini, David J.; Calvo, Sarah; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Pagliarini, David J.; Calvo, Sarah; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02446 USA. [Pagliarini, David J.; Calvo, Sarah; Mootha, Vamsi K.] MIT, Broad Inst, Cambridge, MA 02142 USA. [Pagliarini, David J.; Calvo, Sarah; Mootha, Vamsi K.] Harvard Univ, Cambridge, MA 02142 USA. [McKenzie, Matthew; Ryan, Michael T.] La Trobe Univ, Dept Biochem, Melbourne, Vic 3086, Australia. [Kirby, Denise M.; Thorburn, David R.] Royal Childrens Hosp, Genet Hlth Serv Victoria, Melbourne, Vic 3052, Australia. [Abu-Amero, Khaled K.] King Saud Univ, Coll Med, Mol Genet Lab, Riyadh 11461, Saudi Arabia. [Newbold, Robert F.] Brunel Univ, Inst Cancer Genet & Pharmacogenom, Uxbridge UB8 3PH, Middx, England. [Christodoulou, John] Childrens Hosp, Western Sydney Genet Program, Westmead, NSW 2145, Australia. [Christodoulou, John] Univ Sydney, Discipline Paediat, Westmead, NSW 2145, Australia. [Christodoulou, John] Univ Sydney, Discipline Child Hlth & Genet Med, Westmead, NSW 2145, Australia. RP Thorburn, DR (reprint author), Royal Childrens Hosp, Mitochondrial & Metab Res Grp, Flemington Rd, Parkville, Vic 3052, Australia. EM david.thorburn@mcri.edu.au RI Ryan, Michael/C-6673-2011; Thorburn, David/G-6266-2013; Christodoulou, John/E-5866-2015; OI Ryan, Michael/0000-0003-2586-8829; thorburn, david/0000-0002-7725-9470; Christodoulou, John/0000-0002-8431-0641; McKenzie, Matthew/0000-0001-7508-1800; Pagliarini, Dave/0000-0002-0001-0087 FU Australian National Health; Medical Research Council; Australian Research Council; University of Melbourne; Muscular Dystrophy Association; Ramaciotti Foundation; National Institutes of Health [GM077465] FX We thank Andrew Cuthbert for advice on monochromosomal transfer. This work was supported by grants (D.R.T. and M.T.R.), postdoctoral fellowships (M.McK. and D.M.K.), and a principal research fellowship (D.R.T.) from the Australian National Health and Medical Research Council and a grant from the Australian Research Council (M.T.R.). C.S. was supported by a University of Melbourne postgraduate research scholarship. Grant funding was also received from the Muscular Dystrophy Association (D.R.T.), the Ramaciotti Foundation (M.McK.), and the National Institutes of Health (GM077465) (V.K.M.). NR 58 TC 104 Z9 107 U1 0 U2 10 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 OCT 10 PY 2008 VL 83 IS 4 BP 468 EP 478 DI 10.1016/j.ajhg.2008.09.009 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 363AV UT WOS:000260239200004 PM 18940309 ER PT J AU Kim, HG Kurth, I Lan, F Meliciani, I Wenzel, W Eom, SH Kang, GB Rosenberger, G Tekin, M Ozata, M Bick, DP Sherins, RJ Walker, SL Shi, Y Gusella, JF Layman, LC AF Kim, Hyung-Goo Kurth, Ingo Lan, Fei Meliciani, Irene Wenzel, Wolfgang Eom, Soo Hyun Kang, Gil Bu Rosenberger, Georg Tekin, Mustafa Ozata, Metin Bick, David P. Sherins, Richard J. Walker, Steven L. Shi, Yang Gusella, James F. Layman, Lawrence C. TI Mutations in CHD7, Encoding a Chromatin-Remodeling Protein, Cause Idiopathic Hypogonadotropic Hypogonadism and Kallmann Syndrome SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID CHARGE-SYNDROME; HORMONE RECEPTOR; HISTONE H3; GENE; CHROMODOMAINS; FAMILY; PREVALENCE; MOLECULES; ADHESION; NEURONS AB CHARGE syndrome and Kallmann syndrome (KS) are two distinct developmental disorders sharing overlapping features of impaired olfaction and hypogonadism. KS is a genetically heterogeneous disorder consisting of idiopathic hypogonadotropic hypogonadism (IHH) and anosmia, and is most commonly due to KAL1 or FGFR1 mutations. CHARGE syndrome, a multisystem autosomal-dominant disorder, is caused by CHD7 mutations. We hypothesized that CHD7 would be involved in the pathogenesis of IHH and KS (IHH/KS) without the CHARGE phenotype and that IHH/KS represents a milder allelic variant of CHARGE syndrome. Mutation screening of the 37 protein-coding exons of CHD7 was performed in 101 IHH/KS patients without a CHARGE phenotype. In an additional 96 IHH/KS patients, exons 6-10, encoding the conserved chromodomains, were sequenced. RT-PCR, SIFT, protein-structure analysis, and in situ hybridization were performed for additional supportive evidence. Seven heterozygous mutations, two splice and five missense, which were absent in >= 180 controls, were identified in three sporadic KS and four sporadic normosmic IHH patients. Three mutations affect chromodomains critical for proper CHD7 function in chromatin remodeling and transcriptional regulation, whereas the other four affect conserved residues, suggesting that they are deleterious. CHD7's role is further corroborated by specific expression in IHH/KS-relevant tissues and appropriate developmental expression. Sporadic CHD7 mutations occur in 6% of IHH/KS patients. CHD7 represents the first identified chromatin-remodeling protein with a role in human puberty and the second gene to cause both normosmic IHH and KS in humans. Our findings indicate that both normosmic IHH and KS are mild allelic variants of CHARGE syndrome and are caused by CHD7 mutations. C1 [Walker, Steven L.; Layman, Lawrence C.] Med Coll Georgia, Dept Obstet & Gynecol, Sect Reprod Endocrinol Infertil & Genet, Augusta, GA 30912 USA. [Walker, Steven L.; Layman, Lawrence C.] Med Coll Georgia, Inst Mol Med & Genet, Reprod Med Program, Augusta, GA 30912 USA. [Walker, Steven L.; Layman, Lawrence C.] Med Coll Georgia, Inst Mol Med & Genet, Dev Neuobiol Program, Augusta, GA 30912 USA. [Kim, Hyung-Goo; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. [Kim, Hyung-Goo; Gusella, James F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Kurth, Ingo; Rosenberger, Georg] Univ Klinikum Hamburg Eppendorf, Inst Human Genet, D-20246 Hamburg, Germany. [Lan, Fei; Shi, Yang] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Meliciani, Irene] Univ Roma La Sapienza, Fac Sci, I-00185 Rome, Italy. [Wenzel, Wolfgang] Forschungszentrum Karlsruhe, Inst Nanotechnol, D-76021 Karlsruhe, Germany. [Eom, Soo Hyun; Kang, Gil Bu] Gwangju Inst Sci & Technol, Cell Dynam Res Ctr, Dept Life Sci, Kwangju 500712, South Korea. [Tekin, Mustafa] Ankara Univ, Sch Med, Dept Pediat, Div Clin Mol Pathol & Genet, TR-06100 Ankara, Turkey. [Ozata, Metin] GATA Haydarpasa Training Hosp, Dept Endocrinol, TR-34660 Istanbul, Turkey. [Bick, David P.] Med Coll Wisconsin, Dept Pediat, Div Med Genet, Milwaukee, WI 53226 USA. [Bick, David P.] Med Coll Wisconsin, Dept Obstet & Gynecol, Milwaukee, WI 53226 USA. [Sherins, Richard J.] Columbia Fertil Associates, Washington, DC 20037 USA. [Walker, Steven L.; Layman, Lawrence C.] Med Coll Georgia, Neurosci Program, Augusta, GA 30912 USA. RP Layman, LC (reprint author), Med Coll Georgia, Dept Obstet & Gynecol, Sect Reprod Endocrinol Infertil & Genet, 1120 15th st, Augusta, GA 30912 USA. EM Ilayman@mcg.edu RI Wenzel, Wolfgang/B-3207-2009; OI Wenzel, Wolfgang/0000-0001-9487-4689; Kurth, Ingo/0000-0002-5642-8378 FU National Institutes of Health (NIH) [HD33004, HD040287]; Medical College of Georgia Research Institute (MCGRI); NIH [GM061354]; Deutsche Forschungsgemeinschaft (DFG) [WE1863/10-2]; DFG Center for Functional Nanostructures; EU Leonardo program "Unipharm Graduates FX We thank all affected individuals and their families for their cooperation. The authors also thank I. Hermans-Borgmeyer for unrestricted support with the in situ hybridizations and interpretation of the data; B. Dierkes for excellent technical assistance; G. Schnitzler for helpful discussions; E. Moutevelis for leucine-zipper-domain structure analysis; the Computational Science Center, KIST (Seoul, Korea), and the volunteers from POEM@HOME for computational resources; Y. Shen for RT-MLPA; S. West for zinc-finger prediction analysis; L. Chorich for her efforts in supervising and running the laboratory; and E. Shah for RT-PCR analysis.; We also acknowledge support to L.C.L. from National Institutes of Health (NIH) grants HD33004 and HD040287, as well as the Medical College of Georgia Research Institute (MCGRI), Dean D.D. Miller, Institute of Molecular Medicine and Genetics (IM-MAG) director R. Yu, and ob/gyn chair A.A. Murphy at MCG. J.F.G. has support from NIH grant GM061354, W.W. from Deutsche Forschungsgemeinschaft (DFG) grant WE1863/10-2 and the DFG Center for Functional Nanostructures, and I.M. from the EU Leonardo program "Unipharm Graduates." NR 42 TC 134 Z9 138 U1 1 U2 9 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 OCT 10 PY 2008 VL 83 IS 4 BP 511 EP 519 DI 10.1016/j.ajhg.2008.09.005 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 363AV UT WOS:000260239200009 PM 18834967 ER PT J AU Marban, E Braunwald, E AF Marban, Eduardo Braunwald, Eugene TI Training the clinician investigator SO CIRCULATION RESEARCH LA English DT Editorial Material C1 [Marban, Eduardo] Cedars Sinai Heart Inst, Los Angeles, CA 90048 USA. [Braunwald, Eugene] Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp, Boston, MA USA. RP Marban, E (reprint author), Cedars Sinai Heart Inst, 8700 Beverly Blvd, Los Angeles, CA 90048 USA. EM eduardo.marban@csmc.edu NR 0 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD OCT 10 PY 2008 VL 103 IS 8 BP 771 EP 772 DI 10.1161/CIRCRESAHA.108.186791 PG 2 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 358NX UT WOS:000259925900001 PM 18845813 ER PT J AU Mack, JW Joffe, S Hilden, JM Watterson, J Moore, C Weeks, JC Wolfe, J AF Mack, Jennifer W. Joffe, Steven Hilden, Joanne M. Watterson, Jan Moore, Caron Weeks, Jane C. Wolfe, Joanne TI Parents' views of cancer-directed therapy for children with no realistic chance for cure SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ORAL ETOPOSIDE; PHASE-I; TREATMENT PREFERENCES; CHEMOTHERAPY USE; NURSING RESEARCH; OVARIAN-CANCER; LIFE; END; CARE; AGGRESSIVENESS AB Purpose Previous literature suggests that parents often wish to continue cancer-directed therapy for their children with incurable cancer. We assessed parents' experiences with treatment for their children with cancer and no realistic chance of cure. Patients and Methods We administered questionnaires to 141 parents of children with cancer who died after receiving care at one of two cancer centers. Parents were asked whether the child benefited and suffered from treatment administered after the parent recognized that cure was not a realistic expectation, and whether they would recommend cancer-directed therapy to other families of children with advanced cancer. Results Fifty-three (38%) of 141 children received cancer-directed therapy after the parent recognized that the child had no realistic chance for cure. Most of these parents felt that their child had experienced at least some suffering resulting from the therapy (61%, 31 of 51) and little to no benefit (57%, 29 of 51). Fifty-one (38%) of 135 parents overall would recommend standard chemotherapy and 46 (33%) of 140 would recommend experimental chemotherapy to families of children with advanced cancer. Even parents who would not recommend standard chemotherapy generally felt the physician should offer it (91%, 88 of 97). Parents who reported that their children experienced suffering resulting from cancer-directed therapy ( odds ratio = 0.46; P = .02) were less likely to recommend standard chemotherapy to other families. Conclusion Although many parents choose treatment for their children with incurable cancer, bereaved parents often would not recommend such therapy. Parents who felt their children suffered as a result of cancer treatment were particularly unlikely to recommend it. C1 [Mack, Jennifer W.] 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 Med Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Peyton Manning Childrens Hosp St Vincent, Dept Pediat, Indianapolis, IN USA. Childrens Hosp & Clin, Dept Pediat Hematol Oncol, St Paul, MN 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 OI Joffe, Steven/0000-0002-0667-7384 FU National Cancer Institute [NCI 5 K07 CA 096746]; American Society of Clinical Oncology FX Supported by Grant No. NCI 5 K07 CA 096746 from the National Cancer Institute (J.W) and a Career Development Award from the American Society of Clinical Oncology (J.W.M.). NR 32 TC 38 Z9 38 U1 0 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 10 PY 2008 VL 26 IS 29 BP 4759 EP 4764 DI 10.1200/JCO.2007.15.6059 PG 6 WC Oncology SC Oncology GA 358FP UT WOS:000259902800012 PM 18779605 ER PT J AU Chanan-Khan, A Sonneveld, P Schuster, MW Stadtmauer, EA Facon, T Harousseau, JL Ben-Yehuda, D Lonial, S Goldschmidt, H Reece, D Neuwirth, R Anderson, KC Richardson, PG AF Chanan-Khan, Asher Sonneveld, Pieter Schuster, Michael W. Stadtmauer, Edward A. Facon, Thierry Harousseau, Jean-Luc Ben-Yehuda, Dina Lonial, Sagar Goldschmidt, Hartmut Reece, Donna Neuwirth, Rachel Anderson, Kenneth C. Richardson, Paul G. TI Analysis of herpes zoster events among bortezomib-treated patients in the phase III APEX study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol ID PROTEASOME INHIBITOR BORTEZOMIB; RELAPSED MULTIPLE-MYELOMA; REFRACTORY MYELOMA; VIRUS-INFECTION; CELLS; APOPTOSIS; DISEASE AB Purpose The aim of this subset analysis was to determine if bortezomib treatment is associated with increased incidence of varicella-zoster virus (VZV) reactivation in patients with relapsed multiple myeloma (MM). Patients and Methods Incidence of herpes zoster was evaluated in 663 patients with relapsed MM from the phase III APEX trial comparing single-agent bortezomib with high-dose dexamethasone. Results Bortezomib was associated with a significantly higher incidence of herpes zoster compared with dexamethasone treatment (13%, 42 of 331 v 5%, 15 of 332; P = .0002). Most herpes zoster infections were grade 1/2; incidences of grade 3/4 events (1.8% v 1.5%) and infections considered serious adverse events (1.5% v 0.9%) were similar between treatment arms, and no herpes zoster-related deaths occurred. Neither the time to onset of the herpes event nor the patients' absolute lymphocyte counts at baseline differed significantly between arms. VZV reactivation was the only herpes viral event noted to be significantly elevated in the bortezomib treatment group compared with the dexamethasone treatment group (P = 0002). The incidence of non-VZV-related herpes viral infections was comparable between arms. No additional risk factors for herpes zoster reactivation were identified. Conclusion Further studies are needed to explain these observations and their implications; however, for patients treated with bortezomib or bortezomib-containing regimens, the risk of VZV reactivation should be monitored and routine use of antiviral prophylaxis considered. C1 [Chanan-Khan, Asher] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. New York Presbyterian Hosp, New York, NY USA. Alta Bates Canc Ctr, Berkeley, CA USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Emory Univ, Atlanta, GA 30322 USA. Millennium Pharmaceut Inc, Cambridge, MA USA. Dana Farber Canc Inst, Boston, MA USA. Univ Rotterdam Hosp, Rotterdam, Netherlands. Hosp Claude Huriez, Lille, France. Hop Hotel Dieu, Nantes, France. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. Univ Klinikum Heidelberg, Heidelberg, Germany. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. RP Chanan-Khan, A (reprint author), Roswell Pk Canc Inst, Elm & Carlton St, Buffalo, NY 14263 USA. EM asher.chanan-khan@roswellpark.org RI FACON, THIERRY/M-9736-2014 OI FACON, THIERRY/0000-0001-7705-8460 NR 26 TC 130 Z9 133 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 10 PY 2008 VL 26 IS 29 BP 4784 EP 4790 DI 10.1200/JCO.2007.14.9641 PG 7 WC Oncology SC Oncology GA 358FP UT WOS:000259902800016 PM 18711175 ER PT J AU Bracht, LK Wen, P Meyerhardt, JA Kulke, MH Hornick, JL Redston, M LaFrankie, DC Black, PM Kesari, S Norden, A Drappatz, J AF Bracht, Lynn-Kristin Wen, Patrick Meyerhardt, Jeffrey A. Kulke, Matthew H. Hornick, Jason L. Redston, Mark LaFrankie, Debra Conrad Black, Peter M. Kesari, Santosh Norden, Andrew Drappatz, Jan TI DNA repair enzyme expression and differential response to temozolomide in a patient with both glioblastoma and metastatic pancreatic neuroendocrine tumor SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MGMT C1 [Bracht, Lynn-Kristin] Ctr Neurooncol, Boston, MA USA. [Bracht, Lynn-Kristin] Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Dana Farber Brigham & Womens Canc Ctr,Ctr Neuroon, Boston, MA 02115 USA. [Bracht, Lynn-Kristin] Univ Gottingen, Univ Klinikum, Fak Med, Gottingen, Germany. [Meyerhardt, Jeffrey A.; Kulke, Matthew H.] Dana Farber Brigham & Womens Canc Ctr, Dept Med Oncol, Boston, MA USA. [Hornick, Jason L.; Redston, Mark] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Redston, Mark] AmeriPath Inc, Palm Beach Gardens, FL USA. [Black, Peter M.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. RP Bracht, LK (reprint author), Ctr Neurooncol, Boston, MA USA. RI Kesari, Santosh/E-8461-2013 NR 7 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 10 PY 2008 VL 26 IS 29 BP 4843 EP 4844 DI 10.1200/JCO.2008.18.1776 PG 2 WC Oncology SC Oncology GA 358FP UT WOS:000259902800024 PM 18779600 ER PT J AU Gazzin, S Strazielle, N Schmitt, C Fevre-Montange, M Ostrow, JD Tiribelli, C Ghersi-Egea, JF AF Gazzin, Silvia Strazielle, Nathalie Schmitt, Charlotte Fevre-Montange, Michelle Ostrow, J. Donald Tiribelli, Claudio Ghersi-Egea, Jean-Francois TI Differential expression of the multidrug resistance-related proteins ABCb1 and ABCc1 between blood-brain interfaces SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE blood-brain barrier; choroid plexus; postnatal development; neuroprotection ID P-GLYCOPROTEIN EXPRESSION; CHOROID-PLEXUS; ENDOTHELIAL-CELLS; RAT-BRAIN; POSTNATAL MATURATION; BARRIER; TRANSPORT; MRP1; EFFLUX; DRUGS AB Cerebral homeostasis results from the presence of the protective blood-brain and blood-cerebrospinal fluid barriers located respectively at the brain capillary endothelium and the choroid plexus epithelium. ABCb1. (Pgp) and ABCc1 (Mrp1) transporters are two major proteins of neuroprotection whose localization and functional significance at both barriers remain partly unsettled. We conducted a comparative analysis of their relative protein content between the two blood-brain interfaces. Microvessels and choroid plexuses located in the fourth and lateral ventricles were isolated from developing and adult rat brains, and whole homogenates were submitted to quantitative Western blot analysis by using standard curves generated from one of the samples. In adult, choroid plexus-associated Pgp content was less than 0.5% of the level in microvessels, whereas Mrp1 content in microvessels was 4% of that in the fourth ventricle choroid plexus. Pgp but not Mrp1 was enriched in microvessels over parenchyma. In choroid plexuses, Mrp1 displayed a basolateral epithelial localization, and reached its high adult protein level, early during postnatal development. In postnatal as in adult microvessels, Pgp localization appeared luminal. However, by contrast to Mrp1, the level of this transporter increased 4.6-fold between 9-day-old and adult animals. Western blot analysis of human samples confirmed the mirror image of Pgp and Mrp1. expression between the two barriers. We conclude that there are major differences in the mechanisms by which blood-brain interfaces fulfill their neuroprotective functions. The data also highlight the significance of the neuroprotective function of the choroid plexus during brain maturation, when the microvasculature is still developing. C1 [Gazzin, Silvia; Strazielle, Nathalie; Schmitt, Charlotte; Fevre-Montange, Michelle; Ghersi-Egea, Jean-Francois] Univ Lyon, INSERM, U842, Fac Med Laennec, F-69372 Lyon, France. [Gazzin, Silvia; Tiribelli, Claudio] Univ Trieste, Ctr Fegato, Basovizza & Dept Life Sci, I-34012 Trieste, Italy. [Strazielle, Nathalie] Brain i, F-69008 Lyon, France. [Ostrow, J. Donald] Univ Washington, Sch Med, Div Gastroenterol Hepatol, Seattle, WA 98195 USA. [Ostrow, J. Donald] VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98195 USA. RP Ghersi-Egea, JF (reprint author), Univ Lyon, INSERM, U842, Fac Med RTH Laennec, Rue Guillaume Paradin, F-69372 Lyon 08, France. EM jean-francois.ghersi-egea@inserm.fr OI Ghersi-Egea, Jean-Francois/0000-0002-0181-4909 FU ANR [ANR-06-SEST-38-03]; Amelie la vie-ANOCEF; Telethon (Italy) [GGP 05062] FX Grant sponsor ANR; Grant number: ANR-06-SEST-38-03; Grant sponsor: Amelie la vie-ANOCEF; (to J.F.G.E.); Grant sponsor: Telethon (Italy): Grant number: GGP 05062 (to C.T.). NR 47 TC 72 Z9 73 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD OCT 10 PY 2008 VL 510 IS 5 BP 497 EP 507 DI 10.1002/cne.21808 PG 11 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 347ES UT WOS:000259124000004 PM 18680196 ER PT J AU Imamura, S Uchiyama, J Koshimizu, E Hanai, JI Raftopoulou, C Murphey, RD Bayliss, PE Imai, Y Burns, CE Masutomi, K Gagos, S Zon, LI Roberts, TM Kishi, S AF Imamura, Shintaro Uchiyama, Junzo Koshimizu, Eriko Hanai, Jun-ichi Raftopoulou, Christina Murphey, Ryan D. Bayliss, Peter E. Imai, Yoichi Burns, Caroline Erter Masutomi, Kenkichi Gagos, Sarantis Zon, Leonard I. Roberts, Thomas M. Kishi, Shuji TI A Non-Canonical Function of Zebrafish Telomerase Reverse Transcriptase Is Required for Developmental Hematopoiesis SO PLOS ONE LA English DT Article AB Although it is clear that telomerase expression is crucial for the maintenance of telomere homeostasis, there is increasing evidence that the TERT protein can have physiological roles that are independent of this central function. To further examine the role of telomerase during vertebrate development, the zebrafish telomerase reverse transcriptase (zTERT) was functionally characterized. Upon zTERT knockdown, zebrafish embryos show reduced telomerase activity and are viable, but develop pancytopenia resulting from aberrant hematopoiesis. The blood cell counts in TERT-depleted zebrafish embryos are markedly decreased and hematopoietic cell differentiation is impaired, whereas other somatic lineages remain morphologically unaffected. Although both primitive and definitive hematopoiesis is disrupted by zTERT knockdown, the telomere lengths are not significantly altered throughout early development. Induced p53 deficiency, as well as overexpression of the anti-apoptotic proteins Bcl-2 and E1B-19K, significantly relieves the decreased blood cells numbers caused by zTERT knockdown, but not the impaired blood cell differentiation. Surprisingly, only the reverse transcriptase motifs of zTERT are crucial, but the telomerase RNA-binding domain of zTERT is not required, for rescuing complete hematopoiesis. This is therefore the first demonstration of a non-canonical catalytic activity of TERT, which is different from 'authentic'' telomerase activity, is required for during vertebrate hematopoiesis. On the other hand, zTERT deficiency induced a defect in hematopoiesis through a potent and specific effect on the gene expression of key regulators in the absence of telomere dysfunction. These results suggest that TERT non-canonically functions in hematopoietic cell differentiation and survival in vertebrates, independently of its role in telomere homeostasis. The data also provide insights into a non-canonical pathway by which TERT functions to modulate specification of hematopoietic stem/progenitor cells during vertebrate development. (276 words) C1 [Imamura, Shintaro; Koshimizu, Eriko; Kishi, Shuji] Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02115 USA. [Uchiyama, Junzo; Bayliss, Peter E.; Roberts, Thomas M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA USA. [Hanai, Jun-ichi] Beth Israel Deaconess Med Ctr, Dept Med, Renal Div, Boston, MA USA. [Murphey, Ryan D.; Burns, Caroline Erter; Zon, Leonard I.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp Boston,Div Hematol Oncol, Boston, MA USA. [Raftopoulou, Christina; Gagos, Sarantis] Biomed Res Fdn Acad Athens Greece, Lab Genet, Athens, Greece. [Imai, Yoichi] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA USA. [Masutomi, Kenkichi] Natl Canc Ctr, Canc Stem Cell Project, Tokyo, Japan. RP Imamura, S (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02115 USA. EM s.kishi@mac.com FU A-T Childrens Project; Ellison Medical Foundation; NIA/NIH FX This work is funded by research grants from the A-T Childrens Project, the Ellison Medical Foundation and NIA/NIH to S.K.. NR 110 TC 28 Z9 28 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 10 PY 2008 VL 3 IS 10 AR e3364 DI 10.1371/journal.pone.0003364 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 432DU UT WOS:000265114500005 PM 18846223 ER PT J AU Casali, M Zambonelli, C Goldwasser, J Vu, HN Yarmush, ML AF Casali, Monica Zambonelli, Carlo Goldwasser, Jonathan Vu, Halong N. Yarmush, Martin L. TI Moloney murine leukemia virus decay mediated by retroviral reverse transcriptase degradation of genomic RNA SO VIROLOGY LA English DT Article DE gamma-retrovirus; moloney murine leukemia virus; virus decay; RNA and protein stability; viral reverse transcriptase ID RESPIRATORY SYNCYTIAL VIRUS; GENE-THERAPY; HUMAN SERUM; INFLUENZA-VIRUS; VIRAL VECTORS; RECOMBINANT RETROVIRUSES; LIPID-PEROXIDATION; CELL-LINES; TRANSDUCTION; MATURATION AB Retroviral vectors are powerful tools for the introduction of transgenes into mammalian cells and for long-term gene expression. However, their application is often limited by a rapid loss of bioactivity: retroviruses spontaneously loose activity at 37 degrees C, with a half-life of 4 to 9 h depending on the retrovirus type. We sought to determine which components of the retrovirus are responsible for this loss in bioactivity and to obtain a quantitative characterization of their stability. To this end, we focused on RNA and viral proteins, two major components that we hypothesized may undergo degradation and negatively influence viral infectivity. Reverse transcription PCR (RT-PCR) targeting RNA encoding portions of the viral genome clearly demonstrated time-dependent degradation of RNA which correlated with the loss in viral bioactivity. Circular dichroism spectroscopy, SDS-PAGE and two-dimensional SDS-PAGE analyses of viral proteins did not show any change in secondary structure or evidence of proteolysis. The mechanism underlying the degradation of viral RNA was investigated by site-directed mutagenesis of proteins encoded by the viral genome. Reverse transcriptase and protease mutants exhibited enhanced RNA stability in comparison to wild type recombinant virus, suggesting that the degradation of RNA, and the corresponding virus loss of activity, is mediated by the reverse transcriptase enzyme. (C) 2008 Elsevier Inc. All rights reserved. C1 [Casali, Monica; Goldwasser, Jonathan; Vu, Halong N.; Yarmush, Martin L.] Harvard Univ, Sch Med, Shriners Burn Hosp,Ctr Engn Med, Massachusetts Gen Hosp,Dept Surg, Boston, MA 02114 USA. [Zambonelli, Carlo] Harvard Univ, Mol & Cellular Biol Dept, Cambridge, MA 02138 USA. [Casali, Monica; Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Mscataway, NJ 08854 USA. RP Casali, M (reprint author), 51 Blossom St,Room 417, Boston, MA 02114 USA. EM mcasali@hms.harvard.edu; ireis@sbi.org FU National Science Foundation [CBET-0828244] FX We would like to thank Dr. Zaki Megeed for useful discussions, Z. L. Kelley for the excellent technical assistance and Dr. Xumbao Duan for his help with the two-dimensional electrophoresis gel analysis. The authors would like to thank also Professor Mary Roberts, Boston College Chemistry Department, for the use of the CD instrument.; This work was supported by National Science Foundation Grant CBET-0828244. NR 57 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 10 PY 2008 VL 380 IS 1 BP 91 EP 98 DI 10.1016/j.virol.2008.07.011 PG 8 WC Virology SC Virology GA 356TM UT WOS:000259800500012 PM 18706668 ER PT J AU Wang, X Qin, ZH Shi, H Savitz, SI Qin, AP Jiang, Y Zhang, HL AF Wang, Xuan Qin, Zheng-Hong Shi, Hong Savitz, Sean Isaac Qin, Ai-Ping Jiang, Yan Zhang, Hui-Ling TI Protective effect of Ginkgolids (A plus B) is associated with inhibition of NIK/IKK/I kappa B/NF-kappa B signaling pathway in a rat model of permanent focal cerebral ischemia SO BRAIN RESEARCH LA English DT Article DE Ginkgolids (A plus B); Ischemia; Neuroprotection; NF-kappa B; NIK-IKK ID CELL-DEATH; ACTIVATION; EXPRESSION; IKK; KINASE; ALPHA; PHOSPHORYLATION; JNK AB Background and purpose: We have previously reported that Ginkgolids which contain Ginkgolids A and B (Ginkgolids (A+B), GKAB) reduce infarct size in a rat model of focal ischemia. NF-kappa B-inducing kinase (NIK)I kappa B alpha kinase (IKK) pathway plays an important role in activation of nuclear factor kappaB (NF-kappa B). A previous study demonstrated that Ginkgolid B inhibited lipopolysaccharide (LPS)- and platelet activating factor (PAF)induced NF-kappa B activation in rat pleural polymorphonuclear granulocytes. However, little is known about the inhibitory mechanisms of Ginkgolids on the activation of NF-kappa B. The present study evaluated the effects of GKAB on NIK/IKK/I kappa B/NF-kappa B signaling pathway in a rat model of permanent focal cerebral ischemia.Methods: Rats were subjected to permanent middle cerebral artery occlusion (pMCAO) by intraluminal suture blockade. GKAB was injected intravenously (iv) immediately after ischemic onset. Western blot analysis was employed to determine alterations in I kappa B alpha, phosphorylated NIK (p-NIK) and phosphorylated IKK alpha (p-IKK alpha). Immunohistochemistry was used to confirm the nuclear translocation of NF-kappa B p65. RT-PCR was used to detect induction of NF-kappa B target gene c-Myc mRNA. Results: The results showed a brief increase in p-NIK levels after ischemia. GKAB blocked ischemia-induced increases in p-NIK and p-IKK alpha levels, and reversed the decline in I kappa B alpha levels. Ischemia-induced nuclear translocation of NF-kappa B p65 was attenuated by GKAB. GKAB also repressed the ischemia-induced increase in expression of NF-KB target gene c-Myc mRNA. Conclusions: These findings suggest that C1 [Wang, Xuan; Qin, Zheng-Hong; Qin, Ai-Ping; Zhang, Hui-Ling] Soochow Univ, Dept Pharmacol, Sch Med, Suzhou 215123, Peoples R China. [Wang, Xuan; Qin, Zheng-Hong; Qin, Ai-Ping; Zhang, Hui-Ling] Soochow Univ, Dept Pharmacol, Lab Aging & Nervous Dis, Suzhou 215123, Peoples R China. [Savitz, Sean Isaac; Jiang, Yan; Zhang, Hui-Ling] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. [Shi, Hong] Zhejiang Acad Med Sci, Dept Pharmacol, Hangzhou, Zhejiang, Peoples R China. [Wang, Xuan] Shanghai Putuo Dist Peoples Hosp, Dept Pharm, Shanghai, Peoples R China. RP Zhang, HL (reprint author), Soochow Univ, Dept Pharmacol, Sch Med, 199 Ren Ai Rd, Suzhou 215123, Peoples R China. EM huilingzhang07@hotmail.com FU Department of Education of Jinagsu Province [03KJB310123]; Natural Science Foundation of Jiangsu Province [BK2004037]; Zhejiang Province [Y205708]; Natural Science Foundation of China [30470587] FX This work was supported by grants from the Department of Education of Jinagsu Province (03KJB310123); The Natural Science Foundation of Jiangsu Province (BK2004037) and Zhejiang Province (Y205708); and The Natural Science Foundation of China (30470587). NR 32 TC 11 Z9 15 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 9 PY 2008 VL 1234 BP 8 EP 15 DI 10.1016/j.brainres.2008.07.102 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 363RZ UT WOS:000260285700002 PM 18722355 ER PT J AU Holschneider, DP Yang, J Sadler, TR Galifianakis, NB Bozorgzadeh, MH Bading, JR Conti, PS Maarek, JMI AF Holschneider, D. P. Yang, J. Sadler, T. R. Galifianakis, N. B. Bozorgzadeh, M. H. Bading, J. R. Conti, P. S. Maarek, J. -M. I. TI Changes in regional brain perfusion during functional brain activation: Comparison of [Cu-64]-PTSM with [C-14]-Iodoantipyrine SO BRAIN RESEARCH LA English DT Article DE Brain mapping; Motor activity; Cerebral blood flow; Copper radioisotope ID CEREBRAL-BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; GLUCOSE-METABOLISM; PET; TRACER; COPPER-62-PTSM; RADIOPHARMACEUTICALS; EXTRACTION; WALKING; MODEL AB A dilemma in behavioral brain mapping is that conventional techniques immobilize the subject, extinguishing all but the simplest behaviors. This is avoided if brain activation is imaged after completion of the behavior and tissue capture of the tracer. A single-pass flow tracer proposed for positron emission tomography (PET) is a radiolabeled copper(II) complex of pyruvaldehyde bis(N-4-methylthiosemicarbazone), [Cu-64]-PTSM. [Cu-64]-PTSM reaches steady-state cerebral distribution more rapidly than the metabolic tracer [F-18]fluorodeoxyglucose, allowing imaging with substantially greater temporal resolution. Using dual-label autoradiography, this study compares the relative regional cerebral blood flow tracer distribution (CBF-TR) of [Cu-64]-PTSM to that of the classic perfusion tracer [C-14]-iodoantipyrine in a rat model during treadmill walking. Rats were exposed to continuous walking on a treadmill and compared to quiescent controls. [Cu-64]-PTSM was bolus injected (iv) after 1 min, followed by a 5-minute uptake and subsequent bolus injection of [C-14]-iodoantipyrine. CBF-TR was quantified by autoradiography and analyzed in the three-dimensionally reconstructed brain by statistical parametric mapping, as well as by region-of-interest analysis. A high homology was found between the [Cu-64] -PTSM and [C-14]-iodoantipyrine patterns of cerebral activation in cortical and subcortical regions. For white matter, however, [Cu-64] -PTSM showed lower perfusion than [Cu-14] -iodoantipyrine. [Cu-64]-PTSM is a useful tracer for functional brain mapping in freely-moving subjects. Its application in conjunction with PET promises to increase our understanding of the neural circuitry of behaviors dependent on locomotion. (c) 2008 Elsevier B.V. All rights reserved. C1 [Holschneider, D. P.] Univ So Calif, Dept Cell & Neurobiol, Keck Sch Med, Los Angeles, CA 90089 USA. [Holschneider, D. P.; Yang, J.] Univ So Calif, Dept Psychiat & Behav Sci, Keck Sch Med, Los Angeles, CA 90089 USA. [Holschneider, D. P.; Galifianakis, N. B.] Univ So Calif, Dept Neurol, Keck Sch Med, Los Angeles, CA 90089 USA. [Sadler, T. R.] Univ So Calif, Dept Pathol, Keck Sch Med, Los Angeles, CA 90089 USA. [Bozorgzadeh, M. H.; Bading, J. R.; Conti, P. S.] Univ So Calif, Dept Radiol, Keck Sch Med, PET Imaging Sci Ctr, Los Angeles, CA 90089 USA. [Holschneider, D. P.; Conti, P. S.; Maarek, J. -M. I.] Univ So Calif, Dept Biomed Engn, Viterbi Sch Engn, Los Angeles, CA 90089 USA. [Holschneider, D. P.; Yang, J.] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. RP Holschneider, DP (reprint author), Univ So Calif, Dept Cell & Neurobiol, Keck Sch Med, 1333 San Pablo St,BMT 403,MC 9112, Los Angeles, CA 90089 USA. EM holschne@usc.edu FU Mallinckrodt Institute at Washington University; NCI [5R24CA086307-03]; NIMH [R21 MH073000]; NCRR [S10 RR15703] FX We would like to acknowledge Dr. X. Chen, Michel Tohme and Ryan Park, for their technical help in conducting the dynamic PET study, Pooja Sharma for her help with the selection of the regions of interest, and Dr. Oscar U. Scremin for his comments AA regarding the manuscript. [64CU] was obtained through the Research Resource in Radionuclide Research at the Mallinckrodt Institute at Washington University, St. Louis (NCI grant 5R24CA086307-03). Supported by grants from NIMH #R21 MH073000 (DH) and NCRR S10 RR15703 (PC). NR 35 TC 6 Z9 6 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 OCT 9 PY 2008 VL 1234 BP 32 EP 43 DI 10.1016/j.brainres.2008.07.038 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 363RZ UT WOS:000260285700005 PM 18687316 ER PT J AU Ay, I Francis, JW Brown, RH AF Ay, Ilknur Francis, Jonathan W. Brown, Robert H., Jr. TI VEGF increases blood-brain barrier permeability to Evans blue dye and tetanus toxin fragment C but not adeno-associated virus in ALS mice SO BRAIN RESEARCH LA English DT Article DE BBB; VEGF; Evans blue dye; Tetanus toxin fragment C; AAV2/5; SOD1(G93A) mice ID ENDOTHELIAL GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; CEREBRAL-ISCHEMIA; VIRAL VECTORS; NITRIC-OXIDE; DELIVERY; ANGIOGENESIS; DISRUPTION; CHEMOTHERAPY; EXPRESSION AB Entry of most compounds into the CNS is impeded by the blood-brain barrier (BBB). Because vascular endothelial growth factor (VEGF) is important in the formation and maintenance of the BBB and is known to modulate BBB permeability in newborn rodents, we tested the hypothesis that VEGF may enhance BBB permeability in adult mice. We examined the effect of VEGF on the CNS distribution of three different agents: a small molecule (Evans blue dye) that is known to bind plasma proteins, an exogenous protein (tetanus toxin fragment C; TTC), and a viral vector (recombinant adeno-associated virus serotype 2/5 marked with lacZ; rAAV2/S-lacZ). Pretreatment with VEGF (20 mu g; i.v.) increased permeability of the BBB to Evans blue dye and TTC as detected by augmented concentrations of these substances in the cerebrum, brainstem, and spinal cord. By contrast, VEGF did not alter BBB permeability to AAV2/S-lacZ, as defined by beta-galactosidase activity assay. These data demonstrate the potential utility of VEGF for pharmacological modulation of the BBB, and indicate that increase in BBB permeability mediated by VEGF is limited by the size of the delivered substance. (C) 2008 Elsevier B.V. All rights reserved. C1 [Ay, Ilknur; Francis, Jonathan W.; Brown, Robert H., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Day Neuromuscular Res Lab, Charlestown, MA USA. RP Ay, I (reprint author), Massachusetts Gen Hosp East, AA Martinos Ctr Biomed Imaging, Dept Radiol, 149 13th St, Boston, MA 02129 USA. EM iay@partners.org FU NIA; NINDS; ALS Association; Angel Fund; Al-Athel ALS Research Foundation; ALS Research Foundation; Muscular Dystrophy Association FX We thank Drs. Michele M. Maxwell and Zhanyun Fan for their assistance with these experiments. Robert H. Brown, Jr receives support from the NIA and NINDS, Project ALS, the ALS Association, the Angel Fund, the Al-Athel ALS Research Foundation, and the Pierre L. deBourghknect ALS Research Foundation. Jonathan W. Francis is supported by NINDS and the Muscular Dystrophy Association. NR 32 TC 26 Z9 26 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 9 PY 2008 VL 1234 BP 198 EP 205 DI 10.1016/j.brainres.2008.07.121 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 363RZ UT WOS:000260285700021 PM 18725212 ER PT J AU Viatour, P Somervaille, TC Venkatasubrahmanyam, S Kogan, S McLaughlin, ME Weissman, IL Butte, AJ Passegue, E Sage, J AF Viatour, Patrick Somervaille, Tim C. Venkatasubrahmanyam, Shivkumar Kogan, Scott McLaughlin, Margaret E. Weissman, Irving L. Butte, Atul J. Passegue, Emmanuelle Sage, Julien TI Hematopoietic Stem Cell Quiescence Is Maintained by Compound Contributions of the Retinoblastoma Gene Family SO CELL STEM CELL LA English DT Article ID BONE-MARROW MICROENVIRONMENT; SELF-RENEWAL; TUMOR-SUPPRESSOR; CYCLE; RB; MICE; STRESS; ERYTHROPOIESIS; LEUKEMIA; BMI-1 AB Individual members of the retinoblastoma (Rb) tumor suppressor gene family serve critical roles in the control of cellular proliferation and differentiation, but the extent of their contributions is masked by redundant and compensatory mechanisms. Here we employed a conditional knockout strategy to simultaneously inactivate all three members, Rb, p107, and p130, in adult hematopoietic stem cells (HSCs). Rb family triple knockout (TKO) mice develop a cell-intrinsic myeloproliferation that originates from hyperproliferative early hematopoietic progenitors and is accompanied by increased apoptosis in lymphoid progenitor populations. Loss of quiescence in the TKO HSC pool is associated with an expansion of these mutant stem cells but also with an enhanced mobilization and an impaired reconstitution potential upon transplantation. The presence of a single p107 allele Is sufficient to largely rescue these defects. Thus, Rb family members collectively maintain HSC quiescence and the balance between lymphoid and myeloid cell fates in the hematopoietic system. C1 [Viatour, Patrick; Venkatasubrahmanyam, Shivkumar; Butte, Atul J.; Sage, Julien] Stanford Med Sch, Dept Pediat, Stanford, CA 94305 USA. [Viatour, Patrick; Sage, Julien] Stanford Med Sch, Dept Genet, Stanford, CA 94305 USA. [Somervaille, Tim C.; Weissman, Irving L.] Stanford Med Sch, Dept Pathol, Stanford, CA 94305 USA. [Venkatasubrahmanyam, Shivkumar; Butte, Atul J.] Stanford Med Sch, Dept Med, Stanford, CA 94305 USA. [McLaughlin, Margaret E.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Kogan, Scott] Univ Calif San Francisco, Ctr Comprehens Canc, Dept Lab Med, San Francisco, CA 94143 USA. [Passegue, Emmanuelle] Univ Calif San Francisco, Ctr Comprehens Canc, Inst Regenerat Med, San Francisco, CA 94143 USA. [Viatour, Patrick] Univ Liege, Dept Med Chem, B-4000 Liege, Belgium. RP Sage, J (reprint author), Stanford Med Sch, Dept Pediat, Stanford, CA 94305 USA. EM julsage@stanford.edu OI Somervaille, Tim/0000-0002-9188-4379 FU Lucile Packard Foundation for Children's Health; Damon Runyon Cancer Research Foundation; NIH-NCI [RO1 CA114102, PO1 CA049605]; Human Frontier Science Program; European Molecular Biology Organization; Fonds de la Recherche Scientifique; Leon Fredericq Foundation; California Institute for Regenerative Medicine; Leukemia and Lymphoma Society FX The authors thank Tom Serwold, Anne Brunet, and Steven Artandi for critical reading of the manuscript; Jinkuk Choi for his help with the initial microarray analysis; Michael Cleary for his support and helpful discussions; and Tyler Jacks for the generous provision of mutant mice generated in his laboratory. This work was supported by the Lucile Packard Foundation for Children's Health (J.S. and A.J.B.); the Damon Runyon Cancer Research Foundation and NIH-NCI RO1 CA114102 (J.S.); fellowships from the Human Frontier Science Program, the European Molecular Biology Organization, the Fonds de la Recherche Scientifique, and the Leon Fredericq Foundation (P.V.); and the California Institute for Regenerative Medicine and NIH-NCI PO1 CA049605 (A.J.B.). S.K. is a Leukemia and Lymphoma Society scholar. NR 44 TC 90 Z9 91 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD OCT 9 PY 2008 VL 3 IS 4 BP 416 EP 428 DI 10.1016/j.stem.2008.07.009 PG 13 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 361TK UT WOS:000260149800012 PM 18940733 ER PT J AU Makris, N Gasic, GP Kennedy, DN Hodge, SM Kaiser, JR Lee, MJ Kim, YW Blood, AJ Evins, AE Seidman, LJ Iosifescu, DV Lee, S Baxter, C Perlis, RH Smoller, JW Fava, M Breiter, HC AF Makris, Nikos Gasic, Gregory P. Kennedy, David N. Hodge, Steven M. Kaiser, Jonathan R. Lee, Myung Joo Kim, Byoung Woo Blood, Anne J. Evins, A. Eden Seidman, Larry J. Iosifescu, Dan V. Lee, Sang Baxter, Claudia Perlis, Roy H. Smoller, Jordan W. Fava, Maurizio Breiter, Hans C. TI Cortical Thickness Abnormalities in Cocaine Addiction-A Reflection of Both Drug Use and a Pre-existing Disposition to Drug Abuse? SO NEURON LA English DT Article ID ANTERIOR CINGULATE CORTEX; VERBAL WORKING-MEMORY; HUMAN CEREBRAL-CORTEX; HEART-RATE-VARIABILITY; LEFT-RIGHT ASYMMETRY; DECISION-MAKING; ORBITOFRONTAL CORTEX; PREFRONTAL CORTEX; HUMAN BRAIN; NONPSYCHOTIC RELATIVES AB The structural effects of cocaine on neural systems mediating cognition and motivation are not well known. By comparing the thickness of neocortical and paralimbic brain regions between cocaine-dependent and matched control subjects, we found that four of 18 a priori regions involved with executive regulation of reward and attention were significantly thinner in addicts. Correlations were significant between thinner prefrontal cortex and reduced key-presses during judgment and decision making of relative preference in addicts, suggesting one basis for restricted behavioral repertoires in drug dependence. Reduced effortful attention performance in addicts also correlated with thinner paralimbic cortices. Some thickness differences in addicts were correlated with cocaine use independent of nicotine and alcohol, but addicts also showed diminished thickness heterogeneity and altered hemispheric thickness asymmetry. These observations suggest that brain structure abnormalities in addicts are related in part to drug use and in part to predisposition toward addiction. C1 [Makris, Nikos; Blood, Anne J.; Evins, A. Eden; Seidman, Larry J.; Iosifescu, Dan V.; Lee, Sang; Perlis, Roy H.; Smoller, Jordan W.; Fava, Maurizio; Breiter, Hans C.] Massachusetts Gen Hosp, Addict Res Program, Depress Clin & Res Program, Boston, MA 02114 USA. [Makris, Nikos; Blood, Anne J.; Evins, A. Eden; Seidman, Larry J.; Iosifescu, Dan V.; Lee, Sang; Perlis, Roy H.; Smoller, Jordan W.; Fava, Maurizio; Breiter, Hans C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Makris, Nikos; Blood, Anne J.; Evins, A. Eden; Seidman, Larry J.; Iosifescu, Dan V.; Lee, Sang; Perlis, Roy H.; Smoller, Jordan W.; Fava, Maurizio; Breiter, Hans C.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Perlis, Roy H.; Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Perlis, Roy H.; Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Gasic, Gregory P.; Kennedy, David N.; Lee, Myung Joo; Kim, Byoung Woo; Seidman, Larry J.; Lee, Sang; Baxter, Claudia; Breiter, Hans C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, MENC, Charlestown, MA 02129 USA. [Gasic, Gregory P.; Kennedy, David N.; Lee, Myung Joo; Kim, Byoung Woo; Seidman, Larry J.; Lee, Sang; Baxter, Claudia; Breiter, Hans C.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. [Makris, Nikos; Gasic, Gregory P.; Kennedy, David N.; Hodge, Steven M.; Kaiser, Jonathan R.; Lee, Myung Joo; Kim, Byoung Woo; Seidman, Larry J.; Lee, Sang; Baxter, Claudia; Breiter, Hans C.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Makris, Nikos; Kennedy, David N.; Hodge, Steven M.; Kaiser, Jonathan R.] Massachusetts Gen Hosp, Ctr Integrat Informat, Ctr Morphometr Anal, Charlestown, MA 02129 USA. [Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Publ Psychiat Div, Massachusetts Mental Hlth Ctr, Boston, MA 02215 USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Boston, MA 02215 USA. EM hbreiter@partners.org RI Kennedy, David/H-3627-2012; OI Lee, Sang Han/0000-0001-9760-393X FU NCCIH NIH HHS [P01 AT002048]; NCRR NIH HHS [P41 RR014075, M01 RR001066, P41RR14075]; NIDA NIH HHS [K23 DA000510]; PHS HHS [14118, 34189] NR 91 TC 62 Z9 62 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD OCT 9 PY 2008 VL 60 IS 1 BP 174 EP 188 DI 10.1016/j.neuron.2008.08.011 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 363AC UT WOS:000260237300017 PM 18940597 ER PT J AU Merkel, PA McCarty, D Sharma, A Stone, JR Rosenberg, ES Seton, M AF Merkel, Peter A. McCarty, David Sharma, Amita Stone, James R. Rosenberg, Eric S. Seton, Margaret TI A man with chest pain, arthralgias, and a mediastinal mass - Wegener's granulomatosis involving the mediastinum, heart, and pulmonary artery SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; ANTIMYELOPEROXIDASE ANTIBODIES; VASCULITIS; PREVALENCE; COHORT C1 [Merkel, Peter A.] Boston Univ, Sch Med, Ctr Arthritis, Boston Med Ctr, Boston, MA 02118 USA. [Merkel, Peter A.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [McCarty, David] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Sharma, Amita] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Stone, James R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [McCarty, David] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Sharma, Amita] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Stone, James R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Merkel, PA (reprint author), Boston Univ, Sch Med, Ctr Arthritis, Boston Med Ctr, Boston, MA 02118 USA. FU Merck; Muscle Tech; GlaxoSmithKline; Proteon Therapeutics; Genzyme; Bristol-Myers Squibb; Genentech FX Dr. Stone reports receiving consulting fees from Merck, Muscle Tech, GlaxoSmithKline, and Proteon Therapeutics. Dr. Merkel reports receiving research support from Genzyme (to Boston University) and from Bristol-Myers Squibb and Genentech (for research also sponsored by the National Institutes of Health). NR 16 TC 1 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 9 PY 2008 VL 359 IS 15 BP 1603 EP 1614 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 358FS UT WOS:000259903100011 PM 18843125 ER PT J AU Nandakumar, V Singh, T Katiyar, SK AF Nandakumar, Vijayalakshmi Singh, Tripti Katiyar, Santosh K. TI Multi-targeted prevention and therapy of cancer by proanthocyanidins SO CANCER LETTERS LA English DT Review DE Proanthocyanidins; Cancer prevention; Interleukin; Matrix metalloproteinases; Ultraviolet radiation ID GRAPE SEED PROANTHOCYANIDINS; NF-KAPPA-B; INDUCED OXIDATIVE STRESS; PROSTATE TUMOR-GROWTH; SKH-1 HAIRLESS MICE; IN-VITRO; CARCINOMA-CELLS; INDUCE APOPTOSIS; PHENOLIC-ACIDS; DIETARY AGENTS AB In recent years, a considerable emphasis has been focused on the importance of the naturally available botanicals that can be consumed in an individual's everyday diet and that can also be useful as a chemopreventive or chemotherapeutic agent for certain diseases, including cancers. A wide variety of botanicals, mostly dietary flavonoids or polyphenolic substances, have been reported to possess substantial anti-carcinogenic and antimutagenic activities because of their antioxidant and anti-inflammatory properties. Proanthocyanidins are considered as one of them, and are abundantly available in various parts of the plants, such as fruits, berries, bark and seeds. Their modes of action were evaluated through a number of in vitro and in vivo studies which showed their potential role as anti-carcinogenic agent. We summarize and highlight the latest developments on anti-carcinogenic activities of proanthocyanidins from different sources, specifically from grape seeds, and their molecular targets, such as NF-kappa B, mitogen-activated protein kinases, PI3K/Akt, caspases, cytokines, angiogenesis and cell cycle regulatory proteins and other check points, etc. Although the bioavailability and metabolism data on proanthocyanidins is still largely unavailable, certain reports indicate that at least monomers and smaller oligomeric procyanidins are absorbed in the gut. The modulation of various molecular targets by proanthocyanidins in vitro and in vivo tumor models suggests their importance, contribution and mechanism of action to the prevention of cancers of different organs. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Nandakumar, Vijayalakshmi; Singh, Tripti; Katiyar, Santosh K.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama, Clin Nutr Res Ctr, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham VA Med Ctr, Birmingham, AL 35294 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 National Cancer Institute/NIH [CA104428]; Veterans Affairs Merit Review Award FX The work reported from the author's laboratory was supported by the funds from National Cancer Institute/NIH (CA104428) and Veterans Affairs Merit Review Award (S.K.K.). The content of this article does not necessarily reflect the views or policies of the funding sources. The authors apologize for not discussing and citing several valuable publications because of the limitations of space and the number of references. NR 58 TC 138 Z9 142 U1 5 U2 34 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD OCT 8 PY 2008 VL 269 IS 2 BP 378 EP 387 DI 10.1016/j.canlet.2008.03.049 PG 10 WC Oncology SC Oncology GA 361QZ UT WOS:000260143500017 PM 18457915 ER PT J AU Liu, LB Brown, D Mckee, M LeBrasseur, NK Yang, D Albrecht, KH Ravid, K Pilch, PF AF Liu, Libin Brown, Dennis McKee, Mary LeBrasseur, Nathan K. Yang, Dan Albrecht, Kenneth H. Ravid, Katya Pilch, Paul F. TI Deletion of Cavin/PTRF Causes Global Loss of Caveolae, Dyslipidemia, and Glucose Intolerance SO CELL METABOLISM LA English DT Article ID TRANSCRIPT RELEASE FACTOR; RIPPLING MUSCLE DISEASE; INSULIN-RESISTANCE; LIPID DROPLETS; MUSCULAR-DYSTROPHY; ADIPOCYTE CAVEOLAE; SKELETAL-MUSCLE; KNOCKOUT MICE; POLYMERASE-I; GENE FAMILY AB Caveolae are specialized invaginations of the plasma membrane found in numerous cell types. They have been implicated as playing a role in a variety of physiological processes and are typically characterized by their association with the caveolin family of proteins. We show here by means of targeted gene disruption in mice that a distinct caveolae-associated protein, Cavin/PTRF, is an essential component of caveolae. Animals lacking Cavin have no morphologically detectable caveolae in any cell type examined and have markedly diminished protein expression of all three caveolin isoforms while retaining normal or above normal caveolin mRNA expression. Cavin-knockout mice are viable and of normal weight but have higher circulating triglyceride levels, significantly reduced adipose tissue mass, glucose intolerance, and hyperinsulinemia-characteristics that constitute a lipodystrophic phenotype. Our results underscore the multiorgan role of caveolae in metabolic regulation and the obligate presence of Cavin for caveolae formation. C1 [Liu, Libin; Yang, Dan; Ravid, Katya; Pilch, Paul F.] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. [Brown, Dennis; McKee, Mary] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. [Brown, Dennis; McKee, Mary] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Brown, Dennis; McKee, Mary] Harvard Univ, Sch Med, Boston, MA 02114 USA. [LeBrasseur, Nathan K.] Boston Univ, Sch Med, Dept Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA. [Albrecht, Kenneth H.] Boston Univ, Sch Med, Dept Med, Genet Program, Boston, MA 02118 USA. [Albrecht, Kenneth H.] Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA. RP Pilch, PF (reprint author), Boston Univ, Sch Med, Dept Biochem, 715 Albany St, Boston, MA 02118 USA. EM ppilch@bu.edu OI Albrecht, Kenneth/0000-0002-9769-3362; Ravid, Katya/0000-0002-9918-3024; Pilch, Paul/0000-0003-1997-0499; LeBrasseur, Nathan/0000-0002-2002-0418 FU National Institutes of Health [DK38452, DK42596, AG031154, NH13262, HD42779, DK30425, DK56935]; Microscopy Core Facility; Boston Area Diabetes and Endocrinology Research Center [DK 57521] FX We thank Greg Martin from the Boston University School of Medicine Transgenic Core, Michelle Ganno from the Metabolic Phenotypic Core, and Maria Makitalo for assistance in producing targeted ES cells. Mouse BAC clones were kindly provided by The Wellcome Trust Sanger Institute (Cambridge, UK), This work was supported by National Institutes of Health grants DK38452 and DK42596 to D.B., AG031154 to N.K.L., NH13262 to K.R., HD42779 to K.H.A., and DK30425 and DK56935 to P.F.P. D.B. is also supported by the Microscopy Core Facility of the MGH Program in Membrane Biology and by the Boston Area Diabetes and Endocrinology Research Center grant, DK 57521. NR 44 TC 154 Z9 157 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD OCT 8 PY 2008 VL 8 IS 4 BP 310 EP 317 DI 10.1016/j.cmet.2008.07.008 PG 8 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 358DP UT WOS:000259897200007 PM 18840361 ER PT J AU Wright, AA Zhang, BH Ray, A Mack, JW Trice, E Balboni, T Mitchell, SL Jackson, VA Block, SD Maciejewski, PK Prigerson, HG AF Wright, Alexi A. Zhang, Baohui Ray, Alaka Mack, Jennifer W. Trice, Elizabeth Balboni, Tracy Mitchell, Susan L. Jackson, Vicki A. Block, Susan D. Maciejewski, Paul K. Prigerson, Holly G. TI Associations between end-of-life discussions, patient mental health, medical care near death, and caregiver bereavement adjustment SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ADVANCED CANCER-PATIENTS; TREATMENT PREFERENCES; FAMILY CAREGIVERS; IMMINENT DEATH; SERIOUSLY ILL; BAD-NEWS; COMMUNICATION; PROGNOSIS; PHYSICIANS; ILLNESS AB Context Talking about death can be difficult. Without evidence that end- of- life discussions improve patient outcomes, physicians must balance their desire to honor patient autonomy against a concern of inflicting psychological harm. Objective To determine whether end- of- life discussions with physicians are associated with fewer aggressive interventions. Design, Setting, and Participants A US multisite, prospective, longitudinal cohort study of patients with advanced cancer and their informal caregivers ( n= 332 dy-ads), September 2002- February 2008. Patients were followed up from enrollment to death, a median of 4.4 months later. Bereaved caregivers' psychiatric illness and quality of life was assessed a median of 6.5 months later. Main Outcome Measures Aggressive medical care ( eg, ventilation, resuscitation) and hospice in the final week of life. Secondary outcomes included patients' mental health and caregivers' bereavement adjustment. Results One hundred twenty- three of 332 ( 37.0%) patients reported having end-of-life discussions before baseline. Such discussions were not associated with higher rates of major depressive disorder ( 8.3% vs 5.8%; adjusted odds ratio [ OR], 1.33; 95% confidence interval [ CI], 0.54- 3.32), or more worry ( mean McGill score, 6.5 vs 7.0; P=. 19). After propensity- score weighted adjustment, end- of- life discussions were associated with lower rates of ventilation ( 1.6% vs 11.0%; adjusted OR, 0.26; 95% CI, 0.08- 0.83), resuscitation ( 0.8% vs 6.7%; adjusted OR, 0.16; 95% CI, 0.03- 0.80), ICU admission ( 4.1% vs 12.4%; adjusted OR, 0.35; 95% CI, 0.14- 0.90), and earlier hospice enrollment ( 65.6% vs 44.5%; adjusted OR, 1.65; 95% CI, 1.04- 2.63). In adjusted analyses, more aggressive medical care was associated with worse patient quality of life ( 6.4 vs 4.6; F= 3.61, P=. 01) and higher risk of major depressive disorder in bereaved caregivers ( adjusted OR, 3.37; 95% CI, 1.12- 10.13), whereas longer hospice stays were associated with better patient quality of life ( mean score, 5.6 vs 6.9; F= 3.70, P=. 01). Better patient quality of life was associated with better caregiver quality of life at follow- up (beta=. 20; P=. 001). Conclusions End- of- life discussions are associated with less aggressive medical care near death and earlier hospice referrals. Aggressive care is associated with worse patient quality of life and worse bereavement adjustment. C1 [Wright, Alexi A.; Trice, Elizabeth] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wright, Alexi A.; Zhang, Baohui; Ray, Alaka; Trice, Elizabeth; Balboni, Tracy; Block, Susan D.; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. [Mack, Jennifer W.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Ray, Alaka; Jackson, Vicki A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Balboni, Tracy] Harvard Univ, Harvard Radiat Oncol Program, Boston, MA USA. [Jackson, Vicki A.; Block, Susan D.; Prigerson, Holly G.] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. [Mitchell, Susan L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Block, Susan D.; Maciejewski, Paul K.; Prigerson, Holly G.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Wright, AA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 550 Shields Warren,44 Binney St, Boston, MA 02115 USA. EM awright2@partners.org FU National Cancer Institute [CA 106370]; National Institute of Mental Health [MH63892]; National Cancer Institute's "Program in Cancer Outcomes Research Training" [CA 92044343]; Dana-Farber Cancer Institute's Friends Fellowship FX This study was supported by grants CA 106370 from the National Cancer Institute and MH63892 from the National Institute of Mental Health. Dr Wright was supported, in part, by grant CA 92044343, which is part of the National Cancer Institute's "Program in Cancer Outcomes Research Training" and by the Dana-Farber Cancer Institute's Friends Fellowship. NR 50 TC 729 Z9 732 U1 16 U2 84 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 8 PY 2008 VL 300 IS 14 BP 1665 EP 1673 DI 10.1001/jama.300.14.1665 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 356YF UT WOS:000259812800028 PM 18840840 ER PT J AU Chung, DC AF Chung, Daniel C. TI Stool DNA testing and colon cancer prevention: Another step forward SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID FECAL OCCULT-BLOOD; COLORECTAL-CANCER; TASK-FORCE; NEOPLASIA; METHYLATION; MUTATIONS C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Chung, DC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825,50 Blossom St, Boston, MA 02114 USA. EM dchung@partners.org NR 14 TC 9 Z9 9 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 7 PY 2008 VL 149 IS 7 BP 509 EP 510 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 359QY UT WOS:000260004400008 PM 18838731 ER PT J AU Kalaitzidis, D Gilliland, DG AF Kalaitzidis, Demetrios Gilliland, D. Gary TI Going with the flow: JAK-STAT signaling in JMML SO CANCER CELL LA English DT Editorial Material ID JUVENILE MYELOMONOCYTIC LEUKEMIA; COLONY-STIMULATING FACTOR; MICE; DISEASE; CANCER; CELLS AB Knowledge of the distinctive cellular and genetic traits of a cancer aids in diagnosis, prognosis, and potentially treatment. In this issue of Cancer Cell, Kotecha et al. (2008) demonstrate using a sophisticated flow cytometry approach that signal transduction responses to exogenous stimulation can inform diagnosis and pathobiology of myeloproliferative neoplasms. C1 Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Howard Hughes Med Inst, Broad Inst MIT, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Kalaitzidis, D (reprint author), Brigham & Womens Hosp, Dept Med, Div Hematol, 75 Francis St, Boston, MA 02115 USA. EM ggilliland@rics.bwh.harvard.edu; dkalaitzidis@partners.org FU Howard Hughes Medical Institute NR 10 TC 6 Z9 7 U1 0 U2 5 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 OCT 7 PY 2008 VL 14 IS 4 BP 279 EP 280 DI 10.1016/j.ccr.2008.09.006 PG 2 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 358DI UT WOS:000259896500001 PM 18835028 ER PT J AU Antman, EM AF Antman, Elliott M. TI Time is muscle - Translation into practice SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE ST-segment elevation myocardial infarction; reperfusion; guidelines ID ACUTE MYOCARDIAL-INFARCTION; PERCUTANEOUS CORONARY INTERVENTION; ST-SEGMENT-ELEVATION; PRIMARY ANGIOPLASTY; FIBRINOLYTIC THERAPY; PREHOSPITAL FIBRINOLYSIS; REPERFUSION STRATEGY; THROMBOLYTIC THERAPY; RANDOMIZED-TRIALS; CARE AB In the future, advances in the care of patients with ST-segment elevation myocardial infarction (STEMI) will not come from the analysis of trials that do not reflect current practice in an effort to rationalize extending the percutaneous coronary intervention (PCI)-related delay time. We must move beyond such arguments and find ways to shorten total ischemic time. With the launching of the American College of Cardiology's D2B Alliance and the American Heart Association's Mission: Lifeline programs, the focus is now on systems improvement for reperfusion in patients with STEMI. The D2B Alliance was developed to focus on improvement in door-to-balloon times for patients with STEMI who are undergoing primary PCI. The American Heart Association Mission: Lifeline program is a broad, comprehensive national initiative to improve the quality of care and outcomes of patients with STEMI by improving health care system readiness and response to STEMI. Improvements in access to timely care for patients with STEMI will require a multifaceted approach involving patient education, improvements in the Emergency Medical Services and emergency department components of care, the establishment of networks of STEMI-referral hospitals (not PCI capable) and STEMI-receiving hospitals (PCI capable), as well as coordinated advocacy efforts to work with payers and policy makers to implement a much-needed health care system redesign. By focusing now on system efforts for improvements in timely care for STEMI, we will complete the cycle of research initiated by Reimer and Jennings 30 years ago. Time is muscle... we must translate that into practice. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. RP Antman, EM (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM eantman@rics.bwh.harvard.edu NR 37 TC 53 Z9 56 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 7 PY 2008 VL 52 IS 15 BP 1216 EP 1221 DI 10.1016/j.jacc.2008.07.011 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 355RY UT WOS:000259727200003 PM 18926324 ER PT J AU Upadhyay, GA Choudhry, NK Auricchio, A Ruskin, J Singh, JP AF Upadhyay, Gaurav A. Choudhry, Niteesh K. Auricchio, Angelo Ruskin, Jeremy Singh, Jagmeet P. TI Cardiac resynchronization in patients with atrial fibrillation - A meta-analysis of prospective cohort studies SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE atrial fibrillation; biventricular pacemaker; cardiac resynchronization; congestive heart failure treatment ID CHRONIC HEART-FAILURE; ATRIOVENTRICULAR JUNCTION ABLATION; RANDOMIZED CONTROLLED-TRIALS; SINUS RHYTHM; PERMANENT PACEMAKER; CONDUCTION DELAY; THERAPY; SURVIVAL; TRENDS; IMPLANTATION AB Objectives This study is a meta-analysis of prospective cohort studies comparing the impact of cardiac resynchronization therapy (CRT) for patients in atrial fibrillation (AF) and sinus rhythm (SR). Background Although close to one-third of advanced heart failure patients exhibit AF, the impact of CRT in this group remains unclear. Methods Prospective cohort studies comparing patients in normal SR and chronic AF treated with CRT were included. All studies reported death, New York Heart Association functional class, rejection fraction, 6-min walk test, and the Minnesota score or its equivalent as outcomes. Data sources included Ovid MEDLINE In-Process & Other Non-Indexed Citations, the Cochrane Central Register of Controlled Trials, the Database of Abstracts of Reviews of Effects, and the American College of Physicians Journal Club. Results Of 2,487 reports identified, 5 studies following a total of 1,164 patients were included. Both AF and SR patients benefited significantly from CRT. Mortality was not significantly different at 1 year (relative risk ratio: 1.57, 95% confidence interval [ CI]: 0.87 to 2.81). The New York Heart Association functional class improved similarly for both groups (-0.90 for SR patients,-0.84 for AF patients). SR patients showed greater relative improvement in the 6-min walk test (11.6 m greater, 95% CI: 10.4 to 12.8 m) and the Minnesota score (3.9 points less, 95% CI: 3.4 to 4.5 points) than AF patients. AF patients, however, achieved a small but statistically significant greater change in ejection fraction (0.39% greater change in ejection fraction, 95% CI: 0.22% to 0.55%). Conclusions Patients in AF show significant improvement after CRT, with similar or improved ejection fraction as SR patients, but smaller benefits in regard to functional outcomes. C1 [Singh, Jagmeet P.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Div Cardiol, Boston, MA 02114 USA. [Upadhyay, Gaurav A.; Ruskin, Jeremy; Singh, Jagmeet P.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Choudhry, Niteesh K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Auricchio, Angelo] Fdn Cardioctr Ticino, Div Cardiol, Lugano, Switzerland. RP Singh, JP (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Div Cardiol, Gray Bldg 109,55 Fruit St, Boston, MA 02114 USA. EM jsingh@partners.org FU Boston Scientific; Medtronic; St. Jude Medical; Biotronik FX Dr. Auricchio is a consultant to Medtronic and the Sorin Group; has received research grants from Boston Scientific, Medtronic, St. Jude Medical and Biotronik; and has lectured for Boston Scientific, Medtronic, St. Jude Medical, Sorin, and Biotronik. Dr. Ruskin is a consultant to Medtronic; is a part of the Fellows programs for St. Jude Medical and Boston Scientific; and has received research support from St. Jude Medical. Dr. Singh is a consultant to Biotronik, Boston Scientific, Medtronic, and St. Jude Medical; has lectured for Biotronik, Boston Scientific, Medtronic, St. Jude Medical, and the Sorin Group; and has received research grants from Biotronik, Boston Scientific, Medtronic, and St. Jude Medical. NR 34 TC 93 Z9 97 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 7 PY 2008 VL 52 IS 15 BP 1239 EP 1246 DI 10.1016/j.jacc.2008.06.043 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 355RY UT WOS:000259727200006 PM 18926327 ER PT J AU Li, ZJ Lu, J Sun, M Mi, SL Zhang, H Luo, RT Chen, P Wang, YG Yan, M Qian, ZJ Neilly, MB Jin, J Zhang, YM Bohlander, SK Zhang, DE Larson, RA Le Beau, MM Thirman, MJ Golub, TR Rowley, JD Chen, JJ AF Li, Zejuan Lu, Jun Sun, Miao Mi, Shuangli Zhang, Hao Luo, Roger T. Chen, Ping Wang, Yungui Yan, Ming Qian, Zhijian Neilly, Mary Beth Jin, Jie Zhang, Yanming Bohlander, Stefan K. Zhang, Dong-Er Larson, Richard A. Le Beau, Michelle M. Thirman, Michael J. Golub, Todd R. Rowley, Janet D. Chen, Jianjun TI Distinct microRNA expression profiles in acute myeloid leukemia with common translocations SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE apoptosis and cell viability and proliferation; core binding factor (CBF); microRNA expression profiling; miR-126; PLK2 ID ACUTE LYMPHOBLASTIC-LEUKEMIA; GENE-EXPRESSION; CANCER; TARGET; CELLS; DIFFERENTIATION; POLO-LIKE-KINASE-2; IDENTIFICATION; ORGANIZATION; MALIGNANCIES AB MicroRNAs (miRNAs) are postulated to be important regulators in cancers. Here, we report a genome-wide miRNA expression analysis in 52 acute myeloid leukemia (AML) samples with common translocations, including t(8;21)/AML1(RUNX1)-ETO(RUNX1T1), inv(16)/CBFB-MYH11, t(15;17)/PML-RARA, and MLL rearrangements. Distinct miRNA expression patterns were observed for t(15;17), MLL rearrangements, and core-binding factor (CBF) AMLs including both t(8;21) and inv(16) samples. Expression signatures of a minimum of two (i.e., miR-126/126*), three (i.e., miR-224, miR-368, and miR-382), and seven (miR-17-5p and miR-20a, plus the aforementioned five) miRNAs could accurately discriminate CBF, t(15;17), and MLL-rearrangement AMLs, respectively, from each other. We further showed that the elevated expression of miR-126/126* in CBF AMLs was associated with promoter demethylation but not with amplification or mutation of the genomic locus. Our gain- and loss-of-function experiments showed that miR-126/ 126* inhibited apoptosis and increased the viability of AML cells and enhanced the colony-forming ability of mouse normal bone marrow progenitor cells alone and particularly, in cooperation with AML1-ETO, likely through targeting Polo-like kinase 2 (PLK2), a tumor suppressor. Our results demonstrate that specific alterations in miRNA expression distinguish AMLs with common translocations and imply that the deregulation of specific Ill may play a role in the development of leukemia with these associated genetic rearrangements. C1 [Lu, Jun; Zhang, Hao; Golub, Todd R.] Broad Inst, Cambridge, MA 02141 USA. [Li, Zejuan; Sun, Miao; Mi, Shuangli; Luo, Roger T.; Chen, Ping; Qian, Zhijian; Neilly, Mary Beth; Zhang, Yanming; Larson, Richard A.; Le Beau, Michelle M.; Thirman, Michael J.; Rowley, Janet D.; Chen, Jianjun] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Lu, Jun; Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Wang, Yungui; Jin, Jie] Zhejiang Univ, Coll Med, Affiliated Hosp 1, Inst Hematol, Hangzhou 310003, Zhejiang, Peoples R China. [Yan, Ming; Zhang, Dong-Er] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Zhang, Dong-Er] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. [Zhang, Dong-Er] Univ Calif San Diego, Div Biol, La Jolla, CA 92093 USA. [Bohlander, Stefan K.] Univ Munich, Hosp Grosshadern, Dept Med 3, D-81377 Munich, Germany. [Bohlander, Stefan K.] Natl Res Ctr Environm & Hlth, Clin Cooperat Grp Leukemia, D-81377 Munich, Germany. [Golub, Todd R.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Golub, TR (reprint author), Broad Inst, Cambridge, MA 02141 USA. EM golub@broad.mit.edu; jrowley@medicine.bsd.uchicago.edu; jchen@medicine.bsd.uchicago.edu OI Bohlander, Stefan/0000-0002-2202-9088; Larson, Richard/0000-0001-9168-3203 FU National Institutes of Health (NIH) [CA127277, CA40046, CA104509, CA014599]; Cancer Research Foundation; Leukemia and Lymphoma Society; Spastic Paralysis Foundation of the Illinois; Eastern Iowa Branch of Kiwanis International FX We thank Drs. G. J. Hannon, S. M. Hammond, and L. He at Cold Spring Harbor Laboratory for providing MSCVpuro-PlG vector, Dr. P. P. Liu at National Human Genome Research Institute for providing the ME-1 cell line, and Drs. Y. Sato and K. Sugita at Yamanashi University for providing the KOCL-48 cell line. We also thank Dr. L. Pelloso at the University of Chicago for helpful discussion and Drs. J. Xu and Y. Chen at the University of Chicago for technical help with the methylation analysis. This work was supported in part by National Institutes of Health (NIH) Grant CA127277 (to J.C.), the G. Harold and Leila Y. Mathers Charitable Foundation (J.C.), a Cancer Research Foundation Young Investigator Award (to (J.C.), a Leukemia and Lymphoma Society Translational Research Grant (to J.D.R.), the Spastic Paralysis Foundation of the Illinois, the Eastern Iowa Branch of Kiwanis International (J.D.R.), NIH Grants CA40046 (to M.M.L.B. and R.A.L) and CA104509 (to D.-E.Z.). T.R.G. is an Investigator of the Howard Hughes Medical Institute. The sequencing was done by the Cancer Research Center DNA Sequencing Facility with the support of NIH Cancer Center Support Grant CA014599. NR 57 TC 256 Z9 277 U1 1 U2 22 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 OCT 7 PY 2008 VL 105 IS 40 BP 15535 EP 15540 DI 10.1073/pnas.0808266105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 364UI UT WOS:000260360500058 PM 18832181 ER PT J AU Oral, E Beckos, CG Muratoglu, OK AF Oral, Ebru Beckos, Christine Godleski Muratoglu, Orhun K. TI Free radical elimination in irradiated UHMWPE through crystal mobility in phase transition to the hexagonal phase SO POLYMER LA English DT Article DE Free radicals; Crystal mobility; Cross-linking ID MOLECULAR-WEIGHT POLYETHYLENE; HIGH-PRESSURE PHASE; PROPAGATION RESISTANCE; CRYSTALLIZATION; OXIDATION; WEAR; GROWTH; MELT AB Ultra-high molecular weight polyethylene (UHMWPE) is radiation cross-linked to decrease wear in total joint applications. Irradiation decreases the strength of UHMWPE and introduces residual free radicals, which can cause oxidation in the long-term. We advanced a method eliminating the free radicals without a reduction in strength. UHMWPE exhibits a hexagonal phase at high pressure and temperature, where chain mobility in the crystalline phase is increased, leading to the formation of extended chain crystals. We hypothesized that the increased chain mobility during transformation from the orthorhombic to hexagonal phase could be used to eliminate the residual free radicals in irradiated UHMWPE. We eliminated the free radicals in 25-, 65- and 100-kGy irradiated UHMWPEs and these materials did not show oxidation after accelerated aging. The ultimate tensile strength and work-to-failure of 25 and 65-kGy irradiated UHMWPEs were improved significantly while that of 100-kGy irradiated UHMWPE was lower compared to irradiated UHMWPE melted at ambient pressure. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Oral, Ebru; Beckos, Christine Godleski; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. [Oral, Ebru; Muratoglu, Orhun K.] Harvard Univ, Sch Med, Boston, MA USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Biomech & Biomat Lab, 55 Fruit St,GRJ 1206, Boston, MA 02114 USA. EM omuratoglu@partners.org FU National Institutes of Health [AR110542]; Zimmer, Inc. FX This study was funded by a grant from the National Institutes of Health (AR110542) and a research grant from Zimmer, Inc. The authors would also like to thank Prof. M. Shah Jahan and his group at the University of Memphis for their help with the ESR experiments. NR 21 TC 12 Z9 15 U1 0 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0032-3861 J9 POLYMER JI Polymer PD OCT 6 PY 2008 VL 49 IS 21 BP 4733 EP 4739 DI 10.1016/j.polymer.2008.07.049 PG 7 WC Polymer Science SC Polymer Science GA 360MZ UT WOS:000260062900033 PM 18985170 ER PT J AU Mick, E Kim, JW Biederman, J Wozniak, J Wilens, T Spencer, T Smoller, JW Faraone, SV AF Mick, Eric Kim, Jang Woo Biederman, Joseph Wozniak, Janet Wilens, Timothy Spencer, Thomas Smoller, Jordan W. Faraone, Stephen V. TI Family Based Association Study of Pediatric Bipolar Disorder and the Dopamine Transporter Gene (SLC6A3) SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE bipolar disorder; dopamine transporter; pediatric ID DEFICIT-HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; EARLY ADOLESCENT BIPOLARITY; LINKAGE DISEQUILIBRIUM; TRANSMISSION DISEQUILIBRIUM; ONSET; POLYMORPHISMS; EXPRESSION; HAPLOTYPE; DAT1 AB The dopamine transporter gene (SLC6A3) is a compelling candidate for pediatric bipolar disorder because (a) it has been associated with ADHD, (b) bipolar comorbidity with ADHD has been hypothesized to be an etiologically distinct familial subtype (c) blockade of the dopamine transporter with psychostimulants can induce mania in susceptible individuals and (d) previous studies have implicated the gene in bipolar disorder in adults. We conducted a family-based association study of SLC6A3 in 170 affected offspring trios defined by a child (12.9 +/- 5.3 years of age)with DSM-IV Bipolar-I disorder. Twenty-eight tag SNPs were chosen from the CEU (European) population of the International HapMap project (www.hapmap.org). Results indicated nominally positive association for 4 SNPs (rs40184, rs11133767, rs3776512, and rs464049), but only rs40184 survived correction for multiple statistical comparisons (P = 0.038). This is the first examination of the association with SLC6A3 and bipolar disorder in children and, like previous findings in adults with bipolar disorder, we found evidence of association with SNPs in the 3' region of the gene. These data provide suggestive evidence supporting a role for SLC6A3 in the etiology of pediatric bipolar disorder. (C) 2008 Wiley-Liss, Inc. C1 [Mick, Eric; Biederman, Joseph; Wozniak, Janet; Wilens, Timothy; Spencer, Thomas; Smoller, Jordan W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mick, Eric; Biederman, Joseph; Wozniak, Janet; Wilens, Timothy; Spencer, Thomas; Smoller, Jordan W.] Harvard Univ, Sch Med, Boston, MA USA. [Kim, Jang Woo; Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA. RP Mick, E (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,Warren 705, Boston, MA 02114 USA. EM mick@helix.mgh.harvard.edu OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIH [K08MH001503, R01MH066237, R01MH050657, R01HD036317, R01DA012945, K01MH065523]; Heinz C. Prechter Bipolar Research Fund FX Grant sponsor: NIH; Grant numbers: K08MH001503, R01MH066237, R01MH050657, R01HD036317, R01DA012945, K01MH065523; Grant sponsor: Heinz C. Prechter Bipolar Research Fund. NR 43 TC 25 Z9 27 U1 2 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2008 VL 147B IS 7 BP 1182 EP 1185 DI 10.1002/ajmg.b.30745 PG 4 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 359IK UT WOS:000259979500024 PM 18361424 ER PT J AU Kay, DM Factor, SA Samii, A Higgins, DS Griffith, A Roberts, JW Leis, BC Nutt, JG Montimurro, JS Keefe, RG Atkins, AJ Yearout, D Zabetian, CP Payami, H AF Kay, Denise M. Factor, Stewart A. Samii, Ali Higgins, Donald S. Griffith, Alida Roberts, John W. Leis, Berta C. Nutt, John G. Montimurro, Jennifer S. Keefe, Robert G. Atkins, April J. Yearout, Dora Zabetian, Cyrus P. Payami, Haydeh TI Genetic Association Between alpha-Synuclein and Idiopathic Parkinson's Disease SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE REP1; risk; age at onset; relative predispositional effects; mode of inheritance ID LOCUS TRIPLICATION; ALLELIC VARIATION; NACP-REP1; SUSCEPTIBILITY; SNCA; RELIABILITY; DUPLICATION; ONSET; RISK AB Point mutations and copy number variations in SNCA, the gene encoding a-synuclein, cause familial Parkinson's disease (PD). A dinucleotide polymorphism. (REPI.) in the SNCA promoter may be a risk factor for common forms of PD. We studied 1,802 PD patients and 2,129 controls from the NeuroGenetics Research Consortium, using uniform, standardized protocols for diagnosis, subject recruitment, data collection, genotyping, and data analysis. Three common REP1 alleles (257, 259, and 261 bp, with control frequencies of 0.28, 0.65, and 0.06) and several rare alleles (combined frequency <0.01) were detected. We confirmed association of REP1 with PD risk [odds ratio (OR)=0.86, P=0.006 for 257-carriers; OR=1.25, P=0.022 for 261-carriers]. Using a normalization procedure, we showed that the 257 and 261 alleles are both independently associated with PD risk (for 257, P=0.002 in overall data, 0.003 in non-familial PD, 0.001 in early-onset PD; for 261, P=0.056 in overall data, 0.024 in non-familial PD, 0.052 in early-onset PD). The 257-associated risk was consistent with a dominant model [hazard ratio (HR)=0.99, P=0.91 for 257/257 vs. 257/X where X denotes all other common alleles; HR=1.16, P=0.004 for X/X vs. 257/X]. The 261-associated risk was consistent with a recessive model (HR=1.89, P=0.026 for 261/261 vs. 261/X; HR=0.95, P=0.42 for X/X vs. 261/X). Genotype-specific mean onset ages (+/- SD) ranged from 54.8 +/- 12.1 for 261/261 to 59.4 +/- 11.5 for 257/257, displaying a trend of decreasing onset age with increasing allele size (P=0.055). Genetic variation in SNCA and its regulatory regions play an important role in both familial and sporadic PD. (C) 2008 Wiley-Liss, Inc. C1 [Kay, Denise M.; Montimurro, Jennifer S.; Keefe, Robert G.; Atkins, April J.; Payami, Haydeh] New York State Dept Hlth, Wadsworth Ctr, Div Genet Disorders, Albany, NY 12208 USA. [Factor, Stewart A.; Higgins, Donald S.] Albany Med Ctr, Parkinsons Dis & Movement Disorder Clin, Albany, NY USA. [Factor, Stewart A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Samii, Ali; Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. [Samii, Ali; Yearout, Dora; Zabetian, Cyrus P.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Griffith, Alida; Leis, Berta C.] Evergreen Hosp Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA. [Roberts, John W.] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Nutt, John G.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Yearout, Dora; Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. RP Payami, H (reprint author), New York State Dept Hlth, Wadsworth Ctr, Div Genet Disorders, POB 22002, Albany, NY 12208 USA. EM hpayami@wadsworth.org OI Kay, Denise/0000-0002-9928-2698 FU Michael J. Fox Foundation; National Institutes of Health (NIH) [NS R01-36960, K08-NS044138, AG 08017]; VA Merit Award; Mental Health and Geriatric Research Education and Clinical Centers; Genomics Institute of the New York State Department of Health Wadsworth Center FX Grant sponsor: Michael J. Fox Foundation Edmond J. Safra Global Genetics Consortia Grant-Grant sponsor: National Institutes of Health (NIH) National Institute for Neurological Disorders and Stroke grants; Grant numbers: NS R01-36960, K08-NS044138; Grant sponsor: VA Merit Award; Grant sponsor: NIH National Institutes of Aging grant; Grant number: AG 08017; Grant sponsor: Mental Health and Geriatric Research Education and Clinical Centers at the VA Puget Sound Health Care System; Grant sponsor: Genomics Institute of the New York State Department of Health Wadsworth Center. NR 26 TC 35 Z9 36 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2008 VL 147B IS 7 BP 1222 EP 1230 DI 10.1002/ajmg.b.30758 PG 9 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 359IK UT WOS:000259979500029 PM 18404644 ER PT J AU Platko, JV Wood, FB Pelser, I Meyer, M Gericke, GS O'Rourke, J Birns, J Purcell, S Pauls, DL AF Platko, Jill V. Wood, Frank B. Pelser, Izelda Meyer, Marianne Gericke, George S. O'Rourke, Julia Birns, Julie Purcell, Shaun Pauls, David L. TI Association of Reading Disability on Chromosome 6p22 in the Afrikaner Population SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE dyslexia; Afrikaner; reading disability; association ID QUANTITATIVE-TRAIT LOCUS; DEVELOPMENTAL DYSLEXIA; LINKAGE DISEQUILIBRIUM; LEARNING-DISABILITIES; SUSCEPTIBILITY LOCUS; SPELLING DISABILITY; CANADIAN FAMILIES; GENETIC ETIOLOGY; MAPPING PROVIDES; CONFIRMATION AB The genetic basis of reading disability (RD) has long been established through family and twin studies. More recently genetic linkage studies have identified genomic regions that appear to harbor susceptibility genes for RD. Association studies have been shown to have greater power for detecting genes of modest effect, particularly in genetically isolated populations. Hence, a case control study of RD was undertaken in the Afrikaner population in South Africa. Sixty-eight microsatellite markers in regions where linkages had been reported in previous studies were genotyped on 122 children with reading disability and 112 typically reading controls drawn from the same school population. A single allele of marker D6S299 showed a highly significant association with the RD phenotype (D6S299[229], P-value 0.000014). Other markers on other chromosomes also showed suggestive associations. Of particular interest were markers on chromosomes 1 and 15. These two regions have been implicated in studies of populations that formed the founding population in the Afrikaner population. (C) 2008 Wiley-Liss, Inc. C1 [Platko, Jill V.; O'Rourke, Julia; Birns, Julie; Purcell, Shaun; Pauls, David L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Wood, Frank B.; Meyer, Marianne] Wake Forest Univ, Bowman Gray Sch Med, Sect Neuropsychol, Winston Salem, NC 27109 USA. [Pelser, Izelda] Univ Limpopo, Ga Rankuwa, South Africa. [Gericke, George S.] Tshwane Univ Technol Pretoria, Brain Behav Res Programme, Pretoria, South Africa. RP Pauls, DL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, 185 Cambridge St,6th Floor, Boston, MA 02114 USA. EM dpauls@pngu.mgh.harvard.edu NR 73 TC 6 Z9 6 U1 3 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2008 VL 147B IS 7 BP 1278 EP 1287 DI 10.1002/ajmg.b.30774 PG 10 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 359IK UT WOS:000259979500036 PM 18452150 ER PT J AU Neale, BM Purcell, S AF Neale, Benjamin M. Purcell, Shaun TI The Positives, Protocols, and Perils of Genome-Wide Association SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Review DE genome-wide association; linkage disequilibrium; review; SNP chip ID SINGLE-NUCLEOTIDE POLYMORPHISMS; COMMON GENETIC VARIANT; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION; CARDIAC REPOLARIZATION; LINKAGE-DISEQUILIBRIUM; SUSCEPTIBILITY LOCI; NICOTINE DEPENDENCE; CROHNS-DISEASE; RISK LOCUS AB Genome-wide association aims to comprehensively survey genetic variation for the purposes of disease and trait mapping. We provide a brief history of the development of genetic technology necessary to realize genome-wide association. From there we identify and review the publicly available resources for conducting such work including the molecular technologies, genomic databases, and analytic tools. Following on from the analytic tools, we highlight common analytic considerations, ranging from study design, quality control, and data cleaning to association analysis and replication. We conclude with a look toward future developments such as the analysis of copy number variation and integration of expression and epigenetic phenomenon into genome-wide association. (C) 2008 Wiley-Liss, Inc. C1 [Neale, Benjamin M.] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England. [Neale, Benjamin M.; Purcell, Shaun] Broad Inst Harvard, Cambridge, MA USA. [Neale, Benjamin M.; Purcell, Shaun] MIT, Cambridge, MA 02139 USA. [Purcell, Shaun] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodevelopmental Genet Unit, Boston, MA 02114 USA. [Purcell, Shaun] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Neale, Benjamin M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boson, MA USA. RP Neale, BM (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Richard B Simches Res Ctr, 185 Cambridge St, Boston, MA 02114 USA. EM b.neale@iop.kcl.ac.uk NR 78 TC 26 Z9 27 U1 2 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2008 VL 147B IS 7 BP 1288 EP 1294 DI 10.1002/ajmg.b.30747 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 359IK UT WOS:000259979500037 PM 18500721 ER PT J AU Blackwell, TK Walker, AK AF Blackwell, T. Keith Walker, Amy K. TI OMA-gosh, where's that TAF? SO CELL LA English DT Editorial Material ID OOCYTE MATURATION; C-ELEGANS; TRANSCRIPTION; ELONGATION; PROTEINS; PIE-1 AB How transcription is silenced in early embryos has long been a mystery. In this issue, Guven-Ozkan et al. (2008) report that transcriptional repression during worm embryogenesis is mediated through sequestration of the general transcription factor TAF-4 and is regulated by mechanisms that orchestrate the transition between maternal and zygotic gene expression. C1 [Blackwell, T. Keith] Harvard Univ, Sch Med,Harvard Stem Cell Inst, Sect Dev & Stem Cell Biol, Joslin Diabet Ctr,Dept Pathol, Boston, MA 02215 USA. [Walker, Amy K.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. RP Blackwell, TK (reprint author), Harvard Univ, Sch Med,Harvard Stem Cell Inst, Sect Dev & Stem Cell Biol, Joslin Diabet Ctr,Dept Pathol, Boston, MA 02215 USA. EM keith.blackwell@joslin.harvard.edu; awalker6@partners.org NR 8 TC 0 Z9 1 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD OCT 3 PY 2008 VL 135 IS 1 BP 18 EP 20 DI 10.1016/j.cell.2008.09.021 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 355SH UT WOS:000259728100004 PM 18854150 ER PT J AU Yu, HY Braun, P Yildirim, MA Lemmens, I Venkatesan, K Sahalie, J Hirozane-Kishikawa, T Gebreab, F Li, N Simonis, N Hao, T Rual, JF Dricot, A Vazquez, A Murray, RR Simon, C Tardivo, L Tam, S Svrzikapa, N Fan, CY de Smet, AS Motyl, A Hudson, ME Park, J Xin, XF Cusick, ME Moore, T Boone, C Snyder, M Roth, FP Barabasi, AL Tavernier, J Hill, DE Vidal, M AF Yu, Haiyuan Braun, Pascal Yildirim, Muhammed A. Lemmens, Irma Venkatesan, Kavitha Sahalie, Julie Hirozane-Kishikawa, Tomoko Gebreab, Fana Li, Na Simonis, Nicolas Hao, Tong Rual, Jean-Francois Dricot, Amelie Vazquez, Alexei Murray, Ryan R. Simon, Christophe Tardivo, Leah Tam, Stanley Svrzikapa, Nenad Fan, Changyu de Smet, Anne-Sophie Motyl, Adriana Hudson, Michael E. Park, Juyong Xin, Xiaofeng Cusick, Michael E. Moore, Troy Boone, Charlie Snyder, Michael Roth, Frederick P. Barabasi, Albert-Laszlo Tavernier, Jan Hill, David E. Vidal, Marc TI High-quality binary protein interaction map of the yeast interactome network SO SCIENCE LA English DT Article ID SACCHAROMYCES-CEREVISIAE; REGULATORY NETWORKS; MASS-SPECTROMETRY; ESCHERICHIA-COLI; 2-HYBRID SCREENS; GENOMIC ANALYSIS; C-ELEGANS; SCALE; COMPLEXES; ANNOTATION AB Current yeast interactome network maps contain several hundred molecular complexes with limited and somewhat controversial representation of direct binary interactions. We carried out a comparative quality assessment of current yeast interactome data sets, demonstrating that high- throughput yeast two- hybrid ( Y2H) screening provides high- quality binary interaction information. Because a large fraction of the yeast binary interactome remains to be mapped, we developed an empirically controlled mapping framework to produce a "second- generation" high- quality, high- throughput Y2H data set covering similar to 20% of all yeast binary interactions. Both Y2H and affinity purification followed by mass spectrometry ( AP/ MS) data are of equally high quality but of a fundamentally different and complementary nature, resulting in networks with different topological and biological properties. Compared to co- complex interactome models, this binary map is enriched for transient signaling interactions and intercomplex connections with a highly significant clustering between essential proteins. Rather than correlating with essentiality, protein connectivity correlates with genetic pleiotropy. C1 [Yu, Haiyuan; Braun, Pascal; Yildirim, Muhammed A.; Venkatesan, Kavitha; Sahalie, Julie; Hirozane-Kishikawa, Tomoko; Gebreab, Fana; Li, Na; Simonis, Nicolas; Hao, Tong; Rual, Jean-Francois; Dricot, Amelie; Murray, Ryan R.; Simon, Christophe; Tardivo, Leah; Tam, Stanley; Svrzikapa, Nenad; Fan, Changyu; Park, Juyong; Cusick, Michael E.; Roth, Frederick P.; Barabasi, Albert-Laszlo; Hill, David E.; Vidal, Marc] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. [Yu, Haiyuan; Braun, Pascal; Yildirim, Muhammed A.; Venkatesan, Kavitha; Sahalie, Julie; Hirozane-Kishikawa, Tomoko; Gebreab, Fana; Li, Na; Simonis, Nicolas; Hao, Tong; Rual, Jean-Francois; Dricot, Amelie; Murray, Ryan R.; Simon, Christophe; Tardivo, Leah; Tam, Stanley; Svrzikapa, Nenad; Fan, Changyu; Cusick, Michael E.; Hill, David E.; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Yu, Haiyuan; Braun, Pascal; Yildirim, Muhammed A.; Venkatesan, Kavitha; Sahalie, Julie; Hirozane-Kishikawa, Tomoko; Gebreab, Fana; Li, Na; Simonis, Nicolas; Hao, Tong; Rual, Jean-Francois; Dricot, Amelie; Murray, Ryan R.; Simon, Christophe; Tardivo, Leah; Tam, Stanley; Svrzikapa, Nenad; Fan, Changyu; Cusick, Michael E.; Hill, David E.; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Yildirim, Muhammed A.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Lemmens, Irma; de Smet, Anne-Sophie; Tavernier, Jan] Univ Ghent VIB, Dept Med Prot Res, Fac Med & Hlth Sci, B-9000 Ghent, Belgium. [Lemmens, Irma; de Smet, Anne-Sophie; Tavernier, Jan] Univ Ghent, Dept Biochem, Fac Med & Hlth Sci, B-9000 Ghent, Belgium. [Vazquez, Alexei] Inst Adv Study, Simons Ctr Syst Biol, Princeton, NJ 08540 USA. [Motyl, Adriana; Hudson, Michael E.; Snyder, Michael] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06620 USA. [Park, Juyong; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. [Park, Juyong; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Park, Juyong; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Biol, Boston, MA 02115 USA. [Park, Juyong; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Comp Sci, Boston, MA 02115 USA. [Xin, Xiaofeng; Boone, Charlie] Univ Toronto, Banting & Best Dept Med Res, Terrence Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada. [Xin, Xiaofeng; Boone, Charlie] Univ Toronto, Dept Med Genet & Microbiol, Terrence Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada. [Moore, Troy] Open Biosyst, Huntsville, AL 35806 USA. [Roth, Frederick P.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Vidal, M (reprint author), Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. EM marc_vidal@dfci.harvard.edu RI Roth, Frederick/H-6308-2011; Yildirim, Muhammed/J-3695-2014; Braun, Pascal/B-9669-2013; Xin, Xiaofeng/G-7736-2016; Simonis, Nicolas/E-5124-2010; Hill, David/B-6617-2011; Park, Juyong/I-2290-2012; OI Yildirim, Muhammed/0000-0003-2826-1766; Braun, Pascal/0000-0003-2012-6746; Xin, Xiaofeng/0000-0002-2439-7183; Rual, Jean-Francois/0000-0003-4465-8819; Roth, Frederick/0000-0002-6628-649X FU W. M. Keck Foundation; Institute Sponsored Research funds from the Dana-Farber Cancer Institute Strategic Initiative; NIH [R01-HG001715, U01-A1070499-01, U56- CA113004, HG003224]; University of Ghent [GOA12051401]; Fund for Scientific Research Flanders [FWO-V G. 0031.06]; National Cancer Institute of Canada FX Supported by funds from the W. M. Keck Foundation (M.V. and F. P. R.); by Institute Sponsored Research funds from the Dana-Farber Cancer Institute Strategic Initiative (M.V. and CCSB); by NIH grant R01- HG001715 (M.V. and F.P.R.); by NIH grants U01-A1070499- 01 and U56-CA113004 (A.-L.B.); by grant GOA12051401 from the University of Ghent and grant FWO-VG. 0031.06 from the Fund for Scientific Research Flanders (J.T.); by a grant from the National Cancer Institute of Canada (C.B.); and by NIH grant HG003224 (F.P.R.). I.L. is a postdoctoral fellow with the Fonds Wetenschappelijk Onderzoek-Vlanderen. M.V. is a "Chercheur Qualifi, Honoraire" from the Fonds de la Recherche Scientifique (FRS-FNRS, French Community of Belgium). We thank members of our laboratories for helpful discussions and Agencourt Biosciences for sequencing assistance. All data sets can be downloaded from our Web site (http://interactome.dfci.harvard.edu/S_cerevisiae). NR 45 TC 716 Z9 733 U1 11 U2 108 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 3 PY 2008 VL 322 IS 5898 BP 104 EP 110 DI 10.1126/science.1158684 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 355AE UT WOS:000259680200048 PM 18719252 ER PT J AU Tamborlane, WV Beck, RW Bode, BW Buckingham, B Chase, HP Clemons, R Fiallo-Scharer, R Fox, LA Gilliam, LK Hirsch, IB Huang, ES Kollman, C Kowalski, AJ Laffel, L Lawrence, JM Lee, J Mauras, N O'Grady, M Ruedy, KJ Tansey, M Tsalikian, E Weinzimer, S Wilson, DM Wolpert, H Wysocki, T Xing, DY AF Tamborlane, William V. Beck, Roy W. Bode, Bruce W. Buckingham, Bruce Chase, H. Peter Clemons, Robert Fiallo-Scharer, Rosanna Fox, Larry A. Gilliam, Lisa K. Hirsch, Irl B. Huang, Elbert S. Kollman, Craig Kowalski, Aaron J. Laffel, Lori Lawrence, Jean M. Lee, Joyce Mauras, Nelly O'Grady, Michael Ruedy, Katrina J. Tansey, Michael Tsalikian, Eva Weinzimer, Stuart Wilson, Darrell M. Wolpert, Howard Wysocki, Tim Xing, Dongyuan CA Juvenile Diabet Res Fdn Continuous TI Continuous glucose monitoring and intensive treatment of type 1 diabetes SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GLYCEMIC CONTROL; PEDIATRIC-PATIENTS; PILOT TRIAL; YOUTH; SYSTEM; COMPLICATIONS; ACCURACY; CHILDREN; MELLITUS; IMPACT AB Background The value of continuous glucose monitoring in the management of type 1 diabetes mellitus has not been determined. Methods In a multicenter clinical trial, we randomly assigned 322 adults and children who were already receiving intensive therapy for type 1 diabetes to a group with continuous glucose monitoring or to a control group performing home monitoring with a blood glucose meter. All the patients were stratified into three groups according to age and had a glycated hemoglobin level of 7.0 to 10.0%. The primary outcome was the change in the glycated hemoglobin level at 26 weeks. Results The changes in glycated hemoglobin levels in the two study groups varied markedly according to age group ( P = 0.003), with a significant difference among patients 25 years of age or older that favored the continuous- monitoring group ( mean difference in change, - 0.53%; 95% confidence interval [ CI], - 0.71 to - 0.35; P< 0.001). The between- group difference was not significant among those who were 15 to 24 years of age ( mean difference, 0.08; 95% CI, - 0.17 to 0.33; P = 0.52) or among those who were 8 to 14 years of age ( mean difference, - 0.13; 95% CI, - 0.38 to 0.11; P = 0.29). Secondary glycated hemoglobin outcomes were better in the continuous- monitoring group than in the control group among the oldest and youngest patients but not among those who were 15 to 24 years of age. The use of continuous glucose monitoring averaged 6.0 or more days per week for 83% of patients 25 years of age or older, 30% of those 15 to 24 years of age, and 50% of those 8 to 14 years of age. The rate of severe hypoglycemia was low and did not differ between the two study groups; however, the trial was not powered to detect such a difference. Conclusions Continuous glucose monitoring can be associated with improved glycemic control in adults with type 1 diabetes. Further work is needed to identify barriers to effectiveness of continuous monitoring in children and adolescents. ( ClinicalTrials. gov number, NCT00406133.). C1 [Beck, Roy W.; Kollman, Craig; Ruedy, Katrina J.; Xing, Dongyuan] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA. [Chase, H. Peter; Fiallo-Scharer, Rosanna] Univ Colorado, Barbara Davis Ctr Childhood Diabet, Denver, CO 80202 USA. [Laffel, Lori] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. [Buckingham, Bruce; Wilson, Darrell M.] Stanford Univ, Stanford, CA 94305 USA. [Tansey, Michael; Tsalikian, Eva] Univ Iowa, Carver Coll Med, Iowa City, IA USA. [Wolpert, Howard] Joslin Diabet Ctr, Adult Sect, Boston, MA 02215 USA. [Gilliam, Lisa K.; Hirsch, Irl B.] Univ Washington, Seattle, WA 98195 USA. [Fox, Larry A.; Mauras, Nelly; Wysocki, Tim] Nemours Childrens Clin, Jacksonville, FL USA. [Bode, Bruce W.] Atlanta Diabet Assoc, Atlanta, GA USA. [Clemons, Robert; Lawrence, Jean M.] Kaiser Permanente, San Diego, CA USA. [Weinzimer, Stuart] Yale Univ, Sch Med, New Haven, CT USA. [Huang, Elbert S.; O'Grady, Michael] Univ Chicago, Natl Opin Res Ctr, Chicago, IL 60637 USA. [Lee, Joyce] Univ Michigan, Ann Arbor, MI 48109 USA. RP Beck, RW (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr 350, Tampa, FL 33647 USA. EM rbeck@jaeb.org RI Meltzer, David/C-2926-2009 OI Meltzer, David/0000-0003-2790-7393 FU Juvenile Diabetes Research Foundation [22-2006-1107, 22-2006-1117, 22-20061112, 22-2006-1123, 01-2006-8031]; Abbott Diabetes Care; Lifescan; Medtronic; DexCom; Novo Nordisk; Sanofi-Aventis; Symlin; Roche; Charles Hood Foundation; AstraZeneca FX Supported by grants (22-2006-1107, 22-2006-1117, 22-20061112, 22-2006-1123, and 01-2006-8031) from the Juvenile Diabetes Research Foundation.; Dr. Tamborlane reports receiving consulting fees from Abbott Diabetes Care and Lifescan and consulting and lecture fees and grant support from Medtronic; Dr. Bode, receiving consulting and lecture fees, travel reimbursement, and grant support from Abbott Diabetes Care and Medtronic and grant support from DexCom; Dr. Buckingham, receiving lecture fees and grant support from Abbott Diabetes Care, lecture and consulting fees and grant support from Medtronic, and consulting fees from Novo Nordisk and serving on an advisory board for Lifescan; Dr. Chase, receiving lecture fees from Abbott Diabetes Care and Sanofi-Aventis and grant support from Symlin; Dr. Fiallo-Scharer, receiving supplies for research from Abbott Diabetes Care and Medtronic; Dr. Fox, receiving supplies for research from Abbott Diabetes Care; Dr. Hirsch, receiving consulting fees and travel reimbursement from Abbott Diabetes Care and grant support from Medtronic; Dr. Laffel, receiving consulting fees from Lifescan and Roche, consulting and lecture fees from Abbott Diabetes Care, consulting fees and grant support from Medtronic, and grant support from the Charles Hood Foundation; Dr. Mauras, receiving grant support from AstraZeneca; Dr. Weinzimer, receiving lecture fees and travel reimbursement from Medtronic; Dr. Wilson, receiving equipment and software from Abbott Diabetes Care and Medtronic and grant support from Medtronic; and Dr. Wolpert, receiving consulting fees from Abbott Diabetes Care and grant support from Medtronic. No other potential conflict of interest relevant to this article was reported. NR 31 TC 519 Z9 529 U1 6 U2 55 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 OCT 2 PY 2008 VL 359 IS 14 BP 1464 EP U65 PG 21 WC Medicine, General & Internal SC General & Internal Medicine GA 354ID UT WOS:000259631700007 ER PT J AU Dienstag, JL AF Dienstag, Jules L. TI Drug therapy - Hepatitis B virus infection SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID SEVERELY DECOMPENSATED CIRRHOSIS; AWAITING LIVER-TRANSPLANTATION; EXTENDED LAMIVUDINE TREATMENT; ALPHA-INTERFERON TREATMENT; CHRONIC ACTIVE HEPATITIS; ADEFOVIR DIPIVOXIL ADV; LONG-TERM THERAPY; TENOFOVIR DF TDF; E-ANTIGEN; VIRAL SUPPRESSION C1 [Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Off Dean Med Educ, Boston, MA USA. RP Dienstag, JL (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Jackson 7,55 Fruit St, Boston, MA 02114 USA. EM jdienstag@partners.org NR 123 TC 482 Z9 525 U1 1 U2 31 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 OCT 2 PY 2008 VL 359 IS 14 BP 1486 EP 1500 DI 10.1056/NEJMra0801644 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 354ID UT WOS:000259631700009 PM 18832247 ER PT J AU Goldberger, ZD Weinberger, SE Nicosia, RF Saint, S Young, BA AF Goldberger, Zachary D. Weinberger, Steven E. Nicosia, Roberto F. Saint, Sanjay Young, Bessie A. TI Variations on a theme SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID GLOMERULAR BASEMENT-MEMBRANE; GOODPASTURES-SYNDROME; ALVEOLAR HEMORRHAGE; ANTIBODY DISEASE; GLOMERULONEPHRITIS; EXPOSURE C1 [Goldberger, Zachary D.; Saint, Sanjay] Univ Michigan Hlth Syst, Dept Internal Med, Div Cardiovasc Med, CVC Cardiovasc Med, Ann Arbor, MI 48109 USA. [Saint, Sanjay] Ann Arbor Vet Affairs Med Ctr, Ann Arbor, MI 48109 USA. [Saint, Sanjay] Univ Michigan Hlth Syst, Patient Safety Enhancement Program, Ann Arbor, MI 48109 USA. [Goldberger, Zachary D.; Young, Bessie A.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. [Nicosia, Roberto F.] Vet Affairs Puget Sound Hlth Care Syst, Pathol Serv, Seattle, WA USA. [Nicosia, Roberto F.] Vet Affairs Puget Sound Hlth Care Syst, Lab Serv, Seattle, WA USA. [Nicosia, Roberto F.] Vet Affairs Puget Sound Hlth Care Syst, Dept Pathol, Seattle, WA USA. [Young, Bessie A.] Vet Affairs Puget Sound Hlth Care Syst, Div Nephrol, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA USA. [Weinberger, Steven E.] Amer Coll Physicians, Philadelphia, PA USA. RP Goldberger, ZD (reprint author), Univ Michigan Hlth Syst, Dept Internal Med, Div Cardiovasc Med, CVC Cardiovasc Med, 1500 E Med Ctr Dr,SPC 5853, Ann Arbor, MI 48109 USA. EM zgoldber@med.umich.edu FU Advanced Career Development Award; Health Services Research and Development Program of the Department of Veterans Affairs; National Institutes of Health [RO1 DK079745-01] FX We thank Drs. David Au, Vijay Reddy, and Heather Davidson for their care of the patient. NR 15 TC 2 Z9 3 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 2 PY 2008 VL 359 IS 14 BP 1502 EP 1507 DI 10.1056/NEJMcps0708762 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 354ID UT WOS:000259631700012 PM 18832249 ER PT J AU Upadhyay, G Goessling, W North, TE Xavier, R Zon, LI Yajnik, V AF Upadhyay, G. Goessling, W. North, T. E. Xavier, R. Zon, L. I. Yajnik, V. TI Molecular association between beta-catenin degradation complex and Rac guanine exchange factor DOCK4 is essential for Wnt/beta-catenin signaling SO ONCOGENE LA English DT Article DE Wnt/beta-catenin; Rac; GSK3 beta; Axin; APC; DOCK4 ID GLYCOGEN-SYNTHASE KINASE-3; DESTRUCTION COMPLEX; NUCLEOTIDE EXCHANGE; PHOSPHORYLATION; ZEBRAFISH; PATHWAY; GTPASE; ACTIVATION; MECHANISM; PROTEINS AB The canonical Wnt/beta-catenin pathway is a highly conserved signaling cascade that is involved in development and stem cell renewal. The deregulation of this pathway is often associated with increased cell growth and neoplasia. The small GTPase Rac has been shown to influence canonical Wnt signaling by regulating beta-catenin stability through an unknown mechanism. We report that DOCK4, a guanine nucleotide exchange factor (GEF) for Rac and a member of the CDM family of unconventional GEFs, mediates Wnt-induced Rac activation in the canonical Wnt/beta-catenin pathway. DOCK4 expression regulates cellular beta-catenin levels in response to the Wnt signal, in vitro. Biochemical studies demonstrate that DOCK4 interacts with the beta-catenin degradation complex, consisting of the proteins adenomatosis polyposis coli, Axin and glycogen synthase kinase 3 beta (GSK3 beta). This molecular interaction enhances beta-catenin stability and Axin degradation. Furthermore, we observe that DOCK4 is phosphorylated by GSK3 beta, which enhances Wnt-induced Rac activation. Using a T-cell factor reporter zebrafish we confirm that DOCK4 is required for Wnt/beta-catenin activity, in vivo. These results elucidate a novel intracellular signaling mechanism in which a Rac GEF, DOCK4 acts as a scaffold protein in the Wnt/beta-catenin pathway. C1 [Upadhyay, G.; Goessling, W.; Xavier, R.; Yajnik, V.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Gastrointestinal Unit, Boston, MA 02114 USA. [Goessling, W.; North, T. E.; Zon, L. I.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02114 USA. RP Yajnik, V (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Gastrointestinal Unit, 55 Fruit St,GRJ-825, Boston, MA 02114 USA. EM gu6@georgetown.edu; vyajnik@partners.org OI Goessling, Wolfram/0000-0001-9972-1569 FU NIH [DK 63933]; MGH GI unit FX We thank Lars von Buchholtz (NIH, MD, USA), Parool Meelu (MGH, MA, USA), Tiffany M Blake (Georgetown University, DC, USA) and Denver Matthew Lough (Georgetown University, DC, USA) for the help in the preparation of the paper. This study was supported by grant NIH DK 63933 (VY) and MGH GI unit startup funds (VY). NR 44 TC 33 Z9 34 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 2 PY 2008 VL 27 IS 44 BP 5845 EP 5855 DI 10.1038/onc.2008.202 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 355QC UT WOS:000259722400008 PM 18641688 ER PT J AU Loerch, PM Lu, T Dakin, KA Vann, JM Isaacs, A Geula, C Wang, J Pan, Y Gabuzda, DH Li, C Prolla, TA Yankner, BA AF Loerch, Patrick M. Lu, Tao Dakin, Kelly A. Vann, James M. Isaacs, Adrian Geula, Chengiz Wang, Jianbin Pan, Ying Gabuzda, Dana H. Li, Cheng Prolla, Tomas A. Yankner, Bruce A. TI Evolution of the Aging Brain Transcriptome and Synaptic Regulation SO PLOS ONE LA English DT Article AB Alzheimer's disease and other neurodegenerative disorders of aging are characterized by clinical and pathological features that are relatively specific to humans. To obtain greater insight into how brain aging has evolved, we compared age-related gene expression changes in the cortex of humans, rhesus macaques, and mice on a genome-wide scale. A small subset of gene expression changes are conserved in all three species, including robust age-dependent upregulation of the neuroprotective gene apolipoprotein D (APOD) and downregulation of the synaptic cAMP signaling gene calcium/calmodulin-dependent protein kinase IV (CAMK4). However, analysis of gene ontology and cell type localization shows that humans and rhesus macaques have diverged from mice due to a dramatic increase in age-dependent repression of neuronal genes. Many of these age-regulated neuronal genes are associated with synaptic function. Notably, genes associated with GABA-ergic inhibitory function are robustly age-downregulated in humans but not in mice at the level of both mRNA and protein. Gene downregulation was not associated with overall neuronal or synaptic loss. Thus, repression of neuronal gene expression is a prominent and recently evolved feature of brain aging in humans and rhesus macaques that may alter neural networks and contribute to age-related cognitive changes. C1 [Loerch, Patrick M.; Lu, Tao; Dakin, Kelly A.; Isaacs, Adrian; Pan, Ying; Yankner, Bruce A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Vann, James M.; Prolla, Tomas A.] Univ Wisconsin, Dept Genet & Med Genet, Madison, WI 53706 USA. [Geula, Chengiz] Northwestern Univ, Cognit Neurol & Alzheimers Dis Ctr, Chicago, IL USA. [Wang, Jianbin; Gabuzda, Dana H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Loerch, Patrick M.; Li, Cheng] Harvard Uni, Harvard Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA USA. RP Loerch, PM (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM bruce_yankner@hms.harvard.edu FU National Institute on Aging [AG26651, AG27040, AG27916]; Ellison Medical Foundation Senior Scholar award; NIH [T32GM074897] FX This work was supported by grants from the National Institute on Aging (grant numbers AG26651, AG27040, AG27916), and an Ellison Medical Foundation Senior Scholar award to B.A.Y.. P.L. was supported by NIH training grant T32GM074897. NR 37 TC 128 Z9 131 U1 1 U2 8 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 OCT 2 PY 2008 VL 3 IS 10 AR e3329 DI 10.1371/journal.pone.0003329 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 427RV UT WOS:000264797300013 PM 18830410 ER PT J AU Damore, D Mansbach, JM Clark, S Ramundo, M Camargo, CA AF Damore, Dorothy Mansbach, Jonathan M. Clark, Sunday Ramundo, Maria Camargo, Carlos A., Jr. TI Prospective Multicenter Bronchiolitis Study: Predicting Intensive Care Unit Admissions SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Societies/Academic-Pediatric-Association/Society-for- Pediatric-Research National Conference CY MAY 02-06, 2008 CL Honolulu, HI SP Pediat Acad Soc, Acad Pediat Assoc, Soc Pediat Res DE bronchiolitis; risk factors; multivariate predictors; ICU admission ID RESPIRATORY SYNCYTIAL VIRUS; RISK-FACTORS; YOUNG-CHILDREN; EMERGENCY-DEPARTMENTS; CANADIAN CHILDREN; US CHILDREN; INFECTION; INFANTS; HOSPITALIZATION; MANAGEMENT AB Objectives: The authors sought to identify predictors of intensive care unit (ICU) admission among children hospitalized with bronchiolitis for 24 hours. Methods: The authors conducted a prospective cohort study during two consecutive bronchiolitis seasons, 2004 through 2006, in 30 U.S. emergency departments (EDs). All included patients were aged <2 years and had a final diagnosis of bronchiolitis. Regular floor versus ICU admissions were compared. Results: Of 1,456 enrolled patients, 533 (37%) were admitted to the regular floor and 50 (3%) to the ICU. Comparing floor and ICU admissions, multivariate ED predictors of ICU admission were age <2 months (26% vs. 53%; odds ratio [OR] = 4.1; 95% confidence interval [CI] = 2.1 to 8.3), an ED visit the past week (25% vs. 40%; OR = 2.2; 95% CI = 1.1 to 4.4), moderate/severe retractions (31% vs. 48%; OR = 2.6; 95%, CI = 1.3 to 5.2), and inadequate oral intake (31% vs. 53%; OR = 3.3; 95% CI = 1.6 to 7.1). Unlike previous studies, no association with male gender, socioeconomic factors, insurance status, breast-feeding, or parental asthma was found with ICU admission. Conclusions: In this prospective multicenter ED-based study of children admitted for bronchiolitis, four independent predictors of ICU admission were identified. The authors did not confirm many putative risk factors, but cannot rule out modest associations. ACADEMIC EMERGENCY MEDICINE 2008; 15:887-894 (C) 2008 by the Society for Academic Emergency Medicine C1 [Damore, Dorothy; Clark, Sunday] New York Presbyterian Hosp, Weill Cornell Medial Ctr, Dept Emergency Med, New York, NY USA. [Mansbach, Jonathan M.] Harvard Univ, Childrens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Ramundo, Maria] Northeastern Ohio Univ Coll Med & Pharm, Akron Childrens Hosp, Dept Emergency Med, Akron, OH USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Damore, D (reprint author), New York Presbyterian Hosp, Weill Cornell Medial Ctr, Dept Emergency Med, New York, NY USA. EM djt2001@med.cornell.edu NR 43 TC 30 Z9 30 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD OCT PY 2008 VL 15 IS 10 BP 887 EP 894 DI 10.1111/j.1553-2712.2008.00245.x PG 8 WC Emergency Medicine SC Emergency Medicine GA 359FO UT WOS:000259972000002 PM 18795902 ER PT J AU Huddle, TS Heudebert, GR AF Huddle, Thomas S. Heudebert, Gustavo R. TI Internal Medicine Training in the 21st Century SO ACADEMIC MEDICINE LA English DT Article ID RECOMMENDATIONS AB Many are calling for changes for internal medicine training, arguing that changes in the practice environment mandate changes in how the internal medicine residency is structured. Residency could be shorter, more conducive to role differentiation among general internists, and more supportive of subspecialization. Training could provide more experience in ambulatory care, multidisciplinary team-based care, chronic disease management, and quality improvement. The authors contend that the claim that internal medicine training ought to mirror internal medicine practice is mistaken. Many changes now proposed would likely damage if not destroy the consultant-generalist ideal of traditional internal medicine training which remains critical to effective medical care in the 21st century. The authors propose a model for training similar in structure but different in spirit from contending models. This model, like others, would involve a core experience in the first two years with tracking in the final year; unlike others, it would provide a conceptually coherent experience based on internal medicine's traditional ideal. Outpatient experience would be subsidiary to a predominantly inpatient experience, and it would be structured in blocks rather than continuity clinics. Twenty-first-century internists will continue to face what has always been the internist's task: the resolution of complex and ill-defined patient problems into proper diagnoses and therapeutic options. Contemporary internal medicine training must fit trainees for that task and must, thus, continue to offer the training experience necessary for the realization of the Oslerian ideal: a substantial apprenticeship taking care of inpatients with a wide range of medical illnesses. C1 [Huddle, Thomas S.] UAB, Sch Med, Div Gen Internal Med, Birmingham, AL 35294 USA. [Huddle, Thomas S.] Birmingham VA Med Ctr, Birmingham, AL USA. [Heudebert, Gustavo R.] Univ Alabama, Sch Med, Dept Med, Birmingham, AL 35294 USA. RP Huddle, TS (reprint author), UAB, Sch Med, Div Gen Internal Med, 1530 3rd Ave S,FOT 720, Birmingham, AL 35294 USA. EM thuddle@uab.edu NR 14 TC 19 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD OCT PY 2008 VL 83 IS 10 BP 910 EP 915 DI 10.1097/ACM.0b013e3181850a92 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 466IJ UT WOS:000267654500006 PM 18820519 ER PT J AU Bagic, A Theodore, WH Boudreau, EA Bonwetsch, R Greenfield, J Elkins, W Sato, S AF Bagic, A. Theodore, W. H. Boudreau, E. A. Bonwetsch, R. Greenfield, J. Elkins, W. Sato, S. TI Towards a non-invasive interictal application of hypothermia for treating seizures: a feasibility and pilot study SO ACTA NEUROLOGICA SCANDINAVICA LA English DT Article DE brain; core temperature; cortical excitability; epilepsy; non-invasive hypothermia; interictal cooling; seizures; treatment ID EXPERIMENTAL NEOCORTICAL SEIZURES; TEMPERATURE-MEASUREMENT; FOCAL SEIZURES; TECHNICAL NOTE; CRITICAL-CARE; EPILEPSY; BRAIN; PLACEBO; CORTEX; TERMINATION AB Objectives - To evaluate the feasibility and safety of head-neck cooling in conscious normal volunteers (10) and patients with medically refractory epilepsy (5) without causing shivering. Patients and methods - We used a non-invasive head-neck cooling system (CoolSystems Inc., Lincoln, CA, USA). The tympanic temperature (TT) and intestinal temperature (IT) were measured as two measurements of 'core temperature' (CT), and multi-site external temperatures, several physiologic variables and EEG were monitored. Seizure counts over 4-week precooling, treatment and follow-up phases were compared. Results - All 15 participants completed all the cooling sessions without significant complaints. At the end of 60 min of cooling, scalp temperature fell on average by 12.2 degrees C (P < 0.001), TT by 1.67 degrees C (P < 0.001), and IT by 0.12 degrees C (P = NS). Average weekly seizure frequency decreased from 2.7 to 1.7 events per patient per week (MANOVA: P < 0.05). Conclusions - Non-invasive head-neck cooling is safe and well-tolerated. Initial pilot data in patients suggest that additional therapeutic studies are warranted. C1 [Bagic, A.] Univ Pittsburgh, Sch Med, CABMSI, Pittsburgh, PA 15213 USA. [Bagic, A.; Bonwetsch, R.; Greenfield, J.; Sato, S.] NINDS, NIH, EEG Sect, Bethesda, MD 20892 USA. [Bagic, A.; Theodore, W. H.] NINDS, NIH, Clin Epilepsy Sect, Bethesda, MD 20892 USA. [Boudreau, E. A.] Portland VA Med Ctr, Portland, OR USA. [Elkins, W.] CoolSyst Inc, Lincoln, CA USA. BioCool Technol, Lincoln, CA USA. RP Bagic, A (reprint author), Univ Pittsburgh, Sch Med, CABMSI, Suite 811,Kaufmann Med Bldg,3471 5th Ave, Pittsburgh, PA 15213 USA. EM bagica@upmc.edu FU Intramural NIH HHS [Z01 NS002236-33] NR 38 TC 9 Z9 9 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0001-6314 J9 ACTA NEUROL SCAND JI Acta Neurol. Scand. PD OCT PY 2008 VL 118 IS 4 BP 240 EP 244 DI 10.1111/j.1600-0404.2008.01008.x PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 345BC UT WOS:000258970000005 PM 18355392 ER PT J AU Kiernan, TJ Yan, BP Jaff, MR AF Kiernan, Thomas J. Yan, Bryan P. Jaff, Michael R. TI Renal Artery Revascularization: Collaborative Approaches for Specialists SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE Renal artery stenosis; Stent angioplasty; Renal artery surgery; Embolic protection device; Restenosis ID ATHEROSCLEROTIC RENOVASCULAR DISEASE; BLOOD-PRESSURE CONTROL; TERM-FOLLOW-UP; STENT REVASCULARIZATION; BALLOON ANGIOPLASTY; HYPERTENSIVE PATIENTS; EMBOLIC PROTECTION; RANDOMIZED-TRIAL; MEDICAL THERAPY; STENOSIS AB Endovascular revascularization for atherosclerotic renal artery stenosis (RAS) is the revascularization strategy of choice for patients with hemodynamically and clinically significant renal artery stenosis. Surgical revascularization is reserved for failed endovascular therapy or concomitant abdominal aortic surgery. Endovascular renal artery stenting is associated with excellent technical success, low complication rates, and acceptable long-term patency. This technique has been proven to be beneficial for preserving kidney function and stabilizing or improving blood pressure control in selected patients. Nevertheless, deterioration in kidney function after the procedure in 10% to 20% of cases may limit the immediate benefits of this technique. Atheroembolism appears to play an important role in the cause of kidney dysfunction after renal revascularization. Renal revascularization with a distal embolic protection device is a promising strategy in reducing the risk of atheroembolism and deterioration in kidney function. (C) 2008 by the National Kidney Foundation, Inc. All rights reserved. C1 [Kiernan, Thomas J.; Yan, Bryan P.; Jaff, Michael R.] Massachusetts Gen Hosp, Dept Vasc Med & Intervent, Boston, MA 02114 USA. RP Jaff, MR (reprint author), Massachusetts Gen Hosp, Dept Vasc Med & Intervent, 55 Fruit St, Boston, MA 02114 USA. EM mjaff@partners.org RI Yan, Bryan/C-3390-2008; Yan, Bryan/P-5928-2015 NR 43 TC 1 Z9 1 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 1548-5595 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD OCT PY 2008 VL 15 IS 4 BP 363 EP 369 DI 10.1053/j.ackd.2008.07.005 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 360YH UT WOS:000260094200006 PM 18805382 ER PT J AU Casserly, IP AF Casserly, Ivan P. TI Interventional Management of Critical Limb Ischemia in Renal Patients SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE Kidney insufficiency; End-stage renal disease; Critical limb ischemia; Revascularization; Endovascular therapy; Limb salvage ID PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; PERIPHERAL ARTERIAL-DISEASE; SURGICAL REVASCULARIZATION; BYPASS-SURGERY; INSUFFICIENCY; MORTALITY; FIBROSIS; DIALYSIS; OUTCOMES; SALVAGE AB Critical limb ischemia (CLI) represents the most severe clinical manifestation of peripheral arterial disease (PAD), defined as the presence of chronic ischemic rest pain, ulcers, or gangrene attributable to objectively proven arterial occlusive disease. The occurrence of CLI in patients with kidney insufficiency portends a strikingly high rate of subsequent morbidity and mortality. Generally, the primary therapy for CLI is revascularization of the affected limb. However, patients with CLI and kidney insufficiency represent a unique and challenging patient subset, and data from surgical series suggest reduced rates of limb salvage and higher medium and long-term mortality rates for patients with kidney insufficiency compared with those with normal kidney function. In contemporary practice, endovascular techniques are fast replacing surgical bypass as the first-line revascularization strategy for CLI, based on high technical success rates and low rates of procedure-related morbidity and mortality. However, a large series on endovascular outcomes for the treatment of CLI in patients with kidney insufficiency is lacking. Based on the severely reduced long-term survival rates of patients with CLI and kidney insufficiency, future efforts should focus on early detection of PAD in patients with kidney insufficiency and institution of aggressive medical therapy to prevent progression in the global burden of atherosclerosis in this patient population. Published by Elsevier Inc. C1 Denver VA Med Ctr, Denver, CO USA. Univ Colorado Hlth Sci Aurora, Aurora, CO USA. RP Casserly, IP (reprint author), Univ Colorado Hosp, Cardiac & Vasc Ctr, Mail Stop B-132,Anschutz Med Campus,Leprino Bldg,, Aurora, CO 80045 USA. EM ivan.casserly@uchsc.edu NR 27 TC 13 Z9 14 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1548-5595 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD OCT PY 2008 VL 15 IS 4 BP 384 EP 395 DI 10.1053/j.ackd.2008.07.008 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 360YH UT WOS:000260094200009 PM 18805385 ER PT J AU Selesniemi, K Lee, HJ Tilly, JL AF Selesniemi, Kaisa Lee, Ho-Joon Tilly, Jonathan L. TI Moderate caloric restriction initiated in rodents during adulthood sustains function of the female reproductive axis into advanced chronological age SO AGING CELL LA English DT Article DE aging; caloric restriction; fecundity; fertility; menopause; oocyte; ovary; reproduction ID NONGROWING FOLLICLE NUMBER; AGING C57BL/6J MICE; DIETARY RESTRICTION; OOCYTE QUALITY; RHESUS-MONKEYS; BONE-MARROW; FOOD-INTAKE; FERTILITY; MENOPAUSE; MIMETICS AB Age-related ovarian failure in women heralds the transition into postmenopausal life, which is characterized by a loss of fertility and increased risk for cardiovascular disease, osteoporosis and cognitive dysfunction. Unfortunately, there are no options available for delaying loss of ovarian function with age in humans. Rodent studies have shown that caloric restriction (CR) can extend female fertile lifespan; however, much of this work initiated CR at weaning, which causes stunted adolescent growth and a delayed onset of sexual maturation. Herein we tested in mice if CR initiated in adulthood could delay reproductive aging. After 4 months of CR, the ovarian follicle reserve was doubled compared to ad libitum (AL)-fed age-matched controls, which in mating trials exhibited a loss of fertility by 15.5 months of age. In CR females returned to AL feeding at 15.5 months of age, approximately one-half remained fertile for 6 additional months and one-third continued to deliver offspring through 23 months of age. Notably, fecundity of CR-then-AL-fed females and postnatal offspring survival rates were dramatically improved compared with aging AL-fed controls. For example, between 10 and 23 months of age, only 22% of the 54 offspring delivered by AL-fed females survived. In contrast, over 73% of the 94 pups delivered by 15.5- to 23-month-old CR-then-AL-fed mice survived without any overt complications. These data indicate that in mice adult-onset CR maintains function of the female reproductive axis into advanced age and dramatically improves postnatal survival of offspring delivered by aged females. C1 [Selesniemi, Kaisa; Lee, Ho-Joon; Tilly, Jonathan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent OB GYN Serv, Boston, MA 02114 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent OB GYN Serv, THR 901B,55 Fruit St, Boston, MA 02114 USA. EM jtilly@partners.org FU National Institute on Aging [R37-AG012279]; Rubin Shulsky Philanthropic Fund; Henry and Vivian Rosenberg Philanthropic Fund; Sea Breeze Foundation; JM Foundation; Vincent Memorial Research Funds FX This work was supported by a MERIT Award from the National Institute on Aging (R37-AG012279), the Rubin Shulsky Philanthropic Fund, the Henry and Vivian Rosenberg Philanthropic Fund, the Sea Breeze Foundation, the JM Foundation, and Vincent Memorial Research Funds. NR 49 TC 55 Z9 58 U1 4 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1474-9718 J9 AGING CELL JI Aging Cell PD OCT PY 2008 VL 7 IS 5 BP 622 EP 629 DI 10.1111/j.1474-9726.2008.00409.x PG 8 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 349TU UT WOS:000259307000003 PM 18549458 ER PT J AU Strong, R Miller, RA Astle, CM Floyd, RA Flurkey, K Hensley, KL Javors, MA Leeuwenburgh, C Nelson, JF Ongini, E Nadon, NL Warner, HR Harrison, DE AF Strong, Randy Miller, Richard A. Astle, Clinton M. Floyd, Robert A. Flurkey, Kevin Hensley, Kenneth L. Javors, Martin A. Leeuwenburgh, Christiaan Nelson, James F. Ongini, Ennio Nadon, Nancy L. Warner, Huber R. Harrison, David E. TI Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice SO AGING CELL LA English DT Article DE aging; aspirin; longevity; mice; nordihydroguaiaretic acid ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; TERT-BUTYL NITRONE; COLORECTAL-CANCER; BREAST-CANCER; RATS; 5-LIPOXYGENASE; ACTIVATION; GROWTH; CELLS; MODEL AB The National Institute on Aging's Interventions Testing Program was established to evaluate agents that are purported to increase lifespan and delay the appearance of age-related disease in genetically heterogeneous mice. Up to five compounds are added to the study each year and each compound is tested at three test sites (The Jackson Laboratory, University of Michigan, and University of Texas Health Science Center at San Antonio). Mice in the first cohort were exposed to one of four agents: aspirin, nitroflurbiprofen, 4-OH-alpha-phenyl-N-tert-butyl nitrone, or nordihydroguaiaretic acid (NDGA). Sample size was sufficient to detect a 10% difference in lifespan in either sex, with 80% power, using data from two of the three sites. Pooling data from all three sites, a log-rank test showed that both NDGA (p = 0.0006) and aspirin (p = 0.01) led to increased lifespan of male mice. Comparison of the proportion of live mice at the age of 90% mortality was used as a surrogate for measurement of maximum lifespan; neither NDGA (p = 0.12) nor aspirin (p = 0.16) had a significant effect in this test. Measures of blood levels of NDGA or aspirin and its salicylic acid metabolite suggest that the observed lack of effects of NDGA or aspirin on lifespan in females could be related to gender differences in drug disposition or metabolism. Further studies are warranted to find whether NDGA or aspirin, over a range of doses, might prove to postpone death and various age-related outcomes reproducibly in mice. C1 [Strong, Randy] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. [Strong, Randy] S Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX 78229 USA. [Miller, Richard A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Miller, Richard A.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Miller, Richard A.] Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA. [Miller, Richard A.] Ann Arbor VA Med Ctr, Ann Arbor, MI 48109 USA. [Astle, Clinton M.; Flurkey, Kevin; Harrison, David E.] Jackson Lab, Bar Harbor, ME 04609 USA. [Floyd, Robert A.; Hensley, Kenneth L.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Floyd, Robert A.] Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73104 USA. [Javors, Martin A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Leeuwenburgh, Christiaan] Univ Florida, Dept Aging & Geriatr, Gainesville, FL 32610 USA. [Nelson, James F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Nelson, James F.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Ongini, Ennio] Nicox Res Inst, Milan, Italy. [Nadon, Nancy L.] NIA, Biol Aging Program, Bethesda, MD 20892 USA. [Warner, Huber R.] Univ Minnesota, Coll Biol Sci, St Paul, MN 55108 USA. RP Strong, R (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM strong@uthscsa.edu FU National Institute on Aging [AG022303, AG025707, AG022308, AG022307, AG13319]; Department of Veterans Affairs FX This work was supported by National Institute on Aging grants AG022303 (R.A.M.), AG025707 and AG022308 (D.E.H.), and AG022307 and AG13319 (R.S.), and the Department of Veterans Affairs (R.M. and R.S.). We wish to thank Vivian Diaz, Elizabeth Fernandez, Greg Friesenhahn, Melissa Han, Patricia Harrison, Roni Kobrosly, Bill Kohler, Pam Krason, Jessica Sewald, and Maggie Lauderdale for technical support. We thank Scott Pletcher and Andrzej Galecki for assistance in power analysis and study design. NR 51 TC 103 Z9 106 U1 0 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1474-9718 J9 AGING CELL JI Aging Cell PD OCT PY 2008 VL 7 IS 5 BP 641 EP 650 DI 10.1111/j.1474-9726.2008.00414.x PG 10 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 349TU UT WOS:000259307000005 PM 18631321 ER PT J AU Sands, LP Xu, H Craig, BA Eng, C Covinsky, KE AF Sands, Laura P. Xu, Huiping Craig, Bruce A. Eng, Catherine Covinsky, Kenneth E. TI Predicting change in functional status over quarterly intervals for older adults enrolled in the PACE community-based long-term care program SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ADL status; change in functioning; long-term care ID PHYSICAL PERFORMANCE; UNITED-STATES; RISK-FACTORS; HOME HEALTH; UNMET NEED; DISABILITY; DEPENDENCE; DECLINE; SERVICES; RECOVERY AB Background and aims: Many frail older adults experience multiple changes in activities of daily living (ADL) functioning over the course of a year. Accurate predictions of ADL status over quarterly intervals may improve the precision of care planning for older adults who seek long-term care in the community. The study sought to develop and validate a model that predicts older adults' ADL status over quarterly intervals. Methods: The study included 3127 enrollees from 11 Program of All Inclusive Care for the Elderly (PACE) sites. Nurses assessed ADL status quarterly. Potential predictors included baseline assessment of age, sex, race, and living situation and quarterly assessments of prior functioning, co-morbidities, prior hospitalizations, and mental status. Results: Change in level of functioning occurred for 30% of quarterly observations. Predictors of functioning at the end of a quarter were prior ADL change, prior hospitalization, living with others, impaired mental status., cancer, dementia, coronary artery disease, congestive heart failure and chronic obstructive pulmonary disease. When the model was applied to the validation observations, 93% of predictions were within one level and 72% of the predictions were the same level of ADL functioning observed at the end of the quarter. Conclusions: In a sample of community-living ADL-disabled older adults, changes in functional status over a quarter were common and associated with functional and health status at the beginning of the quarter. Further validation of the model may result in an index that helps clinicians better predict future ADL needs of community-living older adults who need long-term care. (Aging Clin Exp Res 2008; 20: 419-427) (c) 2008, Editrice Kurtis. C1 [Sands, Laura P.] Purdue Univ, Sch Nursing, W Lafayette, IN 47907 USA. [Sands, Laura P.; Craig, Bruce A.] Purdue Univ, Ctr Aging & Life Course, W Lafayette, IN 47907 USA. [Eng, Catherine] OnLok Senior Hlth Serv, San Francisco, CA USA. [Eng, Catherine; Covinsky, Kenneth E.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Covinsky, Kenneth E.] Univ Calif San Francisco, MT Z Ctr Aging, San Francisco, CA 94143 USA. [Covinsky, Kenneth E.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Sands, LP (reprint author), Purdue Univ, Sch Nursing, 502 N Univ St, W Lafayette, IN 47907 USA. EM lsands@nursing.purdue.edu RI Craig, Bruce/D-5797-2017; Sands, Laura/E-8919-2015 OI Craig, Bruce/0000-0001-9346-467X; Sands, Laura/0000-0003-2446-4486 FU NIH [R01AG-022090, R01AG023626] FX This work was supported by NIH grants R01AG-022090 and R01AGO23626 to L. Sands and K. Covinsky, respectively. A portion of this paper was presented at the 58th Annual Scientific meeting of the Gerontological Society of America, Washington DC. NR 36 TC 5 Z9 5 U1 0 U2 4 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 OCT PY 2008 VL 20 IS 5 BP 419 EP 427 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 381BR UT WOS:000261510300006 PM 19039283 ER PT J AU Schackman, BR Scott, CA Walensky, RP Losina, E Freedberg, KA Sax, PE AF Schackman, Bruce R. Scott, Callie A. Walensky, Rochelle P. Losina, Elena Freedberg, Kenneth A. Sax, Paul E. TI The cost-effectiveness of HLA-B*5701 genetic screening to guide initial antiretroviral therapy for HIV SO AIDS LA English DT Article DE abacavir; antiretroviral therapy; cost-effectiveness; genetic testing; HIV ID ABACAVIR HYPERSENSITIVITY REACTION; NAIVE PATIENTS; TENOFOVIR DF; COMBINATION; PHARMACOGENOMICS; EMTRICITABINE; EFAVIRENZ; SAFETY; COHORT; CARE AB Objective: To evaluate the clinical impact and cost-effectiveness of HLA-B*5701 testing to guide selection of first-line HIV regimens in the United States. Design: Cost-effectiveness analysis using a simulation model of HIV disease. The prevalence of HLA-B*5701 and the probabilities of confirmed and unconfirmed severe systemic hypersensitivity reaction among patients taking abacavir testing HLA-B*5701 positive and negative were from the Prospective Randomized Evaluation of DNA Screening in a Clinical Trial study. The monthly costs of abacavir-based and tenofovir-based regimens were $1135 and $1139, respectively; similar virologic efficacy was assumed and this assumption was varied in sensitivity analysis. Patients: Simulated cohort of patients initiating HIV therapy. Interventions: The interventions are first-line abacavir, lamivudine, and efavirenz without pretreatment HLA-B*5701 testing; the same regimen with HLA-B*5701 testing; and first-line tenofovir, emtricitabine, and efavirenz. Main outcome measures: Quality-adjusted life years and lifetime medical costs discounted at 3% per annum, cost-effectiveness ratios ($/QALY). Results: Abacavir-based treatment without HLA-B*5701 testing resulted in a projected 30.93 years life expectancy, 16.23 discounted quality-adjusted life years, and $472 200 discounted lifetime cost per person. HLA-B*5701 testing added 0.04 quality-adjusted months at all incremental cost of $110, resulting in a cost-effectiveness ratio of $36 700/ QALY compared with no testing. Initiating treatment with a tenofovir-based regimen increased costs without improving quality-adjusted life expectancy. HLA-B*5701 testing remained the preferred strategy only if abacavir-based treatment had equal efficacy and cost less per month than tenofovir-based treatment. Results were also sensitive to the cost of HLA-B*5701 testing and the prevalence of HLA-B*5701. Conclusion: Pharmacogenetic testing for HLA-B*5701 is cost-effective only if abacavir-based treatment is as effective and costs less than tenofovir-based treatment. (c) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Schackman, Bruce R.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY 10021 USA. [Scott, Callie A.; Walensky, Rochelle P.; Losina, Elena; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Scott, Callie A.; Walensky, Rochelle P.; Losina, Elena; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Scott, Callie A.; Walensky, Rochelle P.; Losina, Elena; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. [Walensky, Rochelle P.; Losina, Elena; Freedberg, Kenneth A.; Sax, Paul E.] Harvard Univ, Sch Med, Div AIDS, Boston, MA USA. [Walensky, Rochelle P.; Losina, Elena; Freedberg, Kenneth A.; Sax, Paul E.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. [Walensky, Rochelle P.; Sax, Paul E.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Schackman, BR (reprint author), Weill Cornell Med Coll, Dept Publ Hlth, 411 E 69th St, New York, NY 10021 USA. EM brs2006@med.cornell.edu OI Walensky, Rochelle P./0000-0002-8795-379X FU National Institute of Allergy and Infectious Diseases [K24 AI062476, K25 AI50436, R37 AI42006]; National Institute on Drug Abuse [K01 DA017179] FX Financial Support: National Institute of Allergy and Infectious Diseases (K24 AI062476, K25 AI50436 and R37 AI42006), National Institute on Drug Abuse (K01 DA017179). NR 34 TC 79 Z9 84 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD OCT 1 PY 2008 VL 22 IS 15 BP 2025 EP 2033 DI 10.1097/QAD.0b013e3283103ce6 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 355AD UT WOS:000259680100015 PM 18784465 ER PT J AU Pyne, JM Asch, SM Lincourt, K Kilbourne, AM Bowman, C Atkinson, H Gifford, A AF Pyne, Jeffrey M. Asch, Steven M. Lincourt, Katherine Kilbourne, Amy M. Bowman, Candice Atkinson, Hamp Gifford, Allen TI Quality indicators for depression care in HIV patients SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE depression; expert panel; HIV; quality of care ID MULTICENTER AIDS COHORT; ANTIRETROVIRAL THERAPY; HEALTH-CARE; PSYCHIATRIC COMORBIDITY; INFECTED PATIENTS; RISK-FACTORS; DRUG-USERS; ADHERENCE; SYMPTOMS; DISORDERS AB HIV patients are at increased risk for depression. However, a comprehensive set of quality of care indicators for depression in the context of HIV does not exist. We report the results of a recent expert panel convened to develop a comprehensive set of HIV depression quality indicators. We systematically reviewed the depression and HIV depression literature to provide the evidence for the quality indicators. The HIV depression quality indicators were divided into six chapters: general, bereavement, substance abuse, viral hepatitis, cognitive impairment and drug interactions. A modified Delphi expert panel method was used to evaluate the validity and feasibility of the candidate quality indicators. The expert panel included HIV physicians, psychiatrists and a pharmacist, all with experience with HIV depression. The in-person eleven-member panel rated 80 candidate HIV-depression quality indicators. Indicators were evaluated using main and sensitivity analysis criteria for validity and feasibility. Seventy-four percent (59/80) of the quality indicators met a priori main analysis criteria for validity and feasibility and 61% met sensitivity analysis criteria. Approved indicators that are more specific to HIV depression include: depression screening frequency; depression screening and treatment in the context of hepatitis C optimizing depression and HIV treatment in the context of cognitive impairment;, and starting antidepressants at lower doses but advancing to doses typical for the general population. Most adverse medication interaction indicators did not meet main analysis validity criteria. The quality indicators identified in this study provide a useful tool for measuring and informing the quality of HIV-depression care. C1 [Pyne, Jeffrey M.; Lincourt, Katherine] Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. [Asch, Steven M.] GLAHS, Dept Vet Affairs, Los Angeles, CA USA. [Kilbourne, Amy M.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Kilbourne, Amy M.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Kilbourne, Amy M.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Bowman, Candice] VA San Diego Healthcare Syst, QUERI HIV, Hlth Serv Res & Dev, San Diego, CA USA. [Atkinson, Hamp] San Diego Vet Healthcare Syst, Psychiat Serv, San Diego, CA USA. [Atkinson, Hamp] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Gifford, Allen] VA Bedford Ctr Hlth Qual, Ctr Hlth Qual Outcomes & Econ Res, Boston, MA USA. EM jmpyne@uams.edu NR 44 TC 9 Z9 9 U1 5 U2 7 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD OCT PY 2008 VL 20 IS 9 BP 1075 EP 1083 DI 10.1080/09540120701796884 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 363WN UT WOS:000260298300007 PM 18825515 ER PT J AU Pereyra, F Heckerman, D Rothchild, A Brian, B Baker, B Walker, BD AF Pereyra, F. Heckerman, D. Rothchild, A. Brian, B. Baker, B. Walker, B. D. TI Epitope Specific CD8+T-Cell Responses Predict Spontaneous HIV Virus Replication SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2008 Conference CY OCT 13-16, 2008 CL Cape Town, SOUTH AFRICA SP NIAID, Div AIDS, NIH, Div AIDS C1 [Pereyra, F.; Heckerman, D.; Rothchild, A.; Brian, B.; Baker, B.; Walker, B. D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 OCT PY 2008 VL 24 BP 19 EP 20 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 367CT UT WOS:000260530800045 ER PT J AU Schneidewind, A Tang, Y Ryland, E Dunkley-Thompson, J Steel-Duncan, J Singh-Minott, I John, AS Kalams, S Conrad, J Christie, CD Walker, BD Allen, TM Feeney, ME AF Schneidewind, A. Tang, Y. Ryland, E. Dunkley-Thompson, J. Steel-Duncan, J. Singh-Minott, I. John, A. St. Kalams, S. Conrad, J. Christie, C. D. Walker, B. D. Allen, T. M. Feeney, M. E. TI Control of Viremia in B57+Infants is Mediated by Fitness-Attenuating Mutations SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2008 Conference CY OCT 13-16, 2008 CL Cape Town, SOUTH AFRICA SP NIAID, Div AIDS, NIH, Div AIDS C1 [Schneidewind, A.; Tang, Y.; Ryland, E.; Dunkley-Thompson, J.; Steel-Duncan, J.; Singh-Minott, I.; Christie, C. D.; Allen, T. M.] Univ Hosp W Indies, Kingston, Mona, Jamaica. [John, A. St.] Queen Elizabeth Hosp, Bridgetown, Barbados. [Kalams, S.; Conrad, J.] Vanderbilt Univ, Nashville, TN USA. [Walker, B. D.; Feeney, M. E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. 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 OCT PY 2008 VL 24 BP 20 EP 20 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 367CT UT WOS:000260530800047 ER PT J AU Wang, YE Li, B Carlson, JM Streeck, H Gladden, AD Schneidewind, A Power, KA Toth, I Frahm, N Alter, G Brander, C Carrington, M Walker, BD Altfeld, M Heckerman, D Allen, T AF Wang, Y. E. Li, B. Carlson, J. M. Streeck, H. Gladden, A. D. Schneidewind, A. Power, K. A. Toth, I. Frahm, N. Alter, G. Brander, C. Carrington, M. Walker, B. D. Altfeld, M. Heckerman, D. Allen, T. TI Protective HLA Class I Alleles Restrict Acute-Phase CD8 Responses that Select for Viral Escape in Highly Conserved Regions of HIV SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2008 Conference CY OCT 13-16, 2008 CL Cape Town, SOUTH AFRICA SP NIAID, Div AIDS, NIH, Div AIDS C1 [Wang, Y. E.; Li, B.; Streeck, H.; Gladden, A. D.; Schneidewind, A.; Power, K. A.; Toth, I.; Frahm, N.; Alter, G.; Brander, C.; Altfeld, M.; Allen, T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. [Heckerman, D.] Microsoft Res, Redmond, WA USA. [Carrington, M.] NCI, Lab Genom Div, Frederick, MD 21701 USA. [Walker, B. D.] Howard Hughes Med Inst, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2008 VL 24 BP 21 EP 22 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 367CT UT WOS:000260530800050 ER PT J AU Alter, G Rihn, S Kavanagh, D Altfeld, M AF Alter, G. Rihn, S. Kavanagh, D. Altfeld, M. TI NK Cell Mediated Deletion of Dendritic Cell Populations SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2008 Conference CY OCT 13-16, 2008 CL Cape Town, SOUTH AFRICA SP NIAID, Div AIDS, NIH, Div AIDS C1 [Alter, G.; Rihn, S.; Kavanagh, D.; Altfeld, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2008 VL 24 BP 29 EP 29 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 367CT UT WOS:000260530800070 ER PT J AU Carr, WH Naranbhai, V Arase, H Lanier, LL Cavrois, M Neidleman, JA Greene, WC AF Carr, W. H. Naranbhai, V. Arase, H. Lanier, L. L. Cavrois, M. Neidleman, J. A. Greene, W. C. TI KIR2DS1, an HLA-Cw4 Specific Stimulatory NK Cell Receptor, Preferentially Binds to HIV-1 Infected Cells Presenting HLA-Cw4-Restricted HIV-1 Epitopes SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2008 Conference CY OCT 13-16, 2008 CL Cape Town, SOUTH AFRICA SP NIAID, Div AIDS, NIH, Div AIDS C1 [Carr, W. H.] Massachusetts Gen Hosp, Charlestown, MA USA. [Naranbhai, V.] Univ KwaZulu Natal, Sch Med, HPP, Durban, Kwazulu Natal, South Africa. [Naranbhai, V.] Univ KwaZulu Natal, Sch Med, CAPRISA, Durban, Kwazulu Natal, South Africa. [Arase, H.] Osaka Univ, Inst Microbial Dis, Osaka, Japan. [Lanier, L. L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Cavrois, M.; Neidleman, J. A.; Greene, W. C.] Gladstone Inst Virol & Immunol, San Francisco, CA USA. [Carr, W. H.] Univ KwaZulu Natal, Nelson Mandela Sch Med, Doris Duke Med Res Ctr, HIV Pathogenesis Programme, Durban, South Africa. 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 OCT PY 2008 VL 24 BP 30 EP 30 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 367CT UT WOS:000260530800072 ER PT J AU Brumme, ZL John, M Brumme, CJ Carlson, JM Haubrich, R Riddler, S Swenson, L Tao, I Szeto, S Chan, D Kadie, C Frahm, N Brander, C Walker, BD Heckerman, D Harrigan, P Mallal, S AF Brumme, Z. L. John, M. Brumme, C. J. Carlson, J. M. Haubrich, R. Riddler, S. Swenson, L. Tao, I. Szeto, S. Chan, D. Kadie, C. Frahm, N. Brander, C. Walker, B. D. Heckerman, D. Harrigan, P. Mallal, S. TI Relationship between HLA Class I-driven Evolution in Gag, Pol and Nef and Clinical Markers of HIV Disease: A Multicenter Collaborative Study SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2008 Conference CY OCT 13-16, 2008 CL Cape Town, SOUTH AFRICA SP NIAID, Div AIDS, NIH, Div AIDS C1 [Brumme, Z. L.; Brumme, C. J.; Frahm, N.; Brander, C.; Walker, B. D.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. [John, M.; Mallal, S.] Ctr Clin Immunol & Biomed Stat, Perth, WA, Australia. [Carlson, J. M.; Kadie, C.; Heckerman, D.] Microsoft Res, Redmond, WA USA. [Haubrich, R.] Univ Calif San Diego, San Diego, CA 92103 USA. [Riddler, S.] Univ Pittsburgh, Pittsburgh, PA USA. [Swenson, L.; Tao, I.; Szeto, S.; Chan, D.; Harrigan, P.] BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada. RI Grandhi, Manasa/A-7711-2008 NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2008 VL 24 BP 75 EP 75 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 367CT UT WOS:000260530800186 ER PT J AU Matthews, PC Leslie, A Katzourakis, A Power, K Kelleher, AD Allen, T Pybus, OG Goulder, PJ AF Matthews, P. C. Leslie, A. Katzourakis, A. Power, K. Kelleher, A. D. Allen, T. Pybus, O. G. Goulder, P. J. TI HLA Footprints in HIV-1 Drive Phylogenetic Clustering and Inter-Clade Variation SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2008 Conference CY OCT 13-16, 2008 CL Cape Town, SOUTH AFRICA SP NIAID, Div AIDS, NIH, Div AIDS C1 [Power, K.; Allen, T.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. [Kelleher, A. D.] St Vincent Hosp, Ctr Immunol, Sydney, NSW, Australia. [Leslie, A.; Goulder, P. J.] Univ Oxford, Dept Paediat, Oxford, Oxon, England. [Katzourakis, A.; Pybus, O. G.] Univ Oxford, Dept Zool, Oxford, Oxon, England. 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 OCT PY 2008 VL 24 BP 75 EP 75 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 367CT UT WOS:000260530800187 ER PT J AU Brumme, CJ Brumme, ZL Carlson, J Markowitz, M Jessen, H Kelleher, A John, M Mallal, S Allen, T Heckerman, D Walker, BD AF Brumme, C. J. Brumme, Z. L. Carlson, J. Markowitz, M. Jessen, H. Kelleher, A. John, M. Mallal, S. Allen, T. Heckerman, D. Walker, B. D. TI Reversion of HLA-Associated Polymorphisms in Gag, Pol and Nef during the First Year of HIV Infection: Sites, Rates and pVL Correlations SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2008 Conference CY OCT 13-16, 2008 CL Cape Town, SOUTH AFRICA SP NIAID, Div AIDS, NIH, Div AIDS C1 [Brumme, Z. L.; Walker, B. D.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. [Carlson, J.; Heckerman, D.] Microsoft Res, Redmond, WA USA. [Markowitz, M.] Aaron Diamond AIDS Res Ctr, New York, NY USA. [Jessen, H.] Jessen Praxis, Berlin, Germany. [Kelleher, A.] Univ New S Wales, Sydney, NSW, Australia. [John, M.; Mallal, S.] Murdoch Univ, Perth, WA, Australia. RI Grandhi, Manasa/A-7711-2008 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 OCT PY 2008 VL 24 BP 76 EP 77 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 367CT UT WOS:000260530800190 ER PT J AU Miura, T Brumme, C Brockman, MA Pereyra, F Block, B Trocha, A Brumme, Z John, M Mallal, S Harrigan, R Walker, B AF Miura, T. Brumme, C. Brockman, M. A. Pereyra, F. Block, B. Trocha, A. Brumme, Z. John, M. Mallal, S. Harrigan, R. Walker, B. TI HLA-Associated Mutations Occur Less Frequently in HIV Elite Controllers than in Chronically Infected Individuals SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2008 Conference CY OCT 13-16, 2008 CL Cape Town, SOUTH AFRICA SP NIAID, Div AIDS, NIH, Div AIDS C1 [Brockman, M. A.; Pereyra, F.; Block, B.; Trocha, A.; Brumme, Z.; Walker, B.] Massachusetts Gen Hosp, Charlestown, MA USA. [Miura, T.; Brumme, C.; John, M.; Mallal, S.] Murdoch Univ, Perth, WA, Australia. [Miura, T.; Brumme, C.; John, M.; Mallal, S.] Royal Perth Hosp, Perth, WA, Australia. [Harrigan, R.] St Pauls Hosp, BC Ctr Excellence HIV AIDS, Vancouver, BC V6Z 1Y6, Canada. NR 0 TC 1 Z9 1 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 OCT PY 2008 VL 24 BP 77 EP 78 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 367CT UT WOS:000260530800193 ER PT J AU Hempel, U Buranapraditkun, S Chatkulkawin, P Allgaier, RL Thantivorasit, P Pitakpolrat, P Lorenzen, S Sirivichayakul, S Hildebrand, WH Brander, C Walker, BD Phanuphak, P Allen, TM Ruxrungtham, K AF Hempel, U. Buranapraditkun, S. Chatkulkawin, P. Allgaier, R. L. Thantivorasit, P. Pitakpolrat, P. Lorenzen, S. Sirivichayakul, S. Hildebrand, W. H. Brander, C. Walker, B. D. Phanuphak, P. Allen, T. M. Ruxrungtham, K. TI Viral Escape from a Dominant HLA-Cw01-Restricted Gag Epitope in HIV-1 Clade A/E Infection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2008 Conference CY OCT 13-16, 2008 CL Cape Town, SOUTH AFRICA SP NIAID, Div AIDS, NIH, Div AIDS C1 [Hempel, U.; Allgaier, R. L.; Brander, C.; Walker, B. D.; Allen, T. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Buranapraditkun, S.; Chatkulkawin, P.; Thantivorasit, P.; Pitakpolrat, P.; Lorenzen, S.; Sirivichayakul, S.; Phanuphak, P.; Ruxrungtham, K.] Chulalongkorn Univ, Vaccine & Cellular Immunol Lab, Bangkok, Thailand. [Hildebrand, W. H.] Univ Oklahoma, Dept Microbiol & Immunol, Oklahoma City, OK USA. 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 OCT PY 2008 VL 24 BP 78 EP 78 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 367CT UT WOS:000260530800194 ER PT J AU Schneidewind, A Brumme, ZL Brume, CJ Power, KA Reyor, LL O'Sullivan, K Jessen, H Markowitz, M Rosenberg, ES Sekaly, R Kelleher, AD Walker, BD Allen, TM AF Schneidewind, A. Brumme, Z. L. Brume, C. J. Power, K. A. Reyor, L. L. O'Sullivan, K. Jessen, H. Markowitz, M. Rosenberg, E. S. Sekaly, R. Kelleher, A. D. Walker, B. D. Allen, T. M. TI Long-term Stability of Compensated CTL Escape Mutations following Acute HIV Infection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2008 Conference CY OCT 13-16, 2008 CL Cape Town, SOUTH AFRICA SP NIAID, Div AIDS, NIH, Div AIDS C1 [Schneidewind, A.; Brumme, Z. L.; Brume, C. J.; Power, K. A.; Reyor, L. L.; O'Sullivan, K.; Rosenberg, E. S.; Walker, B. D.; Allen, T. M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. [Jessen, H.] Jessen Praxis, Berlin, Germany. [Markowitz, M.] Aaron Diamond AIDS Res Ctr, New York, NY USA. [Markowitz, M.] Univ Montreal, Motnreal, PQ, Canada. [Kelleher, A. D.] Univ New S Wales, Sydney, NSW, Australia. 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 OCT PY 2008 VL 24 BP 78 EP 78 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 367CT UT WOS:000260530800195 ER PT J AU Liu, Q Sun, Y Rihn, S Pereyra, F Walker, B Alter, G AF Liu, Q. Sun, Y. Rihn, S. Pereyra, F. Walker, B. Alter, G. TI Protective Antibody Dependent Cellular Cytotoxicity Depends on the Coordinated Presence of Both Highly Functional NK Cells and HIV-Specific Antibodies SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2008 Conference CY OCT 13-16, 2008 CL Cape Town, SOUTH AFRICA SP NIAID, Div AIDS, NIH, Div AIDS C1 [Liu, Q.; Rihn, S.; Pereyra, F.; Walker, B.; Alter, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sun, Y.] Fourth Mil Med Univ, Tangdu Hosp, Xian 710032, Peoples R China. 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 OCT PY 2008 VL 24 BP 81 EP 82 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 367CT UT WOS:000260530800203 ER PT J AU Wong, AH Williams, K Reddy, S Van Der Stok, M Giddy, J Wilson, D Alter, G Ghebremichael, MS Carrington, M Ndung'u, T Walker, B Altfeld, M Carr, WH AF Wong, A. H. Williams, K. Reddy, S. Van der Stok, M. Giddy, J. Wilson, D. Alter, G. Ghebremichael, M. S. Carrington, M. Ndung'u, T. Walker, B. Altfeld, M. Carr, W. H. TI Alterations in Natural Killer Cell Receptor Profiles during HIV-1 Disease Progression among Chronically Infected South African Adults SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2008 Conference CY OCT 13-16, 2008 CL Cape Town, SOUTH AFRICA SP NIAID, Div AIDS, NIH, Div AIDS C1 [Wong, A. H.; Williams, K.; Reddy, S.; Van der Stok, M.; Alter, G.; Ndung'u, T.; Walker, B.; Altfeld, M.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. [Giddy, J.] MCcord Hosp, Durban, Kwazulu Natal, South Africa. [Wilson, D.] Edendale Hosp, Dept Med, Edendale, Kwazulu Natal, South Africa. [Ghebremichael, M. S.] Harvard Univ, Boston, MA 02115 USA. [Ghebremichael, M. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Carrington, M.] NCI, SAIC Frederick, Frederick, MD 21701 USA. [Carr, W. H.] Univ Kwazulu Natal, Doris Duke Med Res Ctr, Durban, Kwazulu Natal, South Africa. NR 0 TC 0 Z9 0 U1 0 U2 3 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 OCT PY 2008 VL 24 BP 83 EP 84 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 367CT UT WOS:000260530800208 ER PT J AU Brumme, Z Nair, K Wang, B van der Stok, M Brumme, C Bishop, K Reddy, S Mncube, Z Chonco, F Frahm, N Goulder, P Ndung'u, T Freedberg, K Losina, E Walker, B AF Brumme, Z. Nair, K. Wang, B. van der Stok, M. Brumme, C. Bishop, K. Reddy, S. Mncube, Z. Chonco, F. Frahm, N. Goulder, P. Ndung'u, T. Freedberg, K. Losina, E. Walker, B. TI Combined Clinical and Immunological Biomarkers Predict Rates of CD4 Decline in Chronic Untreated HIV Infection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2008 Conference CY OCT 13-16, 2008 CL Cape Town, SOUTH AFRICA SP NIAID, Div AIDS, NIH, Div AIDS C1 [Brumme, Z.; Brumme, C.; Frahm, N.; Walker, B.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. [Nair, K.; van der Stok, M.; Bishop, K.; Reddy, S.; Mncube, Z.; Chonco, F.; Ndung'u, T.] Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, Kwazulu Natal, South Africa. [Wang, B.; Freedberg, K.; Losina, E.] Massachusetts Gen Hosp, Program HIV Outcomes Res, Boston, MA 02114 USA. [Goulder, P.] Nuffield Dept Med, Dept Pediat, Oxford, England. 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 OCT PY 2008 VL 24 BP 122 EP 122 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 367CT UT WOS:000260530800312 ER PT J AU Kwon, DS Brockman, MA Tighe, DP Pavlik, DF Addo, MM Kavanagh, DG Waring, M Walker, BD Kaufmann, DE AF Kwon, D. S. Brockman, M. A. Tighe, D. P. Pavlik, D. F. Addo, M. M. Kavanagh, D. G. Waring, M. Walker, B. D. Kaufmann, D. E. TI Role of CD4+CD25+Regulatory T Cells in IL-10 Mediated T Cell Impairment in Chronic HIV Infection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2008 Conference CY OCT 13-16, 2008 CL Cape Town, SOUTH AFRICA SP NIAID, Div AIDS, NIH, Div AIDS C1 [Kwon, D. S.; Brockman, M. A.; Tighe, D. P.; Pavlik, D. F.; Addo, M. M.; Kavanagh, D. G.; Waring, M.; Walker, B. D.; Kaufmann, D. E.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 9 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 OCT PY 2008 VL 24 BP 128 EP 128 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 367CT UT WOS:000260530800327 ER PT J AU Juelg, B Pereyra, F Piechocka-Trocha, A Rothchild, A Baker, B Walker, BD AF Juelg, B. Pereyra, F. Piechocka-Trocha, A. Rothchild, A. Baker, B. Walker, B. D. TI Defining the Correlates of Immune Protection Using the Viral Inhibition Assay: Does Immunodominance Correlate with Antiviral Suppressive Capacity? SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2008 Conference CY OCT 13-16, 2008 CL Cape Town, SOUTH AFRICA SP NIAID, Div AIDS, NIH, Div AIDS C1 [Juelg, B.; Pereyra, F.; Piechocka-Trocha, A.; Rothchild, A.; Baker, B.; Walker, B. D.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2008 VL 24 BP 129 EP 129 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 367CT UT WOS:000260530800330 ER PT J AU Frahm, N Price, DA Hartman, K Pereyra, F Walker, BD Douek, DC Brander, C AF Frahm, N. Price, D. A. Hartman, K. L. Pereyra, F. Walker, B. D. Douek, D. C. Brander, C. TI The Functional Avidity of HIV-Specific CTL Responses is Associated with Control of Viral Replication In Vivo SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2008 Conference CY OCT 13-16, 2008 CL Cape Town, SOUTH AFRICA SP NIAID, Div AIDS, NIH, Div AIDS C1 [Frahm, N.] Fred Hutchinson Canc Res Ctr, HVTN, Seattle, WA 98104 USA. [Price, D. A.; Douek, D. C.] NIAID, Human Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Hartman, K. L.; Pereyra, F.; Walker, B. D.; Brander, C.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. [Hartman, K. L.; Pereyra, F.; Walker, B. D.; Brander, C.] HMS, Charlestown, MA USA. RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 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 OCT PY 2008 VL 24 BP 131 EP 131 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 367CT UT WOS:000260530800335 ER PT J AU Al-Khatib, SM Sanders, GD Carlson, M Cicic, A Curtis, A Fonarow, GC Groeneveld, PW Hayes, D Heidenreich, P Mark, D Peterson, E Prystowsky, EN Sager, P Salive, ME Thomas, K Yancy, CW Zareba, W Zipes, D AF Al-Khatib, Sana M. Sanders, Gillian D. Carlson, Mark Cicic, Aida Curtis, Anne Fonarow, Gregg C. Groeneveld, Peter W. Hayes, David Heidenreich, Paul Mark, Daniel Peterson, Eric Prystowsky, Eric N. Sager, Philip Salive, Marcel E. Thomas, Kevin Yancy, Clyde W. Zareba, Wojciech Zipes, Douglas TI Preventing tomorrow's sudden cardiac death today: Dissemination of effective therapies for sudden cardiac death prevention SO AMERICAN HEART JOURNAL LA English DT Editorial Material ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; ACUTE MYOCARDIAL-INFARCTION; CONGESTIVE-HEART-FAILURE; INITIATE LIFESAVING TREATMENT; LEFT-VENTRICULAR DYSFUNCTION; QUALITY-OF-CARE; TRIAL SCD-HEFT; COST-EFFECTIVENESS; RACIAL DISPARITY; ELDERLY-PATIENTS AB Because the burden of sudden cardiac death (SCD) is substantial, it is important to use all guideline-driven therapies to prevent SCD. Among those therapies is the implantable cardioverter defibrillator (ICD). When indicated, ICD use is beneficial and cost-effective. Unfortunately, studies suggest that most patients who have indications for this therapy for primary or secondary prevention of SCD ore not receiving it. To explore potential reasons for this underuse and to propose potential facilitators for ICD dissemination, the Duke Center for the Prevention of SCD at the Duke Clinical Research Institute (Durham, NC) organized a think tank meeting of experts on this issue. The meeting took place on December 12 and 13, 2007, and it included representatives of clinical cardiology, cardiac electrophysiology, general internal medicine, economics, health policy, the US Food and Drug Administration, the Centers for Medicare and Medicaid Services, the Agency for Health care Research and Quality, and the device and pharmaceutical industry. Although the meeting was funded by industry participants, this article summarizing the presentations and discussions that occurred of the meeting presents the expert opinion of the authors. C1 [Al-Khatib, Sana M.; Sanders, Gillian D.; Mark, Daniel; Peterson, Eric; Thomas, Kevin] Duke Clin Res Inst, Durham, NC 27715 USA. [Carlson, Mark] St Jude Med, Sylmar, CA USA. [Cicic, Aida] Medtronic Inc, Mounds View, MN USA. [Curtis, Anne] Univ S Florida, Tampa, FL USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. [Groeneveld, Peter W.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Hayes, David] Mayo Clin, Rochester, MN USA. [Heidenreich, Paul] Palo Alto Vet Affairs Hlth Care Syst, Palo Alto, CA USA. [Prystowsky, Eric N.] St Vincents Hosp, Indianapolis, IN USA. [Sager, Philip] CardioDx Inc, Palo Alto, CA USA. [Salive, Marcel E.] Ctr Medicare, Baltimore, MD USA. [Salive, Marcel E.] Ctr Medicaid Serv, Baltimore, MD USA. [Yancy, Clyde W.] Baylor Univ, Med Ctr, Dallas, TX USA. [Zareba, Wojciech] Univ Rochester, Rochester, NY USA. [Zipes, Douglas] Indiana Univ, Indianapolis, IN 46204 USA. RP Al-Khatib, SM (reprint author), Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM alkha001@mc.duke.edu OI Mark, Daniel/0000-0001-6340-8087; Zipes, Douglas/0000-0001-7141-6829; Heidenreich, Paul/0000-0001-7730-8490 NR 60 TC 30 Z9 32 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 OCT PY 2008 VL 156 IS 4 BP 613 EP 622 DI 10.1016/j.ahj.2008.05.027 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 359CH UT WOS:000259963300001 PM 18926144 ER PT J AU Steinberg, BA Bhatt, DL Mehta, S Poole-Wilson, PA O'Hagan, P Montalescot, G Ballantyne, CM Cannon, CP AF Steinberg, Benjamin A. Bhatt, Deepalk L. Mehta, Shamir Poole-Wilson, Philip A. O'Hagan, Philip Montalescot, Gilles Ballantyne, Christie M. Cannon, Christopher P. TI Diabetes and metabolism - Nine-year trends in achievement of risk factor goals in the US and European outpatients with cardiovascular disease SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CORONARY SYNDROMES; BLOOD-GLUCOSE CONTROL; HEART SURVEY; STABLE ANGINA; SECONDARY PREVENTION; MYOCARDIAL-INFARCTION; LOWERING TREATMENT; EUROASPIRE-II; GUIDELINES; MANAGEMENT AB Background Although control of major cardiovascular risk factors (hypertension, hyperlipidemia, diabetes) has been the centerpiece of guidelines for the prevention of cardiovascular disease, periodic surveys suggest adherence to recommendations and achievement of goals is poor. Few data are available in outpatients, and no studies describe trends in meeting clinical targets. Methods A survey of outpatients with cardiovascular disease or risk factors was conducted annually, with a unique cohort each year, and included medical history, clinical data, and pharmacologic therapies. Data from 1998 to 2006 in the United States, United Kingdom, France, Italy, Spain, and Germany were analyzed for achievement of evidenced-based goals for hypertension, hyperlipidemia, and diabetes. Results Over 9 years, 102,318 patients were entered, with a mean age of 60 years, half were male, and each had at least one cardiovascular disease risk factor. In 1998, nearly half of patients in the United States were not at their target for blood pressure or low-density lipoprotein cholesterol. In Europe, < 1 in 3 was at blood pressure goal, and a minority had low-density lipoprotein recorded. Only modest improvements were observed by 2006. Hemoglobin A(1c) levels improved from 2005 to 2006 in the United States and Europe, indicating improving glycemic control in these cohorts. Conclusions Adherence to guidelines in these outpatients was suboptimal and lower in Europe than in the United States. Increases adherence to evidence-based targets for the treatment of hypertension, hyperlipidemia, and diabetes is needed to achieve ideal cardiovascular prevention. C1 [Steinberg, Benjamin A.] Johns Hopkins Sch Med, Baltimore, MD USA. [Bhatt, Deepalk L.] Cleveland Clin, Cleveland, OH 44106 USA. [Mehta, Shamir] McMaster Univ, Hamilton, ON, Canada. [Poole-Wilson, Philip A.] Univ London Imperial Coll Sci Technol & Med, London, England. [O'Hagan, Philip] Taylor Nelson Sofres Healthcare, Epsom, Surrey, England. [Montalescot, Gilles] Pitie Salpetriere Univ Hosp, Inst Cardiol, Paris, France. [Ballantyne, Christie M.] Baylor Coll Med, Houston, TX USA. [Ballantyne, Christie M.] Methodist DeBakey Heart Ctr, Houston, TX USA. [Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. RP Cannon, CP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. EM cpcannon@partners.org NR 39 TC 59 Z9 60 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 OCT PY 2008 VL 156 IS 4 BP 719 EP 727 DI 10.1016/j.ahj.2008.05.020 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 359CH UT WOS:000259963300014 PM 18926153 ER PT J AU Maddox, TM Ross, C Ho, PM Masoudi, FA Magid, D Daugherty, SL Peterson, P Rumsfeld, JS AF Maddox, Thomas M. Ross, Colleen Ho, P. Michael Masoudi, Frederick A. Magid, David Daugherty, Stacie L. Peterson, Pam Rumsfeld, John S. TI Imaging and diagnostic testing - The prognostic importance of abnormal heart rate recovery and chronotropic response among exercise treadmill test patients SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-ARTERY DISEASE; BAROREFLEX SENSITIVITY; MYOCARDIAL-INFARCTION; RATE-VARIABILITY; MORTALITY; PREDICTOR; SCORE; INCOMPETENCE; ELECTROCARDIOGRAM; FAILURE AB Background Heart rate recovery (HRR) and chronotropic response to exercise (CR) each have prognostic value among patients undergoing exercise treadmill testing (ETT). However, little is known about their prognostic use in combination and in addition to the Duke Treadmill Score (DTS). Methods We studied 9,519 outpatients undergoing ETT between 2001 and 2004. Patients were categorized by HRR and CR. The primary outcome was all-cause mortality or nonfatal myocardial infarction (MI). Cox proportional hazards modeling was used to control for demographics, clinical history, and DTS. Results After multivariable adjustment for DTS and other demographic and clinical variables, patients with abnormal HRR and CR had higher rates of all-cause mortality or nonfatal MI, as compared to patients with normal HRR and CR (hazard ratio [HR] = 1.90, 95% CI 1.35-2.69). Addition of the HRR and CR to the DTS improved outcome prediction (c-statistic improved from 0.61 to 0.68). Low-risk DTS patients with abnormal HRR and CR had significantly higher rates of all-cause mortality or nonfatal MI (HR 2.59, 95% CI 1.55-4.32), compared to low-risk DTS patients with normal HRR and CR. Conclusions Abnormal HRR and CR identified ETT patients with higher rates of all-cause mortality or nonfatal MI and provided additional risk stratification among low-risk DTS patients. These results support the routine incorporation of HRR and CR in ETT reporting and suggest the need to evaluate whether further testing and/or more intensive treatment of these higher risk patients can improve outcomes. C1 [Maddox, Thomas M.; Ho, P. Michael; Rumsfeld, John S.] Univ Colorado, Denver VAMC, Cardiol Sect 111B, Denver, CO 80209 USA. [Ross, Colleen; Magid, David] Kaiser Permanente, Inst Hlth Res, Denver, CO USA. [Masoudi, Frederick A.; Peterson, Pam] Univ Colorado, Denver Hlth, Denver, CO 80209 USA. RP Maddox, TM (reprint author), Univ Colorado, Denver VAMC, Cardiol Sect 111B, 1055 Clermont St, Denver, CO 80209 USA. EM thomas.maddox@va.gov NR 29 TC 26 Z9 28 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 OCT PY 2008 VL 156 IS 4 BP 736 EP 744 DI 10.1016/j.ahj.2008.05.025 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 359CH UT WOS:000259963300016 PM 18926155 ER PT J AU Garcia, S Moritz, TE Ward, HB Pierpont, G Goldman, S Larsen, GC Littooy, F Krupski, W Thottapurathu, L Reda, DJ McFalls, EO AF Garcia, Santiago Moritz, Thomas E. Ward, Herbert B. Pierpont, Gordon Goldman, Steve Larsen, Greg C. Littooy, Fred Krupski, William Thottapurathu, Lizy Reda, Domenic J. McFalls, Edward O. TI Usefulness of revascularization of patients with multivessel coronary artery disease before elective vascular surgery for abdominal aortic and peripheral occlusive disease SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LONG-TERM SURVIVAL; NONCARDIAC SURGERY; CARDIAC RISK; CARP TRIAL; MORTALITY; OUTCOMES AB The Coronary Artery Revascularization Prophylaxis (CARP) study showed no survival benefit with preoperative coronary artery revascularization before elective vascular surgery. The generalizability of the trial results to all patients with multivessel. coronary artery disease (CAD) has been questioned. The objective of this study was to determine the impact of prophylactic coronary revascularization on long-term survival in patients with multivessel CAD. Over a 4-year period, 1,048 patients underwent coronary angiography before vascular surgery during screening into the CARP trial. The cohort was composed of registry (n = 586) and randomized (n = 462) patients, and their survival was determined at 2.5 years after vascular surgery. High-risk coronary anatomy without previous bypass surgery included 2-vessel disease (n = 204 [19.5%]), 3-vessel disease (n = 130 [12.4%]), and left main coronary artery stenosis >= 50% (n = 48 [4.6%]). By log-rank test, preoperative revascularization was associated with improved survival in patients with a left main coronary artery stenoses (0.84 vs 0.52, p <0.01) but not those with either 2-vessel (0.80 vs 0.79, p = 0.83) or 3-vessel (0.79 vs 0.71, p = 0.15) disease. In conclusion, unprotected left main coronary artery disease was present in 4.6% of patients who underwent coronary angiography before vascular surgery, and this was the only subset of patients showing a benefit with preoperative coronary artery revascularization. (C) 2008 Elsevier Inc. All rights reserved. C1 [Garcia, Santiago; Ward, Herbert B.; Pierpont, Gordon; McFalls, Edward O.] Univ Minnesota, Vet Affairs Med Ctr, Cardiol Sect, Minneapolis, MN 55455 USA. [Littooy, Fred] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Goldman, Steve] Univ Arizona, So Arizona Vet Affairs Hlth Care Ctr, Tucson, AZ USA. [Larsen, Greg C.] Portland VA Med Ctr, Portland, OR USA. [Larsen, Greg C.] Oregon Hlth & Sci Univ, Portland, OR USA. [Krupski, William] Univ Colorado, Denver Vet Affairs Med Ctr, Denver, CO 80202 USA. RP McFalls, EO (reprint author), Univ Minnesota, Vet Affairs Med Ctr, Cardiol Sect, Minneapolis, MN 55455 USA. EM mcfal001@umn.edu FU United States Department of Veterans Affairs, Office of Research and Development, Washington, District of Columbia FX This study was supported by the Cooperative Studies Program of the United States Department of Veterans Affairs, Office of Research and Development, Washington, District of Columbia. NR 16 TC 31 Z9 31 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 1 PY 2008 VL 102 IS 7 BP 809 EP 813 DI 10.1016/j.amjcard.2008.05.022 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 354CI UT WOS:000259616100003 PM 18805102 ER PT J AU Sorgente, A Truong, QA Conca, C Singh, JP Hoffmann, U Faletra, FF Klersy, C Bhatia, R Pedrazzini, GB Pasotti, E Moccetti, T Auricchio, A AF Sorgente, Antonio Truong, Quynh A. Conca, Cristina Singh, Jagmeet P. Hoffmann, Udo Faletra, Francesco F. Klersy, Catherine Bhatia, Rinky Pedrazzini, Giovanni B. Pasotti, Elena Moccetti, Tiziano Auricchio, Angelo TI Influence of left atrial and ventricular volumes on the relation between mitral valve annulus and coronary sinus SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIAC RESYNCHRONIZATION THERAPY; VENOUS ANATOMY; COMPUTED-TOMOGRAPHY; ANNULOPLASTY; REGURGITATION; ECHOCARDIOGRAPHY; VISUALIZATION; TACHYCARDIA; VENOGRAPHY; ABLATION AB The aim of this study was to evaluate the anatomic relation between the coronary sinus (CS), mitral annulus, and coronary arteries using 64-multislice computed tomography (MSCT) in patients presenting with a wide range of atrial volumes and left ventricular functions to determine the potential clinical use for percutaneous mitral annuloplasty (PMA). The MSCT data of 165 patients (age 63.65 +/- 12.89 years, 67.3% men) were evaluated. The following variables were measured: CS length, CS ostium area, area of the section of CS when it becomes great cardiac vein, area between CS and atrioventricular groove assessed in volume-rendered 3-dimensional images, axial angle measured as the angle between CS and mitral annulus assessed in axial section, mitral valve annulus (MVA) area, left atrium volume, and left circumflex artery/marginal branch-CS relation referring to mitral annulus. The correlation was inversed between the reduction of the axial angle and all following variables: enlargement of both left ventricular end-systolic (r = -0.429, p <0.001) and end-diastolic (r = -0.428, p <0.001) volumes, left atrial volume (r = -0.361, p <0.001), and MVA (r = -0.324, p <0.001). Similarly, there was inverse correlation between the reduction of the area between CS and atrioventricular groove, and enlargement of both left ventricular end-systolic (r = -0.376, p <0.001) and end-diastolic (r = -0.291, p <0.001) volumes, left atrial volume (r = -0.221, p = 0.001), and MVA (r = -0.155, p = 0.019). Of note, circumflex artery was located between CS and MVA in 77% of the patients, but in patients with severe mitral regurgitation CS crossed circumflex/marginal branch artery more frequently (97% of cases). In conclusion, a close proximity of the CS to the mitral annulus but also to circumflex artery is more likely to occur with left atrial and ventricular enlargement. Thus, MSCT should be considered as part of the selection process of potential candidate to PMA to avoid external compression of circumflex artery/marginal branch by the device. (C) 2008 Elsevier Inc. All rights reserved. C1 [Sorgente, Antonio; Conca, Cristina; Faletra, Francesco F.; Pedrazzini, Giovanni B.; Pasotti, Elena; Moccetti, Tiziano; Auricchio, Angelo] Fondaz Cardioctr Ticino, Dept Cardiol, Lugano, Switzerland. [Truong, Quynh A.; Hoffmann, Udo; Bhatia, Rinky] Harvard Univ, Sch Med, Cardiac MR PET CT Program, Dept Radiol, Cambridge, MA 02138 USA. [Truong, Quynh A.; Hoffmann, Udo; Bhatia, Rinky] Harvard Univ, Sch Med, Massachusetts Gen Hosp, CIMIT, Cambridge, MA 02138 USA. [Singh, Jagmeet P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Cambridge, MA 02138 USA. [Singh, Jagmeet P.] Harvard Univ, Sch Med, Cardiac Resynchronizat Therapy Program, MGH Heart Ctr, Cambridge, MA 02138 USA. [Klersy, Catherine] Policlin San Matteo, Fondaz IRCCS, Res Dept, Biometry & Clin Epidemiol Serv, I-27100 Pavia, Italy. RP Auricchio, A (reprint author), Fondaz Cardioctr Ticino, Dept Cardiol, Lugano, Switzerland. EM angelo.auricchio@cardiocentro.org OI Klersy, Catherine/0000-0003-0314-8548 FU NHLBI NIH HHS [T32 HL076136, T32 HL076136-05] NR 19 TC 4 Z9 4 U1 0 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 1 PY 2008 VL 102 IS 7 BP 890 EP 896 DI 10.1016/j.amjcard.2008.05.044 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 354CI UT WOS:000259616100018 PM 18805117 ER PT J AU Martinez-Rumayor, A Camargo, CA Green, SM Baggish, AL O'Donoghue, M Januzzi, JL AF Martinez-Rumayor, Abelardo Camargo, Carlos A., Jr. Green, Sandy M. Baggish, Aaron L. O'Donoghue, Michelle Januzzi, James L., Jr. TI Soluble ST2 plasma concentrations predict 1-year mortality in acutely dyspneic emergency department patients with pulmonary disease SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE interleukin-1 receptor; ST2; dyspnea; pulmonary disease; mortality ID COMMUNITY-ACQUIRED PNEUMONIA; ACUTE CORONARY SYNDROMES; RECEPTOR FAMILY-MEMBER; RISK STRATIFICATION; NATRIURETIC PEPTIDE; ACUTE EXACERBATION; IL-1 RECEPTOR; HEART-FAILURE; TH2 CELLS; EXPRESSION AB We evaluated the association between ST2 concentrations and mortality at 1 year in 231 acutely, dyspneic patients with pulmonary diseases seen in the emergency, department. Blood concentrations of ST2 were ascertained: using 1-year survival as the reference standard, receiver operating characteristic re curves with resultant area under the curve (AUC) were measured Cox proportional hazards models identified independent predictors of 1-year death. Hazard curves compared rates of death as a function of ST2 concentration. Concentrations of ST2 were siganificantly higher in patients with pulmonary diseases compared with 153 subjects without cardiopulmonary disease (0.23 vs 0.11 ng/mL: P =.01). Among patients with pulmonary diseases, concentrations of ST2 were higher among decedents compared with survivors (1.14 ng/mL vs 0.19 ng/mL P < .001). ST2 had an AUC of 0.72 as a predictor of death (P < .0001). An ST2 of 0.20 ng/mL had a hazard ratio for death of 6.1 (95% confidence interval, 1.8-21.0; P = .004). Compared with patients with lower ST2 concentrations, mortality rates for patients with an enrollment ST2 of 0.20 ng/mL or more diverged early, and rose progressively in 1 year (P < .001). ST2 concentrations are frequently elevated in acute pulmonary diseases and are markedly prognostic for death by 1 year. C1 [Baggish, Aaron L.; O'Donoghue, Michelle; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Martinez-Rumayor, Abelardo; Green, Sandy M.; Baggish, Aaron L.; O'Donoghue, Michelle; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,Yawkey 5984, Boston, MA 02114 USA. NR 39 TC 33 Z9 35 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 OCT PY 2008 VL 130 IS 4 BP 578 EP 584 DI 10.1309/WMG2BFRC97MKKQKP PG 7 WC Pathology SC Pathology GA 349ZY UT WOS:000259323400011 PM 18794051 ER PT J AU Roehrl, MHA Rho, J Wang, JY AF Roehrl, Michael H. A. Rho, Jung-hyun Wang, Julia Y. TI Glycoproteomic analysis of human lung adenocarcinomas using glycoarrays and tandem mass spectrometry: Differential expression and glycosylation patterns of vimentin and fetuin a isoforms SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Pathology CY OCT 16-19, 2008 CL Baltimore, MD SP Amer Soc Clin Pathol C1 [Roehrl, Michael H. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rho, Jung-hyun; Wang, Julia Y.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wang, Julia Y.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 OCT PY 2008 VL 130 IS 4 MA 7 BP 650 EP 650 PG 1 WC Pathology SC Pathology GA 349ZY UT WOS:000259323400030 ER PT J AU Ahmed, AAR Garcia-Godoy, F Kunzelmann, KH AF Rashid Ahmed, Aya Abdulla Garcia-Godoy, Franklin Kunzelmann, Karl-Heinz TI Self-limiting caries therapy with proteolytic agents SO AMERICAN JOURNAL OF DENTISTRY LA English DT Article ID ELECTRON-MICROSCOPIC OBSERVATIONS; ORGANIC MATRIX COMPONENTS; BOVINE INCISOR ROOTS; DENTIN IN-VITRO; CARIOUS DENTIN; CHEMOMECHANICAL REMOVAL; DEMINERALIZED DENTIN; COLLAGENOUS MATRIX; LESION FORMATION; DECIDUOUS TEETH AB Purpose: To determine the extent to which artificial carious dentin can be removed by agents that do not seem to attack sound dentin such as pepsin, trypsin, collagenase and NaOCl, and to evaluate the effect of the enzyme pepsin and a new enzymatic solution SFC-V (pepsin in mild acidic buffer) as a self-limiting caries therapy in deep dentin carious lesions using our new model for artificial dentin caries. Methods: Artificial dentin caries was used to investigate different proteolytic agents which have the potential to remove carious tissue. 408 slices of coronal dentin were subjected to a demineralization regime which produces dentin caries very similar to natural lesions: acetic acid (pH 5) or lactic acid (pH 4) were used (7 days). Subsequently, sodium hypochlorite, collagenase, trypsin and pepsin were dissolved each in a suitable buffer and the demineralized dentin was treated for 10 minutes or 24 hours with these solutions. To differentiate the influence of the acidic buffer in case of pepsin, a second experiment was performed. 192 slices were exposed to lactic acid for 1 week. Subsequently the demineralized dentin surfaces were treated with either the enzyme pepsin in its acidic buffer, the acidic buffer alone, and in addition a neutral buffer as a control. In addition a fourth group was added where a new enzyme-based solution SFC-V was used. This second experiment differentiated further the influence of "diffusion enhanced by agitation" versus "diffusion" alone. The application time of the solutions was 3 minutes with and without agitation using a stiff nylon brush. To obtain information on the morphology of the pre- and post-treatment dentin surfaces, high resolution FE-SEM was used. Descriptive statistics were used based on cross tabulation of the morphological criteria. Results: Lactic acid produced demineralized dentin covered with a surface layer removable by proteolytic enzymes while acetic acid produced only demineralized dentin. The amount of tissue removed with the current proteolytic agents ranked as follows: trypsin 50% from WT values (P < 0.05) and were accompanied by a twofold higher collagen content (P < 0.05). Persistent myocardial EMMPRINexp in aging mice caused increased levels of both soluble and membrane type MMPs, fibrosis, and was associated with adverse LV remodeling. These findings suggest that EMMPRIN is an upstream signaling pathway that can play a mechanistic role in adverse remodeling within the myocardium. C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Spinale, FG (reprint author), Rm 625,770 MUSC Complex,114 Doughty St, Charleston, SC 29425 USA. EM wilburnm@musc.edu OI Chang, Eileen/0000-0002-3444-7260 FU Veterans Affairs Health Administration FX This study was supported by a merit award from the Veterans Affairs Health Administration (to F. G. Spinale). NR 53 TC 23 Z9 27 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD OCT PY 2008 VL 295 IS 4 BP H1394 EP H1402 DI 10.1152/ajpheart.00346.2008 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 357PB UT WOS:000259857500006 PM 18689500 ER PT J AU Albers, AB Biener, L Siegel, M Cheng, DM Rigotti, N AF Albers, Alison B. Biener, Lois Siegel, Michael Cheng, Debbie M. Rigotti, Nancy TI Household smoking bans and adolescent antismoking attitudes and smoking initiation: Findings from a longitudinal study of a Massachusetts youth cohort SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID ENVIRONMENTAL TOBACCO-SMOKE; ESTABLISHED SMOKING; SOCIAL ACCEPTABILITY; UNITED-STATES; RESTRICTIONS; REGULATIONS; PROGRESSION; RESTAURANT; EXPOSURE; SOCIALIZATION AB Objectives. We sought to determine whether adolescents living in households in which smoking was banned were more likely to develop antismoking attitudes and less likely to progress to smoking compared with those living in households in which smoking was not banned. Methods. We completed a longitudinal 4-year, 3-wave study of a representative sample of 3834 Massachusetts youths aged 12 to 17 years at baseline; 2791 (72.8%) were reinterviewed after 2 years, and 2217 (57.8%) were reinterviewed after 4 years. We used a 3-level hierarchical linear model to analyze the effect of a household ban on antismoking attitudes and smoking behaviors. Results. The absence of a household smoking ban increased the odds that youths perceived a high prevalence of adult smoking, among both youths living with a smoker (odds ratio [OR]=1.56; 95% confidence interval [CI]=1.15, 2.13) and those living with nonsmokers (OR=1.75; 95% CI=1.29, 2.37). Among youths who lived with nonsmokers, those with no home ban were more likely to transition from nonsmoking to early experimentation (OR=1.89; 95% CI=1.30, 2.74) than were those with a ban. Conclusions. Home smoking bans may promote antismoking attitudes among youths and reduce progression to smoking experimentation among youths who live with nonsmokers. C1 [Albers, Alison B.; Siegel, Michael] Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02118 USA. [Biener, Lois] Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. [Cheng, Debbie M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Rigotti, Nancy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rigotti, Nancy] Harvard Univ, Sch Med, Boston, MA USA. RP Albers, AB (reprint author), Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, 801 Massachusetts Ave,Crosstown Ctr 4th Moor, Boston, MA 02118 USA. EM aalbers@bu.edu OI Biener, Lois/0000-0002-4130-8138 FU Flight Attendant Medical Research Institute; National Cancer Institute's State and Community Tobacco Control Interventions Research [21301 CA86257] FX This work was supported by the Flight Attendant Medical Research Institute and the National Cancer Institute's State and Community Tobacco Control Interventions Research Grant Program (grant 21301 CA86257). NR 31 TC 36 Z9 36 U1 0 U2 1 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 OCT PY 2008 VL 98 IS 10 BP 1886 EP 1893 DI 10.2105/AJPH.2007.129320 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 354HT UT WOS:000259630400030 PM 18703438 ER PT J AU Chang, DW Hayashi, S Gharib, SA Vaisar, T King, ST Tsuchiya, M Ruzinski, JT Park, DR Matute-Bello, G Wurfel, MM Bumgarner, R Heinecke, JW Martin, TR AF Chang, Dong W. Hayashi, Shinichi Gharib, Sina A. Vaisar, Tomas King, S. Trevor Tsuchiya, Mitsuhiro Ruzinski, John T. Park, David R. Matute-Bello, Gustavo Wurfel, Mark M. Bumgarner, Roger Heinecke, Jay W. Martin, Thomas R. TI Proteomic and computational analysis of bronchoalveolar proteins during the course of the acute respiratory distress syndrome SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; acute lung injury; proteomic analysis; bronchoalveolar lavage; 2D gel electrophoresis ID ACUTE LUNG INJURY; POSTTRAUMATIC CYTOKINE RELEASE; STIMULATED WHOLE-BLOOD; GENDER-DIFFERENCES; TRAUMA-HEMORRHAGE; SEX-DIFFERENCES; SEVERE SEPSIS; EDEMA FLUID; P38 MAPK; ARDS AB Rationale: Acute lung injury causes complex changes in protein expression in the lungs. Whereas most prior studies focused on single proteins, newer methods allowing the simultaneous study of many proteins could lead to a better understanding of pathogenesis and new targets for treatment. Objectives: The purpose of this study was to examine the changes in protein expression in the bronchoalveolar lavage fluid (BALF) of patients during the course of the acute respiratory distress syndrome (ARDS). Methods: Using two-dimensional difference gel electrophoresis (DIGE), the expression of proteins in the BALF from patients on Days 1 (n = 7), 3 (n = 8), and 7 (n = 5) of ARDS were compared with findings in normal volunteers (n = 9). The patterns of protein expression were analyzed using principal component analysis (PCA). Biological processes that were enriched in the BALF proteins of patients with ARDS were identified using Gene Ontology (GO) analysis. Protein networks that model the protein interactions in the BALF were generated using Ingenuity Pathway Analysis. Measurements and Main Results: An average of 991 protein spots were detected using DIGE. Of these, 80 protein spots, representing 37 unique proteins in all of the fluids, were identified using mass spectrometry. PCA confirmed important differences between the proteins in the ARDS and normal samples. GO analysis showed that these differences are due to the enrichment of proteins involved in inflammation, infection, and injury. The protein network analysis showed that the protein interactions in ARDS are complex and redundant, and revealed unexpected central components in the protein networks. Conclusions: Proteomics and protein network analysis reveals the complex nature of lung protein interactions in ARDS. The results provide new insights about protein networks in injured lungs, and identify novel mediators that are likely to be involved in the pathogenesis and progression of acute lung injury. C1 [Martin, Thomas R.] VA Puget Sound Hlth Care Syst, Pulm Res Labs, Med Res Serv, Seattle, WA 98108 USA. [Chang, Dong W.; Hayashi, Shinichi; Gharib, Sina A.; Ruzinski, John T.; Park, David R.; Matute-Bello, Gustavo; Wurfel, Mark M.; Martin, Thomas R.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Vaisar, Tomas; Heinecke, Jay W.] Univ Washington, Div Endocrinol & Metab, Dept Med, Seattle, WA 98195 USA. [King, S. Trevor; Tsuchiya, Mitsuhiro; Bumgarner, Roger] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Gharib, Sina A.] Univ Washington, Ctr Lung Biol, Seattle, WA 98195 USA. [Gharib, Sina A.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. RP Martin, TR (reprint author), VA Puget Sound Hlth Care Syst, Pulm Res Labs, Med Res Serv, 1660 S Columbian Way,151L, Seattle, WA 98108 USA. EM trmartin@u.washington.edu RI Bumgarner, Roger/K-3531-2015 OI Bumgarner, Roger/0000-0002-8168-6985 FU NIH/NHLBI [HL073996, HL090298] FX Funding: NIH/NHLBI HL073996, NIH/NHBLI HL090298. NR 35 TC 41 Z9 41 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 1 PY 2008 VL 178 IS 7 BP 701 EP 709 DI 10.1164/rccm.200712-1895OC PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 353RJ UT WOS:000259585600010 PM 18658106 ER PT J AU Kleweno, CP Brynat, WK Jacir, AM Levine, WN Ahmad, CS AF Kleweno, Conor P. Brynat, Whitney K. Jacir, Albert M. Levine, William N. Ahmad, Christopher S. TI Discrepancies and rates of publication in orthopaedic sports medicine abstracts SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE abstract; publication; sports medicine; AOSSM ID SOCIETY MEETINGS; PRESENTATIONS; SURGEONS; ACADEMY AB Background: Presentations of clinically relevant data at AOSSM national meetings are presented yearly and may influence clinical decision making. Hypothesis: The incidence of presentations that do not subsequently get published is high, and the numbers of major and minor inconsistencies, once published, are also high. Study Design: Systematic review. Methods: A database was created of all abstracts presented at AOSSM meetings from 1999 to 2001 from official program books. To assess whether each abstract had been followed by publication in a peer-reviewed journal, a PubMed search was conducted to include a 5-year follow-up for each conference. Minor inconsistencies included differences in title, authors, presentation of all outcomes, and authors' interpretation of data. Major inconsistencies included discrepancies in study objective and/or hypothesis, study design, primary and secondary outcome measures, sample size, statistical analysis, results, and standard deviations/confidence intervals. Results: Overall, 98 of the 165 abstracts presented at AOSSM national meetings from 1999 to 2001 were published in a peer-reviewed journal within 5 years, a publication rate of 59.4%. The median time to publication for all articles was 21 (range, 1-60) months. The majority of articles (61) were published in the American Journal of Sports Medicine (62.2%). The median number of major and minor inconsistencies from abstract to publication was 1 (range, 0-5) and 1 (range, 0-4), respectively. Sixty-two of the 98 published abstracts (63%) had at least 1 major inconsistency, while 79 (81%) had at least 1 minor inconsistency. In 5 manuscripts (5%), the authors' interpretation of the data had changed, and in 2 (2%), the change essentially invalidated the abstract. Conclusion: A large number of scientific presentations do not get published in a peer-reviewed journal. In addition, those published have a significant number of changes that, in a small percentage of cases, alter the validity of the original presentation. Clinical Relevance: Orthopaedic surgeons and other attendees as well as nonattendees who reference conference abstracts need to exercise good judgment when considering the implications of oral presentations of unpublished materials. When reviewing meeting presentation abstracts, readers should remember that the material being presented is often not in its definitive or ultimate form. C1 [Ahmad, Christopher S.] Columbia Univ, Dept Orthopaed Surg, Ctr Shoulder Elbow & Sports Med, New York, NY 10032 USA. [Kleweno, Conor P.] Columbia Univ, Coll Phys & Surg, New York, NY 10032 USA. [Kleweno, Conor P.] Massachusetts Gen Hosp, Harvard Combined Orthopaed Surg Residency Program, Boston, MA 02114 USA. [Brynat, Whitney K.] NYU, Bellevue Hosp Ctr, Dept Emergency Med, New York, NY 10016 USA. [Jacir, Albert M.] St Johns Hosp, Dept Family Practice, Detroit, MI USA. [Levine, William N.] Columbia Univ, New York Orthopaed Hosp, Dept Orthopaed Surg, New York, NY 10032 USA. RP Ahmad, CS (reprint author), Columbia Univ, Dept Orthopaed Surg, Ctr Shoulder Elbow & Sports Med, 622 W 168th St,PH-11th Floor, New York, NY 10032 USA. EM csa4@columbia.edu NR 10 TC 24 Z9 25 U1 0 U2 3 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 OCT PY 2008 VL 36 IS 10 BP 1875 EP 1879 DI 10.1177/0363546508319054 PG 5 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 354MA UT WOS:000259642500002 PM 18667625 ER PT J AU Barkley, CR Ligibel, JA Wong, JS Lipsitz, S Smith, BL Golshan, M AF Barkley, Christina R. Ligibel, Jennifer A. Wong, Julia S. Lipsitz, Stuart Smith, Barbara L. Golshan, Mehra TI Mucinous breast carcinoma: a large contemporary series SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 9th Annual Meeting of the American-Society-of-Breast-Surgeons CY APR 30-MAY 04, 2008 CL New York, NY SP Amer Soc Breast Surg DE Breast cancer; Mucinous carcinoma; Sentinel lymph node AB BACKGROUND: Mucinous breast cancer is typically associated with a favorable prognosis. This study aimed to assess recent trends and prognostic features in the treatment of mucinous breast carcinoma. METHODS: A retrospective review of our database of patients who presented with mucinous breast cancer was performed. We evaluated patient and tumor characteristics and examined the relationships between these factors and risk for locoregional recurrence. RESULTS: One hundred eleven patients with mucinous breast cancer were identified. Severity-one (64%) underwent lumpectomy with radiotherapy. Fourteen (13%) had lymph node metastasis, and node positivity was associated with larger tumor sized node-positive patients had a mean tumor size of 2.7 cm compared with 1.5 cm for node-negative patients (P = .0003). No patients with tumor size < 1 cm had lymph node metastasis. Five patients (5%) had local and/or distant recurrence. CONCLUSIONS: Mucinous breast cancer is associated with a low recurrence rate as well as a low incidence of lymph node metastasis. In patients with small (< 1cm) tumors, consideration for deferring nodal evaluation may be made. (C) 2008 Elsevier Inc. All rights reserved. C1 [Barkley, Christina R.; Lipsitz, Stuart; Golshan, Mehra] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Ligibel, Jennifer A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Wong, Julia S.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA USA. [Smith, Barbara L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Golshan, M (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM mgolshan@partners.org NR 7 TC 24 Z9 31 U1 1 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD OCT PY 2008 VL 196 IS 4 BP 549 EP 551 DI 10.1016/j.amjsurg.2008.06.013 PG 3 WC Surgery SC Surgery GA 358IL UT WOS:000259910300017 PM 18809061 ER PT J AU Murphy, CD Jones, JL Javid, SH Michaelson, JS Nolan, ME Lipsitz, SR Specht, MC Lesnikoski, BA Hughes, KS Gadd, MA Smith, BL AF Murphy, Colleen D. Jones, Julie L. Javid, Sara Hughes Michaelson, James S. Nolan, Matthew E. Lipsitz, Stuart R. Specht, Michelle C. Lesnikoski, Beth-Ann Hughes, Kevin S. Gadd, Michele A. Smith, Barbara L. TI Do sentinel node micrometastases predict recurrence risk in ductal carcinoma in situ and ductal carcinoma in situ with microinvasion? SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 9th Annual Meeting of the American-Society-of-Breast-Surgeons CY APR 30-MAY 04, 2008 CL New York, NY SP Amer Soc Breast Surg DE Breast neoplasm; Ductal carcinoma in situ; Ductal carcinoma in situ with microinvasion; Sentinel lymph node biopsy; Sentinel lymph node micrometastases ID BREAST-CANCER; BIOPSY; MASTECTOMY AB BACKGROUND: Because the implications of micrometastases found on sentinel node biopsy (SNB) for ductal carcinoma in situ (DCIS) or ductal carcinoma in situ with microinvasion (DCISM)are largely unknown, we wished to determine if SNB pathology predicted recurrence risk in DCIS/DCISM. METHODS: Retrospective chart review identified patients with DCIS/DCISM who underwent SNB. SNB findings and all local and distant recurrences were determined. RESULTS: A total of 322 patients underwent SNB for DCIS/DCISM. There were 13 local recurrences (4.0%) and 1 (.03%) distant recurrence at a median follow-up of 47.9 months (range 0 to 110.6). 12 in patients with negative SNBs: 1 patient had a positive SNB. There were 4 recurrences after mastectomy and 9 after lumpectomy. In 29 patients with positive SNBs, there was only 1 recurrence (3.4%). CONCLUSIONS: Positive SNBs in patients with DCIS or DCISM are not associated with higher risk of local or distant recurrence. Other features of DCIS and DCISM may be important in predicting recurrence risk. (C) 2008 Elsevier Inc. All rights reserved. C1 [Murphy, Colleen D.; Javid, Sara Hughes; Michaelson, James S.; Nolan, Matthew E.; Specht, Michelle C.; Hughes, Kevin S.; Gadd, Michele A.; Smith, Barbara L.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Jones, Julie L.; Lesnikoski, Beth-Ann] Brigham & Womens Hosp, Div Surg Oncol, Boston, MA 02115 USA. [Lipsitz, Stuart R.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Lipsitz, Stuart R.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Murphy, CD (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. EM blsmith@partners.org OI Hughes, Kevin/0000-0003-4084-6484 NR 10 TC 13 Z9 19 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD OCT PY 2008 VL 196 IS 4 BP 566 EP 568 DI 10.1016/j.amjsurg.2008.06.011 PG 3 WC Surgery SC Surgery GA 358IL UT WOS:000259910300022 PM 18760400 ER PT J AU Vakiani, E Young, RH Carcangiu, ML Klimstra, DS AF Vakiani, Efsevia Young, Robert H. Carcangiu, Maria Luisa Klimstra, David S. TI Acinar cell carcinoma of the pancreas metastatic to the ovary - A report of 4 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE acinar cell carcinoma; pancreas; ovary; metastasis ID ENDOCRINE TUMORS; MUCINOUS TUMORS; DIFFERENTIATION; NEOPLASMS; KRUKENBERG; MARKERS; SERIES AB We report 4 cases of acinar cell carcinoma of the pancreas, 3 presenting as metastases in the ovary, the first report of this circumstance, which may pose a broad differential diagnosis and caused significant diagnostic difficulty in all the cases. The average patient age was 57 (range: 28 to 81) years. In 3 cases, the ovarian tumors were detected before the pancreatic tumor; in I case, a large abdominal mass and ovarian tumors were discovered synchronously. The ovarian tumors were large, solid, white-tan on gross examination, and bilateral in 3 cases; the single case involving only 1 ovary had 2 discrete masses of tumor. Microscopic examination showed highly cellular neoplasms with a small amount of fibrous stroma. Two cases had a predominant acinar growth pattern of cells with brightly eosinophilic, granular cytoplasm. In 2 cases, the pattern was predominantly solid-cribriform with areas of comedolike necrosis, and the cells had pale eosinophilic, finely granular cytoplasm. Nuclei in all cases were uniform with prominent nucleoli. The main differential diagnostic consideration was well-differentiated neuroendocrine neoplasm (carcinoid tumor); positive immunostaining with antibodies against chymotrypsin and trypsin and negative immunostaining with antibodies against synaptophysin and chromogranin helped exclude this diagnosis. We observed focal a-inhibin immunostaining in 2 cases, which may represent a potential diagnostic pitfall, as a Sertoli cell tumor or unusual granulosa cell tumor may also enter the differential diagnosis. Inclusion of antibodies against the pancreatic enzymes chymotrypsin and trypsin in the immunohistochemical panel is critical in establishing the correct diagnosis and should be considered when evaluating ovarian tumors with architectural (mainly acinar) and cytologic (granular eosinophilic cytoplasm) characteristics that should bring a metastatic acinar cell carcinoma into consideration. C1 [Vakiani, Efsevia; Klimstra, David S.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. [Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Lab, Boston, MA 02115 USA. [Carcangiu, Maria Luisa] Natl Canc Inst, Dept Pathol, I-20133 Milan, Italy. RP Klimstra, DS (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10065 USA. EM klimstrd@mskcc.org NR 29 TC 9 Z9 9 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 OCT PY 2008 VL 32 IS 10 BP 1540 EP 1545 DI 10.1097/PAS.0b013e31817a8ebb PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 355BQ UT WOS:000259684300013 PM 18724247 ER PT J AU Koporc, Z Pilat, N Nierlich, P Blaha, P Bigenzahn, S Pree, I Selzer, E Sykes, M Muehlbacher, F Wekerle, T AF Koporc, Z. Pilat, N. Nierlich, P. Blaha, P. Bigenzahn, S. Pree, I. Selzer, E. Sykes, M. Muehlbacher, F. Wekerle, T. TI Murine mobilized peripheral blood stem cells have a lower capacity than bone marrow to induce mixed chimerism and tolerance SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE costimulation blockade; mixed chimerism; PBSC; tolerance ID COLONY-STIMULATING FACTOR; DONOR-SPECIFIC TOLERANCE; WHOLE-BODY IRRADIATION; LARGE-ANIMAL-MODEL; COSTIMULATION BLOCKADE; HEMATOPOIETIC CHIMERISM; TRANSPLANTATION TOLERANCE; ALLOGENEIC MARROW; IN-VIVO; PREPARATIVE REGIMEN AB Allogeneic bone marrow transplantation (BMT) under costimulation blockade allows induction of mixed chimerism and tolerance without global T-cell depletion (TCD). The mildest such protocols without recipient cytoreduction, however, require clinically impracticable bone marrow (BM) doses. The successful use of mobilized peripheral blood stem cells (PBSC) instead of BM in such regimens would provide a substantial advance, allowing transplantation of higher doses of hematopoietic donor cells. We thus transplanted fully allogeneic murine granulocyte colony-stimulating factor (G-CSF) mobilized PBSC under costimulation blockade (anti-CD40L and CTLA4Ig). Unexpectedly, PBSC did not engraft, even when very high cell doses together with nonmyeloablative total body irradiation (TBI) were used. We show that, paradoxically, T cells contained in the donor PBSC triggered rejection of the transplanted donor cells. Rejection of donor BM was also triggered by the cotransplantation of unmanipulated donor T cells isolated from naive (nonmobilized) donors. Donor-specific transfusion and transient immunosuppression prevented PBSC-triggered rejection and mixed chimerism and tolerance were achieved, but graft-versus-host disease (GVHD) occurred. The combination of in vivo TCD with costimulation blockade prevented rejection and GVHD. Thus, if allogeneic PBSC are transplanted instead of BM, costimulation blockade alone does not induce chimerism and tolerance without unacceptable GVHD-toxicity, and the addition of TCD is required for success. C1 [Koporc, Z.; Pilat, N.; Nierlich, P.; Blaha, P.; Bigenzahn, S.; Pree, I.; Muehlbacher, F.; Wekerle, T.] Med Univ Vienna, Dept Surg, Div Transplantat, Vienna, Austria. [Selzer, E.] Med Univ Vienna, Vienna Gen Hosp, Dept Radiotherapy & Radiobiol, Vienna, Austria. [Sykes, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. RP Wekerle, T (reprint author), Med Univ Vienna, Dept Surg, Div Transplantat, Vienna, Austria. EM Thomas.Wekerle@meduniwien.ac.at RI Selzer, Edgar/K-7547-2015; OI Wekerle, Thomas/0000-0001-5159-2796 FU Roche Organ Transplantation Research Foundation (ROTRF) [110578928]; Austrian National Bank [10809]; Austrian Science Fund [F2310] FX We thank Maria Weiss, Helga Bergmeister; Martin Ploder and Franz Winkler, for technical assistance, and Andreas Heitger for critical review of the article. The authors declare no competing financial interests. This work was supported by grants from the Roche Organ Transplantation Research Foundation (ROTRF, # 110578928), from the Jubilee Fund of the Austrian National Bank (# 10809), and from the Austrian Science Fund (FWF, F2310). NR 50 TC 9 Z9 9 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD OCT PY 2008 VL 8 IS 10 BP 2025 EP 2036 DI 10.1111/j.1600-6143.2008.02371.x PG 12 WC Surgery; Transplantation SC Surgery; Transplantation GA 349GS UT WOS:000259269900010 PM 18828766 ER PT J AU Reese, PP Feldman, HI McBride, MA Anderson, K Asch, DA Bloom, RD AF Reese, P. P. Feldman, H. I. McBride, M. A. Anderson, K. Asch, D. A. Bloom, R. D. TI Substantial variation in the acceptance of medically complex live kidney donors across US renal transplant centers SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE kidney transplantation; live donor; outcomes research ID HYPERTENSIVE LIVING DONORS; GLOMERULAR-FILTRATION-RATE; BODY-MASS INDEX; BLOOD-PRESSURE; FOLLOW-UP; ORGAN PROCUREMENT; DONATION; DISEASE; RISK; ASSOCIATION AB Concern exists about accepting live kidney donation from 'medically complex donors'-those with risk factors for future kidney disease. This study's aim was to examine variation in complex kidney donor use across US transplant centers. We conducted a retrospective cohort study of live kidney donors using organ procurement and transplantation network data. Donors with hypertension, obesity or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) were considered medically complex. Among 9319 donors, 2254 (24.2%) were complex: 1194 (12.8%) were obese, 956 (10.3%) hypertensive and 392 (4.2%) had low eGFR. The mean proportion of medically complex donors at a center was 24% (range 0-65%). In multivariate analysis, donor characteristics associated with medical complexity included spousal relationship to the recipient (OR 1.29, CI 1.06-1.56, p < 0.01), low education (OR 1.19, CI 1.04-1.37, p = 0.01), older age (OR 1.01 per year, CI 1.01-1.02, p < 0.01) and non-US citizenship (OR 0.70, CI 0.51-0.97, p = 0.03). Renal transplant centers with the highest transplant volume (OR 1.26, CI 1.02-1.57, p = 0.03), and with a higher proportion of (living donation)/(all kidney transplants) (OR 1.97, CI 1.23-3.16, p < 0.01) were more likely to use medically complex donors. Though controversial, the use of medically complex donors is widespread and varies widely across centers. C1 [Reese, P. P.; Feldman, H. I.; Bloom, R. D.] Univ Penn, Dept Med, Div Renal, Philadelphia, PA 19104 USA. [McBride, M. A.; Anderson, K.] United Network Organ Sharing, Richmond, VA USA. [Asch, D. A.] Univ Penn, Dept Med, Leonard Davis Inst, Philadelphia, PA 19104 USA. [Asch, D. A.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Reese, PP (reprint author), Univ Penn, Dept Med, Div Renal, Philadelphia, PA 19104 USA. EM peter.reese@uphs.upenn.edu OI Asch, David/0000-0002-7970-286X FU NIH [K23 DK078688-01] FX Dr. Reese is supported by NIH Career Development Award, K23 DK078688-01. NR 50 TC 78 Z9 78 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD OCT PY 2008 VL 8 IS 10 BP 2062 EP 2070 DI 10.1111/j.1600-6143.2008.02361.x PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 349GS UT WOS:000259269900014 PM 18727695 ER PT J AU Sandberg, WS AF Sandberg, Warren S. TI Anesthesia information management systems: Almost there SO ANESTHESIA AND ANALGESIA LA English DT Editorial Material ID DOCUMENTATION; PERFORMANCE C1 [Sandberg, Warren S.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Sandberg, Warren S.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. RP Sandberg, WS (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Jackson 4, Boston, MA 02114 USA. EM wsandberg@partners.org OI Sandberg, Warren/0000-0002-9246-777X NR 10 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD OCT PY 2008 VL 107 IS 4 BP 1100 EP 1102 DI 10.1213/ane.0b013e3181867fd0 PG 3 WC Anesthesiology SC Anesthesiology GA 352UE UT WOS:000259522100004 PM 18806010 ER PT J AU Lee, IH Culley, DJ Baxter, MG Xie, ZC Tanzi, RE Crosby, G AF Lee, In Ho Culley, Deborah J. Baxter, Mark G. Xie, Zhongcong Tanzi, Rudolph E. Crosby, Gregory TI Spatial memory is intact in aged rats after propofol anesthesia SO ANESTHESIA AND ANALGESIA LA English DT Article ID RADIAL-ARM MAZE; NITROUS OXIDE ANESTHESIA; LONG-TERM POTENTIATION; METHYL-D-ASPARTATE; SYNAPTIC-TRANSMISSION; COGNITIVE DYSFUNCTION; HIPPOCAMPAL-NEURONS; ISOFLURANE; DEFICITS; RECEPTOR AB BACKGROUND: We have previously demonstrated that aged rats have persistent impairment of spatial memory after sedation with nitrous oxide or general anesthesia with isoflurane-nitrous oxide. Propofol has different receptor mechanisms of action and a favorable short-term recovery profile, and it has been proposed that propofol is devoid of enduring effects on cognitive performance. No studies have investigated this question in aged subjects, however, so we designed an experiment to examine the long-term effects of propofol anesthesia on spatial working memory. METHODS: Eighteen-mo-old rats were randomized to 2h of 100% oxygen-propofol anesthesia (n = 11) or to a control group that breathed 100% oxygen (n = 10). Propofol was administered by continuous infusion via a tail vein catheter. Rats breathed spontaneously and rectal temperature was maintained. Mean arterial blood pressure was measured noninvasively and a venous blood gas was obtained just before discontinuation of propofol. After a 2-day recovery, spatial working memory was assessed for 14 days using a 12-arm radial maze. The number of total errors, number of correct choices to first error, and time to complete the maze was recorded and analyzed using a repeated measure analysis of variance (ANOVA), with P < 0.05 being considered statistically significant. RESULTS: The average propofol infusion rate was 0.6 +/- 0.1 mg center dot kg(-1) center dot min(-1), a rate corresponding to a 50% effective concentration dose in adult rats. Mean arterial blood pressure during anesthesia was 1.00 +/- 2 mm Hg and venous blood gases remained in the normal range. There was no difference between the control and previously anesthetized rats on any measure of radial arm maze performance, indicating propofol anesthesia produces no lasting impairment in spatial working memory in aged rats. CONCLUSIONS: In aged rats, propofol anesthesia is devoid of the persistent memory effects observed with other general anesthetics in this model. Thus, while it appears that the state of general anesthesia is neither necessary nor sufficient for development of postanesthetic memory impairment, the choice of anesthetics may play a role in late cognitive outcome in the aged. C1 [Culley, Deborah J.; Crosby, Gregory] Harvard Univ, Sch Med, Dept Anesthesia, Brigham & Womens Hosp, Boston, MA 02115 USA. [Lee, In Ho] Korea Univ, Guro Hosp, Dept Anesthesiol, Seoul, South Korea. [Baxter, Mark G.] Univ Oxford, Oxford, England. [Xie, Zhongcong] Harvard Univ, Sch Med, Dept Anesthesia, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Tanzi, Rudolph E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Genet & Aging Res Unit, Charlestown, MA USA. RP Crosby, G (reprint author), Brigham & Womens Hosp, Dept Anesthesiol, Lab Aging Neurosci, 75 Francis St, Boston, MA 02115 USA. EM gcrosby@zeus.bwh.harvard.edu FU American Geriatrics Society Jahnigen Award [GM077057, AG20253, NS048140]; Harvard University; Alzheimer's Association; Cure Alzheimer's Fund [AG014713, MH60009] FX This research was supported by GM077057, American Geriatrics Society Jahnigen Award (DC); AG20253 (GC); NS048140, American Geriatrics Society Jahnigen Award, William F. Milton Fund from Harvard University, Investigator-Initiated Research Grant from Alzheimer's Association (ZX); and AG014713, MH60009, Cure Alzheimer's Fund (RT). NR 38 TC 25 Z9 32 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD OCT PY 2008 VL 107 IS 4 BP 1211 EP 1215 DI 10.1213/ane.0b013e31817ee879 PG 5 WC Anesthesiology SC Anesthesiology GA 352UE UT WOS:000259522100023 PM 18806029 ER PT J AU Nagasaka, Y Fernandez, BO Garcia-Saura, MF Petersen, B Ichinose, F Bloch, KD Feelisch, M Zapol, WM AF Nagasaka, Yasuko Fernandez, Bernadette O. Garcia-Saura, Maria F. Petersen, Bodil Ichinose, Fumito Bloch, Kenneth D. Feelisch, Martin Zapol, Warren M. TI Brief periods of nitric oxide inhalation protect against myocardial ischemia-reperfusion injury SO ANESTHESIOLOGY LA English DT Article ID DECREASES INFARCTION SIZE; ISCHEMIA/REPERFUSION INJURY; BIOLOGICAL TISSUES; GUANYLATE-CYCLASE; CORONARY-ARTERY; S-NITROSYLATION; INHALED NO; IN-VIVO; HEMOGLOBIN; BLOOD AB Background: Prolonged breathing of nitric oxide reduces myocardial ischemia-reperfusion injury, but the precise mechanisms responsible for the cardioprotective effects of inhaled nitric oxide are incompletely understood. Methods: The authors investigated die fate of inhaled nitric oxide (80 parts per million) in mice and quantified the formation of nitric oxide metabolites in blood and tissues. The authors tested whether the accumulation of nitric oxide metabolites correlated with the ability of inhaled nitric oxide to protect against cardiac ischemia-reperfusion injury. Results: Mice absorbed nitric oxide in a nearly linear fashion (0.19 +/- 0.02 mu mol/g (.) h). Breathing nitric oxide rapidly increased a broad spectrum of nitric oxide metabolites. Levels of erythrocytic S-nitrosothiols, N-nitrosamines, and nitrosyl-hemes increased dramatically within 30 s of commencing nitric oxide inhalation. Marked increases of lung S-nitrosothiol and liver N-nitrosamine levels were measured, as, well as elevated cardiac and brain nitric oxide metabolite levels. Breathing low oxygen concentrations potentiated die ability of inhaled nitric oxide to increase cardiac nitric oxide metabolite levels. Concentrations of each nitric oxide metabolite, except nitrate, rapidly reached a plateau and were similar after 5 and 60 min. In a murine cardiac ischemia-reperfusion injury model, breathing nitric oxide for either 5 or 60 min before reperfusion decreased myocardial infarction size as a fraction of myocardial area at risk by 31% or 32%, respectively. Conclusions: Breathing nitric oxide leads to the rapid accumulation of a variety of nitric oxide metabolites in blood and tissues, contributing to the ability of brief periods of nitric oxide inhalation to provide cardioprotection against ischemia-reperfusion injury. The nitric oxide metabolite concentrations achieved in a target tissue may be more important than the absolute amounts of nitric oxide absorbed. C1 [Zapol, Warren M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Anesthesia Ctr Crit C, Boston, MA 02114 USA. [Feelisch, Martin] Univ Warwick, Warwick Med Sch, Clin Sci Res Inst, Coventry CV4 7AL, W Midlands, England. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02215 USA. RP Zapol, WM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Anesthesia Ctr Crit C, 55 Fruit St, Boston, MA 02114 USA. EM wzapol@partners.org RI Feelisch, Martin/C-3042-2008 OI Feelisch, Martin/0000-0003-2320-1158 FU National Institutes of Helath, Bethesda, Maryland [HL07224]; Massachusetts General Hospital, Boston, Massachusetts, and IKARIA, Clinton, New Jersey; [HL42397]; [DA020644]; [HL70896] FX Received from the Anesthesia Center for Critical Care Research, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; and the Whitaker Cardiovascular Institute, Boston University School of Medicine. Boston, Massachusetts. Submitted for publication February 1, 2008. Accepted tor publication June 27, 2008. Supported in part by grant Nos. HL42397 (to Dr. Zapol), DA020644 (to Dr. Feelisch), and HL70896 to (Dr. Bloch) and multidisciplinary training in cardiovascular research grant No. HL07224 (to Dr. Fernandez) from the National Institutes of Helath, Bethesda, Maryland; and a sponsored research agreement between Massachusetts General Hospital, Boston, Massachusetts, and IKARIA, Clinton, New Jersey (to Dr. Bloch). Drs. Zapol and Bloch have obtained patents relating to the use of inhaled nitric oxide. These patents are assigned to Massachusetts General Hospital, which has licensed them to IKARIA and Linde Gas Therapeutics, Lidingo, Sweden. Dr. Zapol receives royalties and Dr. Bloch has received grants from IKARIA and Linde, which helped the authors to study inhaled nitric oxide. Presented at the Annual Meeting of the American Heart Association. Orlando, Florida, November 7, 2007 (Abstract Oral Sessions, presentation No. 1484). The first two authors (Drs. Nagasaka and Fernandez) contributed equally to this work. The senior authors (Drs. Feelisch and Zapol) contributed equally to this work. NR 33 TC 52 Z9 53 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 OCT PY 2008 VL 109 IS 4 BP 675 EP 682 PG 8 WC Anesthesiology SC Anesthesiology GA 352TY UT WOS:000259521500015 PM 18813047 ER PT J AU Antman, EM AF Antman, Elliott M. TI The specialty of emergency medicine: Needed now more than ever before SO ANNALS OF EMERGENCY MEDICINE LA English DT Editorial Material ID CARE C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. RP Antman, EM (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. NR 9 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2008 VL 52 IS 4 BP 317 EP 319 DI 10.1016/j.annemergmed.2008.07.025 PG 3 WC Emergency Medicine SC Emergency Medicine GA 354PP UT WOS:000259651800003 PM 18809101 ER PT J AU Pollack, CV Antman, EM Hollander, JE AF Pollack, Charles V., Jr. Antman, Elliott M. Hollander, Judd E. TI 2007 focused update to the ACC/AHA guidelines for the management of patients with ST-segment elevation myocardial infarction: Implications for emergency department practice SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; ASSOCIATION TASK-FORCE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; INTRAVENOUS THROMBOLYTIC THERAPY; RANDOMIZED CLINICAL-TRIALS; PLACEBO-CONTROLLED TRIAL; TO-BALLOON TIME; PRIMARY ANGIOPLASTY; FIBRINOLYTIC THERAPY; AMERICAN-COLLEGE AB The American College of Cardiology and American Heart Association have issued a "focused update" of their 2004 guidelines for the management of ST-segment elevation myocardial infarction (STEMI). Several of the issues addressed involve new data and new recommendations on treatment decisions that may be made in the emergency department. In this review, we present the new recommendations that are pertinent to emergency medicine practice and comment on their potential implementation into an evidence-based, multidisciplinary approach to the timely care of the STEMI patient. C1 [Pollack, Charles V., Jr.] Univ Penn, Dept Emergency Med, Penn Hosp, Philadelphia, PA 19107 USA. [Antman, Elliott M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp, Boston, MA 02115 USA. [Hollander, Judd E.] Univ Penn, Hosp Univ Penn, Philadelphia, PA 19104 USA. RP Pollack, CV (reprint author), Univ Penn, Dept Emergency Med, Penn Hosp, Philadelphia, PA 19107 USA. EM pollackc@pahosp.com OI Hollander, Judd/0000-0002-1318-2785 NR 66 TC 33 Z9 35 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 OCT PY 2008 VL 52 IS 4 BP 344 EP 355 DI 10.1016/j.annemergmed.2008.04.004 PG 12 WC Emergency Medicine SC Emergency Medicine GA 354PP UT WOS:000259651800010 PM 18519158 ER PT J AU Camargo, CA Ginde, AA Blanc, PG Tsai, C AF Camargo, Jr C. A. Ginde, A. A. Blanc, P. G. Tsai, C. TI Improved Emergency Department Management of Acute Exacerbation of Chronic Obstructive Pulmonary Disease SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 24-28, 2008 CL Chicago, IL SP Amer Coll Emergency Phys C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Colorado, Denver Sch Med, Aurora, CO USA. NR 0 TC 0 Z9 0 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 OCT PY 2008 VL 52 IS 4 MA 15 BP S46 EP S46 DI 10.1016/j.annemergmed.2008.06.080 PG 1 WC Emergency Medicine SC Emergency Medicine GA 354PQ UT WOS:000259651900016 ER PT J AU Capp, R Bosson, N Noble, VE Lamhaut, L Marx, JS Liteplo, A Carli, P AF Capp, R. Bosson, N. Noble, V. E. Lamhaut, L. Marx, J. S. Liteplo, A. Carli, P. TI Can Physicians Who Work in the Out-of-Hospital System Accurately Interpret Chest Ultrasound Images for Pneumothorax and Pulmonary Edema Following Focused Training? SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 24-28, 2008 CL Chicago, IL SP Amer Coll Emergency Phys C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NYU Emergency Med, New York, NY USA. SAMU Hop Necker, Paris, France. NR 0 TC 0 Z9 0 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 OCT PY 2008 VL 52 IS 4 MA 341 BP S145 EP S145 DI 10.1016/j.annemergmed.2008.06.367 PG 1 WC Emergency Medicine SC Emergency Medicine GA 354PQ UT WOS:000259651900342 ER PT J AU Capp, R Murray, A Noble, VE Steele, D Liteplo, A AF Capp, R. Murray, A. Noble, V. E. Steele, D. Liteplo, A. TI The Dynamics of B-lines: A Useful Tool in the Evaluation of Pulmonary Fluid Status as Fluid Shifts Occur in the Body SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 24-28, 2008 CL Chicago, IL SP Amer Coll Emergency Phys C1 [Capp, R.; Murray, A.; Noble, V. E.; Steele, D.; Liteplo, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2008 VL 52 IS 4 MA 62 BP S61 EP S61 DI 10.1016/j.annemergmed.2008.06.128 PG 1 WC Emergency Medicine SC Emergency Medicine GA 354PQ UT WOS:000259651900063 ER PT J AU Ginde, AA Espinola, JA Sullivan, AF Blurn, FC Camargo, CA AF Ginde, A. A. Espinola, J. A. Sullivan, A. F. Blurn, F. C. Camargo, Jr C. A. TI Use of Physician Assistants and Nurse Practitioners in United States Emergency Departments, 1993-2005: Implications for the Emergency Physician Workforce SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 24-28, 2008 CL Chicago, IL SP Amer Coll Emergency Phys C1 Univ Colorado Denver, Sch Med, Aurora, CO USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. W Virginia Univ, Sch Med, Morgantown, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2008 VL 52 IS 4 MA 145 BP S87 EP S87 DI 10.1016/j.annemergmed.2008.06.059 PG 1 WC Emergency Medicine SC Emergency Medicine GA 354PQ UT WOS:000259651900146 ER PT J AU Janishidi, S Kandiah, P Singhal, AB Resnick, JB Furie, KL Botczuk, P Parry, BA Lev, M Koroshetz, WJ Nagurney, JT AF Janishidi, S. Kandiah, P. Singhal, A. B. Resnick, J. B. Furie, K. L. Botczuk, P. Parry, B. A. Lev, M. Koroshetz, W. J. Nagurney, J. T. TI Clinical Predictors of Significant Findings on Head Computed Tomographic Angiography SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 24-28, 2008 CL Chicago, IL SP Amer Coll Emergency Phys C1 [Janishidi, S.; Kandiah, P.; Singhal, A. B.; Resnick, J. B.; Furie, K. L.; Botczuk, P.; Parry, B. A.; Lev, M.; Koroshetz, W. J.; Nagurney, J. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2008 VL 52 IS 4 MA 380 BP S158 EP S158 PG 1 WC Emergency Medicine SC Emergency Medicine GA 354PQ UT WOS:000259651900381 ER PT J AU Lozner, A Connolly, J Millen, J Shaltis, P Reisner, A Thomas, SH AF Lozner, A. Connolly, J. Millen, J. Shaltis, P. Reisner, A. Thomas, S. H. TI How Frequently Do Patients Want Their Pain Assessed? SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 24-28, 2008 CL Chicago, IL SP Amer Coll Emergency Phys C1 [Lozner, A.; Connolly, J.; Millen, J.; Shaltis, P.; Reisner, A.; Thomas, S. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2008 VL 52 IS 4 BP S164 EP S165 DI 10.1016/j.annemergmed.2008.06.429 PG 2 WC Emergency Medicine SC Emergency Medicine GA 354PQ UT WOS:000259651900402 ER PT J AU Millen, JC Ginde, AA Anderson, AT Fang, P Camargo, CA AF Millen, J. C. Ginde, A. A. Anderson, A. T. Fang, P. Camargo, Jr C. A. TI Multicenter Study of HPV Knowledge and Attitudes in Emergency Department Patients SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 24-28, 2008 CL Chicago, IL SP Amer Coll Emergency Phys C1 Harvard Affiliated Emergency Med Residency, Boston, MA USA. Univ Colorado, Sch Med, Dept Emergency Med, Aurora, CO USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2008 VL 52 IS 4 MA 260 BP S121 EP S122 DI 10.1016/j.annemergmed.2008.06.279 PG 2 WC Emergency Medicine SC Emergency Medicine GA 354PQ UT WOS:000259651900260 ER PT J AU Patel, SN Kilgannon, H Boudreaux, ED Sullivan, AF Blumenthal, D Camargo, CA AF Patel, S. N. Kilgannon, H. Boudreaux, E. D. Sullivan, A. F. Blumenthal, D. Camargo, Jr C. A. TI Multicenter Study of Cigarette Smoking Among Patients Presenting to the Emergency Department With Acute Asthma SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 24-28, 2008 CL Chicago, IL SP Amer Coll Emergency Phys C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2008 VL 52 IS 4 MA 9 BP S44 EP S44 DI 10.1016/j.annemergmed.2008.06.074 PG 1 WC Emergency Medicine SC Emergency Medicine GA 354PQ UT WOS:000259651900010 ER PT J AU Richman, P Kabrhel, C Mandell, M Beam, D Courtney, D Moore, C Kline, JA AF Richman, P. Kabrhel, C. Mandell, M. Beam, D. Courtney, D. Moore, C. Kline, J. A. TI Age Differences in the Clinical Presentation of Department Patients With Venous Thromboembolism SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 24-28, 2008 CL Chicago, IL SP Amer Coll Emergency Phys C1 Mayo Clin Hosp, Phoenix, AZ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Morristown Mem Hosp, Morristown, NJ USA. E Carolina Univ, Greenville, NC USA. Northwestern Univ, Chicago, IL 60611 USA. Yale Univ, New Haven, CT USA. Carolinas Med Ctr, Charlotte, NC 28203 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2008 VL 52 IS 4 MA 14 BP S45 EP S46 DI 10.1016/j.annemergmed.2008.06.079 PG 2 WC Emergency Medicine SC Emergency Medicine GA 354PQ UT WOS:000259651900015 ER PT J AU Soremekun, OA Noble, V Litepio, A Brown, D AF Soremekun, O. A. Noble, V Litepio, A. Brown, D. TI Financial Impact of Emergency Department Ultrasound: Current and Potential Revenue SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 24-28, 2008 CL Chicago, IL SP Amer Coll Emergency Phys C1 [Soremekun, O. A.; Noble, V; Litepio, A.; Brown, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2008 VL 52 IS 4 MA 127 BP S81 EP S81 DI 10.1016/j.annemergmed.2008.06.041 PG 1 WC Emergency Medicine SC Emergency Medicine GA 354PQ UT WOS:000259651900128 ER PT J AU Sullivan, AF Kansagra, SM Rao, SR Gordon, JA Kaushal, R Magid, DJ Camargo, CA Blumenthal, D AF Sullivan, A. F. Kansagra, S. M. Rao, S. R. Gordon, J. A. Kaushal, R. Magid, D. J. Camargo, C. A., Jr. Blumenthal, D. TI Personal Safety and Prevalence of Violence and Weapons in the Emergency Department SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 24-28, 2008 CL Chicago, IL SP Amer Coll Emergency Phys C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. New York Presbyterian Hosp, New York, NY USA. Colorado Permanente Med Grp, Clin Res Unit, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2008 VL 52 IS 4 MA 425 BP S171 EP S171 DI 10.1016/j.annemergmed.2008.06.453 PG 1 WC Emergency Medicine SC Emergency Medicine GA 354PQ UT WOS:000259651900425 ER PT J AU Temin, E Harrington, L Mitchell, P Rebholz, C Dyer, K Doyle, J Hughes, P Moyer, P AF Temin, E. Harrington, L. Mitchell, P. Rebholz, C. Dyer, K. Doyle, J. Hughes, P. Moyer, P. TI Success Rates in Out-of-Hospital Intubation SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 24-28, 2008 CL Chicago, IL SP Amer Coll Emergency Phys C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Med Ctr, Boston, MA USA. Boston Emergency Med Serv, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2008 VL 52 IS 4 MA 364 BP S153 EP S153 DI 10.1016/j.annemergmed.2008.06.391 PG 1 WC Emergency Medicine SC Emergency Medicine GA 354PQ UT WOS:000259651900365 ER PT J AU Waseem, M Mansbach, JM Clark, S Camargo, CA AF Waseem, M. Mansbach, J. M. Clark, S. Camargo, Jr C. A. TI Prospective Multicenter Study of Bronchiolitis: Predictors of Relapse Following Treatment in the Emergency Department SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 24-28, 2008 CL Chicago, IL SP Amer Coll Emergency Phys C1 Lincoln Med & Mental Hlth Ctr, Bronx, NY 10451 USA. Childrens Hosp Boston, Boston, MA USA. Univ Pittsburgh, Pittsburgh, PA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2008 VL 52 IS 4 MA 4 BP S42 EP S42 DI 10.1016/j.annemergmed.2008.06.069 PG 1 WC Emergency Medicine SC Emergency Medicine GA 354PQ UT WOS:000259651900005 ER PT J AU Weed, S Caterino, JM Espinola, JA Camargo, CA AF Weed, S. Caterino, J. M. Espinola, J. A. Camargo, Jr C. A. TI National Patterns in Emergency Department Antibiotic Prescribing for Elderly Patients With Urinary Tract Infections, 1996-2005 SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 24-28, 2008 CL Chicago, IL SP Amer Coll Emergency Phys C1 Duke Univ, Coll Med, Raleigh, NC USA. Ohio State Univ, Columbus, OH 43210 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2008 VL 52 IS 4 MA 370 BP S155 EP S155 DI 10.1016/j.annemergmed.2008.06.397 PG 1 WC Emergency Medicine SC Emergency Medicine GA 354PQ UT WOS:000259651900371 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Birth-Cohort Patterns of Mortality From Ulcerative Colitis and Peptic Ulcer SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Birth Cohorts; Duodenal Ulcer; Enteric Infections; Etiology of Ulcerative Colitis; Gastric Ulcer; Mortality; Time Trends ID INFLAMMATORY-BOWEL-DISEASE; HELICOBACTER-PYLORI INFECTION; TIME TRENDS; CROHNS-DISEASE; RISK-FACTORS; PREVALENCE; EPIDEMIOLOGY; ENGLAND; COUNTY; PERIOD AB PURPOSE: The aim was to follow the time trends of mortality from ulcerative colitis and compare them with those of gastric and duodenal ulcer. METHODS: Mortality data from 21' different countries between 1941 and 2004 were analyzed. The age-specific death rates of each individual country, as well as the average age-specific rates of all countries, were plotted against the periods of birth and death. RESULTS: The average trends of mortality from ulcerative colitis, gastric and duodenal ulcer reveal distinctive and unique birth-cohort patterns of all three diseases. Similar to both types of peptic ulcer, the risk of developing ulcerative colitis started to rise in successive generations born during the second half of the 19(th) century. It peaked shortly before the turn of the century and has continued to decline since then. The rise and fall in the occurrence of ulcerative colitis preceded those of both ulcer types. CONCLUSION: The birth-cohort pattern indicates that exposure to the relevant risk factors of ulcerative colitis occurs during early life. As the model of H. pylori and its associated birth-cohort patterns of gastric and duodenal ulcer suggest, an enteric infection provides a possible explanation for such temporal trends of ulcerative colitis as well. Ann Epidemiol 2008;18:813-819. (C) 2008 Elsevier Inc. All rights reserved. C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR 97239 USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-G1,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 18 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD OCT PY 2008 VL 18 IS 10 BP 813 EP 819 DI 10.1016/j.annepidem.2008.07.006 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 359XS UT WOS:000260022200010 PM 18922397 ER PT J AU Hickey, M Saunders, C Partridge, A Santoro, N Joffe, H Stearns, V AF Hickey, M. Saunders, C. Partridge, A. Santoro, N. Joffe, H. Stearns, V. TI Practical clinical guidelines for assessing and managing menopausal symptoms after breast cancer SO ANNALS OF ONCOLOGY LA English DT Review DE atrophic vaginitis; breast cancer; hot flashes; nonhormonal treatment; sexual dysfunction after breast cancer ID RANDOMIZED CONTROLLED-TRIAL; HORMONE-REPLACEMENT THERAPY; QUALITY-OF-LIFE; INDUCED HOT FLASHES; VAGINAL ESTROGEN THERAPY; POSTMENOPAUSAL WOMEN; VASOMOTOR SYMPTOMS; DOUBLE-BLIND; CLIMACTERIC SYMPTOMS; MAMMOGRAPHIC DENSITY AB Background: The purpose of this study was to provide practical, evidence-based guidelines for evaluating and treating common menopausal symptoms following breast cancer. Methods: Literature review of the causes, assessment and management of menopausal symptoms in breast cancer patients. Results: A number of nonhormonal treatments are effective in treating hot flashes. Whether pharmacological treatment is given will depend on the severity of symptoms and on patient wishes. For severe and frequent hot flashes, the best data support the use of venlafaxine, paroxetine and gabapentin in women with breast cancer. Side-effects are relatively common with all these agents. For vaginal dryness, topical estrogen treatment is the most effective but the safety of estrogens following breast cancer is not established. There are limited data on effective treatments for sexual dysfunction during menopause. Conclusion: Menopausal symptoms after breast cancer should be evaluated and managed as warranted using a systematic approach and may benefit from multidisciplinary input. C1 [Hickey, M.] Univ Western Australia, Sch Womens & Infants Hlth, King Edward Mem Hosp, Perth, WA 6008, Australia. [Saunders, C.] Univ Western Australia, Sch Surg & Pathol, Perth, WA 6008, Australia. [Partridge, A.] Dana Farber Canc Inst, Dept Obstet Gynecol & Womens Hlth, Boston, MA 02115 USA. [Santoro, N.] Yeshiva Univ Albert Einstein Coll Med, Bronx, NY 10461 USA. [Joffe, H.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Joffe, H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA USA. [Stearns, V.] Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RP Hickey, M (reprint author), Univ Western Australia, Sch Womens & Infants Hlth, 374 Bagot Rd, Perth, WA 6008, Australia. EM mhickey@meddent.uwa.edu.au RI Saunders, Christobel/H-5779-2014; OI Saunders, Christobel/0000-0003-2281-9829; Hickey, Martha/0000-0002-3941-082X NR 123 TC 55 Z9 56 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2008 VL 19 IS 10 BP 1669 EP 1680 DI 10.1093/annonc/mdn353 PG 12 WC Oncology SC Oncology GA 353PT UT WOS:000259581200002 PM 18522932 ER PT J AU Ng, AK Li, S Neuberg, D Chi, R Fisher, DC Silver, B Mauch, PM AF Ng, A. K. Li, S. Neuberg, D. Chi, R. Fisher, D. C. Silver, B. Mauch, P. M. TI A prospective study of pulmonary function in Hodgkin's lymphoma patients SO ANNALS OF ONCOLOGY LA English DT Article DE bleomycin; hodgkin lymphoma; lung toxicity; radiation parameters ID PREDICTING RADIATION PNEUMONITIS; VOLUME HISTOGRAM PARAMETERS; MANTLE-FIELD IRRADIATION; LUNG-CANCER; MEDIASTINAL IRRADIATION; DISEASE; BLEOMYCIN; RADIOTHERAPY; CHEMOTHERAPY; TOXICITY AB Background: To prospectively study changes in lung function in Hodgkin's lymphoma (HL) patients and to explore predictors for these changes over time. Methods: In all, 52 patients with HL receiving bleomycin-based chemotherapy with (n = 23) or without (n = 29) mediastinal radiotherapy were enrolled. Pretreatment pulmonary function tests were carried out. These were repeated at 1 month, 6 months, and 1 year after therapy. Results: With chemotherapy alone, the median %DLCO declined significantly at 1 month but returned to baseline by 6 months. The median %DLCO did not further decrease with radiotherapy, but remained persistently reduced at 1 year. In patients who received radiotherapy, having > 33% of lung volume receive 20 Gy (V20) and a mean lung dose (MLD) of > 13 Gy significantly predicted for persistently reduced %DLCO at 6 months (P = 0.035). Smoking significantly predicted for a persistently reduced %DLCO at 1 year (P = 0.036). On multivariable analysis, significant predictors for decline in %DLCO at 1 year were higher baseline %DLCO (P = 0.01), higher MLD (P = 0.02), and a smoking history (P = 0.02). Conclusions: Several factors contribute to decline in %DLCO in HL patients who received bleomycin-based computed tomography. The identification of threshold radiation dosimetric parameters for reduced lung function may provide guidance in the radiation planning of these patients. C1 [Ng, A. K.; Chi, R.; Silver, B.; Mauch, P. M.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Li, S.; Neuberg, D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Fisher, D. C.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Ng, AK (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02114 USA. EM ang@lroc.harvard.edu FU American Society of Hematology Junior Faculty Clinical Research Award FX American Society of Hematology Junior Faculty Clinical Research Award. NR 26 TC 13 Z9 15 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2008 VL 19 IS 10 BP 1754 EP 1758 DI 10.1093/annonc/mdn284 PG 5 WC Oncology SC Oncology GA 353PT UT WOS:000259581200013 PM 18467315 ER PT J AU Esnaola, NF Hall, BL Hosokawa, PW Ayanian, JZ Henderson, WG Khuri, SE Zinner, MJ Rogers, SO AF Esnaola, Nestor F. Hall, Bruce L. Hosokawa, Patrick W. Ayanian, John Z. Henderson, William G. Khuri, Shukri E. Zinner, Michael J. Rogers, Selwyn O., Jr. TI Race and Surgical Outcomes It Is Not All Black and White SO ANNALS OF SURGERY LA English DT Article ID QUALITY IMPROVEMENT PROGRAM; 30-DAY POSTOPERATIVE MORTALITY; UNIVERSITY MEDICAL-CENTERS; VETERANS-AFFAIRS HOSPITALS; CLINICAL COMORBIDITY INDEX; HIGH-VOLUME HOSPITALS; 8 COMMON OPERATIONS; RISK-ADJUSTMENT; RACIAL-DIFFERENCES; COLORECTAL-CANCER AB Background: Studies using Medicare data have suggested that African American race is an independent predictor of death after major surgery. We hypothesized that the apparent adverse effect of race on surgical outcomes is due to confounding by comorbidity, not race itself Methods: We identified all non-Hispanic white and African American general surgery, private sector patients included in the National Surgery Quality Improvement Program (NSQIP) Patient Safety in Surgery Study (2001-2004). Patient characteristics, comorbidities, and postoperative outcomes were collected/analyzed using NSQIP methodology. Characteristics between races were compared using Student t and chi(2) tests. Odds ratios (OR) for 30-day morbidity and mortality were calculated using multivariable logistic regression. Results: We identified 34,141 white and 5068 African American patients. African Americans were younger but more likely to undergo emergency surgery and present with hypertension, dyspnea, diabetes, renal failure, open wounds/infection, or advanced American Society of Anesthesiology class (all P < 0.001). African Americans underwent less complex procedures but had higher unadjusted 30-day morbidity (14.33% vs. 12.35%; P < 0.001) and mortality (2.09% vs. 1.65%; P = 0.02). After controlling for comorbidity, African American race had no independent effect on mortality (OR 0.95, (0.74-1.23)) but was associated with a higher risk of postoperative cardiac arrest (OR 2.49, (1.80-3.45)) and renal insufficiency/failure (OR 1.70 (1.32-2.18)). Conclusion: African American race is associated with greater comorbidity and cardiac/renal complications but is not an independent predictor of perioperative mortality after general surgery. Efforts to improve postoperative outcomes in African Americans should focus on reducing the need for emergency surgery and improving perioperative management of comorbid conditions. C1 [Esnaola, Nestor F.] Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. [Esnaola, Nestor F.] Ralph H Johnson VA Med Ctr, Dept Surg, Charleston, SC USA. [Hall, Bruce L.] John Cochran Vet Affairs Med Ctr, Dept Surg, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Barnes Jewish Hosp, Dept Surg, Sch Med, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, John M Olin Sch Business, St Louis, MO 63130 USA. [Hall, Bruce L.] Washington Univ, Ctr Hlth Policy, St Louis, MO 63130 USA. [Hosokawa, Patrick W.; Henderson, William G.] Colorado Hlth Outcomes Program, Aurora, CO USA. [Ayanian, John Z.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Ayanian, John Z.; Zinner, Michael J.; Rogers, Selwyn O., Jr.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Ayanian, John Z.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Khuri, Shukri E.] Vet Adm Med Ctr, Dept Surg, W Roxbury, MA USA. [Zinner, Michael J.; Rogers, Selwyn O., Jr.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Esnaola, NF (reprint author), Med Univ S Carolina, Dept Surg, 25 Courtenay Dr Suite 7018 MSC 295, Charleston, SC 29425 USA. EM esnaolan@musc.edu FU Agency for Healthcare Research and Quality [1U18HS11913-03] FX Supported by Agency for Healthcare Research and Quality grant 1U18HS11913-03. NR 53 TC 24 Z9 24 U1 1 U2 1 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 OCT PY 2008 VL 248 IS 4 BP 647 EP 654 DI 10.1097/SLA.0b013e31818a159a PG 8 WC Surgery SC Surgery GA 366LT UT WOS:000260483700029 PM 18936578 ER PT J AU Smith, MJ Culhane, AC Killeen, S Kelly, MA Wang, JH Cotter, TG Redmond, HP AF Smith, Myles J. Culhane, Aedin C. Killeen, Shane Kelly, Maura A. Wang, Jiang H. Cotter, Thomas G. Redmond, Henry P. TI Mechanisms driving local breast cancer recurrence in a model of breast-conserving surgery SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE breast cancer; local recurrence; animal model; microarray; vaccine ID GENE-EXPRESSION SIGNATURE; SMALL-MOLECULE INHIBITOR; HEAT-SHOCK PROTEINS; RANDOMIZED-TRIAL; SURVIVAL; AKT; METASTASIS; THERAPY; CELLS; PCR AB Objective: We aimed to identify mechanisms driving local recurrence in a model of breast-conserving surgery (BCS) for breast cancer. Background: Breast cancer recurrence after BCS remains a clinically significant, but poorly understood problem. We have previously reported that recurrent colorectal tumours demonstrate altered growth dynamics, increased metastatic burden and resistance to apoptosis, mediated by upregulation of phosphoinositide-3-kinase/Akt (PI3K/Akt). We investigated whether similar characteristics were evident in a model of locally recurrent breast cancer. Methods: Tumours were generated by orthotopic inoculation of 4T1 cells in two groups of female Balb/c mice and cytoreductive surgery performed when mean tumour size was above 150 mm(3). Local recurrence was observed and gene expression was examined using Affymetrix GeneChips in primary and recurrent tumours. Differential expression was confirmed with quantitative real-time polymerase chain reaction (qRT-PCR). Phosphorylation of Akt was assessed using Western immunoblotting. An ex vivo heat shock protein (HSP)-loaded dendritic cell vaccine was administered in the perioperative period. Results: We observed a significant difference in the recurrent 4T1 tumour volume and growth rate (p < 0.05). Gene expression studies suggested roles for the PI3K/Akt system and local immunosuppression driving the altered growth kinetics. We demonstrated that perioperative vaccination with an ex vivo HSP-loaded dendritic cell vaccine abrogated recurrent tumour growth in vivo (p = 0.003 at day 15). Conclusion: Investigating therapies which target tumour survival pathways such as PI3K/Akt and boost immune surveillance in the perioperative period may be useful adjuncts to contemporary breast cancer treatment. C1 [Smith, Myles J.; Killeen, Shane; Kelly, Maura A.; Wang, Jiang H.; Redmond, Henry P.] Cork Univ Hosp, Acad Dept Surg, Cork, Ireland. [Smith, Myles J.; Cotter, Thomas G.] Natl Univ Ireland Univ Coll Cork, Cork Univ Hosp, Cork, Ireland. [Culhane, Aedin C.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Culhane, Aedin C.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Smith, MJ (reprint author), Cork Univ Hosp, Acad Dept Surg, Cork, Ireland. EM mylessmith@hotmail.com RI Smith, Myles/B-7803-2009 OI Smith, Myles/0000-0002-3254-4817 NR 42 TC 7 Z9 7 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD OCT PY 2008 VL 15 IS 10 BP 2954 EP 2964 DI 10.1245/s10434-008-0037-5 PG 11 WC Oncology; Surgery SC Oncology; Surgery GA 348BP UT WOS:000259186300044 PM 18622646 ER PT J AU Roedl, JB Harisinghani, MG Colen, RR Fischman, AJ Blake, MA Mathisen, DJ Mueller, PR AF Roedl, Johannes B. Harisinghani, Mukesh G. Colen, Rivka R. Fischman, Alan J. Blake, Michael A. Mathisen, Douglas J. Mueller, Peter R. TI Assessment of treatment response and recurrence in esophageal carcinoma based on tumor length and standardized uptake value on positron emission tomography-computed tomography SO ANNALS OF THORACIC SURGERY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; NEOADJUVANT CHEMORADIOTHERAPY; ESOPHAGOGASTRIC JUNCTION; FDG-PET; CANCER; SURVIVAL; TRIAL; CHEMOTHERAPY; SURGERY; CT AB Background. Previous studies demonstrated that a decrease of the standardized uptake value between pretreatment and posttreatment positron emission tomography (PET) scans can predict histopathologic treatment response in patients with esophageal cancer. Methods. Forty-seven patients who underwent PET computed tomography (CT) scans before (scan 1) and after (scan 2) neoadjuvant chemoradiotherapy and during the follow-up period after surgery (scan 3) were included in this study. It was evaluated whether decrease of metabolic tumor length between scan 1 and scan 2 can predict histopathologic response to treatment. Moreover, the value of PET-CT was compared with PET in the assessment of tumor recurrence based on a visual analysis of scan 3. Reference standards for treatment response and recurrence were histopathology results. Results. The reduction of tumor length between before and after chemoradiotherapy scans (between scan 1 and scan 2) was a better predictor of histopathologic response and of time to recurrence than the decrease in standardized uptake value. The most accurate differentiation was achieved when using a cut-off value of 33% reduction of the initial tumor length. Using this threshold to define metabolic response, the sensitivity was 91% (19 of 21) and the specificity was 92% (24 of 26) for predicting histopathologic treatment response. Based on a visual analysis, PET-CT was more accurate than PET in the differentiation of tumor recurrence from posttreatment tissue changes. Integrated PET-CT achieved a sensitivity of 91% (48 of 53) and a specificity of 81% (30 of 37) in identifying sites of tumor recurrence, compared with 83% (44 of 53) and 65% (24 of 37) with PET. Conclusions. Decrease of tumor length was shown to be a better predictor of treatment response and disease-free survival than decrease of standardized uptake value. Furthermore, PET-CT is more accurate in the evaluation of recurrence than PET. C1 [Roedl, Johannes B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Abdominal & Intervent Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA. RP Roedl, JB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Fruit St 55, Boston, MA 02114 USA. EM johannes.roedl@gmail.com NR 31 TC 24 Z9 28 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 2008 VL 86 IS 4 BP 1131 EP 1138 DI 10.1016/j.athoracsur.2008.05.019 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 357LT UT WOS:000259848000012 PM 18805147 ER PT J AU Chu, D Bakaeen, FG Wang, XL Dao, TK LeMaire, SA Coselli, JS Huh, J AF Chu, Danny Bakaeen, Faisal G. Wang, Xing Li Dao, Tam K. LeMaire, Scott A. Coselli, Joseph S. Huh, Joseph TI The impact of peripheral vascular disease on long-term survival after coronary artery bypass graft surgery SO ANNALS OF THORACIC SURGERY LA English DT Article ID INTERMITTENT CLAUDICATION; CARDIAC-SURGERY; RISK-FACTORS; MORTALITY; REVASCULARIZATION; MORBIDITY; MODEL AB Background. Although peripheral vascular disease is known to negatively affect overall survival, its effects on survival after surgical myocardial revascularization have not been well described. The objective of this study was to examine the impact of peripheral vascular disease on long-term survival after coronary artery bypass grafting. Methods. We reviewed records of 1,164 consecutive patients (370 with peripheral vascular disease and 794 without it) who underwent primary isolated coronary artery bypass graft surgery between 1997 and 2007. Univariate and multivariate logistic regression methods were used to analyze variables associated with early outcomes. We assessed long-term survival by using Kaplan-Meier curves generated by log-rank tests, adjusting for confounding factors with Cox proportional hazards regression analysis. Results. Patients with peripheral vascular disease were generally sicker and had more comorbidities than patients without peripheral vascular disease. The presence of peripheral vascular disease does not predict increased rates of 30- day mortality or major adverse cardiac events. However, after controlling for potential confounding factors, patients with peripheral vascular disease had a significantly worse 9- year survival rate than patients without peripheral vascular disease (72.9% +/- 4.1% versus 82.8% +/- 2.4%; adjusted hazard ratio, 1.7; 95% confidence interval: 1.2 to 2.4; p = 0.004). Conclusions. Although peripheral vascular disease does not affect early outcomes in coronary artery bypass operations, it is an independent predictor of poor long-term survival among patients undergoing coronary artery bypass graft surgery. Identifying the mechanism that underlies this difference is important for improving survival in patients with peripheral vascular disease who undergo surgical myocardial revascularization. C1 [Chu, Danny] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Div Cardiothorac Surg, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. St Lukes Episcopal Hosp, Texas Heart Inst, Sect Adult Cardiac Surg, Houston, TX USA. RP Chu, D (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Div Cardiothorac Surg, Dept Psychiat & Behav Sci, 2002 Holcombe Blvd,OCL 112, Houston, TX 77030 USA. EM dchumd@gmail.com NR 19 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 2008 VL 86 IS 4 BP 1175 EP 1180 DI 10.1016/j.athoracsur.2008.06.024 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 357LT UT WOS:000259848000018 PM 18805156 ER PT J AU Craig, WA Andes, DR AF Craig, W. A. Andes, D. R. TI In vivo pharmacodynamics of ceftobiprole against multiple bacterial pathogens in murine thigh and lung infection models SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID METHICILLIN-RESISTANT STAPHYLOCOCCI; PARENTERAL CEPHALOSPORIN; SPECTRUM CEPHALOSPORIN; BAL9141; PHARMACOKINETICS; VITRO; ANTIBIOTICS; PNEUMONIA; EFFICACY; BAL5788 AB Ceftobiprole medocaril is the parenteral prodrug of ceftobiprole, a novel pyrrolidinone broad-spectrum cephalosporin with in vitro and in vivo bactericidal activities against methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae (PRSP). We have used murine thigh and lung infection models in neutropenic and normal mice to characterize the in vivo pharmacokinetic (PK)-pharmacodynamic (PD) activities of ceftobiprole against multiple strains of S. aureus (including MRSA), S. pneumoniae (including PRSP), and gram-negative bacilli. Serum levels of ceftobiprole following the administration of multiple doses were determined by a microbiological assay. In vivo bactericidal activities and postantibiotic effects (PAEs) of ceftobiprole against MRSA and PRSP strains were determined from serial CFU/thigh values following single doses of ceftobiprole (40 and 160 mg/kg of body weight). Dose fractionation studies were used to determine which PK-PD index correlated best with activity. Magnitudes of the PK-PD indices were calculated from MICs and PK parameters. A sigmoid dose-response model was used to estimate the dose (mg/kg/24 h) required to achieve a static and 2-log(10) kill effects over 24 h. PK results showed area under the concentration-time curve/dose values of 1.8 to 2.8 and half-lives of 0.29 to 0.51 h. MICs ranged from 0.015 to 2 mu g/ml. Ceftobiprole demonstrated time-dependent killing; its in vivo PAEs varied from 3.8 h to 4.8 h for MRSA and from 0 to 0.8 h for PRSP. The time above MIC (T > MIC) correlated best with efficacy for both MRSA and PRSP. The T > MIC values required for the static doses were significantly longer (P < 0.001) for Enterobacteriaceae (36 to 45%) than for S. aureus (14 to 28%) and S. pneumoniae (15 to 22%). The drug showed activities in the lung model similar to those in the thigh model. The presence of neutrophils significantly enhanced the activity of ceftobiprole against S. pneumoniae but only slightly against Klebsiella pneumoniae. Based on its PD profile, ceftobiprole is a promising new beta-lactam agent with activity against gram-negative and gram-positive organisms including MRSA and PRSP. C1 [Craig, W. A.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. [Craig, W. A.; Andes, D. R.] Univ Wisconsin, Dept Med, Infect Dis Sect, Sch Med & Publ Hlth, Madison, WI 53706 USA. RP Craig, WA (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace, Madison, WI 53705 USA. EM wac@medicine.wisc.edu NR 25 TC 45 Z9 46 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 2008 VL 52 IS 10 BP 3492 EP 3496 DI 10.1128/AAC.01273-07 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 352FJ UT WOS:000259480800004 PM 18676887 ER PT J AU Forrest, GN Roghmann, MC Toombs, LS Johnson, JK Weekes, E Lincalis, DP Venezia, RA AF Forrest, Graeme N. Roghmann, Mary-Claire Toombs, Latoya S. Johnson, Jennifer K. Weekes, Elizabeth Lincalis, Durry P. Venezia, Richard A. TI Peptide nucleic acid fluorescent in situ hybridization for hospital-acquired enterococcal bacteremia: Delivering earlier effective antimicrobial therapy SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID VANCOMYCIN-RESISTANT ENTEROCOCCUS; BLOOD-STREAM INFECTIONS; STEM-CELL TRANSPLANT; RISK-FACTORS; FAECIUM BACTEREMIA; STAPHYLOCOCCUS-AUREUS; CANDIDA-ALBICANS; RAPID DETECTION; MORTALITY; IDENTIFICATION AB Hospital-acquired vancomycin-resistant enterococcal bacteremia has been associated with increased hospital costs, length of stay, and mortality. The peptide nucleic acid fluorescent in situ hybridization (PNA FISH) test for Enterococcus faecalis and other enterococci (EFOE) is a multicolor probe that differentiates E. faecalis from other enterococcal species within 3 h directly from blood cultures demonstrating gram-positive cocci in pairs and chains (GPCPC). A quasiexperimental study was performed over two consecutive years beginning in 2005 that identified GPCPC by conventional microbiological methods, and in 2006 PNA FISH was added with a treatment algorithm developed by the antimicrobial team (AMT). The primary outcome assessed was the time from blood culture draw to the implementation of effective antimicrobial therapy before and after PNA FISH. The severity of illness, patient location, and empirical antimicrobial therapy were measured. A total of 224 patients with hospital-acquired enterococcal bacteremia were evaluated, with 129 in the preintervention period and 95 in the PNA FISH period. PNA FISH identified E. faecalis 3 days earlier than conventional cultures (1.1 versus 4.1 days; P < 0.001). PNA FISH identified Enterococcus faecium a median 2.3 days earlier (1.1 versus 3.4 days; P < 0.001) and was associated with statistically significant reductions in the time to initiating effective therapy (1.3 versus 3.1 days; P < 0.001) and decreased 30-day mortality (26% versus 45%; P = 0.04). The EFOE PNA FISH test in conjunction with an AMT treatment algorithm resulted in earlier initiation of appropriate empirical antimicrobial therapy for patients with hospital-acquired E. faecium bacteremia. C1 [Forrest, Graeme N.] Univ Maryland, Sch Med, Div Infect Dis, Baltimore, MD 21201 USA. [Roghmann, Mary-Claire] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. [Toombs, Latoya S.; Weekes, Elizabeth] Univ Maryland, Dept Pharm, Med Ctr, Baltimore, MD 21201 USA. [Johnson, Jennifer K.; Lincalis, Durry P.; Venezia, Richard A.] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. RP Forrest, GN (reprint author), Portland VA Med Ctr, 3701 SW US Vet Hosp Rd,P31D, Portland, OR 97239 USA. EM forrestg@ohsu.edu OI Roghmann, Mary-Claire/0000-0003-1063-9257 FU AdvanDx; Cubist Pharmaceuticals, Inc.; Pfizer Inc; 3M FX Potential conflicts of interest: G.N.F. has received research funding and speaking honoraria from AdvanDx, Cubist Pharmaceuticals, Inc., and Pfizer Inc. M.-C.R. has received research funding from 3M and Merck. R.A.V. and J.K.J. have received speaking honoraria from AdvanDx. NR 40 TC 81 Z9 83 U1 0 U2 2 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 OCT PY 2008 VL 52 IS 10 BP 3558 EP 3563 DI 10.1128/AAC.00283-08 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 352FJ UT WOS:000259480800013 PM 18663022 ER PT J AU Rodrigues, MS Reddy, MM Sattler, M AF Rodrigues, Margret S. Reddy, Mamatha M. Sattler, Martin TI Cell cycle regulation by oncogenic tyrosine kinases in myeloid neoplasias: From molecular redox mechanisms to health implications SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID NF-KAPPA-B; CHRONIC MYELOGENOUS LEUKEMIA; HYPOXIA-INDUCIBLE FACTOR; FORKHEAD TRANSCRIPTION FACTOR; ENDOTHELIAL GROWTH-FACTOR; P210 BCR-ABL; GUANINE-NUCLEOTIDE EXCHANGE; TUMOR-SUPPRESSOR PTEN; UBIQUITIN-PROTEASOME PATHWAY; ANTIOXIDANT GENE-EXPRESSION AB Neoplastic expansion of myeloid cells is associated with specific genetic changes that lead to chronic activation of signaling pathways, as well as altered metabolism. It has become increasingly evident that transformation relies on the interdependency of both events. Among the various genetic changes, the oncogenic BCR-ABL tyrosine kinase in patients with Philadelphia chromosome positive chronic myeloid leukemia (CML) has been a focus of extensive research. Transformation by this oncogene is associated with elevated levels of intracellular reactive oxygen species (ROS). ROS have been implicated in processes that promote viability, cell growth, and regulation of other biological functions such as migration of cells or gene expression. Currently, the BCR-ABL inhibitor imatinib mesylate (Gleevec) is being used as a first-line therapy for the treatment of CML. However, BCR-ABL transformation is associated with genomic instability, and disease progression or resistance to imatinib can occur. Imatinib resistance is not known to cause or significantly alter signaling requirements in transformed cells. Elevated ROS are crucial for transformation, making them an ideal additional target for therapeutic intervention. The underlying mechanisms leading to elevated oxidative stress are reviewed, and signaling mechanisms that may serve as novel targeted approaches to overcome ROS-dependent cell growth are discussed. C1 [Sattler, Martin] Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Sattler, M (reprint author), Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM martin_sattler@dfci.harvard.edu FU American Cancer Society; United States Department of Defense; Adams Barr Program in Innovative Cancer Research FX This work was supported by grants from the American Cancer Society, the United States Department of Defense, and the Adams Barr Program in Innovative Cancer Research. NR 416 TC 30 Z9 31 U1 0 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD OCT PY 2008 VL 10 IS 10 BP 1813 EP 1848 DI 10.1089/ars.2008.2071 PG 36 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 340DI UT WOS:000258625900006 PM 18593226 ER PT J AU Marijon, E Lung, B Mocumbi, AO Kamblock, J Thanh, CV Gamra, H Esteves, C Palacios, IF Vahanian, A AF Marijon, Eloi Lung, Bernard Mocumbi, Ana-Olga Kamblock, Joel Thanh, Chien Vo Gamra, Habib Esteves, Cesar Palacios, Igor F. Vahanian, Alec TI What are the differences in presentation of candidates for percutaneous mitral commissurotomy across the world and do they influence the results of the procedure? SO ARCHIVES OF CARDIOVASCULAR DISEASES LA English DT Article DE Mitral stenosis; Rheumatic fever; Balloon mitral commissurotomy ID RHEUMATIC HEART-DISEASE; TERM-FOLLOW-UP; BALLOON VALVULOPLASTY; STENOSIS; VALVOTOMY; VARIABLES; PERIOD AB Background. - Despite marked global differences in the prevalence of rheumatic heart disease, little is known about geographic variations in the characteristics of patients with severe mitral stenosis. Aim. - To determine if differences in rheumatic fever epidemiology influence the characteristics of patients with mitral stenosis and the immediate results of percutaneous mitral commissurotomy (PMC). Methods. - We compared 350 patients (mean age: 41 +/- 17 years, 81% women) scheduled for PMC in five non-Western and two Western countries. Fifty consecutive patients were included in each centre. All presented a mitral valve area less than 1.5 cm(2) and were in New York Heart Association (NYHA) functional class greater or equal to 11, with no contraindications to PMC. Results. - The 250 patients from non-Western countries were younger than the 100 patients from Western countries (35 +/- 12 vs 57 +/- 15 years, p < 0.0001) and had more severe valve disease, assessed by indexed valve area (0.57 +/- 0.14 vs 0.62 +/- 0.14 cm(2)/m(2) body surface area, p = 0.006), mean gradient (15 +/- 6 vs 8 +/- 4 mmHg, p < 0.0001) and systolic pulmonary artery pressure (57 +/- 21 vs 42 +/- 14 mmHg, p < 0.0001). PMC complication rates did not differ significantly. Good immediate PMC results were observed in 225 patients (90%) in non-Western and 88 (88%) in Western centres (p = 0.58). Conclusions. - Compared with Western countries, PMC candidates from non-Western countries are younger, with more severe valve stenosis. However, PMC achieves good immediate results in a similarly high proportion of patients, showing the wide applicability of this technique. (C) 2008 Elsevier Masson SAS. All rights reserved. C1 [Marijon, Eloi; Lung, Bernard; Vahanian, Alec] Hop Xavier Bichat, Dept Cardiol, AP HP, F-75018 Paris, France. [Mocumbi, Ana-Olga] Inst Coracao, Maputo, Mozambique. [Kamblock, Joel] Taaone Hosp, Dept Cardiol, Papeete, Fr Polynesia. [Thanh, Chien Vo] Cho Ray Hosp, Dept Cardiol, Ho Chi Minh City, Vietnam. [Gamra, Habib] Fattouma Bourguiba Hosp, Dept Cardiol, Monastir, Tunisia. [Esteves, Cesar] Dante Pazzanese Inst, Dept Cardiol, Sao Paulo, Brazil. [Palacios, Igor F.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Marijon, E (reprint author), Hop Xavier Bichat, Dept Cardiol, AP HP, 46 Rue Henri Huchard, F-75018 Paris, France. EM eloi_marijon@yahoo.fr NR 24 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 1875-2136 EI 1875-2128 J9 ARCH CARDIOVASC DIS JI Arch. Cardiovasc. Dis. PD OCT PY 2008 VL 101 IS 10 BP 611 EP 617 DI 10.1016/j.acvd.2008.09.012 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 386ZT UT WOS:000261922200004 PM 19056067 ER PT J AU Schaffer, BAJ Bertram, L Miller, BL Mullin, K Weintraub, S Johnson, N Bigio, EH Mesulam, M Wiedau-Pazos, M Jackson, GR Cummings, JL Cantor, RM Levey, AI Tanzi, RE Geschwind, DH AF Schaffer, Barbara A. J. Bertram, Lars Miller, Bruce L. Mullin, Kristina Weintraub, Sandra Johnson, Nancy Bigio, Eileen H. Mesulam, Marsel Wiedau-Pazos, Martina Jackson, George R. Cummings, Jeffrey L. Cantor, Rita M. Levey, Allan I. Tanzi, Rudolph E. Geschwind, Daniel H. TI Association of GSK3B with Alzheimer disease and frontotemporal dementia SO ARCHIVES OF NEUROLOGY LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3-BETA; PRIMARY PROGRESSIVE APHASIA; NEUROFIBRILLARY TANGLES; GENETIC ASSOCIATION; APOLIPOPROTEIN-E; NEURODEGENERATION; POLYMORPHISMS; VARIANTS; ONSET; CDK5 AB Background: Deposits of abnormally hyperphosphorylated tau are a hallmark of several dementias, including Alzheimer disease ( AD), and about 10% of familial frontotemporal dementia (FTD) cases are caused by mutations in the tau gene. As a known tau kinase, GSK3B is a promising candidate gene in the remaining cases of FTD and in AD, for which tau mutations have not been found. Objective: To examine the promoter of GSK3B and all 12 exons, including the surrounding intronic sequence, in patients with FTD, patients with AD, and aged healthy subjects to identify single-nucleotide polymorphisms associated with disease. Design, Setting, and Participants: Single-nucleotide polymorphism frequency was examined in a case-control cohort of 48 patients with probable AD, 102 patients with FTD, 38 patients with primary progressive aphasia, and 85 aged healthy subjects. Results were followed up in 2 independent AD family samples consisting of 437 multiplex families with AD (National Institute of Mental Health Genetics Initiative AD Study) or 150 sibships discordant for AD (Consortium on Alzheimer's Genetics Study). Results: Several rare sequence variants in GSK3B were identified in the case-control study. An intronic polymorphism (IVS2-68G > A) occurred at more than twice the frequency among patients with FTD (10.8%) and patients with AD (14.6%) than in aged healthy subjects (4.1%). The polymorphism showed association with disease in both follow-up samples independently, although only the Consortium on Alzheimer's Genetics sample showed the same direction of association as the case-control sample. Conclusions: To our knowledge, this is the first evidence that a gene known to be involved in tau phosphorylation, GSK3B, is associated with risk for primary neurodegenerative dementias. This supports previous work in animal models suggesting that such genes are therapeutic targets. C1 [Schaffer, Barbara A. J.; Wiedau-Pazos, Martina; Jackson, George R.; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Program Neurogenet, Los Angeles, CA 90095 USA. [Cummings, Jeffrey L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Cantor, Rita M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. [Cantor, Rita M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. [Bertram, Lars; Mullin, Kristina; Tanzi, Rudolph E.] Harvard Univ, MassGeneral Inst Neurodegenerat Dis, Massachusetts Gen Hosp, Dept Neurol,Sch Med,Genet & Aging Res Unit, Charlestown, MA USA. [Miller, Bruce L.] Univ Calif San Francisco, Dept Neurol, Ctr Memory & Aging, San Francisco, CA 94143 USA. [Weintraub, Sandra; Johnson, Nancy; Mesulam, Marsel] Northwestern Univ, Feinberg Sch Med, Cognit Neurol & Alzheimers Dis Ctr, Chicago, IL 60611 USA. [Bigio, Eileen H.] Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA. [Levey, Allan I.] Emory Univ, Alzheimers Dis Ctr, Atlanta, GA 30322 USA. [Levey, Allan I.] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. RP Geschwind, DH (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Program Neurogenet, 2506 Gonda,695 Charles E Young Dr S, Los Angeles, CA 90095 USA. EM dhg@ucla.edu RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X FU National Institute on Aging [AG16570, AG19724, AG13854, AG025688]; National Institute of Mental Health [MH60009] FX This work was supported by grants AG16570 (Ms Schaffer and Dr Geschwind), AG19724 (Dr Miller), AG13854 (Dr Mesulam), and AG025688 (Dr Levey) from the National Institute on Aging, grant MH60009 from the National Institute of Mental Health (Dr Tanzi), The John Douglas French Alzheimer's Foundation (Drs Wiedau-Pazos and Geschwind), the Cure Alzheimer's Fund (Dr Tanzi), and the Turken Family Scholarship Award from the Alzheimer's Association of Los Angeles (Dr Geschwind). At the time of this work, Dr Bertram was a fellow of the Harvard Center for Neurodegeneration and Repair and was a fellow of the Deutsche Forschungsgemeinschaft. NR 32 TC 51 Z9 54 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD OCT PY 2008 VL 65 IS 10 BP 1368 EP 1374 DI 10.1001/archneur.65.10.1368 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 359JY UT WOS:000259984200016 PM 18852354 ER PT J AU Dighe, AS Jones, JB Parham, S Lewandrowski, KB AF Dighe, Anand S. Jones, Jay B. Parham, Sue Lewandrowski, Kent B. TI Survey of Critical Value Reporting and Reduction of False-Positive Critical Value Results SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID LABORATORY CRITICAL-VALUES; NOTIFICATION; INSTITUTIONS; INFORMATION AB Context.-Reporting of laboratory critical values has become an issue of national attention because of important regulatory, medicolegal, and clinical concerns. Objective.-To survey aspects of the laboratory critical-value reporting process at a broad range of institutions. Design.-A survey was developed regarding the operational and information-technology aspects of critical value reporting. Results.-More than 730 responses were obtained from a broad distribution of hospitals. In addition, we analyzed more than 700 written responses from survey participants. Conclusions.-The survey results provide insight into the standard of practice and level of compliance with current Joint Commission and College of American Pathologists requirements for critical values, demonstrate considerable heterogeneity, and suggest areas for improvement. A common issue raised during the survey and follow-up teleconference was the incidence of outpatient false-positive critical values. In this report, we also demonstrate that attention to preanalytic transport and processing issues can assist in minimizing this issue. (Arch Pathol Lab Med. 2008; 132: 1666-1671) C1 [Dighe, Anand S.; Lewandrowski, Kent B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Jones, Jay B.] Geisinger Med Labs, Danville, PA USA. [Parham, Sue] Amer Assoc Clin Chem, Washington, DC USA. RP Lewandrowski, KB (reprint author), Massachusetts Gen Hosp, Dept Pathol, Bigelow 510,55 Fruit St, Boston, MA 02114 USA. EM klewandrowski@partners.org NR 16 TC 17 Z9 23 U1 2 U2 6 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD OCT PY 2008 VL 132 IS 10 BP 1666 EP 1671 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 358FT UT WOS:000259903200027 PM 18834227 ER PT J AU Wilens, TE Adamson, J Monuteaux, MC Faraone, SV Schillinger, M Westerberg, D Biederman, J AF Wilens, Timothy E. Adamson, Joel Monuteaux, Michael C. Faraone, Stephen V. Schillinger, Mary Westerberg, Diana Biederman, Joseph TI Effect of prior stimulant treatment for attention-deficit/hyperactivity disorder on subsequent risk for cigarette smoking and alcohol and drug use disorders in adolescents SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; SUBSTANCE USE DISORDERS; PSYCHIATRIC COMORBIDITY; EARLY EXPOSURE; YOUNG-ADULTS; ADHD; CHILDREN; ABUSE; METHYLPHENIDATE; PREVALENCE AB Objective: To examine the effects of early stimulant treatment on subsequent risk for cigarette smoking and substance use disorders (SUDs) in adolescents with attentiondeficit/hyperactivity disorder (ADHD). Design: Case-controlled, prospective, 5-year follow-up study. Setting: Massachusetts General Hospital, Boston. Participants: Adolescents with and without ADHD from psychiatric and pediatric sources. Blinded interviewers determined all diagnoses using structured interviews. Intervention: Naturalistic treatment exposure with psychostimulants for ADHD. Main Outcome Measures: We modeled time to onset of SUDs and smoking as a function of stimulant treatment. Results: We ascertained 114 subjects with ADHD (mean age at follow-up, 16.2 years) having complete medication and SUD data; 94 of the subjects were treated with stimulants. There were no differences in SUD risk factors between naturalistically treated and untreated groups other than family history of ADHD. We found no increased risks for cigarette smoking or SUDs associated with stimulant therapy. We found significant protective effects of stimulant treatment on the development of any SUD (hazard ratio [HR], 0.27; 95% confidence interval [CI], 0.13-0.60; chi(2)(113) = 10.57, P =. 001) and cigarette smoking(HR, 0.28; 95% CI, 0.14-0.60; chi(2)(111) = 10.05, P=. 001) that were maintained when controlling for conduct disorder. We found no effects of time to onset or duration of stimulant therapy on subsequent SUDs or cigarette smoking in subjects with ADHD. Conclusion: Stimulant therapy does not increase but rather reduces the risk for cigarette smoking and SUDs in adolescents with ADHD. C1 [Wilens, Timothy E.; Adamson, Joel; Monuteaux, Michael C.; Schillinger, Mary; Westerberg, Diana; Biederman, Joseph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Program, Boston, MA 02114 USA. [Faraone, Stephen V.] NYU, Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, Stephen V.] NYU, Upstate Med Univ, Dept Neurosci, Syracuse, NY USA. [Faraone, Stephen V.] NYU, Upstate Med Univ, Dept Physiol, Syracuse, NY USA. RP Wilens, TE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Program, 55 Parkman St,Yawkey 6A, Boston, MA 02114 USA. EM twilens@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU National Institutes of Health [DA R01 DA14419, K24 DA016264]; Lilly Foundation FX This study was supported by grants DA R01 DA14419 and K24 DA016264 from the National Institutes of Health (Dr Wilens) and by the Lilly Foundation. NR 39 TC 54 Z9 54 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD OCT PY 2008 VL 162 IS 10 BP 916 EP 921 DI 10.1001/archpedi.162.10.916 PG 6 WC Pediatrics SC Pediatrics GA 356VY UT WOS:000259806900003 PM 18838643 ER PT J AU Pagulayan, KF Hoffman, JM Temkin, NR Machamer, JE Dikmen, SS AF Pagulayan, Kathleen Farrell Hoffman, Jeanne M. Temkin, Nancy R. Machamer, Joan E. Dikmen, Sureyya S. TI Functional Limitations and Depression After Traumatic Brain Injury: Examination of the Temporal Relationship SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Brain injuries; Depression; Longitudinal studies; Rehabilitation; Sickness Impact Profile ID MAJOR DEPRESSION; RANDOMIZED-TRIAL; PRIMARY-CARE; CHRONIC PAIN; HEAD-INJURY; SCALE; RELIABILITY; DISORDER; VALIDITY; PREVALENCE AB Objective: To examine the temporal relationship between self-reported injury-related functional limitations and depressive symptomatology after traumatic brain injury (TBI). Design: A longitudinal cohort study with 3 evaluation points. Setting: A level I trauma center. Participants: Adolescents and adults (N=135) with complicated mild to severe TBI (72% had complicated mild injuries) who were recruited within 24 hours of injury and then completed the measure at all 3 time points. Interventions: Not applicable. Main Outcome Measures: Sickness Impact Profile and Center for Epidemiological Studies-Depression Scale. Results: Individuals who reported more depressive symptomatology consistently endorsed more injury-related difficulties, showing the strong relationship between depression and perceived psychosocial functioning. Examination of these relationships over time revealed that increased depressive symptomatology follows higher levels of perceived injury-related changes but that reports of injury-related changes are not associated with earlier depression. These findings suggest a unidirectional temporal relationship between these variables. Conclusions: Perceived changes in daily functioning appear to influence emotional well-being over time after TBI. However, depressive symptoms do not appear to negatively impact individuals' perception of later functioning. These results further our understanding of the complicated relationship between these variables and may have important implications for treatment of depression after TBI. C1 [Pagulayan, Kathleen Farrell; Hoffman, Jeanne M.; Temkin, Nancy R.; Machamer, Joan E.; Dikmen, Sureyya S.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Temkin, Nancy R.; Dikmen, Sureyya S.] Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA. [Temkin, Nancy R.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Pagulayan, KF (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-116 MHC, Seattle, WA 98108 USA. EM farkat@u.washington.edu FU National Institute of Neurological Disorders and Stroke; National Institutes of Health [RO1 NS19643, F32 HD048030]; National Center for Medical Rehabilitation Research FX Supported by the National Institute of Neurological Disorders and Stroke, National Institutes of Health (grant no. RO1 NS19643) and the National Center for Medical Rehabilitation Research, National Institutes of Health (grant no. F32 HD048030). NR 56 TC 45 Z9 45 U1 1 U2 6 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 OCT PY 2008 VL 89 IS 10 BP 1887 EP 1892 DI 10.1016/j.apmr.2008.03.019 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 366LY UT WOS:000260484200006 PM 18929017 ER PT J AU Kaafarani, HMA Atluri, PV Thornby, J Itani, KMF AF Kaafarani, Haytham M. A. Atluri, Prasad V. Thornby, John Itani, Kamal M. F. TI beta-Blockade in Noncardiac Surgery Outcome at All Levels of Cardiac Risk SO ARCHIVES OF SURGERY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; VASCULAR-SURGERY; MYOCARDIAL-INFARCTION; MORTALITY; METOPROLOL; ISCHEMIA AB Hypothesis: We hypothesized that the relationship among beta-blocker use, heart rate control, and perioperative cardiovascular outcome would be similar in patients at all levels of cardiac risk. Design: Retrospective cohort study. Setting: Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas. Patients: Among all patients who underwent various noncardiac surgical procedures in 2000, those who received perioperative beta-blockers were matched and compared with a control group from the same patient population. Main Outcome Measures: Thirty-day stroke, cardiac arrest, myocardial infarction, and mortality, as well as mortality at 1 year. Results: Patients at all levels of cardiac risk who received beta-blockers had lower preoperative and intraoperative heart rates. The beta-blocker group had higher rates of 30-day myocardial infarction (2.94% vs 0.74%, P=.03) and 30-day mortality (2.52% vs 0.25%, P=.007) compared with the control group. In the beta-blocker group, patients who died perioperatively had significantly higher preoperative heart rate (86 vs 70 beats/min, P=.03). None of the deaths occurred among the patients at high cardiac risk. Conclusion: Among patients at all levels of cardiac risk undergoing noncardiac surgery, administration of beta-blockers should achieve adequate heart rate control and should be carefully monitored in patients who are not at high cardiac risk. C1 [Kaafarani, Haytham M. A.] Univ S Florida, Dept Surg, Tampa, FL 33620 USA. [Kaafarani, Haytham M. A.; Itani, Kamal M. F.] Vet Affairs Boston Hlth Care Syst, W Roxbury, MA USA. [Kaafarani, Haytham M. A.; Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA. [Kaafarani, Haytham M. A.; Itani, Kamal M. F.] Boston Univ, Boston, MA 02215 USA. [Atluri, Prasad V.] Baylor Coll Med, Dept Anesthesia, Houston, TX 77030 USA. [Thornby, John] Michael E DeBakey Vet Affairs Med Ctr, Biostat Lab, Houston, TX USA. RP Itani, KMF (reprint author), Vet Affairs Boston Healthcare Syst 112, Dept Surg, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM kitani@med.va.gov NR 14 TC 18 Z9 19 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 OCT PY 2008 VL 143 IS 10 BP 940 EP 944 DI 10.1001/archsurg.143.10.940 PG 5 WC Surgery SC Surgery GA 360GG UT WOS:000260045400005 PM 18936371 ER PT J AU Berger, DL AF Berger, David L. TI Pancreatogastrostomy as a Salvage Procedure to Treat Severe Postoperative Pancreatic Fistula After Pancreatoduodenectomy INVITED CRITIQUE SO ARCHIVES OF SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Berger, DL (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,Wang 465, Boston, MA 02114 USA. EM dberger@partners.org NR 0 TC 0 Z9 0 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 OCT PY 2008 VL 143 IS 10 BP 971 EP 971 DI 10.1001/archsurg.143.10.971 PG 1 WC Surgery SC Surgery GA 360GG UT WOS:000260045400011 ER PT J AU Musunuru, K Nasir, K Pandey, S Campbell, CC Carvalho, JAM Meneghello, R Budoff, MJ Blumenthal, RS Santos, RD AF Musunuru, Kiran Nasir, Khurram Pandey, Shivda Campbell, Catherine C. Carvalho, Jose A. M. Meneghello, Romeu Budoff, Matthew J. Blumenthal, Roger S. Santos, Raul D. TI A synergistic relationship of elevated low-density lipoprotein cholesterol levels and systolic blood pressure with coronary artery calcification SO ATHEROSCLEROSIS LA English DT Article DE Coronary calcification; Systolic blood pressure; LDL-cholesterol; Electron beam tomography; Risk factors; Subclinical atherosclerosis ID BEAM COMPUTED-TOMOGRAPHY; INTIMA-MEDIA THICKNESS; PROGNOSTIC VALUE; HEART-DISEASE; RISK-FACTORS; CALCIUM; ATHEROSCLEROSIS; QUANTIFICATION; PATHOGENESIS; ASSOCIATION AB We sought to evaluate this "response-to-injury" hypothesis of atherosclerosis by studying the interaction between systolic blood pressure (SBP) and LDL-cholesterol (LDL-C) in predicting the presence of coronary artery calcification (CAC) in asymptomatic men. We Studied 526 men (46 +/- 7 years of age) referred for electron-beam tomography (EBT) exam. The prevalence of CAC was determined across LDL-C tertiles (low: <115 mg/dl; middle: 115-139 mg/dl high: >= 140 mg/dl) within tertiles of SBP (low: <121 mmHg; middle: 121-130 mmHg; high: >= 131 mmHg). CAC was found in 220 (42%) men. There was no linear trend in the presence of CAC across LDL-C tertiles in the low (p = 0.6 for trend) and middle (p = 0.3 for trend) SBP tertile groups, respectively. In contrast, there was a significant trend for increasing CAC with increasing LDL-C (1st: 44%; 2nd: 49%; 3rd: 83%; p < 0.0001 for trend) in the high SBP tertile group. In multivariate logistic analyses (adjusting for age, smoking, triglyceride levels, HDL-cholesterol levels, body mass index, and fasting glucose levels), the odds ratio for any CAC associated with increasing LDL-C was significantly higher in those with highest SBP levels, whereas no such relationship was observed among men with SBP in the lower two tertiles. An interaction term (LDL-C x SBP) incorporated in the multivariate analyses was statistically significant (p = 0.038). The finding of an interaction between SBP and LDL-C relation to CAC in asymptomatic men support the response-to-injury model of atherogenesis. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Musunuru, Kiran; Campbell, Catherine C.; Blumenthal, Roger S.] Johns Hopkins Univ, Sch Med, Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA. [Nasir, Khurram; Pandey, Shivda] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac PET CT MRI Program, Boston, MA USA. [Carvalho, Jose A. M.; Meneghello, Romeu; Santos, Raul D.] Albert Einstein Hosp Sao Paulo, Prevent Med Ctr, Sao Paulo, Brazil. [Budoff, Matthew J.] Harbor UCLA, Torrance, CA USA. [Santos, Raul D.] Univ Sao Paulo, Lipid Clin Heart Inst InCor, Sch Med, Hosp Sao Paulo, BR-05508 Sao Paulo, Brazil. RP Santos, RD (reprint author), Unidade Clin Lipides InCor HCFMUSP, Av Dr Eneas C Aguiar 44,Anexo 2 Sala 4, BR-05403900 Sao Paulo, Brazil. EM rdsf@uol.com.br RI Santos, Raul/A-1170-2010 OI Santos, Raul/0000-0002-9860-6582 NR 22 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD OCT PY 2008 VL 200 IS 2 BP 368 EP 373 DI 10.1016/j.atherosclerosis.2007.12.015 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 368UJ UT WOS:000260647700019 PM 18243213 ER PT J AU Swanlund, JM Kregel, KC Oberley, TD AF Swanlund, Jamie M. Kregel, Kevin C. Oberley, Terry D. TI Autophagy following heat stress - The role of aging and protein nitration SO AUTOPHAGY LA English DT Article DE mitochondria; 3-nitrotyrosine; autophagy; heat stress; oxidative stress; nitric oxide ID OXIDATIVE STRESS; RAT HEPATOCYTES; CELLS; PEROXYNITRITE; SECTIONS AB Stress can originate from a variety of sources (e.g., physical, chemical, etc.,) and cause protein denaturation, DNA damage and possibly death. In an effort to prevent such deleterious consequences, most organisms possess one or more ways to counteract or even prevent the harmful effect(s) from a given stressor. Such compensation by an organism is known as a stress response; this involves inhibition of housekeeping genes and subsequent activation of genes associated with the stress response.(1) One of the most widely studied groups of stress response genes Is a family of molecular chaperones known as heat shock proteins (HSPs). Work from our laboratory agrees with many other studies showing an age-related decline in stress-induced synthesis of HSPs.(2) A decline in the availability and/or function of HSPs with age can lead to accumulation of damaged proteins, which in turn damages cells. Recently, our laboratory found a significant increase in mitochondrial damage as well as evidence of increased autophagy in rat hepatocytes following heat stress.(3) These results, along with findings of increased protein nitration with age, suggest a major role for reactive nitrogen species (RNS) in both the decline in HSP induction and increased hepatocyte pathology observed in old rats following heat stress. C1 [Swanlund, Jamie M.; Oberley, Terry D.] William S Middleton Mem Vet Adm Med Ctr, Dept Pathol & Lab Med, Madison, WI 53705 USA. [Oberley, Terry D.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI USA. [Kregel, Kevin C.] Univ Iowa, Dept Radiat Oncol, Dept Integrat Physiol, Iowa City, IA USA. [Kregel, Kevin C.] Univ Iowa, Dept Radiat Oncol, Free Radical & Radiat Biol Program, Iowa City, IA USA. RP Oberley, TD (reprint author), William S Middleton Mem Vet Adm Med Ctr, Dept Pathol & Lab Med, Room A-35,2500 Overlook Terrace, Madison, WI 53705 USA. EM toberley@wisc.edu FU NIA NIH HHS [R01 AG012350-09A1] NR 25 TC 19 Z9 19 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD OCT 1 PY 2008 VL 4 IS 7 BP 936 EP 939 PG 4 WC Cell Biology SC Cell Biology GA 357ES UT WOS:000259829700016 PM 18758235 ER PT J AU Guichard, C Moreau, R Pessayre, D Epperson, TK Krause, KH AF Guichard, Cecile Moreau, Richard Pessayre, Dominique Epperson, Terry Kay Krause, Karl-Heinz TI NOX family NADPH oxidases in liver and in pancreatic islets: a role in the metabolic syndrome and diabetes? SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 3rd Intracellular Proteolysis Meeting CY MAR 05-07, 2008 CL Canary Isl, SPAIN SP Joint Biochem Soc, INPROTEOLYS Network DE diabetes; liver; metabolic Syndrome; NADPH oxidase; NOX family; pancreatic islet ID HEPATIC STELLATE CELLS; ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; ENZYME GENE-EXPRESSION; OXIDATIVE STRESS; BETA-CELL; NAD(P)H OXIDASE; INSULIN-RESISTANCE; MITOCHONDRIAL DYSFUNCTION; HEPATOCYTE APOPTOSIS AB The incidence of obesity and non-esterified ('free') fatty acid-associated metabolic disorders such as the metabolic syndrome and diabetes is increasing dramatically in most countries. Although the pathogenesis of these metabolic disorders is complex, there is emerging evidence that ROS (reactive oxygen species) are critically involved in the aberrant signalling and tissue damage observed in this context. indeed, it is now widely accepted that ROS not only play an important role in physiology, but also contribute to cell and tissue dysfunction. inappropriate ROS generation may contribute to tissue dysfunction in two ways: (i) dysregulation of redox-sensitive signalling pathways, and (ii) oxidative damage to biological structures (DNA, proteins, lipids, etc.). An important source of ROS is the NOX family of NADPH oxidases. Several NOX isoforms are expressed in the liver and pancreatic beta-cells. There is now evidence that inappropriate activation of NOX enzymes may damage the liver and pancreatic beta-cells. in the context of the metabolic syndrome, the emerging epidemic of non-alcoholic steatohepatitis is thought to be NOX/ROS-dependent and of particular medical relevance. NOX/ROS-dependent beta-cell damage is thought to be involved in glucolipotoxicity and thereby leads to progression from the metabolic syndrome to Type 2 diabetes. Thus understanding the role of NOX enzymes in liver and beta-cell damage should lead to an increased understanding of pathomechanisms in the metabolic syndrome and diabetes and may identify useful targets for novel therapeutic strategies. C1 [Guichard, Cecile; Pessayre, Dominique; Krause, Karl-Heinz] Geneva Med Fac, Dept Pathol & Immunol, CH-1211 Geneva 4, Switzerland. [Guichard, Cecile; Pessayre, Dominique; Krause, Karl-Heinz] Univ Hosp Geneva, CH-1211 Geneva, Switzerland. [Guichard, Cecile; Pessayre, Dominique; Krause, Karl-Heinz] Geneva Med Fac, Dept Genet, CH-1211 Geneva 4, Switzerland. [Guichard, Cecile; Pessayre, Dominique; Krause, Karl-Heinz] Geneva Med Fac, Lab Med, CH-1211 Geneva 4, Switzerland. [Guichard, Cecile; Moreau, Richard] Ctr Rech Biomed Bichat Beaujon CRB3, U773, INSERM, F-75870 Paris, France. [Pessayre, Dominique] Univ Beaujon, Grp Hosp, Serv Hepatol, F-92110 Clichy, France. [Epperson, Terry Kay] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Epperson, Terry Kay] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. RP Krause, KH (reprint author), Geneva Med Fac, Dept Pathol & Immunol, CH-1211 Geneva 4, Switzerland. EM Karl-Heinz.Krause@medecine.unige.ch RI Krause, Karl-Heinz/E-8030-2011; OI Moreau, Richard /0000-0003-0862-403X NR 86 TC 61 Z9 64 U1 0 U2 4 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 OCT PY 2008 VL 36 BP 920 EP 929 DI 10.1042/BST0360920 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 360RW UT WOS:000260076300027 PM 18793162 ER PT J AU Gulbahce, N Lehmann, S AF Gulbahce, Natali Lehmann, Sune TI The art of community detection SO BIOESSAYS LA English DT Article ID PROTEIN INTERACTION NETWORK; COMPLEX NETWORKS; METABOLIC NETWORKS; MODULARITY; GENOME AB Networks in nature possess a remarkable amount of structure. Via a series of data-driven discoveries, the cutting edge of network science has recently progressed from positing that the random graphs of mathematical graph theory might accurately describe real networks to the current viewpoint that networks in nature are highly complex and structured entities. The identification of high order structures in networks unveils insights into their functional organization. Recently, Clauset, Moore, and Newman,((1)) introduced a new algorithm that identifies such heterogeneities in complex networks by utilizing the hierarchy that necessarily organizes the many levels of structure. Here, we anchor their algorithm in a general community detection framework and discuss the future of community detection. BioEssays 30:934-938, 2008. (C) 2008 Wiley Periodicals, Inc. C1 [Gulbahce, Natali; Lehmann, Sune] NE Univ, Ctr Complex Networks Res, Boston, MA 02115 USA. [Gulbahce, Natali; Lehmann, Sune] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA. RP Gulbahce, N (reprint author), NE Univ, Ctr Complex Networks Res, 110 Forsyth St, Boston, MA 02115 USA. EM natali.gulbahce@gmail.com OI Lehmann, Sune/0000-0001-6099-2345 FU NHGRI NIH HHS [P50 HG004233] NR 39 TC 26 Z9 32 U1 0 U2 7 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0265-9247 EI 1521-1878 J9 BIOESSAYS JI Bioessays PD OCT PY 2008 VL 30 IS 10 BP 934 EP 938 DI 10.1002/bies.20820 PG 5 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 359AX UT WOS:000259959700004 PM 18800363 ER PT J AU Berriz, GF Roth, FP AF Berriz, Gabriel F. Roth, Frederick P. TI The Synergizer service for translating gene, protein and other biological identifiers SO BIOINFORMATICS LA English DT Article ID RESOURCES; DATABASES AB The Synergizer is a database and web service that provides translations of biological database identifiers. It is accessible both programmatically and interactively. C1 [Berriz, Gabriel F.; Roth, Frederick P.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Roth, Frederick P.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. RP Roth, FP (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 250 Longwood Ave, Boston, MA 02115 USA. RI Roth, Frederick/H-6308-2011; OI Roth, Frederick/0000-0002-6628-649X FU National Institutes of Health [HG003224, HG0017115, HL081341]; Keck Foundation FX Funding: National Institutes of Health. (grants HG003224, HG0017115, and HL081341), Keck Foundation. NR 9 TC 23 Z9 24 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD OCT 1 PY 2008 VL 24 IS 19 BP 2272 EP 2273 DI 10.1093/bioinformatics/btn424 PG 2 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 353PZ UT WOS:000259581900028 PM 18697767 ER PT J AU Bashey, A Perez, WS Zhang, MJ Anderson, KC Ballen, K Berenson, JR To, LB Fonseca, R Freytes, CO Gale, RP Gibson, J Giralt, SA Kyle, RA Lazarus, HM Maharaj, D McCarthy, PL Milone, GA Nimer, S Pavlovsky, S Reece, DE Schiller, G Vesole, DH Hari, P AF Bashey, Asad Perez, Waleska S. Zhang, Mei-jie Anderson, Kenneth C. Ballen, Karen Berenson, James R. To, L. Bik Fonseca, Rafael Freytes, Cesar O. Gale, Robert Peter Gibson, John Giralt, Sergio A. Kyle, Robert A. Lazarus, Hillard M. Maharaj, Dipnarine McCarthy, Philip L. Milone, Gustavo A. Nimer, Stephen Pavlovsky, Santiago Reece, Donna E. Schiller, Gary Vesole, David H. Hari, Parameswaran CA Plasma Cell Disorders Working Comm TI Comparison of twin and autologous transplants for multiple myeloma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE twin; autotransplant; multiple myeloma; graft-versus-myeloma ID STEM-CELL TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; BONE-MARROW-TRANSPLANTATION; TUMOR CONTAMINATION; BLOOD; HARVESTS; PREDICT; GRAFTS AB Relapse is the overwhelming cause of treatment failure after autologous transplantation for multiple myeloma (MM). For patients with a syngeneic donor, twin transplants provide a healthy graft that is free of myeloma. The relative impact of the graft on posttransplant relapse can be estimated by comparing risk of relapse after hematopoietic cell transplantation from genetically identical twins versus autotransplants because confounding differences in minor or major histocompatibility antigens are absent in the syngeneic transplant setting. Outcomes of 43 subjects who received twin transplants for MM were compared to 170 matched autotransplant recipients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Multivariate analysis was performed by fitting a Cox model stratified on matched pairs. The matched transplant patients studied were similar with respect to subject-, disease-, and transplant-related characteristics. Cumulative incidence of relapse/progression was significantly lower, and progression free survival (PFS) was significantly higher following twin transplants. In multivariate analysis, the probability of relapse/progression was lower in twins (relative risk [RR] = 0.49, 95% confidence interval [CI] 0.28-0.86, P = .011). Twin transplants have a significantly lower relapse risk than autotransplants in MM, suggesting that graft composition may impact outcomes following high-dose chemotherapy. C1 [Perez, Waleska S.; Zhang, Mei-jie; Hari, Parameswaran] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Bashey, Asad] BMT Grp Georgia, Atlanta, GA USA. [Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ballen, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Berenson, James R.] Inst Myeloma & Bone Canc Res, W Hollywood, CA USA. [To, L. Bik] Inst Med & Vet Sci, Adelaide, SA 5000, Australia. [Fonseca, Rafael] Mayo Clin Scottsdale, Scottsdale, AZ USA. [Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Gale, Robert Peter] Celgene Corp, Summit, NJ USA. [Gibson, John] Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia. [Giralt, Sergio A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Kyle, Robert A.] Mayo Clin Rochester, Rochester, MN USA. [Lazarus, Hillard M.] Univ Hosp, Case Med Ctr, Cleveland, OH USA. [Maharaj, Dipnarine] S Florida Bone Marrow Stem Cell Transplant Inst, Boynton Beach, FL USA. [McCarthy, Philip L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Milone, Gustavo A.; Pavlovsky, Santiago] FUNDALEU, Buenos Aires, DF, Argentina. [Nimer, Stephen] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Reece, Donna E.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Schiller, Gary] Univ Calif Los Angeles, Los Angeles, CA USA. [Vesole, David H.] St Vincents Comprehens Canc Ctr, New York, NY USA. RP Hari, P (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, 9200 W Wisconsin Ave,Suits C5500, Milwaukee, WI 53226 USA. EM phari@mcw.edu OI Fonseca, Rafael/0000-0002-5938-3769; Hari, Parameswaran/0000-0002-8800-297X FU National Cancer Institute [U24-CA76518]; National Institute of Allergy and Infectious Diseases; National Heart, Lung and Blood Institute; Office of Naval Research; Health Services Research Administration (DHHS); AABB; Abbott Laboratories; Aetna; American International Group, Inc; Amgen, Inc FX The CIBMTR is supported by Public Health Service Grant U24-CA76518 from the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and the National Heart, Lung and Blood Institute; Office of Naval Research; Health Services Research Administration (DHHS); and grants from AABB; Abbott Laboratories; Aetna; American International Group, Inc.; Amgen, Inc.; anonymous donation to the Medical College of Wisconsin;, AnorNIED, Inc.; Astellas Pharma US, Inc.; Baxter International, Inc., Berlex Laboratories, Inc.; Biogen IDEC, Inc.; BioOne Corporation; Blood Center of Wisconsin;, Blue Cross and Blue Shield Association; Bone Marrow Foundation; Bristol-Myers Squibb Company; Cangene Corporation; Celgene Corporation; CellGenix, GrnbH; Cerus Corporation; Cylex Inc.; CytoTherm; DOR BIoPharma, Inc.; Dynal Biotech, an Invitrogen Company; EKR Therapeutics; Enzon Pharmaceuticals, Inc.; Gambro BCT, Inc.; Gamida Cell, Ltd.; Genzyme Corporation; Gift of Life Bone Marrow Foundation, GlaxoSmitliKline, Inc.; Histogenetics, Inc.; HKS Medical Information Systems; Hospira, Inc.; Kiadis Pharma; Kirin Brewery Co., Ltd.; Merck & Company; The Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Miller Pharmacal Group; Millunan USA, Inc.; Miltenyi Biotec, Inc.; MultiPlan, Inc.; National Marrow Donor Program; Nature Publishing Group; Oncology Nursing Society; Osiris Therapeutics, Inc.; Pall Life Sciences; PDL BioPharma, Inc;, Pfizer Inc; Pharmion Corporation; Roche Laboratories; Sanofi-aventis- Schering Plough Corporation, StemCyte, Inc.; StemSoft Software, Inc. SuperGen, Inc.; Sysmex; Teva Pharmaceutical Industries; The Marrow Foundation; THERAKOS, Inc.; University of Colorado Cord Blood Bank; ViaCell, Inc.; Vidocare Corporation; ViraCor Laboratories; ViroPharma, Inc.; Wellpoint, Inc.; and Zelos Therapeutics, Inc. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the NR 22 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD OCT PY 2008 VL 14 IS 10 BP 1118 EP 1124 DI 10.1016/j.bbmt.2008.07.007 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 354WF UT WOS:000259669100005 PM 18804041 ER PT J AU Kumar, S Perez, WS Zhang, MJ Ballen, K Bashey, A To, LB Bredeson, CN Cairo, MS Elfenbein, GJ Freytes, CO Gale, RP Gibson, J Kyle, RA Lacy, MQ Lazarus, HM McCarthy, PL Milone, GA Moreb, JS Pavlovsky, S Reece, DE Vesole, DH Wiernik, PH Hari, P AF Kumar, Shaji Perez, Waleska S. Zhang, Mei-Jie Ballen, Karen Bashey, Asad To, L. Bik Bredeson, Christopher N. Cairo, Mitchell S. Elfenbein, Gerald J. Freytes, Cesar O. Gale, Robert Peter Gibson, John Kyle, Robert A. Lacy, Martha Q. Lazarus, Hillard M. McCarthy, Philip L. Milone, Gustavo A. Moreb, Jan S. Pavlovsky, Santiago Reece, Donna E. Vesole, David H. Wiernik, Peter H. Hari, Parameswaran TI Comparable outcomes in nonsecretory and secretory multiple myeloma after autologous stem cell transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE nonsecretory myeloma; autologous hematopoietic stem cell transplantation ID AMINO-ACID SUBSTITUTION; VARIABLE REGION; BENCE-JONES; CHAIN; SINGLE; IMMUNOGLOBULIN; CHEMOTHERAPY; THERAPY; SURVIVAL; KAPPA AB Nonsecretory myeloma (NSM) accounts for <5% of cases of multiple myeloma (MM). The outcome of these patients following autologous stem cell transplantation (ASCT) has not been evaluated in clinical trials. We compared the outcomes after ASCT for patients with NSM reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) between 1989 and 2003, to a matched group of 438 patients (4 controls for each patient) with secretory myeloma (SM). The patients were matched using propensity scores calculated using age, Durie-Salmon stage, sensitivity to pretransplant therapy, time from diagnosis to transplant, and year of transplant. Disease characteristics were similar in both groups at diagnosis and at transplant except higher risk of anemia, hypoalbuminemia, and marrow plasmacytosis (in SM) and plasmacytoma (more in NSM). Cumulative incidence of treatment-related mortality (TRM), relapse, progression-free survival (PFS), and overall survival (OS) were similar between the groups. In multivariate analysis, based on a Cox model stratified on matched pairs and adjusted for covariates not considered in the propensity score, we found no difference in outcome between the NSM and SM groups. In this large cohort of patients undergoing ASCT we found no difference in outcomes of patients with NSM compared to those with SM. C1 [Perez, Waleska S.; Zhang, Mei-Jie; Hari, Parameswaran] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Kumar, Shaji; Kyle, Robert A.; Lacy, Martha Q.] Mayo Clin, Rochester, MN USA. [Ballen, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bashey, Asad] Blood & Marrow Transplant Grp Georgia, Atlanta, GA USA. [To, L. Bik] Inst Med & Vet Sci, Adelaide, SA 5000, Australia. [Bredeson, Christopher N.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Cairo, Mitchell S.] New York Presbyterian Hosp, New York, NY USA. [Elfenbein, Gerald J.] Boston Univ, Boston, MA 02215 USA. [Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Gale, Robert Peter] Celgene Corp, Summit, NJ USA. [Gibson, John] Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia. [Lazarus, Hillard M.] Univ Hosp, Case Med Ctr, Cleveland, OH USA. [McCarthy, Philip L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Milone, Gustavo A.; Pavlovsky, Santiago] Fundaleu, Buenos Aires, DF, Argentina. [Moreb, Jan S.] Univ Florida, Gainesville, FL USA. [Reece, Donna E.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Vesole, David H.] St Vincents Comprehens Canc, New York, NY USA. [Wiernik, Peter H.] New York Med Coll, Our Lady Mercy Med Ctr, Bronx, NY USA. RP Hari, P (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, 9200 W Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA. EM phari@mcw.edu RI Kumar, Shaji/A-9853-2008; OI Kumar, Shaji/0000-0001-5392-9284; Hari, Parameswaran/0000-0002-8800-297X FU National Cancer Institute [U24-CA76518]; National Institute of Allergy and Infectious Diseases,; National Heart, Lung and Blood Institute; Office of Naval Research; Health Resources and Services Administration (DHHS); AABB; Aetna; American Soclety for Blood and Marrow Transplantation; Amgen, Inc; Anonymous donation to the Medical College of Wisconsin; Association of Medical Microbiology and Infectious Disease Canada; Astellas Pharma US, Inc; Baxter International, Inc; Bayer HealthCare Pharmaceuticals; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Canadian Blood and Marrow Transplant Group; Celgene Corporation; CellGenix, GmbH; Centers for Disease Control and Prevention; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Cubist Pharmaceuticals; Cylex Inc; Cylex Inc.; CytoTherm; DOR BioPhama, Inc; Dynal Biotech, an Invitrogen Company; Enzon Pharmaceuticals, Inc; European Group for Blood and Marrow Transplantation; Garnbro BCT, Inc; Gamida Cell, Ltd; Genzyme Corporation; Histogenetics, Inc; HKS Medical Information Systems; Hospira, Inc; Infectious Diseases Society of America; Kiadis Pharma; Kirin Brewery Co., Ltd; Merck Company; The Medical College of Wisconsin; MGI Pharma, Inc FX Financial disclosure: The CIBMTR is supported by Public Health Service Grant U24-CA76518 from the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and the National Heart, Lung and Blood Institute; Office of Naval Research; Health Resources and Services Administration (DHHS); and grants from AABB; Aetna; American Soclety for Blood and Marrow Transplantation; Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Association of Medical Microbiology and Infectious Disease Canada; Astellas Pharma US, Inc.; Baxter International, Inc.; Bayer HealthCare Pharmaceuticals; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Canadian Blood and Marrow Transplant Group; Celgene Corporation; CellGenix, GmbH; Centers for Disease Control and Prevention; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Cubist Pharmaceuticals; Cylex Inc.; CytoTherm; DOR BioPhama, Inc., Dynal Biotech, an Invitrogen Company; Enzon Pharmaceuticals, Inc.; European Group for Blood and Marrow Transplantation; Garnbro BCT, Inc.; Gamida Cell, Ltd.; Genzyme Corporation; Histogenetics, Inc.; HKS Medical Information Systems; Hospira, Inc.; Infectious Diseases Society of America; Kiadis Pharma; Kirin Brewery Co., Ltd.; Merck & Company; The Medical College of Wisconsin; MGI Pharma, Inc.; Michigan Community Blood Centers; Millennium Pharmaceuticals, Inc.; Miller Pharniacal Group; Milliman USA, Inc., Miltenyl Biotec, Inc., National Marrow Donor Program; Nature Publishing Group; New York Blood Center; Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics, Inc.; Otsuka Pharmaceutical Development & Commercialization, Inc.; Pall Life Sciences; PDL BioPharma, Inc; Pfizer Inc, Pharmion Corporation; Saladax Biomedical, Inc.; Schering Plough Corporation-, Society for Healthcare Epidemiology of America; StemCyte, Inc.; StemSoft Software, Inc.; Sysmex; Teva Pharmaceutical Industries; The Marrow Foundation; THERAKOS, Inc.; Viclacare Corporation; Vion Pharmaceuticals, Inc.; ViraCor Laboratories-, ViroPharma, Inc.; and Wellpoint, Inc. NR 25 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD OCT PY 2008 VL 14 IS 10 BP 1134 EP 1140 DI 10.1016/j.bbmt.2008.07.011 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 354WF UT WOS:000259669100007 PM 18804043 ER PT J AU Cho, CH Berthiaume, F Tilles, AW Yarmush, ML AF Cho, Chenl H. Berthiaume, Francois Tilles, Arno W. Yarmush, Martin L. TI A new technique for primary hepatocyte expansion in vitro SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE hepatocyte proliferation; coculture; DNA synthesis; cell patterning; subculture ID ADULT-RAT HEPATOCYTES; ACUTE LIVER-FAILURE; EMBRYONIC STEM-CELLS; PRIMARY CULTURE; DIFFERENTIATED FUNCTIONS; NONPARENCHYMAL CELLS; CONTROLLED-TRIAL; JUNCTIONAL COMMUNICATION; SANDWICH CONFIGURATION; CELLULAR INTERACTIONS AB The current application for many potential cell-based treatments for liver failure is limited by the low availability of mature functional hepatocytes. Although adult hepatocytes have a remarkable ability to proliferate in vivo, attempts to proliferate adult hepatocytes in vitro have been less successful. In this study, we investigated the effect of coculture cell type on the proliferative response and the functional activities of hepatocytes. We show, for the first time, a robust proliferative response of primary adult rat hepatocytes when cocultured with mouse 3T3-J2 fibroblasts. Hepatocytes cultured at low density on growth-arrested 3T3-J2 fibroblast feeder layers underwent significantly higher proliferation rates than when cultured on feeder layers made of four other cell types. Increasing colony size correlaled with an increase in hepatocellular functions. The proliferating hepatocytes retained their morphologic, phenotypic, and functional characteristics. Using a cell patterning technique, we found that 3T3-J2 fibroblasts stimulate DNA synthesis in hepatocytes by short-range heterotypic cell-cell interactions. When hepatocytes that proliferated in cocultures were harvested and further subcultured either on 3T3-J2 fibroblast feeders or in the collagen sandwich configuration, their behavior was similar to that of freshly isolated hepatocytes. We conclude that adult rat hepatocytes can proliferate in vitro in a coculture cell type-dependent manner, and can be serially propagated by coculturing with 3T3-J2 fibroblasts while maintaining their differentiated characteristics. Our results also suggest that one of the major reasons for the functional differences in hepatocyte cocultures may be due to the different proliferative responses of hepatocytes as a function of coculture cell type. This study provides new insights in the roles of coculture cell types and cell-cell interactions in the modulation of hepatic proliferation and function. C1 [Yarmush, Martin L.] Harvard Univ, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Harvard Univ, Sch Med, Ctr Engn Med, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org RI Yu, weiting/I-7417-2013 FU National Institutes of Health [R01 DK43371, K08 DK066040, K18 DK076819] FX We thank Dr. Jaesung Park for providing PDMS stencils, and Dr. Yaakov Nahmias and Dr. Laurent Bathe for their assistance with LSFC isolation. This study was partially supported by the National Institutes of Health (grain numbers R01 DK43371, K08 DK066040, and K18 DK076819) and the Shriners Hospitals for Children. NR 57 TC 31 Z9 31 U1 0 U2 9 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD OCT 1 PY 2008 VL 101 IS 2 BP 345 EP 356 DI 10.1002/bit.21911 PG 12 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 352QS UT WOS:000259512900013 PM 18465801 ER PT J AU Cao, HH Ackerman, J Ecklund, K Steigman, S Glimcher, M Wu, YT AF Cao, Haihui Ackerman, Jerome Ecklund, Kirsten Steigman, Shaun Glimcher, Melvin Wu, Yaotang TI Water and Fat Suppressed Proton Projection MRI (WASPI)/micro CT measurements of bone mineralization SO BONE LA English DT Meeting Abstract CT International Conference on Osteoporosis and Bone Research CY OCT 22-25, 2008 CL Beijing, PEOPLES R CHINA SP Chinese Med Assoc, Int Bone & Mineral Soc, Int Chinese Hard Tissue Soc C1 [Cao, Haihui; Glimcher, Melvin; Wu, Yaotang] Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Cao, Haihui; Ackerman, Jerome; Ecklund, Kirsten; Steigman, Shaun; Glimcher, Melvin; Wu, Yaotang] Harvard Univ, Sch Med, Boston, MA USA. [Ackerman, Jerome] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Ecklund, Kirsten] Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. [Steigman, Shaun] Childrens Hosp, Dept Surg, 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 8756-3282 J9 BONE JI Bone PD OCT PY 2008 VL 43 SU 1 BP S95 EP S95 DI 10.1016/j.bone.2008.07.188 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 360TT UT WOS:000260081500223 ER PT J AU Hadjikhani, N Hoge, R Snyder, J de Gelder, B AF Hadjikhani, Nouchine Hoge, Rick Snyder, Josh de Gelder, Beatrice TI Pointing with the eyes: The role of gaze in communicating danger SO BRAIN AND COGNITION LA English DT Article DE Face processing; Gaze; Emotion; Fear recognition; Action representation ID SUPERIOR TEMPORAL SULCUS; SURFACE-BASED ANALYSIS; HUMAN NEURAL SYSTEM; FACIAL EXPRESSIONS; HUMAN AMYGDALA; FACE PERCEPTION; CEREBRAL-CORTEX; FUSIFORM GYRUS; FEAR; BRAIN AB Facial expression and direction of gaze are two important sources of social information, and what message each conveys may ultimately depend on how the respective information interacts in the eye of the perceiver. Direct gaze signals an interaction with the observer but averted gaze amounts to "pointing with the eyes", and in combination with a fearful facial expression may signal the presence of environmental danger. We used fMRI to examine how gaze direction influences brain processing of facial expression of fear. The combination of fearful faces and averted gazes activated areas related to gaze shifting (STS, IPS) and fear-processing (amygdala, hypothalamus, pallidum). Additional modulation of activation was observed in motion detection areas, in premotor areas and in the somatosensory cortex, bilaterally. Our results indicate that the direction of gaze prompts a process whereby the brain combines the meaning of the facial expression with the information provided by gaze direction, and in the process computes the behavioral implications for the observer. (c) 2008 Elsevier Inc. All rights reserved. C1 [Hadjikhani, Nouchine; Hoge, Rick; Snyder, Josh; de Gelder, Beatrice] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Hadjikhani, Nouchine; Hoge, Rick] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Hadjikhani, Nouchine] Ecole Polytech Fed Lausanne, Brain Mind Inst, Lausanne, Switzerland. [de Gelder, Beatrice] Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. RP Hadjikhani, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM nouchine@nmr.mgh.harvard.edu RI Hadjikhani, Nouchine/C-2018-2008 OI Hadjikhani, Nouchine/0000-0003-4075-3106 FU NIH [RO1 NS44824-01]; Swiss National Foundation [PPOOB-110741] FX This research was supported by NIH Grant RO1 NS44824-01 and Swiss National Foundation Grant PPOOB-110741 to Nouchine Hadjikhani. We thank Reginald Adams and an anonymous reviewer for their comments on our manuscript. NR 57 TC 61 Z9 61 U1 4 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD OCT PY 2008 VL 68 IS 1 BP 1 EP 8 DI 10.1016/j.bandc.2008.01.008 PG 8 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 360RD UT WOS:000260074300001 PM 18586370 ER PT J AU Patil, S Perry, A MacCollin, M Dong, S Betensky, RA Yeh, TH Gutmann, DH Stemmer-Rachamimov, AO AF Patil, Sushama Perry, Arie MacCollin, Mia Dong, Shumin Betensky, Rebecca A. Yeh, Tu-Hsueh Gutmann, David H. Stemmer-Rachamimov, Anat O. TI Immunohistochemical analysis supports a role for INI1/SMARCB1 in hereditary forms of schwannomas, but not in solitary, sporadic schwannomas SO BRAIN PATHOLOGY LA English DT Article DE Schwannoma; NF2; Schwannomatosis; INI1; SMARCB1; expression ID FAMILIAL SCHWANNOMATOSIS; RHABDOID TUMORS; EXPRESSION; MUTATION AB The INI1/SMARCB1 protein product (INI1), a component of a transcription complex, was recently implicated in the pathogenesis of schwannomas in two members of a single family with familial schwannomatosis. Tumors were found to have both constitutional and somatic mutations of the SMARCB1 gene and showed a mosaic pattern of loss of INI1 expression by immunohistochemistry, suggesting a tumor composition of mixed null and haploinsufficient cells. To determine if this finding could be extended to all tumors arising in familial schwannomatosis, and how it compares with other multiple schwannoma syndromes [sporadic schwannomatosis and neurofibromatosis 2 (NF2)] as well as to sporadic, solitary schwannomas, we performed an immunohistochemistry analysis on 45 schwannomas from patients with multiple schwannoma syndromes and on 38 solitary, sporadic schwannomas from non-syndromic patients. A mosaic pattern of INI1 expression was seen in 93% of tumors from familial schwannomatosis patients, 55% of tumors from sporadic schwannomatosis, 83% of NF2-associated tumors and only 5% of solitary, sporadic schwannomas. These results confirm a role for INI1/SMARCB1 in multiple schwannoma syndromes and suggest that a different pathway of tumorigenesis occurs in solitary, sporadic tumors. C1 [Patil, Sushama; Perry, Arie] Washington Univ, Sch Med, Div Neuropathol, St Louis, MO USA. [Yeh, Tu-Hsueh; Gutmann, David H.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [MacCollin, Mia] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Div Neuropathol, Boston, MA 02114 USA. [Dong, Shumin; Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Mol Neuro Oncol Lab, Boston, MA 02114 USA. [Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Yeh, Tu-Hsueh] Chang Gung Mem Hosp & Univ, Dept Neurol, Taipei, Taiwan. RP Stemmer-Rachamimov, AO (reprint author), Massachusetts Gen Hosp, Mol Neurooncol Lab, MGH East,Bldg 149,13th St, Charlestown, MA 02129 USA. EM astemmerrachamimov@partners.org OI Perry, Arie/0000-0002-8300-7261 FU Children's Tumor Foundation (ASR); Congressionally Directed Medical Research Program (MM) FX This work was supported by grants from the Children's Tumor Foundation (ASR) and from the Congressionally Directed Medical Research Program (MM). The authors thank Drs Michael Lawlor and Pavan Auluck for their help with the graph. NR 10 TC 65 Z9 65 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD OCT PY 2008 VL 18 IS 4 BP 517 EP 519 DI 10.1111/j.1750-3639.2008.00155.x PG 3 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 347MW UT WOS:000259146700006 PM 18422762 ER PT J AU O'Callaghan, P Sandwall, E Li, JP Yu, H Ravid, R Guan, ZZ van Kuppevelt, TH Nilsson, LNG Ingelsson, M Hyman, BT Kalimo, H Lindahl, U Lannfelt, L Zhang, X AF O'Callaghan, Paul Sandwall, Elina Li, Jin-Ping Yu, Hong Ravid, Rivka Guan, Zhi-Zhong van Kuppevelt, Toin H. Nilsson, Lars N. G. Ingelsson, Martin Hyman, Bradley T. Kalimo, Hannu Lindahl, Ulf Lannfelt, Lars Zhang, Xiao TI Heparan sulfate accumulation with A beta deposits in Alzheimer's disease and Tg2576 mice is contributed by glial cells SO BRAIN PATHOLOGY LA English DT Article DE beta-Amyloid; glial cells; heparan sulfate ID FIBROBLAST GROWTH FACTOR-2; CEREBRAL-CORTEX; SENILE PLAQUES; DOWN-SYNDROME; PROTEOGLYCANS; BRAIN; EXPRESSION; GLYCOSAMINOGLYCANS; A-BETA-40; PROTEINS AB Amyloid beta-peptide (A beta) plaques, one of the major neuropathological lesions in Alzheimer's disease (AD), can be broadly subdivided into two morphological categories: neuritic and diffuse. Heparan sulfate (HS) and HS proteoglycans (HSPGs) are codeposits of multiple amyloidoses, including AD. Although HS has been considered a limiting factor in the initiation of amyloid deposition, the pathological implications of HS in A beta deposits of AD remain unclear. In this study, immunohistochemistry combined with fluorescence and confocal microscopy was employed to gain deeper insight into the accumulation of HS with A beta plaques in sporadic and familial AD. Here we demonstrate that HS preferentially accumulated around the A beta 40 dense cores of neuritic plaques, but was largely absent from diffuse A beta 42 plaques, suggesting that A beta 42 deposition may occur independently of HS. A codeposition pattern of HS with A beta deposits in Tg2576 mice was also examined. We identified the membrane-bound HSPGs, glypican-1 (GPC1) and syndecan-3 (SDC3), in glial cells associated with A beta deposits, proximal to sites of HS accumulation. In mouse primary glial cultures, we observed increased levels of GPC1 and SDC3 following A beta stimulation. These results suggest that HS codeposits with A beta 40 in neuritic plaques and is mainly derived from glial cells. C1 [O'Callaghan, Paul; Nilsson, Lars N. G.; Ingelsson, Martin; Lannfelt, Lars; Zhang, Xiao] Uppsala Univ, Dept Publ Hlth & Caring Sci, Div Mol Geriatr, Rudbeck Lab, SE-75185 Uppsala, Sweden. [Sandwall, Elina; Li, Jin-Ping; Lindahl, Ulf] Uppsala Univ, Biomed Ctr, Dept Med Biochem & Microbiol, SE-75185 Uppsala, Sweden. [Yu, Hong] AstraZeneca R&D, CNS & Pain Control, Local Discovery Res Area, Dept Dis Biol, Sodertalje, Sweden. [Guan, Zhi-Zhong] Karolinska Inst, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden. [Ravid, Rivka] Netherlands Brain Bank, Amsterdam, Netherlands. [van Kuppevelt, Toin H.] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mol Life Sci, Dept Biochem, Nijmegen, Netherlands. [Hyman, Bradley T.] Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Charlestown, MA USA. RP Zhang, X (reprint author), Uppsala Univ, Dept Publ Hlth & Caring Sci, Div Mol Geriatr, Rudbeck Lab, SE-75185 Uppsala, Sweden. EM xiao.zhang@pubcare.uu.se RI Kuppevelt, A.H.M.S.M./L-4463-2015; OI O'Callaghan, Paul/0000-0003-3117-5367 FU The Swedish Research Council [2006-2822, 2006-2818, 32X-15023]; Landstinget i Uppsala lan; European Commission (EURAMY); Polysackaridforskning AB Uppsala; Alzheimerfonden; Stohnes Stiftelse; Stiftelsen for Gamla Tjanarinnor; Stiftelsen Demensfonden; Swedish Brain Foundation; Bertil Hallstens Forskningsstiftelse; Massachusetts Alzheimer Disease Research Center [PS0AG05134] FX We would like to thank Guido David (University of Leuven), Lars-Ake Fransson and Fang Cheng (Lund University) for contributing antibodies.; Supported by The Swedish Research Council (2006-2822, 2006-2818, 32X-15023), Landstinget i Uppsala lan, European Commission (EURAMY), Polysackaridforskning AB Uppsala, Alzheimerfonden, Stohnes Stiftelse, Stiftelsen for Gamla Tjanarinnor, Stiftelsen Demensfonden, The Swedish Brain Foundation, Bertil Hallstens Forskningsstiftelse and the Massachusetts Alzheimer Disease Research Center PS0AG05134. NR 42 TC 34 Z9 34 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD OCT PY 2008 VL 18 IS 4 BP 548 EP 561 DI 10.1111/j.1750-3639.2008.00152.x PG 14 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 347MW UT WOS:000259146700009 PM 18422760 ER PT J AU Niesvizky, R Richardson, PG Rajkumar, SV Coleman, M Rosinol, L Sonneveld, P Schuster, MW Irwin, D Stadtmauer, EA Facon, T Harousseau, JL Boral, AL Esseltine, DL Anderson, KC Blade, J AF Niesvizky, Ruben Richardson, Paul G. Rajkumar, S. Vincent Coleman, Morton Rosinol, Laura Sonneveld, Pieter Schuster, Michael W. Irwin, David Stadtmauer, Edward A. Facon, Thierry Harousseau, Jean-Luc Boral, Anthony L. Esseltine, Dixie-Lee Anderson, Kenneth C. Blade, Joan TI The relationship between quality of response and clinical benefit for patients treated on the bortezomib arm of the international, randomized, phase 3 APEX trial in relapsed multiple myeloma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE multiple myeloma; bortezomib; complete response; clinical benefit; minimal response ID STEM-CELL TRANSPLANTATION; MINIMAL RESIDUAL DISEASE; HIGH-DOSE THERAPY; BONE-MARROW; AUTOLOGOUS TRANSPLANTATION; COMPLETE REMISSION; PROGNOSTIC PARAMETER; MOLECULAR REMISSION; FREE SURVIVAL; CHEMOTHERAPY AB Quality of response is associated with prolonged overall survival (OS) in newly diagnosed multiple myeloma patients. This cohort study within the phase 3 Assessment of Proteasome Inhibition for Extending Remissions (APEX) trial of bortezomib versus dexamethasone in relapsed myeloma assessed the relationship between quality of response to bortezomib (n = 315) and clinical benefit. Treatment-free interval (TFI), time to alternative therapy (TTAT), time to progression (TTP) and OS were assessed in response-evaluable patients in the bortezomib arm in cohorts defined by achievement of complete response (CR; n = 27), very good partial response (VGPR; n = 31), partial response (PR; n = 77), minimal response (MR; n = 21) or non-response (NR, including stable and progressive disease; n = 159). CR was associated with significantly longer median TFI (24.1 vs. 6.9/6.4 months) and TTAT (27.1 vs. 13.6/14 months) versus VGPR/PR. Median TTP was similar in CR, VGPR and PR cohorts; median OS was not reached. Patients achieving MR appeared to have prolonged median TFI (3.8 vs. 2.3 months), TTAT (8.7 vs. 6.2 months), TTP (4.9 vs. 2.8 months) and OS (24.9 vs. 18.7 months) versus NR. In conclusion, bortezomib had substantial activity in relapsed myeloma patients; CR may be a surrogate marker for significant clinical benefit with bortezomib. MR appeared to be valid as a separate response category in this setting. C1 [Niesvizky, Ruben] Cornell Univ, Weill Med Coll, Ctr Excellence Lymphoma & Myeloma, New York Presbyterian Hosp, New York, NY 10021 USA. [Richardson, Paul G.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rajkumar, S. Vincent] Mayo Clin, Rochester, MN USA. [Rosinol, Laura; Blade, Joan] Hosp Clin Barcelona, IDIBAPS, Barcelona, Spain. [Sonneveld, Pieter] Erasmus MC, Rotterdam, Netherlands. [Irwin, David] Alta Bates Canc Ctr, Berkeley, CA USA. [Stadtmauer, Edward A.] Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. [Facon, Thierry] Hosp Claude Huriez, Lille, France. [Harousseau, Jean-Luc] Hop Hotel Dieu, Nantes, France. [Boral, Anthony L.; Esseltine, Dixie-Lee] Millennium Pharmaceut Inc, Cambridge, MA USA. RP Niesvizky, R (reprint author), Cornell Univ, Weill Med Coll, Ctr Excellence Lymphoma & Myeloma, New York Presbyterian Hosp, New York, NY 10021 USA. EM run9001@med.cornell.edu RI FACON, THIERRY/M-9736-2014; OI FACON, THIERRY/0000-0001-7705-8460; Rajkumar, S. Vincent/0000-0002-5862-1833 FU Millennium Pharmaceuticals, Inc; Johnson & Johnson Pharmaceutical Research Development FX The authors would like to thank Steve Hill and Rosemary Washbrook for editorial assistance in the development of this manuscript. Steve Hill is a medical writer and Rosemary Washbrook is a medical editor with Gardiner-Caldwell London.; This research was supported by Millennium Pharmaceuticals, Inc. and Johnson & Johnson Pharmaceutical Research & Development L. L. C. NR 31 TC 71 Z9 73 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2008 VL 143 IS 1 BP 46 EP 53 DI 10.1111/j.1365-2141.2008.07303.x PG 8 WC Hematology SC Hematology GA 345BH UT WOS:000258970500005 PM 18673366 ER PT J AU Lonial, S Richardson, PG Miguel, JS Sonneveld, P Schuster, MW Blade, J Cavenagh, J Rajkumar, SV Jakubowiak, AJ Esseltine, DL Anderson, KC Harousseau, JL AF Lonial, Sagar Richardson, Paul G. Miguel, Jesus San Sonneveld, Pieter Schuster, Michael W. Blade, Joan Cavenagh, Jamie Rajkumar, S. Vincent Jakubowiak, Andrzej J. Esseltine, Dixie-Lee Anderson, Kenneth C. Harousseau, Jean-Luc TI Characterisation of haematological profiles and low risk of thromboembolic events with bortezomib in patients with relapsed multiple myeloma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE bortezomib; haematological toxicity; multiple myeloma; thromboembolic event ID LENALIDOMIDE PLUS DEXAMETHASONE; PEGYLATED LIPOSOMAL DOXORUBICIN; INDUCTION TREATMENT PRIOR; NEWLY-DIAGNOSED MYELOMA; DEEP VENOUS THROMBOSIS; TERM-FOLLOW-UP; FACTOR-KAPPA-B; PHASE-II; THALIDOMIDE-DEXAMETHASONE; RECEIVING THALIDOMIDE AB Haematological toxicities and thromboembolic (TE) events are common complications of myeloma therapy. TE risk may be elevated with combination regimens, notably thalidomide/lenalidomide plus high-dose dexamethasone; concomitant erythropoietin appears to further increase the risk with lenalidomide-dexamethasone. We characterised thrombocytopenia and neutropenia in the phase 3 APEX (Assessment of Proteasome Inhibition for Extending Remissions) study of bortezomib versus high-dose dexamethasone in relapsed myeloma, and calculated the incidences of deep-vein thrombosis (DVT)/pulmonary embolism (PE) with: bortezomib or dexamethasone +/- erythropoietin in APEX; bortezomib +/- dexamethasone +/- erythropoietin in two phase 2 studies of relapsed/refractory myeloma. Bortezomib-associated thrombocytopenia and neutropenia were transient, predictable and manageable; mean platelet and neutrophil counts followed a cyclical pattern, and improved over the treatment course. Grade 3/4 thrombocytopenia incidence was higher with bortezomib versus dexamethasone (26%/4% vs. 5%/1%), but significant bleeding events were comparable (4% vs. 5%). DVT/PE incidence was low (<= 3.1%) in all analyses; addition of dexamethasone/erythropoietin did not affect TE risk. In APEX, TE risk appeared lower with bortezomib versus dexamethasone. Bortezomib caused transient and cyclical thrombocytopenia and was not associated with elevated TE risk, alone or with dexamethasone +/- erythropoietin. Preliminary data suggest bortezomib may reduce the thrombogenic potential of combination regimens via inhibition of platelet function or other mechanism-specific effects on coagulation. C1 [Lonial, Sagar] Emory Univ, Winship Canc Ctr, Atlanta, GA 30322 USA. [Richardson, Paul G.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Miguel, Jesus San] Hosp Univ Salamanca, CIC, IBMCC, USAL,CSIC, Salamanca, Spain. [Sonneveld, Pieter] Univ Rotterdam Hosp, Rotterdam, Netherlands. [Schuster, Michael W.] NY Presbyterian Hosp, New York, NY USA. [Blade, Joan] Hosp Clin Barcelona, IDIBAPS, Dept Haematol, Barcelona, Spain. [Cavenagh, Jamie] St Bartholomews Hosp, London, England. [Rajkumar, S. Vincent] Mayo Clin, Rochester, MN USA. [Jakubowiak, Andrzej J.] Univ Michigan, Ann Arbor, MI 48109 USA. [Esseltine, Dixie-Lee] Millennium Pharmaceut Inc, Cambridge, MA USA. [Harousseau, Jean-Luc] Hop Hotel Dieu, Nantes, France. RP Lonial, S (reprint author), Emory Univ, Winship Canc Ctr, Bldg C,1365 Clifton Rd, Atlanta, GA 30322 USA. EM sloni01@emory.edu RI 2008, Ibsal/A-1268-2012; OI Rajkumar, S. Vincent/0000-0002-5862-1833; SAN MIGUEL, JESUS/0000-0002-9183-4857 FU Millennium Pharmaceuticals, Inc; Johnson & Johnson Pharmaceutical Research & Development L. L. C. FX This research was supported by Millennium Pharmaceuticals, Inc. and Johnson & Johnson Pharmaceutical Research & Development L. L. C. Editorial assistance in preparation of this manuscript was provided by Gardiner-Caldwell London. NR 56 TC 54 Z9 55 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2008 VL 143 IS 2 BP 222 EP 229 DI 10.1111/j.1365-2141.2008.07321.x PG 8 WC Hematology SC Hematology GA 352OF UT WOS:000259505900007 PM 18713253 ER PT J AU Farwell, WR Gaziano, JM Norkus, EP Sesso, HD AF Farwell, Wildon R. Gaziano, J. Michael Norkus, Edward P. Sesso, Howard D. TI The relationship between total plasma carotenoids and risk factors for chronic disease among middle-aged and older men SO BRITISH JOURNAL OF NUTRITION LA English DT Article DE Carotenoids; Risk factors; Chronic disease ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; ALPHA-TOCOPHEROL; BETA-CAROTENE; CARDIOVASCULAR-DISEASE; SERUM CONCENTRATIONS; ENZYMATIC DETERMINATION; LYCOPENE; RETINOL; ZEAXANTHIN AB Individual plasma carotenoids have been associated with various chronic diseases but little is known about the relationship between total plasma carotenoids and risk-factors lot chronic diseases. In the Physicians' Health Study, we examined 492 men free of CVD and cancer for the relationship between total plasma carotenoids (the sum of alpha-carotene. beta-carotene, lycopene, zeaxanthin, lutein and beta-cryptoxanthin) and a wide variety of factors that predict chronic disease. Multivariate linear and logistic regression was performed to calculate parameter estimates (95% CI) and OR (95% CI) for total plasma carotenoids. In linear regression models, BMI, hypertension, alcohol intake and plasma levels of each lipid parameter and alpha-tocopherol significantly predicted levels of total plasma carotenoids. Upon adjustment for multiple chronic disease risk factors. the OR for levels of total plasma carotenoids greater than or equal to the median (>= 1.301 mu mol/l) was statistically significant for Current smoking. (OR 0.21; 95% CI 0.06; 0.77), weekly alcohol ingestion (OR 2.30; 95% CI 1.06; 4.99), daily alcohol ingestion (OR 2.46; 95 % CI 1.29; 467). each 100 mg/l increase in total cholesterol (OR 0.73; 95% CI 0.58; 0.91), HDL-cholesterol (OR 1.48; 95% CI 1.17; 1.89) and HDL-cholesterol (OR 1.58; 95% CI 1.26; 1.99), each 100 mg/ml increase in intercellular adhesion molecule-l (OR 0.70; 95% CI 0.53; 0.93) and each 10 mu mol/l increase in alpha-tocopherol (OR 1.33; 95% CI 1.12; 1.57), using logistic regression. Few lifestyle and clinical risk factors appear to be related to levels of total plasma carotenoid however, levels of biomarkers Such as plasma lipids and alpha-tocopheiol may he strongly related. C1 [Farwell, Wildon R.; Gaziano, J. Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston Div 151 MAV, Boston, MA 02130 USA. [Farwell, Wildon R.; Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Farwell, Wildon R.; Gaziano, J. Michael; Sesso, Howard D.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Norkus, Edward P.] New York Med Coll, Dept Med Res, Our Lady Mercy Med Ctr & Community & Prevent Med, Bronx, NY USA. RP Farwell, WR (reprint author), VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston Div 151 MAV, 150 S Huntington Ave, Boston, MA 02130 USA. EM Wildon.Farwell@va.gov FU NIH [CA 97193, CA 34944, CA 40360, HL 26490, HL 34595]; BASF AG; Roche Vitamins, Inc; Cooperative Studies Program; Department of Veterans Affairs Office of Research and Development; Roche Vitamins. Inc; PHS; [29071] FX The present study was funded by NIH CA 97193 and BASF AG, plus a grant from Roche Vitamins, Inc. Approximately half of the participants in PHS II also participated in PHS 1, which was established through NIH CA 34944. CA 40360, HL 26490 and HL 34595. Work on the present Study was also supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development.; This research was supported in part by a grant from Roche Vitamins. Inc. The authors have no other financial or personal interests related to this research. The authors would like to acknowledge the crucial contributions of the entire staff of the PHS. We are also indebted to the 29071 dedicated and committed participants randomised into the PHS starting in either 1982 or 1995. NR 24 TC 6 Z9 6 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0007-1145 J9 BRIT J NUTR JI Br. J. Nutr. PD OCT PY 2008 VL 100 IS 4 BP 883 EP 889 DI 10.1017/S0007114508944111 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 359QT UT WOS:000260003900028 PM 18334043 ER PT J AU Miller, DD Caroff, SN Davis, SM Rosenheck, RA McEvoy, JP Saltz, BL Riggio, S Chakos, MH Swartz, MS Keefe, RSE Stroup, TS Lieberman, JA AF Miller, Del D. Caroff, Stanley N. Davis, Sonia M. Rosenheck, Robert A. McEvoy, Joseph P. Saltz, Bruce L. Riggio, Silvana Chakos, Miranda H. Swartz, Marvin S. Keefe, Richard S. E. Stroup, T. Scott Lieberman, Jeffrey A. CA CATIE Investigators TI Extrapyramidal side-effects of antipsychotics in a randomised trial SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID TARDIVE-DYSKINESIA; CHRONIC-SCHIZOPHRENIA; ATYPICAL ANTIPSYCHOTICS; 2ND-GENERATION ANTIPSYCHOTICS; SCHIZOAFFECTIVE DISORDER; ACUTE EXACERBATION; CLINICAL-TRIAL; RISPERIDONE; HALOPERIDOL; OLANZAPINE AB Background There are claims that second-generation antipsychotics produce fewer extrapyramidal side-effects (EPS) compared with first-generation drugs. Aims To compare the incidence of treatment-emergent EPS between second-generation antipsychotics and perphenazine in people with schizophrenia. Method Incidence analyses integrated data from standardised rating scales and documented use of concomitant medication or treatment discontinuation for EPS events. mixed model analyses of change in rating scales from baseline were also conducted. Results There were no significant differences in incidence or change in rating scales for parkinsonism, dystonia, akathisia or tardive dyskinesia when comparing second-generation antipsychotics with perphenazine or comparing between second-generation antipsychotics. Secondary analyses revealed greater rates of concomitant antiparkinsonism medication among individuals on risperidone and lower rates among individuals on quetiapine, and lower rates of discontinuation because of parkinsonism among people on quetiapine and ziprasidone. There was a trend for a greater likelihood of concomitant medication for akathisia among individuals on risperidone and perphenazine. Conclusions The incidence of treatment-emergent EPS and change in EPS ratings indicated that there are no significant differences between second-generation antipsychotics and perphenazine or between second-generation antipsychotics in people with schizophrenia. C1 [Miller, Del D.] Univ Iowa, Carver Coll Med, Iowa City, IA 52242 USA. [Caroff, Stanley N.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Caroff, Stanley N.] Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Davis, Sonia M.] Quintiles Inc, Morrisville, NC USA. [Rosenheck, Robert A.] Yale Univ, Sch Med, West Haven, CT 06516 USA. [McEvoy, Joseph P.; Swartz, Marvin S.] Duke Univ, Med Ctr, Durham, NC USA. [Saltz, Bruce L.] Mental Hlth Advocates Inc, Boca Raton, FL USA. [Riggio, Silvana] Mt Sinai Sch Med James J Peter VAMC, Bronx, NY USA. [Chakos, Miranda H.] SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. [Stroup, T. Scott] Neurosci Hosp, N Carolina Sch Med, Chapel Hill, NC USA. [Lieberman, Jeffrey A.] Columbia Univ, Coll Phys & Surg, New York, NY USA. RP Miller, DD (reprint author), Univ Iowa, Carver Coll Med, 2-105 MEB,500 Newton Rd, Iowa City, IA 52242 USA. EM del-miller@uiowa.edu RI Stroup, Thomas/F-9188-2014 OI Adler, Lawrence/0000-0002-6619-2493; Stroup, Thomas/0000-0002-3123-0672 FU NIMH NIH HHS [N01 MH90001, N01MH90001] NR 51 TC 103 Z9 106 U1 2 U2 9 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 EI 1472-1465 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD OCT PY 2008 VL 193 IS 4 BP 279 EP 288 DI 10.1192/bjp.bp.108.050088 PG 10 WC Psychiatry SC Psychiatry GA 363RS UT WOS:000260285000004 PM 18827289 ER PT J AU Yu, EW Blackwell, T Ensrud, KE Hillier, TA Lane, NE Orwoll, E Bauer, DC AF Yu, Elaine W. Blackwell, Terri Ensrud, Kristine E. Hillier, Teresa A. Lane, Nancy E. Orwoll, Eric Bauer, Douglas C. TI Acid-Suppressive Medications and Risk of Bone Loss and Fracture in Older Adults SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE Bone density; Fracture; H2 receptor antagonist; Proton pump inhibitor ID PROTON PUMP INHIBITORS; OSTEOPOROTIC FRACTURES; CALCIUM-ABSORPTION; HIP FRACTURE; MINERAL DENSITY; K+-ATPASE; WOMEN; MEN; OMEPRAZOLE; AGE AB Recent studies have suggested an increased fracture risk with acid-suppressive medication use. We studied two cohorts of men and women over age 65 who were enrolled in the Osteoporotic Fractures in Men Study (MrOS) and the Study of Osteoporotic Fractures (SOF), respectively. We used dual-energy X-ray absorptiometry and assessed baseline use of proton pump inhibitors (PPIs) and/or H2 receptor antagonists (H2RAs) in 5,755 men and 5,339 women. Medication use and bone mineral density (BMD) were assessed, and hip and other nonspine fractures were documented. On multivariate analysis, men using either PPIs or H2RAs had lower cross-sectional bone mass. No significant BMD differences were observed among women. However, there was an increased risk of nonspine fracture among women using PPIs (relative hazard [RH] = 1.34, 95% confidence interval [CI] 1.10-1.64). PPI use was also associated with an increased risk of nonspine fracture in men but only among those who were not taking calcium supplements (RH = 1.49, 95% CI 1.04-2.14). H2RA use was not associated with nonspine fractures, and neither H2RA use nor PPI use was associated with incident hip fractures in men or women. The use of PPIs in older women, and perhaps older men with low calcium intake, may be associated with a modestly increased risk of nonspine fracture. C1 [Yu, Elaine W.] Massachusetts Gen Hosp, Div Endocrine, Boston, MA 02114 USA. [Blackwell, Terri] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Ensrud, Kristine E.] VA Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Ensrud, Kristine E.] Univ Minnesota, Dept Epidemiol & Community Hlth, Minneapolis, MN USA. [Hillier, Teresa A.] Kaiser Permanente Ctr Hlth Res, NW & Hawaii, Portland, OR USA. [Lane, Nancy E.] Univ Calif Davis, Davis, CA 95616 USA. [Orwoll, Eric] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Bauer, Douglas C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Yu, EW (reprint author), Massachusetts Gen Hosp, Div Endocrine, Thier 1101,50 Blossom St, Boston, MA 02114 USA. EM ewyu@partners.org; TBlackwell@sfcc-cpmc.net; Ensru001@umn.edu; Teresa.Hillier@kpchr.org; NeLane@ucdavis.edu; Orwoll@ohsu.edu; DBauer@psg-ucsf.org OI Orwoll, Eric/0000-0002-8520-7355 FU National Institutes of Health funding; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Institute on Aging (NIA) [AG05407, AR35582, AG05394, AR35584, AR35583, R01 AG005407, R01 AG027576-22, 2 R01 AG005394-22A1, 2 R01 AG02757422A1] FX The SOF is supported by National Institutes of Health funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and the National Institute on Aging (NIA) under grant numbers AG05407, AR35582, AG05394, AR35584, AR35583, R01 AG005407, R01 AG027576-22, 2 R01 AG005394-22A1, and 2 R01 AG02757422A1. The MrOS is supported by National Institutes of Health (NIH) funding. The following institutes provide support: NIAMS, NIA, the National Center for Research Resources, and the NIH Roadmap for Medical Research under grant numbers U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 RR024140. Midcareer mentoring awards have been given to D.C.B. and N.E.L. ( K24-AR-04884). NR 29 TC 94 Z9 100 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD OCT PY 2008 VL 83 IS 4 BP 251 EP 259 DI 10.1007/s00223-008-9170-1 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 363IO UT WOS:000260261200002 PM 18813868 ER PT J AU Motzer, RJ Bukowski, RM Figlin, RA Hutson, TE Michaelson, MD Kim, ST Baum, CM Kaftan, MW AF Motzer, Robert J. Bukowski, Ronald M. Figlin, Robert A. Hutson, Thomas E. Michaelson, M. Dror Kim, Sindy T. Baum, Charles M. Kaftan, Michael W. TI Prognostic nomogram for sunitinib in patients with metastatic renal cell carcinoma SO CANCER LA English DT Article DE sunitinib; nomogram; metastatic renal cell carcinoma; progression-free survival ID ENDOTHELIAL GROWTH-FACTOR; INTERFERON-ALPHA; FACTOR RECEPTOR; SURVIVAL; EFFICACY; THERAPY; CANCER AB BACKGROUND. in a randomized, phase 3 trial, sunitinib demonstrated superior efficacy over interferon-alfa as first-line therapy in patients with metastatic clear-cell renal cell carcinoma (RCC). On the basis Of outcome data from that trial, the authors developed a nomogram for predicting the probability of 12-month progression-free survival for patients who received sunitinib therapy. METHODS. Three-hundred seventy-five patients who received sunitinib in the phase 3 trial were the Subject of the Current analysis. Nomogram pretreatment predictor variables included corrected serum calcium levels, the number of metastatic sites, hemoglobin levels, prior nephrectomy, the presence Of lung and liver metastases, thrombocytosis, Eastern Cooperative Oncology Group performance status, time from diagnosis to treatment, and serum levels of alkaline phosphatase and lactate dehydrogenase. Investigator-assessed progression-free survival was the predicted outcome endpoint. Internal validation of the nomogram consisted of quantification of the discrimination with the concordance index and assessment of calibration. RESULTS. One-hundred seventy-four of 375 patients (46%) who received sunitinib achieved an objective response, and the median progression-free survival was 10.8 months (95% confidence interval, 10.6-12.6 months). A nomogram for predicting the probability of 12-month progression-free survival for patients who received sunitinib therapy was constructed on the basis of a Cox regression model from 11 parameters that were determined before treatment. The concordance index was 0.633. CONCLUSIONS. A nomogram was developed from pretreatment clinical features to predict the probability of achieving 12-month progression-free survival with sunitinib therapy for metastatic clear-cell RCC. The authors concluded that independent validation of the nomogram and additional studies to identify tumor specific prognostic factors are warranted. C1 [Motzer, Robert J.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Bukowski, Ronald M.] Cleveland Clin, Taussig Canc Ctr, Expt Therapeut Program, Cleveland, OH 44106 USA. [Figlin, Robert A.] City Hope Natl Med Ctr, Div Med Oncol & Therapeut Res, Duarte, CA 91010 USA. [Hutson, Thomas E.] Baylor Sammons Canc Ctr Texas Oncol, Genitourinary Oncol Program, Dallas, TX USA. [Michaelson, M. Dror] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA USA. [Kim, Sindy T.; Baum, Charles M.] Pfizer Global Res & Dev, Oncol Clin Dev, San Diego, CA USA. RP Motzer, RJ (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA. EM motzerr@mskcc.org OI Michaelson, Dror/0000-0001-9249-6338 FU Pfizer [NCT00083889] FX Supported by funding from Pfizer (clinicaltrials.gov no. NCT00083889). NR 28 TC 109 Z9 119 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 1 PY 2008 VL 113 IS 7 BP 1552 EP 1558 DI 10.1002/cncr.23776 PG 7 WC Oncology SC Oncology GA 354TK UT WOS:000259661700010 PM 18720362 ER PT J AU Marsit, CJ Posner, MR McClean, MD Kelsey, KI AF Marsit, Carmen J. Posner, Marshall R. McClean, Michal D. Kelsey, Karl T. TI Hypermethylation of E-cadherin is an independent predictor of improved survival in head and neck squamous cell carcinoma SO CANCER LA English DT Article DE hypermethylation; epigenetic; head and neck squamous cell carcinoma; survival; E-cadherin ID HUMAN-PAPILLOMAVIRUS; RISK-FACTORS; PROMOTER HYPERMETHYLATION; EPIGENETIC INACTIVATION; SFRP GENES; CANCER; ALCOHOL; TOBACCO; METHYLATION; EXPRESSION AB BACKGROUND. The loss of E-cadherin (ECAD) protein expression has been linked to aggressive head and neck squamous cell carcinoma (HNSCC). Promoter hypermethylation of the cadherin 1, type 1 (CDH1) gene (encoding ECAD) is 1 mechanism by which this protein can be inactivated, although this epigenetic alteration of the gene has not been linked conclusively to poorer patient outcome and, in fact, may be associated with better patient prognosis. METHODS. The authors investigated the prevalence of CDH1 promoter hypermethylation in a population-based case series of 340 primary HNSCC tumors using methylation-specific polymerase chain reaction. They also studied the association between CDH1 hypermethylation and patient demographic characteristics using multivariate analysis and examined the impact of CDH1 hypermethylation on patient survival using both univariate and multivariate methods. RESULTS. Hypermethylation of CDH1 was significantly more prevalent (P <.03) among individuals with a low smoking history independent of whether they were seropositive for human papillomavirus type 16 (HPV-16). Patients who had tumors with CDH1 hypermethylation had significantly better overall survival compared with patients who had tumors without hypermethylation (P <.02; log-rank test). This effect was independent of HPV-16 status and demonstrated a significant hazard ratio of 0.5 (95% confidence interval, 0.3-0.9) in a model that controlled for HPV-16 serology, age, sex, and tumor stage. CONCLUSIONS. The current results suggested that hypermethylation of CDH1 occurs more commonly in patients with HNSCC who are low smokers, suggesting that an additional factor may be driving this epigenetic alteration. Clinically, CDH1 hypermethylation may hold powerful prognostic potential in addition to that observed with HPV serology, and the authors concluded that it should be pursued in additional studies. C1 [Marsit, Carmen J.; Kelsey, Karl T.] Brown Univ, Dept Pathol & Lab Med, Providence, RI 02912 USA. [Posner, Marshall R.] Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. [McClean, Michal D.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Kelsey, Karl T.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. RP Marsit, CJ (reprint author), Brown Univ, Dept Pathol & Lab Med, Box G-E537, Providence, RI 02912 USA. EM carmen_marsit@brown.edu RI McClean, Michael/J-2934-2015; OI Marsit, Carmen/0000-0003-4566-150X FU National Institutes of Health [R01CA078609, R01CA100679]; Friends of Dana-Farber; Flight Attendants Medical Research Institute FX Supported by National Institutes of Health grants R01CA078609 and R01CA100679, by the Friends of Dana-Farber, and by the Flight Attendants Medical Research Institute (C.J.M.). NR 33 TC 32 Z9 33 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 OCT 1 PY 2008 VL 113 IS 7 BP 1566 EP 1571 DI 10.1002/cncr.23770 PG 6 WC Oncology SC Oncology GA 354TK UT WOS:000259661700012 PM 18711702 ER PT J AU Tanabe, KK AF Tanabe, Kenneth K. TI The past 60 years in liver surgery SO CANCER LA English DT Review ID MAJOR HISTOCOMPATIBILITY COMPLEX; SEROLOGY PREDICTS TUMOR; HEPATIC RESECTION; HEPATOCELLULAR-CARCINOMA; RADIOFREQUENCY ABLATION; PORTAL-VEIN; DISEASE CHARACTERISTICS; COLORECTAL METASTASES; VASCULAR ISOLATION; VENOUS BYPASS AB The anniversary of the first publication of Cancer provides an opportunity to review the progress in liver cancer surgery in the past 60 years. Indeed, the past half century has been witness to remarkable advances in liver surgery that have provided benefit to so many patients afflicted with primary or secondary liver Minors. However, no matter now astounding these past achievements may be, it is clear that the future holds even greater promise. C1 [Tanabe, Kenneth K.] Massachusetts Gen Hosp, Ctr Canc, Div Surg Oncol, Boston, MA 02114 USA. [Tanabe, Kenneth K.] Harvard Univ, Sch Med, Boston, MA USA. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Surg Oncol, Yawkey 7-924,55 Fruit St, Boston, MA 02114 USA. EM ktanabe@partners.org FU National Institutes of Health [5R01CA076183, 5R21CA119600]; Tucker Gosnell Gastrointestinal Cancer Center FX Supported by grants 5R01CA076183 and 5R21CA119600 from the National Institutes of Health and by and the Tucker Gosnell Gastrointestinal Cancer Center. NR 103 TC 5 Z9 7 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 OCT 1 PY 2008 VL 113 IS 7 SI SI BP 1888 EP 1896 DI 10.1002/cncr.23652 PG 9 WC Oncology SC Oncology GA 354TL UT WOS:000259661800015 PM 18798530 ER PT J AU Schemhammer, ES Giovannuccci, E Fuchs, CS Ogino, S AF Schemhammer, Eva S. Giovannuccci, Edward Fuchs, Charles S. Ogino, Shuji TI A prospective study of dietary folate and vitamin B and colon cancer according to microsatellite instability and KRAS mutational status SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; COLORECTAL-CANCER; MULTIVITAMIN USE; COMPETING RISKS; NURSES HEALTH; LIFE-STYLE; K-RAS; WOMEN; REPRODUCIBILITY; METHYLATION AB Sporadic microsatellite instability (MSI)-high colon cancers are positively associated with MLH1 promoter methylation and inversely with KRAS mutation. One-carbon metabolism is critical for methylation reactions and nucleotide biosynthesis, but the influence of dietary one-carbon nutrients such as folate and B vitamins on molecular changes in colon cancer is not known. Using the database of two independent prospective cohort studies (88,691 women and 47,371 men), we examined the relation between dietary intake of one-carbon nutrients and the incidence of microsatellite instability and KRAS mutation in 669 incident colon cancers. The overall inverse association between folate and colon cancer did not differ significantly according to MSI status [relative ratio (RR), 0.79; 95% confidence interval (95% CI), 0.60-1.03 for microsatellite stable/MSI-low colon cancers; and RR, 0.61, 95% CI, 0.37-1.02 for MSI-high colon cancers; P-heterogeneity 0.53] or KRAS status (RR, 0.66; 95% CI, 0.49-0.87 for KRAS wild-type colon cancers; and RR, 1.05; 95% CI, 0.68-1.61 for KRAS mutated colon cancers; Pheterogeneity = 0.12), although our analyses had limited power to preclude an effect of folate on KRAS wild-type colon cancers. Similarly, high vitamin B-6 or B-12 intake was inversely associated with colon cancers, regardless of MSI or KRAS status. No significant effect of methionine intake or alcohol consumption was observed for colon cancers with MSI high or KRAS mutation. In conclusion, the influence of dietary one-carbon nutrient intake on colon cancer risk does not seem to differ according to MSI or KRAS mutational status. C1 [Schemhammer, Eva S.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02215 USA. [Schemhammer, Eva S.; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA. [Schemhammer, Eva S.; Giovannuccci, Edward; Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. [Schemhammer, Eva S.] KFJ Spital, Ludwig Boltzmann Inst Appl Canc Res, Vienna, Austria. [Schemhammer, Eva S.] Appl Canc Res Inst Translat Res Vienna, Vienna, Austria. RP Schemhammer, ES (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02215 USA. EM eva.schemhammer@channing.harvard.edu FU NIH [CA70817, CA87969, CA55075, CA42812, CA58684, CA90598, CA122826]; Bennett Family Fund and Entertainment Industry Foundation; Entertainment Industry Foundation National Colorectat Cancer Research Alliance FX Grant support: NIH research grants CA70817, CA87969, CA55075, CA42812, CA58684, CA90598, CA122826, the Bennett Family Fund and Entertainment Industry Foundation, and the Entertainment Industry Foundation National Colorectat Cancer Research Alliance. NR 24 TC 27 Z9 28 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2008 VL 17 IS 10 BP 2895 EP 2898 DI 10.1158/1055-9965.EPI-08-0638 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 360IK UT WOS:000260051000049 PM 18843035 ER PT J AU Wirth, LJ Krane, JF Li, Y Othus, M Moran, AE Dorfman, DM Norris, CM Goguen, L Posner, MR Haddad, RI Bertagnolli, MM AF Wirth, Lori J. Krane, Jeffrey F. Li, Yi Othus, Megan Moran, Amy E. Dorfman, David M. Norris, Charles M., Jr. Goguen, Laura Posner, Marshall R. Haddad, Robert I. Bertagnolli, Monica M. TI A Pilot Surrogate Endpoint Biomarker Study of Celecoxib in Oral Premalignant Lesions SO CANCER PREVENTION RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; PARTIAL HYDATIDIFORM MOLES; GROWTH-FACTOR RECEPTOR; 2ND PRIMARY TUMORS; RANDOMIZED-TRIAL; NECK-CANCER; MALIGNANT-TRANSFORMATION; COLORECTAL ADENOMAS; PROSTAGLANDIN E-2; CYCLOOXYGENASE-2 EXPRESSION AB This study evaluated changes in prostaglandin E(2) (PGE(2)) levels and related biomarkers in oral premalignant lesions (OPL) in response to celecoxib treatment. Twenty-two subjects were enrolled and treated with celecoxib. Pretreatment and 12-week biopsies were done. Subjects whose biopsy showed >= 30% decrease in PGE(2) remained on celecoxib for a total of 12 months when repeat biopsy was done. Biopsies were examined to assess degree of dysplasia, DNA ploidy, and immunohistochemical expression of BCL2, pAKT-Ser473, Ki-67, and CD31 (microvessel density). In 18 paired biopsies available at baseline and 12 weeks, mean normalized PGE(2) levels decreased by 38% (P = 0.002). After 12 months, PGE2 decreased by 31% (P = 0.340). Twelve biopsies (67%; P = 0.0129) showed improvement in degree of dysplasia after 12 weeks, and 8 of 11 biopsies (73%; P = 0.0703) continued to show an improvement in the degree of dysplasia after 12 months. Trends suggested down-modulation of cyclooxygenase-2 and Ki-67 in some tissues, increased pAKT-Ser473 expression, and an inverse relationship between PGE(2) and BCL2 expression. This study documents the feasibility of measuring potential surrogate endpoint biomarkers of chemopreventive agent response in OPLs. Treatment with celecoxib in subjects with OPLs favorably modulates the primary mediator of cyclooxygenase-2 activity, PGE(2), after 12 weeks. C1 [Moran, Amy E.; Norris, Charles M., Jr.; Goguen, Laura; Bertagnolli, Monica M.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Wirth, Lori J.; Posner, Marshall R.; Haddad, Robert I.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. [Wirth, Lori J.; Posner, Marshall R.; Haddad, Robert I.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Krane, Jeffrey F.; Dorfman, David M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Bertagnolli, MM (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM mbertagnolli@partners.org NR 48 TC 11 Z9 11 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD OCT PY 2008 VL 1 IS 5 BP 339 EP 348 DI 10.1158/1940-6207.CAPR-07-0003 PG 10 WC Oncology SC Oncology GA 420MK UT WOS:000264293700006 PM 19138978 ER PT J AU Nemenoff, R Meyer, AM Hudish, TM Mozer, AB Snee, A Narumiya, S Stearman, RS Winn, RA Weiser-Evans, M Geraci, MW Keith, RL AF Nemenoff, Raphael Meyer, Amy M. Hudish, Tyler M. Mozer, Anthony B. Snee, Amy Narumiya, Shuh Stearman, Robert S. Winn, Robert A. Weiser-Evans, Mary Geraci, Mark W. Keith, Robert L. TI Prostacyclin Prevents Murine Lung Cancer Independent of the Membrane Receptor by Activation of Peroxisomal Proliferator-Activated Receptor gamma SO CANCER PREVENTION RESEARCH LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PULMONARY PROSTACYCLIN; SYNTHASE OVEREXPRESSION; PROSTANOID RECEPTORS; TRANSGENIC MICE; A/J MICE; CELL; INHIBITION; TUMORIGENESIS; EXPRESSION AB Overexpression of prostacyclin synthase (PGIS) decreases lung tumor multiplicity in chemical- and cigarette-smoke-induced murine lung cancer models. Prostacyclin signals through a single G-protein-coupled receptor (IP), which signals through cyclic AMP. To determine the role of this receptor in lung cancer chemoprevention by prostacyclin, PGIS-overexpressing mice were crossed to mice that lack the IP receptor [IP(-/-)]. Carcinogen-induced lung tumor incidence was similar in IP(+/+), IP(+/-), and IP(-/-) mice, and overexpression of PGIS gave equal protection in all three groups, indicating that the protective effects of prostacyclin are not mediated through activation of IP. Because prostacyclin can activate members of the peroxisomal proliferator-activated receptor (PPAR) family of nuclear receptors, we examined the role of PPAR. in the protection of prostacyclin against lung tumorigenesis. Iloprost, a stable prostacyclin analogue, activated PPAR. in nontransformed bronchial epithelial cells and in a subset of human non-small-cell lung cancer cell lines. Iloprost-impregnated chow fed to wild-type mice resulted in elevated lung macrophages and decreased lung tumor formation. Transgenic animals with lung-specific PPAR. overexpression also developed fewer lung tumors. This reduction was not enhanced by administration of supplemental iloprost. These studies indicate that PPAR. is a critical target for prostacyclin-mediated lung cancer chemoprevention and may also have therapeutic activity. C1 [Hudish, Tyler M.; Mozer, Anthony B.; Keith, Robert L.] Denver VA Med Ctr, Dept Med, Div Pulm Sci & Crit Care Med, Denver, CO 80220 USA. [Nemenoff, Raphael; Meyer, Amy M.; Snee, Amy; Weiser-Evans, Mary] Univ Colorado, Hlth Sci Ctr, Dept Med, Div Renal Dis & Hypertens, Denver, CO 80262 USA. [Stearman, Robert S.; Winn, Robert A.; Geraci, Mark W.; Keith, Robert L.] Univ Colorado, Hlth Sci Ctr, Dept Med, Div Pulm Sci & Crit Care Med, Denver, CO 80262 USA. [Narumiya, Shuh] Kyoto Univ, Fac Med, Dept Pharmacol, Kyoto 606, Japan. [Narumiya, Shuh] Kyoto Univ, Fac Pharmaceut Sci, Dept Physiol Chem, Kyoto 606, Japan. RP Keith, RL (reprint author), Denver VA Med Ctr, Dept Med, Div Pulm Sci & Crit Care Med, 1055 Clermont St,Box 111A, Denver, CO 80220 USA. EM Robert.Keith@UCHSC.edu FU NIH [CA103618, CA108610, CA58187]; Department of Veterans Affairs FX Grant support: NIH grants CA103618, CA108610, and CA58187. R.L. Keith was supported by VA Advanced Career Development and Merit Review Awards from the Department of Veterans Affairs. NR 42 TC 36 Z9 36 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD OCT PY 2008 VL 1 IS 5 BP 349 EP 356 DI 10.1158/1940-6207.CAPR-08-0145 PG 8 WC Oncology SC Oncology GA 420MK UT WOS:000264293700007 PM 19138979 ER PT J AU Shen, CH Chen, HY Lin, MS Li, FY Chang, CC Kuo, ML Settleman, J Chen, RH AF Shen, Che-Hung Chen, Hsin-Yi Lin, Ming-Shien Li, Fang-Yen Chang, Cheng-Chi Kuo, Min-Liang Settleman, Jeffrey Chen, Ruey-Hwa TI Breast tumor kinase phosphorylates p190RhoGAP to regulate Rho and Ras and promote breast carcinoma growth, migration, and invasion SO CANCER RESEARCH LA English DT Article ID GTPASE-ACTIVATING PROTEIN; BRK TYROSINE KINASE; MAMMARY EPITHELIAL-CELLS; C-SRC; DUCTAL MORPHOGENESIS; P190 RHOGAP; EXPRESSION; CANCER; LOCALIZATION; INACTIVATION AB Breast tumor kinase (Brk), an Src-like nonreceptor tyrosine kinase, is overexpressed in breast cancer and several other cancer types. Our previous study indicates that Brk promotes cell migration and tumor invasion by phosphorylating the focal adhesion protein paxillin. Here, we report the identification of p190RhoGAP-A (p190) as a Brk substrate. Brk phosphorylates p190 at the Y-1105 residue both in vitro and in vivo, thereby promoting the association of p190 with p120RasGAP (p120). As a consequence, Brk stimulates p190 and attenuates p120 functions, leading to RhoA inactivation and Ras activation, respectively. In carcinoma cells expressing high levels of Brk, endogenous Brk functions as a key contributor to epidermal growth factor-induced p190 tyrosine phosphorylation. We present evidence showing that p190 phosphorylation plays essential roles in both migratory and proliferative effects of Brk. Furthermore, disruption of p190 phosphorylation-induced p190/p120 complex in breast cancer cells abolishes not only the abilities of Brk to regulate RhoA and Ras but also the stimulatory effects of Brk on proliferation, migration, invasion, transformation, and tumorigenicity. Together, our findings reveal a previously unknown function of Brk in regulating both RhoA and Ras by phosphorylating p190 and provide evidence for the crucial roles of this Brk-elicited signaling pathway in promoting breast malignancy. C1 [Chen, Hsin-Yi; Chen, Ruey-Hwa] Acad Sinica, Inst Biol Chem, Taipei, Taiwan. [Shen, Che-Hung; Lin, Ming-Shien; Chen, Ruey-Hwa] Natl Taiwan Univ, Inst Mol Med, Taipei 10764, Taiwan. [Chang, Cheng-Chi; Kuo, Min-Liang] Natl Taiwan Univ, Coll Med, Inst Toxicol, Taipei 10764, Taiwan. [Li, Fang-Yen; Chen, Ruey-Hwa] Natl Taiwan Univ, Inst Biochem Sci, Taipei, Taiwan. [Settleman, Jeffrey] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Gen Hosp Canc Ctr, Charlestown, MA USA. RP Chen, RH (reprint author), Acad Sinica, Inst Biol Chem, Taipei, Taiwan. EM rhchen@gate.sinica.edu.tw RI Kuo , Min-Liang/C-4872-2009; OI KUO, MIN-LIANG/0000-0002-7139-0144 FU National Health Research Institute [NHRI-EX97-9502BI] FX Grant support: National Health Research Institute grant. NHRI-EX97-9502BI. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 38 TC 48 Z9 51 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2008 VL 68 IS 19 BP 7779 EP 7787 DI 10.1158/0008-5472.CAN-08-0997 PG 9 WC Oncology SC Oncology GA 360AR UT WOS:000260029900012 PM 18829532 ER PT J AU Yi, CL Wilker, EW Yaffe, MB Stemmer-Rachamimov, A Kissil, JL AF Yi, Chunling Wilker, Erik W. Yaffe, Michael B. Stemmer-Rachamimov, Anat Kissil, Joseph L. TI Validation of the p21-activated kinases as targets for inhibition in neurofibromatosis type SO CANCER RESEARCH LA English DT Article ID NF2 TUMOR-SUPPRESSOR; SCHWANNOMA CELLS; MERLIN; TRANSFORMATION; RAC; PHOSPHORYLATION; ACTIVATION; EXPRESSION; GROWTH; GENE AB Neurofibromatosis type 2 (NF2) is a dominantly inherited cancer disorder caused by mutations at the NF2 gene locus. Merlin, the protein product of the NF2 gene, has been shown to negatively regulate Rac1 signaling by inhibiting its downstream effector kinases, the p21-activated kinases (Pak). Given the implication of Paks in tumorigenesis, it Is plausible that merlin's tumor suppressive function might be mediated, at least in part, via inhibition of the Paks. We present data indicating this is indeed the case. First, analysis of primary schwannoma samples derived from NF2 patients showed that in a significant fraction of the tumors, the activity of Pak1 was highly elevated. Second, we used shRNAs to knockdown Pak1, 2, and 3 in NIH3T3 cells expressing a dominant-negative form of merlin, NF2(BBA) (NIH3T3/NF2(BBA)), and find that simultaneous knockdown of Pak1-3 in these cells significantly reduced their growth rates in vitro and inhibited their ability to form tumors in vivo. Finally, while attempting to silence Pak1 in rat schwannoma cells, we found that these cells were unable to tolerate long-term Pak1 inhibition and rapidly moved to restore Pak1 levels by shutting down Pak1 shRNA expression through a methylation-dependent mechanism. These data suggest that inhibiting Pak could be a beneficial approach for the development of therapeutics toward NF2. In addition, the finding that the shRNA-mediated Pak1 suppression was silenced rapidly by methylation raises questions about the future application of such technologies for the treatment of diseases such as cancer. C1 [Kissil, Joseph L.] Wistar Inst Anat & Biol, Mol & Cellular Oncogenesis Program, Philadelphia, PA 19104 USA. [Wilker, Erik W.; Yaffe, Michael B.] MIT, Ctr Canc Res, Cambridge, MA 02139 USA. [Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kissil, JL (reprint author), Wistar Inst Anat & Biol, Mol & Cellular Oncogenesis Program, 3601 Spruce St, Philadelphia, PA 19104 USA. EM jkissil@wistar.org FU Department of Defense Neurofibromatosis Research Program; Ruth L. Kirschstein NRSA fellowship FX Department of Defense Neurofibromatosis Research Program. C. Yi is a recipient of Ruth L. Kirschstein NRSA fellowship. NR 20 TC 35 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 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2008 VL 68 IS 19 BP 7932 EP 7937 DI 10.1158/0008-5472.CAN-08-0866 PG 6 WC Oncology SC Oncology GA 360AR UT WOS:000260029900030 PM 18829550 ER PT J AU Kutuk, O Letai, A AF Kutuk, Ozgur Letai, Anthony TI Alteration of the mitochondrial apoptotic pathway is key to acquired paclitaxel resistance and can be reversed by ABT-737 SO CANCER RESEARCH LA English DT Article ID BH3 MIMETIC ABT-737; BREAST-CANCER CELLS; ACUTE LYMPHOBLASTIC-LEUKEMIA; DRUG-INDUCED APOPTOSIS; BCL-2 FAMILY PROTEINS; III BETA-TUBULIN; LUNG-CANCER; CHEMOTHERAPY; BIM; INHIBITOR AB Paclitaxel is a microtubule-targeting antineoplastic drug widely used in human cancers. Even when tumors are initially responsive, progression of disease despite continued taxane therapy is all too common in the treatment of many of the most common epithelial cancers, including breast cancer. However, the mechanisms underlying paclitaxel resistance in cancer cells are not completely understood. Our hypothesis is that changes in the intrinsic (or mitochondrial) cell death pathway controlled by the BCL-2 family are key to the development of acquired paclitaxel resistance. Here we show that paclitaxel activates the mitochondrial apoptosis pathway, which can be blocked by BCL-2 overexpression. Treatment with ABT-737, a small-molecule BCL-2 antagonist, restores sensitivity to paclitaxel in BCL-2-overexpressing cells. To investigate the importance of changes in the intrinsic apoptotic pathway in the absence of enforced BCL-2 expression, we generated two independent breast cancer cell lines with acquired resistance to apoptosis induced by paclitaxel. In these lines, acquired resistance to paclitaxel is mediated either by increased antiapoptotic BCL-2 proteins or decreased proapoptotic BCL-2 proteins. In both cases, ABT-737 can engage the mitochondrial apoptosis pathway to restore sensitivity to paclitaxel to cell lines with acquired paclitaxel resistance. In summary, these findings suggest that alterations in the intrinsic apoptotic pathway controlled by BCL-2 protein family members may be crucial to causing paclitaxel resistance. Furthermore, our results suggest that combining small-molecule BCL-2 antagonists with paclitaxel may offer benefit to patients with paclitaxel-resistant tumors, an oncologic problem of great prevalence. C1 [Kutuk, Ozgur; Letai, Anthony] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Letai, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 530B,44 Binney St, Boston, MA 02115 USA. EM anthony_letai@dfci.harvard.edu FU National Cancer Institute [K08 CA 102548, R01 CA129974] FX National Cancer Institute grants K08 CA 102548 and R01 CA129974. NR 39 TC 73 Z9 82 U1 0 U2 8 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 OCT 1 PY 2008 VL 68 IS 19 BP 7985 EP 7994 DI 10.1158/0008-5472.CAN-08-1418 PG 10 WC Oncology SC Oncology GA 360AR UT WOS:000260029900036 PM 18829556 ER PT J AU Aqel, R Zoghbi, GJ Hage, F Dell'Italia, L Iskandrian, AE AF Aqel, Raed Zoghbi, Gilbert J. Hage, Fadi Dell'Italia, Louis Iskandrian, Ami E. TI Hemodynamic Evaluation of Coronary Artery Bypass Graft Lesions Using Fractional Flow Reserve SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE bypass grafts; coronary; coronary flow; hemodynamics; quantitative coronary angiography ID EMISSION COMPUTED-TOMOGRAPHY; MYOCARDIAL-PERFUSION; PRESSURE MEASUREMENT; BLOOD-FLOW; FOLLOW-UP; ANGIOGRAPHY; STENOSIS; VELOCITY; DISEASE; PREDICT AB Background: Coronary angiography is limited by its inability to assess the hemodynamic significance of a coronary artery stenosis. The assessment of the physiological significance of saphenous vein graft (SVG) lesions with a pressure wire to determine the fractional flow reserve (FFR) is lacking. Methods: FFR was determined in 10 SVG lesions of 10 males who had stress myocardial perfusion imaging (MPI) prior to referral for percutaneous coronary intervention for clinical indications. Results: All SVGs had a diameter stenosis (DS) >50% and 30% had a DS >= 70%. A significant FFR was present in 30% of patients. Ischemia along the territory of the SVG was present in 20% of patients. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FFR <0.75 for the detection of ischemia on stress MPI were 50, 75, 33, 85, and 70%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FFR <0.75 for detecting >= 70% DS on angiography were 33, 71, 33, 71, and 60%, respectively. There was no significant correlation between FFR and % DS (R(2) = 0.1, P = 0.35). Conclusion: The use of FFR to assess the physiological significance of SVG lesions is feasible and provides an acceptable specificity and negative predictive value compared to stress MPI. (C) 2008 Wiley-Liss, Inc. C1 [Aqel, Raed; Zoghbi, Gilbert J.; Hage, Fadi; Dell'Italia, Louis] Birmingham VA Med Ctr, Birmingham, VA USA. [Aqel, Raed; Zoghbi, Gilbert J.; Hage, Fadi; Dell'Italia, Louis; Iskandrian, Ami E.] Univ Alabama, Birmingham, VA USA. RP Aqel, R (reprint author), 1808 7th Ave S,BDB 383, Birmingham, AL 35294 USA. EM raed.aqel@va.gov OI Hage, Fadi/0000-0002-1397-4942 FU Radi Medical Systems, Inc FX Dr. Aqel received a grant from Radi Medical Systems, Inc. NR 19 TC 18 Z9 18 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD OCT 1 PY 2008 VL 72 IS 4 BP 479 EP 485 DI 10.1002/ccd.21675 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 379JM UT WOS:000261392500008 PM 18814221 ER PT J AU Adly, MA Assaf, HA Hussein, MRA AF Adly, Mohamed A. Assaf, Hanan A. Hussein, Mahmoud Rezk A. TI Heat shock protein 27 expression in the human testis showing normal and abnormal spermatogenesis SO CELL BIOLOGY INTERNATIONAL LA English DT Article DE Testis; HSP27; Spermatogenesis ID CUTANEOUS MALIGNANT MELANOMAS; MALE GERM-CELLS; IMMUNE-RESPONSE; MICROSATELLITE INSTABILITY; TRANSCRIPTION FACTOR-1; DECREASED EXPRESSION; MOLECULAR CHAPERONES; SERTOLI-CELLS; TUMOR-CELLS; HEAT-SHOCK-PROTEIN-70 AB Heat shock proteins (HSPs) are molecular chaperones involved in protein folding, assembly and transport, and which play critical roles in the regulation of cell growth, survival and differentiation. We set out to test the hypothesis that HSP27 protein is expressed in the human testes and its expression varies with the state of spermatogenesis. HSP27 expression was examined in 30 human testicular biopsy specimens (normal spermatogenesis, maturation arrest and Sertoli cell only syndrome, 10 cases each) using immunofluorescent methods. The biopsies were obtained from patients undergoing investigations for infertility. The seminiferous epithelium of the human testes showing normal spermatogenesis had a cell type-specific expression of HSP27. HSP27 expression was strong in the cytoplasm of the Sertoli cells, spermatogonia, and Leydig cells. Alternatively, the expression was moderate in the spermatocytes, weak in the spermatids and absent in the spermatozoa. In testes showing maturation arrest, HSP27 expression was strong in the Sertoli cells, weak in the spermatogonia, and spermatocytes. It was absent in the spermatids and Leydig cells. In Sertoli cell only syndrome, HSP27 expression was strong in the Sertoli cells and absent in the Leydig cells. We report for the first time the expression patterns of HSP27 in the human testes and show differential expression during normal spermatogenesis, indicating a possible role in this process. The altered expression of this protein in testes showing abnormal spermatogenesis may be related to the pathogenesis of male infertility. (c) 2008 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved. C1 [Hussein, Mahmoud Rezk A.] Assuit Univ Hosp, Fac Med, Dept Pathol, Assiut, Egypt. [Adly, Mohamed A.] S Valley Univ, Sohag Fac Sci, Dept Zool, Kena, Egypt. [Adly, Mohamed A.] King Khalid Univ, Fac Sci, Dept Life Sci, Abha, Saudi Arabia. [Assaf, Hanan A.] S Valley Univ, Sohag Fac Med, Dept Dermatol & Venerol, Kena, Egypt. [Hussein, Mahmoud Rezk A.] KKU, Assir Cent Hosp, Dept Pathol, Abha, Saudi Arabia. [Hussein, Mahmoud Rezk A.] Univ Wisconsin, Sch Med, Madison, WI 53705 USA. [Hussein, Mahmoud Rezk A.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Hussein, MRA (reprint author), Assuit Univ Hosp, Fac Med, Dept Pathol, Assiut, Egypt. EM mrh17@gawab.com NR 54 TC 13 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PD OCT PY 2008 VL 32 IS 10 BP 1247 EP 1255 DI 10.1016/j.cellbi.2008.07.009 PG 9 WC Cell Biology SC Cell Biology GA 369CT UT WOS:000260671800009 PM 18692580 ER PT J AU Qiao, M Sheng, SJ Pardee, AB AF Qiao, Meng Sheng, Shijie Pardee, Arthur B. TI Metastasis and AKT activation SO CELL CYCLE LA English DT Review DE cancer; metastasis; PI3K; PTEN; AKT activation; GSK-3 beta; SNAIL; E-cadherin ID EPITHELIAL-MESENCHYMAL TRANSITION; CELL-CELL ADHESION; PROTEIN-TYROSINE PHOSPHATASES; GLYCOGEN-SYNTHASE KINASE-3; HUMAN BREAST-CANCER; E-CADHERIN; TUMOR PROGRESSION; BETA-CATENIN; PHOSPHATIDYLINOSITOL-3 KINASE; SIGNALING CASCADES AB Metastasis is responsible for 90% of cancer patient deaths. More information is needed about the molecular basis for its potential detection and treatment. The activated AKT kinase is necessary for many events of the metastatic pathway including escape of cells from the tumor's environment, into and then out of the circulation, activation of proliferation, blockage of apoptosis, and activation of angiogenesis. A series of steps leading to metastatic properties can be initiated upon activation of AKT by phosphorylation on Ser-473. These findings lead to the question of how this activation is connected to metastasis. Activated AKT phosphorylates GSK-3 beta causing its proteolytic removal. This increases stability of the negative transcription factor SNAIL, thereby decreasing transcription of the transmembrane protein E-cadherin that forms adhesions between adjacent cells, thereby permitting their detachment. How is AKT hyperactivated in metastatic cells? Increased PI3K or TORC2 kinase activity- or decreased PHLPP phosphatase could be responsible. Furthermore, a positive feedback mechanism is that the decrease of E-cadherin lowers PTEN and thereby increases PIP3, further activating AKT and metastasis. C1 [Qiao, Meng; Pardee, Arthur B.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sheng, Shijie] Wayne State Univ, Sch Med, Detroit, MI USA. [Sheng, Shijie] Barbara Ann Karmanos Canc Inst, Detroit, MI USA. RP Qiao, M (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM meng_qiao@dfci.harvard.edu NR 63 TC 126 Z9 133 U1 3 U2 8 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD OCT 1 PY 2008 VL 7 IS 19 BP 2991 EP 2996 DI 10.4161/cc.7.19.6784 PG 6 WC Cell Biology SC Cell Biology GA 363JG UT WOS:000260263000011 PM 18818526 ER PT J AU Feng, P Yee, KK Rawson, NE Feldman, LM Feldman, RS Breslin, PAS AF Feng, Pu Yee, Karen K. Rawson, Nancy E. Feldman, Lauren M. Feldman, Roy S. Breslin, Paul A. S. TI Immune Cell Populations in Healthy Human Fungiform Papillae SO CHEMICAL SENSES LA English DT Meeting Abstract CT 15th International Symposium on Olfaction and Taste CY JUL 21-26, 2008 CL San Francisco, CA C1 [Feng, Pu; Yee, Karen K.; Rawson, Nancy E.; Feldman, Roy S.; Breslin, Paul A. S.] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. [Feldman, Lauren M.] Barnard Coll, New York, NY USA. [Feldman, Roy S.] Philadelphia Vet Affairs Med Ctr, Dent Serv, Philadelphia, PA USA. [Feldman, Lauren M.] Univ Penn, Sch Dent Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0379-864X J9 CHEM SENSES JI Chem. Senses PD OCT PY 2008 VL 33 IS 8 BP S73 EP S73 PG 1 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA 359GE UT WOS:000259973600289 ER PT J AU Holbrook, EH Schwob, JE AF Holbrook, Eric H. Schwob, James E. TI An Integrated Immunohistochemical Analysis of Human Whole-Mount and Cryosectioned Olfactory Tissue SO CHEMICAL SENSES LA English DT Meeting Abstract CT 15th International Symposium on Olfaction and Taste CY JUL 21-26, 2008 CL San Francisco, CA C1 [Holbrook, Eric H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Schwob, James E.] Tufts Univ, Sch Med, Boston, MA 02111 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0379-864X J9 CHEM SENSES JI Chem. Senses PD OCT PY 2008 VL 33 IS 8 BP S78 EP S78 PG 1 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA 359GE UT WOS:000259973600307 ER PT J AU Maurer, J Rebbapragada, V Borson, S Goldstein, R Kunik, ME Yohannes, AM Hanania, NA AF Maurer, Janet Rebbapragada, Venkata Borson, Soo Goldstein, Roger Kunik, Mark E. Yohannes, Abebaw M. Hanania, Nicola A. CA ACCP Workshop Panel Anxiety Depr TI Anxiety and Depression in COPD Current Understanding, Unanswered Questions, and Research Needs SO CHEST LA English DT Review DE anxiety; comorbidities; COPD; depression; mood disorders ID OBSTRUCTIVE PULMONARY-DISEASE; QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; COGNITIVE-BEHAVIORAL THERAPY; CHRONIC BREATHING DISORDERS; AIR-FLOW LIMITATION; HEALTH-STATUS; PRIMARY-CARE; MYOCARDIAL-INFARCTION; COLLABORATIVE CARE AB Background: Approximately 60 million people in the United States live with one of four chronic conditions: heart disease, diabetes, chronic respiratory disease, anti major depression. Anxiety and depression are very common comorbidities in COPD and have significant impact on patients, their families, society, and the course of the disease. Methods: We report the proceedings of a multidisciplinary, workshop on anxiety and depression in COPD that aimed to shed light on the current understanding of these comorbidities, and outline unanswered questions and areas of future research needs. Results: Estimates of prevalence of anxiety and depression in COPD vary widely but are generally higher than those reported in sonic other advanced chronic diseases. Untreated and undetected anxiety and depressive symptoms may increase physical disability, morbidity, and health-care utilization. Several patient, physician, and system barriers contribute to the underdiagnosis of these disorders in patients with COPD. While few published studies demonstrate that these disorders associated with COPD respond well to appropriate pharmacologic and nonpharmacologic therapy, only a small proportion of COPD patients with these disorders receive effective treatment. Conclusion: Future research is needed to address the impact, early detection, and management of anxiety and depression in COPD. (CHEST 2008; 134:43S-56S) C1 [Rebbapragada, Venkata; Hanania, Nicola A.] Baylor Coll Med, Pulm & Crit Care Med Sect, Houston, TX 77030 USA. [Maurer, Janet] Hlth Dialog Inc, Phoenix, AZ USA. [Borson, Soo] Univ Washington, Sch Med, Seattle, WA USA. [Goldstein, Roger] Univ Toronto, Toronto, ON, Canada. [Kunik, Mark E.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Yohannes, Abebaw M.] Manchester Metropolitan Univ, Manchester M15 6BH, Lancs, England. RP Hanania, NA (reprint author), Baylor Coll Med, Pulm & Crit Care Med Sect, 1504 Taub Loop, Houston, TX 77030 USA. EM Hanania@bcm.edu FU National Institute of Mental Health and the Alpha-1 Foundation [R13-MH07322S-01A1] FX This workshop was supported by grant R13-MH07322S-01A1 from the National Institute of Mental Health and the Alpha-1 Foundation. NR 105 TC 180 Z9 185 U1 4 U2 28 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2008 VL 134 IS 4 SU S BP 43S EP 56S DI 10.1378/chest.08-0342 PG 14 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 360ZQ UT WOS:000260097700001 PM 18842932 ER PT J AU Vasan, RS MacRae, CA AF Vasan, Ramachandran S. MacRae, Calum A. TI A Dream, a Journey, and a Promise The Inauguration of Circulation: Cardiovascular Genetics SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Editorial Material C1 [Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA 01701 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01701 USA. EM vasan@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970 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 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD OCT PY 2008 VL 1 IS 1 BP 1 EP 2 DI 10.1161/CIRCGENETICS.108.813352 PG 2 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA V11AF UT WOS:000207503800001 PM 20031535 ER PT J AU Musunuru, K Kathiresan, S AF Musunuru, Kiran Kathiresan, Sekar TI HapMap and Mapping Genes for Cardiovascular Disease SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE cardiovascular diseases; genes; mapping C1 [Musunuru, Kiran; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Musunuru, Kiran; Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Musunuru, Kiran; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Musunuru, Kiran; Kathiresan, Sekar] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Musunuru, Kiran; Kathiresan, Sekar] MIT, Cambridge, MA 02139 USA. RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 185 Cambridge St,CPZN 5-252, Boston, MA 02114 USA. EM skathiresan@partners.org FU NHLBI NIH HHS [K23 HL083102-02, K23 HL083102] NR 32 TC 9 Z9 10 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD OCT PY 2008 VL 1 IS 1 BP 66 EP 71 DI 10.1161/CIRCGENETICS.108.813675 PG 6 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA V11AF UT WOS:000207503800011 PM 20031544 ER PT J AU Long, AA Camargo, CA AF Long, A. A. Camargo, C. A., Jr. TI Current practice of venom immunotherapy in the UK SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Editorial Material ID STINGING INSECT HYPERSENSITIVITY; ANAPHYLAXIS; ALLERGY C1 [Long, A. A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Camargo, C. A., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Long, AA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Rheumatol Allergy & Immunol, Cox 201,55 Fruit St, Boston, MA 02114 USA. EM aalong@mgh.harvard.edu NR 15 TC 0 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0954-7894 EI 1365-2222 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD OCT PY 2008 VL 38 IS 10 BP 1576 EP 1578 DI 10.1111/j.1365-2222.2008.03077.x PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 356RS UT WOS:000259795900003 PM 18665844 ER PT J AU Maine, GT Edwards, M Haverstick, DM Sluss, P Young, J Schmidt, E Kettlety, T AF Maine, G. T. Edwards, M. Haverstick, D. M. Sluss, P. Young, J. Schmidt, E. Kettlety, T. TI Analytical evaluation of the Abbott ARCHITECT cyclosporine assay in comparison to LC/MS/MS and Abbott TDX/FLX SO CLINICAL BIOCHEMISTRY LA English DT Meeting Abstract C1 [Maine, G. T.] Abbott Diagnost, Abbott Pk, IL USA. [Edwards, M.; Haverstick, D. M.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Sluss, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Young, J.; Schmidt, E.; Kettlety, T.] Fujirebio Diagnost, Malvern, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0009-9120 J9 CLIN BIOCHEM JI Clin. Biochem. PD OCT PY 2008 VL 41 IS 14-15 MA 129 BP 1274 EP 1274 DI 10.1016/j.clinbiochem.2008.08.031 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 366MT UT WOS:000260486900053 ER PT J AU Goss, PE Muss, HB Ingle, JN Whelan, TJ Wu, M AF Goss, Paul E. Muss, Hyman B. Ingle, James N. Whelan, Timothy J. Wu, Melinda TI Extended Adjuvant Endocrine Therapy in Breast Cancer: Current Status and Future Directions SO CLINICAL BREAST CANCER LA English DT Review DE Anastrozole; Aromatase inhibitors; Hormone receptor; Letrozole; Tamoxifen ID QUALITY-OF-LIFE; PLACEBO-CONTROLLED TRIAL; LETROZOLE VS. PLACEBO; TO-TREAT ANALYSIS; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; NCICCTG MA.17; HORMONAL-THERAPY; UPDATED FINDINGS; ATAC ARIMIDEX AB Women with hormone receptor-positive breast cancer have traditionally been treated with 5 years of adjuvant tamoxifen to reduce their risk of subsequent recurrent disease. Among those who experience subsequent disease recurrence, the majority do so after 5 years, suggesting that longer durations of endocrine therapy might be beneficial. Two options tested include longer tamoxifen and, in postmenopausal women, a switch to an aromatase inhibitor (AI). In the National Cancer Institute of Canada Cooperative Trials Group MA.17 trial, we tested the Al letrozole given to postmenopausal women for 5 years after tamoxifen as extended adjuvant therapy because of its efficacy in patients with advanced breast cancer in progression on previous tamoxifen. The first interim analysis (median, 2.4 patient years) showed substantial benefits from letrozole, and all patients were unblinded and offered the option of letrozole. Despite two thirds of the patients crossing over to letrozole, an intent-to-treat analysis at 54 months' follow-up continued to demonstrate the strong beneficial effect of extended adjuvant letrozole. Furthermore, significant benefit was demonstrated among patients who had been randomized to placebo but elected to take letrozole after a prolonged washout from previous tamoxifen (late extended adjuvant therapy). A trial examining the merits of > 5 years of treatment with an Al, MA.17R, is ongoing, as are a number of other trials of duration of therapy. This article reviews results from MA.17 and the design of these trials of duration. C1 [Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Goss, Paul E.] Harvard Univ, Sch Med, Boston, MA USA. [Muss, Hyman B.] Univ Vermont, Burlington, VT 05405 USA. [Ingle, James N.] Mayo Clin, Div Med Oncol, Rochester, MN USA. [Whelan, Timothy J.] McMaster Univ, Juravinski Canc Ctr, Hamilton, ON L8S 4L8, Canada. [Wu, Melinda] Univ Toronto, Toronto, ON M5S 1A1, Canada. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,LH-302, Boston, MA 02114 USA. EM pgoss@partners.org RI Whelan, Timothy/D-3185-2017 NR 49 TC 25 Z9 25 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD OCT PY 2008 VL 8 IS 5 BP 411 EP 417 DI 10.3816/CBC.2008.n.049 PG 7 WC Oncology SC Oncology GA 365KW UT WOS:000260406300004 PM 18952554 ER PT J AU Toschi, L Janne, PA AF Toschi, Luca Janne, Pasi A. TI Single-Agent and Combination Therapeutic Strategies to Inhibit Hepatocyte Growth Factor/MET Signaling in Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID SMALL-MOLECULE INHIBITOR; CELL LUNG-CANCER; RECEPTOR TYROSINE KINASE; SUPPRESSES TUMOR-GROWTH; FACTOR SCATTER FACTOR; C-MET INHIBITOR; COLORECTAL-CANCER; GASTRIC-CANCER; OVARIAN-CANCER; IN-VIVO AB Receptor tyrosine kinases are often aberrantly activated in human malignancies and contribute to cancer development and progression. Specific receptor tyrosine kinase inhibitors have been shown to be clinically effective therapies in subsets of cancer patients with either hematologic or solid tumors. Activation of the hepatocyte growth factor (HGF)/MET signaling pathway has been found to play a critical role in oncogenesis, cancer metastasis, and drug resistance. These observations have led to the development of agents that can effectively inhibit HGF/MET signaling through direct inhibition of the receptor (anti-MET antibodies), through inactivation of its ligand HGF (AMG102, L2G7), by interfering with HGF binding to MET (NK4), or by inhibiting MET kinase activity (PHA-665752 and SU11274). Moreover, the combination of anti-MET therapeutic agents with either signal transduction inhibitors (ERBB family or mTOR inhibitors) or with cytotoxic chemotherapy has been evaluated in preclinical models. These studies provide insight into the rational development of combination therapeutic strategies that can be evaluated in clinical trials. This review will discuss different strategies of MET inhibition with a specific focus on combination therapeutic approaches. C1 [Toschi, Luca; Janne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Toschi, Luca; Janne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Janne, Pasi A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Janne, Pasi A.] Harvard Univ, Sch Med, Boston, MA USA. [Toschi, Luca] Ist Ricovero & Cura Carattere Sci, Ist Clin Humanitas, Dept Hematol Oncol, Rozzano, Italy. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, D820,44 Binney St, Boston, MA 02115 USA. EM pjanne@partners.org FU American Cancer Society [RSG-06-102-01-CCE]; Hazel and Sam Bellin Research Fund for Thoracic Oncology FX American Cancer Society grant RSG-06-102-01-CCE (P.A. Janne) and the Hazel and Sam Bellin Research Fund for Thoracic Oncology (P.A. Janne). NR 71 TC 67 Z9 72 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 OCT 1 PY 2008 VL 14 IS 19 BP 5941 EP 5946 DI 10.1158/1078-0432.CCR-08-0071 PG 6 WC Oncology SC Oncology GA 361QP UT WOS:000260142500002 PM 18829470 ER PT J AU Ansen, S Butler, MO Berezovskaya, A Murray, AP Stevenson, K Nadler, LM Hirano, N AF Ansen, Sascha Butler, Marcus O. Berezovskaya, Alla Murray, Andrew P. Stevenson, Kristen Nadler, Lee M. Hirano, Naoto TI Dissociation of Its Opposing Immunologic Effects Is Critical for the Optimization of Antitumor CD8(+) T-Cell Responses Induced by Interleukin 21 SO CLINICAL CANCER RESEARCH LA English DT Article ID ANTIGEN-PRESENTING CELLS; TUMOR-ASSOCIATED ANTIGEN; CANCER-IMMUNOTHERAPY; DENDRITIC CELL; REGULATORY CELLS; IL-21; THERAPY; MEMORY; GENERATION; EXPANSION AB Purpose: Interleukin 21 (IL-21) is a promising new cytokine, which is undergoing clinical testing as an anticancer agent. Although IL-21 provides potent stimulation of CD8(+) T cells, it has also been suggested that IL-21 is immunosuppressive by counteracting the maturation of dendritic cells. The dissociation of these two opposing effects may enhance the utility of IL-21 as an immunotherapeutic. In this study, we used a cell-based artificial antigen-presenting cell (aAPC) lacking a functional IL-21 receptor (IL-21R) to investigate the immunostimulatory properties of IL-21. Experimental Design: The immunosuppressive activity of IL-21 was studied using human IL-21R(+) dendritic cells. Antigen-specific CD8(+) T cells stimulated with human cell - based IL-21R(-) aAPC were used to isolate the T-cell immunostimulatory effects of IL-21. The functional outcomes, including phenotype, cytokine production, proliferation, and cytotoxicity were evaluated. Results: IL-21 limits the immune response by maintaining immunologically immature dendritic cells. However, stimulation of CD8(+) T cells with IL-21R- aAPC, which secrete IL-21, results in significant expansion. Although priming in the presence of IL-21 temporarily modulated the T-cell phenotype, chronic stimulation abrogated these differences. Importantly, exposure to IL-21 during restimulation promoted the enrichment and expansion of antigen-specific CD8(+) T cells that maintained IL-2 secretion and gained enhanced IFN-gamma secretion. Tumor antigen-specific CTL generated in the presence of IL-21 recognized tumor cells efficiently, demonstrating potent effector functions. Conclusions: IL-21 induces opposing effects on antigen-presenting cells and CD8(+) T cells. Strategic application of IL-21 is required to induce optimal clinical effects and may enable the generation of large numbers of highly avid tumor-specific CTL for adoptive immunotherapy. C1 [Ansen, Sascha; Butler, Marcus O.; Berezovskaya, Alla; Murray, Andrew P.; Nadler, Lee M.; Hirano, Naoto] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Stevenson, Kristen] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Ansen, Sascha; Butler, Marcus O.; Nadler, Lee M.; Hirano, Naoto] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Ansen, Sascha; Butler, Marcus O.; Stevenson, Kristen; Nadler, Lee M.; Hirano, Naoto] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Hirano, N (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM Naoto_-Hirano@dfci.harvard.edu FU Dr. Mildred Scheel Stiftung der Deutschen Krebshilfe; NIH [CA87720, CA92625, HL54785, CA129240]; Cancer Research Institute FX Dr. Mildred Scheel Stiftung der Deutschen Krebshilfe (S. Ansen); NIH grants CA87720 (M.D. Butler), CA92625 (L.M. Nadler), HL54785 (N. Hirano), and CA129240 (N. Hirano); and Cancer Research Institute grant (L.M. Nadler). NR 48 TC 15 Z9 15 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2008 VL 14 IS 19 BP 6125 EP 6136 DI 10.1158/1078-0432.CCR-08-1146 PG 12 WC Oncology SC Oncology GA 361QP UT WOS:000260142500024 PM 18829491 ER PT J AU Arteaga, CL O'Neill, A Moulder, SL Pins, M Sparano, JA Sledge, GW Davidson, NE AF Arteaga, Carlos L. O'Neill, Anne Moulder, Stacy L. Pins, Michael Sparano, Joseph A. Sledge, George W. Davidson, Nancy E. TI A Phase I-II Study of Combined Blockade of the ErbB Receptor Network with Trastuzumab and Gefitinib in Patients with HER2 (ErbB2)-Overexpressing Metastatic Breast Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; CELL LUNG-CANCER; DIMERIZATION INHIBITOR; ZD1839 IRESSA; MONOCLONAL-ANTIBODY; ADJUVANT CHEMOTHERAPY; NEGATIVE PHENOTYPE; DOWN-REGULATION; SINGLE-AGENT AB Purpose: To determine the safety, and efficacy of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib in combination with trastuzumab in patients with metastatic HER2-positive metastatic breast cancer. Experimental Design: Patients with HER2-overexpressing breast cancer were treated with trastuzumab 2 mg/kg/week and gefitinib 250 to 500 mg/day. The primary end point of the study was to increase the proportion progression-free from 50% to 65% at 6 months in chemotherapynaive patients and from 50% to 70% at 3 months in patients previously treated with chemotherapy in the metastatic setting. Results: In the phase I study, all patients treated with gefitinib 500 mg/day developed grade 3 diarrhea. The phase 11 study was conducted using trastuzumab and gefitinib 250 mg/day. One patient achieved a complete response, 2 had a partial response, and 6 had stable disease for an overall response rate of 9% and a clinical benefit rate of 28% (9 of 32). Median time to progression (TTP) was 3 months (95% confidence interval, 2.3-4.1) in patients with no prior systemic therapy in the metastatic setting (n = 23). In patients treated with prior systemic therapy (n = 9), the median TTP of 5.3 months (95% confidence interval, 2.8-8.1). Overall median survival was 27 months. TTP was similar in EGFR-positive compared with EGFR-negative patients. Conclusions: Gefitinib 250 mg/day was the maximal dose that can be safely administered with weekly trastuzumab. Interim analysis of the efficacy suggested that the combination was unlikely to result in clinical benefit compared with trastuzumab alone. These results do not support the use of this combination in patients with HER2-positive breast cancer. C1 [Arteaga, Carlos L.] Vanderbilt Univ, Div Oncol, Med Ctr, Vanderbilt Ingram Comprehens Canc Ctr, Nashville, TN 37232 USA. [O'Neill, Anne] Dana Farber Canc Inst, Boston, MA 02115 USA. [O'Neill, Anne] Eastern Cooperat Oncol Grp, Boston, MA USA. [Moulder, Stacy L.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Pins, Michael] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Sparano, Joseph A.] Albert Einstein Canc Ctr, Montefiore Med Ctr, New York, NY USA. [Sledge, George W.] Indiana Univ, Ctr Canc, Indianapolis, IN 46204 USA. [Davidson, Nancy E.] Johns Hopkins Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RP Arteaga, CL (reprint author), Vanderbilt Univ, Div Oncol, Med Ctr, Vanderbilt Ingram Comprehens Canc Ctr, 2200 Pierce Ave,777 PRB, Nashville, TN 37232 USA. EM carlos.arteaga@vanderbilt.edu FU NCI NIH HHS [CA 21115, CA 23318, CA 66636, P30 CA 68485, P30 CA068485, P50 CA098131, R01 CA 80195, R01 CA080195, R01 CA080195-09, U10 CA021115, U10 CA023318, U10 CA066636] NR 55 TC 48 Z9 49 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2008 VL 14 IS 19 BP 6277 EP 6283 DI 10.1158/1078-0432.CCR-08-0482 PG 7 WC Oncology SC Oncology GA 361QP UT WOS:000260142500043 PM 18829509 ER PT J AU Christo, K Cord, J Mendes, N Miller, KK Goldstein, MA Klibanski, A Misra, M AF Christo, Karla Cord, Jennalee Mendes, Nara Miller, Karen K. Goldstein, Mark A. Klibanski, Anne Misra, Madhusmita TI Acylated ghrelin and leptin in adolescent athletes with amenorrhea, eumenorrheic athletes and controls: a cross-sectional study SO CLINICAL ENDOCRINOLOGY LA English DT Article ID BONE-DENSITY; LUTEINIZING-HORMONE; HEALTHY ADOLESCENTS; SECRETORY DYNAMICS; PHYSICAL-ACTIVITY; ANOREXIA-NERVOSA; PLASMA GHRELIN; WOMEN; GIRLS; EXERCISE AB Objectives Neuroendocrine factors may predict which athletes develop amenorrhea and which athletes remain eugonadal. Specifically, ghrelin and leptin have been implicated in regulation of GnRH secretion, with ghrelin having inhibitory and leptin, facilitatory effects. We hypothesized that adolescent athletes with amenorrhea (AA) would have higher ghrelin and lower leptin levels than eumenorrheic athletes (EA) and would predict levels of gonadal steroids. Design Cross-sectional Subjects and measurements We enrolled 58 girls, 21 AA, 19 EA and 18 nonathletic controls 12-18 years old. Fasting blood was drawn for active ghrelin, leptin, E(2) and testosterone. Athletes were > 85% of ideal body weight for age based on body mass index (BMI). Results AA girls had lower BMI than EA and controls (P = 0.003). Log ghrelin was higher in AA than in EA and controls (P < 0.0001), and remained higher after controlling for BMI Z-scores. Leptin was lower in AA than in the other groups (P < 0.0001), however, the differences did not persist after controlling for BMI Z-scores. Testosterone was lower in AA than in EA and controls (P = 0.002) and log E(2) trended lower in AA (P = 0.07). We observed inverse associations of log active ghrelin with testosterone (P = 0.01), and positive associations of leptin with testosterone and log E(2) (P = 0.02 and 0.009). Conclusion Higher ghrelin levels, even after controlling for BMI, and lower leptin in AA compared with EA and controls, and their inverse and positive associations, respectively, with gonadal steroids suggest endocrine perturbations that may explain why hypogonadism occurs in some but not all athletes. C1 [Christo, Karla; Cord, Jennalee; Mendes, Nara; Miller, Karen K.; Klibanski, Anne; Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Christo, Karla; Cord, Jennalee; Mendes, Nara; Miller, Karen K.; Klibanski, Anne; Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA USA. [Misra, Madhusmita] Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Boston, MA USA. [Goldstein, Mark A.] Massachusetts Gen Hosp Children, Adolescent Med Unit, Boston, MA USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St, Boston, MA 02114 USA. EM mmisra@partners.org RI Mendes Estella, Nara/E-4682-2013; Mendes Estella, Nara/A-1469-2015 FU NIH [R01 DK 062249, K23 RR018851, P30DK040561, M01-RR-01066] FX We would like to thank the skilled nurses of the General Clinical Research Center (GCRC) of Massachusetts General Hospital and Ellen Anderson and the Bionutrition team for their help in carrying out this study. We would also like to thank Jeff Breu at MIT for running our assays. Finally, we would like to thank our subjects, without whom this study would not have been possible. This work was supported in part by NIH grants R01 DK 062249, K23 RR018851, P30DK040561 and M01-RR-01066. NR 33 TC 32 Z9 33 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD OCT PY 2008 VL 69 IS 4 BP 628 EP 633 DI 10.1111/j.1365-2265.2008.03237.x PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 347MX UT WOS:000259146800018 PM 18331605 ER PT J AU Sonnenberg, A Rodriguez, SA Faigel, DO AF Sonnenberg, Amnon Rodriguez, Sarah A. Faigel, Douglas O. TI Diagnostic Ascertainment of Suspicious Pancreatic Mass: A Threshold Analysis SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID FINE-NEEDLE-ASPIRATION; QUALITY-OF-LIFE; ENDOSCOPIC ULTRASOUND; COST-EFFECTIVENESS; AUTOIMMUNE PANCREATITIS; COMPUTED-TOMOGRAPHY; CYSTIC NEOPLASMS; CANCER; PANCREATICODUODENECTOMY; EUS AB Background & Aims: it is frequently difficult to differentiate between a benign and malignant pancreatic mass. The aim of this study was to assess the parameters that affect the decision to perform surgery on a suspicious pancreatic head lesion. Methods : A cost-benefit analysis, using decision tree and threshold analysis, accumulates costs and quality-adjusted life years in patients undergoing pancreaticoduodenectomy or expectant management. The threshold value is defined as the diagnostic probability for pancreatic cancer when the cost-benefit relationships of pancreaticoduodenectomy or expectant management are equal. Results: For a localized pancreatic head lesion, the threshold probability of cancer is 43%. Any higher probability of pancreatic cancer makes pancreaticoduodenectomy the preferred treatment option. Within a range of $20,000 to $80,000 spent on surgery, the threshold in favor of Whipple procedure remains relatively low at 40% to 65%. A reduced quality of life after surgery weighs against surgery and raises its threshold. Varying quality of life between 100% and 80% changes the threshold between 31% and 67%. The threshold also is increased in younger patients because of the potentially more dire consequences of unnecessary surgery in instances of long life expectancy. Conclusion : Even if diagnostic certainty cannot be achieved, it frequently is beneficial to perform surgery despite the risk of subjecting the occasional patient with benign pancreatic head lesion to an unnecessary pancreaticoduodenectomy. C1 Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Div Gastroenterol, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 36 TC 4 Z9 7 U1 0 U2 2 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 OCT PY 2008 VL 6 IS 10 BP 1162 EP 1166 DI 10.1016/j.cgh.2008.05.015 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 360VS UT WOS:000260086900020 PM 18928941 ER PT J AU Boyd, C Smith, MJ Kluwe, L Balogh, A MacCollin, M Plotkin, SR AF Boyd, C. Smith, M. J. Kluwe, L. Balogh, A. MacCollin, M. Plotkin, S. R. TI Alterations in the SMARCB1 (INI1) tumor suppressor gene in familial schwannomatosis SO CLINICAL GENETICS LA English DT Article DE INI1; neurofibromatosis; schwannoma; schwannomatosis; SMARCB1; tumor suppressor gene ID ATYPICAL TERATOID/RHABDOID TUMORS; RHABDOID PREDISPOSITION SYNDROME; HSNF5/INI1 GENE; BRAIN-TUMORS; NEUROFIBROMATOSIS TYPE-1; MOLECULAR ANALYSIS; GERMLINE MUTATION; NF2; PHENOTYPE; FREQUENCY AB Schwannomatosis is a third major form of neurofibromatosis that has recently been linked to mutations in the SMARCB1 (hSnf5/INI1) tumor suppressor gene. We analyzed the coding region of SMARCB1 by direct sequencing and multiplex ligation-dependent probe amplification (MLPA) in genomic DNA from 19 schwannomatosis kindreds. Microsatellite markers in the SMARCB1 region were developed to determine loss of heterozygosity (LOH) in associated tumors. We detected four alterations in conserved splice acceptor or donor sequences of exons 3, 4 and 6. Two alterations that likely affect splicing were seen in introns 4 and 5. An additional four alterations of unclear pathogenicity were found to segregate on the affected allele in eight families including two non-conservative missense alterations in three families. No constitutional deletions or duplications were detected by MLPA. Nine of 13 tumors examined showed partial LOH of the SMARCB1 region consistent with 'second hits.' Alterations were detected in tumors both with and without somatic NF2 gene changes. These findings support the hypothesis that SMARCB1 is a tumor suppressor for schwannomas in the context of familial disease. Further work is needed to determine its role in other multiple and single tumor syndromes. C1 [Plotkin, S. R.] Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Boyd, C.; Smith, M. J.; Balogh, A.; MacCollin, M.; Plotkin, S. R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Kluwe, L.] Univ Hosp Eppendorf, Dept Maxillofacial Surg, Hamburg, Germany. RP Plotkin, SR (reprint author), Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM splotkin@partners.org RI Smith, Miriam/J-4001-2015 OI Smith, Miriam/0000-0002-3184-0817 FU NF, Inc; Congressionally Directed Medical Research Fund FX We thank many patients and families who have so generously contributed to this study, the health care providers who have coordinated their participation and Drs Anat Stemmer-Rachamimov and Charles Roberts for their thoughtful reading of the manuscript. Expert chart review was provided by Ms Melanie O'Leary who is supported by NF, Inc. through the Harvard Center for Human Genetic Research. M. M. was supported by a grant from the Congressionally Directed Medical Research Fund. NR 38 TC 76 Z9 76 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD OCT PY 2008 VL 74 IS 4 BP 358 EP 366 DI 10.1111/j.1399-0004.2008.01060.x PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 349GW UT WOS:000259270300011 PM 18647326 ER PT J AU Bradshaw, EM Kent, SC Tripuraneni, V Orban, T Ploegh, HL Hafler, DA Love, JC AF Bradshaw, Elizabeth M. Kent, Sally C. Tripuraneni, Vinay Orban, Tiharner Ploegh, Hidde L. Hafler, David A. Love, J. Christopher TI Concurrent detection of secreted products from human lymphocytes by microengraving: Cytokines and antigen-reactive antibodies SO CLINICAL IMMUNOLOGY LA English DT Article DE human; microengraving; type 1 diabetes; single cell analysis; autoantibodies; cytokines; proinsulin ID MEMORY B-CELLS; CD4(+) T-CELLS; PERIPHERAL-BLOOD; AUTOANTIBODIES; INSULIN; AUTOANTIGEN; PROFILES; DISEASE; TYPE-1; FREQUENCY AB Cell surface determinants, cytokines and antibodies secreted by hematopoietic cells are used to classify their lineage and function. Currently available techniques are unable to elucidate multiple secreted proteins white also assigning phenotypic surface-displayed markers to the individual living cells. Here, a soft lithographic method, microengraving, was adapted for the multiplexed interrogation of populations of individual human peripheral blood mononuclear cells for secreted cytokines (IFN-gamma and IL-6), antigen-specific antibodies, and lineage-specific surface-expressed markers. Application of the method to a clinical sample from a recent-onset Type 1 diabetic subject with a positive titer of anti-insulin antibodies showed that similar to 0.58% of circulating CD19(+) B cells secreted proinsulin-reactive antibodies of the IgG isotype and 2-3% of circulating cells secreted IL-6. These data demonstrate the utility of microengraving for interrogating multiple phenotypes of single human cells concurrently and for detecting rare populations of cells by their secreted products. (C) 2008 Elsevier Inc. All rights reserved. C1 [Bradshaw, Elizabeth M.; Kent, Sally C.; Hafler, David A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, NRB,Ctr Neurol Dis,Div Mol Immunol, Boston, MA 02115 USA. [Tripuraneni, Vinay; Love, J. Christopher] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Orban, Tiharner] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02115 USA. [Ploegh, Hidde L.] MIT, Dept Biol, Whitehead Inst Biomed Res, Cambridge, MA 02139 USA. [Ploegh, Hidde L.; Hafler, David A.] MIT & Harvard, Broad Inst, Cambridge, MA 02139 USA. RP Hafler, DA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, NRB,Ctr Neurol Dis,Div Mol Immunol, Room 641,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM dhafler@rics.bwh.harvard.edu; clove@mit.edu FU NIH Autoimmunity Prevention Center; Broad Institute of MIT; Harvard; Juvenile Diabetes Research Foundation International [NIH Al651003]; National Institutes of Health [R01 Al39229, R01 Al44447, P01 Al39671]; Jacob Javits Merit Award [NS2427]; National Institute of Neurological Disorders and Stroke; National Multiple Sclerosis Society FX Support for these studies was provided by grants from the NIH Autoimmunity Prevention Center and the Broad Institute of MIT and Harvard (H.L.P. and J.C.L.), S.C.K. (Juvenile Diabetes Research Foundation International), E.M.B. (NIH Al651003), National Institutes of Health Grants R01 Al39229, R01 Al44447, and P01 Al39671 (to D.A.H.); and a Jacob Javits Merit Award (NS2427 to D.A.H.) from the National Institute of Neurological Disorders and Stroke and a grant from the National Multiple Sclerosis Society. The authors thank Khadir Raddassi for helpful discussions. NR 32 TC 38 Z9 38 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD OCT PY 2008 VL 129 IS 1 BP 10 EP 18 DI 10.1016/j.clim.2008.06.009 PG 9 WC Immunology SC Immunology GA 351XM UT WOS:000259459200003 PM 18675591 ER PT J AU Bradshaw, S Zheng, WJ Tsoi, LC Gilkeson, G Zhang, XK AF Bradshaw, Sarah Zheng, W. Jim Tsoi, Lam C. Gilkeson, Gary Zhang, Xian K. TI A role for Fli-1 in B cell proliferation: Implications for SLE pathogenesis SO CLINICAL IMMUNOLOGY LA English DT Article DE B cell; BCR; Fli-1; IL12; NFAT; proliferation; SLE; TNF beta; TLR ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PRIMARY SJOGRENS-SYNDROME; BLOOD MONONUCLEAR-CELLS; MRL/MP-LPR/LPR MICE; TOLL-LIKE RECEPTORS; TRANSCRIPTION FACTOR; ETS FAMILY; PERIPHERAL-BLOOD; RENAL-DISEASE; SOLUBLE CD23 AB Transgenic overexpression of Fli-1 in normal mice leads to SLE-like disease and increased expression was reported in SLE-affected human and murine lymphocytes. Reducing Fli-1 expression in MRL/lpr mice decreased antibody production, proteinuria, renal pathology, and mortality. Compared to those with wild-type expression of Fli-1, we report here that proliferative responses of Fli-1-deficient naive B cells to several mitogens were reduced in lupus-prone and control mice. Expression of mitogen receptors, including BCR, TLR4, and TLR9, was not significantly impacted in Fli-1-deficient naive B cells. IL12a transcripts were upregulated and NFAT transcripts were downregulated in Fli-1-deficient MRL/lpr B cells. These results demonstrate that Fli-1 deficiency affects B cell proliferative responses to mitogens, independent of BCR and TLR expression. IL12a and NFAT, known to influence proliferation, were identified as potential mediators of this effect. This may be a mechanism by which overexpression of Fli-1 contributes to B cell hyperactivity and subsequent SLE pathogenesis. (C) 2008 Elsevier Inc. All rights reserved. C1 [Bradshaw, Sarah; Gilkeson, Gary; Zhang, Xian K.] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Zheng, W. Jim; Tsoi, Lam C.] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. [Gilkeson, Gary] Ralph H Johnson Vet Adm Med Ctr, Med Res Serv, Charleston, SC USA. RP Bradshaw, S (reprint author), 96 Jonathan Lucas St,Suite 912,MSC 637, Charleston, SC 29425 USA. EM gallant@musc.edu OI Tsoi, Lam Cheung/0000-0003-1627-5722 FU NIAMS NIH HHS [K01 AR051385, R03 AR054546, K01 AR051385-01A1, R03 AR054546-01] NR 86 TC 15 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 EI 1521-7035 J9 CLIN IMMUNOL JI Clin. Immunol. PD OCT PY 2008 VL 129 IS 1 BP 19 EP 30 DI 10.1016/j.clim.2008.05.010 PG 12 WC Immunology SC Immunology GA 351XM UT WOS:000259459200004 PM 18692443 ER PT J AU Musher, DM AF Musher, Daniel M. TI Neurosyphilis: Diagnosis and response to treatment SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; CEREBROSPINAL-FLUID; SYPHILIS; PENICILLIN C1 [Musher, Daniel M.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Houston, TX 77030 USA. [Musher, Daniel M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Musher, Daniel M.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. RP Musher, DM (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, 2002 Holcombe Blvd,Rm 4B-370, Houston, TX 77030 USA. EM daniel.musher@med.va.gov NR 16 TC 3 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2008 VL 47 IS 7 BP 900 EP 902 DI 10.1086/591535 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 345ZO UT WOS:000259038400006 PM 18715158 ER PT J AU Asmal, M Factor, RE Walensky, RP AF Asmal, Mohammed Factor, Rachel E. Walensky, Rochelle P. TI An HIV-infected man with an upset stomach SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID EXTRACEREBRAL TOXOPLASMOSIS; PATIENT; GONDII C1 [Asmal, Mohammed; Walensky, Rochelle P.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. [Factor, Rachel E.] Brigham & Womens Hosp, Div Anat Pathol, Boston, MA 02115 USA. [Walensky, Rochelle P.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis & Gen Med, Boston, MA 02114 USA. [Walensky, Rochelle P.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. RP Asmal, M (reprint author), 41 Ave Louis Pasteur, Boston, MA 02115 USA. EM masmal@partners.org NR 7 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2008 VL 47 IS 7 BP 935 EP + DI 10.1086/591694 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 345ZO UT WOS:000259038400014 PM 18778229 ER PT J AU Souza, FF Israel, DA AF Souza, Frederico F. Israel, David A. TI PET/CT Appearance of Non-Hodgkin Lymphoma of the Vermiform Appendix SO CLINICAL NUCLEAR MEDICINE LA English DT Editorial Material DE appendix; F-18FDG PET/CT; lymphoma ID PATHOLOGICAL CORRELATION; MALIGNANT-LYMPHOMA; CT AB We present a case of a 53-year-old man with large B-cell non-Hodgkin lymphoma that infiltrated the vermiform appendix. The patient underwent F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT scan) for staging, which demonstrated intense abnormal tracer uptake in the appendix. After 2 cycles of chemotherapy (R-CHOP), a follow-up PET/CT scan demonstrated complete resolution of the abnormal tracer uptake within the appendix. This case highlights the contribution of F-18 FDG PET/CT in the diagnosis and post-therapy evaluation of this involvement. C1 [Souza, Frederico F.; Israel, David A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02215 USA. RP Souza, FF (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, 44 Binney St, Boston, MA 02215 USA. EM ffsouza@partners.org NR 9 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD OCT PY 2008 VL 33 IS 10 BP 694 EP 696 DI 10.1097/RLU.0b013e318184c8dc PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 357UE UT WOS:000259871300009 PM 18806571 ER PT J AU Sung, AD Anderson, ME Zurakowski, D Hornicek, FJ Gebhardt, MC AF Sung, Anthony D. Anderson, Megan E. Zurakowski, David Hornicek, Francis J. Gebhardt, Mark C. TI Unicameral bone cyst - A retrospective study of three surgical treatments SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID LONG BONES; FOLLOW-UP; METHYLPREDNISOLONE ACETATE; SUBTOTAL RESECTION; STEROID INJECTION; MARROW; PATHOGENESIS; MATRIX; ALLOGRAFT; CHILDREN AB Between 1979 and 2004, 167 patients younger than 20 years were treated surgically for humeral or femoral unicameral bone cysts with either injection of corticosteroids (steroids), curettage plus bone grafting (curettage), or a combination injection of steroids, demineralized bone matrix, and bone marrow aspirate (SDB) at Children's Hospital of Boston and Massachusetts General Hospital (mean followup, 7.3 years; range, 1 month-27 years). Outcomes included treatment failure (defined clinically as subsequent pathologic fracture or need for retreatment to prevent pathologic fracture) and complications. Information was obtained from medical records and by telephone questionnaire. After one treatment, 84% of cysts treated with steroids experienced failed treatment versus 64% with curettage and 50% with SDB. For unicameral bone cysts requiring retreatment (regardless of first treatment), 76% retreated with steroids had failed treatment versus 63% with curettage and 71% with SDB. Curettage was associated with the lowest rate of posttreatment pathologic fractures and highest rate of pain and other complications. Multivariate logistic regression indicated treatment with steroids alone and younger age were independent predictors of failure. We believe SDB is a reasonable first treatment for unicameral bone cysts in the humerus and femur in patients younger than 20 years, being less invasive yet comparable to curettage in preventing recurrence. C1 [Sung, Anthony D.] Harvard Univ, Sch Med, Boston, MA USA. [Anderson, Megan E.; Zurakowski, David; Gebhardt, Mark C.] Childrens Hosp, Boston, MA 02115 USA. [Hornicek, Francis J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Anderson, ME (reprint author), 330 Brookline Ave, Boston, MA 02215 USA. EM manders6@bidmc.harvard.edu NR 42 TC 30 Z9 32 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD OCT PY 2008 VL 466 IS 10 BP 2519 EP 2526 DI 10.1007/s11999-008-0407-0 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 347KX UT WOS:000259141600030 PM 18679761 ER PT J AU Spencer, TJ AF Spencer, Thomas J. TI ADULT ADHD: DIVERSION AND MISUSE OF MEDICATIONS SO CNS SPECTRUMS LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; SUBSTANCE USE DISORDERS; COCAINE ABUSERS; PRESCRIPTION STIMULANTS; CONDUCT DISORDER; PREVALENCE; ADOLESCENTS; METHYLPHENIDATE; SMOKING C1 [Spencer, Thomas J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Spencer, Thomas J.] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. RP Spencer, TJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 28 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2008 VL 13 IS 10 SU 15 BP 9 EP 13 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 371HD UT WOS:000260821500003 PM 18955949 ER PT J AU Sano, M AF Sano, Mary TI NON-AMYLOID APPROACHES TO NEUROPROTECTION SO CNS SPECTRUMS LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; MODERATE ALZHEIMERS-DISEASE; MILD COGNITIVE IMPAIRMENT; GLOBAL FUNCTION; DOUBLE-BLIND; PLACEBO; ROFECOXIB; ATORVASTATIN; INDIVIDUALS; DONEPEZIL C1 [Sano, Mary] Mt Sinai Sch Med, Alzheimers Dis Res Ctr, New York, NY 10029 USA. [Sano, Mary] James J Peters VAMC, Bronx, NY USA. [Sano, Mary] Bristol Myers Squibb Co, New York, NY 10154 USA. Eisai & Co Ltd, Teaneck, NJ 07666 USA. [Sano, Mary] GlaxoSmithKline Inc, Res Triangle Pk, NC 27709 USA. [Sano, Mary] Pfizer, New York, NY USA. RP Sano, M (reprint author), Mt Sinai Sch Med, Alzheimers Dis Res Ctr, New York, NY 10029 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2008 VL 13 IS 10 SU 16 BP 42 EP 44 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 364ZF UT WOS:000260373900013 PM 18955963 ER PT J AU Linden, M Golier, J AF Linden, Maria Golier, Julia TI Challenges in the Implementation of Manualized Psychotherapy in Combat-related PTSD SO CNS SPECTRUMS LA English DT Article C1 [Linden, Maria; Golier, Julia] Mt Sinai Sch Med, New York, NY 10029 USA. [Golier, Julia] Bronx Vet Adm Med Ctr, PTSD Clin, Dept Psychiat, New York, NY USA. RP Linden, M (reprint author), Mt Sinai Sch Med, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM maria.linden@mssm.edu NR 4 TC 2 Z9 2 U1 0 U2 0 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 OCT PY 2008 VL 13 IS 10 BP 872 EP 877 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 363KT UT WOS:000260266900008 PM 18955942 ER PT J AU Smith, FA Wittmann, CW Stern, TA AF Smith, Felicia A. Wittmann, Curtis W. Stern, Theodore A. TI Medical Complications of Psychiatric Treatment SO CRITICAL CARE CLINICS LA English DT Article ID SEROTONIN-REUPTAKE INHIBITORS; ATYPICAL ANTIPSYCHOTIC-DRUGS; NEUROLEPTIC MALIGNANT SYNDROME; PLACEBO-CONTROLLED TRIALS; PULMONARY-EMBOLISM; PSYCHOTROPIC-DRUGS; DIABETES-MELLITUS; CEREBRAL VASOCONSTRICTION; SCHIZOPHRENIA-PATIENTS; PLACENTAL PASSAGE AB Psychiatric medications are frequently an essential component of care for critically ill patients. Their use may lead to medical complications, however, as a result of (1) direct toxicity from psychotropic medications, (2) drug-drug interactions, or (3) intoxication or withdrawal states. These complications may be a nuisance (eg, dry mouth and nausea) or serious and life-threatening (eg, neuroleptic malignant syndrome and cardiac arrhythmias). This article addresses the most important medical complications (organized by organ systems) of psychiatric treatment. C1 [Smith, Felicia A.; Stern, Theodore A.] Massachusetts Gen Hosp, Dept Psychiat, Avery D Weisman MD Psychiat Consultat Serv, Boston, MA 02114 USA. [Smith, Felicia A.; Wittmann, Curtis W.; Stern, Theodore A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Smith, FA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Avery D Weisman MD Psychiat Consultat Serv, Warren 605,55 Fruit St, Boston, MA 02114 USA. EM fsmith2@partners.org NR 77 TC 5 Z9 5 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0704 J9 CRIT CARE CLIN JI Crit. Care Clin. PD OCT PY 2008 VL 24 IS 4 BP 635 EP + DI 10.1016/j.ccc.2008.05.004 PG 23 WC Critical Care Medicine SC General & Internal Medicine GA 371WI UT WOS:000260863000002 PM 18929938 ER PT J AU Robertson, TE Mann, HJ Hyzy, R Rogers, A Douglas, I Waxman, AB Weinert, C Alapat, P Guntupalli, KK Buchman, TG AF Robertson, T. Elizabeth Mann, Henry J. Hyzy, Robert Rogers, Angela Douglas, Ivor Waxman, Aaron B. Weinert, Craig Alapat, Philip Guntupalli, Kalpalatha K. Buchman, Timothy G. CA Partnership Excellence Critical Ca TI Multicenter implementation of a consensus-developed, evidence-based, spontaneous breathing trial protocol SO CRITICAL CARE MEDICINE LA English DT Article DE respirator; acute respiratory distress syndrome artificial; ventilator weaning; practice guideline; interdisciplinary communication; professional practice; guideline adherence ID INTENSIVE-CARE-UNIT; MANAGED CLINICAL NETWORK; CRITICALLY-ILL PATIENTS; MECHANICAL VENTILATION; HEALTH-CARE; GUIDELINES; INTERVENTION; DURATION; QUALITY; PNEUMONIA AB Objective: Evidence-based practice recommendations abound, but implementation is often unstructured and poorly audited. We assessed the ability of a peer network to implement an evidence-based best practice protocol and to measure patient outcomes. Design: Consensus definition of spontaneous breathing trial followed by implementation in eight academic medical centers. Setting: Six medical, two surgical, and two combined medical/surgical adult intensive care units among eight academic medical centers. Study Population: Patients initiating mechanical ventilation through an endotracheal tube during a 12-wk interval formed the study population. Interventions: Adoption and implementation of a common spontaneous breathing trial protocol across multiple intensive care units. Measurements and Main Results: Seven hundred five patients had 3,486 safety screens for conducting a spontaneous breathing trial; 2072 (59%) patients failed the safety screen. Another 379 (11%) patients failed a 2-min tolerance screen and 1,122 (34%) patients had a full 30-120 min spontaneous breathing trial performed. Seventy percent of eligible patients were enrolled. Only 55% of passing spontaneous breathing trials resulted in liberation from mechanical ventilatory support before another spontaneous breathing trial was performed. Conclusions: Peer networks can be effective in promoting and implementing evidence-based best practices. Implementation of a best practice (spontaneous breathing trial) may be necessary for, but by itself insufficient to achieve, consistent and timely liberation from ventilator support. C1 [Robertson, T. Elizabeth; Buchman, Timothy G.] Washington Univ, Dept Surg, St Louis, MO 63130 USA. [Mann, Henry J.] Univ Minnesota, Coll Pharm, Minneapolis, MN 55455 USA. [Hyzy, Robert] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Rogers, Angela; Waxman, Aaron B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Douglas, Ivor] Denver Hlth Med Ctr, Denver, CO USA. [Weinert, Craig] Univ Minnesota, Dept Med, Div Pulm Allergy & Crit Care, Minneapolis, MN USA. [Alapat, Philip; Guntupalli, Kalpalatha K.] Baylor Coll Med, Dept Med, Div Pulm & Crit Care, Houston, TX 77030 USA. RP Robertson, TE (reprint author), Washington Univ, Dept Surg, St Louis, MO 63130 USA. EM robertsont@wudosis.wustl.edu OI Douglas, Ivor/0000-0002-4541-1431; Buchman, Timothy/0000-0001-7350-5921 FU James S. McDonnell Foundation; NIGMS [GM008795] FX Supported in part by a grant from the James S. McDonnell Foundation and NIGMS postdoctoral fellowship, GM008795 (to TER). NR 38 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD OCT PY 2008 VL 36 IS 10 BP 2753 EP 2762 DI 10.1097/CCM.0b013e3181872833 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 356GF UT WOS:000259766000006 PM 18828193 ER PT J AU Hamdy, O Carver, C AF Hamdy, Osama Carver, Catherine TI The Why WAIT Program: Improving Clinical Outcomes Through Weight Management in Type 2 Diabetes SO CURRENT DIABETES REPORTS LA English DT Article ID LIFE-STYLE MODIFICATION; INSULIN-RESISTANCE; GLYCEMIC CONTROL; OBESE-PATIENTS; RENAL-FUNCTION; LIVER-DISEASE; HIGH-PROTEIN; FOLLOW-UP; LOSS DIET; ADULTS AB Targeting body weight, as an alternative model to targeting hemoglobin A(1c), is emerging as a viable and potentially cost-effective approach to diabetes management in clinical practice. Why WAIT (Weight Achievement and Intensive Treatment) is a 12-week multidisciplinary program for weight control and intensive diabetes management specifically designed for application in routine diabetes practice. The program, which is generally covered by insurance, is followed by continuous support aimed at long-term maintenance of weight loss and diabetes control. This model was effective in improving key metabolic abnormalities observed in diabetic patients. Eighty-two percent of participants achieved the target hemoglobin A(1c) of less than 7% on less diabetes medications. The achieved weight reduction after 12 weeks of intervention was maintained for an additional year. Future dissemination of this intervention model in routine clinical practice may require wider endorsement by third-party payers and support of governmental health care agencies to halt the progression of the epidemic of obesity and diabetes in the United States. C1 [Hamdy, Osama] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Hamdy, O (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM Osama.Hamdy@joslin.harvard.edu NR 32 TC 29 Z9 29 U1 0 U2 3 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD OCT PY 2008 VL 8 IS 5 BP 413 EP 420 DI 10.1007/s11892-008-0071-5 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 375GH UT WOS:000261101600011 PM 18778592 ER PT J AU Carman, CV Springer, TA AF Carman, Christopher V. Springer, Timothy A. TI Trans-cellular migration: cell-cell contacts get intimate SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID ABSORBING LYMPHATIC VESSEL; BLOOD-BRAIN-BARRIER; ENDOTHELIAL-CELLS; TRANSCELLULAR MIGRATION; PHENOTYPIC HETEROGENEITY; TRANSENDOTHELIAL PASSAGE; INFLAMMATORY RESPONSE; VASCULAR ENDOTHELIUM; PEYERS-PATCHES; TUMOR-CELL AB Trans-cellular migration, the movement of one cell directly through another, seems an unlikely, counterintuitive, and even bizarre process. Trans-cellular migration has been reported for nearly half a century in leukocyte transendothelial migration in vivo, but is not well enough accepted to widely feature in textbook accounts of diapedesis. Recently, the first in vitro and additional in vivo observations of trans-cellular diapedesis have been reported. Mechanisms by which this occurs are just beginning to be elucidated and point to podosome-like protrusive activities in leukocytes and specific fusogenic functions in endothelial cells. Emerging evidence for a quantitatively significant contribution of trans-cellular migration to leukocyte trafficking in increasingly diverse settings suggests that this phenomenon represents an important and physiologic cell biological process. C1 [Carman, Christopher V.] Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Springer, Timothy A.] Harvard Univ, Sch Med, Dept Pathol, Immune Dis Inst, Boston, MA 02115 USA. RP Carman, CV (reprint author), Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. EM ccarman@bidmc.harvard.edu; springeroffice@idi.harvard.edu RI Carman, Christopher/L-8108-2016 OI Carman, Christopher/0000-0001-7358-2548 FU Arthritis Foundation; NIH FX We would like to thank Ann Dvorak for her comments and discussion and both Ann Dvorak and Tracey Sciuto for providing electron micrographs for Figure 1. This work was supported by grants from the Arthritis Foundation (CVC) and the NIH (TAS). NR 65 TC 104 Z9 107 U1 0 U2 11 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 OCT PY 2008 VL 20 IS 5 BP 533 EP 540 DI 10.1016/j.ceb.2008.05.007 PG 8 WC Cell Biology SC Cell Biology GA 358TJ UT WOS:000259940100008 PM 18595683 ER PT J AU Traum, AZ Ko, DSC Kawai, T AF Traum, Avram Z. Ko, Dicken S. C. Kawai, Tatsuo TI The potential for tolerance in pediatric renal transplantation SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE adolescent; kidney transplantation; pediatric; tolerance ID TOTAL-LYMPHOID IRRADIATION; DONOR BONE-MARROW; ALLOGRAFT TOLERANCE; LYMPHOHEMATOPOIETIC CHIMERISM; KIDNEY-TRANSPLANTATION; CARDIOVASCULAR RISK; STEROID WITHDRAWAL; MULTIPLE-MYELOMA; ACUTE REJECTION; RECIPIENTS AB Purpose of review Immune tolerance has remained the Holy Grail in transplantation since the first kidney transplantation was performed over 50 years ago. Children present unique challenges in renal transplantation because of increased infectious risks and adolescent nonadherence to the intensive medication regimen necessary for allograft function. The current review presents recent studies and approaches toward achieving tolerance in renal transplantation and the prospects for pediatric patients. Recent findings A number of approaches have been used toward minimization of immunosuppression in pediatric patients, but none has yet achieved true operational tolerance with maintenance of allograft function of all immunosuppression. Recent work in adult renal transplant recipients using combined kidney-bone marrow transplantation by the induction of transient mixed chimerism has allowed for full withdrawal of immunosuppression with stable long-term renal function. Summary On the basis of recent adult studies, the prospect of immune tolerance in pediatric renal transplantation remains hopeful and may be ready for extension to the adolescent population. C1 [Kawai, Tatsuo] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Unit, Dept Surg,Transplant Ctr, Boston, MA 02114 USA. [Traum, Avram Z.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Pediat Nephrol Unit, Boston, MA 02114 USA. RP Kawai, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Unit, Dept Surg,Transplant Ctr, 55 Fruit St,White 510, Boston, MA 02114 USA. EM tkawai@partners.org FU National Institutes of Health [NO1-Al-15416] FX This work was supported in part by grants from the Immune Tolerance Network (NO1-Al-15416) of the National Institutes of Health. NR 61 TC 7 Z9 7 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 OCT PY 2008 VL 13 IS 5 BP 489 EP 494 DI 10.1097/MOT.0b013e328310b0cd PG 6 WC Transplantation SC Transplantation GA 363CN UT WOS:000260243600003 PM 19060531 ER PT J AU Kotton, CN AF Kotton, Camille Nelson TI Update on infectious diseases in pediatric solid organ transplantation SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE BK virus; cytomegalovirus; infection; pediatric solid organ transplant; vaccine/vaccination/immunization ID ORTHOTOPIC LIVER-TRANSPLANTATION; URINARY-TRACT-INFECTION; VARICELLA-ZOSTER-VIRUS; RENAL-TRANSPLANTATION; SINGLE-CENTER; POLYOMAVIRUS BK; HEPATITIS-B; RECIPIENTS; CHILDREN; VACCINE AB Purpose of review Numerous recent advances have been made in the field of infectious diseases and pediatric solid organ transplant. Recent findings Although many studies contain somewhat small cohorts of individuals, when summarized together they contribute significantly to our knowledge about pediatric solid organ transplant, especially regarding risk factors for infection, management of BK virus nephropathy, the use of live viral vaccines, and consideration for rare infections as well as donor-derived infections. Summary In sum, these recent advances in infection in the field of pediatric solid organ transplant will help decrease infection, thus improving morbidity and mortality, as well as transplant outcomes, especially by decreasing direct (graft injury) and indirect (immune upregulation) effects on organ transplantation. This review will focus on recent advances in the field of infectious diseases in pediatric solid organ transplant by highlighting some of the most important and interesting articles in the field within the past few years. C1 [Kotton, Camille Nelson] Massachusetts Gen Hosp, Div Infect Dis, Transplant Infect Dis & Compromised Host Program, Boston, MA 02114 USA. [Kotton, Camille Nelson] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Kotton, CN (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Transplant Infect Dis & Compromised Host Program, 55 Fruit St,Cox 5, Boston, MA 02114 USA. EM ckotton@partners.org NR 40 TC 4 Z9 4 U1 1 U2 2 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 OCT PY 2008 VL 13 IS 5 BP 500 EP 505 DI 10.1097/MOT.0b013e328310b0a4 PG 6 WC Transplantation SC Transplantation GA 363CN UT WOS:000260243600005 PM 19060533 ER PT J AU Liu, YL Chacko, BK Ricksecker, A Shingarev, R Andrews, E Patel, RP Lang, JD AF Liu, Yuliang Chacko, Balu K. Ricksecker, Ana Shingarev, Roman Andrews, Eric Patel, Rakesh P. Lang, John D., Jr. TI Modulatory effects of hypercapnia on in vitro and in vivo pulmonary endothelial-neutrophil adhesive responses during inflammation SO CYTOKINE LA English DT Article DE Hypercapnia; Neutrophil; Endothelium; Adhesion molecule; Lung injury ID RESPIRATORY-DISTRESS-SYNDROME; INDUCED LUNG INJURY; FACTOR-KAPPA-B; MECHANICAL VENTILATION; ESCHERICHIA-COLI; GENE-EXPRESSION; CELL-ADHESION; INTERLEUKIN-8; ACTIVATION; CYTOKINE AB Reducing tidal volume as a part of a protective ventilation strategy may result in hypercapnia. In this study, we focused on the influence of hypercapnia on endothelial-neutrophil responses in models of inflammatory-stimulated human pulmonary microvascular endothelial cells (HMVEC) and in an animal model of lipopolysaccharide (LPS)-induced acute lung injury. Neutrophil adhesion and adhesion molecules expression and nuclear factor-kappa B (NF-kappa B) were analyzed in TNF-alpha and LPS-treated HMVEC exposed to either eucapnia or hypercapnia. In the in vivo limb, bronchoalveolar lavage fluid cell counts and differentials, adhesion molecule and chemokine expression were assessed in LPS-treated rabbits ventilated with either low tidal volume ventilation and eucapnia or hypercapnia. In both the in vitro and in vivo models, hypercapnia significantly increased neutrophil adhesion and adhesion molecule expression compared to eucapnia. Activity of NF-kappa B was significantly enhanced by hypercapnia in the in vitro experiments. IL-8 expression was greatest both in vitro and in vivo under conditions of hypercapnia and concomitant inflammation. CD11a expression was greatest in isolated human neutrophils exposed to hypercapnia + LPS. Our results demonstrate that endothelial-neutrophil responses per measurement of fundamental molecules of adhesion are significantly increased during hypercapnia and that hypercapnia mimics conditions of eucapnia + inflammation. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Liu, Yuliang; Lang, John D., Jr.] Univ Washington, Sch Med, Dept Anesthesiol, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Ricksecker, Ana] Univ Alabama, Dept Anesthesiol, Birmingham, AL 35294 USA. [Chacko, Balu K.; Patel, Rakesh P.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. [Shingarev, Roman; Andrews, Eric] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. RP Liu, YL (reprint author), Univ Washington, Sch Med, Dept Anesthesiol, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM yuliang6@u.washington.edu OI Patel, Rakesh/0000-0002-1526-4303 FU National Institutes of Health [HL067982] FX This work was supported by a National Institutes of Health Grant, #HL067982 to John D. Lang, Jr., M.D. NR 41 TC 14 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2008 VL 44 IS 1 BP 108 EP 117 DI 10.1016/j.cyto.2008.06.016 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 369NG UT WOS:000260700600018 PM 18713668 ER PT J AU Beuling, E Bosse, T aan de Kerk, DJ Piaseckyj, CM Fujiwara, Y Katz, SG Orkin, SH Grand, RJ Krasinski, SD AF Beuling, Eva Bosse, Tjalling aan de Kerk, Daniel J. Piaseckyj, Christina M. Fujiwara, Yuko Katz, Samuel G. Orkin, Stuart H. Grand, Richard J. Krasinski, Stephen D. TI GATA4 mediates gene repression in the mature mouse small intestine through interactions with friend of GATA (FOG) cofactors SO DEVELOPMENTAL BIOLOGY LA English DT Article DE GATA4; friend of GATA; FOG; intestinal differentiation; apical sodium-dependent; bile acid transporter; ASBT ID BILE-ACID TRANSPORTER; HEPATOCYTE NUCLEAR FACTOR-1-ALPHA; TRANSCRIPTION FACTOR GATA-1; BINDING PROTEIN GENE; ZINC-FINGER PROTEIN; PHLORHIZIN HYDROLASE PROMOTER; HEART TUBE FORMATION; TRANSGENIC MICE; VENTRAL MORPHOGENESIS; TARGETED MUTATION AB GATA4, a transcription factor expressed in the proximal small intestine but not in the distal ileum, maintains proximal-distal distinctions by multiple processes involving gene repression, gene activation, and cell fate determination. Friend of GATA (FOG) is an evolutionarily conserved family of cofactors whose members physically associate with GATA factors and mediate GATA-regulated repression in multiple tissues. Using a novel, inducible, intestine-specific Gata4 knock-in model in mice, in which wild-type GATA4 is specifically inactivated in the small intestine, but a GATA4 mutant that does not bind FOG cofactors (GATA4ki) continues to be expressed, we found that ileal-specific genes were significantly induced in the proximal small intestine (P<0.01); in contrast, genes restricted to proximal small intestine and cell lineage markers were unaffected, indicating that GATA4-FOG interactions contribute specifically to the repression function of GATA4 within this organ. Fog1 mRNA displayed a proximal-distal pattern that parallels that of Gata4, and FOG1 protein was co-expressed with GATA4 in intestinal epithelia[ cells, implicating FOG] as the likely mediator of GATA4 function in the small intestine. Our data are the first to indicate FOG function and expression in the mammalian small intestine. (c) 2008 Elsevier Inc. All rights reserved. C1 [Piaseckyj, Christina M.; Grand, Richard J.; Krasinski, Stephen D.] Childrens Hosp, Div Gastroenterol & Nutr, Dept Med, Boston, MA 02115 USA. [Beuling, Eva; Bosse, Tjalling] Erasmus Univ, Sch Med, NL-3000 DR Rotterdam, Netherlands. [Bosse, Tjalling; aan de Kerk, Daniel J.] Univ Amsterdam, Sch Med, NL-1100 DD Amsterdam, Netherlands. [Fujiwara, Yuko; Katz, Samuel G.; Orkin, Stuart H.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Fujiwara, Yuko; Katz, Samuel G.; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. [Fujiwara, Yuko; Katz, Samuel G.; Orkin, Stuart H.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Krasinski, Stephen D.] Tufts Univ, Gerald J & Dorothy R Friedman Sch Nutr Sci & Poli, Boston, MA 02111 USA. RP Krasinski, SD (reprint author), Childrens Hosp, Div Gastroenterol & Nutr, Dept Med, EN 720,300 Longwood Ave, Boston, MA 02115 USA. EM stephen.krasinski@childrens.harvard.edu OI Bosse, Tjalling/0000-0002-6881-8437 FU Children's Hospital Boston; National Institute of Diabetes and Digestive and Kidney Diseases [R01 -DK-061382, R37-DK-32658]; Harvard Digestive Disease Center [5P30-DK-34854]; Nutricia Research Foundation; De Drie Lichten; Doctor Catharine van Tussenbroek FX We thank Drs. W. T. Pu (Children's Hospital Boston, Boston, MA) for the floxed Gata Mouse line, S. Robine (Institut Curie, Paris, France) for the VillinCreERT2 transgenic mouse line, and P.A. Dawson (Wake Forest School of Medicine, Winson-Salem, NC) for the ASBT antibody. We also thank Lena Liu (Department of Pathology, Children's Hospital Boston, Boston, MA) for the technical support.; This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases Grants R01 -DK-061382 (SDK) and R37-DK-32658 (RJG), the Harvard Digestive Disease Center (5P30-DK-34854), the Nutricia Research Foundation (EB and TB), the Foundation De Drie Lichten (EB) and the Foundation Doctor Catharine van Tussenbroek (EB) in The Netherlands. NR 51 TC 21 Z9 21 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD OCT 1 PY 2008 VL 322 IS 1 BP 179 EP 189 DI 10.1016/j.ydbio.2008.07.022 PG 11 WC Developmental Biology SC Developmental Biology GA 356PL UT WOS:000259790000017 PM 18692040 ER PT J AU Simone, S Gorin, Y Velagapudi, C Abboud, HE Habib, SL AF Simone, Simona Gorin, Yves Velagapudi, Chakradhar Abboud, Hanna E. Habib, Samy L. TI Mechanism of oxidative DNA damage in diabetes - tuberin inactivation and downregulation of DNA repair enzyme 8-oxo-7,8-dihydro-2'-deoxyguanosine-DNA glycosylase SO DIABETES LA English DT Article ID RENAL EPITHELIAL-CELLS; AKT/PROTEIN KINASE-B; HIGH GLUCOSE; PHOSPHOINOSITIDE 3-KINASE; PROTEIN-KINASE; SIGNALING PATHWAYS; MITOCHONDRIAL-DNA; NAD(P)H OXIDASE; SKELETAL-MUSCLE; MESANGIAL CELLS AB OBJECTIVE-To investigate potential mechanisms of oxidative DNA damage in a rat model of type 1 diabetes and in murine proximal tubular epithelial cells and primary culture of rat proximal tubular epithelial cells. RESEARCH DESIGN AND METHODS-Phosphorylation of Akt and tuberin, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) levels, and 8-oxoG-DNA glycosylase (OGG1) expression were measured in kidney cortical tissue of control and type 1 diabetic animals and in proximal tubular cells incubated with normal or high glucose. RESULTS-In the renal cortex of diabetic rats, the increase in Akt phosphorylation is associated with enhanced phosphorylation of tuberin, decreased OGG1 protein expression, and 8-oxodG accumulation. Exposure of proximal tubular epithelial cells to high glucose causes a rapid increase in reactive oxygen species (ROS) generation that correlates with the increase in Akt and tuberin phosphorylation. High glucose also resulted in downregulation of OGG1 protein expression, paralleling its effect on Akt and tuberin. Inhibition of phosphatidylinositol 3-kinase/Akt significantly reduced high glucose-induced tuberin phosphorylation and restored OGG1 expression. Hydrogen peroxide stimulates Akt and tuberin phosphorylation and decreases OGG1 protein expression. The antioxidant N-acetylcysteine significantly inhibited ROS generation, Akt/protein kinase B, and tuberin phosphorylation and resulted in deceased 8-oxodG accumulation and upregulation of OGG1 protein expression. CONCLUSIONS-Hyperglycemia in type 1 diabetes and treatment of proximal tubular epithelial cells with high glucose leads to phosphorylation/inactivation of tuberin and downregulation of OGG1 via a redox-dependent activation of Akt in renal tubular epithelial cells. This signaling cascade provides a mechanism of oxidative stress-mediated DNA damage in diabetes. C1 [Simone, Simona; Gorin, Yves; Velagapudi, Chakradhar; Abboud, Hanna E.; Habib, Samy L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX 78284 USA. [Simone, Simona] Univ Bari, Dept Emergency & Transplantat, Bari, Italy. [Abboud, Hanna E.; Habib, Samy L.] S Texas Vet Healthcare Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. RP Habib, SL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX 78284 USA. EM habib@uthscsa.edu RI Velagapudi, Chakradhar/F-9750-2015; OI Gorin, Yves/0000-0003-4048-6925 FU NIDDK NIH HHS [R37 DK033665, R37-DK-33665] NR 49 TC 43 Z9 44 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD OCT PY 2008 VL 57 IS 10 BP 2626 EP 2636 DI 10.2337/db07-1579 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 360FT UT WOS:000260043800012 PM 18599524 ER PT J AU Jiang, Y Nishimura, W Devor-Henneman, D Kusewitt, D Wang, H Holloway, MP Dohi, T Sabo, E Robinson, ML Altieri, DC Sharma, A Altura, RA AF Jiang, Yuying Nishimura, Wataru Devor-Henneman, Deborah Kusewitt, Donna Wang, Haijuan Holloway, Michael P. Dohi, Takehiko Sabo, Edmond Robinson, Michael L. Altieri, Dario C. Sharma, Arun Altura, Rachel A. TI Postnatal expansion of the pancreatic beta-cell mass is dependent on survivin SO DIABETES LA English DT Article ID ANTI-APOPTOSIS GENE; EXPRESSION; GROWTH; PROLIFERATION; DEATH; DIFFERENTIATION; REPLICATION; INHIBITOR; PROTEINS; CANCER AB OBJECTIVE-Diabetes results from a deficiency of functional beta-cells due to both an increase in beta-cell death and an inhibition of beta-cell replication. The molecular mechanisms responsible for these effects in susceptible individuals are mostly unknown. The objective of this study was to determine whether a gene critical for cell division and cell survival in cancer cells, survivin, might also be important for beta-cells. RESEARCH DESIGN AND METHODS-We generated mice harboring a conditional deletion of survivin in pancreatic endocrine cells using mice with a Pax-6-Cre transgene promoter construct driving tissue-specific expression of Cre-recombinase in these cells. We performed metabolic studies and immunohistochemical analyses to determine the effects of a mono- and biallelic deletion of survivin. RESULTS-Selective deletion of survivin in pancreatic endocrine cells in the mouse had no discernible effects during embryogenesis but was associated with striking decreases in beta-cell number after birth, leading to hyperglycemia and early-onset diabetes by 4 weeks of age. Serum insulin levels were significantly decreased in animals lacking endocrine cell survivin, with relative stability of other hormones. Exogenous expression of survivin in mature beta-cells lacking endogenous survivin completely rescued the hyperglycemic phenotype and the decrease in P-cell mass, confirming the specificity of the survivin effect in these cells. CONCLUSIONS-Our findings implicate survivin in the maintenance of beta-cell mass through both replication and antiapoptotic mechanisms. Given the widespread involvement of survivin in cancer, a novel role for survivin may well be exploited in beta-cell regulation in diseased states, such as diabetes. C1 [Jiang, Yuying; Holloway, Michael P.; Altura, Rachel A.] Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA. [Nishimura, Wataru; Sharma, Arun] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Devor-Henneman, Deborah; Kusewitt, Donna] Ohio State Univ, Dept Vet Biosci, Columbus, OH 43210 USA. [Wang, Haijuan; Holloway, Michael P.; Altura, Rachel A.] Brown Univ, Dept Pediat, Providence, RI 02912 USA. [Dohi, Takehiko; Altieri, Dario C.] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA USA. [Sabo, Edmond] Brown Univ, Dept Pathol & Lab Med, Providence, RI 02912 USA. [Robinson, Michael L.] Miami Univ, Dept Zool, Oxford, OH 45056 USA. RP Altura, RA (reprint author), Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA. EM rachel_altura@brown.edu RI Kusewitt, Donna/E-8107-2011; OI Nishimura, Wataru/0000-0002-8068-1277 FU National Institutes of Health [CA-78810, CA-90917, HL-54131, DK-060127, 1R21-DK-078300-01]; Juvenile Diabetes Research Foundation FX W.N. is a recipient of the Mary K. Iacocca Fellowship. D.C.A. has received National Institutes of Health grants CA-78810, CA-90917, and HL-54131. A.S. has received National Institutes of Health Grant DK-060127. R.A.A. has received support from the Juvenile Diabetes Research Foundation and National Institutes of Health Grant 1R21-DK-078300-01. NR 56 TC 26 Z9 28 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2008 VL 57 IS 10 BP 2718 EP 2727 DI 10.2337/db08-0170 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 360FT UT WOS:000260043800023 PM 18599523 ER PT J AU Kawahara, S Hata, Y Kita, T Arita, R Miura, M Nakao, S Mochizuki, Y Enaida, H Kagimoto, T Goto, Y Hafezi-Moghadam, A Ishibashi, T AF Kawahara, Shuhei Hata, Yasuaki Kita, Takeshi Arita, Ryoichi Miura, Muneki Nakao, Shintaro Mochizuki, Yasutaka Enaida, Hiroshi Kagimoto, Tadahisa Goto, Yoshinobu Hafezi-Moghadam, Ali Ishibashi, Tatsuro TI Potent inhibition of cicatricial contraction in proliferative vitreoretinal diseases by statins SO DIABETES LA English DT Article ID MASSIVE PERIRETINAL PROLIFERATION; PIGMENT EPITHELIAL-CELLS; COLLAGEN GEL CONTRACTION; COA REDUCTASE INHIBITORS; TISSUE GROWTH-FACTOR; RHO-KINASE; EPIRETINAL MEMBRANES; HYALOCYTES; INVOLVEMENT; SIMVASTATIN AB OBJECTIVE-Despite tremendous progress in vitreoretinal surgery, certain postsurgical complications limit the success in the treatment of proliferative vitreoretinal diseases (PVDs), such as proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). One of the most significant complications is the cicatricial contraction of proliferative membranes, resulting in tractional retinal detachment and severe vision loss. Novel pharmaceutical approaches are thus urgently needed for the management of these vision-threatening diseases. In the current study, we investigated the inhibitory effects of statins on the progression of PVDs. RESEARCH DESIGN AND METHODS-Human vitreous concentrations of transforming growth factor-beta 2 (TGF-beta 2) were measured by enzyme-linked immunosorbent assay. TGF-beta 2- and vitreous-dependent phosphorylation of myosin light chain (MLC), a downstream mediator of Rho-kinase pathway, and collagen gel contraction simulating cicatrical contraction were analyzed using cultured hyalocytes. Inhibitory effects of simvastatin on cicatrical contraction were assessed both in vitro and in vivo. RESULTS-Human vitreous concentrations of TGF-beta 2 were significantly higher in the samples from patients with PVD compared with those without PVD. Simvastatin inhibited TGF beta 2-dependent MLC phosphorylation and gel contraction in a dose- and time-dependent manner and was capable of inhibiting translocation of Rho protein to the plasma membrane in the presence of TGF-beta 2. Vitreous samples from patients with PVD enhanced MLC phosphorylation and gel contraction, whereas simvastatin almost completely inhibited these phenomena. Finally, intravitreal injection of simvastatin dose-dependently prevented the progression of diseased states in an in vivo model of PVR. CONCLUSIONS-Statins might have therapeutic potential in the prevention of PVDs. C1 [Kawahara, Shuhei; Hata, Yasuaki; Kita, Takeshi; Arita, Ryoichi; Miura, Muneki; Mochizuki, Yasutaka; Enaida, Hiroshi; Ishibashi, Tatsuro] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, Fukuoka, Japan. [Nakao, Shintaro; Hafezi-Moghadam, Ali] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Kagimoto, Tadahisa] Aqumen Biopharmaceut, Tenjin, Chuo Ku, Fukuoka, Japan. [Goto, Yoshinobu] Int Univ Hlth & Welf Okawa, Fac Rehabil, Dept Occupat Therapy, Fukuoka, Japan. RP Hata, Y (reprint author), Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, Fukuoka, Japan. EM hatachan@med.kyushu-u.ac.jp OI Hafezi-Moghadam, Ali/0000-0002-5336-0697 FU Bausch Lomb; Japan Eye Bank Association; National Institutes of Health [AI050775, HL086933]; Ministry of Education, Science, Sports and Culture, Japan [19592026, 18791283, 18591925]; National Eye Institute Core [EY14104]; Massachusetts Lions Eye Research Fund; Edward F. Knight Age-Related and Macular Degeneration Fund; Research to Prevent Blindness FX S.N. has received a Research Fellowship Award from Bausch & Lomb and a Fellowship Award from the Japan Eye Bank Association. A.H.-M. has received National Institutes of Health Grants AI050775 and HL086933. This study has received Grants-in-Aid for Scientific Research 19592026, 18791283, and 18591925 from the Ministry of Education, Science, Sports and Culture, Japan; National Eye Institute Core Grant EY14104; and support from the Massachusetts Lions Eye Research Fund, the Marion W. and Edward F. Knight Age-Related and Macular Degeneration Fund, and Research to Prevent Blindness. NR 50 TC 31 Z9 37 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 OCT PY 2008 VL 57 IS 10 BP 2784 EP 2793 DI 10.2337/db08-0302 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 360FT UT WOS:000260043800031 PM 18599521 ER PT J AU Musen, G Jacobson, AM Ryan, CM Cleary, PA Waberski, BH Weinger, K Dahms, W Bayless, M Silvers, N Harth, J White, N AF Musen, Gail Jacobson, Alan M. Ryan, Christopher M. Cleary, Patricia A. Waberski, Barbara H. Weinger, Katie Dahms, William Bayless, Meg Silvers, Nancy Harth, Judith White, Neil CA DCCT EDIC Res Grp TI Impact of Diabetes and Its Treatment on Cognitive Function Among Adolescents Who Participated in the Diabetes Control and Complications Trial SO DIABETES CARE LA English DT Article ID SEVERE HYPOGLYCEMIA; CHILDREN; INTERVENTIONS; EPIDEMIOLOGY; MELLITUS; ONSET AB OBJECTIVE - The purpose of this study was to evaluate whether severe hypoglycemia or intensive therapy affects cognitive performance over time in a subgroup of patients who were aged 13-19 years at entry in the Diabetes Control and Complications Trial (DCCT). RESEARCH DESIGN AND METHODS - This was a longitudinal Study involving 249 patients with type I diabetes who were between 13 and 19 years old when they were randomly assigned in the DCCT. Scores on a comprehensive battery of cognitive tests obtained during the Epidemiology of Diabetes Interventions and Complications follow-up study, similar to 18 years later, were compared with baseline performance. We assessed the effects of the original DCCT treatment. group assignment, mean A1C values, and frequency of severe hypoglycemic events on eight domains of cognition. RESULTS - There were a total of 294 reported episodes of coma or seizure. Neither frequency of hypoglycemia nor previous treatment group was associated with decline on any cognitive domain. As in a previous analysis of the entire study cohort, higher A1C values were associated with declines in the psychomotor and mental efficiency domain (P < 0.01); however, the previous finding of improved motor speed with lower A1C values was not replicated in this subgroup analysis. CONCLUSIONS - Despite relatively high rates of severe hypoglycemia, cognitive function did not decline over an extended period of time in the youngest cohort of patients with type I diabetes. C1 [Musen, Gail; Jacobson, Alan M.; Weinger, Katie] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Ryan, Christopher M.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Cleary, Patricia A.; Waberski, Barbara H.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Dahms, William] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Bayless, Meg] Univ Iowa, Coll Med, Iowa City, IA USA. [Silvers, Nancy] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Harth, Judith] Univ Western Ontario, Schulich Sch Med, London, ON, Canada. [White, Neil] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. RP Musen, G (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. EM gail.musen@joslin.harvard.edu FU National Instiute of Diabetes and Digestive and Kidney Diseases [5 R01 DK062218-02]; General Clinical Research Centers Program; National Center for Research Resources; Herbert Graetz Psychosocial Research Fund FX Funding for this study was provided by grant 5 R01 DK062218-02 from the National Instiute of Diabetes and Digestive and Kidney Diseases and by contracts with the Division of Diabetes, Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases, the General Clinical Research Centers Program, National Center for Research Resources, and the Herbert Graetz Psychosocial Research Fund. NR 25 TC 51 Z9 53 U1 1 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2008 VL 31 IS 10 BP 1933 EP 1938 DI 10.2337/dc08-0607 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 360FR UT WOS:000260043600002 PM 18606979 ER PT J AU Pani, LN Korenda, L Meigs, JB Driver, C Chamany, S Fox, CS Sullivan, L D'Agostino, RB Nathan, DM AF Pani, Lydir N. Korenda, Leslie Meigs, James B. Driver, Cynthia Chamany, Shadi Fox, Caroline S. Sullivan, Lisa D'Agostino, Ralph B. Nathan, David M. TI Effect of Aging on A1C Levels in Individuals Without Diabetes SO DIABETES CARE LA English DT Article ID GLYCATED HEMOGLOBIN; GLYCOSYLATED HEMOGLOBIN; SEVERE HYPOGLYCEMIA; HBA(1C); AGE; POPULATION; DIAGNOSIS; MELLITUS; GLYCOHEMOGLOBIN; DISEASE AB OBJECTIVE - Although glycemic levels are known to rise with normal aging, the nondiabetic A1C range is not age specific. We examined whether A1C was associated with age in nondiabetic subjects and in subjects with normal glucose tolerance (NGT) in two population-based cohorts. RESEARCH DESIGN AND METHODS - We performed cross-sectional analyses 01 A1C across age categories in 2,473 nondiabetic participants of the Framingham Offspring Study (FOS) and in 3,270 nondiabetic participants from the National Health and Nutrition Examination Survey (NHANES) 2001-2004. In FOS, we examined A1C by age in a subset With NGT, i.e., after excluding those With impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Multivariate analyses were performed, adjusting for sex, BMI, fasting glucose, and 2-h postload glucose values. RESULTS- In the FOS and NHANES cohorts, A1C levels were positively associated with age in nondiabetic subjects. Linear regression revealed 0.014- and 0.010-unit increases in A1C per year in the nondiabetic FOS and NHANES populations, respectively. The 97.5th percentiles for A1C were 6.0% and 5.6% for nondiabetic individuals aged < 40 years in FOS and NHANES, respectively, compared With 6.6% and 6.2% for individuals aged >= 70 years (P-trend < 0.001). The association of A1C With age was similar when restricted to the subset of FOS Subjects With NGT and after adjustments for sex, BMI, lasting glucose, and 2-h postload glucose values. CONCLUSIONS- A1C levels are positively associated with age in nondiabetic populations even after exclusion of subjects With IFG and/or IGT. Further Studies are needed to determine whether age-specific diagnostic and treatment criteria would be appropriate. C1 [Pani, Lydir N.; Meigs, James B.; Nathan, David M.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Pani, Lydir N.; Meigs, James B.; Nathan, David M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Pani, Lydir N.; Meigs, James B.; Nathan, David M.] Harvard Univ, Sch Med, Boston, MA USA. [Korenda, Leslie; Driver, Cynthia; Chamany, Shadi] Dept Hlth & Mental Hyg, New York, NY USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol Metab & Hypertens, Boston, MA 02115 USA. [Sullivan, Lisa; D'Agostino, Ralph B.] Boston Univ, Dept Biostat, Boston, MA 02215 USA. RP Pani, LN (reprint author), Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. EM lpani@partners.org FU National Heart, Lung and Blood Institute's Framingham Heart Study (National Heart, Lung and Blood Institute/National Institutes of Health) [N01-HC-25195]; Boston University School of Medicine; American Diabetes Association Career Development Award; National Institute of Diabetes and Digestive and Kidney Diseases [K24 DK080140]; Earl P. Charlton Fund for Innovative Diabetes Research; National Research Service Award [T32] FX This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (National Heart, Lung and Blood Institute/National Institutes of Health Contract N01-HC-25195) and Boston University School of Medicine. J.B.M. is supported by an American Diabetes Association Career Development Award and National Institute of Diabetes and Digestive and Kidney Diseases Grant K24 DK080140D.M.N. is supported in part by the Earl P. Charlton Fund for Innovative Diabetes Research. L.P. is supported by an institutional National Research Service Award (T32).; We thank Peter Shrader and Sharon Saydah for assistance with Statistical analyses. For contribution to the study, we thank Deborah Wexler, Diana Berger, Randie Little, Eran Bellin, and Curt Rohlfing. NR 33 TC 141 Z9 157 U1 0 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2008 VL 31 IS 10 BP 1991 EP 1996 DI 10.2337/dc08-0577 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 360FR UT WOS:000260043600013 PM 18628569 ER PT J AU Lopes-Virella, MF Carter, RE Gilbert, GE Klein, RL Jaffa, M Jenkins, AJ Lyons, TJ Garvey, WT Virella, G AF Lopes-Virella, Maria F. Carter, Rickey E. Gilbert, Gregory E. Klein, Richard L. Jaffa, Miran Jenkins, Alicia J. Lyons, Timothy J. Garvey, W. Timothy Virella, Gabriel CA DCCT EDIC Cohort Study Grp TI Risk Factors Related to Inflammation and Endothelial Dysfunction in the DCCT/EDIC Cohort and Their Relationship With Nephropathy and Macrovascular Complications SO DIABETES CARE LA English DT Article ID TYPE-1 DIABETIC-PATIENTS; INTIMA-MEDIA THICKNESS; C-REACTIVE PROTEIN; LOW-GRADE INFLAMMATION; ADHESION MOLECULE-1; CLINICAL-EVIDENCE; PLASMA MARKERS; MELLITUS; ASSOCIATION; PROGRESSION AB OBJECTIVE - Because endothelial cell dysfunction and inflammation are key contributors to the development of complications in type 1 diabetes, we studied risk factors related to endothelial dysfunction and inflammation (C-reactive protein and fibrinogen, soluble vascular cell adhesion molecule-1, intracellular adhesion molecule-1 , and E-selectin, and fibrinolytic markers) in a subgroup) Of patients from the Diabetes Control and Complications Trial (DCCT)/Epidemiology, of Diabetes Intervention and Complications (EDIC) Study cohort. RESEARCH DESIGN AND METHODS - We determined which of these risk factors or clusters thereof -,ire associated with the presence of and Subsequent development of nephropathy and macrovascular complications (reflected by carotid intima-media thickness [IMT]). RESULTS - After adjustment for conventional risk factors (age, sex, DCCT treatment group, diabetes duration, A1C, systolic blood pressure, waist-to-hip ratio, total and HDL cholesterol,a nd smoking status), fibrinogen remained strongly associated with progression of internal and common carotid IMT (P < 0.01) and soluble E-selectin had a strong association with nephropathy (P < 0.01). CONCLUSIONS - The best predictor for IMT progression in the DCCT/EDIC cohort was plasma fibrinogen, and the levels of soluble E-selectin discriminate patients with albuminuria better than conventional risk factors. C1 [Lopes-Virella, Maria F.; Klein, Richard L.; Jenkins, Alicia J.; Lyons, Timothy J.; Garvey, W. Timothy] Med Univ S Carolina, Dept Med & Lab Serv, Charleston, SC 29425 USA. [Lopes-Virella, Maria F.; Klein, Richard L.; Jenkins, Alicia J.; Lyons, Timothy J.; Garvey, W. Timothy] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Carter, Rickey E.; Gilbert, Gregory E.; Jaffa, Miran] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. [Jenkins, Alicia J.; Lyons, Timothy J.] Univ Oklahoma, Hlth Sci Ctr, Endocrinol Sect, Oklahoma City, OK USA. [Garvey, W. Timothy] Univ Alabama, Dept Nutr, Birmingham, AL USA. [Virella, Gabriel] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP Lopes-Virella, MF (reprint author), Med Univ S Carolina, Dept Med & Lab Serv, Charleston, SC 29425 USA. EM virellam@musc.edu RI Gilbert, Gregory/C-7735-2016 OI Gilbert, Gregory/0000-0003-0879-5496 FU Merit Review Program of the Department of Veterans Affairs; National Institutes of Health and Juvenile Diabetes Research Foundation [PO1 HL55782]; National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health FX This research was supported by funding of the Merit Review Program of the Department of Veterans Affairs and by joint funding of the National Institutes of Health and Juvenile Diabetes Research Foundation (PO1 HL55782). The DCCT/EDIC Research Group is sponsored through research contracts from the National Institute of Diabetes, Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institutes of Health.; The technical assistance of Charlyne Chassereau, Andrea Semler, and Karma Moller and efforts of stud), coordinators jenny Smith, Leslie Nicholson, Marlene Brabham, and Erica Hood are gratefully acknowledged. Finally, the authors are grateful to the patients in the DCCT/EDIC cohort for their long-term participation in this important trial. NR 25 TC 53 Z9 55 U1 0 U2 2 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 OCT PY 2008 VL 31 IS 10 BP 2006 EP 2012 DI 10.2337/dc08-0659 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 360FR UT WOS:000260043600017 PM 18628568 ER PT J AU Huang, JM Karakucuk, V Levitsky, LL Rhoads, DB AF Huang, Jianmin Karakucuk, Vildan Levitsky, Lynne L. Rhoads, David B. TI Expression of HNF4 alpha variants in pancreatic islets and Ins-1 beta cells SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Article DE hormone nuclear receptor; alternative splicing; transcriptional activity ID NUCLEAR FACTOR 4; TRANSCRIPTION FACTOR; GENE-EXPRESSION; DIABETES-MELLITUS; MISSENSE MUTATION; INSULIN-RELEASE; FACTOR 4-ALPHA; MESSENGER-RNA; MOUSE-LIVER; HNF-4 GENE AB Background Hepatocyte nuclear factor (HNF4 alpha) is a nuclear receptor essential for endodermal differentiation and cell functions in the adult pancreas, liver, and other tissues. Mutations in the HNF4A gene cause MODY1. Up to nine protein variants arise from two developmentally regulated promoters. Because some variants lack the N-terminal activation function 1 (AF-1) and/or C-terminal inhibitory F domain, defining their tissue-specific regulation and function is important for understanding pancreatic cell behaviour. Methods Expression of HNF4 alpha. variants in islets, rat Ins-1 insulinoma cells, and human Hep3B hepatocellular carcinoma cells was assessed using a long-range reverse transcription-polymerase chain reaction (RT-PCR) strategy capable of recognizing each combination of mRNA termini. Protein expression was verified by immuno-blotting with terminus-specific antibodies and DNA-binding assays. Results Mouse islets and both cell lines express HNF4 alpha 9, which lacks both AF-1 and the F domain. Islets also expressed the HNF4 alpha PI promoter variants HNF4 alpha 1/alpha 2, and Hep3B cells expressed HNF4 alpha 3. When ectopically expressed in COS-7 cells, HNF4 alpha 1, alpha 3, alpha 7, and alpha 9 each stimulated an HNF4 alpha-dependent promoter. Variants containing exon 1B (HNF4 alpha 4 - alpha 6) were not detected. Lack of canonical splicing signals and species conservation argues against exon 1B usage. Conclusions This is the first report of HNF4 alpha 9 expression in any tissue. Our findings extend our understanding of HNF4 alpha gene transcription and function. This knowledge may be useful in efforts to recover or establish regulated insulin secretion. Copyright (c) 2008 John Wiley & Sons, Ltd. C1 [Rhoads, David B.] MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Rhoads, DB (reprint author), MassGen Hosp Children, Pediat Endocrine Unit, 55 Fruit St,BHX410, Boston, MA 02114 USA. EM rhoads@helix.mgh.harvard.edu FU American Diabetes Association Research [7-0S-RA-121]; Diabetes Action Research & Education Foundation [204]; Nicholas Dulong Diabetes Research Fund (LLL) FX We appreciate reagent gifts from FM Sladek, W Hwa ng-Verslues, R Cortese, CB Wollheim, MK Thomas, and V Stanojevic. We thank D DuGuerre and L Zhang for technical assistance, A Torjesen for assistance constructing plasmids, AK Leonberg for a critical reading, and a peer reviewer for very insightful and thorough comments. We are grateful to the islet Cell Resource Centers of the University of Minnesota and the University of Alabama for providing human islets.; This study was supported by American Diabetes Association Research Grant 7-0S-RA-121 (DBR), Diabetes Action Research & Education Foundation Grant #204 (DBR), and the Nicholas Dulong Diabetes Research Fund (LLL). NR 50 TC 5 Z9 6 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD OCT PY 2008 VL 24 IS 7 BP 533 EP 543 DI 10.1002/dmrr.870 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 364YM UT WOS:000260371700003 PM 18561282 ER PT J AU Akashi, T Shigematsu, H Hamamoto, Y Iwasaki, H Yatoh, S Bonner-Weir, S Akashi, K Weir, GC AF Akashi, Tomoyuki Shigematsu, Hirokazu Hamamoto, Yoshiyuki Iwasaki, Hiromi Yatoh, Shigeru Bonner-Weir, Susan Akashi, Koichi Weir, Gordon C. TI Bone marrow or foetal liver cells fail to induce islet regeneration in diabetic Akita mice SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Article DE diabetes; islets; beta-cells; bone marrow; foetal liver; regeneration ID PANCREATIC BETA-CELLS; INSULIN-PRODUCING CELLS; MESENCHYMAL STEM-CELLS; IN-VIVO; TRANSCRIPTION FACTORS; PROGENITOR CELLS; GENE-EXPRESSION; MUTANT MICE; REVERSAL; TRANSPLANTATION AB Background In this study, we carried out bone marrow and foetal liver cell transplantation to determine if these cells could differentiate into pancreatic beta-cells or promote regeneration. Methods To exclude an artificial or immunological influence for induction of diabetes to recipients, Akita mice, which develop diabetes spontaneously,were used. In addition, we used mice harbouring the transgenic green fluorescent protein (GFP) reporter for insulin I gene as donors to mark donor-derived beta-cells. Results All transplanted Akita mice after intravenous injection showed full donor chimerism in peripheral blood analysis. Their diabetic state represented by blood glucose levels did not change after transplantation. In spite of examination of more than 200 islets in each group, we could not find GFP-positive cells in any of the recipients. Conclusions Bone marrow cells or foetal liver cells do not differentiate to new pancreatic beta-cells or promote regeneration in Akita mice, a non-chemical or non-immune model of diabetes. Copyright (c) 2008 John Wiley & Sons, Ltd. C1 [Akashi, Tomoyuki; Hamamoto, Yoshiyuki; Yatoh, Shigeru; Bonner-Weir, Susan; Weir, Gordon C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. [Shigematsu, Hirokazu; Iwasaki, Hiromi; Akashi, Koichi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Weir, GC (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM gordon.weir@joslin.harvard.edu OI Bonner-Weir, Susan/0000-0003-4682-0656 FU National Institute of Health [U19DK6125]; Juvenile Diabetes Research Foundation; Diabetes Research and Wellness Foundation; National Institutes of Health [P30 DK36836]; Manpei Suzuki Diabetes Foundation FX This study was supported by grants from the National Institute of Health (U19DK6125), the Juvenile Diabetes Research Foundation, the Diabetes Research and Wellness Foundation and an important group of private donors. Help was also provided by the Advanced Microscopy Core of the Diabetes Endocrinology Research Center (DERC) of Joslin supported by the National Institutes of Health (P30 DK36836). S.Y. was the recipient of a fellowship from Manpei Suzuki Diabetes Foundation. NR 37 TC 9 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD OCT PY 2008 VL 24 IS 7 BP 585 EP 590 DI 10.1002/dmrr.884 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 364YM UT WOS:000260371700010 PM 18727153 ER PT J AU Hirsch, IB Abelseth, J Bode, BW Fischer, JS Kaufman, FR Mastrototaro, J Parkin, CG Wolpert, HA Buckingham, BA AF Hirsch, Irl B. Abelseth, Jill Bode, Bruce W. Fischer, Jerome S. Kaufman, Francine R. Mastrototaro, John Parkin, Christopher G. Wolpert, Howard A. Buckingham, Bruce A. TI Sensor-augmented insulin pump therapy: Results of the first randomized treat-to-target study SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID BLOOD-GLUCOSE; INFUSION; IMPROVEMENT; TRIAL AB Background: The objective of the study was to evaluate the clinical effectiveness and safety of a device that combines an insulin pump with real-time continuous glucose monitoring (CGM), compared to using an insulin pump with standard blood glucose monitoring systems. Methods: This 6-month, randomized, multicenter, treat-to-target study enrolled 146 subjects treated with continuous subcutaneous insulin infusion between the ages of 12 and 72 years with type 1 diabetes and initial A1C levels of >= 7.5%. Subjects were randomized to pump therapy with real-time CGM (sensor group [SG]) or to pump therapy and self-monitoring of blood glucose only (control group [CG]). Clinical effectiveness and safety were evaluated. Results: A1C levels decreased (P < 0.001) from baseline (8.44 +/- 0.70%) in both groups (SG, -0.71 +/- 0.71%; CG, -0.56 +/- 0.072%); however, between-group differences did not achieve significance. SG subjects showed no change in mean hypoglycemia area under the curve (AUC), whereas CG subjects showed an increase (P = 0.001) in hypoglycemia AUC during the blinded periods of the study. The between-group difference in hypoglycemia AUC was significant (P < 0.0002). Greater than 60% sensor utilization was associated with A1C reduction (P = 0.0456). Fourteen severe hypoglycemic events occurred (11 in the SG group and three in the CG group, P = 0.04). Conclusions: A1C reduction was no different between the two groups. Subjects in the CG group had increased hypoglycemia AUC and number of events during blinded CGM use; however, there was no increase in hypoglycemia AUC or number of events in the SG group. Subjects with greater sensor utilization showed a greater improvement in A1C levels. C1 [Hirsch, Irl B.] Univ Washington, St Lukes Roosevelt Med Ctr, Seattle, WA 98105 USA. [Abelseth, Jill] Endocrine Grp LLP, Albany, NY USA. [Bode, Bruce W.] Atlanta Diabet Associates, Atlanta, GA USA. [Fischer, Jerome S.] Diabet & Glandular Dis Clin San Antonio, San Antonio, TX USA. [Kaufman, Francine R.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Mastrototaro, John] Medtron Minimed, Northridge, CA USA. [Parkin, Christopher G.] CGParkin Commun Inc, Carmel, IN USA. [Wolpert, Howard A.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Buckingham, Bruce A.] Stanford Univ, Dept Pediat Endocrinol, Stanford, CA 94305 USA. RP Hirsch, IB (reprint author), Univ Washington, St Lukes Roosevelt Med Ctr, 4225 Roosevelt Way NE,Suite 101,Box 354691, Seattle, WA 98105 USA. EM ihirsch@u.washington.edu FU Medtronic, Inc FX This research was supported by a grant from Medtronic, Inc. NR 14 TC 133 Z9 135 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD OCT PY 2008 VL 10 IS 5 BP 377 EP 383 DI 10.1089/dia.2008.0068 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 347YL UT WOS:000259177600007 PM 18715214 ER PT J AU Frayling, TM Colhoun, H Florez, JC AF Frayling, T. M. Colhoun, H. Florez, J. C. TI A genetic link between type 2 diabetes and prostate cancer - Commentary SO DIABETOLOGIA LA English DT Editorial Material DE epidemiology; genes; genome-wide association study; pleiotropy; prostate cancer; transcription factors; type 2 diabetes ID GENOME-WIDE ASSOCIATION; METABOLIC SYNDROME; REDUCED RISK; US MEN; VARIANTS; MELLITUS; MUTATIONS; MULTIPLE; LOCI; SUSCEPTIBILITY AB Epidemiological studies suggest that men with type 2 diabetes are less likely than non-diabetic men to develop prostate cancer. The cause of this association is not known. Recent genetic studies have highlighted a potential genetic link between the two diseases. Two studies have identified a version (allele) of a variant in the HNF1B (also known as TCF2) gene that predisposes to type 2 diabetes, and one of them showed that the same allele protects men from prostate cancer. Other, separate, studies have identified different variants in the JAZF1 gene, one associated with type 2 diabetes, another associated with prostate cancer. These findings are unlikely to completely explain the epidemiological association between the two diseases but they provide new insight into a possible direct causal link, rather than one that is confounded or biased in some way. C1 [Frayling, T. M.] Univ Exeter, Peninsula Coll Med & Dent, Exeter EX1 2LU, Devon, England. [Colhoun, H.] Univ Dundee, Dundee, Scotland. [Florez, J. C.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Florez, J. C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Frayling, TM (reprint author), Univ Exeter, Peninsula Coll Med & Dent, Magdalen Rd, Exeter EX1 2LU, Devon, England. EM Tim.frayling@pms.ac.uk NR 29 TC 52 Z9 52 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD OCT PY 2008 VL 51 IS 10 BP 1757 EP 1760 DI 10.1007/s00125-008-1114-9 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 344WQ UT WOS:000258958400001 PM 18696045 ER PT J AU Gonzalez, JS Delahanty, LM Safren, SA Meigs, JB Grant, RW AF Gonzalez, J. S. Delahanty, L. M. Safren, S. A. Meigs, J. B. Grant, R. W. TI Differentiating symptoms of depression from diabetes-specific distress: relationships with self-care in type 2 diabetes SO DIABETOLOGIA LA English DT Article DE adherence; depression; diabetes-specific distress; self-care; self-management; type 2 diabetes AB Aims/hypothesis The aim of this study was to examine the relationship between depressive symptoms and diabetes-specific distress and the independent relationships of each of these factors with diabetes self-care. We expected that symptoms of depression would be associated with poorer diabetes self-care, independent of diabetes-specific distress. Methods We surveyed 848 primary care patients with type 2 diabetes using the Harvard Department of Psychiatry/National Depression Screening Day Scale (HANDS), Problem Areas in Diabetes scale (PAID), Summary of Diabetes Self-Care Activities, and self-reported medication adherence. Results The PAID and HANDS scores were positively correlated in the overall sample (r=0.54, p < 0.0001), among those who did not meet diagnostic criteria for major depressive disorder (MDD) based on the HANDS screening result (n=685; r=0.36, p < 0.001) and in patients who did meet the screening criteria for MDD (n=163; r=0.36, p < 0.001). Higher PAID scores significantly predicted lower levels of diet, exercise and medication adherence (all p values < 0.05). However, once depression symptom scores were entered into these models, most relationships were reduced to non-significance, while the HANDS score retained significant relationships with most indices of diabetes self-care. The same pattern of results was found in the subset of patients who did not screen positive for MDD. Conclusions/interpretation These results suggest that specific symptoms of depression have a greater negative relationship with diabetes self-care than diabetes-specific distress, even among those patients who do not meet screening criteria for MDD. Interventions that focus on improving the management of specific symptoms of depression may be more effective in improving self-care than those that focus on reducing distress. C1 [Gonzalez, J. S.; Safren, S. A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Gonzalez, J. S.; Delahanty, L. M.; Safren, S. A.; Meigs, J. B.; Grant, R. W.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Delahanty, L. M.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Meigs, J. B.; Grant, R. W.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. RP Gonzalez, JS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, One Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM jsgonzalez@partners.org OI Grant, Richard/0000-0002-6164-8025 FU National Institute of Mental Health [1R01MH078571]; American Diabetes Association Career Development Award; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [K24 DK080140, K23 DK067452]; GlaxoSmithKline FX J. S. Gonzalez's and S. A. Safren's efforts on this manuscript were supported by a grant from the National Institute of Mental Health (no. 1R01MH078571). J. B. Meigs was supported by an American Diabetes Association Career Development Award and by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant no. K24 DK080140. J. B. Meigs currently has research grants from GlaxoSmithKline and sanofi-aventis, and consults for GlaxoSmithKline, sanofi-aventis, Interleukin Genetics, Kalypsis and Outcomes Science. R. W. Grant is supported by a Career Development Award (no. K23 DK067452) from the NIDDK. NR 9 TC 39 Z9 42 U1 4 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD OCT PY 2008 VL 51 IS 10 BP 1822 EP 1825 DI 10.1007/s00125-008-1113-x PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 344WQ UT WOS:000258958400011 PM 18690422 ER PT J AU Baddley, JW Sankara, IR Rodriquez, JM Pappas, PG Many, WJ AF Baddley, John W. Sankara, Ishwara R. Rodriquez, J. Martin Pappas, Peter G. Many, Wickliffe J., Jr. TI Histoplasmosis in HIV-infected patients in a Southern regional medical center: poor prognosis in the era of highly active antiretroviral therapy SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE Histoplasma capsulatum; HIV; histoplasmosis; mortality ID HUMAN-IMMUNODEFICIENCY-VIRUS; RISK-FACTORS; DIAGNOSIS; BRAZIL AB Histoplasmosis is an important opportunistic infection among HIV-infected patients in endemic areas, and clinical outcomes are often poor. Additional data on factors associated with outcomes are needed to better identify patients who may require aggressive care. Using a cohort of 46 HIV-infected patients with histoplasmosis from an underserved city endemic for histoplasmosis, we explored epidemiology, outcomes, and prognostic factors. Histoplasmosis was the 1st recognized manifestation of HIV Infection in 12 (26.1%) of 46 patients. Death occurred in IS (39%) patients within 3 months of diagnosis of histoplasmosis. Fungemia (odds ratio [OR], 12. 1; 95% confidence interval [0], 1.9-76; P = 0.008), renal insufficiency (OR, 11.3; 95% Cl, 1.7-77.2; P = 0.01), and age (OR, 0.9; 95% CI, 0.8-0.98; P = 0.02) were independent predictors of poor prognosis. Histoplasmosis in HIV patients is associated with poor outcomes. Identification of prognostic factors may be helpful in identifying patients who require more aggressive care. Published by Elsevier Inc. C1 [Baddley, John W.; Pappas, Peter G.] Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. [Baddley, John W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35322 USA. [Sankara, Ishwara R.; Rodriquez, J. Martin; Many, Wickliffe J., Jr.] UAB Hlth Ctr Montgomery, Dept Med, Montgomery, AL 36116 USA. RP Baddley, JW (reprint author), Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. EM jbaddley@uab.edu NR 13 TC 24 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD OCT PY 2008 VL 62 IS 2 BP 151 EP 156 DI 10.1016/j.diagmicrobio.2008.05.006 PG 6 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 356SG UT WOS:000259797300005 PM 18597967 ER PT J AU Leung, FW AF Leung, Felix W. TI Risk factors for gastrointestinal complications in aspirin users: Review of clinical and experimental data SO DIGESTIVE DISEASES AND SCIENCES LA English DT Review DE aspirin; stomach; NSAID; smoking; alcohol; nitric oxide; nitroglycerin ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; LOW-DOSE ASPIRIN; PROTON PUMP INHIBITORS; INDUCED GASTRIC-ULCERS; NITRIC-OXIDE-DONORS; MUCOSAL BLOOD-FLOW; FIBROBLAST-GROWTH-FACTOR; TOBACCO CIGARETTE-SMOKE; ACETIC-ACID ULCERS; PEPTIC-ULCER AB This paper reviews recent clinical evidence that suggests that aspirin prophylaxis against cardiac and cerebral vascular ischemia is associated with significant gastrointestinal complications. The clinical and experimental evidence to confirm the role of risk factors of concomitant use of nonsteroidal anti-inflammatory drugs (NSAID), tobacco cigarette smoking, and alcohol consumption are discussed. The limitations of long-term acid suppression treatment for the prevention of these complications are considered. Future experimental studies to guide the clinical approach to develop novel and potentially cost-effective management strategies are discussed. C1 [Leung, Felix W.] VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Div Gastroenterol Res & Med Serv, Sepulveda, CA 91343 USA. [Leung, Felix W.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Leung, FW (reprint author), VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Div Gastroenterol Res & Med Serv, 111G,16111 Plummer St, Sepulveda, CA 91343 USA. EM felix.leung@va.gov FU VA Medical Research Funds FX This work was supported in part by VA Medical Research Funds. NR 102 TC 4 Z9 6 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 2008 VL 53 IS 10 BP 2604 EP 2615 DI 10.1007/s10620-007-0178-6 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 343DV UT WOS:000258833800003 PM 18306040 ER PT J AU Rosman, AS Chaparala, G Monga, A Spungen, AM Bauman, WA Korsten, MA AF Rosman, Alan S. Chaparala, Geeta Monga, Amit Spungen, Ann M. Bauman, William A. Korsten, Mark A. TI Intramuscular neostigmine and glycopyrrolate safely accelerated bowel evacuation in patients with spinal cord injury and defecatory disorders SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE bowel care; difficulty with evacuation; glycopyrrolate; neostigmine; spinal cord injury ID ACUTE COLONIC PSEUDOOBSTRUCTION; INTRANASAL NEOSTIGMINE; MYASTHENIA-GRAVIS; ATROPINE; CARE AB Difficulty with evacuation after spinal cord injury (SCI) may be due to a lack of parasympathetic stimulation of the colon. Prior studies in persons with spinal cord injury have suggested that intravenous administration of neostigmine stimulates colonic motility while glycopyrrolate attenuates some of the cholinergic side effects of neostigmine. We thus performed a double-blind, cross-over study to evaluate the effect of neostigmine/glycopyrrolate injections in patients with SCI and defecatory difficulties. Seven subjects received active treatment (neostigmine 2 mg and glycopyrrolate 0.4 mg intramuscularly) during three consecutive bowel evacuation sessions and were crossed-over to placebo injections for three consecutive sessions. Compared with placebo, neostigmine/glycopyrrolate reduced the total bowel evacuation time from 98.1 +/- 7.2 to 74.8 min +/- 5.8 (p < 0.05). The lowest heart rate or blood pressure was not significantly different between the treatment and placebo groups. In conclusion, neostigmine/glycopyrrolate may improve bowel evacuation in patients with SCI-related defecatory disorders. C1 [Rosman, Alan S.; Korsten, Mark A.] James J Peters VA Med Ctr, Gastroenterol Practice & Spinal Cord Ctr Excellen, Bronx, NY 10468 USA. [Chaparala, Geeta; Monga, Amit; Spungen, Ann M.; Bauman, William A.] James J Peters VA Med Ctr, Spinal Cord Ctr Excellence, Bronx, NY 10468 USA. [Rosman, Alan S.; Chaparala, Geeta; Monga, Amit; Spungen, Ann M.; Bauman, William A.; Korsten, Mark A.] NYU, Mt Sinai Sch Med, New York, NY USA. RP Korsten, MA (reprint author), James J Peters VA Med Ctr, Gastroenterol Practice & Spinal Cord Ctr Excellen, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Mark.Korsten@VA.gov NR 18 TC 17 Z9 18 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 2008 VL 53 IS 10 BP 2710 EP 2713 DI 10.1007/s10620-008-0216-z PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 343DV UT WOS:000258833800018 PM 18338263 ER PT J AU Leung, FW AF Leung, Felix W. TI Unsedated colonoscopy introduced to ensure access is acceptable to a subgroup of veterans SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE unsedated colonoscopy; access; trainee; nursing shortage ID FLEXIBLE SIGMOIDOSCOPY; SEDATION; ENDOSCOPY; INTUBATION; SKILLS AB Background Nurses for monitoring and recovery are required for sedated colonoscopy. A nursing shortage necessitated discontinuation of sedated colonoscopy at a VA academic training program. Aim Elements of a case series that documented acceptance of unsedated colonoscopy are reviewed to raise awareness of the feasibility of this option. Method The pros and cons of sedation and no sedation were summarized. After discussion, patients who chose the unsedated option were scheduled for examination locally while those who desired sedation were scheduled at another VA site. Colonoscopy was performed by supervised trainees. Results From September 2002 to June 2005 scheduled unsedated colonoscopy was accepted by 145 of 483 veterans. Cecal intubation was achieved in 81%. Thus, of the cohort 30% had local access to and 24% completed unsedated colonoscopy. Implementation of unsedated colonoscopy obviated the need for two registered nurses previously required for sedated colonoscopy. Conclusion Unsedated colonoscopy offered as an option to ensure access was acceptable to a subgroup of our veteran patients. Implementation required less nursing resources. Techniques to enhance the cecal intubation rate of unsedated colonoscopy performed by supervised trainees deserves to be assessed in future studies. C1 [Leung, Felix W.] Univ Calif Los Angeles, David Geffen Sch Med, VAGLAHS, Sepulveda Ambulatory Care Ctr,Div Gastroenterol, Sepulveda, CA 91343 USA. [Leung, Felix W.] Vet Affairs Greater Los Angeles Healthcare Syst, W Los Angeles Vet Affairs Med Ctr, Sepulveda Ambulatory Care Ctr, Res & Med Serv, Los Angeles, CA USA. RP Leung, FW (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VAGLAHS, Sepulveda Ambulatory Care Ctr,Div Gastroenterol, 111G,16111 Plummer St, Sepulveda, CA 91343 USA. EM Felix.leung@va.gov FU Veterans Affairs Medical Research Funds; ASGE Endoscopic Career Development Award FX This work was supported in part by the Veterans Affairs Medical Research Funds and ASGE Endoscopic Career Development Award (FWL 1985). The author has full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The author has no conflict of interest to declare. NR 25 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 2008 VL 53 IS 10 BP 2719 EP 2722 DI 10.1007/s10620-007-0192-8 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 343DV UT WOS:000258833800020 PM 18274901 ER PT J AU Adla, M Downey, KK Ahmad, J AF Adla, Mahathi Downey, Kathy K. Ahmad, Jawad TI Hepatic sarcoidosis associated with pegylated interferon alfa therapy for chronic hepatitis C: Case report and review of literature SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article ID OF-THE-LITERATURE; VIRUS-INFECTION; RIBAVIRIN THERAPY; PLUS RIBAVIRIN C1 [Adla, Mahathi; Ahmad, Jawad] Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. [Downey, Kathy K.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. RP Ahmad, J (reprint author), Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. EM ahmadj@msx.upmc.edu NR 17 TC 11 Z9 11 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 2008 VL 53 IS 10 BP 2810 EP 2812 DI 10.1007/s10620-008-0209-y PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 343DV UT WOS:000258833800035 PM 18320314 ER PT J AU Kwon, DS Gandhi, RT AF Kwon, Douglas S. Gandhi, Rajesh T. TI HIV vaccines: current approaches and new developments SO DRUGS OF THE FUTURE LA English DT Review ID SIMIAN IMMUNODEFICIENCY VIRUS; CYTOTOXIC T-LYMPHOCYTES; ANKARA BOOST REGIMEN; CELL RESPONSES; TYPE-1 INFECTION; AIDS VACCINE; THERAPEUTIC IMMUNIZATION; ANTIBODY NEUTRALIZATION; ANTIRETROVIRAL THERAPY; MONOCLONAL-ANTIBODY AB The challenge of developing an acquired immune deficiency syndrome (AIDS) vaccine continues to be paramount as the global AIDS epidemic progresses. Traditional vaccine strategies that induce broadly neutralizing antibodies have so far been ineffective, and focus is now turning toward more novel approaches that seek to elicit T-lymphocyte responses. Recent results from the STEP vaccine trial, a test-of-concept trial of an adenoviral serotype 5-based vaccine, failed to show a protective effect despite clear induction of human immunodeficiency virus (HIV) immunogenicity and early promising results in nonhuman primate studies. The results from the STEP trial demonstrate that innovative approaches and a better understanding of the immunopathogenesis of HIV disease are needed for the goal of a safe, globally effective HIV vaccine to be realized. C1 [Kwon, Douglas S.; Gandhi, Rajesh T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA 02115 USA. [Kwon, Douglas S.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Gandhi, RT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA 02115 USA. EM rgandhi@partners.org FU Harvard University [1 P30AI060354-02]; National Institutes of Health (NIH) [1 R01 AI066992-01A1]; Howard Hughes Medical Institute FX RTG would like to acknowledge grant support from the Harvard University Center for AIDS Research (1 P30AI060354-02), a National Institutes of Health (NIH) funded program, and the NIH (1 R01 AI066992-01A1). DSK would like to acknowledge fellowship support from the Howard Hughes Medical Institute. NR 78 TC 0 Z9 0 U1 1 U2 4 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 OCT PY 2008 VL 33 IS 10 BP 861 EP 868 DI 10.1358/dof.2008.033.10.1253844 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 388JB UT WOS:000262015000005 ER PT J AU Gallun, F Souza, P AF Gallun, Frederick Souza, Pamela TI Exploring the role of the modulation spectrum in phoneme recognition SO EAR AND HEARING LA English DT Article ID AMPLITUDE-MODULATION; FREQUENCY-SELECTIVITY; TEMPORAL INFORMATION; RELATIVE IMPORTANCE; SPEECH RECOGNITION; INTELLIGIBILITY; RECEPTION; MASKING; CUES AB Objectives: The ability of human listeners to identify consonants (presented as nonsense syllables) on the basis of primarily temporal information was compared with the predictions of a simple model based on the amplitude modulation spectra of the stimuli calculated for six octave-spaced carrier frequencies (250 to 8000 Hz) and six octave-spaced amplitude modulation frequencies (1 to 32 Hz). Design: The listeners and the model were presented with 16 phonemes each spoken by four different talkers processed so that one, two, four, or eight bands of spectral information remained. The average modulation spectrum of each of the processed phonemes was extracted and similarity across phonemes was calculated by the use of a spectral correlation index (SCI). Results: The similarity of the modulation spectra across phonemes as assessed by the spectral correlation index was a strong predictor of the confusions made by human listeners. Conclusions: This result suggests that a sparse set of time-averaged patterns of modulation energy can capture a meaningful aspect of the information listeners use to distinguish among speech signals. C1 [Gallun, Frederick] Portland VA Med Ctr, VA RR&D Natl Ctr Rehabilitat Auditory Res, Portland, OR USA. [Souza, Pamela] Univ Washington, Dept Speech & Hearing Sci, Seattle, WA 98195 USA. RP Gallun, F (reprint author), VA NCRAR, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM Frederick.Gallun@va.gov OI Gallun, Frederick/0000-0002-4145-2199 FU Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service [DC006014]; National Institute for Deaffness and Communication Disorders [DC04661]; Bloedel Hearing Research Center FX The research was supported by the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service (to F. G.), grants DC006014 and DC04661 from the National Institute for Deaffness and Communication Disorders (to P. S.), and by the Bloedel Hearing Research Center (to P. S.). NR 39 TC 24 Z9 24 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-0202 J9 EAR HEARING JI Ear Hear. PD OCT PY 2008 VL 29 IS 5 BP 800 EP 813 DI 10.1097/AUD.0b013e31817e73ef PG 14 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 350FS UT WOS:000259338700012 PM 18596640 ER PT J AU Khandaker, GM Barnett, JH Jones, PB AF Khandaker, G. M. Barnett, J. H. Jones, P. B. TI Systematic review and meta-analysis of population-based Studies of premorbid intelligence and schizophrenia SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Khandaker, G. M.] Cambridge & Peterborough Mental Hlth Partnership, Cambridge, England. [Barnett, J. H.; Jones, P. B.] Univ Cambridge, Dept Psychiat, Cambridge, England. [Barnett, J. H.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1751-7885 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD OCT PY 2008 VL 2 BP A69 EP A69 PG 1 WC Psychiatry SC Psychiatry GA 449PB UT WOS:000266341400256 ER PT J AU Tranulis, C Park, L Freudenreich, O Goff, DC Good, BJ AF Tranulis, C. Park, L. Freudenreich, O. Goff, D. C. Good, B. J. TI Early psychosis experiences - IPSOS report for the Boston site SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Tranulis, C.; Good, B. J.] Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA. [Park, L.; Freudenreich, O.; Goff, D. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1751-7885 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD OCT PY 2008 VL 2 BP A27 EP A27 PG 1 WC Psychiatry SC Psychiatry GA 449PB UT WOS:000266341400104 ER PT J AU Chiu, Y Rudin, CM Shapiro, GI Roberts, AW Brown, JR Wilson, W O'Connor, O Xiong, H Enschede, S Krivoshik, A AF Chiu, Y. Rudin, C. M. Shapiro, G. I. Roberts, A. W. Brown, J. R. Wilson, W. O'Connor, O. Xiong, H. Enschede, S. Krivoshik, A. TI Advantages of a modified continual reassessment method (CRM) for dose finding studies: experience in ongoing phase I trials with ABT-263 SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY OCT 21-24, 2008 CL Geneva, SWITZERLAND SP EORTC, NCI, AACR C1 [Chiu, Y.] Abbott Labs, Clin Pharmacol & Pharmacometr, Abbott Pk, IL 60064 USA. [Rudin, C. M.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Shapiro, G. I.; Brown, J. R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Roberts, A. W.] Royal Melbourne Hosp, Dept Clin Haematol & Med Oncol, Parkville, Vic 3050, Australia. [Wilson, W.] NCI, Canc Res Ctr, Bethesda, MD 20892 USA. [O'Connor, O.] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY USA. [Xiong, H.; Enschede, S.; Krivoshik, A.] Abbott Labs, Abbott Oncol, Abbott Pk, IL 60064 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2008 VL 6 IS 12 BP 14 EP 14 DI 10.1016/S1359-6349(08)71966-9 PG 1 WC Oncology SC Oncology GA 376ZJ UT WOS:000261221200032 ER PT J AU Anderson, K AF Anderson, K. TI Bortezomib therapy of multiple myeloma SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY OCT 21-24, 2008 CL Geneva, SWITZERLAND SP EORTC, NCI, AACR C1 [Anderson, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2008 VL 6 IS 12 BP 15 EP 16 DI 10.1016/S1359-6349(08)71970-0 PG 2 WC Oncology SC Oncology GA 376ZJ UT WOS:000261221200036 ER PT J AU Spratlin, J Arkenau, HT George, S Serkova, NJ Germuska, M Brock, K Gedrich, R Scurr, M Demetri, GD Camidge, DR AF Spratlin, J. Arkenau, H. T. George, S. Serkova, N. J. Germuska, M. Brock, K. Gedrich, R. Scurr, M. Demetri, G. D. Camidge, D. R. TI Analyses of pharmacodynamic (PD) assessments collected during expanded cohorts (EC) of a phase I trial with OSI-930, a multi-targeted oral tyrosine kinase inhibitor (TKI) SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY OCT 21-24, 2008 CL Geneva, SWITZERLAND SP EORTC, NCI, AACR C1 [Spratlin, J.; Serkova, N. J.; Camidge, D. R.] Univ Colorado, Ctr Canc, Dev Therapeut Program, Aurora, CO USA. [Arkenau, H. T.; Germuska, M.; Scurr, M.] Royal Marsden Hosp, Drug Dev Unit, Sutton, Surrey, England. [George, S.; Demetri, G. D.] Harvard Univ, Sch Med, Ludwig Ctr, Boston, MA USA. [George, S.; Demetri, G. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Brock, K.] OSI Pharmaceut Inc, Oxford, England. [Gedrich, R.] OSI Pharmaceut Inc, Boulder, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2008 VL 6 IS 12 BP 19 EP 19 DI 10.1016/S1359-6349(08)71981-5 PG 1 WC Oncology SC Oncology GA 376ZJ UT WOS:000261221200047 ER PT J AU Besse, B Eaton, KD Soria, JC Lynch, TJ Miller, V Wong, KK Powell, C Quinn, S Zacharchuk, C Sequist, LV AF Besse, B. Eaton, K. D. Soria, J. C. Lynch, T. J. Miller, V. Wong, K. K. Powell, C. Quinn, S. Zacharchuk, C. Sequist, L. V. TI Neratinib (HKI-272), an irreversible pan-ErbB receptor tyrosine kinase inhibitor: preliminary results of a phase 2 trial in patients with advanced non-small cell lung cancer SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY OCT 21-24, 2008 CL Geneva, SWITZERLAND SP EORTC, NCI, AACR C1 [Sequist, L. V.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Lynch, T. J.; Sequist, L. V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Besse, B.; Soria, J. C.] Inst Gustave Roussy, Dept Med, Serv Gard 7, Villejuif, France. [Eaton, K. D.] Univ Washington, Dept Med, Seattle, WA USA. [Lynch, T. J.] Harvard Univ, Sch Med, Div Hematol & Oncol, Boston, MA USA. [Miller, V.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Quinn, S.; Zacharchuk, C.] Wyeth Ayerst Res, Oncol, Cambridge, MA USA. [Powell, C.] Wyeth Ayerst Res, Global Biostat & Programming, Cambridge, MA USA. [Wong, K. K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wong, K. K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 7 Z9 8 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2008 VL 6 IS 12 BP 64 EP 64 DI 10.1016/S1359-6349(08)72135-9 PG 1 WC Oncology SC Oncology GA 376ZJ UT WOS:000261221200201 ER PT J AU Wagner, AJ Yazji, S Morgan, JA Choy, E George, S Hohos, M O'Mara, M Demetri, GD AF Wagner, A. J. Yazji, S. Morgan, J. A. Choy, E. George, S. Hohos, M. O'Mara, M. Demetri, G. D. TI A phase II study of the KIT inhibitor XL820 in patients with advanced gastrointestinal stromal tumors (GIST) resistant to or intolerant of imatinib and/or sunitinib SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY OCT 21-24, 2008 CL Geneva, SWITZERLAND SP EORTC, NCI, AACR C1 [Choy, E.] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. [Yazji, S.] Exelixis Inc, Oncol Clin Dev, San Francisco, CA USA. [Wagner, A. J.; Morgan, J. A.; George, S.; Hohos, M.; O'Mara, M.; Demetri, G. D.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2008 VL 6 IS 12 BP 67 EP 67 DI 10.1016/S1359-6349(08)72144-X PG 1 WC Oncology SC Oncology GA 376ZJ UT WOS:000261221200210 ER PT J AU Calvo, E Edelman, G Baselga, J Kwak, E Scheffold, C Nguyen, L Shapiro, GI AF Calvo, E. Edelman, G. Baselga, J. Kwak, E. Scheffold, C. Nguyen, L. Shapiro, G. I. TI A phase I dose-escalation study of the safety, pharmacokinetics and pharmacodynamics of XL147, a novel PI3K inhibitor administered orally to patients with advanced solid tumors SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY OCT 21-24, 2008 CL Geneva, SWITZERLAND SP EORTC, NCI, AACR C1 [Calvo, E.; Baselga, J.] Hosp Univ Vall Hebron, Barcelona, Spain. [Edelman, G.] Texas Onc, Med Oncol, Irving, TX USA. [Kwak, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Scheffold, C.] Exelixis Inc, Clin Dev, San Francisco, CA USA. [Nguyen, L.] Exelixis Inc, Nonclin Dev, San Francisco, CA USA. [Shapiro, G. I.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 5 Z9 5 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2008 VL 6 IS 12 BP 69 EP 69 DI 10.1016/S1359-6349(08)72150-5 PG 1 WC Oncology SC Oncology GA 376ZJ UT WOS:000261221200216 ER PT J AU LoRusso, P Sarker, D Von Hoff, D Tibes, R Derynck, MK Ware, JA Yan, Y Demetri, GD de Bono, JS Wagner, AJ AF LoRusso, P. Sarker, D. Von Hoff, D. Tibes, R. Derynck, M. K. Ware, J. A. Yan, Y. Demetri, G. D. de Bono, J. S. Wagner, A. J. TI Pharmacokinetics and pharmacodynamic biomarkers for the pan-PI3K inhibitor GDC-0941: Initial Phase I evaluation SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY OCT 21-24, 2008 CL Geneva, SWITZERLAND SP EORTC, NCI, AACR C1 [LoRusso, P.] Karmanos Canc Inst, Detroit, MI USA. [Sarker, D.; de Bono, J. S.] Royal Marsden Hosp, Inst Canc Res, London SW3 6JJ, England. [Von Hoff, D.; Tibes, R.] TGen Scottsdale Healthcare Oncol, Scottsdale, AZ USA. [Derynck, M. K.; Ware, J. A.; Yan, Y.] Genentech Inc, Oncol, San Francisco, CA 94080 USA. [Demetri, G. D.; Wagner, A. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2008 VL 6 IS 12 BP 70 EP 71 DI 10.1016/S1359-6349(08)72155-4 PG 2 WC Oncology SC Oncology GA 376ZJ UT WOS:000261221200221 ER PT J AU Pishvajan, MJ Wagner, A Deeken, J He, AR Hwang, J Malik, S Cotarla, I Demetri, G Marshall, JL Wojtowicz-Praga, S AF Pishvajan, M. J. Wagner, A. Deeken, J. He, A. R. Hwang, J. Malik, S. Cotarla, I. Demetri, G. Marshall, J. L. Wojtowicz-Praga, S. TI A Phase 1 clinical trial of the oral PPAR gamma agonist, CS-7017 in patients with advanced malignancies SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY OCT 21-24, 2008 CL Geneva, SWITZERLAND SP EORTC, NCI, AACR C1 [Pishvajan, M. J.; Deeken, J.; He, A. R.; Hwang, J.; Malik, S.; Cotarla, I.; Marshall, J. L.] Lombardi Comprehens Canc Ctr, Washington, DC USA. [Wagner, A.; Demetri, G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wojtowicz-Praga, S.] Daiichi Sankyo Pharma Dev, Clin Dev Oncol, Edison, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2008 VL 6 IS 12 BP 128 EP 129 DI 10.1016/S1359-6349(08)72343-7 PG 2 WC Oncology SC Oncology GA 376ZJ UT WOS:000261221200408 ER PT J AU Castaigne, JP Elian, KM Bouchard, D Neale, A Rosenfeld, S Drappatz, J Groves, M Wen, P Bento, P Lawrence, B AF Castaigne, J. P. Elian, K. M. Bouchard, D. Neale, A. Rosenfeld, S. Drappatz, J. Groves, M. Wen, P. Bento, P. Lawrence, B. TI ANG1005: Preliminary clinical safety and tolerability in patients with recurrent malignant glioma SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY OCT 21-24, 2008 CL Geneva, SWITZERLAND SP EORTC, NCI, AACR C1 [Castaigne, J. P.; Elian, K. M.; Bouchard, D.; Bento, P.] Angiochem Inc, Clin Res, Montreal, PQ, Canada. [Neale, A.] WinPharm Associates LLC, Clin Res, Danville, PA USA. [Rosenfeld, S.] Columbia Univ, Med Ctr, Brain Tumor Ctr, New York, NY USA. [Drappatz, J.; Wen, P.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [Groves, M.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Lawrence, B.] Angiochem Inc, Drug Dev, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2008 VL 6 IS 12 BP 133 EP 134 DI 10.1016/S1359-6349(08)72359-0 PG 2 WC Oncology SC Oncology GA 376ZJ UT WOS:000261221200424 ER PT J AU Hurwitz, H LoRusso, P Shapiro, GI Wolanksi, A Chemidlin, J Masson, E Syed, S Kollia, G Conlon, K AF Hurwitz, H. LoRusso, P. Shapiro, G. I. Wolanksi, A. Chemidlin, J. Masson, E. Syed, S. Kollia, G. Conlon, K. TI Phase I study of food effects on pharmacokinetics of brivanib alaninate in patients with advanced or metastatic solid tumors SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY OCT 21-24, 2008 CL Geneva, SWITZERLAND SP EORTC, NCI, AACR C1 [Hurwitz, H.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [LoRusso, P.] Karmanos Canc Inst, Detroit, MI USA. [Shapiro, G. I.; Wolanksi, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chemidlin, J.; Masson, E.; Syed, S.; Kollia, G.; Conlon, K.] Bristol Myers Squibb Co, Princeton, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2008 VL 6 IS 12 BP 135 EP 135 DI 10.1016/S1359-6349(08)72363-2 PG 1 WC Oncology SC Oncology GA 376ZJ UT WOS:000261221200428 ER PT J AU Matthews, CM Ho, SN Barve, M Bell-McGuinn, KM Gilbert, L Penson, RT Lengyel, E Weymer, S Gilder, K Schilder, RJ AF Matthews, C. M. Ho, S. N. Barve, M. Bell-McGuinn, K. M. Gilbert, L. Penson, R. T. Lengyel, E. Weymer, S. Gilder, K. Schilder, R. J. TI A phase 2, single-arm study of volociximab (an anti-a5 beta 1 integrin antibody) monotherapy in patients with platinum-resistant advanced epithelial ovarian cancer or primary peritoneal cancer SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY OCT 21-24, 2008 CL Geneva, SWITZERLAND SP EORTC, NCI, AACR C1 [Matthews, C. M.] Mary Crowley Canc Res Ctr, Dallas, TX USA. [Ho, S. N.] Biogen Idec, Translat Oncobiol, San Diego, CA USA. [Barve, M.] Texas Oncol Presbyterian, Med Oncol, Dallas, TX USA. [Bell-McGuinn, K. M.] Mem Sloan Kettering, Gynecol Med Oncol, New York, NY USA. [Gilbert, L.] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Penson, R. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lengyel, E.] Univ Chicago, Dept Obstet & Gynecol Gynecol Oncol, Chicago, IL 60637 USA. [Weymer, S.] Biogen Idec, Clin Operat Oncol, San Diego, CA USA. [Gilder, K.] Biogen Idec, Biostat, San Diego, CA USA. [Schilder, R. J.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RI Lengyel, Ernst/D-9220-2014 OI Lengyel, Ernst/0000-0001-8624-1507 NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2008 VL 6 IS 12 BP 164 EP 165 DI 10.1016/S1359-6349(08)72453-4 PG 2 WC Oncology SC Oncology GA 376ZJ UT WOS:000261221200516 ER PT J AU Janne, PA Wax, M Leach, J Engelman, J AF Janne, P. A. Wax, M. Leach, J. Engelman, J. TI Targeting MET with XL184 to reverse EGFR tyrosine kinase inhibitor (TKI) resistance in NSCLC: impact of preclinical studies on clinical trial design SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY OCT 21-24, 2008 CL Geneva, SWITZERLAND SP EORTC, NCI, AACR C1 [Janne, P. A.] Brigham & Womens Hosp, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Wax, M.] Summit Med Grp, Berkeley Hts, NJ USA. [Leach, J.] Pk Nicollet Clin, St Louis, MN USA. [Engelman, J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2008 VL 6 IS 12 BP 174 EP 174 DI 10.1016/S1359-6349(08)72486-8 PG 1 WC Oncology SC Oncology GA 376ZJ UT WOS:000261221200549 ER PT J AU Schellens, J Guo, F Janne, PA Eckhardt, SG Camidge, DR Taylor, I Lucca, J Boss, DS Wong, SG Britten, CD AF Schellens, J. Guo, F. Jaenne, P. A. Eckhardt, S. G. Camidge, D. R. Taylor, I. Lucca, J. Boss, D. S. Wong, S. G. Britten, C. D. TI First-in-human (FIH) study of PF-00299804 in advanced cancer patients: correlation between pharmacokinetics (PK) and pharmacodynamics (PD) SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY OCT 21-24, 2008 CL Geneva, SWITZERLAND SP EORTC, NCI, AACR C1 [Schellens, J.; Boss, D. S.] Netherlands Canc Inst, Amsterdam, Netherlands. [Guo, F.] Pfizer Global Res & Dev, Clin Pharmacol, New London, CT USA. [Jaenne, P. A.; Lucca, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Eckhardt, S. G.; Camidge, D. R.] Univ Colorado, Ctr Canc, Denver, CO 80262 USA. [Taylor, I.] Pfizer Global Res & Dev, Groton New London Labs, New London, CT USA. [Britten, C. D.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2008 VL 6 IS 12 BP 177 EP 178 DI 10.1016/S1359-6349(08)72498-4 PG 2 WC Oncology SC Oncology GA 376ZJ UT WOS:000261221200561 ER PT J AU Bouillon, R Carmeliet, G Verlinden, L van Etten, E Verstuyf, A Luderer, HF Lieben, L Mathieu, C Demay, M AF Bouillon, Roger Carmeliet, Geert Verlinden, Lieve van Etten, Evelyne Verstuyf, Annemieke Luderer, Hilary F. Lieben, Liesbet Mathieu, Chantal Demay, Marie TI Vitamin D and Human Health: Lessons from Vitamin D Receptor Null Mice SO ENDOCRINE REVIEWS LA English DT Review ID PROSTATE-CANCER RISK; NONOBESE DIABETIC MICE; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MINERAL ION HOMEOSTASIS; D-DEFICIENCY RICKETS; D-RESISTANT RICKETS; D-3 1-ALPHA-HYDROXYLASE GENE; INFLAMMATORY-BOWEL-DISEASE; PARATHYROID-HORMONE GENE; DNA MICROARRAY ANALYSIS AB The vitamin D endocrine system is essential for calcium and bone homeostasis. The precise mode of action and the full spectrum of activities of the vitamin D hormone, 1,25-dihydroxy-vitamin D [1,25-(OH)(2)D], can now be better evaluated by critical analysis of mice with engineered deletion of the vitamin D receptor (VDR). Absence of a functional VDR or the key activating enzyme, 25-OHD-1 alpha-hydroxylase (CYP27B1), in mice creates a bone and growth plate phenotype that mimics humans with the same congenital disease or severe vitamin D deficiency. The intestine is the key target for the VDR because high calcium intake, or selective VDR rescue in the intestine, restores a normal bone and growth plate phenotype. The VDR is nearly ubiquitously expressed, and almost all cells respond to 1,25-(OH)(2)D exposure; about 3% of the mouse or human genome is regulated, directly and/or indirectly, by the vitamin D endocrine system, suggesting a more widespread function. VDR-deficient mice, but not vitamin D- or 1 alpha-hydroxylase-deficient mice, and man develop total alopecia, indicating that the function of the VDR and its ligand is not fully overlapping. The immune system of VDR- or vitamin D- deficient mice is grossly normal but shows increased sensitivity to autoimmune diseases such as inflammatory bowel disease or type 1 diabetes after exposure to predisposing factors. VDR- deficient mice do not have a spontaneous increase in cancer but are more prone to oncogene- or chemocarcinogen-induced tumors. They also develop high renin hypertension, cardiac hypertrophy, and increased thrombogenicity. Vitamin D deficiency in humans is associated with increased prevalence of diseases, as predicted by the VDR null phenotype. Prospective vitamin D supplementation studies with multiple noncalcemic endpoints are needed to define the benefits of an optimal vitamin D status. (Endocrine Reviews 29: 726-776, 2008) C1 [Bouillon, Roger; Carmeliet, Geert; Verlinden, Lieve; van Etten, Evelyne; Verstuyf, Annemieke; Lieben, Liesbet; Mathieu, Chantal] Katholieke Univ Leuven, Lab Expt Med & Endocrinol, B-3000 Louvain, Belgium. [Luderer, Hilary F.; Demay, Marie] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Bouillon, R (reprint author), Katholieke Univ Leuven, Lab Expt Med & Endocrinol, Herestr 49,O&N 1 Bus 902, B-3000 Louvain, Belgium. EM Roger.Bouillon@med.kuleuven.be RI Verlinden, Lieve/E-6517-2011 FU University of Leuven [GOA/04/10, EF/05/007]; Flanders Research Foundation [G.0084.02, G.0233.04, G.0508.05, G.0552.06, G.0553.06, G.0649.08]; Juvenile Diabetes Research Foundation (JDRF) [4-2005-1237, 3-2006-33]; Belgium Program on Interuniversity Poles of Attraction initiated by the Belgian State [IUAP P5/17, P6/34]; Clinical Research Fellowship (FWO, Belgium); National Institutes of Health [DK46974] FX The work in the authors' laboratories was supported by the University of Leuven (GOA/04/10, EF/05/007), Flanders Research Foundation [Fonds voor Wetenschappelijk onderzoek Vlaanderen (FWO), Grants G.0084.02, G.0233.04, G.0508.05, G.0552.06, G.0553.06, and G.0649.08], the Juvenile Diabetes Research Foundation (JDRF; Grant 4-2005-1237), and the Belgium Program on Interuniversity Poles of Attraction initiated by the Belgian State (Grants IUAP P5/17 and P6/34). C.M. is holder of a Clinical Research Fellowship (FWO, Belgium), E. v. E. holds a Post-doctoral Fellowship (JDRF, 3-2006-33), and L.L. is a fellow of the IWT-Flanders. The work in Boston was supported by National Institutes of Health Grant DK46974. NR 668 TC 640 Z9 673 U1 13 U2 62 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD OCT PY 2008 VL 29 IS 6 BP 726 EP 776 DI 10.1210/er.2008-0004 PG 51 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 358CB UT WOS:000259893000004 PM 18694980 ER PT J AU Knauf, C Cani, PD Ait-Belgnaoui, A Benani, A Dray, C Cabou, C Colom, A Uldry, M Rastrelli, S Sabatier, E Godet, N Waget, A Penicaud, L Valet, P Burcelin, R AF Knauf, Claude Cani, Patrice D. Ait-Belgnaoui, Afifa Benani, Alexandre Dray, Cedric Cabou, Cendrine Colom, Andre Uldry, Marc Rastrelli, Sophie Sabatier, Eric Godet, Natacha Waget, Aurelie Penicaud, Luc Valet, Philippe Burcelin, Remy TI Brain glucagon-like peptide 1 signaling controls the onset of high-fat diet-induced insulin resistance and reduces energy expenditure SO ENDOCRINOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; MUSCLE GLYCOGEN-SYNTHESIS; ACTIVATED RECEPTOR-ALPHA; GLUCOSE-HOMEOSTASIS; KNOCKOUT MOUSE; BINDING-SITES; FOOD-INTAKE; RAT-BRAIN; NULL MICE; GLP-1 AB Glucagon-like peptide-1 (GLP-1) is a peptide released by the intestine and the brain. We previously demonstrated that brain GLP-1 increases glucose-dependent hyperinsulinemia and insulin resistance. These two features are major characteristics of the onset of type 2 diabetes. Therefore, we investigated whether blocking brain GLP-1 signaling would prevent high-fat diet (HFD)-induced diabetes in the mouse. Our data show that a 1-month chronic blockage of brain GLP-1 signaling by exendin-9 (Ex9), totally prevented hyperinsulinemia and insulin resistance in HFD mice. Furthermore, food intake was dramatically increased, but body weight gain was unchanged, showing that brain GLP-1 controlled energy expenditure. Thermogenesis, glucose utilization, oxygen consumption, carbon dioxide production, muscle glycolytic respiratory index, UCP2 expression in muscle, and basal ambulatory activity were all increased by the exendin-9 treatment. Thus, we have demonstrated that in response to a HFD, brain GLP-1 signaling induces hyperinsulinemia and insulin resistance and decreases energy expenditure by reducing metabolic thermogenesis and ambulatory activity. C1 [Knauf, Claude; Cani, Patrice D.; Dray, Cedric; Cabou, Cendrine; Colom, Andre; Rastrelli, Sophie; Sabatier, Eric; Godet, Natacha; Waget, Aurelie; Valet, Philippe; Burcelin, Remy] Univ Toulouse 3, CHU Rangueil, Inst Med Mol Rangueil 12MR, Unite 858,Inst Federatif Rech 31,Inst Natl Sante, F-31432 Toulouse 4, France. [Cani, Patrice D.] Catholic Univ Louvain, Unit Pharmacokinet Metab Nutr & Toxicol, B-1200 Brussels, Belgium. [Ait-Belgnaoui, Afifa] Inst Natl Rech Agron ESAP, Unite Mixte Rech 1054, Neurogastroenterol & Nutr Unit, F-31931 Toulouse, France. [Benani, Alexandre; Penicaud, Luc] Univ Toulouse 3, Ctr Natl Rech Sci, Unite Mixte Rech 5241, Lab Metab Plasticite Mitochondrie, F-31432 Toulouse, France. [Uldry, Marc] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Uldry, Marc] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Burcelin, R (reprint author), Univ Toulouse 3, CHU Rangueil, Inst Med Mol Rangueil 12MR, Unite 858,Inst Federatif Rech 31,Inst Natl Sante, BP84225, F-31432 Toulouse 4, France. EM remy.burcelin@inserm.fr RI burcelin, remy/M-6013-2014; Benani, Alexandre/F-4002-2012; OI Benani, Alexandre/0000-0003-2046-0162; Cani, Patrice D./0000-0003-2040-2448 FU CESNA (Club d'Etude du Systeme Nerveux Autonome) FX We thank Prof. Louis Casteilla for helpful discussion. R.B., C.K., and P.D.C. are members of CESNA (Club d'Etude du Systeme Nerveux Autonome) and are grateful for its financial support. We fully acknowledge the expertise of Laurent Montbrun and Sophie Le Gonidec from the functional exploration platform, Toulouse-Midi-Pyrenees-Genopole concerning energy expenditure measurements, and Daniele Daviaud for technical advice. We also thank Dr. John Woodley for editing the English. NR 47 TC 65 Z9 67 U1 0 U2 5 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 OCT PY 2008 VL 149 IS 10 BP 4768 EP 4777 DI 10.1210/en.2008-0180 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351BW UT WOS:000259400300002 PM 18556349 ER PT J AU Sang, XP Curran, MS Wood, AW AF Sang, Xianpeng Curran, Matthew S. Wood, Antony W. TI Paracrine insulin-like growth factor signaling influences primordial germ cell migration: In vivo evidence from the zebrafish model SO ENDOCRINOLOGY LA English DT Article ID ADHESION MOLECULES; EMBRYONIC GROWTH; STEM-CELLS; EXPRESSION; RECEPTOR; CHEMOKINE; SURVIVAL; GENE; CANCER; CXCR4 AB IGF signaling has been shown to stimulate migration of multiple cell types in vitro, but few studies have confirmed an equivalent function for IGF signaling in vivo. We recently showed that suppression of IGF receptors in the zebrafish embryo disrupts primordial germ cell (PGC) migration, but the mechanism underlying these effects has not been elucidated. We hypothesized that PGCs are intrinsically dependent upon IGF signaling during the migratory phase of development. To test this hypothesis, we first examined the spatial expression patterns of IGF ligand genes (igf1, igf2a, and igf2b) in the zebrafish embryo. In situ analyses revealed distinct expression patterns for each IGF ligand gene, with igf2b mRNA expressed in a spatial pattern that correlates strongly with PGC migration. To determine whether PGC migration is responsive to IGF signaling in vivo, we synthesized gene hybrid expression constructs that permit conditional overexpression of IGF ligands by PGCs into the PGC microenvironment. Conditional overexpression of IGF ligands consistently disrupted PGC migration, confirming that PGC migration is sensitive to local aberrations in IGF signaling. Finally, we show that conditional suppression of IGF signaling, via PGC-specific overexpression of a mutant IGF-I receptor, disrupts PGC migration, confirming that zebrafish PGCs intrinsically require IGF signaling for directional migration in vivo. Collectively, these studies confirm an in vivo role for IGF signaling in cell migration and identify a candidate ligand gene (igf2b) regulating PGC migration in the zebrafish. C1 Harvard Univ, Sch Med, Vincent Obstet & Gynecol Serv, Vincent Ctr Reprod Biol,Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Wood, AW (reprint author), 55 Fruit St,THR 933, Boston, MA 02114 USA. EM awwood@partners.org FU Vincent Memorial Research Funds; Harvard University; Harvard Undergraduate Research Program; Harvard Stem Cell Institute Summer Undergraduate Research Program FX The study was supported financially by Vincent Memorial Research Funds. X. S. received a fellowship from the Program for Research in Science and Engineering at Harvard University, and was supported by the Harvard Undergraduate Research Program. X. S. and M. S. C. were further supported by the Harvard Stem Cell Institute Summer Undergraduate Research Program. NR 41 TC 19 Z9 19 U1 0 U2 12 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 OCT PY 2008 VL 149 IS 10 BP 5035 EP 5042 DI 10.1210/en.2008-0534 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351BW UT WOS:000259400300029 PM 18566124 ER PT J AU Lin, D Bucci, MK Eisele, DW Wang, SJ AF Lin, Doris Bucci, M. Kara Eisele, David W. Wang, Steven J. TI Squamous cell carcinoma of the buccal mucosa: A retrospective analysis of 22 cases SO ENT-EAR NOSE & THROAT JOURNAL LA English DT Article AB We examined our institution's experience with 22 cases of previously untreated buccal squamous cell carcinoma via a retrospective chart review. Eleven of these patients had been treated with a combination of surgical excision and postoperative radiation therapy, 8 patients with surgical excision alone, and 3 patients with radiation therapy alone. The overall 3-year locoregional recurrence rate was 32% (n = 7). The 3-year survival rates were 82% after surgery plus radiation (9 of 11 patients), 63% after surgery alone (5 of 8), and 33% after radiation alone (1 of 3). Three-year T-category-specific survival rates were 100% for category T1 tumors (3 of 3 patients), 73% for T2 (8 of 11), 50% for T3 (3 of 6), and 50% for T4 (1 of 2). Although the small size of our study precluded any statistically significant conclusions, we believe that locoregional control and survival rates may be greater with surgical excision plus postoperative radiation than with treatment with either modality alone. C1 [Lin, Doris; Eisele, David W.; Wang, Steven J.] Univ Calif San Francisco, Sch Med, Dept Otolaryngol Head & Neck Surg, San Francisco, CA USA. [Bucci, M. Kara] Univ Calif San Francisco, Sch Med, Dept Radiat Oncol, San Francisco, CA 94143 USA. RP Wang, SJ (reprint author), San Francisco VA Med Ctr, 4150 Clement St 111B, San Francisco, CA 94121 USA. EM swang@ohns.ucsf.edu NR 15 TC 3 Z9 3 U1 0 U2 0 PU VENDOME GROUP LLC PI NEW YORK PA 149 FIFTH AVE, 10TH FLOOR, NEW YORK, NY 10010 USA SN 0145-5613 J9 ENT-EAR NOSE THROAT JI ENT-Ear Nose Throat J. PD OCT PY 2008 VL 87 IS 10 BP 582 EP 586 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA V10PD UT WOS:000207475000012 PM 18833538 ER PT J AU Garshick, E Laden, F Hart, JE Rosner, B Davis, ME Eisen, EA Smith, TJ AF Garshick, Eric Laden, Francine Hart, Jaime E. Rosner, Bernard Davis, Mary E. Eisen, Ellen A. Smith, Thomas J. TI Lung cancer and vehicle exhaust in trucking industry workers SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE diesel exhaust; lung cancer; occupational exposure; particulate matter; traffic ID PARTICULATE AIR-POLLUTION; IN-USE DIESEL; SIZE DISTRIBUTION; RAILROAD WORKERS; EMISSION RATES; FOLLOW-UP; EXPOSURE; MATTER; SMOKING; PARTICLES AB BACKGROUND: An elevated risk of lung cancer in truck drivers has been attributed to diesel exhaust exposure. Interpretation of these studies specifically implicating diesel exhaust as a carcinogen has been limited because of limited exposure measurements and lack of work records relating job title to exposure-related job duties. OBJECTIVES We established a large retrospective cohort of trucking company workers to assess the association of lung cancer mortality and measures of vehicle exhaust exposure. METHODS: Work records were obtained for 31,135 male workers employed in the unionized U.S. trucking industry in 1985. We assessed lung cancer mortality through 2000 using the National Death Index, and we used an industrial hygiene review and current exposure measurements to identify jobs associated with current and historical use of diesel-, gas-, and propane-powered vehicles. We indirectly adjusted for cigarette smoking based on an industry survey. RESULTS: Adjusting for age and a healthy-worker survivor effect, lung cancer hazard ratios were elevated in workers with jobs associated with regular exposure to vehicle exhaust. Mortality risk increased linearly with years of employment and was similar across job categories despite different current and historical patterns of exhaust-related particulate matter from diesel trucks, city and highway traffic, and loading dock operations. Smoking behavior did not explain variations in lung cancer risk. CONCLUSIONS: Trucking industry workers who have had regular exposure to vehicle exhaust from diesel and other types of vehicles on highways, city streets, and loading docks have an elevated risk of lung cancer with increasing years of work. C1 [Garshick, Eric] VA Boston Healthcare Syst, Med Serv, Pulm & Crit Care Med Sect, Boston, MA USA. [Garshick, Eric; Laden, Francine; Hart, Jaime E.; Rosner, Bernard] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA USA. [Laden, Francine; Hart, Jaime E.; Davis, Mary E.; Smith, Thomas J.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA. [Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Davis, Mary E.] Univ Maine, Sch Econ, Orono, ME USA. [Eisen, Ellen A.] Univ Calif Berkeley, Sch Publ Hlth, Environm Hlth Sci Div, Berkeley, CA 94720 USA. [Eisen, Ellen A.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. RP Garshick, E (reprint author), VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, 1400 VFW Pkwy, Boston, MA 02132 USA. EM eric.garshick@va.gov FU National Institutes of Health [R01 CA90792]; National Cancer Institute; National Institute of Environmental Health Sciences [ES00002] FX This work was supported by grant R01 CA90792 from the National Institutes of Health/National Cancer Institute and grant ES00002 from the National Institute of Environmental Health Sciences. NR 52 TC 55 Z9 56 U1 3 U2 17 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 OCT PY 2008 VL 116 IS 10 BP 1327 EP 1332 DI 10.1289/chp.11293 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 355TA UT WOS:000259730100024 PM 18941573 ER PT J AU Borges, K Gearing, M Rittling, S Sorensen, ES Kotloski, R Denhardt, DT Dingledine, R AF Borges, Karin Gearing, Maria Rittling, Susan Sorensen, Esben S. Kotloski, Robert Denhardt, David T. Dingledine, Raymond TI Characterization of osteopontin expression and function after status epilepticus SO EPILEPSIA LA English DT Article DE Seizure; Pilocarpine; Inflammation; Axonal degeneration; Neuronal degeneration ID AMYLOID PRECURSOR PROTEIN; UP-REGULATION; FOCAL STROKE; PARKINSONS-DISEASE; FOREBRAIN ISCHEMIA; DEFICIENT MICE; MESSENGER-RNA; AXONAL INJURY; BRAIN-DAMAGE; RAT-BRAIN AB Purpose: Osteopontin is a cytokine found in many tissues and plays a role in tissue injury and repair. This study had two goals: to characterize osteopontin expression after status epilepticus (SE), and to test the hypotheses that osteopontin affects the susceptibility to seizures or alters cell death and inflammation after SE. Methods: Pilocarpine was used to induce SE in OPN-/- and OPN+/+ mice to compare seizure susceptibility, neuropathological markers including real time PCR for inflammatory genes, and osteopontin immunohistochernistry. The effect of added osteopontin on excitotoxicity by N-methyl-D-aspartate in neuronal cultures of ONP-/- mice was determined. Results: Neurons undergoing degeneration showed osteopontin immunoreactivity 2-3 days after SE. After 10 to 31 days degenerating axons in the thalamus were osteoponti n -positive. The susceptibility to seizures of OPN-/- and OPN+/+ mice in the pilocarpine, fluorothyl, and maximal electroshock models was similar. There were no significant differences in the extent of neuronal damage after pilocarpine-induced SE, the expression of several neuropathological markers or the RNA levels of selected inflammatory genes. Recombinant and natural bovine osteopontin did not affect the extent of NMDA-induced cell death in OPN-/- mouse neuronal cultures. Conclusion: We demonstrated that osteopontin is up-regulated in response to SE in distinct temporal sequences in the hippocampus, specifically in degenerating neurons and axons. However, osteopontin did not appear to regulate neurodegeneration or inflammation within the first 3 days after SE. C1 [Borges, Karin] Texas Tech Hlth Sci Ctr, Dept Pharmaceut Sci, Amarillo, TX USA. [Borges, Karin; Dingledine, Raymond] Emory Univ, Dept Pharmacol, Atlanta, GA 30322 USA. [Gearing, Maria] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Rittling, Susan] Forsyth Inst, Dept Cell Biol & Neurosci, Boston, MA USA. [Sorensen, Esben S.] Univ Aarhus, Prot Chem Lab, Dept Mol Biol, Aarhus, Denmark. [Kotloski, Robert] Duke Univ, Dept Neurobiol, Durham, NC USA. [Denhardt, David T.] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ USA. RP Borges, K (reprint author), Texas Tech Univ Hlth Sci, Dept Pharmaceut Sci, 1300 S Coulter, Amarillo, TX 79106 USA. EM karin.borges@ttuhsc.edu RI Borges, Karin/B-4276-2011; dingledine, Ray/F-5173-2011 OI Borges, Karin/0000-0001-7448-0770; FU Epilepsy Foundation; National Institutes of Health [5U54-HG003918] FX We are grateful to the Epilepsy Foundation for funding (KB) and National Institutes of Health Grant 5U54-HG003918 (R.D.). We thank Lucy Liaw for providing OPN-/- and OPN+/+ mice, Aaron Kowalski and Larry Fisher for osteopontin antibodies. James McNamara for help with the electroshock tests, Kroshona Tabb for help with the fluorothyl test. Valerie Boss and James P. O'Callaghan for sharing real time primer sequences, Dayna McDermott for help with the immunohistochemistry and Renee Shaw for help with RNA isolations and real-time PCR. NR 41 TC 13 Z9 13 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2008 VL 49 IS 10 BP 1675 EP 1685 DI 10.1111/j.1528-1167.2008.01613.x PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 362AQ UT WOS:000260171000003 PM 18522644 ER PT J AU Kopp, CMC Muzykewicz, DDA Staley, BA Thiele, EA Pulsifer, MB AF Kopp, Claudine M. C. Muzykewicz, Davi D. A. Staley, Brigid A. Thiele, Elizabeth A. Pulsifer, Margaret B. TI Behavior problems in children with tuberous sclerosis complex and parental stress SO EPILEPSY & BEHAVIOR LA English DT Article DE tuberous sclerosis complex; epilepsy; behavioral problems; mental retardation; autism spectrum disorder; attention; hyperactivity; seizure frequency; mixed seizure disorder; parenting stress ID DIAGNOSTIC-CRITERIA; INFANTILE SPASMS; POPULATION; DISORDERS; AUTISM; CANCER; TSC1; METHYLPHENIDATE; ADOLESCENTS; FAMILIES AB Behavioral problems are common in children with tuberous sclerosis complex (TSC) and can be challenging to manage at home. Standardized measures were used to assess behavior in 99 pediatric patients with TSC and to evaluate parenting stress in their parents. About 40% of the pediatric patients presented clinically significant behavioral problems, most frequently involving symptoms of autism spectrum disorder, inattention, and hyperactivity. Higher seizure frequency, mixed seizure disorder, and low intellectual functioning placed the patient at significant risk for behavior problems. Almost 50% of participating parents reported experiencing clinically significant parenting stress, which was associated with specific characteristics of the child, including the presence of current seizures, a history of psychiatric diagnosis, low intelligence, and behavioral problems. Clinicians should be aware that behavioral problems are prominent in children with TSC. Referrals for behavioral intervention and monitoring of parental stress should be included in the medical management of children with TSC. (C) 2008 Elsevier Inc. All rights reserved. C1 [Pulsifer, Margaret B.] Massachusetts Gen Hosp, Dept Psychiat, Psychol Assessment Ctr, Boston, MA 02114 USA. [Kopp, Claudine M. C.; Muzykewicz, Davi D. A.; Staley, Brigid A.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Pulsifer, MB (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Psychol Assessment Ctr, 1 Bldg Sq,7th Floor, Boston, MA 02114 USA. EM mpulsifer@partners.org FU Carol and James Herscot Center FX This study was supported by the Carol and James Herscot Center for Tuberous Sclerosis Complex at the Massachusetts General Hospital. NR 51 TC 20 Z9 21 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 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD OCT PY 2008 VL 13 IS 3 BP 505 EP 510 DI 10.1016/j.yebeh.2008.05.010 PG 6 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 350DC UT WOS:000259331800015 PM 18602868 ER PT J AU Major, P Greenberg, E Khan, A Thiele, EA AF Major, Philippe Greenberg, Erica Khan, Alisa Thiele, Elizabeth A. TI Pyridoxine supplementation for the treatment of levetiracetam-induced behavior side effects in children: Preliminary results SO EPILEPSY & BEHAVIOR LA English DT Article DE pyridoxine; vitamin B6; levetiracetam; behavior; irritability ID VITAMIN-B-6; SAFETY AB Behavioral side effects related to the use of levetiracetam (LEV) in epilepsy are increasingly being recognized. Patients followed in our center have reported improvement of these side effects after starting pyridoxine (vitamin B-6) supplements. Using mailed questionnaires, retrospective chart reviews, and phone call follow-ups, we analyzed 42 pediatric patients who had been treated with LEV and pyridoxine. Twenty-two patients started pyridoxine after being on LEV, and significant behavioral improvement was observed in nine (41%), no effect in eight (36%), deterioration in four (18%), and an uncertain effect in one. The effects of pyridoxine supplementation were observed during the first week. The remaining patients (20) were already on pyridoxine before LEV was started, started pyridoxine and LEV at the same time, or took pyridoxine intermittently. Pyridoxine is an easily available, inexpensive, and safe therapeutic option. Given these preliminary results, we plan to conduct a placebo-controlled cross-over study to better characterize these observations. (C) 2008 Elsevier Inc. All rights reserved. C1 [Major, Philippe; Greenberg, Erica; Khan, Alisa; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Pediatr Epilepsy Program, Herscot Ctr Tuberous Sclerosis Complex,175 Cambri, Boston, MA 02114 USA. EM ethiele@partners.org NR 12 TC 20 Z9 21 U1 5 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD OCT PY 2008 VL 13 IS 3 BP 557 EP 559 DI 10.1016/j.yebeh.2008.07.004 PG 3 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 350DC UT WOS:000259331800025 PM 18647662 ER PT J AU Michaelides, C Thibert, RL Shapiro, MJ Kinirons, P John, T Manchharam, D Thiele, EA AF Michaelides, Costas Thibert, Ronald L. Shapiro, Michelle J. Kinirons, Peter John, Tanya Manchharam, Dipti Thiele, Elizabeth A. TI Tolerability and dosing experience of intravenous levetiracetam in children and infants SO EPILEPSY RESEARCH LA English DT Article DE Levetiracetam; Intravenous; Dosing; Tolerability; Children; Infants ID REFRACTORY PARTIAL SEIZURES; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; EPILEPSY; SAFETY; MULTICENTER; INFUSION; EFFICACY; THERAPY AB Objective: To evaluate the use and tolerability of intravenous (IV) levetiracetam (LEV) in a pediatric cohort under 14 years of age. Methods: A retrospective analysis of the use of the IV formulation of LEV was performed for the first 9 months that it was available in our institution. Results: Overall, 118 infusions in 15 patients were performed during the period assessed. No adverse reactions were observed during the infusion phase of the IV formulation. Nine minor adverse reactions were observed during the rest of the hospitalization that were potentially related to the IV formulation. Three of these were decreases in the white cell. counts, white the majority of the rest were behavioral adverse effects. The median starting dose in LEV naive patients was 8.8 mg/kg (range = 5.0-50), with a median maintenance dose of 30.4 mg/kg/day for all patients (range = 5.0-92). The majority of these infusions (82/118) were in a subgroup of children under 4 years of age where the median maintenance dose was 28 mg/kg/day. Conclusion: IV LEV was very well tolerated in this cohort of pediatric patients including a subgroup of children under the age of 4 years. (C) 2008 Elsevier B.V. All rights reserved. C1 [Michaelides, Costas; Thibert, Ronald L.; Shapiro, Michelle J.; Kinirons, Peter; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [John, Tanya; Manchharam, Dipti] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. RP Michaelides, C (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. EM cmichaelides@partners.org NR 17 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD OCT PY 2008 VL 81 IS 2-3 BP 143 EP 147 DI 10.1016/j.eplepsyres.2008.05.004 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 374CW UT WOS:000261021000007 PM 18571898 ER PT J AU Murphy, SA Antman, EM Wiviott, SD Weerakkody, G Morocutti, G Huber, K Lopez-Sendon, J McCabe, CH Braunwald, E AF Murphy, Sabina A. Antman, Elliott M. Wiviott, Stephen D. Weerakkody, Govinda Morocutti, Giorgio Huber, Kurt Lopez-Sendon, Jose McCabe, Carolyn H. Braunwald, Eugene CA TRITON-TIMI 38 Investigators TI Reduction in recurrent cardiovascular events with prasugrel compared with clopidogrel in patients with acute coronary syndromes from the TRITON-TIMI 38 trial SO EUROPEAN HEART JOURNAL LA English DT Article DE Acute coronary syndrome; Percutaneous coronary intervention; Prasugrel; Clopidogrel ID ELEVATION MYOCARDIAL-INFARCTION; PLATELET INHIBITION; STENT THROMBOSIS; RISK SCORE; THROMBOLYSIS; REACTIVITY; PREDICTORS; MORTALITY AB Aims In the TRITON-TIMI 38 trial, greater platelet inhibition with prasugrel reduced the first occurrence of the primary end-point (cardiovascular death, MI, or stroke) compared with clopidogrel in patients with an acute coronary syndrome (ACS) undergoing planned percutaneous coronary intervention. We hypothesized that prasugrel would reduce not only first events but also recurrent primary endpoint events and therefore total events compared with clopidogrel. Methods and results Poisson regression analysis was performed to compare the number of occurrences of the primary endpoint between prasugrel and clopidogrel. in TRITON-TIMI 38. Landmark analytic methods were used to evaluate the risk of a recurrent primary endpoint event following an initial non-fatal endpoint event Among patients with an initial non-fatal event, second events were significantly reduced with prasugrel compared to clopidogrel (10.8 vs. 15.4%, HR 0.65, 95% CI 0.46-0.92; P = 0.016), as was CV death following the non-fatal event (3.7 vs. 7.1%, HR 0.46, 95% CI 0.25-0.82; P = 0.008). Overall there was a reduction of 195 total primary efficacy events with prasugrel vs. clopidogrel (rate ratio 0.79, 95% CI 0.71-0.87; P < 0.001). Recurrent bleeding events occurred infrequently (TIMI major non-CABG bleeds: four with prasugrel and two with clopidogrel). Study drug discontinuation was frequent following the initial major bleeding event (42% of patients discontinued study drug). Conclusion While standard statistical analytic techniques for clinical trials censor patients who experience a component of the primary composite endpoint, total cardiovascular events remain important to both patients and clinicians. Prasugrel, a more potent anti-platelet agent, reduced both first and subsequent cardiovascular events compared with dopidogrel in patients with ACS. C1 [Murphy, Sabina A.; Antman, Elliott M.; Wiviott, Stephen D.; McCabe, Carolyn H.; Braunwald, Eugene] Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Cardiovasc Div,Dept Med, Boston, MA 02115 USA. [Weerakkody, Govinda] Eli Lilly Res Labs, Indianapolis, IN USA. [Morocutti, Giorgio] Osped S Maria Misericordia, Udine, Italy. [Huber, Kurt] Wilhelminenhosp, Dept Med 3, Vienna, Austria. [Lopez-Sendon, Jose] Hosp Univ La Paz, Dept Cardiol, Madrid, Spain. RP Antman, EM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Cardiovasc Div,Dept Med, 350 Longwood Ave,1st Off Floor, Boston, MA 02115 USA. EM eantman@partners.org FU Daiichi Sankyo; Eli Lilly FX TRITON-TIMI 38 was supported by research grants from Daiichi Sankyo and Eli Lilly. Funding to pay the Open Access publication charges for this article was provided by Eli Lilly. NR 19 TC 90 Z9 95 U1 0 U2 4 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 OCT PY 2008 VL 29 IS 20 BP 2473 EP 2479 DI 10.1093/eurheartj/ehn362 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 366ZZ UT WOS:000260523600005 PM 18682445 ER PT J AU Poh, KK Levine, RA Solis, J Shen, L Flaherty, M Kang, YJ Guerrero, JL Hung, J AF Poh, Kian Keong Levine, Robert A. Solis, Jorge Shen, Liang Flaherty, Mary Kang, Yue-Jian Guerrero, J. Luis Hung, Judy TI Assessing aortic valve area in aortic stenosis by continuity equation: a novel approach using real-time three-dimensional echocardiography SO EUROPEAN HEART JOURNAL LA English DT Article DE Aortic stenosis; Real-time three-dimensional echocardiography; Colour Doppler; Valvular heart disease; Continuity equation ID COLOR DOPPLER-ECHOCARDIOGRAPHY; EFFECTIVE ORIFICE AREA; STROKE VOLUME; CARDIAC-OUTPUT; QUANTIFICATION AB Aims Two-dimensional echocardiographic (2DE) continuity-equation derived aortic valve area (AVA) in aortic stenosis (AS) relies on non-simultaneous measurement of left ventricular outflow tract (LVOT) velocity and geometric assumptions of LVOT area, which can amplify error, especially in upper septal hypertrophy (USH). We hypothesized that real-time three-dimensional echocardiography (RT3DE) can improve accuracy of AVA by directly measuring LVOT stroke volume (SV) in one window. Methods and results RT3DE colour Doppler and 2DE were acquired in 68 AS patients (74 +/- 12 yrs) prospectively. SV was derived from flow obtained from a sampling curve placed orthogonal to LVOT (Tomtec Imaging). Agreement between continuity-equation derived AVA by RT3DE (AVA(3D-SV)) and 2DE (AVA(2D)) and predictors of discrepancies were analysed. Validation of LVOT SV was performed by aortic flow probe in a sheep model with balloon inflation of septum to mimic USH. There was only modest correlation between AVA(2D) and AVA(3D-SV) (r = 0.71, difference 0.11 +/- 0.23 cm(2)). The degree of USH was significantly associated with difference in AVA calculation (r = 0.4, P = 0.005). In experimentally distorted LVOT geometry in sheep, RT3DE correlated better with flow probe assessment (r = 0.96, P < 0.001) than 2DE (r = 0.71, P = 0.006). Conclusion RT3DE colour Doppler-derived LVOT SV in the calculation of AVA by continuity equation is more accurate than 2D, including in situations such as USH, common in the elderly, which modify LVOT geometry. C1 [Poh, Kian Keong; Levine, Robert A.; Solis, Jorge; Flaherty, Mary; Kang, Yue-Jian; Hung, Judy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab,Div Cardiol, Boston, MA 02114 USA. [Poh, Kian Keong] Natl Univ Singapore Hosp, Dept Cardiac, Singapore 117548, Singapore. [Shen, Liang] Natl Univ Singapore, Yong Loo Lin Sch Med, Biostat Unit, Singapore 117595, Singapore. RP Hung, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab,Div Cardiol, Blake 256,55 Fruit St, Boston, MA 02114 USA. EM jhung@partners.org FU NIH NIBIB [R21 EB005294, R01 038176]; National Medical Research Council, Singapore FX This work was supported in part by NIH NIBIB R21 EB005294 (J.H.) and NIH NHLBI R01 038176 (R.A.L.) and a fellowship award from the National Medical Research Council, Singapore (K.K.P.). NR 32 TC 68 Z9 68 U1 0 U2 4 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 OCT PY 2008 VL 29 IS 20 BP 2526 EP 2535 DI 10.1093/eurheartj/ehn022 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 366ZZ UT WOS:000260523600013 PM 18263866 ER PT J AU Alsayed, Y Leleu, X Leontovich, A Oton, AB Melhem, M George, D Ghobrial, IM AF Alsayed, Yazan Leleu, Xavier Leontovich, Alexey Oton, Ana B. Melhem, Mona George, Diane Ghobrial, Irene M. TI Proteomics analysis in post-transplant lymphoproliferative disorders SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE post-transplant lymphoproliferative disorders; proteomic analysis; targeted therapy ID ORGAN TRANSPLANT RECIPIENTS; WALDENSTROM MACROGLOBULINEMIA; MULTIPLE-MYELOMA; IN-VITRO; B-CELLS; IDENTIFICATION; SURVIVAL AB Little is known about the biology of post-transplant lymphoproliferative disorders (PTLDs). The objective of this study was to determine the molecular alterations that occur at the protein level in patients with PTLDs. Six tumor samples from adult patients with PTLD and four benign lymph nodes were studied using protein microrarray technique. Proteins that were dysregulated included proteins in the PI3K/mTOR, NFkB and HSP90 pathways. Inhibitors of these proteins induced cytotoxicity and apoptosis in EBV+ve and -ve cell lines. These results provide insight into pathways that are dysregulated in PTLD and can be targeted in future clinical trials. C1 [Leleu, Xavier; Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Leleu, Xavier; Ghobrial, Irene M.] Harvard Univ, Sch Med, Boston, MA USA. [Alsayed, Yazan; Oton, Ana B.] Univ Pittsburgh, Pittsburgh, PA USA. [Leleu, Xavier] CHRU, Serv Malad Sang, Lille, France. [Leleu, Xavier] CHRU, Immunol Lab, Lille, France. [Leontovich, Alexey] Mayo Clin, Coll Med, Rochester, MN USA. [Melhem, Mona; George, Diane] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, 44 Binney St,Mayer 548A, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu FU Franco-American Fulbright Foundation FX This work was supported in part by the Leukemia and Lymphoma Society. XL is supported by a grant from the Franco-American Fulbright Foundation. NR 18 TC 8 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD OCT PY 2008 VL 81 IS 4 BP 298 EP 303 DI 10.1111/j.1600-0609.2008.01106.x PG 6 WC Hematology SC Hematology GA 348QH UT WOS:000259224500008 PM 18573174 ER PT J AU Gohler, A Conrads-Frank, A Worrell, SS Geisler, BP Halpern, EF Dietz, R Anker, SD Gazelle, GS Siebert, U AF Goehler, Alexander Conrads-Frank, Annette Worrell, Stewart S. Geisler, Benjamin P. Halpern, Elkan F. Dietz, Rainer Anker, Stefan D. Gazelle, G. Scott Siebert, Uwe TI Decision-analytic evaluation of the clinical effectiveness and cost-effectiveness of management programmes in chronic heart failure SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Hearth failure; Management programme; Cost-effectiveness analysis; Markov model ID HEALTH-CARE COSTS; QUALITY-OF-CARE; DISEASE MANAGEMENT; INTERVENTION; METAANALYSIS; STANDARD; EUROPE; TRIALS; RISK AB Background and aims: While management programmes (MPs) for chronic heart failure (CHF) are clinically effective, their cost-effectiveness remains uncertain. Thus, this study sought to determine the cost-effectiveness of MPs. Methods and results: We developed a Markov model to estimate life expectancy, quality-adjusted life expectancy, lifetime costs, and the incremental cost-effectiveness of MPs as compared to standard care. Standard care was defined by the EuroHeart Failure Survey for Germany, MP efficacy was derived from our recent meta-analysis and cost estimates were based on the German healthcare system. For a population with a mean age 67 years (35% female) at onset of CHF, our model predicted an average quality-adjusted life expectancy of 2.64 years for standard care and 2.83 years for MP. MP yielded additional lifetime costs of C 1700 resulting in an incremental cost-utility ratio (ICUR) of is an element of 8900 (95% CI: dominant to 177,100) per quality-adjusted life year (QALY) gained. Sensitivity analyses demonstrated that the ICUR was sensitive to age and sex. Conclusion: MPs increase life expectancy in patients with CHF by an average of 84 days and increase lifetime cost of care by approximately is an element of 1700. MPs improve outcomes in a cost-effective manner, although they are not cost-saving on a lifetime horizon. (c) 2008 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. C1 [Goehler, Alexander; Conrads-Frank, Annette; Worrell, Stewart S.; Geisler, Benjamin P.; Halpern, Elkan F.; Gazelle, G. Scott; Siebert, Uwe] Harvard Univ, Sch Med, Inst Technol Assessment, Boston, MA 02114 USA. [Goehler, Alexander; Conrads-Frank, Annette; Worrell, Stewart S.; Geisler, Benjamin P.; Halpern, Elkan F.; Gazelle, G. Scott; Siebert, Uwe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Goehler, Alexander; Dietz, Rainer; Anker, Stefan D.] Charite Campus Virchow Klinikum, Div Cardiol, Berlin, Germany. [Gazelle, G. Scott; Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Siebert, U (reprint author), Harvard Univ, Sch Med, MGH Inst Technol Assessment, Cardiovasc Res Program, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM usiebert@hsph.harvard.edu OI Geisler, Benjamin/0000-0003-1704-6067 FU German Cardiac Society FX Dr. Gohler was supported by the "Boston-Scientific-Scholarship" of the German Cardiac Society. We thank Dr. Dieter Gohler for his help in conducting the survey to estimate outpatient costs. We thank all colleagues who participated in the survey. We also thank Jennifer Manne for her critical input on this manuscript as well as two anonymous reviewers for their very helpful comments on an earlier version of this manuscript. NR 27 TC 17 Z9 17 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD OCT PY 2008 VL 10 IS 10 BP 1026 EP 1032 DI 10.1016/j.ejheart.2008.07.018 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 370FZ UT WOS:000260749400008 PM 18760666 ER PT J AU Badgaiyan, RD Alpert, NM Spencer, TJ Fischman, AJ AF Badgaiyan, R. D. Alpert, N. M. Spencer, T. J. Fischman, A. J. TI Molecular imaging, response inhibition and ADHD SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. 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 ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD OCT PY 2008 VL 35 SU 2 BP S150 EP S150 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V28OS UT WOS:000208690700107 ER PT J AU Fischman, AJ Spencr, TJ Biederman, J Badgaiyan, RD Meltzer, P Livni, E Bonab, AA AF Fischman, A. J. Spencr, T. J. Biederman, J. Badgaiyan, R. D. Meltzer, P. Livni, E. Bonab, A. A. TI Evaluation of the time course of dopamine transporter (DAT) occupancy by a long-acting formulation of dexmethylphenidate by PET imaging with C-11 Altropane. SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Meeting Abstract C1 [Fischman, A. J.; Spencr, T. J.; Biederman, J.; Badgaiyan, R. D.; Livni, E.; Bonab, A. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Meltzer, P.] Organix Inc, Woburn, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD OCT PY 2008 VL 35 SU 2 BP S216 EP S216 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V28OS UT WOS:000208690701003 ER PT J AU Becerra, L Borsook, D AF Becerra, Lino Borsook, David TI Signal valence in the nucleus accumbens to pain onset and offset SO EUROPEAN JOURNAL OF PAIN LA English DT Article DE fMRI; nucleus accumbens; pain; analgesia; reward; aversion ID NEURAL RESPONSES; FUNCTIONAL MRI; REWARD; FMRI; ACTIVATION; DOPAMINE; BRAIN; EXPECTATIONS; EXPERIENCE; RECEPTORS AB Pain and relief are at opposite ends of the reward-aversion continuum. Studying them provides an opportunity to evaluate dynamic changes in brain activity in reward-aversion pathways as measured by functional magnetic resonance imaging (fMRI). Of particular interest is the nucleus accumbens (NAc), a brain substrate known to be involved in reward-aversion processing, whose activation valence has been observed to be opposite in response to reward or aversive stimuli. Here we have used pain onset (aversive) and pain offset (rewarding) involving a prolonged stimulus applied to the dorsum of the hand in 10 male subjects over 120 s to study the NAc fMRI response. The results show a negative signal change with pain onset and a positive signal change with pain offset in the NAc contralateral to the stimulus. The study supports the idea that the NAc fMRI signal may provide a useful marker for the effects of pain and analgesia in healthy volunteers. (C) 2007 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved. C1 [Becerra, Lino; Borsook, David] McLean Hosp, Brain Imaging Ctr, PAIN Grp, Belmont, MA 02178 USA. [Borsook, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Engn, Cambridge, MA 02138 USA. RP Becerra, L (reprint author), McLean Hosp, Brain Imaging Ctr, PAIN Grp, 115 Mill St, Belmont, MA 02178 USA. EM lbecerra@mclean.harvard.edu FU NINDS [NS 042721] FX This work was supported by a grant from NINDS to DB (NS 042721). NR 30 TC 48 Z9 48 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1090-3801 J9 EUR J PAIN JI Eur. J. Pain PD OCT PY 2008 VL 12 IS 7 BP 866 EP 869 DI 10.1016/j.ejpain.2007.12.007 PG 4 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 350TL UT WOS:000259375900006 PM 18226937 ER PT J AU Ballantyne, JC AF Ballantyne, Jane C. TI Medical use of opioids: what drives the debate? A brief commentary SO EUROPEAN JOURNAL OF PAIN LA English DT Article CT 1st San Matteo International Meeting on Pain Research CY OCT 03-04, 2008 CL Pavia, ITALY DE Opioid; Opioid History; Addiction ID ANTAGONISTS; PAIN AB Medical advances have not obviated the need for opioids to relieve pain and suffering. There are no better analgesics. Pain and suffering have not abated. Scientific endeavor has helped unravel some of the mechanisms of pain and addiction; yet the compelling and addictive properties of opioids continue to plague their use. This article explores the factors that drive the current debate about the use of opioids to relieve the suffering of patients with chronic intractable pain. (C) 2008 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved. C1 [Ballantyne, Jane C.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, MGH Pain Ctr, Boston, MA 02114 USA. [Ballantyne, Jane C.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ballantyne, JC (reprint author), Massachusetts Gen Hosp, Pain Ctr, Div Pain Med, 15 Parkman St,WACC 333, Boston, MA 02114 USA. EM jballantyne@partners.org NR 16 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1090-3801 J9 EUR J PAIN JI Eur. J. Pain PD OCT PY 2008 BP 67 EP 68 PG 2 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 463GU UT WOS:000267419900013 ER PT J AU Diehm, N Pattynama, PM Jaff, MR Cremonesi, A Becker, GJ Hopkins, LN Mahler, F Talen, A Cardella, JF Ramee, S van Sambeek, M Vermassen, F Biamino, G AF Diehm, N. Pattynama, P. M. Jaff, M. R. Cremonesi, A. Becker, G. J. Hopkins, L. N. Mahler, F. Talen, A. Cardella, J. F. Ramee, S. van Sambeek, M. Vermassen, F. Biamino, G. TI Clinical Endpoints in Peripheral Endovascular Revascularization Trials: a Case for Standardized Definitions SO EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY LA English DT Article DE Reporting standards; Outcome analysis; Clinical improvement; Angiography ID FEMORAL-ARTERY DISEASE; LOWER-EXTREMITY; ANGIOGRAPHY; PREDICTION; GUIDELINES; ISCHEMIA; STENT; COLOR AB Background: Endovascular therapy is a rapidly expanding option for the treatment of patients with peripheral arterial disease (PAD), leading to a myriad of published studies reporting on various revascularization strategies. However, these reports are often difficult to interpret and compare because they do not utilize uniform clinical endpoint definitions. Moreover, few of these studies describe clinical outcomes from a patients' perspective. Methods and results: The DEFINE Group is a collaborative effort of an ad-hoc multidisciplinary team from various specialties involved in peripheral arterial disease therapy in Europe and the United States. DEFINE's goat was to arrive at a broad based consensus for baseline and endpoint definitions in peripheral endovascular revascularization trials for chronic tower limb ischemia. In this project, which started in 2006, the individual team members reviewed the existing pertinent literature. Following this, a series of telephone conferences and face-to-face meetings were held to agree upon definitions. Input was also obtained from regulatory (United States Food and Drug Administration) and industry (device manufacturers with an interest in peripheral endovascular revascularization) stakeholders, respectively. The efforts resulted in the current document containing proposed baseline and endpoint definitions in chronic tower limb PAD. Although the consensus has inevitably included certain arbitrary choices and compromises, adherence to these proposed standard definitions would provide consistency across future trials, thereby facilitating evaluation of clinical effectiveness and safety of various endovascular revascularization techniques. Conclusion: This current document is based on a broad based consensus involving relevant stakeholders from the medical community, industry and regulatory bodies. It is proposed that the consensus document may have value for study design of future clinical trials in chronic tower limb ischemia as well as for regulatory purposes. (C) 2008 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved. C1 [Diehm, N.; Mahler, F.] Univ Bern, Inselspital, Div Clin & Intervent Angiol, Swiss Cardiovasc Ctr, CH-3010 Bern, Switzerland. [Pattynama, P. M.] Erasmus Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands. [Jaff, M. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vasc Ctr, Boston, MA USA. [Cremonesi, A.; Biamino, G.] Villa Maria Cecilia Hosp, Grp Villa Maria Endovasc, Cotignola, Italy. [Becker, G. J.] Univ Arizona, Coll Med, Sarver Heart Ctr, Tucson, AZ 85721 USA. [Becker, G. J.] Univ Arizona, Coll Med, Dept Radiol, Vasc & Intervent Sect, Tucson, AZ 85721 USA. [Hopkins, L. N.] Sch Med & Biomed Sci, Dept Neurosurg, Buffalo, NY USA. [Talen, A.] Genae Associates Nv, Antwerp, Belgium. [Cardella, J. F.] Tufts Univ, Sch Med, Dept Radiol, Springfield, MA 01199 USA. [Ramee, S.] Ochsner Heart & Vasc Inst, New Orleans, LA USA. [van Sambeek, M.] Catharina Hosp, Dept Surg, Eindhoven, Netherlands. [Vermassen, F.] Univ Hosp, Dept Vasc Surg, Ghent, Belgium. RP Diehm, N (reprint author), Univ Bern, Inselspital, Div Clin & Intervent Angiol, Swiss Cardiovasc Ctr, Freiburgstr, CH-3010 Bern, Switzerland. EM diehm@gmx.ch FU Abbott Vascular; Biotronik GmbH; Boston Scientific; Cook Corporation; Cordis (a Johnson Et Johnson company); Datascope Corporation; Edwards Lifesciences; Ev3 GmbH; Invatec srl; Medtronic Europe FX Unrestricted grants were provided to the DEFINE to cover costs of travel, meeting rooms, and lodging for academic attendees at the Washington, DC, and New York, NY, meetings by Abbott Vascular, Biotronik GmbH, Boston Scientific, Cook Corporation, Cordis (a Johnson Et Johnson company), Datascope Corporation, Edwards Lifesciences, Ev3 GmbH, Invatec srl, Medtronic Europe. Contributing physicians did not receive honoraria for participation in the DEFINE project. NR 30 TC 62 Z9 62 U1 1 U2 4 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1078-5884 J9 EUR J VASC ENDOVASC JI Eur. J. Vasc. Endovasc. Surg. PD OCT PY 2008 VL 36 IS 4 BP 409 EP 419 DI 10.1016/j.ejvs.2008.06.020 PG 11 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 363BX UT WOS:000260242000009 PM 18692415 ER PT J AU Efstathiou, JA Bae, K Shipley, WU Hanks, GE Pilepich, MV Sandler, HM Smith, MR AF Efstathiou, Jason A. Bae, Kyounghwa Shipley, William U. Hanks, Gerald E. Pilepich, Miljenko V. Sandler, Howard M. Smith, Matthew R. TI Cardiovascular Mortality and Duration of Androgen Deprivation for Locally Advanced Prostate Cancer: Analysis of RTOG 92-02 SO EUROPEAN UROLOGY LA English DT Article DE Cardiovascular mortality; Gonadotropin-releasing hormone agonist; Hormonal therapy; Prostate cancer; Radiation therapy ID BONE-MINERAL DENSITY; HORMONE AGONISTS; BODY-COMPOSITION; THERAPY; MEN; TRIAL; RADIOTHERAPY; SUPPRESSION; IMMEDIATE; CARCINOMA AB Objectives: Gonadotropin-releasing hormone agonists (GnRHa) are associated with greater risk of coronary heart disease and myocardial infarction in men with prostate cancer, but little is known about their potential effects on cardiovascular mortality. We assessed the relationship between duration of GnRHa therapy and cardiovascular mortality in a large randomized trial of men treated with short-term versus longer-term adjuvant goserelin and radiation therapy (RT) for locally advanced prostate cancer. Methods: From 1992 to 1995, 1554 men with locally advanced prostate cancer (T2c-4, prostate-specific antigen [PSA] < 150 ng/ml) received RT and 4mo of goserelin and then were randomized to no additional therapy (arm 1) or 24 mo adjuvant goserelin (arm 2) in a phase 3 trial (Radiation Therapy Oncology Group [RTOG] 92-02). Cox regression analyses were performed to evaluate the relationship between treatment arm and cardiovascular mortality. Covariates included age, prevalent cardiovascular disease (CVD), hypertension, diabetes (DM), race, PSA, Gleason score, and stage. Results: After median follow-up of 8.1 yr, 185 cardiovascular-related deaths had occurred. No increase in cardiovascular mortality occurred for men receiving a longer duration of goserelin. At 5 yr, cardiovascular mortality for men receiving longer-term adjuvant goserelin was 5.9% versus 4.8% with short-term goserelin (Gray's p = 0.16). In multivariate analyses, treatment arm was not significantly associated with increased risk of cardiovascular mortality (adjusted hazard ratio [HR] = 1.09; 95% confidence interval [CI], 0.81-1.47; p = 0.58; when censoring at time of salvage goserelin, HR = 1.02, 95%CI, 0.73-1.43; p = 0.9). Traditional cardiac risk factors, including age, prevalent CVD, and DM, were significantly associated with greater cardiovascular mortality. Conclusions: Longer duration of adjuvant GnRHa therapy does not appear to increase cardiovascular mortality in men with locally advanced prostate cancer. (C) 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Efstathiou, Jason A.; Shipley, William U.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Bae, Kyounghwa] Radiat Therapy Oncol Grp, Dept Stat, Philadelphia, PA USA. [Hanks, Gerald E.] Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. [Pilepich, Miljenko V.] Univ Calif Los Angeles, Sch Med, Dept Radiat Oncol, Los Angeles, CA USA. [Sandler, Howard M.] Univ Michigan, Sch Med, Dept Radiat Oncol, Ann Arbor, MI USA. [Smith, Matthew R.] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. RP Efstathiou, JA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jefstathiou@partners.org FU Radiation Therapy Oncology Group [U10 CA21661]; Community Clinical Oncology Program [U10 CA37422]; National Cancer Institute [Stat U10 CA32115] FX Supported by Radiation Therapy Oncology Group U10 CA21661, Community Clinical Oncology Program U10 CA37422, and Stat U10 CA32115 grants from the National Cancer Institute. NR 32 TC 115 Z9 117 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD OCT PY 2008 VL 54 IS 4 BP 816 EP 824 DI 10.1016/j.eururo.2008.01.021 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 361LG UT WOS:000260128600015 PM 18243498 ER PT J AU Zdychova, J Kazdova, L Pelikanova, T Lindsley, JN Anderson, S Komers, R AF Zdychova, Jana Kazdova, Ludmila Pelikanova, Terezie Lindsley, Jessie N. Anderson, Sharon Komers, Radko TI Renal activity of Akt kinase in obese Zucker rats SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article DE Akt kinase; phosphatidylinositol 3-kinase; Zucker rat; mammalian target of rapamycin; mTOR; endothelial nitric oxide synthase ID MESSENGER-RNA TRANSLATION; DIABETIC KIDNEY-DISEASE; NITRIC-OXIDE SYNTHASE; PROTEIN-KINASE; EPITHELIAL-CELLS; HIGH GLUCOSE; PHOSPHOINOSITIDE 3-KINASE; SIGNAL-TRANSDUCTION; MAMMALIAN TARGET; SKELETAL-MUSCLE AB Insulin resistance (IR) and consequent hyperinsulinemia are hallmarks of Type 2 diabetes (DM2). Akt kinase (Akt) is an important molecule in insulin signaling, implicated in regulation of glucose uptake, cell growth, cell survival, protein synthesis, and endothelial nitric oxide (NO) production. Impaired Akt activation in insulin-sensitive tissues contributes to IR. However, Akt activity in other tissues, particularly those affected by complications of DM2, has been less studied. We hypothesized that hyperinsulinemia could have an impact on activity of Akt and its effectors involved in regulation of renal morphology and function in DM2. To address this issue, renal cortical Akt was determined in obese Zucker rats (ZO), a model of DM2, and lean controls (ZL). We also studied expression and phosphorylation of the mammalian target of rapamycin (mTOR) and endothelial NO synthase (eNOS), molecules downstream of Akt in the insulin signaling cascade, and documented modulators of renal injury. Akt activity was measured by a kinase assay with GSK-3 as a substrate. Expression of phosphorylated (active) and total proteins was measured by immunoblotting and immunohistochemistry. Renal Akt activity was increased in ZO as compared to ZL rats, in parallel with progressive hyperinsulinemia. No differences in Akt were observed in the skeletal muscle. Corresponding to increases in Akt activity, ZO rats demonstrated enhanced phosphorylation of renal mTOR. Acute PI3K inhibition with wortmannin (100 mu g/kg) attenuated renal Akt and mTOR activities in ZO, but not in ZL rats. In contrast to mTOR, eNOS phosphorylation was similar in ZO and ZL rats, despite higher total eNOS expression. In conclusion, ZO rats demonstrated increases in renal Akt and mTOR activity and expression. However, eNOS phosphorylation did not follow this pattern. These data suggest that DM2 is associated with selective IR in the kidney, allowing pro-growth signaling via mTOR, whereas potentially protective effects mediated by eNOS are blunted. C1 [Lindsley, Jessie N.; Anderson, Sharon; Komers, Radko] Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Dept Med, Portland, OR 97239 USA. [Zdychova, Jana; Kazdova, Ludmila; Pelikanova, Terezie; Komers, Radko] Inst Clin & Expt Med, Ctr Diabet, Prague, Czech Republic. [Anderson, Sharon] Portland VA Med Ctr, Portland, OR 97329 USA. RP Komers, R (reprint author), Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Dept Med, PP262,3314 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM komersr@ohsu.edu FU Czech Ministry of Health Care [MZO 00023001]; NIH [DK 63231] FX These studies were supported by the institutional Grant # MZO 00023001 of the Czech Ministry of Health Care (RK), and by DK 63231 from the NIH (SA). NR 50 TC 14 Z9 17 U1 0 U2 2 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD OCT PY 2008 VL 233 IS 10 BP 1231 EP 1241 DI 10.3181/0801-RM-29 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 355SU UT WOS:000259729500005 PM 18641049 ER PT J AU Katsuta, Y Ogura, Y Iriyama, S Goetinck, PF Klement, JF Uitto, J Amano, S AF Katsuta, Yuji Ogura, Yuki Iriyama, Shunsuke Goetinck, Paul F. Klement, John F. Uitto, Jouni Amano, Satoshi TI Fibulin-5 accelerates elastic fibre assembly in human skin fibroblasts SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE elastic fibre; fibulin-5; tropoelastin ID EXTRACELLULAR-MATRIX PROTEIN-1; IN-VIVO; ELASTOTIC MATERIAL; MOLECULAR-CLONING; CUTIS LAXA; MICROFIBRILS; EXPRESSION; HETEROGENEITY; GLYCOPROTEIN; MECHANISMS AB Fibulin-5 null mice display abnormalities in the elastic fibres in the dermis. We postulated, therefore, that fibulin-5 might be a regulator of elastic fibre assembly and stability. To clarify the role of fibulin-5 in elastic fibre formation, we employed in vitro systems that allowed increasing expression of elastic fibre components by gene transduction using retroviral vector constructs. First, the human tropoelastin gene (ELN) was transduced into human dermal fibroblasts, which resulted in elevated gene expression. These cells were then cultured in monolayer, but the overexpression of ELN in this system did not alter the assembly of elastic fibres. However, incubation of fibroblasts with TGF-beta 1 resulted in elastic fibre accumulation, and the expression of fibulin-5 was enhanced by TGF-beta 1. Thus, we overexpressed human fibulin-5 cDNA in dermal fibroblasts using a retroviral vector containing a cytomegalovirus (CMV) promoter. These cells deposited elastic fibres. These results suggest that fibulin-5 is a critical component in the control of elastic fibre assembly by dermal fibroblasts. C1 [Katsuta, Yuji; Ogura, Yuki; Iriyama, Shunsuke; Amano, Satoshi] Shiseido Life Sci Res Ctr, Yokohama, Kanagawa, Japan. [Katsuta, Yuji; Klement, John F.; Uitto, Jouni] Thomas Jefferson Univ, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA. [Katsuta, Yuji; Goetinck, Paul F.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. RP Katsuta, Y (reprint author), Shiseido Life Sci Res Ctr, Yokohama, Kanagawa, Japan. EM yuji.katsuta@to.shiseido.co.jp NR 37 TC 16 Z9 20 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD OCT PY 2008 VL 17 IS 10 BP 837 EP 842 DI 10.1111/j.1600-0625.2008.00709.x PG 6 WC Dermatology SC Dermatology GA 348KX UT WOS:000259210500006 PM 18341572 ER PT J AU Mollenhauer, B Cullen, V Kahn, I Krastins, B Outeiro, TF Pepivani, I Ng, J Schulz-Schaeffer, W Kretzschmar, HA McLean, PJ Trenkwalder, C Sarracino, DA VonSattel, JP Locascio, JJ El-Agnaf, OMA Schlossmacher, MG AF Mollenhauer, Brit Cullen, Valerie Kahn, Ilana Krastins, Bryan Outeiro, Tiago F. Pepivani, Imelda Ng, Juliana Schulz-Schaeffer, Walter Kretzschmar, Hans A. McLean, Pamela J. Trenkwalder, Claudia Sarracino, David A. VonSattel, Jean-Paul Locascio, Joseph J. El-Agnaf, Omar M. A. Schlossmacher, Michael G. TI Direct quantification of CSF alpha-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration SO EXPERIMENTAL NEUROLOGY LA English DT Article DE alpha-synuclein; parkinsonism; dementia; cerebrospinal fluid; mass spectrometry; ELISA; biomarker ID PARKINSONS-DISEASE DEMENTIA; CREUTZFELDT-JAKOB-DISEASE; AMYLOID-BETA-PEPTIDES; CEREBROSPINAL-FLUID; LEWY BODIES; ALZHEIMERS-DISEASE; TAU-PROTEIN; HUMAN PLASMA; WILD-TYPE; CLINICAL-DIAGNOSIS AB Because accumulation of alpha-synuclein (alpha S) in the brain is a hallmark of Parkinson disease (PD) and related disorders, we examined its Occurrence in human cerebrospinal fluid (CSF). Following affinity enrichment and trypsin digestion of CSF collected from a neurologically healthy donor, we identified several alpha S-derived peptides by mass spectrometry. The concentration of us amounted to < 0.001% of the CSF proteome. We then built, validated and optimized a sandwich-type, enzyme-linked immunoadsorbent assay (ELISA) to measure total alpha S levels in unconcentrated CSF. In a cross-sectional study of 100 living donors, we examined cell-free CSF samples from subjects clinically diagnosed with advanced PD, dementia with Lewy bodies (DLB), Alzheimer disease (AD), and a group of non-neurodegenerative disease controls (NCO). In these four groups the CSF alpha S concentrations ranged from 0.8 to 16.2 pg/mu l. Mean CSF aS values were lower in donors with a primary synucleinopathy (PD, DLB: n=57) than in the other two groups (AD, NCO: n=35; p=0.025). By contrast, living Creutzfeldt-Jakob disease patients showed markedly elevated CSF alpha S levels (n=8; mean, 300 pg/mu l; p < 0.001). Our results unequivocally confirm the presence of aS in adult human CSF. In a first feasibility study employing a novel ELISA, we found relatively low CSF alpha S concentrations in subjects with parkinsonism linked to synucleinopathy, PD and DLB. In definite prion disease cases, we recorded a marked rise in total CSF alpha S resulting from rapid cell death. Our results will likely aid future biomarker explorations in neurodegenerative conditions and facilitate target validation studies. (c) 2008 Elsevier Inc. All rights reserved. C1 [Ng, Juliana; Schlossmacher, Michael G.] Univ Ottawa, Ottawa Hlth Res Inst, Div Neurosci, Ottawa, ON K1H 8M5, Canada. [Mollenhauer, Brit; Cullen, Valerie; Kahn, Ilana; Pepivani, Imelda; Schlossmacher, Michael G.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol,Ctr Neurol Dis, Boston, MA USA. [Krastins, Bryan; Sarracino, David A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Proteom Core Facil, Cambridge, MA 02138 USA. [Outeiro, Tiago F.; McLean, Pamela J.; Locascio, Joseph J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Schulz-Schaeffer, Walter] Univ Gottingen, Dept Neuropathol, Gottingen, Germany. [Kretzschmar, Hans A.] Univ Munich, Dept Pathol, D-80539 Munich, Germany. [Trenkwalder, Claudia] Univ Gottingen, Paracelsus Elena Klin, Kassel, Germany. [VonSattel, Jean-Paul] Columbia Univ, Inst Pathol, New York, NY USA. [El-Agnaf, Omar M. A.] United Arab Emirates Univ, Fac Med & Hlth Sci, Dept Biochem, Al Ain, U Arab Emirates. RP Schlossmacher, MG (reprint author), Univ Ottawa, Ottawa Hlth Res Inst, Div Neurosci, 451 Smyth Rd 1462, Ottawa, ON K1H 8M5, Canada. EM mschlossmacher@ohri.ca FU Dr. W. Jackstaedt Fellowship des Stifterverbandes fuer die Deutsche Wissenschaft; American Parkinson Disease Association; Michael J Fox Foundation; NIH/NINDS [5P50-NS038375]; Parkinson Research Consortium at the University of Ottawa FX We are grateful to the CSF donors for their participation and to the family members for tissue donation. We thank P.T. Lansbury for his gifts of recombinant proteins and encouragement; H. Zetterberg for sharing his mass spectrometry results; A. Ivinson, D. Grimes and D. Park for the critical reading of earlier versions of this manuscript. This work was supported by a "Dr. W. Jackstaedt Fellowship des Stifterverbandes fuer die Deutsche Wissenschaft" and the American Parkinson Disease Association (to B.M.), Michael J Fox Foundation (to O.M.A.E., M.G.S.), M.S.A. Fund at BWH, NIH/NINDS 5P50-NS038375, and the Parkinson Research Consortium at the University of Ottawa (to M.G.S.). NR 70 TC 186 Z9 190 U1 0 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 2008 VL 213 IS 2 BP 315 EP 325 DI 10.1016/j.expneurol.2008.06.004 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 351ZG UT WOS:000259464200008 PM 18625222 ER PT J AU Brown, JR AF Brown, Jennifer R. TI Inherited predisposition to chronic lymphocytic leukemia SO EXPERT REVIEW OF HEMATOLOGY LA English DT Review DE association; familial chronic lymphocytic leukemia; linkage; lymphocytosis; monoclonal B cell AB Inherited susceptibility to chronic lymphocytic leukemia (CLL) has been recognized for decades Approximately 10% of individuals with CLL report a family history of CLL or a related lymphoproliferative disorder and genetic predisposition is the best understood risk factor for CLL Studies of familial CLL have suggested that the disease features are largely similar to sporadic CLL, although recent data suggest that familial CLL may more commonly show somatic hypermutation of the immunoglobulin heavy-chain variable region suggesting a more indolent disease course Monoclonal B-cell lymphocytosis (MBL) has been identified recently as a likely precursor to CLL, it is found in the general population with increasing age and enriched in unaffected relatives of individuals with familial CLL Studies of MBL as well as mouse models of CLL may lead to better understanding of early CLL pathogenesis that is relevant to familial predisposition To date the identification of genes that predispose to familial CLL has been slow primarily due to the relatively few families available for study the small size of those families and disease causation most likely by multiple genes that each confer smaller risks In the coming years the application of systematic genomics approaches to familial CLL should hopefully lead to the identification of novel loci involved in the disease C1 [Brown, Jennifer R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Brown, Jennifer R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Brown, JR (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [K23 CA115682-01, K23 CA115682-03, K23 CA115682, K23 CA115682-02, K23 CA115682-04] NR 122 TC 6 Z9 6 U1 0 U2 0 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1747-4086 J9 EXPERT REV HEMATOL JI Expert Rev. Hematol. PD OCT PY 2008 VL 1 IS 1 BP 51 EP 61 DI 10.1586/17474086.1.1.51 PG 11 WC Hematology SC Hematology GA V14KV UT WOS:000207734200013 PM 19802369 ER PT J AU Koreth, J Antin, JH AF Koreth, John Antin, Joseph H. TI Current and future approaches for control of graft-versus-host disease SO EXPERT REVIEW OF HEMATOLOGY LA English DT Review DE allogeneic stem cell transplantation; graft versus host disease AB Graft-versus-host disease (GVHD) both acute and chronic remains one of the major barriers to improving outcomes after allogeneic stem cell transplantation The pathophysiology of GVHD is complex and incompletely understood GVHD is believed to arise from the interaction of tissue damage and proinflammatory cytokines causing activation of antigen-presenting cells (APCs, donor T-cell activation by APCs and cytokines and host tissue injury by effector T lymphocytes and proinflammatory cytokines There is also a role for additional lymphocyte subtypes (naive and memory T cells regulatory T cells, natural killer T cells and B cells) in GVHD pathogenesis Strategies to improve donor recipient HLA match and to minimize conditioning toxicity cytokine release and ARC and effector T-lymphocyte activation will likely improve prophylaxis of acute (and possibly chronic) GVHD Therapy of established acute and chronic GVHD is still heavily dependent on corticosteroids despite their limited efficacy and considerable toxicity Novel agents (and/or combinations of agents) comprising pharmacologic biologic and cellular therapies targeting specific steps or subsets involved in immune activation will likely comprise future advances in GVHD control This article reviews the current state of knowledge regarding the prevention and treatment of acute and chronic GVHD Novel approaches currently undergoing evaluation are also highlighted C1 [Koreth, John; Antin, Joseph H.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Koreth, J (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [P01 HL070149, P01 HL070149-05] NR 245 TC 15 Z9 18 U1 0 U2 3 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1747-4086 J9 EXPERT REV HEMATOL JI Expert Rev. Hematol. PD OCT PY 2008 VL 1 IS 1 BP 111 EP 128 DI 10.1586/17474086.1.1.111 PG 18 WC Hematology SC Hematology GA V14KV UT WOS:000207734200018 PM 20151032 ER PT J AU Traum, AZ AF Traum, Avram Z. TI Urine proteomic profiling to identify biomarkers of steroid resistance in pediatric nephrotic syndrome SO EXPERT REVIEW OF PROTEOMICS LA English DT Review DE focal segmental glomerulosclerosis; high-abundance protein; nephrotic syndrome; normal urine proteome; pediatric; urine proteomics ID AMINO-ACID OXIDATION; MASS-SPECTROMETRY; PRIMARY CULTURES; PROTEINS; AMMONIA; PHOSPHORYLATION; ASTROCYTES; NEURONS; SERUM; UREA AB Long-term prognosis for children with nephrotic syndrome (NS) is directly related to steroid responsiveness. There are currently no diagnostic tests that accurately predict steroid responsiveness in pediatric NS. The initial prolonged course of daily, high-dose corticosteroid therapy thus serves both as a diagnostic and therapeutic maneuver. Urine proteomics is emerging as a potentially rich source of noninvasive biomarkers of drug responsiveness in NS. In this article, we discuss some of the initial studies of the urinary proteome in NS as well as ongoing and future challenges, define the normal urinary proteome and address the overwhelming abundance of urinary albumin and its impact on biomarker discovery. C1 [Traum, Avram Z.] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. [Traum, Avram Z.] Harvard Univ, Sch Med, Boston, MA USA. RP Traum, AZ (reprint author), Massachusetts Gen Hosp, Pediat Nephrol Unit, 55 Fruit St, Boston, MA 02114 USA. EM atraum@partners.org FU National Kidney Foundation of MA/RI/ VT/NH FX This work was supported by the National Kidney Foundation of MA/RI/ VT/NH. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 29 TC 8 Z9 10 U1 0 U2 7 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-9450 J9 EXPERT REV PROTEOMIC JI Expert Rev. Proteomics PD OCT PY 2008 VL 5 IS 5 BP 715 EP 719 DI 10.1586/14789450.5.5.715 PG 5 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 369NK UT WOS:000260701000012 PM 18937561 ER PT J AU Kim, DH Daskalakis, C Plumb, JD Adams, S Brawer, R Orr, N Hawtborne, K Toto, EC Whellan, DJ AF Kim, Dae Hyun Daskalakis, Constantine Plumb, James D. Adams, Suzanne Brawer, Rickie Orr, Nicole Hawtborne, Katie Toto, Erin Cunningham Whellan, David J. TI Modifiable cardiovascular risk factors among individuals in low socioeconomic communities and homeless shelters SO FAMILY & COMMUNITY HEALTH LA English DT Article DE cardiovascular disease; borneless persons; risk factors; socioeconomic factors ID CORONARY-HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; MANAGEMENT; NEIGHBORHOOD; ATHEROSCLEROSIS; ENVIRONMENTS; DISPARITIES AB To understand cardiovascular health in low socioeconomic populations, we analyzed the data from 426 low socioeconomic community-dwelling males and females and 287 homeless males in Philadelphia. Despite higher prevalence of smoking and hypertension, the proportion of homeless participants at increased risk for coronary heart disease was comparable with that of low socioeconomic community-dwelling participants. Among various characteristics, emotional stress was significantly associated with coronary heart disease risk in low socioeconomic community-dwelling participants only, suggestive of a differential psychosocial effect of stress. Our findings suggest that low socioeconomic populations are heterogeneous with respect to their risk factors and needs for interventions. C1 [Kim, Dae Hyun; Adams, Suzanne; Orr, Nicole] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Daskalakis, Constantine] Massachusetts Gen Hosp, Div Biostat, Boston, MA 02114 USA. [Plumb, James D.] Massachusetts Gen Hosp, Dept Family & Community Med, Boston, MA 02114 USA. [Brawer, Rickie] Massachusetts Gen Hosp, Off Adv Populat Hlth, Boston, MA 02114 USA. [Hawtborne, Katie] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Toto, Erin Cunningham] NW Mem Hosp, Chicago, IL 60611 USA. [Whellan, David J.] Thomas Jefferson Univ, Div Cardiol, Philadelphia, PA 19107 USA. RP Whellan, DJ (reprint author), 925 Chestnut St,Mezzanine Level, Philadelphia, PA 19107 USA. EM david.whellan@jefferson.edu NR 24 TC 12 Z9 12 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-6379 J9 FAM COMMUNITY HEALTH JI Fam. Community Health PD OCT-DEC PY 2008 VL 31 IS 4 BP 269 EP 280 PG 12 WC Family Studies; Public, Environmental & Occupational Health SC Family Studies; Public, Environmental & Occupational Health GA 350LQ UT WOS:000259354400004 PM 18794634 ER PT J AU Venkatesan, B Ghosh-Choudhury, N Das, F Mahimainathan, L Kamat, A Kasinath, BS Abboud, HE Choudhury, GG AF Venkatesan, Balachandar Ghosh-Choudhury, Nandini Das, Falguni Mahimainathan, Lenin Kamat, Amrita Kasinath, Balakuntalam S. Abboud, Hanna E. Choudhury, Goutam Ghosh TI Resveratrol inhibits PDGF receptor mitogenic signaling in mesangial cells: role of PTP1B SO FASEB JOURNAL LA English DT Article DE SIRT1; Akt kinase; CDK2 ID PROTEIN-TYROSINE PHOSPHATASE-1B; INDUCED DNA-SYNTHESIS; CARCINOMA A431 CELLS; SMOOTH-MUSCLE-CELLS; GROWTH-FACTOR; INSULIN SENSITIVITY; SIRT1 DEACETYLASE; IN-VIVO; C-FOS; PROLIFERATIVE GLOMERULONEPHRITIS AB Mesangioproliferative glomerulonephritis is associated with overactive PDGF receptor signal transduction. We show that the phytoalexin resveratrol dose dependently inhibits PDGF-induced DNA synthesis in mesangial cells with an IC50 of 10 mu M without inducing apoptosis. Remarkably, the increased SIRT1 deacetylase activity induced by resveratrol was not necessary for this inhibitory effect. Resveratrol significantly blocked PDGF-stimulated c-Src and Akt kinase activation, resulting in reduced cyclin D1 expression and attenuated pRb phosphorylation and cyclin-dependent kinase-2 (CDK2) activity. Furthermore, resveratrol inhibited PDGFR phosphorylation at the PI 3 kinase and Grb-2 binding sites tyrosine-751 and tyrosine-716, respectively. This deficiency in PDGFR phosphorylation resulted in significant inhibition of PI 3 kinase and Erk1/2 MAPK activity. Interestingly, resveratrol increased the activity of protein tyrosine phosphatase PTP1B, which dephosphorylates PDGF-stimulated phosphorylation at tyrosine-751 and tyrosine-716 on PDGFR with concomitant reduction in Akt and Erk1/2 kinase activity. PTP1B significantly inhibited PDGF-induced DNA synthesis without inducing apoptosis. These results for the first time provide evidence that the stilbene resveratrol targets PTP1B to inhibit PDGFR mitogenic signaling. C1 [Venkatesan, Balachandar; Das, Falguni; Mahimainathan, Lenin; Kamat, Amrita; Kasinath, Balakuntalam S.; Abboud, Hanna E.; Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, OBrien Kidney Res Ctr, Dept Med, San Antonio, TX 78229 USA. [Ghosh-Choudhury, Nandini] Univ Texas Hlth Sci Ctr San Antonio, OBrien Kidney Res Ctr, Dept Pathol, San Antonio, TX 78229 USA. [Kamat, Amrita; Choudhury, Goutam Ghosh] Audie L Murphy Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA. [Ghosh-Choudhury, Nandini; Kasinath, Balakuntalam S.; Abboud, Hanna E.; Choudhury, Goutam Ghosh] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Choudhury, GG (reprint author), Univ Texas Hlth Sci Ctr San Antonio, OBrien Kidney Res Ctr, Dept Med, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM choudhuryg@uthscsa.edu OI /0000-0001-5077-3552 FU National Institutes of Health (NIH) [RO1 DK 50190]; Juvenile Diabetes Research Foundation; NIH [RO1 AR52425, RO1 DK 33665]; VA Merit Review and Morrison Trust; VA VISN; American Diabetes Association [077295]; VA Research Service Merit FX We thank Dr. Brent Wagner for critically reading the manuscript. This work was supported by National Institutes of Health (NIH) grant RO1 DK 50190, the Juvenile Diabetes Research Foundation, and a VA Merit Review grant to G.G.C., who is a research career scientist in the Department of Veterans Affairs. N.G.C. is supported by NIH RO1 AR52425 and VA Merit Review and Morrison Trust grants. A.K. is a recipient of a VA VISN grant. B.S.K. is supported by grants from the NIH O'Brien Kidney Center, NIH RO1 DK 077295, the American Diabetes Association, and a VA Research Service Merit. Review grant. H.E.A. is supported by NIH RO1 DK 33665 and VA Merit Review grants. NR 95 TC 26 Z9 26 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 OCT PY 2008 VL 22 IS 10 BP 3469 EP 3482 DI 10.1096/fj.08-109488 PG 14 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 354MB UT WOS:000259642600009 PM 18567737 ER PT J AU Ng, AKL Zhang, HM Tan, KM Li, ZL Liu, JH Chan, PKS Li, SM Chan, WY Au, SWN Joachimiak, A Walz, T Wang, JH Shaw, PC AF Ng, Andy Ka-Leung Zhang, Hongmin Tan, Kemin Li, Zongli Liu, Jin-Huan Chan, Paul Kay-Sheung Li, Sui-Mui Chan, Wood-Yee Au, Shannon Wing-Ngor Joachimiak, Andrzej Walz, Thomas Wang, Jia-Huai Shaw, Pang-Chui TI Structure of the influenza virus A H5N1 nucleoprotein: implications for RNA binding, oligomerization, and vaccine design SO FASEB JOURNAL LA English DT Article DE protein-RNA interaction; crystal structure; trimerization ID CYTOTOXIC T-LYMPHOCYTES; LIMIT ESCAPE; POLYMERASE; COMPLEX; IDENTIFICATION; TRANSCRIPTION; PROTEINS; ROLES; MODEL; NP AB The threat of a pandemic outbreak of influenza virus A H5N1 has become a major concern worldwide. The nucleoprotein (NP) of the virus binds the RNA genome and acts as a key adaptor between the virus and the host cell. It, therefore, plays an important structural and functional role and represents an attractive drug target. Here, we report the 3.3-angstrom crystal structure of H5N1 NP, which is composed of a head domain, a body domain, and a tail loop. Our structure resolves the important linker segments (residues 397401, 429-437) that connect the tail loop with the remainder of the molecule and a flexible, basic loop (residues 73-91) located in an arginine-rich groove surrounding Arg150. Using surface plasmon resonance, we found the basic loop and arginine-rich groove, but mostly a protruding element containing Arg174 and Arg175, to be important in RNA binding by NP. We also used our crystal structure to build a ring-shaped assembly of nine NP subunits to model the miniribonucleo-protein particle previously visualized by electron microscopy. Our study of H5N1 NP provides insight into the oligomerization interface and the RNA-binding groove, which are attractive drug targets, and it identifies the epitopes that might be used for universal vaccine development. C1 [Ng, Andy Ka-Leung; Li, Sui-Mui; Au, Shannon Wing-Ngor; Shaw, Pang-Chui] Chinese Univ Hong Kong, Dept Biochem, Shatin, Hong Kong, Peoples R China. [Ng, Andy Ka-Leung; Shaw, Pang-Chui] Chinese Univ Hong Kong, Mol Biotechnol Program, Shatin, Hong Kong, Peoples R China. [Ng, Andy Ka-Leung; Li, Sui-Mui; Au, Shannon Wing-Ngor; Shaw, Pang-Chui] Chinese Univ Hong Kong, Ctr Prot Sci & Crystallog, Shatin, Hong Kong, Peoples R China. [Chan, Paul Kay-Sheung] Chinese Univ Hong Kong, Dept Microbiol, Shatin, Hong Kong, Peoples R China. [Chan, Wood-Yee] Chinese Univ Hong Kong, Dept Anat, Shatin, Hong Kong, Peoples R China. [Li, Zongli; Walz, Thomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Tan, Kemin; Joachimiak, Andrzej] Argonne Natl Lab, Midwest Ctr Struct Genom, Argonne, IL 60439 USA. [Tan, Kemin; Joachimiak, Andrzej] Argonne Natl Lab, Struct Biol Ctr, Argonne, IL 60439 USA. [Zhang, Hongmin; Liu, Jin-Huan; Wang, Jia-Huai] Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med,Dept Pediat,Dept Biol Chem & Mol Pharmaco, Boston, MA 02115 USA. RP Shaw, PC (reprint author), Chinese Univ Hong Kong, Dept Biochem, Shatin, Hong Kong, Peoples R China. EM pcshaw@cuhk.edu.hk RI Zhang, Hongmin/C-4503-2009; Chan, Paul/J-9360-2013 OI Zhang, Hongmin/0000-0001-6357-4106; FU Chinese University [CUHK 472808]; HK-SAR; National Institutes of Health (NIH); Giovanni Armenise Harvard Center for Strucutural Biology FX This work was supported by a Direct Research grant from the Chinese University and a General Research Fund grant (CUHK 472808) from the Research Grants Council of HK-SAR (P.-C.S.), a subcontracted National Institutes of Health (NIH) grant, and the Claudia Adams Barr Program in Cancer Research (J.-H.W.). The molecular EM facility at Harvard Medical School was established with it generous donation from the Giovanni Armenise Harvard Center for Strucutural Biology and is maintained with funds from NIH (T.W.), The authors (flank Professor Ming Luo for advice on the manuscript. NR 40 TC 125 Z9 132 U1 1 U2 17 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 OCT PY 2008 VL 22 IS 10 BP 3638 EP 3647 DI 10.1096/fj.08-112110 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 354MB UT WOS:000259642600025 PM 18614582 ER PT J AU Chen, XZ Li, Q Wu, YL Liang, GQ Lara, CJ Cantiello, HF AF Chen, Xing-Zhen Li, Qiang Wu, Yuliang Liang, Genqing Lara, Carlos J. Cantiello, Horacio F. TI Submembraneous microtubule cytoskeleton: interaction of TRPP2 with the cell cytoskeleton SO FEBS JOURNAL LA English DT Review DE actin filament; autosomal dominant polycystic kidney disease; cellular sensor; fibrocystin; interacting partner; ion channel; kinesin-2; microtubule; polycystin; transient receptor potential ID POLYCYSTIC KIDNEY-DISEASE; CATION CHANNEL FUNCTION; ACTIN CYTOSKELETON; ALPHA-ACTININ; HUMAN SYNCYTIOTROPHOBLAST; CD2-ASSOCIATED PROTEIN; EPITHELIAL-CELLS; PKD2 INTERACTS; NMDA RECEPTOR; PRIMARY CILIA AB TRPP2, also called polycystin-2, the gene product of PKD2, is a membrane protein defective in 10-15% of cases of autosomal dominant polycystic kidney disease. Mutations in PKD2 are also associated with extrarenal disorders, such as hepatic cystogenesis and cardiovascular abnormalities. TRPP2 is a Ca-permeable nonselective cation channel present in the endoplasmic reticulum and plasma membrane, as well as in cilia of renal epithelial and embryonic nodal cells, in which it likely forms part of a flow sensor. Recent studies have identified a number of TRPP2-interacting proteins, of which many are cytoskeletal components. Work from our and other laboratories indicates that cytoskeletal partner proteins seem to play important, albeit highly complex, roles in the regulation of TRPP2 expression, localization and channel function. This minireview covers current knowledge about cytoskeletal interactions with TRPP2, and suggests that mutations in proteins of the TRPP2-cytoskeleton complex may be implicated in the pathogenesis of autosomal dominant polycystic kidney disease. C1 [Chen, Xing-Zhen; Li, Qiang; Wu, Yuliang; Liang, Genqing; Lara, Carlos J.] Univ Alberta, Dept Physiol, Membrane Prot Res Grp, Edmonton, AB T6G 2H7, Canada. [Cantiello, Horacio F.] Harvard Univ, Sch Med, Charlestown, MA USA. [Cantiello, Horacio F.] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA USA. RP Chen, XZ (reprint author), Univ Alberta, Dept Physiol, Membrane Prot Res Grp, 7-29 Med Sci Bldg, Edmonton, AB T6G 2H7, Canada. EM xzchen@ualberta.ca RI Liang, Genqing/B-7180-2011 FU Canadian Institutes of Health Research and the Kidney Foundation of Canada; Alberta Heritage Foundation for Medical Research Senior Scholarship FX This work was supported by the Canadian Institutes of Health Research and the Kidney Foundation of Canada. X. Z. C. is a recipient of the Alberta Heritage Foundation for Medical Research Senior Scholarship. NR 59 TC 23 Z9 23 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1742-464X J9 FEBS J JI FEBS J. PD OCT PY 2008 VL 275 IS 19 BP 4675 EP 4683 DI 10.1111/j.1742-4658.2008.06616.x PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 348KO UT WOS:000259209600004 PM 18754774 ER PT J AU Grady, WM Carethers, JM AF Grady, William M. Carethers, John M. TI Genomic and epigenetic instability in colorectal cancer pathogenesis SO GASTROENTEROLOGY LA English DT Review ID DNA MISMATCH REPAIR; ISLAND METHYLATOR PHENOTYPE; NONPOLYPOSIS COLON-CANCER; TUMOR MICROSATELLITE-INSTABILITY; HMLH1 PROMOTER HYPERMETHYLATION; CAUSE CHROMOSOMAL INSTABILITY; REPLICATION PROTEIN-A; BASE-EXCISION-REPAIR; CELL NUCLEAR ANTIGEN; ABERRANT CRYPT FOCI AB Colorectal cancer arises as a consequence of the accumulation of genetic alterations (gene mutations, gene amplification, and so on) and epigenetic alterations (aberrant DNA methylation, chromatin modifications, and so on) that transform colonic epithelial cells into colon adenocarcinoma cells. The loss of genomic stability and resulting gene alterations are key molecular pathogenic steps that occur early in tumorigenesis; they permit the acquisition of a sufficient number of alterations in tumor suppressor genes and oncogenes that transform cells and promote tumor progression. Two predominant forms of genomic instability that have been identified in colon cancer are microsatellite instability and chromosome instability. Substantial progress has been made to identify causes of chromosomal instability in colorectal cells and to determine the effects of the different forms of genomic instability on the biological and clinical behavior of colon tumors. In addition to genomic instability, epigenetic instability results in the aberrant methylation of tumor suppressor genes. Determining the causes and roles of genomic and epigenomic instability in colon tumor formation has the potential to yield more effective prevention strategies and therapeutics for patients with colorectal cancer. C1 [Carethers, John M.] Univ Calif San Diego, Dept Med, Div Gastroenterol, La Jolla, CA 92093 USA. [Carethers, John M.] Univ Calif San Diego, Rebecca & John Moores Comprehens Canc Ctr, La Jolla, CA 92093 USA. [Carethers, John M.] VA San Diego Healthcare Syst, San Diego, CA USA. [Grady, William M.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Grady, William M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Grady, William M.] VA Puget Sound Healthcare Syst, Seattle, WA USA. RP Carethers, JM (reprint author), Univ Calif San Diego, Dept Med, Div Gastroenterol, UC303,MC 0063,9500 Gilman Dr, La Jolla, CA 92093 USA. EM jcarethers@ucsd.edu FU US Public Health Service [CA11518, DK067287, DK080506]; VA Research Service FX Supported by the US Public Health Service (CA11518 to W.M.G. and DK067287 and DK080506 to J.M.C.) and the VA Research Service (W.M.G. and J.M.C.). NR 215 TC 345 Z9 357 U1 3 U2 29 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 OCT PY 2008 VL 135 IS 4 BP 1079 EP 1099 DI 10.1053/j.gastro.2008.07.076 PG 21 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359JM UT WOS:000259982800015 PM 18773902 ER PT J AU Lieberman, D Moravec, M Holub, J Michaels, L Eisen, G AF Lieberman, David Moravec, Matthew Holub, Jennifer Michaels, Leann Eisen, Glenn TI Polyp size and advanced histology in patients undergoing colonoscopy screening: Implications for CT colonography SO GASTROENTEROLOGY LA English DT Article ID AMERICAN-CANCER-SOCIETY; COLORECTAL-CANCER; ASYMPTOMATIC ADULTS; ADVANCED NEOPLASIA; TASK-FORCE; SURVEILLANCE; ADENOMAS; POLYPECTOMY; GUIDELINES; UPDATE AB Background & Aims: Colorectal cancer screening with diagnostic imaging can detect polyps. The management of patients whose largest polyp is less than 10 mm is uncertain. The primary aim of this study was to determine rates of advanced histology in patients undergoing colorectal cancer screening whose largest polyp is 9 mm or less. Methods: Subjects include all asymptomatic adults receiving colonoscopy for screening during 2005 from 17 practice sites, which provide both colonoscopy and pathology reports to the Clinical Outcomes Research Initiative repository. Patients were classified by size of largest polyp. Advanced histology was defined as an adenoma. with villous or serrated histology, highgrade dysplasia, or an invasive cancer. Risk factors for advanced histology were determined using Pearson X-2 and Fisher exact tests. Results: Among 13,992 asymptomatic patients who had screening colonoscopy, 6360 patients (45%) had polyps, with complete histology available in 5977 (94%) patients. The proportion with advanced histology was 1.7% in the 1- to 5-mm group, 6.6% in the 6- to 9-mm group, 30.6% in the greater than 10-mm group, and 72.1% in the tumor group. Distal location was associated with advanced histology in the 6- to 9-mm group (P = .04) and in the greater than 10-mm group (P = .002). Conclusions: One in 15 asymptomatic patients whose largest polyp is 6 to 9 nun will have advanced histology and would undergo surveillance at 3 years based on current guidelines. Because histology is necessary for this decision, most of these patients should be offered colonoscopy. Further study should determine whether patients whose largest polyp is 1-5 mm. can be safely followed without polypectomy. C1 [Lieberman, David; Moravec, Matthew; Holub, Jennifer; Michaels, Leann; Eisen, Glenn] Oregon Hlth & Sci Univ, Div Gastroenterol & Hepatol, Portland, OR 97239 USA. RP Lieberman, D (reprint author), Oregon Hlth & Sci Univ, Div Gastroenterol, Portland VA Med Ctr, P3-GI,1037 SW Vet Hosp Rd, Portland, OR 97239 USA. EM lieberma@ohsu.edu FU NIDDK [U01 DK57132, R33-DK6177801]; AstraZeneca; Bard International; Pentax USA; ProVation; Endosoft; GIVEN Imaging; Ethicon; federal and industry sources FX Supported with funding from NIDDK U01 DK57132 and R33-DK6177801, and, in addition, the practice network (Clinical Outcomes Research Ini tiative) has received support from the following entities to support the infrastructure of the practice-based network: AstraZeneca, Bard International, Pentax USA, ProVation, Endosoft, GIVEN Imaging, and Ethicon; however, the commercial entities had no involvement in this research.; Financial disclosure and conflicts of interest: Dr Lieberman is the executive director of the Clinical Outcomes Research Initiative (CORI), a nonprofit organization that receives funding from federal and industry sources. The CORI database is used in this study. This relationship has been reviewed and managed by the OHSU and Portland VAMC Conflict of Interest in Research Committee. NR 21 TC 198 Z9 203 U1 2 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2008 VL 135 IS 4 BP 1100 EP 1105 DI 10.1053/j.gastro.2008.06.083 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359JM UT WOS:000259982800016 PM 18691580 ER PT J AU Suter, MJ Vakoc, BJ Yachimski, PS Shishkov, M Lauwers, GY Mino-Kenudson, M Bouma, BE Nishioka, NS Tearney, GJ AF Suter, Melissa J. Vakoc, Benjamin J. Yachimski, Patrick S. Shishkov, Milen Lauwers, Gregory Y. Mino-Kenudson, Mari Bouma, Brett E. Nishioka, Norman S. Tearney, Guillermo J. TI Comprehensive microscopy of the esophagus in human patients with optical frequency domain imaging SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID HIGH-GRADE DYSPLASIA; COHERENCE TOMOGRAPHY; BARRETTS-ESOPHAGUS; IN-VIVO; INTESTINAL METAPLASIA; ULTRAHIGH-RESOLUTION; GI TRACT; SURVEILLANCE; ADENOCARCINOMA; DIAGNOSIS AB Background: Optical coherence tomography (OCT) is a cross-sectional, high-resolution imaging modality that has been shown to accurately differentiate esophageal specialized intestinal metaplasia (SIM) from gastric cardia at the squamocolumnar junction (SCJ) and diagnose high-grade dysplasia and intramucosal carcinoma in patients with SIM. The clinical utility of OCT has been limited, however, by its inability to acquire images over large areas. Objective: The aim of this study was to use recently developed high-speed OCT technology, termed optical frequency domain imaging (OFDI), and a new balloon-centering catheter (2.5 cm diameter) to demonstrate the feasibility of large area, comprehensive optical microscopy of the entire distal esophagus (similar to 6.0 cm) in patients. Design: A pilot feasibility study. Setting: Massachusetts General Hospital. Patients: Twelve patients undergoing routine EGD. Results: Comprehensive microscopy of the distal esophagus was successfully performed in 10 patient with the OFDI system and balloon catheter. There were no complications resulting from the imaging procedure. Volumetric data sets were acquired in less than 2 minutes. OFDI images at the SCJ showed a variety of microscopic features that were consistent with histopathologic findings, including squamous mucosa, cardia, SIM with and without dysplasia, and esophageal erosion. Limitations: Inability to obtain direct correlation of OFDI data and histopathologic diagnoses. Conclusions: Comprehensive volumetric microscopy of the human distal esophagus was successfully demonstrated with OFDI and a balloon-centering, providing a wealth of detailed information about the structure of the esophageal wall. This technique will support future studies to compare OFDI image information with histopathologic diagnoses. C1 [Lauwers, Gregory Y.; Mino-Kenudson, Mari; Tearney, Guillermo J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Suter, Melissa J.; Vakoc, Benjamin J.; Shishkov, Milen; Bouma, Brett E.; Tearney, Guillermo J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Suter, Melissa J.; Vakoc, Benjamin J.; Shishkov, Milen; Bouma, Brett E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Yachimski, Patrick S.; Nishioka, Norman S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Tearney, GJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, 40 Blossom St,BAR 703, Boston, MA 02114 USA. FU National Institutes of Health [R01CA103769]; Center for Integration of Medicine and Innovative Technology (development of the imaging platform) FX The authors report that there are no disclosures relevant to this publication. This work was supported by National Institutes of Health grant No. R01CA103769 and by the Center for Integration of Medicine and Innovative Technology (development of the imaging platform). NR 27 TC 89 Z9 90 U1 2 U2 11 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD OCT PY 2008 VL 68 IS 4 BP 745 EP 753 DI 10.1016/j.gie.2008.05.014 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 355NQ UT WOS:000259716000023 PM 18926183 ER PT J AU Labbe, C Goyette, P Lefebvre, C Stevens, C Green, T Tello-Ruiz, MK Cao, Z Landry, AL Stempak, J Annese, V Latiano, A Brant, SR Duerr, RH Taylor, KD Cho, JH Steinhart, AH Daly, MJ Silverberg, MS Xavier, RJ Rioux, JD AF Labbe, C. Goyette, P. Lefebvre, C. Stevens, C. Green, T. Tello-Ruiz, M. K. Cao, Z. Landry, A. L. Stempak, J. Annese, V. Latiano, A. Brant, S. R. Duerr, R. H. Taylor, K. D. Cho, J. H. Steinhart, A. H. Daly, M. J. Silverberg, M. S. Xavier, R. J. Rioux, J. D. TI MAST3: a novel IBD risk factor that modulates TLR4 signaling SO GENES AND IMMUNITY LA English DT Article DE MAST3; inflammatory bowel disease; TLR4; NF-kappa B ID GENOME-WIDE ASSOCIATION; INFLAMMATORY-BOWEL-DISEASE; KAPPA-B ACTIVATION; CROHNS-DISEASE; SUSCEPTIBILITY LOCI; SERINE/THREONINE KINASES; ULCERATIVE-COLITIS; GENETIC-VARIATION; PATHOGENESIS; EXPRESSION AB Inflammatory bowel disease (IBD) is a chronic disorder caused by multiple factors in a genetically susceptible host. Significant advances in the study of genetic susceptibility have highlighted the importance of the innate immune system in this disease. We previously completed a genome-wide linkage study and found a significant locus (IBD6) on chromosome 19p. We were interested in identifying the causal variant in IBD6. We performed a two-stage association mapping study. In stage 1, 1530 single-nucleotide polymorphisms (SNPs) were selected from the HapMap database and genotyped in 761 patients with IBD. Among the SNPs that passed the threshold for replication, 26 were successfully genotyped in 754 additional patients (stage 2). One intronic variant, rs273506, located in the microtubule-associated serine/threonine- protein kinase gene-3 (MAST3), was found to be associated in both stages (pooled P = 1.8 x 10(-4)). We identified four MAST3 coding variants, including a nonsynonymous SNP rs8108738, correlated to rs273506 and associated with IBD. To test whether MAST3 was expressed in cells of interest, we performed expression assays, which showed abundant expression of MAST3 in antigen-presenting cells and in lymphocytes. The knockdown of MAST3 specifically decreased Toll-like receptor-4-dependent NF-kappa B activity. Our findings are additional proofs of the pivotal role played by modulators of NF-kappa B activity in IBD pathogenesis. C1 [Rioux, J. D.] Univ Montreal, Montreal Heart Inst, Res Ctr, Dept Med, Montreal, PQ H1T 1C8, Canada. [Labbe, C.; Goyette, P.; Lefebvre, C.; Rioux, J. D.] Inst Cardiol Montreal, Montreal, PQ, Canada. [Stevens, C.; Green, T.; Tello-Ruiz, M. K.; Daly, M. J.; Rioux, J. D.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Cao, Z.; Landry, A. L.; Daly, M. J.; Xavier, R. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Cao, Z.; Landry, A. L.; Daly, M. J.; Xavier, R. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Stempak, J.; Steinhart, A. H.; Silverberg, M. S.] Univ Toronto, Mt Sinai Hosp, IBD Ctr, Toronto, ON M5G 1X5, Canada. [Annese, V.; Latiano, A.] IRCCS Hosp, Gastrointestinal & Endoscopy Units, San Giovanni Rotondo, Italy. [Brant, S. R.] Johns Hopkins Univ, Sch Med, Meyerhoff Inflammatory Bowel Dis Ctr, Baltimore, MD USA. [Duerr, R. H.] Univ Pittsburgh, Sch Med, Inflammatory Bowel Dis Genet Program, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. [Taylor, K. D.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Taylor, K. D.] Cedars Sinai Med Ctr, IBD Ctr, Los Angeles, CA 90048 USA. [Cho, J. H.] Yale Univ, Dept Med, IBD Ctr, Div Gastroenterol, New Haven, CT 06520 USA. RP Rioux, JD (reprint author), Univ Montreal, Montreal Heart Inst, Res Ctr, Dept Med, 5000 Belanger St,Rm S-6200, Montreal, PQ H1T 1C8, Canada. EM John.David.Rioux@umontreal.ca RI Silverberg, Mark/B-4183-2008; Rioux, John/A-9599-2015; Latiano, Anna/R-1965-2016; OI Rioux, John/0000-0001-7560-8326; Latiano, Anna/0000-0003-3719-2061; Duerr, Richard/0000-0001-6586-3905 FU National Institute of Diabetes and Digestive and Kidney Diseases [DK062432, AI062773]; Broad Institute Center for Genotyping and Analysis [U54 RR020278]; National Center for Research Resources FX This project was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases DK062432 to JDR and AI062773 to RJX. The Broad Institute Center for Genotyping and Analysis is supported by Grant U54 RR020278 from the National Center for Research Resources. C Labbe is the recipient of a Fond de Recherche en Sante du Quebec studentship award. We thank Marcia Budarf, Marie- Pierre Levesque and Jing Lian for their help in the review of the paper. NR 35 TC 11 Z9 12 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD OCT PY 2008 VL 9 IS 7 BP 602 EP 612 DI 10.1038/gene.2008.57 PG 11 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 362WS UT WOS:000260228500004 PM 18650832 ER PT J AU Poitras, JL Dal Cin, P Aster, JC DeAngelo, DJ Morton, CC AF Poitras, Jennifer L. Dal Cin, Paola Aster, Jon C. DeAngelo, Daniel J. Morton, Cynthia C. TI Novel SSBP2-JAK2 fusion gene resulting from a t(5;9)(q14.1;p24.1) in pre-B acute lymphocytic leukemia SO GENES CHROMOSOMES & CANCER LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; TYROSINE KINASE JAK2; MYELOPROLIFERATIVE DISORDERS; POLYCYTHEMIA-VERA; PCM1-JAK2 FUSION; T(8/9) TRANSLOCATION; BINDING PROTEIN; LIM-DOMAIN; MUTATION; PATIENT AB Activating mutations in JAK2 are found in virtually all patients with polycythemia vera, and about half of those with essential thrombocythemia and primary myelofibrosis. In addition, less common aberrations (particularly gene fusions) involving JAK2 have been described in acute leukemias. With the advent of JAK2 inhibitor trials in myeloproliferative disorders, tumors with JAK2 mutations or rearrangements have become candidates for targeted therapy. In this report, we identify SSBP2 as a new JAK2 fusion partner in a patient with pi cell acute lymphocytic leukemia. This finding adds to the expanding compendium of JAK2 aberrations found in various hematopoietic malignancies, as well as the potential need for a diagnostic FISH analysis in the appropriate clinical setting. (C) 2008 Wiley-Liss, Inc. C1 [Poitras, Jennifer L.; Dal Cin, Paola; Aster, Jon C.; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Dal Cin, Paola; Aster, Jon C.; DeAngelo, Daniel J.; Morton, Cynthia C.] Harvard Univ, Sch Med, Boston, MA USA. [DeAngelo, Daniel J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Morton, Cynthia C.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Morton, CC (reprint author), Brigham & Womens Hosp, Dept Ob Gyn, 77 Ave Louis Pasteur,NRB 160, Boston, MA 02115 USA. EM cmorton@partners.org FU Department of Pathology at Brigham; Women's Hospital; Dana-Farber Cancer Institute [P01CA066996-11A1] FX We thank the Department of Pathology at Brigham and Women's Hospital for support of this investigation. Harvard Partners Center for Genetics and Genomics for kindly providing BAC clones, the Dana-Farber/I larvard Cancer Center DNA Resource Core for the automated DNA sequence analysis (P30CA006516), the Molecular Diagnostics Laboratory at Brigham and Women's Hospital for performing JAK2 V617F screening, and Ilene Galinsky, RN for assistance in sample collection. Samples were stored in the Connell O'Reily Cell Manipulation Core Facility, at the Dana-Farber Cancer Institute, supported by P01CA066996-11A1. NR 28 TC 30 Z9 30 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD OCT PY 2008 VL 47 IS 10 BP 884 EP 889 DI 10.1002/gcc.20585 PG 6 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 340ZM UT WOS:000258683500007 PM 18618714 ER PT J AU Kharchenko, PV Woo, CJ Tolstorukov, MY Kingston, RE Park, PJ AF Kharchenko, Peter V. Woo, Caroline J. Tolstorukov, Michael Y. Kingston, Robert E. Park, Peter J. TI Nucleosome positioning in human HOX gene clusters SO GENOME RESEARCH LA English DT Article ID MICROCOCCAL NUCLEASE; PROMOTER ELEMENTS; CHROMATIN DNA; SEQUENCE; YEAST; TRANSCRIPTION; GENOME; RESOLUTION; OCCUPANCY; STABILITY AB The distribution of nucleosomes along the genome is a significant aspect of chromatin structure and is thought to influence gene regulation through modulation of DNA accessibility. However, properties of nucleosome organization remain poorly understood, particularly in mammalian genomes. Toward this goal we used tiled microarrays to identify stable nucleosome positions along the HOX gene clusters in human cell lines. We show that nucleosome positions exhibit sequence properties and long-range organization that are different from those characterized in other organisms. Despite overall variability of internucleosome distances, specific loci contain regular nucleosomal arrays with 195-bp periodicity. Moreover, such arrays tend to occur preferentially toward the 3' ends of genes. Through comparison of different cell lines, we find that active transcription is correlated with increased positioning of nucleosomes, suggesting an unexpected role for transcription in the establishment of well-positioned nucleosomes. C1 [Woo, Caroline J.; Kingston, Robert E.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Kharchenko, Peter V.; Tolstorukov, Michael Y.; Park, Peter J.] Harvard Partners Ctr Genet & Genom, Boston, MA 02115 USA. [Kharchenko, Peter V.; Park, Peter J.] Childrens Hosp, Informat Program, Boston, MA 02115 USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM kingston@molbio.mgh.harvard.edu; peter_park@harvard.edu FU NLM [T15LM007092]; NSRA [F32 GM062265]; NIH [R01 GM082798, GM49301] FX We thank John Rinn for sharing the design of the tiling microarray. This research was supported by NLM training fellowship T15LM007092 (P. V. K.), NSRA fellowship F32 GM062265 (C. J. W.), NIH R01 GM082798 (P. J. P.), and NIH grant GM49301 (R. E. K.). NR 41 TC 30 Z9 30 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD OCT PY 2008 VL 18 IS 10 BP 1554 EP 1561 DI 10.1101/gr.075952.107 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 355HU UT WOS:000259700800002 PM 18723689 ER PT J AU Karel, M AF Karel, M. TI GEROPSYCHOLOGY INTERNSHIP TRAINING: EVALUATING COMPETENCIES AND FINDING A GOOD FIT SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Karel, M.] VA Boston Healthcare Syst, Brockton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2008 VL 48 SI 3 BP 7 EP 7 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 399PA UT WOS:000262810600027 ER PT J AU Roberge, B Mahoney, E Minaker, K Chuang, S AF Roberge, B. Mahoney, E. Minaker, K. Chuang, S. TI IDENTIFICATION OF NURSES' CONCERNS: THE BASIS FOR IMPROVING GERIATRIC SENSITIVE QUALITY INDICATORS FOR VULNERABLE HOSPITALIZED OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Roberge, B.; Minaker, K.; Chuang, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mahoney, E.] Boston Coll, William F Connell Sch Nursing, Chestnut Hill, MA 02167 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2008 VL 48 SI 3 BP 31 EP 32 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 399PA UT WOS:000262810600109 ER PT J AU Mroczek, D Turiano, N Spiro, A AF Mroczek, D. Turiano, N. Spiro, A., III TI EFFECTS OF NEUROTICISM CHANGE AND WIDOWHOOD ON MORTALITY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Mroczek, D.; Turiano, N.] Purdue Univ, W Lafayette, IN 47907 USA. [Spiro, A., III] VA Boston Healthcare Syst, Boston, MA 02215 USA. [Spiro, A., III] Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2008 VL 48 SI 3 BP 135 EP 135 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 399PA UT WOS:000262810600465 ER EF